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13,000 | 11,034,737 | Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol .
It also , however , causes more nausea and vomiting than the typical drugs , and , at present , there is no data suggesting that it is different to other atypical compounds . | BACKGROUND Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia .
However , the atypical class of antipsychotic drugs are making important inroads into this approach .
Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders and raise serum prolactin .
There is some suggestion that the different adverse effect profiles of atypical antipsychotic group make them more acceptable to people with schizophrenia .
Ziprasidone is one of the newer atypicals with a high serotonin receptor affinity .
OBJECTIVES To determine the effects of ziprasidone compared with placebo , typical and other atypical antipsychotic drugs for schizophrenia and related psychoses . | Abstract A double-blind , placebo-controlled , multicenter study , was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder . Patients were r and omized to receive ziprasidone 40 mg/day , 120 mg/day or placebo for 28 days . Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total , CGI-S , BPRS depression cluster and BPRS anergia cluster scores ( all P < 0.05 ) . Similarly , the percentages of patients classified as responders on the BPRS ( ≥30 % reduction ) and the CGI improvement ( score ≤2 ) were significantly greater with ziprasidone 120 mg/day compared with placebo ( P < 0.05 ) . The number of patients who experienced an adverse event was similar in all three treatment groups , and discontinuation due to adverse events was rare ( five of 91 ziprasidone-treated patients ) . The most frequently reported adverse events , that were more common in either ziprasidone group than in the placebo group , were dyspepsia , constipation , nausea and abdominal pain . There was a notably low incidence extrapyramidal side-effects ( including akathisia ) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain . Ziprasidone-treated patients were not clinical ly different from placebo-treated patients on the Simpson-Angus Rating scale , Barnes Akathisia scale and AIMS assessment s. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive , negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden In this double-blind study , patients with an acute exacerbation of schizophrenia or schizoaffective disorder were r and omized to receive either ziprasidone 80 mg/day ( n = 106 ) or 160 mg/day ( n = 104 ) or placebo ( n = 92 ) , for 6 weeks . Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total , BPRS total , BPRS core items , CGI-S , and PANSS negative subscale scores ( p < .05 ) . Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinical ly significant depression at baseline ( MADRS ≥ 14 , over-all mean 23.5 ) ( p < .05 ) as compared with placebo . The percentage of patients experiencing adverse events was similar in each treatment group , and result ant discontinuation was rare . The most frequent adverse events associated with ziprasidone were generally mild dyspepsia , nausea , dizziness , and transient somnolence . Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain . The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive , negative , and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration AIMS To assess the potential of ziprasidone to alter the renal clearance and steady-state serum levels of lithium . METHODS Healthy subjects who had stable serum lithium levels during the first 7 days of treatment with lithium 900 mg day(-1 ) , given as two divided daily doses , were r and omized to receive concomitant treatment with either ziprasidone , 40 mg day(-1 ) , given as two divided daily doses , on days 9 - 11 followed by 80 mg day(-1 ) , given as two divided daily doses on days 12 - 15 ( n = 12 ) , or placebo twice daily ( n = 13 ) . Ziprasidone or placebo was administered 2 h before each dose of lithium . RESULTS Ziprasidone administration was associated with a 0.07 mmol l(-1 ) ( 13 % ) mean increase in steady-state serum lithium levels compared with a mean increase of 0.06 mmol l(-1 ) ( 10 % ) with placebo . Mean renal clearance of lithium decreased by 0.09 l h(-1 ) ( 5 % ) in the ziprasidone group and by 0.14 l h(-1 ) ( 9 % ) in the placebo group . None of these differences between the two groups was statistically or clinical ly significant . CONCLUSIONS Ziprasidone does not alter steady-state serum lithium concentrations or renal clearance of lithium BACKGROUND Ziprasidone is a novel antipsychotic with a unique pharmacologic profile . This study compared ziprasidone with the conventional antipsychotic haloperidol in out patients with stable schizophrenia . METHOD Three hundred one out patients with stable chronic or subchronic schizophrenia ( DSM-III-R ) were r and omized and participated in this double-blind , multicenter , parallel-group clinical study comparing flexible-dose oral ziprasidone , 80 - 160 mg/day ( N = 148 ) , with haloperidol , 5 - 15 mg/day ( N = 153 ) , over 28 weeks . Patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Severity of Illness scale , the Montgomery-Asberg Depression Rating Scale , the Simpson-Angus Scale , the Barnes Akathisia Scale , and the Abnormal Involuntary Movement Scale . RESULTS Modal doses at endpoint were 80 mg/day for ziprasidone and 5 mg/day for haloperidol . Improvements in all mean efficacy variables with both ziprasidone and haloperidol were observed . Significantly more patients were categorized as negative symptom responders ( > or = 20 % reduction in PANSS negative subscale score ) in the ziprasidone group ( 48 % ) compared with the haloperidol group ( 33 % ) ( p < .05 ) . Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders . Changes in body weight were negligible with both treatments . No pattern of laboratory or cardiovascular changes was observed . CONCLUSION Ziprasidone and haloperidol were both effective in reducing overall psychopathology ; ziprasidone demonstrated effective treatment of negative symptoms and was better tolerated than haloperidol . Ziprasidone appears to offer an effective alternative to haloperidol in the long-term treatment of stable out patients with schizophrenia Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind , exploratory , dose-ranging trial . After a single-blind washout period of 4 to 7 days , patients were r and omly assigned to receive one of four fixed doses of the new antipsychotic , ziprasidone 4 ( N = 19 ) , 10 ( N = 17 ) , 40 ( N = 17 ) , or 160 ( N = 20 ) mg/day or haloperidol 15 mg/day ( N = 17 ) for 4 weeks . A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity ( CGI-S ) score ( p = 0.002 ) but not in Brief Psychiatric Rating Scale ( BPRS ) total score ( p = 0.08 ) . The intent-to-treat analysis of mean changes from baseline in the BPRS total , BPRS Psychosis core , and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day . Despite the small sample size and short duration of the trial , the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day ( p = 0.001 and p = 0.005 , respectively ) . The percentage of patients classified as responders on both the BPRS total ( > or = 30 % improvement ) and CGI-Improvement ( score of 1 or 2 ) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group . On all assessment s of clinical efficacy , the improvements associated with ziprasidone 4 mg/day , 10 mg/day , and 40 mg/day were similar . Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day ( 15 % ) than with haloperidol ( 53 % ) . Haloperidol was associated with a sustained hyperprolactinemia , unlike ziprasidone , where only transient elevations in prolactin that returned to normal within the dosing interval were observed . Ziprasidone was well tolerated , and the incidence of adverse events was similar in all groups . The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors |
13,001 | 30,659,520 | Aerobic IDE had a significant positive effect on the QOL physical component score ( QOL-PSC ) and on mental component score ( QOL-MCS ) of SF36 , but not on serum phosphorus or Kt/V. Conclusions IDE incorporation into clinical practice has a significant positive effect on QOL-PSC and QOL-MCS .
In the review ed studies , IDE did not result in any health hazard in hemodialysis patients . | Objective Intradialytic exercise ( IDE ) is not yet a routine practice for hemodialysis patients , the lack of guidelines supporting it being a major reason .
This systematic review and meta- analysis of aerobic IDE interventions examined the efficacy of IDE regarding quality of life ( QOL ) , serum phosphorus , dialysis efficiency , inflammatory status , vitamin D3 , parathyroid hormone , intake of phosphate binders , mortality and hospitalization rate . | BACKGROUND Cardiovascular disease ( CVD ) mortality rates are greatly elevated in chronic kidney disease patients receiving maintenance haemodialysis therapy . The purpose of this study was to evaluate the efficacy of intradialytic endurance exercise training on novel risk factors that may contribute to this excessive CVD risk . METHODS Seventeen haemodialysis patients were r and omized to either an intradialytic exercise training ( cycling ) group ( EX ; n = 8) or a non-exercising control group ( CON ; n = 9 ) for 4 months . At baseline and following the intervention , we measured serum parameters related to CVD risk and renal function , used echocardiography to measure variables related to cardiac structure and function and assessed physical performance by a vali date d shuttle walk test . RESULTS Performance on the shuttle walk test increased by 17 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in serum lipids or inflammatory markers ( C-reactive protein , interleukin-6 ) in either group . Serum thiobarbituric acid reactive substances , a marker of oxidative stress , were reduced by 38 % in EX ( P < 0.05 ) , but did not change in CON . In addition , serum alkaline phosphatase ( ALP ) , a putative risk factor for vascular calcification , was reduced by 27 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in left atrial volume , left ventricular mass or myocardial performance index in either group . However , the thickness of the epicardial fat layer was reduced by 11 % in EX ( P < 0.05 ) , but did not change in CON . Furthermore , the change in physical performance was inversely correlated to the change in epicardial fat ( r = -0.63 ; P = 0.03 ) . CONCLUSIONS These results suggest that endurance exercise training may improve CVD risk in haemodialysis patients by decreasing novel risk factors including serum oxidative stress , ALP and epicardial fat BACKGROUND Sedentary behavior is associated with an increased risk for death in the general population . However , the association between inactivity and mortality has not been studied in a large cohort of dialysis patients despite the high prevalence of sedentary behavior in this group . METHODS We used the Dialysis Morbidity and Mortality Study Wave 2 , a prospect i ve study of a national sample of 4,024 incident peritoneal dialysis and hemodialysis patients from 1996 to 1997 , to determine whether sedentary behavior is associated with increased mortality during a 1-year period in this group after adjusting for confounding variables . RESULTS The study population consisted of the 2,837 patients with accurate survival data who were able to ambulate and transfer . Eleven percent of the sedentary patients died during the study period compared with 5 % of nonsedentary patients . In a survival analysis , sedentary behavior ( hazard ratio , 1.62 ; 95 % confidence interval , 1.16 to 2.27 ) was associated with an increased risk for death at 1 year after adjusting for all variables that we postulated might be associated with survival and for differences between sedentary and nonsedentary patients . CONCLUSION Sedentary behavior is associated with an increased risk for mortality among dialysis patients similar in magnitude to that of other well-established risk factors , such as a one-point reduction in serum albumin concentration . More attention should be given to exercise behavior in dialysis patients , and controlled clinical trials are needed to further define the association of sedentary behavior with mortality The aim of the review was to assess the effect of patient education in ischaemic heart disease . Thirteen r and omised controlled trials of moderate to good quality including 68,556 patients were selected . The effect on mortality , cardiac morbidity , hospitalisation and health-related quality of life was assessed and only non-significant tendencies of effect were found . The authors of the review nevertheless conclude that the review supports current rehabilitation programmes that include patient education . Further research in patient education , especially concerning the most effective methods of education delivery , is needed BACKGROUND AND OBJECTIVES Reduced muscle mass and strength are prevalent conditions in dialysis patients . However , muscle strength and muscle mass are not congruent ; muscle strength can diminish even though muscle mass is maintained or increased . This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination ( i.e. , concurrent loss of muscle mass and strength/mobility , here defined as sarcopenia ) . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This study included 330 incident dialysis patients ( 203 men , mean age 53±13 years , and mean GFR 7±2 ml/min per 1.73 m(2 ) ) recruited between 1994 and 2010 and followed prospect ively for up to 5 years . Low muscle mass ( by dual-energy x-ray absorptiometry appendicular mass index ) and low muscle strength ( by h and grip ) were defined against young reference population s according to the European Working Group on Sarcopenia in Older People . RESULTS Whereas 20 % of patients had sarcopenia , low muscle mass and low muscle strength alone were observed in a further 24 % and 15 % of patients , respectively . Old age , comorbidities , protein-energy wasting , physical inactivity , low albumin , and inflammation associated with low muscle strength , but not with low muscle mass ( multivariate ANOVA interactions ) . During follow-up , 95 patients ( 29 % ) died and both conditions associated with mortality as separate entities . When combined , individuals with low muscle mass alone were not at increased risk of mortality ( adjusted hazard ratio [ HR ] , 1.23 ; 95 % confidence interval [ 95 % CI ] , 0.56 to 2.67 ) . Individuals with low muscle strength were at increased risk , irrespective of their muscle stores being appropriate ( HR , 1.98 ; 95 % CI , 1.01 to 3.87 ) or low ( HR , 1.93 ; 95 % CI , 1.01 to 3.71 ) . CONCLUSIONS Low muscle strength was more strongly associated with aging , protein-energy wasting , physical inactivity , inflammation , and mortality than low muscle mass . Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation BACKGROUND Individuals on hemodialysis have low physical function and activity levels . Clinical trials have shown improvements in these parameters with exercise programming . Pedometers have not been extensively evaluated in individuals on hemodialysis . This r and omized clinical trial compared the effects of intradialytic cycling versus a pedometer program on physical function , physical activity and quality of life . METHODS Sixty patients were r and omly assigned to two study groups . The ergometer group cycled during each hemodialysis session for 24 weeks . Pedometer participants followed a home-based walking program for 24 weeks . The primary outcome was aerobic capacity [ VO2peak and 6-minute walk ( 6MW ) test ] . Secondary outcomes included lower extremity strength [ sit-to-st and ( SS ) test ] , flexibility [ sit- and -reach ( SR ) test ] , physical activity ( accelerometer ) and health-related quality of life . Measurements were collected at baseline and at 12 and 24 weeks . RESULTS At 12 and 24 weeks , there was no significant change in the VO2peak or 6MW test between or within study groups . SS testing in the ergometer group improved from 10.2 ( SD 3.4 ) to 11.4 ( SD 2.5 ) cycles from baseline to 24 weeks ( P < 0.005 ) . Similarly , in the pedometer group , SS cycles improved from 10.1 ( SD 3.3 ) to 12.2 ( SD 3.5 ) ( P < 0.005 ) . The SR test also significantly improved over time in both the study groups . No significant changes were noted for other secondary outcomes . CONCLUSIONS Both intradialytic cycling and pedometer programming improved aspects of physical function . Neither intervention had a significant effect on aerobic capacity . No significant differences in any outcomes were identified between interventions groups Introduction Despite guidance and evidence for the beneficial effects of intradialytic exercise ( IDE ) , such programmes are rarely adopted within practice and little is known about how they may best be sustained . The Theoretical Domains Framework ( TDF ) was used to guide the underst and ing of the barriers and facilitators to initial and ongoing IDE participation and to underst and how these are influential at each stage . Material s and Methods Focus groups explored patient ( n=24 ) and staff ( n=9 ) perceptions of IDE prior to the introduction of a programme and , six months later , face to face semi-structured interviews captured exercising patients ( n=11 ) and staffs ’ ( n=8 ) actual experiences . Data were collected at private and NHS haemodialysis units within the UK . All data were audio-recorded , translated where necessary , transcribed verbatim and subject to framework analysis . Results IDE initiation can be facilitated by addressing the pre-existing beliefs about IDE through the influence of peers ( for patients ) and training ( for staff ) . Participation was sustained through the observation of positive outcomes and through social influences such as teamwork and collaboration . Despite this , environment and re source limitations remained the greatest barrier perceived by both groups . Conclusions Novel methods of staff training and patient education should enhance engagement . Programmes that clearly highlight the benefits of IDE should be more successful in the longer term . The barrier of staff workload needs to be addressed through specific guidance that includes recommendations on staffing levels , roles , training and skill mix OBJECTIVES The purpose of this study is to determine whether a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling could improve behavioural change , physical fitness , physiological condition and health-related quality of life of sedentary haemodialysis patients in The Netherl and s. METHODS Ninety-six haemodialysis patients of the Groningen Dialysis Center were r and omized into an exercise group ( n = 53 ) and a control group ( n = 43 ) . The exercise programme consists of cycling during dialysis together with a pre-dialysis strength training programme lasting 12 weeks . The intensity of the exercise programme is condition level 12 - 16 according to the rate of perceived exertion ( RPE ) . Motivational interviewing techniques were used for exercise counselling . Before and after the intervention , both groups were tested on behavioural change and physical fitness components such as reaction time , manual dexterity , lower extremity muscle strength and VO2 peak . Physiological conditions such as weight , blood pressure , haemoglobin and haematocrit values , cholesterol and Kt/V were obtained from the medical records . Health-related quality of life assessment included R AND -36 scores , symptoms and depression . RESULTS A group x time analysis with MANOVA ( repeated measures ) demonstrates that participation in a low-to-moderate intensity exercise programme linked with exercise counselling yields a significant increase in behavioural change , reaction time , lower extremity muscle strength , Kt/V and three components of quality of life , and no significant effects in the control group . CONCLUSION Participating in a low-to-moderate intensity pre-conditioning exercise programme showed beneficial effects on behavioural change , physical fitness , physiological conditions and health-related quality of life INTRODUCTION We aim ed determine the impact of an 8-week intradialytic exercise program , consisting of 15 minutes of cumulative duration low-intensity exercise during the first 2 hours of dialysis on serum electrolytes levels and hemoglobin . MATERIAL S AND METHODS In a r and omized controlled trial of in an outpatient hemodialysis unit , clinical ly stable hemodialysis patients ( n = 47 ) were included and assigned into the aerobic exercise group ( n = 25 ) and the control group ( n = 23 ) . Aerobic exercises were done in groups , 15 min/d , 3 times a week , for 2 months . The main outcome measures were biochemical variables including serum levels of calcium , phosphate , and potassium levels and hemoglobin level . RESULTS After an 8-week intervention , significant improvements were seen in serum phosphate levels ( decreased by 1.84 mg/dL ) and serum potassium levels ( decreased by 0.69 mg/dL ) . No side-effects were observed . Serum calcium and hemoglobin levels did not change significantly in the exercise group . CONCLUSIONS A simplified aerobic exercise program is a complementary , safe , and effective clinical treatment modality in patients with end-stage renal disease on dialysis Rational : Patients under regular dialysis can also present alterations in the cardiovascular , musculoskeletal , and metabolic systems . Objectives : The aim of this study is to compare the effects of strength and aerobic exercises performed during hemodialysis ( HD ) in individuals with chronic renal disease . Material s and Methods : R and omized clinical trial . It was developed as a program of exercises three times a week , in the first 2 h of HD for 8 weeks . The patients were divided into three groups : control ( Group 1 , n : 11 ) , strength ( Group 2 , n : 11 ) , and aerobic ( Group 3 , n : 10 ) . G1 has not developed any type of physical training ; G2 utilized a training load of 40 % of one repetition maximum ( 1RM ) with anklets , and developed three series of 15 repetitions . G3 pedaled seated in the dialysis seat , during 20 min , in an ergometric bicycle , with intensity regulated by the perceived effort scale . Before and after 8 weeks , the following variables were evaluated : respiratory muscular strength , pulmonary function , functional capacity , blood biochemistry , and quality of life . Main Findings : In the pre- and post-training comparison , there was statistically significant improvement ( p < 0.05 ) in the maximal inspiratory pressure ( MIP ) , number of steps achieved ( NSA ) , and quality of life ( QoL ) in the trained groups , as compared to the non-exercised group ( G1 ) . Conclusions : The strength and aerobic exercises developed during HD can improve the respiratory muscular strength , functional performance , and quality of life , when compared to individuals presenting the disease who have not developed any type of physical training In chronic kidney disease ( CKD ) , oxidative stress ( OS ) plays a central role in the development of cardiovascular diseases . This pilot program aim ed to determine whether an intradialytic aerobic cycling training protocol , by increasing physical fitness , could reduce OS and improve other CKD-related disorders such as altered body composition and lipid profile . Eighteen hemodialysis patients were r and omly assigned to either an intradialytic training ( cycling : 30 min , 55%-60 % peak power , 3 days/week ) group ( EX ; n = 8) or a control group ( CON ; n = 10 ) for 3 months . Body composition ( from dual-energy X-ray absorptiometry ) , physical fitness ( peak oxygen uptake and the 6-minute walk test ( 6MWT ) ) , lipid profile ( triglycerides ( TG ) , total cholesterol , high-density lipoprotein , and low-density lipoprotein ( LDL ) ) , and pro/antioxidant status ( 15-F2α-isoprostanes ( F2-IsoP ) and oxidized LDL in plasma ; superoxide dismutase , glutathione peroxidase , and reduced/oxidized glutathione in erythrocytes ) were determined at baseline and 3 months later . The intradialytic training protocol did not modify body composition but had significant effects on physical fitness , lipid profile , and pro/antioxidant status . Indeed , at 3 months : ( i ) performance on the 6MWT was increased in EX ( + 23.4 % , p < 0.001 ) but did not change in CON , ( ii ) plasma TG were reduced in EX ( -23 % , p < 0.03 ) but were not modified in CON , and ( iii ) plasma F2-IsoP concentrations were lower in EX than in CON ( -35.7 % , p = 0.02 ) . In conclusion , our results show that 30 min of intradialytic training , 3 times per week for 3 months , are enough to exert beneficial effects on the most sensitive and reliable marker of lipid peroxidation ( IsoP ) while improving CKD-associated disorders ( lipid profile and physical fitness ) . Intradialytic aerobic cycling training represents a useful and easy strategy to reduce CKD-associated disorders . These results need to be confirmed with a larger r and omized study Hemodialyzed ( HD ) patients with end-stage renal disease ( ESRD ) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural , metabolic , and functional abnormalities in skeletal muscles . The aim of this r and omized study was to compare the effect of rehabilitation ( RHB ) training on a bicycle ergometer and electromyostimulation ( EMS ) of leg extensors in HD patients with ESRD . Thirty-two HD patients ( 18 men/14 women ; mean age 61.1 ± 8.8 years ) were r and omized into three groups : ( i ) exercise training ( ET ; n = 11 ) on bicycle ergometer 2 × 20 min ; ( ii ) EMS ( n = 11 ) where stimulation ( 10 Hz ) of leg extensors was applied for 60 min ; and ( iii ) controls ( CON ; n = 10 ) without exercise . Exercising was performed between the 2nd and the 3rd hour of HD , three times a week , 20 weeks in total . Ergometric test was performed in order to evaluate peak workload ( W(peak ) ) , 6-min corridor walking test ( CWT ) to evaluate the distance walked , and dynamometry of leg extensors to assess muscle power ( F(max ) ) . Urea clearance was monitored and expressed as st and ard parameters : spKt/V , spKt/V equilibrated ( spKt/V-e ) , and the urea removal ratio ( URR ) . Quality of life ( QoL ) was assessed by the question naire SF-36 . A significant increase of F(max ) ( P = 0.040 in group ET ; P = 0.032 in group EMS ) , of 6-min CWT ( P < 0.001 in ET group ; P = 0.042 in EMS group ) , and of W(peak ) ( P = 0.041 in ET group ) was observed . In both exercising groups , significant increase of spKt/V , spKt/V-e , and URR was found as compared with initial values ( P < 0.05 ) . In both exercising groups , highly significant changes in summarized mental functions were found ( P = 0.001 ) ; in summarized physical components , significant improvement was observed in the ET group ( P = 0.006 ) . Intradialytic RHB showed comparable positive effects on functional parameters , urea clearance , and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism BACKGROUND Hemodialysis patients show reduced physical function and greater risk of increased arterial stiffness because of hypertension , metabolic disturbances , and vascular calcification . Exercise interventions potentially could improve their vascular risk profile . STUDY DESIGN R and omized controlled pilot clinical study comparing the effects of 6 months of supervised intradialytic exercise training versus home-based exercise training or usual care on physical function and arterial stiffness in hemodialysis patients . SETTING & PARTICIPANTS 70 hemodialysis patients from 3 renal units . INTERVENTION Intradialytic-exercise patients trained 3 times/wk for 6 months on a cycle ergometer and home-based-exercise patients followed a walking program to achieve the same weekly physical activity . Usual-care patients received no specific intervention . OUTCOMES & MEASUREMENTS Primary outcome measures were distance traveled during a 6-minute walk test and aortic pulse wave velocity . Secondary outcome measures included augmentation index ( augmentation pressure as a percentage of central pulse pressure ) , peripheral ( brachial ) and central blood pressures ( measured noninvasively using radial tonometry ) , physical activity , and self-reported physical functioning . Measurements were made at baseline and 6 months . RESULTS At 6 months , there were no significant differences between changes in 6-minute walk test distance ( intradialytic exercise , + 14 % ; home-based exercise , + 11 % ; usual care , + 5 % ) , pulse wave velocity ( intradialytic exercise , -4 % ; home-based exercise , -2 % ; usual care , + 5 % ) , or any secondary outcome measure . LIMITATIONS Lack of medication data limited the analysis of vascular parameters in this study . CONCLUSION There were no differences between intradialytic or home-based exercise training and usual care for either physical function or vascular parameters OBJECTIVE To determine the impact of a 20-week intradialytic exercise program , consisting of 60 minutes of cumulative duration , low-intensity exercise during the first 2 hours of dialysis , on dialysis efficacy , physical performance , and quality of life in self-care hemodialysis ( HD ) patients . DESIGN One-group repeated measures . SETTING Satellite HD units affiliated with a Canadian teaching hospital . PARTICIPANTS A convenience sample of 13 self-care HD patients who were stable on dialysis for a minimum of 6 months and were medically screened for significant cardiac , pulmonary , and /or musculoskeletal pathology that would preclude exercise . INTERVENTION A 5-month intradialytic exercise program in which subjects exercised 3 times a week ( cycle ergometer , mini-stepper ) for 30 minutes in each of the first 2 hours of HD . MAIN OUTCOME MEASURES Dialysis efficacy ( in single-pool model of urea kinetics [ spKt/V ] ) was assessed prior to and at the end of each month of the exercise program . Physical function ( 6-minute walk test [ 6MWT ] ) , and quality of life . ( Kidney Disease Quality of Life-Short Form [ KDQOL ] ) were determined at baseline and at weeks 10 and 20 of the exercise program . RESULTS SpKt/V increased 11 % at the end of the first month of the program ( P<.05 ) and remained elevated for the duration of the program ( 18%-19 % ) . Distance walked on the 6MWT increased by 14 % at both weeks 10 and 20 ( P<.05 ) . No changes were noted in KDQOL scores . CONCLUSIONS A low-intensity intradialytic exercise program is a viable adjunctive therapy , which improves HD efficacy and physical function in HD patients OBJECTIVE This study was conducted to determine the impact of an 8-week intradialytic exercise program ( consisting of 15 minutes low-intensity exercise during the first 2 hours of dialysis ) on dialysis efficacy . METHODS In an open r and omized controlled trial , a total of 50 clinical ly stable hemodialysis patients were enrolled into the study and r and omly allocated into two groups : the aerobic exercise group ( n=25 ) and the control group ( n=25 ) . Aerobic exercises were done in the intervention group for 15 min/day , three times a week for 2 months . The dialysis efficacy was assessed prior to and at the end of each month of the program . RESULTS The efficacy of dialysis increased at the end of the first month and remained elevated for the duration of the program in the exercise group ( p<0.05 ) . CONCLUSION A simplified aerobic exercise program has increased the efficacy of dialysis and may be considered as a safe , complementary and effective modality for hemodialysis patients We present the first study on the influence of exercise training on restless legs syndrome ( RLS ) in patients on hemodialysis ( HD ) . Restless legs syndrome has been treated pharmacologically with satisfactory results ; however , side effects and rebound phenomena have been reported . Intradialytic exercise training effectively counteracts uremia-induced catabolism ; nevertheless , it remains unknown whether patients with RLS undergoing HD benefit from such programs . The aims of the current study were to evaluate the effect of 16-weeks aerobic exercise training in the severity of RLS and in the functional capacity and the quality of life of patients with RLS on HD . Fourteen patients on HD ( four female , mean age 59 ± 16 years ) with untreated RLS were assigned , according to their will , to either the exercise group ( Ex-group , n = 7 ) , and participated in a 16-week supervised intradialytic aerobic exercise training , or to the control group ( Con-group , n = 7 ) , and continued usual activities . Primary aim was to compare the International RLS ( IRLS ) study group rating scale , functional ability , and quality of life in baseline and the end of the 16 weeks . Exercise training reduced IRLS score by 42 % ( p = 0.02 ) . Furthermore , it significantly improved indices of functional ability ( p = 0.02 ) , exercise capacity ( p = 0.01 ) , quality of life ( p = 0.03 ) , and sleep quality ( p = 0.01 ) . In the Con-group no changes were observed . In conclusion , aerobic exercise training is safe and efficacious in reducing RLS symptoms and improving quality of life in patients with RLS on HD Physical function limitation is a common disorder in chronic hemodialysis ( HD ) patients , relating to increased morbidity and mortality . The aim of this study was to determine the effects of aerobic and resistance trainings on blood lipids and inflammation status in HD patients . Out of 30 volunteer males who had been undergoing conventional maintenance HD within an HD unit in Tehran , 21 subjects were enrolled . They were r and omly assigned into aerobic exercise group – resistance training group undergoing an 8-week intradialytic exercise program ( three times/week ) and control group ( n = 7 , each ) . Training program consisted of 10 - 30 min stationary cycling at an intensity of 12–16 out of 20 at the rate of perceived exertion ( RPE ) of Borg scale in aerobic group and using ankle weights for knee extension , hip abduction and flexions at an intensity of 15–17 out of 20 at the RPE of Borg scale in resistance group . Fasting blood sample s for serum biochemistry were drawn at baseline and 8 weeks . The age , HD duration , and physical activity score were 51.6±18.9yrs ; 25.1±13.9 mo , and 19.2±7.6 , respectively . Diabetes mellitus ( 43 % ) , hypertension ( 28 % ) , and obstructive uropathy ( 14 % ) were the most common underlying diseases . Aerobic and resistance exercises were correlated with serum creatinine ( P < 0.0001 and P<0.001 ) and hs-CRP levels ( P=0.005 and P=0.036 ) reduction so that aerobic exercise induced more reduction . These exercises had no influence on weight , Kt/V values , serum urea , albumin , hemoglobin , and lipid levels ( P>0.05 ) . Both intradialytic aerobic and resistance exercises showed beneficial effects on inflammation status without any influences on serum lipid levels probably due to short duration of the study which was not accompanied with body weight changes . Solute removal had no change during exercise programs . There is a need for more investigation on the role of exercise in HD patients AIM We wished to determine if an 8-week program of exercise during dialysis in end-stage renal disease ( ESRD ) patients would increase urea removal ( enhance dialysis efficacy ) with subsequent improvements in work performance and perception of quality of life , and /or alterations in cardiovascular status . METHODS Self-care hemodialysis patients ( EX , n = 6 ) performed cycle ergometry exercise 3 times per week during their dialysis session at 40 - 50 % maximal work capacity for 15 min during each of the first 3 hours of dialysis and were matched for age , protein catabolism rate , and WLmax with a CON group ( n = 7 ) . Dialysis efficacy was measured using serum urea clearance ( Kt/V ) and dialysate urea clearance ( DUC ) during the first 2 hours of dialysis . Resting blood pressure was monitored on a sessional basis , pre- and postdialysis and during exercise in the EX group . QOL , measured using the SF-36 question naire , and WLmax were determined prior to and at 4 and 8 weeks of the exercise program . RESULTS DUC was significantly elevated in the EX group at the end of the exercise program , but was of insufficient magnitude to result in an overall increase in Kt/V. DUC decreased in the CON group but Kt/V remained unchanged . No changes in resting blood pressure occurred in either group over the course of the study , however , pulse pressure tended to increase in the CON group but decrease in the EX group , indicating a potential beneficial adaptation of the cardiovascular system in patients undergoing an exercise program . The exercise program had no effect on QOL scores and this was most likely due to the short duration of the exercise program and high-functioning level of the population studied as compared to normative data for this patient population . We also found that 33 % of the exercise sessions in the 3rd hour of dialysis were not performed due to hypotensive events . CONCLUSION Exercise during dialysis enhanced dialysate urea removal but not serum urea clearance . Alterations in the modality and the timing of exercise during dialysis may be required to elicit increases in serum urea clearance . It is also recommended that exercise during dialysis be performed during the first 2 hours of dialysis Patients who are on hemodialysis commonly experience muscle wasting and weakness , which have a negative effect on physical functioning and quality of life . The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis . A r and omized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California , San Francisco-affiliated dialysis units . Interventions included double-blinded weekly n and rolone decanoate ( 100 mg for women ; 200 mg for men ) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights . Primary outcomes included change in lean body mass ( LBM ) measured by dual-energy x-ray absorptiometry , quadriceps muscle cross-sectional area measured by magnetic resonance imaging , and knee extensor muscle strength . Secondary outcomes included changes in physical performance , self-reported physical functioning , and physical activity . Sixty-eight patients completed the study . Patients who received n and rolone decanoate increased their LBM by 3.1 + /- 2.2 kg ( P < 0.0001 ) . Exercise did not result in a significant increase in LBM . Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise ( P = 0.01 ) and to n and rolone ( P < 0.0001 ) in an additive manner . Patients who exercised increased their strength in a training-specific fashion , and exercise was associated with an improvement in self-reported physical functioning ( P = 0.04 compared with nonexercising groups ) . N and rolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis . Further studies are needed to determine whether these interventions improve survival Objective To investigate the effect of individualized exercise on exercise capacity and health-related quality of life ( HRQoL ) in uraemic patients during maintenance haemodialysis ( MHD ) . Methods Patients receiving MHD were divided r and omly into a test group , who underwent recumbent cycling exercise during dialysis , and a control group , who performed simple stretching exercises . The same dialysis protocol was used for all study participants . At study start and after 12 weeks , exercise capacity was measured using tests of physical ability ; HRQoL was measured using the kidney disease quality of life score ( KDQOL-SF ™ ) . Results A total of 65 patients were included in the study : 33 in the control group and 32 in the test group . There were no significant differences in patient characteristics between the two groups at baseline . After 12 weeks , there were significant improvements in exercise capacity and in many of the items of the KDQOL-SF ™ in the test group compared with the control group . Conclusion Individualized exercise during MHD significantly improved the exercise capacity and HRQoL for uraemic patients within a short time period , and could therefore be used as a simple , cost-effective therapeutic approach |
13,002 | 30,580,180 | Institutional-level risk factors that could be reduced were identified , including academic failure , poor clinical performance , stress , and unrealistic expectations of nursing .
This review gives insights into how a curriculum for undergraduate nursing programmes can be design ed that will engage students and increase the nursing workforce | Attrition rates among nursing students are a global issue , and a possible factor in current nursing shortages .
Numerous studies have been conducted to determine why students drop out of nursing programmes .
The limitations of previous studies have included overly small sample sizes , being largely descriptive , and not focusing on attrition as an outcome .
The aim of this study is to review the issue of attrition among undergraduate nursing students in relation to curriculum design . | Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results BACKGROUND Whilst concern about nursing student retention remains a key priority of governments and educators , much research is focussed on determining the causes and experiences of withdrawal . Further work is required to underst and the perspectives of those students who successfully negotiate their programme of study . OBJECTIVES The study aim ed to explore student motivations , experiences and support requirements during their first year to determine the efficacy of institutional retention initiatives . DESIGN Qualitative data collection through focus groups at two intervals in the year . SETTING S University class rooms . PARTICIPANTS 46 first year nursing and midwifery students . METHODS After collection , the data was subjected to grounded theory-driven coding and thematic analysis . Coding was undertaken independently before mutual verification and theming took place . RESULTS Students utilise a range of support mechanisms before and during their studies in order to maintain their motivation and to juggle the many dem and s on their time . These include university staff , fellow students , friends and family and those they currently know within the profession . CONCLUSIONS Expectations play a significant role in student satisfaction , suggesting that institutions should ensure prospect i ve students have a realistic underst and ing of what a nursing/midwifery programme and career will entail . Nurturing a sense of belonging to both the university and profession appears beneficial in promoting retention OBJECTIVE To review the published scientific literature for studies quantifying or examining factors associated with the attrition of undergraduate nursing students in pre- registration programs and the retention of graduate nurses in the workforce . METHODS The following selection criteria were used to systematic ally search the literature : target population s were either students in pre- registration nursing programs or registered nurses in their graduate year ; the studies were to be primary observational or analytical ( cross-sectional , case-control or prospect i ve cohort studies ) in design ; and outcome measures were attrition in undergraduate programs and /or retention of graduates within the workforce . Three authors guided by a st and ardised procedure performed data extraction and quality assessment independently . Synthesis of the data appears in text and tabular format . Due to the heterogenic nature of the study methods , meta- analysis was not possible . RESULTS This review found only four studies that met all inclusion criteria . All four studies examined undergraduate attrition as an outcome with two studies reporting a range of 25 - 27 % attrition within the first year . No studies were found that quantified or examined retention of new graduates as an outcome measure . Only two of the four studies followed cohorts of students prospect ively and were able to provide a high level of evidence , although each of these studies was design ed to assess specific exposures as potential predictors of attrition , rather than assess actual factors associated with students leaving their program . CONCLUSION There is a paucity of research studies in the literature from which evidence quantifying attrition and retention and the reasons why students leave undergraduate nursing programs or new graduates leave the profession can be obtained . Clearly there is a need to systematic ally track undergraduates and new graduates to quantify and underst and attrition , retention and workforce choices within the nursing profession and begin to build this evidence -base BACKGROUND Stress in nursing students may be related to attrition from nursing programmes and lead to a shortage of nurses entering clinical careers . In addition , stress leads to psychological morbidity which may have profound adverse consequences for individual nursing students . OBJECTIVES To follow a cohort of nursing students from entry to their programme to the end of the first year and to study the interrelationship between a range of psychological variables including personality , stress , coping and burnout . DESIGN Prospect i ve , repeated measures survey using self-administered question naires . SETTING A university school of nursing in Hong Kong . PARTICIPANTS Students were selected on the basis of entry to their nursing programme in 2004 ; 158 students entered the study and 147 completed ; 37 were male and 121 were female at entry . The mean age of the cohort at entry was 19.1 ( S.D. 0.85 ) ; ages ranged from 18 to 26 . METHODS The question naires administered at wave 1 were : the NEO Five Factor Inventory , the Coping in Stressful Situations question naire , the 12-item General Health Question naire , the Maslach Burnout Inventory and the Stress in Nursing Students question naire . At wave 2 the 12-item General Health Question naire , the Maslach Burnout Inventory and the Stress in Nursing Students question naire were administered . RESULTS Students suffered greater levels of psychological morbidity and burnout at the second time wave and this was largely explained by the personality trait of neuroticism . Stress also increased and this was largely explained by emotion-oriented coping . CONCLUSIONS Undertaking a nursing programme leads to increased level of stress , burnout and psychological morbidity and this is largely related to individual personality and coping traits ABSTRACT Due to the difficult and rigorous nature of nursing education , student retention and attrition are major concerns for faculty . This article describes the implementation and outcomes of a peer‐based mentor tutor program ( PMTP ) for at‐risk students in a traditional baccalaureate program . Funding was obtained to provide scholarship incentives for student participants and cover costs of training and material s. Criteria were determined for the selection of student mentors‐tutors and the identification of at‐risk students . Interventions consisted of weekly PMTP sessions offered for the first four semesters of nursing courses . Course grade s were used to determine outcome differences between control and intervention groups . Students in the intervention group were found to score significantly higher than the control group on both summative and final grade |
13,003 | 30,729,351 | There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy .
LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days | Review effectiveness of low-level laser therapy ( LLLT ) in the curative treatment of oral mucositis ( OM ) in patients receiving cancer therapy . | BACKGROUND The aim of the present study was to evaluate the effect of low-level laser therapy ( LLLT ) combined with photochemotherapy ( PCT ) for the treatment of chemotherapy-induced oral mucositis in young patients . METHODS A r and omized , blind , clinical trial with a split-mouth design was conducted involving a sample of 15 cancer patients aged three to 16 years at the Aldenora Bello Hospital in the city of São Luís , Brazil . The treatments ( PCT+LLLT and LLLT alone ) were r and omly determined for each side of the oral cavity . The patients were blinded to the type of therapy performed on each side . The outcome was the area of the lesion measured in cm2 over an eight-day evaluation period . Treatment and follow up of the lesions under evaluation as well as other lesions occurred until complete remission . Friedman and Wilcoxon tests were employed . Significance was set at a 95 % confidence level ( α=0.05 ) and the effect size was calculated . RESULTS A statistically significant difference was found between therapies for lesion area on Days 6 - 8 ( p=0.020 , 0.011 and 0.005 , respectively ) , which was confirmed by the moderate effect size . Lesions su bmi tted to PCT+LLLT had a smaller area at the end of the evaluation period . CONCLUSION Based on the present findings , PCT+LLLT had a greater therapeutic effect in comparison to LLLT alone regarding the reduction in the degree of severity of chemotherapy-induced oral mucositis Oral mucositis in oncologic patients is the most undesirable event of the chemotherapeutic treatment . This study aim ed to identify damage to the oral cavity result ing from chemotherapy in pediatric patients with acute lymphoblastic leukemia ( ALL ) . This is a prospect i ve study with a sample of 42 children and adolescents evaluated for 10 consecutive weeks after diagnosis . The modified Oral Assessment Guide ( OAG ) was used , and data were analyzed by Spearman ’s rank correlation coefficient ( α = 5 % ) . Changes to the normal lips and saliva were positively related to an increase in the OAG score during all 10 weeks of evaluation . Alterations to the labial mucosa were correlated with an increase in the OAG score from the 2nd to 10th week , which was also found for changes in the tongue and in the swallowing function in Weeks 1 , 6 , 8 , 9 , and 10 and for gum changes from the 5th to 7th week . No significant vocal changes were correlated with the total OAG score at any point during the monitoring period . Changes in lips , cheek and /or palatal mucosa , labial mucosa , and gum areas and in swallowing function were positively correlated with an increase in the severity of oral mucositis in patients with ALL after beginning chemotherapeutic treatment Background Low-energy laser ( LEL ) treatment has been suggested as an effective and safe method to prevent and /or treat oral mucositis induced by chemotherapy and /or radiotherapy ; however , it has not gained wide acceptance so far . Material s and methods We conducted two clinical trials testing the LEL technique : firstly , as a secondary prevention in patients with various solid tumors treated with chemotherapy who all developed severe mucositis after a previous identical chemotherapy and , secondly , as therapeutic intervention ( compared to sham illumination in a r and omized way ) in patients with hematological tumors receiving intensive chemotherapy and having developed low- grade oral mucositis . Results We entered 26 eligible patients in the first study and 36 were r and omized in the second study . The success rate was 81 % ( 95%CI = 61–93 % ) when LEL was given as a preventive treatment . In the second study , in patients with existing lesions , the therapeutic success rate was 83 % ( 95%CI = 59–96 % ) , which was significantly different from the success rate reached in the sham-treated patients ( 11 % ; 95%CI = 1–35 % ) ; the time to development of grade 3 mucositis was also significantly shorter in the sham-treated patients ( p < 0.001 ) . Conclusion Our results strongly support the already available literature , suggesting that LEL is an effective and safe approach to prevent or treat oral mucositis result ing from cancer chemotherapy To evaluate the efficacy and safety of carbon‐ion radiotherapy for non‐squamous cell carcinoma of the head and neck , 35 patients were enrolled in this prospect i ve study . The primary end‐point was the 3‐year local control rate , and the secondary end‐points included the 3‐year overall survival rate and adverse events . Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events , version 4.0 . The median follow‐up time for all patients was 39 months . Thirty‐two and three patients received 64.0 Gy ( relative biological effectiveness ) and 57.6 Gy ( relative biological effectiveness ) in 16 fractions , respectively . Adenoid cystic carcinoma was dominant ( 60 % ) . Four patients had local recurrence and five patients died . The 3‐year local control and overall survival rates were 93 % and 88 % , respectively . Acute grade 2–3 radiation mucositis ( 65 % ) and dermatitis ( 31 % ) was common , which improved immediately with conservative therapy . Late mucositis of grade 2 , grade 3 , and grade 4 were observed in 11 , one , and no patients , respectively . There were no adverse events of grade 5 . Carbon‐ion radiotherapy achieved excellent local control and overall survival rates for non‐squamous cell carcinoma . However , the late mucosal adverse events were not rare , and meticulous treatment planning is required . Trial registration no. UMIN000007886 OBJECTIVE A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy ( LLLT ) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis ( OM ) in young patients . BACKGROUND DATA Besides compromising the patient 's nutrition and well-being , oral mucositis represents a portal of entry into the body for microorganisms present in the mouth , which may lead to sepsis if there is hematological involvement . Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment . LLLT appears to be an interesting alternative to other approaches to treating OM , due to its trophic , anti-inflammatory , and analgesic properties . MATERIAL S AND METHODS Patients undergoing chemotherapy ( 22 cycles ) without mucositis were r and omized into a group receiving prophylactic laser-irradiation ( group 1 ) , and a group receiving placebo light treatment ( group 2 ) . Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purpose s ( group 3 , with 10 cycles of CT ) . Serum granulocyte levels were taken and compared to the progression of mucositis . RESULTS In group 1 , most patients ( 73 % ) presented with mucositis of grade 0 ( p = 0.03 when compared with the placebo group ) , and 18 % presented with grade 1 . In group 2 , 27 % had no OM and did not require therapy . In group 3 , the patients had marked pain relief ( as assessed by a visual analogue scale ) , and a decrease in the severity of OM , even when they had severe granulocytopenia . CONCLUSION The ease of use of LLLT , high patient acceptance , and the positive results achieved , make this therapy feasible for the prevention and treatment of OM in young patients OBJECTIVES To demonstrate the efficacy of laser photobiomodulation ( PBM ) compared to that of placebo on severe oral mucositis ( OM ) in pediatric oncology patients . The primary objective was the reduction of OM grade ( World Health Organization [ WHO ] scale ) 7 days after starting PBM . Secondary objectives were reduction of pain , analgesic consumption , and incidence of side effects . METHODS One hundred and one children with WHO grade > 2 chemotherapy-induced OM were enrolled in eight Italian hospitals . Patients were r and omized to either PBM or sham treatment for four consecutive days ( days + 1 to + 4 ) . On days + 4 , + 7 , and + 11 , OM grade , pain ( following a 0 - 10 numeric pain rating scale , NRS ) and need for analgesics were evaluated by an operator blinded to treatment . RESULTS Fifty-one patients were allocated to the PBM group , and 50 were allocated to the sham group . In total , 93.7 % of PBM patients and 72 % of sham patients had OM grade < 3 WHO on day + 7 ( P = 0.01 ) . A significant reduction of pain was registered on day + 7 in the PBM versus sham group ( NRS 1 [ 0 - 3 ] vs. 2.5 [ 1 - 5 ] , P < 0.006 ) . Reduced use of analgesics was reported in the PBM group , although it was not statistically significant . No significant adverse events attributable to treatment were recorded . CONCLUSIONS PBM is a safe , feasible , and effective treatment for children affected by chemotherapy-induced OM , as it accelerates mucosal recovery and reduces pain Oral mucositis ( OM ) is a debilitating and serious side effect in patients undergoing hematopoietic stem cell transplantation ( HSCT ) and chemotherapy ( CT ) . Laser therapy is becoming a promising treatment option in these patients , avoiding the necessity of enteral/parenteral nutrition . The aim of this study was to evaluate the efficacy of laser therapy in patients affected by oral mucositis induced by chemotherapy and HSCT . Sixteen onco-hematological pediatric patients receiving chemotherapy and hematopoietic stem cell transplantation , affected by oral mucositis , were enrolled in this study . They were divided in two r and omized groups : the laser group and the placebo-control group . Patients in the laser group were treated with HPLT ( 970 ± 15 nm , 3.2 W ( 50 % ) , 35–6000 Hz , 240 s ) for four consecutive days , once a day ; and placebo group underwent sham treatment . The assessment of mucositis was recorded through WHO Oral Mucositis Grading Objective Scale , and pain was evaluated through Visual Analogue Scale ( VAS ) . Patients were monitored and evaluated 3 , 7 , and 11 days after the first day of laser therapy . Once OM was diagnosed , the patients had mucositis grading assessment s before laser or sham application at day 3 , 7 , and 11 after first application . All patients of laser group demonstrated improvement in pain sensation from day 3 after first application of laser ( p < 0.05 ) , ulcerations reduced their dimensions and erythema disappeared . The patients of placebo group had improvement from day 7 . In laser group , all mucositis were fully resolved from day 7 ( p < 0.05 ) . Oral mucositis negatively impacts on nutritional intake , oral hygiene , and quality of life . Laser therapy appears to be a safe and innovative approach in the management of oral mucositis . In this preliminary study , HPLT encourages to consider laser therapy as a part of onco-hematological protocol , providing to decrease pain and duration of OM induced by CT and HSCT . Further research es will be needed , especially r and omized , controlled clinical trials with a large number of enrolled patients and a long term of follow-up to confirm the efficacy of laser therapy in prevention and control of OM in onco-hematological pediatric patients BACKGROUND This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis . PROCEDURE A r and omized clinical trial was carried out . Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May , 2003 and February , 2005 were eligible . The intervention group received laser application for 5 days following the start of chemotherapy . The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessment s were made on days 1 , 8 and 15 by a trained examiner blind to the intervention . RESULTS Sixty patients were evaluable for analysis ; thirty-nine ( 65 % ) were males , 35 ( 58 % ) patients had a diagnosis of leukemia or lymphoma , and 25 ( 42 % ) had solid tumors . The mean age was 8.7 + /- 4.3 years . Twenty-nine patients were r and omized in the laser group and 31 in the control group . On day 1 , no patients presented with mucositis . On day 8 , of 20 patients ( 36 % ) who developed mucositis , 13 of them were from the laser group and 7 from the control group . On day 15 , of 24 patients ( 41 % ) who developed mucositis , 13 of them were from the laser group and 11 from the control group . There was no significant difference between groups concerning the grade s of mucositis on day 8 ( P = 0.234 ) or on day 15 ( P = 0.208 ) . CONCLUSIONS This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided Background Oral mucositis ( OM ) is one of the most frequent complications of chemotherapy for which there is no st and ard therapy ; treatment is mostly conservative . This study was conducted to determine whether low-intensity laser therapy ( LLLT ) can reduce the duration of chemotherapy-induced OM . Procedure A placebo-controlled r and omized trial was carried out using LLLT or placebo ( sham treatment ) . Children and adolescents with cancer receiving chemotherapy or hematopoietic stem-cell transplantation between October 2005 and May 2006 were eligible as soon as they developed OM . Patients received intervention for 5 days . The LLLT group was treated with laser GaAlAs , wavelength ( λ ) : 830 nm ( infrared ) , power : 100 mW , dose : 4 J/cm2 , and placebo group underwent sham treatment . The grade of OM was clinical ly assessed by the National Cancer Institute , Common Toxicity Criteria scale . Results Twenty-one patients developed OM and were evaluable for analysis ; 18 ( 86 % ) patients had a diagnosis of leukemia or lymphoma and 3(14 % ) had solid tumors . The mean age was 8.2 ( ±3.1 ) years . Nine patients were r and omized in the laser group and 12 in the placebo-control group . Once OM was diagnosed , the patients had daily OM grading assessment s before laser or sham application and thereafter until complete healing of the lesions . On day 7 after OM diagnosis , 1/9 of patients remained with lesions in laser group and 9/12 of patients in the placebo-control group ( P=0.029 ) . In the laser group , the mean of OM duration was 5.8±2 days and in the placebo group was 8.9±2.4 days ( P=0.004 ) . Conclusions Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy-induced OM . Our results confirm the promising results observed in adult cancer patients and should encourage pediatric oncologists to use laser therapy as first-line option in children with chemotherapy-induced OM OBJECTIVE The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer . BACKGROUND DATA Mucositis occurs in more than 40 % of chemotherapy-treated patients , significantly reducing the quality of their lives . Many different interventions have been evaluated to reduce oral mucositis . Recently , good results have been achieved by phototherapy with photoradiation , a technique which has virtually no side effects . Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes ( LEDs ) may be effective . However , until now , no studies have been available on this subject . METHODS Twelve patients , aged from 34 to 82 , selected on the basis of a diagnosis of chemotherapy-induced oral mucositis , were treated intra-orally through a noncoherent LED emission , wavelength 645 + /- 15 nm , 7.8 mW , fluence 0.99 J/cm(2 ) , three times a day for 1 week . Mucositis was scored daily using the Daily Mucositis Index ( DMI ) , a scale that evaluates the disease evolution through 16 different items . The primary end-point assessed was the time to recovery , from the start of LED treatment , compared to a nonr and omized control group of 12 patients with comparable stomatitis . RESULTS The median healing time , expressed as the DMI decrease , was 1.7 ( range 1 - 2.8 ) and , in seven LED-treated patients , was shorter than in the control group . The healing rate ( measured as the ratio of the DMIs ) increased from 117 % to 164 % . CONCLUSION This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis . This result needs to be confirmed in an adequate phase III study The appearance of mucositis is a frequent and painful secondary effect of anticancer chemotherapy . Patients who develop oral toxicity during the first course of treatment will almost assuredly show identical side effects during each subsequent course unless the drugs are changed or the doses are lowered . In the absence of an efficacious antidote or preventive prophylaxis for such lesions to date , this report presents the results of a preliminary retrospective non-r and omized study of the effect of soft-laser treatments on mucositis in cancer patients receiving combination chemotherapy , including 5-fluorouracil . Iatrogenic mucositis was observed during 43 % of 53 chemotherapy cycles in the case control population . Curative laser therapy reduced the time to repair lesions and the rate of therapeutic modifications . For patients who received soft-laser therapy as a preventive measure , the incidence of oral complications was reduced to 6 % during 101 cycles of chemotherapy . All of these patients , even those who have encountered mucositis before receiving preventive laser therapy , terminated their cancer therapy as originally scheduled . Well design ed and carefully controlled trials will be necessary to define the place of helium-neon laser therapy in the repair and prevention of oral complications due to cancer chemotherapy |
13,004 | 31,761,996 | Changes to key parameters were unlikely to change the conclusions of the CEA when the cost-effectiveness threshold was considered .
When parameter inputs are not exactly aligned , conclusions may still be comparable across jurisdictions . | Differing method ological requirements and decision-making criteria are recognised as barriers to transferability of cost-effectiveness analysis ( CEA ) across jurisdictions .
We assessed the generic and specific transferability of published CEAs of systemic treatments for advanced melanoma to the Irish setting . | Background Nivolumab was the first programmed death receptor 1 ( PD-1 ) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients . Objective To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in Engl and . Methods A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab , dabrafenib , and vemurafenib for BRAF mutation-positive patients . Covariate-adjusted parametric curves for time to progression , pre-progression survival , and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data . Indirect treatment comparisons between nivolumab , ipilimumab , and dacarbazine were informed by these covariate-adjusted parametric curves , controlling for differences in patient characteristics . Kaplan – Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib . Patient utilities and re source use data were based on trial data or the literature . Patients are assumed to receive nivolumab until there is no further clinical benefit , assumed to be the first of progressive disease , unacceptable toxicity , or 2 years of treatment . Results Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients , with incremental cost-effectiveness ratios of £ 24,483 and £ 17,362 per quality -adjusted life year , respectively . The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves . Conclusions Nivolumab is a cost-effective treatment for advanced melanoma patients in Engl and BACKGROUND The aim of this study was to assess the cost-effectiveness of pembrolizumab in treating patients with ipilimumab-naïve advanced melanoma in Portugal . METHODS A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab . The model was parameterized by using data from a head-to-head phase III r and omized clinical trial , KEYNOTE-006 . Extrapolation of long-term outcomes was based on approaches previously applied , combining ipilimumab data and melanoma patients ' registry data . The analysis was conducted from the perspective of the Portuguese National Health Service , and a lifetime horizon ( 40 years ) was used . Portugal-specific disease management costs were estimated by convening a panel of six clinical experts to derive health state re source use and multiplying the results by national unit costs . To test for the robustness of the conclusions , we conducted deterministic and probabilistic sensitivity analyses . RESULTS Pembrolizumab increases life expectancy in 1.57 undiscounted life-years ( LYs ) and is associated with an increase in costs versus that of ipilimumab . The estimated incremental cost-effectiveness ratio is € 47,221 per quality -adjusted life-year ( QALY ) and € 42,956 per LY . Deterministic sensitivity analysis showed that the results were robust to the change of most input values or assumptions and were sensitive to time on treatment scenarios . According to the probabilistic sensitivity analysis performed , pembrolizumab is associated with a cost per QALY gained inferior to € 50,000 in 75 % of the cases . CONCLUSIONS Considering the usually accepted thresholds in oncology , pembrolizumab is a cost-effective alternative for treating patients with advanced melanoma in Portugal BACKGROUND Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma . However , there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication . OBJECTIVE To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U.S. integrated health system perspective . METHODS A partitioned-survival model was developed , which divided overall survival time into progression-free survival and postprogression survival . The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent r and omized phase 3 study ( KEYNOTE-006 ) that compared pembrolizumab and ipilimumab . Extrapolation of progression-free survival and overall survival beyond the clinical trial was based on parametric functions and literature data . The base-case time horizon was 20 years , and costs and health outcomes were discounted at a rate of 3 % per year . Clinical data -including progression-free survival and overall survival data spanning a median follow-up time of 15 months , as well as quality of life and adverse event data from the ongoing KEYNOTE-006 trial- and cost data from public sources were used to populate the model . Costs included those of drug acquisition , treatment administration , adverse event management , and disease management of advanced melanoma . The incremental cost-effectiveness ratio ( ICER ) expressed as cost difference per quality -adjusted life-year ( QALY ) gained was the main outcome , and a series of sensitivity analyses were performed to test the robustness of the results . RESULTS In the base case , pembrolizumab was projected to increase the life expectancy of U.S. patients with advanced melanoma by 1.14 years , corresponding to a gain of 0.79 discounted QALYs over ipilimumab . The model also projected an average increase of $ 63,680 in discounted perpatient costs of treatment with pembrolizumab versus ipilimumab . The corresponding ICER was $ 81,091 per QALY ( $ 68,712 per life-year ) over a 20-year time horizon . With $ 100,000 per QALY as the threshold , when input parameters were varied in deterministic one-way sensitivity analyses , the use of pembrolizumab was cost-effective relative to ipilimumab in most ranges . Further , in a comprehensive probabilistic sensitivity analysis , the ICER was cost-effective in 83 % of the simulations . CONCLUSIONS Compared with ipilimumab , pembrolizumab had higher expected QALYs and was cost-effective for the treatment of patients with unresectable or metastatic melanoma from a U.S. integrated health system perspective . DISCLOSURES This study was supported by funding from Merck & Co. , which review ed and approved the manuscript before journal su bmi ssion . Wang , Pellissier , Xu , Stevinson , and Liu are employees of , and own stock in , Merck & Co. Chmielowski has served as a paid consultant for Merck & Co. and received a consultant fee for clinical input in connection with this study . Chmielowski also reports receiving advisory board and speaker bureau fees from multiple major pharmaceutical companies . Wang led the modeling and writing of the manuscript . Chmielowski , Xu , Stevinson , and Pellissier contributed substantially to the modeling design and methodology . Liu led the data collection work and contributed substantially to writing the manuscript . In conducting the analysis and writing the manuscript , the authors followed Merck publication polices and the " cost-effectiveness analysis alongside clinical trials-good research practice s and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17 % . R and omized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab ( PEM ) , nivolumab ( NIVO ) , and ipilumumab (IPI)-demonstrate improved patient outcomes , but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear . To inform policy makers about the value of these treatments , we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma . Material s and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs ( 2016 US$ ) and quality -adjusted life years ( QALYs ) for treatment sequences with first-line NIVO , IPI , NIVO + IPI , PEM every 2 weeks , and PEM every 3 weeks . Health states were defined for initial treatment , first and second progression , and death . Rates for drug discontinuation , frequency of adverse events , disease progression , and death obtained from r and omized phase III trials were used to determine the likelihood of transition between states . Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty . Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO , or IPI followed by NIVO . Compared with the first-line dacarbazine treatment strategy , NIVO followed by IPI produced an incremental cost effectiveness ratio of $ 90,871/QALY , and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $ 198,867/QALY . Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma , first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective , immune-based treatment strategies for metastatic melanoma |
13,005 | 31,978,255 | Based on low-certainty evidence , basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation .
The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes , including graft rejections . | BACKGROUND Liver transplantation is considered the definitive treatment for people with liver failure .
As part of post-liver transplantation management , immunosuppression ( suppressing the host immunity ) is given to prevent graft rejections .
Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression ( induction immunosuppression ) and those that are used over the entire lifetime of the individual ( maintenance immunosuppression ) , because it is widely believed that graft rejections are more common during the first few months after liver transplantation .
Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action .
There is considerable uncertainty as to whether induction immunosuppression is necessary and if so , the relative efficacy of different immunosuppressive agents .
OBJECTIVES To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta- analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy . | This r and omized , prospect i ve , multicenter trial compared the safety and efficacy of steroid-free immunosuppression ( IS ) to the safety and efficacy of 2 st and ard IS regimens in patients undergoing transplantation for hepatitis C virus ( HCV ) infection . The outcome measures were acute cellular rejection ( ACR ) , severe HCV recurrence , and survival . The patients were r and omized ( 1:1:2 ) to tacrolimus ( TAC ) and corticosteroids ( arm 1 ; n = 77 ) , mycophenolate mofetil ( MMF ) , TAC , and corticosteroids ( arm 2 ; n = 72 ) , or MMF , TAC , and daclizumab induction with no corticosteroids ( arm 3 ; n = 146 ) . In all , 295 HCV RNA-positive subjects were enrolled . At 2 years , there were no differences in ACR , HCV recurrence ( biochemical evidence ) , patient survival , or graft survival rates . The side effects of IS did not differ , although there was a trend toward less diabetes in the steroid-free group . Liver biopsy sample s revealed no significant differences in the proportions of patients in arms 1 , 2 , and 3 with advanced HCV recurrence ( ie , an inflammation grade ≥ 3 and /or a fibrosis stage ≥ 2 ) in years 1 ( 48.2 % , 50.4 % , and 43.0 % , respectively ) and 2 ( 69.5 % , 75.9 % , and 68.1 % , respectively ) . Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV , steroid sparing has no clear advantage in comparison with traditional IS Hepatitis C is the most common indication for liver transplantation ( LT ) in the United States . Recurrence of hepatitis C virus ( HCV ) infection post-LT remains a problem for which there is no completely satisfactory treatment . The aim of the present study is to evaluate mycophenolate mofetil ( MMF ) , which has both immunosuppressive and antiviral properties , to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival . Between August 1995 and May 1998 , a total of 106 patients who were HCV positive before LT were r and omized to tacrolimus ( TAC ) and prednisone versus TAC , prednisone , and MMF therapy . The rate of recurrence of HCV , patient and graft survival , incidences of rejection , and histological findings were examined . Fifty six patients were r and omized to TAC and steroid therapy ( double [ D ] drug ; group D ) , and 50 patients were r and omized to TAC , steroid , and MMF therapy ( triple [ T ] drug ; group T ) . Liver biopsies were performed when liver function was abnormal ; protocol liver biopsies were not performed . Mean follow-up was 4.3 + /- 0.8 years . Actuarial patient survivals at 4 years were 72.6 % in group D and 73.8 % in group T ( P = not significant ) . Actuarial graft survivals at 4 years were 65.6 % in group D and 65.4 % in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV . One patient in each group died of recurrent HCV without re-LT . Twenty-six patients in group D ( 46.4 % ) and 23 patients in group T ( 46.0 % ) showed signs of recurrent HCV . Mean hepatitis activity index ( HAI ) scores were 7.4 + /- 2.7 in group D and 7.0 + /- 3.4 in group T , and mean fibrosis scores were 2.9 + /- 1.7 in group D and 2.6 + /- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period . None of these values reached statistical significance . Rates of HCV recurrence , graft loss or death from recurrent HCV , and 4-year actuarial patient and graft survival were not different between the groups . In liver transplant recipients with HCV , MMF has no impact on patient survival , graft survival , rejection , or rate of HCV recurrence based on biochemical changes and histological findings . In addition , there was no difference in HAI or fibrosis score between the two groups . Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting Basiliximab , a high-affinity chimeric monoclonal antibody , is effective in reducing acute rejection episodes in renal allograft recipients . We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients . Adult recipients of a primary cadaveric liver transplant were r and omized to treatment , stratified by hepatitis C virus ( HCV ) seropositivity . Patients were administered 40 mg of basiliximab ( n = 188 ) or placebo ( n = 193 ) as two 20-mg bolus injections days 0 and 4 , plus cyclosporine and steroids . Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point , including death or graft loss , and were assessed at 6 and 12 months and by HCV cohort . Because of differential efficacy responses between HCV-positive and HCV-negative cohorts , an additional analysis incorporating HCV recurrence as a component of treatment failure , termed problem-free transplant , was introduced . Safety and tolerability were monitored over the 12 months of the study . All 381 patients were assessable , and no meaningful differences in background characteristics were apparent between treatment groups . Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1 % in the basiliximab group versus 43.5 % in the placebo group . For death , graft loss , or first biopsy-confirmed acute rejection , rates were 44.1 % versus 52.8 % , respectively . The reduction in rejection episodes was concentrated in the HCV-negative cohort ( 14.5 % relative to placebo ; P = .034 ) , with a much smaller difference ( 2.9 % ) in the HCV-positive cohort . For HCV-positive patients , problem-free transplant was shown at 12 months in 26.6 % of the basiliximab group versus 11.6 % in the placebo group ( P = .020 ) and for all patients at 12 months in 39.7 % of the basiliximab group versus 30.1 % in the placebo group ( P = .035 ) . The incidence of infection and other adverse events was similar across the two treatment groups . There were 56 deaths ( 25 deaths , basiliximab group ; 31 deaths , placebo group ) over the 12-month study . The intravenous bolus injection was well tolerated . Immunoprophylaxis with 40 mg of basiliximab , in combination with cyclosporine and steroids , reduces the incidence of acute rejection episodes with no clinical ly relevant safety or tolerability concerns . The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant , incorporating recurrence as a component of treatment failure Background . Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation . Interleukin-2 receptor antagonist induction followed by delayed tacrolimus ( Tac ) administration may minimize the renal insult without compromising immunoprotection . Methods . This open , r and omized , multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months ; an observational study was continued for 18 months . Liver transplant patients with a 12-hr serum creatinine ( SrC ) level less than 180 & mgr;mol/L received either delayed Tac with daclizumab induction ( n=98 ) or st and ard Tac ( n=101 ) both combined with mycophenolate mofetil and steroids . The primary endpoint was the incidence of SrC level more than 130 & mgr;mmol/L at 6 months . Results . The incidence was 22.4 % with delayed Tac and 29.7 % with st and ard Tac ( P = ns ) , which remained unchanged at 12 months ( 21.6 % and 23.9 % ) but increasing slightly at 24 months ( 29.0 % and 32.9 % ) , respectively . A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr ( ≤100&mgr;mol/L or > 100 & mgr;mol/L ) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 & mgr;mol/L in the delayed Tac group . Biopsy-proven acute rejection was similar at 6 months ( 17.5 % and 18.75 % ) , 12 months ( 23.5 % and 23.8 % ) , and 24 months ( 24.5 % and 25.7 % ) , respectively . Patient and graft survival in both groups were comparable and good . Similar types and incidences of adverse events were reported in both groups at all time . Conclusions . Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline Sub clinical renal dysfunction is thought to occur as a systemic manifestation of ischaemia‐reperfusion injury of other organs . Liver transplantation is associated with major ischaemia‐reperfusion injury . Thirty‐four patients undergoing elective liver transplantation were r and omly allocated to receive either saline or 10 mg.kg−1 methylprednisolone on induction of anaesthesia . Urine was taken for N‐acetyl‐β‐D‐glucosaminidase , creatinine and other markers of tubular function . Serum chemistry was measured for 7 days . Creatinine concentration increased in the saline group but not in the methylprednisolone group ( p < 0.0001 ) , with the greatest difference on the third postoperative day ( mean ( SD ) 164.8 ( 135.8 ) μmol.l−1vs 88.5 ( 39.4 ) μmol.l−1 , respectively ) . Similar changes were seen in postoperative alanine transferase ( 865 ( 739 ) U.l−1vs 517 ( 608 ) U.l−1 , respectively ; p < 0.0001 ) on the second postoperative day . Both groups exhibited increases in markers of renal tubular dysfunction and of glomerular permeability . Patients in the saline group sustained more adverse events ( 8/17 ( 47 % ) vs 2/17 ( 12 % ) ; p = 0.02 ) . The data confirm increased proximal tubular lysosomal turnover , consistent with an increased tubular protein load , following liver transplantation , and suggest that methylprednisolone protects against renal and hepatic dysfunction OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials We report the results of a prospect i ve r and omized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin ( ATG‐Fresenius ) plus tacrolimus monotherapy at gradually decreasing doses . Patients were r and omized to either : ( a ) st and ard‐dose tacrolimus plus steroids;or ( b ) peritransplant ATG‐Fresenius plus reduced‐dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation . The primary end‐point was the achievement of very low‐dose tacrolimus ( every‐other‐day or once daily dose with < 5 ng/mL trough levels ) at 12 months after transplantation . Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group ( 52.4 % vs. 25 % ) . Moreover , late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end‐point . This motivated the premature termination of the trial . Tacrolimus trough levels were lower in the ATG‐Fresenius group but no benefits in terms of improved renal function , lower metabolic complications or increased prevalence of tolerance‐related biomarkers were observed . In conclusion , the use of ATG‐Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection , did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits . Clinical Trials.gov identifier : NCT00436722 This r and omized , comparative study assessed the long-term efficacy and tolerability of thymoglobulin ( TMG ) induction in 93 liver transplant patients with an initial regimen of tacrolimus ( Tac ) , mycophenolate mofetil ( MMF ) , and steroids . Forty-four patients were r and omly allocated to the TMG+ group , and 49 patients were r and omly allocated to the TMG- group . In both groups , Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily , and MMF was given at the initial daily dose of 2 g/day . Steroid withdrawal was planned at 3 months after liver transplantation . The results were evaluated with respect to acute rejection incidence , patient and graft survival , graft function , and medical complications until 5 years or death for all patients . No significant differences were found between groups for the incidence of acute rejection at 5 years ( 11.4 % versus 14.3 % ) , 5-year patient survival ( 77.3 % versus 87.8 % ) , graft function , or postoperative renal function . One patient in the TMG- group underwent retransplantation . There was no difference between groups with respect to the incidence of medical complications , excepted for a higher rate of leukopenia in the TMG+ group , during the 5-year follow-up . In conclusion , the results of this prospect i ve r and omized study suggest that the addition of TMG to a triple immunosuppressive regimen ( Tac , MMF , and steroids ) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates Background Induction immunosuppression with anti-thymocyte globulin ( ATG ) provides potential benefits after liver transplantation ( LT ) . However , its use in patients with LT and hepatitis C ( HCV ) is controversial . Aim To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression ( IPI ) after LT . Methods A total of 49 patients undergoing their first LT for HCV were r and omized to receive ATG during IPI . Patient survival and HCV recurrence were determined at 1 and 2 years . The frequency of acute cellular rejection ( ACR ) , infections , and neoplasms was also evaluated . Results Twenty-six patients were r and omized to receive ATG ( Arm-1 ) and 23 to st and ard induction therapy ( Arm-2 ) . Those given ATG had lower HCV recurrence ( 26.9 vs 73.9 % , p = 0.001 ) . The 1- and 2-year patient survival rates were similar for both arms ( p = 0.33 ) . Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 ( p = 0.562 ) . There was a greater proportion of fungal infections in Arm-1 ( 19.2 vs 0 % , p = 0.032 ) . Conclusions ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT . This , however , did not affect the 1- and 2-year survival and the frequency of ACR , infections , or neoplasms The aim of this prospect i ve r and omized trial was to study the efficacy and safety of tacrolimus monotherapy ( TACRO ) and compare it with our st and ard treatment of tacrolimus plus steroids ( TACRO + ST ) after liver transplant ( LT ) . Furthermore , the impact of steroid-free immunosuppression on outcome of hepatitis C virus ( HCV ) was analysed . Between 1998 and 2000 , 60 patients ( mean age : 57 years ) were included in the study and r and omized to receive TACRO ( n = 28 ) or TACRO + ST ( n = 32 ) . Indication for LT was postnecrotic cirrhosis in all cases ( 58.3 % were HCV-positive ) . Mean follow-up was 44 months . Survival , incidence of rejection , infection and side-effects were compared between the two groups . In patients with HCV infection , incidence and severity of acute hepatitis C , long-term outcome of recurrent hepatitis C and survival were studied in an intention-to-treat analysis or in the real group analysis ( real-TACRO versus real-TACRO + ST ) . Patient survival at 1 , 3 and 5 years , tacrolimus pharmacokinetics , incidence of rejection infections and side-effects were similar . In patients with HCV , the incidence and severity of graft hepatitis C tended to be lower in TACRO ( 47 % ) compared with TACRO + ST ( 67 % ) ( P = NS ) , and also in real-TACRO ( 42 % ) compared with real-TACRO + ST ( 61 % ) ( P = NS ) . A poor outcome considered as evolution to cirrhosis at 3 years was observed in one ( 9 % ) living patient in real-TACRO and nine ( 45 % ) in real-TACRO + ST ( P = 0.04 ) . Patient survival at 1 , 3 and 5 years was 92 % , 92 % and 73 % for real-TACRO and 78 % , 61 % and 51 % for real TACRO + ST ( P = 0.07 ) . Steroid-free immunosuppression appears to be safe and efficacious . The main advantage of this regimen could be in HCV patients , as recurrence of hepatitis in the graft was less severe in the group of patients in whom steroids could be avoided completely This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients . Patients were r and omized ( N = 260 ) to one of the following immunosuppressive regimens : ( i ) basiliximab + belatacept high dose [ HD ] + mycophenolate mofetil ( MMF ) , ( ii ) belatacept HD + MMF , ( iii ) belatacept low dose [ LD ] + MMF , ( iv ) tacrolimus + MMF , or ( v ) tacrolimus alone . All received corticosteroids . Demographic characteristics were similar among groups . The proportion of patients who met the primary end point ( composite of acute rejection , graft loss , death by month 6 ) was higher in the belatacept groups ( 42–48 % ) versus tacrolimus groups ( 15–38 % ) , with the highest number of deaths and grafts losses in the belatacept LD group . By month 12 , the proportion surviving with a functioning graft was higher with tacrolimus + MMF ( 93 % ) and lower with belatacept LD ( 67 % ) versus other groups ( 90 % : basiliximab + belatacept HD ; 83 % : belatacept HD ; 88 % : tacrolimus ) . Mean calculated GFR was 15–34 mL/min higher in belatacept‐treated patients at 1 year . Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept‐treated patients . Follow‐up beyond month 12 revealed an increase in death and graft loss in another belatacept group ( belatacept HD ) , after which the study was terminated Allograft reinfection with hepatitis C virus ( HCV ) occurs universally in liver transplant recipients . Corticosteroids can contribute to HCV recurrence . This r and omized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression . All patients received tacrolimus ( TAC ) at an initial dose of 0.10–0.15 mg/kg . The steroid-free arm ( TAC/daclizumab ( TAC/DAC , n = 67 ) ) received daclizumab induction , and the steroid arm ( TAC/steroid ( TAC/STR , n = 68 ) ) received a steroid bolus ( ≤ 500 mg ) followed by 15–20 mg/day with discontinuation after month 3 . Median HCV viral load at month 12 , the primary endpoint , was similar at 5.46 ( 0.95–6.54 ) IU/mL with TAC/DAC and 5.91 ( 0.95–6.89 ) IU/mL with TAC/STR . Small numerical differences in the estimated rate of freedom from HCV recurrence ( 19.1 versus 13.8 % ) and freedom from biopsy proven rejection ( 78.4 versus 66.1 % ) were observed between TAC/DAC and TAC/STR . Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR ( 83.1 versus 95.5 % ; 95 % CI , −0.227 to −0.019 % ) , and graft survival was numerically lower ( 80.1 versus 91.1 % , P = NS ) . Completion rates ( 45 versus 82 % ) indicated poorer tolerability with TAC/DAC than with TAC/STR . Steroid-free immunosuppression had no real impact on HCV viral load . HCV recurrence was higher with TAC/STR . Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm DIAMOND : multicenter , 24‐week , r and omized trial investigating the effect of different once‐daily , prolonged‐release tacrolimus dosing regimens on renal function after de novo liver transplantation . Arm 1 : prolonged‐release tacrolimus ( initial dose 0.2mg/kg/day ) ; Arm 2 : prolonged‐release tacrolimus ( 0.15–0.175mg/kg/day ) plus basiliximab ; Arm 3 : prolonged‐release tacrolimus ( 0.2mg/kg/day delayed until Day 5 ) plus basiliximab . All patients received MMF plus a bolus of corticosteroid ( no maintenance steroids ) . Primary endpoint : eGFR ( MDRD4 ) at Week 24 . Secondary endpoints : composite efficacy failure , BCAR and AEs . Baseline characteristics were comparable . Tacrolimus trough levels were readily achieved posttransplant ; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3 . eGFR ( MDRD4 ) was higher in Arms 2 and 3 versus 1 ( p = 0.001 , p = 0.047 ) . Kaplan – Meier estimates of composite efficacy failure‐free survival were 72.0 % , 77.6 % , 73.9 % in Arms 1–3 . BCAR incidence was significantly lower in Arm 2 versus 1 and 3 ( p = 0.016 , p = 0.039 ) . AEs were comparable . Prolonged‐release tacrolimus ( 0.15–0.175mg/kg/day ) immediately posttransplant plus basiliximab and MMF ( without maintenance corticosteroids ) was associated with lower tacrolimus exposure , and significantly reduced renal function impairment and BCAR incidence versus prolonged‐release tacrolimus ( 0.2mg/kg/day ) administered immediately posttransplant . Delayed higher‐dose prolonged‐release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration , but BCAR incidence was comparable A multicenter r and omized trial was performed to compare two immunosuppressive protocol s after first ABO-compatible liver transplantation . Forty six patients were r and omized to a 14-day treatment with Orthoclone ( OKT3 ) in association with steroids and azathioprine , cyclosporine being progressively introduced on day 11 posttransplant . Fifty patients were r and omized to a st and ard protocol of cyclosporine with steroids and azathioprine . Minimum follow-up was 1 year and graft and patient survivals were up date d for the purpose of the study . The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group ( 75 % ) than in the OKT3 group ( 67 % ) , especially when patients who did not receive full-course treatment with OKT3 were excluded ( 59 % ) . Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter . The incidence of severe infections was lower in the OKT3 group ( 13.6 % ) than in the cyclosporine group ( 32 % ) . The 4-year incidences of patient and graft survival in the OKT3 group ( 69 % and 61 % , respectively ) were not different from those in the cyclosporine group ( 62 % versus 54 % , respectively ) . Thus this prospect i ve trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft Background : Minimal immunosuppression ( IS ) is desirable in organ transplantation to reduce side effects and to promote the process of tolerance induction . Material and Methods : Between February 2000 and September 2004 , 156 adults ( > 15 years old ) receiving a primary liver graft were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled , investigator-driven single-center study comparing tacrolimus (TAC)-placebo ( PL ) and TAC-low-dose , short-term ( 64 days ) steroid ( ST ) IS . There were no exclusion criteria at moment of r and omization . All patients had a 12-month follow-up ( range , 12–84 ) . Results : Three- and 12-month patient survival rates were 93.6 % and 87.2 % in the TAC-PL group and 98.7 % and 94.7 % in TAC-ST group ( P = 0.096 and P = 0.093 , respectively ) . Three- and 12-month graft survival rates were 92.3 % and 85.9 % versus 97.4 % and 92.3 % ( P = 0.14 and 0.13 , respectively ) . By 3 and 12 months , rejection treatment had been given in 20.5 % ( 16 pts ) and 23 % ( 18 pts ) of TAC-PL patients and in 12.7 % ( 10 pts ) and 20.5 % ( 16 pts ) of TAC-ST patients ( P = 0.20 and 0.54 ) . Corticosteroid-resistant rejection ( CRR ) at 3 and 12 months was recorded in 12.8 % ( 10 pts ) of TAC-PL patients and 3.8 % ( 3 pts ) of TAC-ST patients ( P = 0.04 ) . When considering the 145 patients transplanted without artificial organ support ( n = 145 ) , CRR at 3 and 12 months was recorded in 8.8 % ( 6/68 pts ) of TAC-PL patients and in 3.9 % ( 3/77 pts ) of TAC-ST patients ( P = 0.22 ) . Vanishing bile duct syndrome was diagnosed in 1 ( 1.2 % ) TAC-PL patient and 4 ( 5.1 % ) TAC-ST patients ( P = 0.17 ) . By 1 year , 78.2 % ( 61/78 ) of TAC-PL patients and 82 % ( 64/78 ) of TAC-ST patients were on TAC monotherapy ( P = 0.54 ) . When considering 67 TAC-PL and 74 TAC-ST survivors , rates of monotherapy were 91 % ( 61 pts ) and 86.5 % ( 64 pts ) ( P = 0.39 ) . At 1 year , 62.5 % ( 42 pts ) of TAC-PL survivors and 64.9 % ( 48 pts ) of TAC-ST survivors were on low-dosage ( < 6 ng/mL ) TAC monotherapy ( P 0.79 ) . Conclusion : TAC monotherapy can be achieved safely without compromising graft nor patient survival in a primary , even unselected , adult liver transplant population . The higher incidence of early CRR in the TAC-PL group related to the significantly higher number of patients transplanted while being on artificial organ support . In such condition , this monodrug immunosuppressive strategy needs to be adapted . TAC monotherapy strategy should lay the basis for further large scale minimization studies in liver transplantation Background . Hepatitis C virus ( HCV ) recurrence in HCV+ liver transplant recipients is almost inevitable and may be promoted by immunosuppression . We compared the amount of liver damage with regard to usage of steroids and basiliximab . Methods . A total of 140 HCV+ adult liver transplant recipients were r and omly allocated to basiliximab+steroids or basiliximab+placebo ( plus cyclosporine and azathioprine ) . Primary endpoint : hepatitis C histological recurrence ( liver damage as for Ishak grading score ≥8 by biopsy at 12 months ) ; secondary endpoints : treatment failure ( death , graft loss , patient withdrawal ) , biopsy proven acute rejection ( BPAR ) , treated acute rejection ( tAR ) , allograft and patient survival rates at 12 months . Results . Any significant difference has been observed in the 12-month hepatitis C histological recurrence rate ( 41.2 % basiliximab+steroids , 37.5 % basiliximab+placebo , P=0.354 ) . The treatment failure rate was significantly higher in basiliximab+steroids ( 28.8 % ) than in basiliximab+placebo ( 15.6 % ) , P=0.03 ; the combination test for the evaluation of the joint hypothesis result ed in a borderline nonsignificant overall result ( P=0.059 ) . BPAR rate was significantly lower in the group treated with steroids ( 24.3 % basiliximab+steroids , 39.4 % basiliximab+placebo , P=0.04 ) , while the tAR rate was similar ( 29.7 % basiliximab+steroids and 37.9 % basiliximab+placebo ) . Any significant differences in 1-year graft and patient survival rates have been observed ( 72.9 % and 84.8 % basiliximab+steroids ; 81.5 % and 89.0 % basiliximab+placebo ) . Conclusions . Results suggest that steroid-free therapy is associated with a significantly lower treatment failure rate , although histological recurrence rate of hepatitis C is similar in the two groups . This benefit is not offset by an evident increase in graft rejection rate requiring treatment We report a multicenter , prospect i ve , r and omized , open‐label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients . Adult patients with good renal function undergoing primary liver transplant were r and omized to either : group A ( st and ard‐dose tacrolimus [ target trough levels > 10 ng/mL ] and corticosteroids ; n = 183 ) ; group B ( mycophenolate mofetil [ MMF ] 2g/day , reduced‐dose tacrolimus [ target trough levels ≤8 ng/mL ] , and corticosteroids ; n = 170 ) ; group C ( daclizumab induction , MMF , reduced‐dose tacrolimus delayed until the fifth day posttransplant and corticosteroids , n = 172 ) . The primary endpoint was change from baseline in estimated glomerular filtration rate ( eGFR ) at 52 weeks . The eGFR decreased by 23.61 , 21.22 and 13.63 mL/min in groups A , B and C , respectively ( A vs C , p = 0.012 ; A vs B , p = 0.199 ) . Renal dialysis was required less frequently in group C versus group A ( 4.2 % vs. 9.9 % ; p = 0.037 ) . Biopsy‐proven acute rejection rates were 27.6 % , 29.2 % and 19.0 % , respectively . Patient and graft survival was similar . In conclusion , daclizumab induction , MMF , corticosteroids and delayed reduced‐dose tacrolimus was associated with less nephrotoxicity than therapy with st and ard‐dose tacrolimus and corticosteroids without compromising efficacy or tolerability This open , r and omized ( 1 : 1 ) , multicenter , 3-month study compared a dual tacrolimus plus steroids ( Tac / steroids ) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy ( Tac / Dac ) in adult liver transplant recipients . The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group . Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups ; mean whole-blood trough levels during month 3 were 10.9 ng/mL ( Tac / steroids ) and 10.6 ng/mL ( Tac / Dac ) . The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups : 26.5 % in the Tac / steroids group and 25.4 % in the Tac / Dac group ( P = .727 ) . However , the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group ( 6.3 vs. 2.8 % ; P = .027 ) . Kaplan-Meier estimates of graft survival ( 92.2 vs. 90.5 % ) and patient survival ( 94.5 vs. 93.7 % ) were similar in both groups . While also the overall adverse event profiles were similar , the incidences of diabetes mellitus ( 15.3 vs. 5.7 % , respectively ; P < .001 ) and cytomegalovirus infection ( 11.5 vs. 5.1 % , respectively ; P = .002 ) were higher in the Tac / steroids group compared with the Tac / Dac group . Mean cholesterol levels increased by 16 % in the Tac / steroids group , but were unchanged in the Tac / Dac group during the study . In conclusion , tacrolimus monotherapy following daclizumab induction is an effective and safe regimen , with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection , and a lower incidence of steroid-resistant acute rejection Background . The administration of alemtuzumab ( Campath-1H [ C1H ] ; Berlex Laboratories , Montville , NJ ) at transplantation prevents a vigorous immune response and is believed to allow a gradual engagement of the host immune system . We report our preliminary experience with C1H and tacrolimus ( Tac ) immunosuppression in adult liver transplantation . Methods . We administered C1H and low-dose Tac to 40 adult recipients of cadaveric liver allografts between December 2001 and April 2003 . A control group who met the same eligibility criteria consisted of 50 liver transplant recipients treated with our st and ard Tac and steroids protocol . Results . Baseline characteristics and patient and graft survival were similar ( P > 0.15 ) . The incidence of acute rejection was significantly lower during the first 2 months posttransplantation ( P = 0.002 ) and slightly lower overall in the study group versus the control group at 12 months ( 46 % vs. 55 % , P = 0.12 , log-rank test ) . Median time to rejection among those experiencing rejection was significantly longer in the study group versus control group ( 2.76 vs. 0.34 months , P = 0.0007 ) . The mean Tac dose , 12-hr trough level , and percentage of patients receiving maintenance steroids were significantly lower in the group receiving C1H and Tac ( P < 0.0001 during the first 3 months , P < 0.05 thereafter ) , as were the mean creatinine levels ( P < 0.05 ) and incidence of nephrotoxicity ( P = 0.004 , conversion from Tac to other agents ) . Finally , in the group receiving C1H/Tac , patients with an average Tac trough level less than 6.5 ng/mL during the first 2 months post-transplantation demonstrated a significantly higher rejection rate beyond that time ( P = 0.02 ) . Conclusion . C1H and low-dose Tac seems to be at least as effective as our st and ard Tac and steroids regimen in preventing acute rejection in adult liver allotransplantation with less renal toxicity and less use of maintenance steroids A prospect i ve trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were r and omly divided into three groups according to immunosuppression during the first 10 days post-OLT : triple drug therapy only ( TDIS : cy-closporine , steroids , azathioprine ) ( group I : n=42 ) ; TDIS with a 10-day course of OKT3 ( group II : n=44 ) ; and LO-Tact-1 ( anti-IL-2 receptor mAb ) ( group III : n=43 ) . Biopsy-proved acute rejection ( AR ) was treated using the same biopsy-guided protocol in the 3 groups . One-year patient survival rates were 67 % , 84 % , and 93 % in groups I , II , and III , respectively ( I vs. II , NS ; I vs. III , P=0.001 ; II vs. III , P=0.044 ) . Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection , with OBJECTIVES Steroids are a mainstay of treatment in orthotopic liver transplantation ( OLT ) and are associated with significant morbidity . This trial was conducted to assess the efficacy of steroids avoidance . METHODS Patients undergoing OLT between June 2002 and April 2005 were entered into a prospect i ve , r and omized trial of complete steroids avoidance and followed until November 2011 . Recipients received either st and ard therapy ( n = 50 ) or complete steroids avoidance ( n = 50 ) . Analyses were performed on an intention-to-treat basis . The mean follow-up of all recipients was 2095 ± 117 days . Sixteen ( 32 % ) recipients r and omized to the steroids avoidance group ultimately received steroids for clinical indications . RESULTS Incidences of diabetes and hypertension prior to or after OLT were similar in both groups , as was the incidence of rejection . Patient and graft survival rates at 1 , 3 and 5 years were lower in the steroids avoidance group than in the st and ard therapy group ( patient survival : 1-year , 80 % versus 86 % ; 3-year , 68 % versus 76 % ; 5-year , 60 % versus 72 % ; graft survival : 1-year , 76 % versus 76 % ; 3-year , 64 % versus 74 % ; 5-year , 56 % versus 72 % ) , but the differences were not statistically different . CONCLUSIONS Complete steroids avoidance provides liver transplant recipients with minimal benefit and appears to result in a concerning trend towards decreased graft and recipient survival . The present data support the use of at least a short course of steroids after liver transplantation Abstract : Background : Interventions that minimize hepatic ischemia/reperfusion injury ( IRI ) can exp and the donor organ pool . Thymoglobulin ( TG ) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients . This controlled r and omized trial was design ated to assess the ability of TG to protect against IRI in liver transplant recipients Recurrence of hepatitis C ( HepC ) has been a most difficult dilemma in liver transplantation ( OLT ) because the effects of immunosuppression with steroid , mycophenolate mofetil ( MMF ) calcineurin antagonists , and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain . In this study , we r and omized OLT recipients with HepC into two treatment arms : tacrolimus+daclizumab+MMF ( study arm ) versus tacrolimus+steroids+MMF ( control arm ) . The study arm only received steroids for the treatment of biopsy-proven rejection episodes . Both arms received preemptive anti-viral therapy with Pegasys and ribavirin . The 39 enrolled patients ( among 50 to be enrolled ) have median follow-up of 458 days with 23 patients ( 8 in study arm , 15 in control arm ) having reached 1 year . The incidences of rejection episodes within 0 to 3 months , 3 to 6 months , and 6 to 12 months were ( study vs control ) : 0 % vs 28 % ; 0 % vs 6 % ; and 13 % vs 20 % ; respectively ( P = NS ) . The 1-year protocol biopsies showed advanced fibrosis ( stage 3 or greater ) in 20 % ( 3 of 15 ) of the control arm , but none ( 0 of 7 ) of the study arm ( P = NS ) . We compared anticipated side effects of steroids in the first 3 months ( study vs control ) : hypertension ( 36 % vs 58 % , P = NS ) , PTDM ( 7 % vs 43 % , P = .02 ) , and wound infections ( 14 % vs 37 % , P = NS ) . In conclusion , liver transplant recipients with HepC tolerate a steroid-free protocol . There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy sample s among patients receiving the steroid-free protocol Background . Basiliximab ( B ) , an anti-CD25 monoclonal antibody , may represent an alternative to steroids ( S ) in immunosuppression after liver transplantation ( LTx ) . The aim of this prospect i ve r and omized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx . Methods . Forty-seven adult recipients of LTx were r and omly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7 . Clinical ly suspected acute cellular rejection ( ACR ) was histologically confirmed . Endpoints include ACR , survival , and disease-free survival . Results . In group B ( 26 patients ) , there were seven biopsy-confirmed ACR with an ACR rate of 15.4 % ; in group S ( 21 patients ) , 8 ACR with an ACR rate of 28.6 % ( P = n.s . ) . Cumulative survival at 36 months after transplantation was 84.3 % for group B and 61.0 % for group S. In hepatitis C virus patients ( n=20 : 12 in group B , 8 in group S ) , the ACR rate was 25 % in group B and 50 % in group S. The incidence of infection and other adverse events was similar in the two treatment groups . Conclusions . B may represent a valid alternative to S in the induction of immunosuppression in LTx . Further studies of basiliximab in a large cohort are needed Background . Due to the known high recurrence rate of hepatitis C virus ( HCV ) among orthotopic liver transplant ( OLT ) recipients who receive tacrolimus+corticosteroid maintenance , use of steroid-free induction was considered . Methods . OLT recipients with HCV were r and omized to receive tacrolimus+daclizumab ( steroid-free ) vs. tacrolimus+corticosteroids during 1999–2001 and then tacrolimus+mycophenolate mofetil (MMF)+daclizumab ( steroid-free ) vs. tacrolimus+MMF+corticosteroids during 2002–2005 . Patients in the steroid-free arm of both periods received no steroids except for treating biopsy-proven rejection . Primary objective was to compare mean fibrosis stage at the 1-year protocol biopsy , between the steroid-free and corticosteroid arms , stratifying by period . Results . No noticeable differences in mean fibrosis stage between the two treatment arms , either averaging across periods ( P=0.99 ) or during either period ( P>0.35 ) were found . Occurrence of acute rejection during the first year was the only factor associated with a significantly increased fibrosis stage at 1 year ( P=0.0003 ) ; stage ≥2 was seen in 63 % ( 17 of 27 ) vs. 19 % ( 8 of 43 ) of those with vs. without rejection . In addition , MMF use was associated with significantly fewer patients experiencing acute rejection during the first 6 and 12 months posttransplant ( P=0.006 and 0.046 ) . Regarding steroid-related side effects , posttransplant diabetes mellitus occurred in 10 % vs. 45 % , and wound infection in 6 % vs. 31 % of steroid-free vs. corticosteroid patients ( P=0.003 and 0.01 ) . Conclusions . OLT recipients with HCV tolerated the steroid-free protocol with fewer side effects ; however , its use had no apparent impact on hepatic fibrosis progression . Occurrence of acute rejection was strongly associated with increased hepatic fibrosis at 1 year , and MMF use appears to have significantly reduced the rejection rate BACKGROUND Corticosteroids are commonly used in the immunosuppression therapy after liver transplantation , yet are associated with considerable side effects . Retrospective studies have shown that corticosteroids can be safely withdrawn from months to years after transplant . We prospect ively investigated the effects of early immunosuppression without the use of corticosteroids on graft outcome and transplant complications . METHODS Forty-five patients undergoing liver transplantation were r and omized to receive immunosuppression composed of cyclosporine microemulsion and azathioprine with ( n=22 ) or without prednisone ( n=23 ) , in conventional doses . In those patients who received prednisone , this was withdrawn within 3 months after transplant . The median follow-up of survivors was 14 months ( range : 6 - 24 ) . The study end points were to determine graft survival and function , infectious complications , including hepatitis C virus (HCV)-RNA levels in HCV-infected recipients , acute rejection , kidney function , and metabolic complications . RESULTS Eleven deaths occurred , 6 of which were in the prednisone group . Two-year survival did not differ between patients treated with or without prednisone ( 70.2 % vs. 78.3 % , P=0.83 ) , nor did the causes of death . No differences were observed with regard to graft function , renal function , and infectious complications . In the subset of patients who received transplants for HCV-related cirrhosis , the dynamics of virus replication HCV-RNA was faster among those treated with prednisone . The incidence and severity of acute rejection was similar in the two groups . More than 80 % of acute rejections in both groups were classified as mild or moderate and underwent spontaneous resolution . Only two patients in each group had severe acute rejection requiring additional treatment with high-dose steroids . Patients receiving prednisone tended to have greater biochemical signs of cholestasis , higher serum cholesterol and glucose levels , and more frequent insulin requirement than those treated without corticosteroids . CONCLUSIONS Liver transplantation can be performed safely without using corticosteroids in the early postoperative course , and there is no need for routine aggressive steroid treatment of established acute rejections BACKGROUND In OLT induction therapy with interleukin-2-receptor antibodies is often applied as part of the st and ard immunosuppression protocol . It was the aim of this study to determine if Basilixirnab mduction therapy serves to reduce the incidence of acute rejection episodes and improves graft function and survival in the long term after OLT . MATERIAL / METHODS We prospect ively analysed 99 patients transplanted at our institution ( 1997 - 2000 ) . Patients were r and omised to two study groups : 51 patients received Basiliximab induction combined with Calcineurin inhibitors and steroids , 48 patients received CNIs and steroids only . Incidence and severity of rejection , graft and patient survival and intensity of long-term immunosuppression were analysed . Frequency of CNI and steroid induced adverse effects were recorded . RESULTS In our patient collective we could not detect a significant impact of Basiliximab induction therapy on the fre queny of acute or chronic rejection . CNI levels were almost identical in both groups ; graft and patient survival rates were not influenced by the application of induction therapy . CONCLUSIONS In our patient collective induction therapy does not have a general positive influence on the post transplant course . A slight improvement in long term renal function could be detected for Basiliximab treated patients This study compares the clinical course of recurrent hepatitis C virus ( HCV ) infection between 64 patients , who were r and omized to receive either rabbit antithymocyte globulin ( RATG ) or steroids as induction therapy with tacrolimus for maintenance . The HCV recurrence was assessed by HCV RNA levels , peak ALT at 3–6 months , the grade of inflammation at biopsy at 3–6 months posttransplant , progression of fibrosis , and survival . All patients had also received antiviral therapy with interferon alpha 2b and ribavirin , if there were no contraindications . There was no statistically significant difference between the two groups in terms of inflammation at 3 months , peak ALT , or HCV RNA . The survival between the two groups of patients was similar . It appears that steroid-free liver transplantation with RATG induction does not have any negative influence on HCV recurrence in hepatitis C patients after liver transplantation Posttransplant chronic renal failure , secondary to calcineurin inhibitor agents , is emerging as a major problem in liver transplantation . We report a r and omized clinical trial comparing daclizumab , delayed low-dose tacrolimus ( target trough level 4 - 8 ng/mL , starting day 4 - 6 ) , Investigational Arm ( n = 72 ) , to st and ard tacrolimus induction/maintenance dosing , St and ard Arm ( n = 76 ) , with mycophenolate mofetil and tapering corticosteroids in both study arms . The end-points were renal function indicated by the Modification of Diet in Renal Disease ( MDRD ) . There was no significant difference in patient survival ( 86.6 % Investigational Arm vs. 92.9 % St and ard Arm ; P = 0.21 ) or acute rejection ( 23.2 % vs. 27.7 % , respectively ; P = 0.68 ) . Statistically significant differences in median glomerular filtration rate ( GFR ) were found in favor of the Investigational Arm . With the CG equation , the GFR at the end of the first week was 110.7 vs. 89.6 mL/min ( P = 0.019 ) without significant differences thereafter . With the MDRD , statistically significant differences extended to the first posttransplant month ( 86.8 vs. 70.1 mL/min/1.73 m(2 ) ; P < 0.001 ) with and was seen at month 6 ( 75.4 vs. 69.5 mL/min/1.73 m(2 ) ; P = 0.038 ) . In conclusion , delayed low-dose tacrolimus , in combination with daclizumab and mycophenolate mofetil , preserves early renal function post-liver transplantation without the cost of increased acute rejection BACKGROUND Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients . This controlled r and omized trial was design ed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury . PATIENTS AND METHODS Twenty-two cadaver liver transplant recipients were r and omized to receive either thymoglobulin ( 1.5 mg/kg per dose ) during the anhepatic period and two doses every other day or no thymoglobulin . No differences in recipient or donor demographics were present . Maintenance immunosupression consisted of tacrolimus ( or cyclosporine ) and steroids for both groups . Donor biopsies were obtained during organ procurement , cold storage , and 1 hour after revascularization . Postoperative liver function tests were monitored . Early graft function , length of stay , patient and graft survival rates , incidence of primary nonfunction , and rate of rejection were assessed . RESULTS Patient and graft survival at 3 months was 100 % . There was no incidence of primary graft nonfunction and no need for retransplantation . The incidence of acute rejection was similar between the two groups . Although donor livers r and omized to thymoglobulin had less optimal preimplantation biopsies , these recipients had significant decreases in ALT at day 1 compared to the control group ( P = .02 ) , near significant decreases of total bilirubin at day 5 , and shorter length of hospitalization . CONCLUSION Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection . Steroids also have been held responsible for increased infections , posttransplantation diabetes , and recurrent hepatitis after orthotopic liver transplantation ( OLT ) . The purpose of this ongoing prospect i ve r and omized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin ( RATG ) . This is the first report of a prospect i ve r and omized trial in OLT achieving complete absence of steroids . Seventy-one adult patients were prospect ively r and omized to administration of RATG or steroids . Thirty-six patients were r and omized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously ( IV ) beginning during the anhepatic phase . No steroids were administered . Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1 . Thirty-five patients were r and omized to the administration of methylprednisolone , which had been our st and ard immunosuppressive protocol . These patients were administered methylprednisolone , 1,000 mg IV , initiated during the anhepatic phase and followed by steroid taper . Maintenance immunosuppression consisted of tacrolimus and mycophenolate , with or without prednisone . Three patients died in each group , for an overall survival rate of 91 % in each group . One patient in each group required re-OLT , for a graft survival rate of 89 % in each group . Seven patients administered RATG had biopsy-proven rejection ( 20.5 % ) , all of whom were successfully treated by increasing tacrolimus doses . Eleven patients administered steroid had biopsy-proven rejection ( 32 % ) , 7 ( 64 % ) of whom required additional steroids for treatment , whereas 4 patients ( 36 % ) were successfully treated by increasing tacrolimus doses . The incidence of rejection was not statistically significant ; however , there was a significant difference in the incidence of steroid-requiring rejection ( P = .01 ) . The incidence of recurrent hepatitis C was 50 % in RATG patients and 71 % in steroid patients ( P = not significant ) . The incidence and severity of infectious complications were slightly lower in RATG patients , accounted for by a greater incidence of cytomegalovirus ( CMV ) infection in the steroid patients . RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate , decreased incidence of post-OLT diabetes and recurrent hepatitis C , and decreased CMV infection . This prospect i ve r and omized trial gives encouraging support that steroids can be safely eliminated in OLT Objective : To investigate the safety of minimal immunosuppression ( IS ) in liver transplantation ( LT ) . Background : The lack of long-term follow-up studies , including pathologic data , has led to a protean h and ling of IS in LT . Methods : Between February 2000 and September 2004 , 156 adults were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled minimization trial comparing tacrolimus placebo ( TAC-PLAC ) and TAC short-term steroid ( TAC-STER ) IS . All patients had a minimum clinical , biochemical , and histological follow-up of 5 years . Results : Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1 % and 82.1 % ( P = 0.89 ) and 74.2 % and 76.9 % ( P = 0.90 ) , respectively . Five-year biopsies were available in 112 ( 89.6 % ) of 125 survivors . Twelve patients refused a biopsy because of their excellent evolution ; tissue material was insufficient in 1 patient ; 11 had normal liver tests ; and 2 patients had developed alcoholic and secondary biliary cirrhosis . Histology was normal in 44 ( 39.3 % ) patients ; 35 ( 31.3 % ) had disease recurrence . The remaining biopsies showed nonspecific chronic hepatitis ( 14.3 % ) , mild inflammatory infiltrates ( 10.7 % ) , and steatosis ( 3.5 % ) . All findings were equally distributed between both groups . In each group , 3 patients ( 4.8 % ) presented with acute cellular rejection after the first year and only 1 ( 0.9 % ) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis . Arterial hypertension , diabetes mellitus , renal insufficiency , hypercholesterolemia , gout , and obesity were equally low in both groups . Conclusions : Excellent long-term results can be obtained under minimal IS and absence of steroids . TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up Steroids are a mainstay in liver transplantation for induction and maintenance immunosuppression but are associated with significant adverse effects . While prior studies have successfully limited the use of steroids , whether complete steroid avoidance will improve outcomes remains unclear . To further evaluate the need for steroids , consenting patients who underwent liver transplantation between June 2002 and May 2004 were entered into a prospect i ve , r and omized trial to receive either st and ard therapy ( tacrolimus , mycophenolate mofetil , steroid induction/maintenance ) or complete steroid avoidance ( st and ard therapy without steroid induction/maintenance ) . Clinical ly suspected rejection was confirmed by biopsy and treated with pulse steroid therapy . Outcomes were compared on an intention to treat basis . Of the 72 patients enrolled , 36 ( 50 % ) were r and omized to the steroid avoidance group with a mean follow up of 412 + /- 41 days . Donor and recipient characteristics were similar between groups . The steroid avoidance group was more likely to have significant infections ( 52 % vs 28 % , P = .03 ) . There was a trend toward an increased rate of acute rejection ( 25 % vs 14 % , P = .23 ) . Twelve of 36 recipients ( 33 % ) enrolled in the steroid avoidance group later received steroids . The incidence of recurrent hepatitis C was similar between groups . The 1-year patient ( 90 % vs 83 % , P = .44 ) and graft survivals ( 90 % vs 81 % , P = .27 ) were similar between groups . These data suggest complete steroid avoidance in liver transplantation results in acceptable patient and graft survival . However , the potential long-term benefits of steroid avoidance , including a decrease in severity of recurrent hepatitis C , remain under investigation This work is a 1-yr interim analysis of a prospect i ve , r and omized , multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive ( HCV(+ ) ) liver transplant recipients following liver transplantation ( LT ) . Patients received tacrolimus and corticosteroids ( Arm 1 ; n = 80 ) ; tacrolimus , corticosteroids , and mycophenolate mofetil ( MMF ) ( Arm 2 ; n = 79 ) ; or daclizumab induction , tacrolimus , and MMF ( Arm 3 ; n = 153 ) . At 1 yr , 64.1 % , 63.4 % , and 69.4 % of patients achieved the composite primary endpoint of freedom from rejection , freedom from HCV recurrence , and freedom from treatment failure , respectively . Excellent patient and graft survival did not differ significantly among treatment arms . Freedom from HCV recurrence at 1 yr was 61.8 + /- 6.2 % , 60.1 + /- 6.1 % , and 67.0 + /- 4.3 % in Arms 1 , 2 , and 3 , respectively ( P = not significant ) . Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 ( 93.0 + /- 2.2 % vs. 81.9 + /- 4.4 % ; P = 0.011 ) . Multivariate analysis identified acute rejection ( hazard ratio = 2.692 ; P = 0.001 ) and donor age ( hazard ratio = 1.015 ; P = 0.001 ) as significant risk factors for HCV recurrence . HCV recurrence was not influenced by recipient demographics , HCV genotype , or immunosuppression . In conclusion , these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+ ) liver transplant recipients Background . In 2001 , we published early results of a prospect i ve r and omized trial of 71 patients who received either steroids or rabbit antithymocyte globulin ( RATG ) for orthotopic liver transplantation ( OLT ) . We now report follow-up on these patients and additional patients undergoing steroid-free OLT . Methods . A total of 119 adult OLT recipients were prospect ively r and omized to receive either methylprednisolone 1,000 mg followed by a 3-month steroid taper or a steroid-free regimen of RATG 1.5 mg/kg during the anhepatic phase followed by a 1.5 mg/kg dose on posttransplant day 1 . Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil in both groups . Mycophenolate mofetil was weaned over 3 months in the first 71 patients and over 2 weeks in the last 48 patients , achieving tacrolimus monotherapy by 2 weeks posttransplant . Subsequently , a group of 24 sequential OLT recipients received the steroid-free ( RATG ) protocol . Endpoints of the study were survival , rejection , infectious complications , posttransplant diabetes , and recurrent hepatitis C virus . Results . One-year patient survival was 85 % in each group of the prospect i ve r and omized trial with a mean follow-up of 18.5 months . One-year graft survival was 82 % in the RATG group and 80 % in the steroid group ( P = not significant ) . Patient and graft survival of the 24 nonr and omized RATG patients was 96 % with a mean follow-up of 3 months . The incidence of rejection was not significantly different ; however , 50 % of the patients in the steroid group required pulse steroids to reverse the rejection compared with only one patient ( 1.6 % ) in the RATG group ( P = .03 ) . The incidence of cytomegalovirus infection ( P < .05 ) and posttransplant diabetes was higher in the steroid group ( P = .03 ) . There was a trend toward decreased severity of hepatitis C virus in the RATG group . Conclusions . Steroid-free liver transplantation using RATG and early tacrolimus monotherapy effectively reduces immunosuppression-related complications with excellent survival Background We conducted a r and omized multicenter open-label trial in de novo liver transplant recipients to assess the feasibility and potential benefit of a corticosteroid (CS)-free regimen coupled with tacrolimus ( Tac ) and dose-intensified mycophenolate mofetil ( MMF ) further adjusted individually . Methods Adult liver transplant recipients were r and omized on the day of transplantation to a CS-free regimen with Tac and MMF starting at 3 g/d and dose adjusted from day 5 according to mycophenolic acid ( MPA ) exposure ( arm A ) or a regimen with CS maintained up to 6 months , Tac and fixed-dose MMF ( 2 g/d ) ( arm B ) . The primary end point was the proportion of patients who experienced treated biopsy-proven acute rejection ( BPAR ) during the first year posttransplant . Results One hundred eighty-seven patients were r and omized , and 174 comprised the per- protocol population ( 87 in each arm ) . The primary objective of noninferiority was met : 7 patients in arm A ( 8 % ) and 8 in arm B ( 9 % ) experienced treated BPAR in the first year . Two patients in arm A ( 2 % ) and 5 in arm B ( 6 % ) lost their graft , and 12-month patient survival was similar in both arms ( 90.8 % vs 89.8 % ; P = 0.86 ) . Adverse events were comparable between arms , except for a lower incidence of de novo diabetes ( 19.8 % vs 32.6 % , P = 0.049 ) and a higher incidence of leukopenia less than 2000/mm3 ( 28.6 % vs 9.8 % ; P = 0.001 ) and neutropenia ( 26.7 % vs 7.9 % ; P < 0.001 ) in arm A. Conclusions Mycophenolate mofetil at intensified and individually adjusted dose in combination with Tac in de novo liver transplant recipients allows CS discontinuation from day 1 posttransplant with good tolerance and very low rejection incidence Previous human studies in renal transplant recipients have shown a lower incidence of acute rejection and cyclosporine-associated acute nephrotoxicity when prostagl and ins are administered in conjunction with st and ard immunosuppressants . This study evaluates the effects of enisoprost ( EP ) , a synthetic PGE methyl ester analog , in a single-center , prospect i ve , r and omized , double-blind , placebo-controlled , parallel group trial in 81 consecutive adult patients undergoing orthotopic liver transplantation ( OLT ) . The subjects received EP 100 mg p.o . t.i.d . ( n=40 ) or placebo ( n=41 ) for the first 12 weeks after OLT . Immunosuppression was based on cyclosporine , azathioprine , and corticosteroids . Effective renal plasma flow and glomerular filtration rate were determined at 4 and 12 weeks after OLT . Eighty-one patients entered the study ; sixty-six patients completed the 16-week study period . There were no statistically significant differences between EP- and placebo-treated groups at 12 weeks for creatinine clearance , glomerular filtration rate , and effective renal plasma flow . At least 1 episode of cyclosporine nephrotoxicity occurred in 7/40 patients ( 17.5 % ) in the EP group compared with 9/41 patients ( 20.0 % ) in the placebo group ( P=0.781 ) . There was no significant difference in the incidence of graft rejection episodes in the 2 groups . Enisoprost , as used in this study , does not have any beneficial effect on renal function or incidence of rejection in OLT recipients BACKGROUND Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation . However , the use of polyclonal antibody preparations ( e.g. antithymocyte globulin [ ATG ] ) is associated with side effects such as fever and tachycardia . To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor ( BT563 ) in comparison with ATG as part of a quadruple induction regimen , a prospect i ve , r and omized study was conducted . METHODS Eighty consecutive adult recipients of primary orthotopic liver transplants were r and omized to receive either BT563 ( 10 mg/day ; days 0 - 12 ; n=39 ) or ATG ( 5 mg/kg/day ; days 0 - 6 ; n=41 ) in addition to the st and ard immunosuppressive protocol consisting of cyclosporine , and prednisolone , and azathioprine . RESULTS Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes ( 3 vs. 11 ; P<0.025 ) and also significantly fewer drug-related side effects ( 4 vs. 18 , P<0.038 ) when compared with patients treated with ATG . The incidence of infectious complications was not different between the two groups . Patient survival did not differ significantly between the two groups ( 84.6 % at 1 , 2 , and 3 years in the BT563 group and 90.2 % at 1 year and 87.8 % at 2 and 3 years for the ATG group ) . Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels . However , no differences were observed in long-term follow-up between the two groups . CONCLUSIONS Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG BACKGROUND Corticosteroids have long been a cornerstone of orthotopic liver transplant ( OLTx ) immunosuppression . Newer , more potent , agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients . We hypothesize that corticosteroids can be safely avoided after the first postoperative day ( POD ) using these newer agents . METHODS Thirty adult OLTx recipients were prospect ively enrolled in a r and omized open-label , institutional review board-approved protocol . Fifteen patients ( group A ) received our st and ard regimen of tacrolimus , mycophenolate mofetil , and corticosteroids , and 15 patients ( group B ) received daclizumab , 2 mg/kg on POD 0 and 14 , with tacrolimus , mycophenolate mofetil , and corticosteroids on POD 0 and 1 and then discontinuation . In both groups , mycophenolate mofetil was tapered off between 3 and 4 months after OLTx . Bone mineral densitometry was performed at 1 , 3 , and 6 months after OLTx . Quantitative hepatitis C virus ( HCV ) polymerase chain reaction was obtained at days 0 , 7 , 14 , 21 , and 28 . Retransplant recipients , patients with autoimmune hepatitis , or status 1 or 2A patients were excluded . RESULTS Patient and graft survival rates were 93 % ( group A ) and 100 % ( group B ) with mean follow-up of 18 months . Patients in group B had more rejection diagnosed ( 25 % ) compared with group A ( 6.7 % ) . Yet , the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7 % in both groups . Hispanic race was common in groups A and B ( 87 % and 74 % ) . A total of six biopsies were performed in group B , with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids . One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function . No patient in either group developed a requirement for additional antihypertensive medication . Likewise , there were no patients with new-onset diabetes . The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance . Serum cholesterol level was significantly ( P=0.03 ) lower in group B at 6 months after OLTx . Serum triglycerides were also lower , but the difference was not significant . Quantitative polymerase chain reaction for HCV-positive patients ( group A , n=7 ; group B , n=8 ) frequently increased after OLTx . There was no correlative decrease associated with daclizumab . At present , two patients in group A have documented HCV recurrence . CONCLUSION Corticosteroids can be safely avoided after POD 1 with the current regimen . With early follow-up , there is no difference in hypertension or diabetes or bone density . Lipid panels tended to be lower in patients who were not on corticosteroids . Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension , diabetes , and possibly HCV recurrence The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus ( HCV ) recurrence . A total of 198 liver transplantation ( LT ) patients were r and omized to receive immunosuppression with basiliximab and cyclosporine , either with prednisone ( steroid [ St ] group ) or without prednisone ( no steroids [ NoSt ] group ) . The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT . This group of HCV patients are the patients evaluated in the present study . The rejection rate was 19 % ( St : 21 % versus NoSt : 17 % ; P = 0.67 ) . Patients in the St group had a slightly higher rate of bacterial infections ( 59 % versus 38 % ; P = 0.05 ) . Almost all patients had histological HCV-recurrence ( St : 39/40 ( 97 % ) versus NoSt : 40/41 ( 97 % ) ; P = 1 ) . The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months , 1 year , and 2 years were , 23 % , 49 % , and 49 % in the NoSt group , compared to 33 % , 55 % , and 69 % in the St group , respectively ( P = 0.04 at 2 years ) . The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months , 1 year , and 2 years were 0 % , 8 % , and 22 % in the NoSt group , compared to 8 % , 19 % , and 31 % in the St group , respectively . Immunosuppression without steroids in HCV patients is safe , reduces bacterial infections and metabolic complications , and improves histological short-term evolution of HCV recurrence Objective : The aim of the study is to evaluate whether intra-operative induction with anti-lymphocytic serum ( ALS ) is superior to no induction in adult liver transplantation ( LT ) . Background : The efficacy of ALS induction remains inconclusive in LT , because of poorly design ed trials . Methods : A r and omized controlled trial was conducted , including 206 adults ( > 15 years ) and comparing tacrolimus monotherapy ( TAC , n = 109 ) and tacrolimus plus a single , intraoperative , high-dose ( 9 mg/kg ) , rabbit anti-T-lymphocyte globulins ( ATLG ; n = 97 ) . All patients had similar follow-up , including Banff-scored biopsies . Rejection was considered clinical ly relevant and treated if pathologic and biochemical changes were concordant . The primary endpoint was immunosuppression minimization to monotherapy ; secondary endpoints were biopsy-proven rejection , clinical rejection , patient ( PS ) and graft ( GS ) survival . Results : At 1 year , 79/81 ( 96.3 % ) ATLG and 101/102 ( 99.0 % ) TAC patients were steroid-free ( P = 0.585 ) ; 28 ( 34.6 % ) ATLG , and 31 ( 30.4 % ) TAC patients were on double-drug immunosuppression ( P = 0.633 ) . One-year PS and GS of ATLG and TAC patients were 84 % and 92 % ( P = 0.260 ) and 76 % and 90 % ( P = 0.054 ) . Despite significantly a fewer day-7 moderate-to-severe acute cellular rejections ( ACR ) in ATLG group ( 10.0 % vs 24.0 % in TAC group , P = 0.019 ) , cumulative proportion of patients experiencing steroid-sensitive ( 11.3 % ATLG vs 14.7 % TAC , P = 0.539 ) , steroid-resistant ( 2.1 % ATLG vs 3.7 % TAC , P = 0.686 ) and chronic rejection ( 1.0 % ATLG vs 0.9 % TAC , P = 1.000 ) were similar . ATLG administration brought about greater hemodynamic instability and blood products use ( P = 0.001 ) . Conclusions : At 1 year from LT , ATLG induction did not significantly affect immunosuppressive load , treated rejection , patient , and graft survival . The observed adverse events justify a modification of dosing and timing of ATLG infusion . Long-term results are required to judge the ATLG possible benefits on immunosuppressive load and tolerance induction Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
13,006 | 25,774,157 | Models showed that the irradiated cercariae vaccine has the potential to achieve protection as high as 78 % with a single dose vaccination .
This declines slowly over time but remains high for at least 8 months after the last immunization . | Schistosomiasis is a water-borne , parasitic disease of major public health importance .
There has been considerable effort for several decades toward the development of a vaccine against the disease .
Numerous mouse experimental studies using attenuated Schistosoma mansoni parasites for vaccination have been published since 1960s .
However , to date , there has been no systematic review or meta- analysis of these data .
The aim of this study is to identify measurable experimental conditions that affect the level of protection against re-infection with S. mansoni in mice vaccinated with radiation attenuated cercariae . | Background Atypical antipsychotics are widely used in the treatment of bipolar disorders . Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia , major depressive disorder and , more recently , acute mania . At the moment , however , no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders . The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with st and ard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing st and ard therapies . Methods The study enrolled fourteen bipolar I out patients , not responding to ongoing st and ard therapy . Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before ( range 3–24 months ) and 5.2 ± 2.7 months after the introduction of amisulpride ( range 3–9 months ) . Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version ( CGI-BP ) score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization . Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride . The relative risk of relapse in the absence of amisulpride therapy was 3.1 ( χ2 = 4.2 , P < 0.05 ) . Similarly , the rates of manic/mixed and depressive relapse were decreased but only manic episodes reached statistical significance ( RR = 5.3 , χ2 = 5.2 , P < 0.02 ) . Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses . Large , r and omized , double-blind , placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to st and ard therapies for bipolar disorder BACKGROUND During 1990 and 1991 a survey of immunity was carried out in Sweden . The main purpose was to estimate the level of immunity to diphtheria , tetanus and polio in the adult population . In total , 4800 people , r and omly selected according to a stratified , two-stage , sampling plan , were contacted and asked to contribute a blood sample . Of those selected , 70.6 % gave a blood sample . METHODS Estimates and confidence intervals of the proportion of the population with antibodies exceeding some titre was calculated . The population was divided according to sex , year of birth ( five age groups ) and residence ( four regions ) . RESULTS In age groups that were born after the introduction of childhood vaccination , > or = 90 % and 75 - 90 % of people have demonstrable antibodies at a protective level against tetanus and diphtheria respectively . Those born earlier , especially women , are poorly protected with less than 50 % having protective antibody levels for both tetanus and diphtheria . Differences between men and women were particularly seen in the age groups born between 1930 and 1950 . Less than 5 % of the Swedish population lacked the protective level antibodies against polio types 1 , 2 and 3 respectively . CONCLUSIONS Vaccination against tetanus , which can be combined with vaccination against diphtheria , can be recommended especially to women born before 1950 and with no documented previous vaccination . The same recommendation can be given for men born before the 1930s . As regards poliomyelitis , general booster vaccination of the adult population does not appear to be necessary at present Background Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment . Therefore , therapeutic vaccines represent an attractive alternative control strategy . The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium ( rSh28GST ) in healthy volunteers , and to determine its immunogenicity . Methodology Volunteers r and omly received 100 µg rSh28GST together with aluminium hydroxide ( Alum ) as adjuvant ( n = 8) , or Alum alone as a comparator ( n = 8) , twice with a 28-day interval between doses . A third dose of rSh28GST or Alum alone was administered to this group at day 150 . In view of the results obtained , another group of healthy volunteers ( n = 8) received two doses of 300 µg of rSh28GST , again with a 28-day interval . A six-month follow-up was performed with both clinical and biological evaluations . Immunogenicity of the vaccine c and i date was evaluated in terms of specific antibody production , the capacity of sera to inhibit enzymatic activity of the antigen , and in vitro cytokine production . Principal Findings Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration . Four subjects under rSh28GST reported mild reactions at the injection site while a clinical ly insignificant increase in bilirubin was observed in 8/24 subjects . No hematological nor biochemical evidence of toxicity was detected . Immunological analysis showed that rSh28GST was immunogenic . The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST . Conclusions rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response . Together with previous pre clinical results , the data of safety , tolerability and quality of the specific immune response provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine c and i date against urinary schistosomiasis BACKGROUND The current recommended control strategy for schistosomiasis is annual treatment using 40 mg/kg of praziquantel . However , praziquantel is only effective on adult worms and giving a second dose may increase its efficacy . We assessed the effect of one versus two doses of praziquantel on cure rate and re-infection with Schistosoma mansoni in a high endemic community along Lake Victoria , Ug and a. METHODOLOGY To investigate the effect of the two regimens , 395 infected people were r and omised into two groups ; one received a single st and ard dose of praziquantel ( Distocide ® 600 mg , Shin Poong Pharmaceuticals , Seoul , Republic of Korea ) , 40mg/kg body weight , while the other group received a second dose 2 weeks later . Cure rate and infection intensity were assessed 9 weeks after the first treatment using st and ard parasitological procedures . Re-infection levels were monitored 8 and 24 months after treatment . RESULTS Those who received two doses were more likely to be cured ( 69.7 % ) compared to those who received a single dose ( 47.9 % ) ( χ(2 ) = 18.5 , p < 0.001 ) . Geometric mean intensity ( GMI ) of infection at 9 weeks ( eggs per gram of faeces [ epg ] ) was 12.0 epg ( CI95 : 8.9 - 16.1 ) for individuals who received 2 doses and 22.1 epg ( CI95 : 16.9 - 28.8 ) for those in the single dose arm . Eight months after treatment , prevalence of re-infection for individuals in the double dose arm ( 61.6 % , CI95 : 50.2 - 73.1 ) was not significantly different from that of those in a single dose arm ( 68.3 % , CI95 : 59.9 - 76.8 ) . The difference in GMI of re-infection for individuals in the single dose arm ( 33.8 epg , CI95 : 23.2 - 49.3 ) and those in the double dose arm ( 34.5 epg , CI95 : 24.7 - 48.1 ) was not significant . Twenty four months after treatment , prevalence of re-infection was not significantly different . The difference in GMI of re-infection for those in the single dose arm ( 57.5 epg , CI95 : 33.9 - 97.5 ) and those in the double dose arm ( 42.2 epg , CI95 : 29.9 - 59.6 ) was also insignificant . CONCLUSION Our results suggest that a second dose of praziquantel given 2 weeks after the first dose improves cure rate and reduces S. mansoni infection intensity . However , there is no added advantage on reduction of S. mansoni re-infection by administering two doses of praziquantel . CLINICAL TRIALS.GOV IDENTIFIER : NCT00215267 Malaria Sporozoite Vaccine Each year , hundreds of millions of people are infected with Plasmodium falciparum , the mosquito-borne parasite that causes malaria . A preventative vaccine is greatly needed . Seder et al. ( p. 1359 , published online 8 August ; see the Perspective by Good ) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole , attenuated sporozoite vaccine . Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection . Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received , suggesting that both arms of the adaptive immune response may have participated in the observed protection . Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial . [ Also see Perspective by Good ] Consistent , high-level , vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum ( Pf ) sporozoites ( SPZ ) by mosquito bites . We report that the PfSPZ Vaccine — composed of attenuated , aseptic , purified , cryopreserved PfSPZ — was safe and wel-tolerated when administered four to six times intravenously ( IV ) to 40 adults . Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection ( P = 0.015 in the five-dose group and P = 0.028 for overall , both versus controls ) . PfSPZ-specific antibody and T cell responses were dose-dependent . These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory st and ards BACKGROUND We have shown that immunity to infection with Plasmodium falciparum can be induced experimentally in malaria-naive volunteers through immunisation by bites of infected mosquitoes while simultaneously preventing disease with chloroquine prophylaxis . This immunity was associated with parasite-specific production of interferon γ and interleukin 2 by pluripotent effector memory cells in vitro . We aim to explore the persistence of protection and immune responses in the same volunteers . METHODS In an open-label study at the Radboud University Nijmegen Medical Centre ( Nijmegen , Netherl and s ) , from November to December , 2009 , we rechallenged previously immune volunteers ( 28 months after immunisation ) with the bites of five mosquitoes infected with P falciparum . Newly recruited malaria-naive volunteers served as infection controls . Our primary outcome was the detection of blood-stage parasitaemia by microscopy . We assessed the kinetics of parasitaemia with real-time quantitative PCR ( rtPCR ) and recorded clinical signs and symptoms . In-vitro production of interferon γ and interleukin 2 by effector memory T cells was studied after stimulation with sporozoites and red blood cells infected with P falciparum . Differences in cellular immune responses between the study groups were assessed with the Mann-Whitney test . This study is registered with Clinical Trials.gov , number NCT00757887 . FINDINGS Four of six immune volunteers were microscopically negative after rechallenge . rtPCR-based detection of blood-stage parasites in these individuals was negative throughout follow-up . Patent parasitaemia was delayed in the remaining two immunised volunteers . In-vitro assays showed the long-term persistence of parasite-specific pluripotent effector memory T-cell responses in protected volunteers . The four protected volunteers reported several mild to moderate adverse events , of which the most commonly reported symptom was headache ( one to three episodes per volunteer ) . The two patients with delayed patency had adverse events similar to those in the control group . INTERPRETATION Artificially induced immunity lasts longer than generally recorded after natural exposure ; providing a new avenue of research into the mechanisms of malaria immunity . FUNDING Dioraphte Foundation The efficacy of a sporozoite-based malaria vaccine is tested in humans , nonhuman primates , and mice . Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum ( Pf ) malaria in ≥80 % of recipients . Pf sporozoites ( PfSPZ ) administered by mosquito bites are the only immunogens shown to induce such protection in humans . Such protection is thought to be mediated by CD8 + T cells in the liver that secrete interferon-γ ( IFN-γ ) . We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe , but suboptimally immunogenic and protective . Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8 + , IFN-γ – producing T cells in the liver ( nonhuman primates , mice ) and conferring protection ( mice ) . Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria |
13,007 | 26,403,470 | Conclusions This systematic review and meta- analysis indicated that use of F-MARC injury prevention programs , particularly the ‘ 11 + ’ program , decreases the risk of injuries among soccer players . | Background The FIFA Medical and Research Centre ( F-MARC ) has design ed a comprehensive warm-up program targeting muscular strength , body kinaesthetic awareness , and neuromuscular control during static and dynamic movements to decrease injury risk for soccer players .
Prior studies have investigated the effectiveness of the F-MARC programs , but have not consistently reported a statistically significant reduction in injury and reduction in time loss due to injury from utilizing the program .
Objective The purpose of this study was to conduct a systematic review and meta- analysis of r and omized controlled trials and interventional studies that evaluated the efficacy of the F-MARC injury prevention programs in soccer . | Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Groin injuries cause major problems in sports and particularly in football . Exercise is effective in treating adductor-related groin pain , but no trials have been published regarding the specific prevention of groin pain or prevention specifically targeting overuse injuries in sport using exercise programs . We performed a cluster-r and omized trial including 55 football clubs representing 1211 players . The clubs were r and omized to an exercise program aim ed at preventing groin injuries ( n=27 ) or to a control group training as usual ( n=28 ) . The intervention program consisted of six exercises including strengthening ( concentric and eccentric ) , coordination , and core stability exercises for the muscles related to the pelvis . Physiotherapists assigned to each club registered all groin injuries . Twenty-two clubs in each group completed the study , represented by 977 players . There was no significant effect of the intervention ( HR=0.69 , 95 % CI 0.40 - 1.19 ) . The risk of a groin injury was reduced by 31 % , but this reduction was not significant . A univariate analysis showed that having had a previous groin injury almost doubles the risk of developing a new groin injury and playing at a higher level almost triples the risk of developing a groin injury Background The incidence rate of soccer injuries is among the highest in sports , particularly for adult male soccer players . Purpose To investigate the effect of the ‘ The11 ’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players . Study design Cluster-r and omised controlled trial . Methods Teams from two high-level amateur soccer competitions were r and omly assigned to an intervention ( n=11 teams , 223 players ) or control group ( n=12 teams , 233 players ) . The intervention group was instructed to perform The11 in each practice session during one soccer season . The11 focuses on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation and plyometrics with straight leg alignment . All participants of the control group continued their practice sessions as usual . Results In total , 427 injuries were recorded , affecting 274 of 456 players ( 60.1 % ) . Compliance with the intervention programme was good ( team compliance=73 % , player compliance=71 % ) . Contrary to the hypothesis , injury incidences were almost equal between the two study groups : 9.6 per 1000 sports hours ( 8.4–11.0 ) for the intervention group and 9.7 ( 8.5–11.1 ) for the control group . No significant differences were found in injury severity , but a significant difference was observed in the location of the injuries : players in the intervention group sustained significantly less knee injuries . Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players . More research is recommended , focusing on injury aetiology and risk factors in adult male amateur soccer players Objective To examine the effect of a comprehensive warm-up programme design ed to reduce the risk of injuries in female youth football . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 125 football clubs from the south , east , and middle of Norway ( 65 clusters in the intervention group ; 60 in the control group ) followed for one league season ( eight months ) . Participants 1892 female players aged 13 - 17 ( 1055 players in the intervention group ; 837 players in the control group ) . Intervention A comprehensive warm-up programme to improve strength , awareness , and neuromuscular control during static and dynamic movements . Main outcome measure Injuries to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . Results During one season , 264 players had relevant injuries : 121 players in the intervention group and 143 in the control group ( rate ratio 0.71 , 95 % confidence interval 0.49 to 1.03 ) . In the intervention group there was a significantly lower risk of injuries overall ( 0.68 , 0.48 to 0.98 ) , overuse injuries ( 0.47 , 0.26 to 0.85 ) , and severe injuries ( 0.55 , 0.36 to 0.83 ) . Conclusion Though the primary outcome of reduction in lower extremity injury did not reach significance , the risk of severe injuries , overuse injuries , and injuries overall was reduced . This indicates that a structured warm-up programme can prevent injuries in young female football players . Trial registration IS RCT N10306290 QUESTION Is an injury prevention program consisting of 10 exercises design ed to improve stability , muscle strength , co-ordination , and flexibility of the trunk , hip and leg muscles ( known as The11 ) cost effective in adult male amateur soccer players ? DESIGN Cost-effectiveness analysis of a cluster-r and omised controlled trial . PARTICIPANTS 479 adult male amateur soccer players aged 18 - 40 years . INTERVENTION The intervention group was instructed to perform the exercises at each training session ( 2 to 3 sessions per week ) during one soccer season . The exercises focus on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation , and plyometrics with straight leg alignment . The control group continued their usual warm-up . OUTCOME MEASURES All injuries and costs associated with these injuries were compared between groups after bootstrapping ( 5000 replications ) . RESULTS No significant differences in the proportion of injured players and injury rate were found between the two groups . Mean overall costs in the intervention group were € 161 ( SD 447 ) per athlete and € 256 ( SD 555 ) per injured athlete . Mean overall costs in the control group were € 361 ( SD 1529 ) per athlete and € 606 ( SD 1944 ) per injured athlete . Statistically significant cost differences in favour of the intervention group were found per player ( mean difference € 201 , 95 % CI 15 to 426 ) and per injured player ( mean difference € 350 , 95 % CI 51 to 733 ) . CONCLUSIONS The exercises failed to significantly reduce the number of injuries in male amateur soccer players within one season , but did significantly reduce injury-related costs . The cost savings might be the result of a preventive effect on knee injuries , which often have substantial costs due to lengthy rehabilitation and lost productivity . TRIAL REGISTRATION NTR2416 The injury rate in football is high , and effective injury prevention methods are needed . An exercise program , the " 11 , " has been design ed to prevent the most common injury types in football . However , the effect of such a program on performance is not known . The aim of this r and omized-controlled trial was to investigate the effect of the " 11 " on performance after a 10-week training period . Thirty-four adolescent female football players were r and omly assigned to either an intervention ( n=18 ) or a control group ( n=16 ) . The " 11 " is a 15-min program consisting of ten exercises for core stability , lower extremity strength , balance and agility . Performance tests included isokinetic and isometric strength protocol s for the quadriceps and hamstrings , isometric hip adduction and abduction strength , vertical jump tests , sprint running and soccer skill tests . There was no difference between the intervention and control groups in the change in performance from the pre- to post-test for any of the tests used . In conclusion , no effect was observed on a series of performance tests in a group of adolescent female football players using the " 11 " as a structured warm-up program Background : Risk factors for soccer injuries and possibilities for prevention have been discussed by several authors , but only a few have investigated the effectiveness of preventive interventions . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of soccer injuries in male youth amateur players . Study Design : Prospect i ve controlled intervention study . Methods : Seven soccer teams took part in a prevention program that focused on education and supervision of coaches and players , while seven other teams were instructed to train and play soccer as usual . Over 1 year all injuries were documented weekly by physicians . Complete weekly injury reports were available for 194 players . Results : The incidence of injury per 1000 hours of training and playing soccer was 6.7 in the intervention group and 8.5 in the control group , which equates to 21 % fewer injuries in the intervention group . The greatest effects were observed for mild injuries , overuse injuries , and injuries incurred during training . The prevention program had greater effects in low-skill than in high-skill teams . Conclusions : The incidence of soccer injuries can be reduced by preventive interventions , especially in low skill level youth teams . Coaches and players need better education regarding injury prevention strategies and should include such interventions as part of their regular training A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 The FIFA 11 + is a structured warm-up programme specially design ed to prevent injuries among football players from age 14 years and above . However , studies to prove its efficacy are generally few and it is yet to be tested in male youth footballers and among African players . The purpose of the study was to examine the efficacy of the FIFA 11 + programme in reducing the risk of injuries among male youth football players of the Lagos Junior League . A cluster r and omised controlled trial was conducted . All the 20 teams ( 414 players aged 14 -19 years ) in the Premier League division were block-r and omised into either an intervention ( INT ) or a control ( CON ) group . The INT group performed the FIFA 11 + exercises as warm-up during training sessions and the CON group performed usual warm-up . Participating teams were prospect ively followed through an entire league season of 6 months in which they were visited every week to assess injured players for time-loss injuries in both groups . The primary outcomes were any injury to the players , injuries by type of exposure and injuries specific to the lower extremities . The secondary outcomes were injuries reported by body location , aetiology , mechanism and severity . In total , 130 injuries were recorded affecting 104 ( 25 % ) of the 416 players . Team and player compliance with the INT was 60 % and 74 % respectively . Based on the primary outcome measures of the study , the FIFA 11 + programme significantly reduced the overall rate of injury in the INT group by 41 % [ RR = 0.59 ( 95 % CI : 0.40 - 0.86 ; p = 0.006 ) ] and all lower extremity injuries by 48 % [ RR = 0.52 ( 95 % CI : 0.34 - 0.82 ; p = 0.004 ) ] . However , the rate of injury reduction based on secondary outcomes mostly did not reach the level of statistical significance . The FIFA 11 + programme is effective in reducing the rates of injuries in male youth football players . Key pointsThe FIFA 11 + has only been tested in r and omised controlled trials conducted on female youth football players ; this study reports its efficacy in male youth football for the first timeThe FIFA 11 + programme significantly reduced the overall rate of injuries and lower extremity injuries in male youth football playersYouth football administrators in Africa and other parts of the world should pursue the implementation of the FIFA 11 + in order to minimize the incidence of injuries among players Background Among female athletes it has not been established whether a neuromuscular and proprioceptive sports-specific training program will consistently reduce the incidence of anterior cruciate ligament injuries . Purpose To determine whether a neuromuscular and proprioceptive performance program was effective in decreasing the incidence of anterior cruciate ligament injury within a select population of competitive female youth soccer players . Study Design Cohort study ; Level of evidence , 2 . Methods In 2000 , 1041 female subjects from 52 teams received a sports-specific training intervention in a prospect i ve non-r and omized trial . The control group consisted of the remaining 1905 female soccer players from 95 teams participating in the same league who were age and skill matched . In the 2001 season , 844 female athletes from 45 teams were enrolled in the study , with 1913 female athletes ( from 112 teams ) serving as the age- and skill-matched controls . All subjects were female soccer players between the ages of 14 and 18 and participated in either their traditional warm-up or a sports-specific training intervention before athletic activity over a 2-year period . The intervention consisted of education , stretching , strengthening , plyometrics , and sports-specific agility drills design ed to replace the traditional warm-up . Results During the 2000 season , there was an 88 % decrease in anterior cruciate ligament injury in the enrolled subjects compared to the control group . In year 2 , during the 2001 season , there was a 74 % reduction in anterior cruciate ligament tears in the intervention group compared to the age- and skill-matched controls . Conclusion Using a neuromuscular training program may have a direct benefit in decreasing the number of anterior cruciate ligament injuries in female soccer players Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players Abstract The warm-up programme “ FIFA 11 + ” has been shown to reduce football injuries in different population s , but so far veteran players have not been investigated . Due to differences in age , skill level and gender , a simple transfer of these results to veteran football is not recommended . The purpose of this study was to investigate the preventive effects of the “ FIFA 11 + ” in veteran football players . Twenty veteran football teams were recruited for a prospect i ve 9-month ( 1 season ) cluster-r and omised trial . The intervention group ( INT , n = 146 ; 45 ± 8 years ) performed the “ FIFA 11 + ” at the beginning of each training session , while the control group ( CON , n = 119 ; 43 ± 6 years ) followed its regular training routine . Player exposure hours and injuries were recorded according to an international consensus statement . No significant difference was found between INT and CON in overall injury incidence ( incidence rate ratio [ IRR ] : 0.91 [ 0.64–1.48 ] ; P = 0.89 ) . Only severe injuries reached statistical significance with higher incidence in CON ( IRR : 0.46 [ 0.21–0.97 ] , P = 0.04 ) . Regular conduction ( i.e. once a week ) of the “ FIFA 11 + ” did not prevent injuries in veteran footballers under real training and competition circumstances . The lack of preventive effects is likely due to the too low overall frequency of training sessions OBJECTIVES To compare muscle recruitment , maximal force , and rate of force development changes following different resistance exercise protocol s with a constant volume-load . DESIGN Within-subjects r and omized crossover trial . METHODS Fourteen ( n=14 ) resistance trained male participants completed three different resistance exercise protocol s involving 20 squat repetitions , prescribed at 80 % of 1-repetition-maximum . Protocol A consisted of 5 sets of 4 repetitions with 3 min inter-set rest intervals , protocol B was 5 sets of 4 repetitions with 20 s inter-set rest intervals , and the rest-pause method was an initial set to failure with subsequent sets performed with a 20 s inter-set rest interval . Maximal squat isometric force output and rate of force development ( RFD ) were measured before , immediately upon completion ( IP ) , and 5 min ( 5P ) following each protocol . Muscle activity from 6 different thigh and hip muscles was measured with surface electromyography ( EMG ) at each time point , and during every squat repetition . RESULTS Participants completed the rest-pause method in 2.1±0.4 sets , with a total protocol duration of 103 s compared to 140 s and 780 s for protocol s B and A , respectively . All protocol s elicited similar decreases ( p<0.05 ) in maximal force and RFD at IP , with full recovery at 5P . Increased motor unit recruitment was observed during the rest-pause method compared to both protocol s A and B for all muscles measured ( p<0.05 ) . CONCLUSIONS As a result of the increased EMG during exercise and no greater post-exercise fatigue , it was concluded that the rest-pause method may be an efficacious training method for resistance-trained individuals |
13,008 | 23,801,421 | Conclusion CTA and CE-MRA are accurate techniques for evaluating disease severity of aortotibial arteries in patients with CLI or IC .
No significant differences in the diagnostic performance of the two techniques between patients with CLI and IC were found .
Key Points• Computed tomography and contrast-enhanced magnetic resonance angiography can both demonstrate arterial disease.• CTA and CE-MRA can both accurately evaluate arteries in peripheral arterial disease.• Diagnostic performances of critical limb ischaemia and intermittent claudication are not different.• Separate imaging technique of tibial arteries by CE-MRA is preferred.• CTA and CE-MRA can distinguish confidently between high- grade stenoses and occlusions | Objective To evaluate the diagnostic performance of computed tomography angiography ( CTA ) and contrast-enhanced magnetic resonance angiography ( CE-MRA ) in detecting haemodynamically significant arterial stenosis or occlusion in patients with critical limb ischaemia ( CLI ) or intermittent claudication ( IC ) . | Purpose : To prospect ively determine feasibility and diagnostic accuracy of 3D contrast-enhanced MR-angiography ( CE-MRA ) at 3.0 tesla ( T ) in patients with peripheral arterial occlusive disease . Digital subtraction angiography ( DSA ) was used as reference st and ard . Material and Methods : Thirty consecutive patients with suspected peripheral arterial occlusive disease were examined on a 3.0 T MR system by using the integrated whole body coil . A 4-station examination protocol in hybrid technique was chosen , containing 2 gadodiamide injections , the first one for imaging the calf and foot arteries ( single-step technique ) and the second injection for the visualization of the aortoiliacal and femoral arteries ( bolus-chase MRA ) . All patients underwent DSA within the following 48 hours . The arterial tree of each leg was divided in 15 segments and 4 anatomic regions ( iliacal , femoral , popliteal/proximal calf , distal calf/foot ) . Two radiologists analyzed the MR-images with regard to image quality , grade of stenosis , and venous overlap . DSA-images were analyzed by 2 radiologists in consensus with regard to the stenosis grade . Results : Eight hundred eighty-five and 884 of 889 arterial segments at CE-MRA were rated with excellent or good diagnostic image quality by observer 1 and observer 2 , respectively . In only 3 segments image quality was affected by venous contamination . Sensitivity of CE-MRA for determination of relevant arterial stenoses ( 50%–99 % ) and occlusions — as compared with DSA — was 95.3 % ( both observer ) and specificity was 98.5 % and 97.8 % for observer 1 and observer 2 , respectively . Conclusion : Peripheral hybrid CE-MRA at 3.0 T is feasible and proved to be reliable at depiction of stenoses and occlusions of the whole pelvic and lower leg arterial system PURPOSE To prospect ively study the diagnostic performance of hybrid single-dose contrast-enhanced MRA of peripheral arterial disease ( PAD ) , with digital subtraction angiography ( DSA ) as the reference st and ard . MATERIAL S AND METHODS Hybrid MRA , combining time resolved imaging of contrast kinetics and two-station bolus-chase sequences , of lower limb was performed in 31 PAD patients ( 21 men , 10 women ; mean age , 72 years ) with two separate gadobenate dimeglumine ( 8 mL ) injections in each sequence . Two independent blinded readers analyzed the vascular stenosis ( 32 segments in each limb ) . Sensitivity , specificity , and accuracy in all vascular segments and segments below popliteal artery were calculated . Interobserver agreements on MRA and intermodality agreements between MRA and DSA were calculated by using k statistics . RESULTS Sensitivity , specificity , and accuracy of the hybrid MRA with regard to hemodynamically significant stenosis in all vascular segments were 92 % , 97 % , and 95 % for reader 1 , and 90 % , 92 % , and 92 % , for reader 2 , respectively . The interobsever agreements on MRA were good ( k = 0.77 - 0.74 ) for all- grade stenosis , and excellent ( k = 0.82 - 0.81 ) for hemadynamically significant stenosis . The intermodality agreements are good to excellent ( k = 0.73 - 0.94 ) . CONCLUSION Single-dose hybrid MRA is a safe and reliable noninvasive alternative to conventional DSA in the assessment of PAD patients The purpose of this study was to assess the diagnostic value of two-dimensional ( 2D ) MR subtraction angiography of lower extremities in patients with symptomatic peripheral arterial occlusive disease with conventional angiography as the st and ard of reference . Twenty patients were prospect ively included . 2D subtraction MR angiography ( MRA ) consisted of multisection gradient-recalled echo ( GRE ) acquisitions with the shortest TE available on our machine ( 4 msec ) , obtained in the coronal plane before and after intravenous bolus administration of gadolinium chelate . MR images were reconstructed after subtraction with a maximum-pixel-intensity-projection ( MIP ) algorithm . MRA was performed in all cases 1 - 4 days before diagnostic angiography . In a prospect i ve blinded analysis , the number and location of significant ( ie , > 50 % ) stenoses and occlusions were evaluated for each vascular segment . Sensitivity and specificity were used to evaluate MRA data . Significant stenoses ( 38 of 46 , 83 % ) and occlusions ( 66 of 67 , 99 % ) seen at conventional angiography were identified with MRA . The sensitivity and specificity of MRA for determination of stenoses > 50 % or occlusions was 100 % and 97 % , respectively . The location and extent of stenoses and /or occlusions on MRA and angiograms were well correlated ( kappa values , r = .73 , P < .05 ) . Contrast 2D MR subtraction angiography , by providing comparable information to that of conventional angiography , is well suited to evaluate the presence and severity of atherosclerotic lesions of the lower limbs PURPOSE To prospect ively compare contrast-enhanced ( CE ) magnetic resonance ( MR ) angiography against digital subtraction angiography ( DSA ) in patients with critical lower-limb ischemia . MATERIAL S AND METHODS Thirty patients with critical lower limb ischemia underwent both CE MR angiography and DSA . CE MR angiography commenced with a dedicated high-resolution study of the below-knee arteries followed by a three-station bolus-chase examination . Two blinded observers recorded the severity of the most significant stenosis within each arterial segment . Interobserver agreement was calculated and , with DSA as the reference st and ard , the sensitivity and specificity of CE MR angiography for the detection of significant stenosis ( > or=50 % luminal narrowing ) or occlusion was calculated . RESULTS All 390 arterial segments were scored by both observers . Sensitivity was higher in the distal segments ( 92%-96 % ) compared with the proximal segments ( 69%-79 % ) . Specificity was similar in distal ( 90%-91 % ) and more proximal segments ( 86%-96 % ) . Overall , interobserver agreement was excellent ( kappa = 0.95 for CE MR angiography and DSA ) and was superior within the distal segments . Twenty-eight segments that were considered occluded on DSA were shown to be patent on CE MR angiography and 16 segments that were considered occluded on CE MR angiography were shown to be patent on DSA . CONCLUSIONS In patients with critical lower-limb ischemia , CE MR angiography with high-resolution distal imaging is highly accurate for assessment of the below-knee arteries . Both DSA and CE MR angiography may identify patent vessels that are considered occluded based on the other modality The purpose of this study was to include the pedal vasculature into the coverage of peripheral multistation magnetic resonance angiography ( 3DceMRA ) . A total of 216 patients suffering from peripheral vascular disease were examined with a modified hybrid dual-bolus technique . The cruropedal arteries were acquired first with two sagittal slabs and time-resolved 3D sequences . Then the aortofemoral vessels were visualized using the bolus-chase technique and a second contrast injection . Interventional procedures were performed in 104 patients , and in 69 of those , the cruropedal vessels were also examined with digital subtraction angiography ( iaDSA ) . Using 3DceMRA , the cruropedal arteries were displayed with both excellent and good quality in 95 % ( 205/216 cases ) , and without any venous overlay in 94 % ( 203/216 cases ) . The aortofemoral vessels were not jeopardized by the first contrast injection . With iaDSA as the st and ard of reference , observed sensitivity of 3DceMRA was found in ranges from 80 % ( 29 % , 99 % ) to 100 % ( 86 % , 100 % ) for assessing significant stenoses , and observed specificity ranged between 93 % [ 80 % , 98 % ] and 100 % ( 82 % , 100 % ) . In conclusion , hybrid dual-bolus 3DceMRA significantly reduces the limitations of st and ard single-bolus 3DceMRA in anatomic coverage and temporal resolution of the cruropedal arteries , thus providing high- quality images of the entire peripheral vasculature PURPOSE To prospect ively determine feasibility of contrast material -enhanced magnetic resonance ( MR ) angiography of the peripheral arteries from distal aorta to pedal arteries with a 1.0-T system and a dedicated phased-array coil . MATERIAL S AND METHODS Twenty-seven patients with peripheral arteriosclerotic occlusive disease underwent contrast-enhanced MR angiography with an automatic moving-table technique . In addition , lower-leg and pedal arteries were examined without table movement ( hybrid technique ) . Two radiologists independently review ed MR angiograms to assess image quality and grade stenosis in 13 segments per leg . Each was blinded to patients ' clinical data . Twenty-five of the patients also underwent conventional angiography . Stenosis grade at conventional angiography was assessed by two radiologists in consensus . Interobserver variability for stenosis grade at MR angiography was calculated with Cohen kappa test . Specificity and sensitivity of MR angiography in detection of stenosis of more than 50 % and occlusion were calculated for both observers . The study was approved by the local ethics committee . RESULTS In 14 of the 27 patients , hybrid technique was superior to moving-table technique because there was less venous overlap ( 11 patients ) , fewer motion artifacts ( one patient ) , or both ( two patients ) . In nine patients , there was no difference between techniques ; in four patients , moving-table technique was superior . Stenosis grade was analyzed in 698 segments with MR angiography and in 638 segments with both conventional and MR angiography . Kappa analysis of interobserver agreement with MR angiography yielded a score of 0.84 . For the 638 segments evaluated with both conventional and MR angiography , observers 1 and 2 assigned same grade of stenosis with both modalities in 558 and 555 segments , respectively . Sensitivity for stenoses greater than 50 % and occlusion was 94.4 % and 91.1 % for observers 1 and 2 , respectively , and specificity was 90.6 % and 91.3 % . More distal runoff vessels were shown with MR angiography in seven cases and with conventional angiography in two cases . CONCLUSION Contrast-enhanced MR angiography of the peripheral vessels with a 1.0-T system and dedicated peripheral angiography coil is feasible , and in some cases , it provides additional information compared with conventional angiography Purpose : To determine whether contrast-enhanced 3D MR angiography ( CE MRA ) could replace digital subtraction angiography ( DSA ) for the evaluation of atherosclerotic peripheral vascular disease of the lower leg and foot . Material and Methods : Thirty-five patients with symptoms of atherosclerotic disease of the leg were examined prospect ively with CE MRA of the foot and the lower legs as well as with DSA from the aorta to the pedal arches . The MRA technique was focused on optimal imaging of the arteries of the foot . Results : The agreement between CE MRA and DSA for grading of stenosis was moderate to good ( weighted κ-values 0.48–0.80 ) . The sensitivity of CE MRA for detection of significant stenosis ( ≥ 50 % ) was 92 % and the specificity was 64 % with DSA as gold st and ard . Conclusion : CE MRA is a fairly accurate method for the demonstration of atherosclerotic disease below the knee including the pedal arches . It can replace DSA for the assessment of distal arteries in patients with impaired renal function . However , image quality and resolution still needs to be improved before CE MRA can become the method of choice in all patients PURPOSE To prospect ively compare the accuracy of 16-detector row computed tomographic ( CT ) angiography with conventional digital subtraction angiography ( DSA ) as the reference st and ard in the assessment of aortoiliac and lower extremity arteries in patients with peripheral arterial disease . MATERIAL S AND METHODS This study was approved by the institutional review board , and informed consent was obtained . A total of 39 consecutive patients ( 27 men [ mean age , 66 years ] and 12 women [ mean age , 64 years ] ) with peripheral arterial disease underwent both conventional DSA and 16-detector row CT angiography . For data analysis , the arterial vascular system was divided into 35 segments . A total of 1365 arterial segments were analyzed for arterial stenosis by two independent blinded readers using a four-point grading system ( grade 1 , < 10 % luminal narrowing ; grade 2 , 10%-49 % luminal narrowing ; grade 3 , 50%-99 % luminal narrowing ; grade 4 , occlusion ) . Interobserver agreements were calculated by using kappa statistics . A third independent blinded reader assessed possible reasons for disagreements between 16-detector row CT angiographic findings and conventional DSA findings . Effective radiation dose was calculated for both imaging modalities . RESULTS Sixteen-detector row CT angiographic and conventional DSA findings were diagnostic in all vascular segments . Compared with conventional DSA , the sensitivity and specificity of 16-detector row CT angiography with regard to detection of hemodynamically significant stenosis in all 35 arterial segments were 96 % and 97 % , respectively , for both readers . Readers 1 and 2 overestimated arterial stenosis in 42 ( 3 % ) and 34 ( 2 % ) arterial segments , respectively , and underestimated arterial stenosis in 13 ( 1 % ) and 10 ( 1 % ) arterial segments , respectively . Interobserver agreement was excellent ( kappa = 0.84 - 1.00 ) . Presence of anteroposteriorly located luminal narrowing and extensive vascular wall calcification were considered main reasons for disagreements between imaging modalities . Effective radiation dose was lower for 16-detector row CT angiography ( 1.6 - 3.9 mSv ) than for conventional DSA ( 6.4 - 16.0 mSv ) . CONCLUSION Sixteen-detector row CT angiography is an accurate and reliable noninvasive alternative to conventional DSA in the assessment of aortoiliac and lower extremity arteries in patients with peripheral arterial disease PURPOSE To prospect ively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material -enhanced magnetic resonance ( MR ) angiography of the pelvis , thigh , and lower-leg ( excluding foot ) for suspected or known peripheral arterial occlusive disease . MATERIAL S AND METHODS Institutional review board approval was granted from each center and informed written consent was obtained from all patients . Between November 2006 and January 2008 , 96 patients ( 62 men , 34 women ; mean age , 63.7 years + /- 10.4 [ st and ard deviation ] ; range , 39 - 86 years ) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and r and omized 0.1-mmol/kg doses of each agent . Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features . Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography . Data were analyzed by using the Wilcoxon signed-rank , McNemar , and Wald tests . Interreader agreement was determined by using generalized kappa statistics . Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed . RESULTS Ninety-two patients received both agents . Significantly better performance ( P < .0001 ; all evaluations ) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features . Contrast enhancement ( P < or = .0001 ) and detection of clinical ly relevant disease ( P < or = .0028 ) were significantly improved with gadobenate dimeglumine . Interreader agreement for stenosis detection and grading was good to excellent ( kappa = 0.749 and 0.805 , respectively ) . Mild adverse events were reported for four ( six events ) and five ( eight events ) patients after gadobenate dimeglumine and gadopentetate dimeglumine , respectively . CONCLUSION Higher- quality vessel visualization , greater contrast enhancement , fewer technical failures , and improved diagnostic performance are obtained with gadobenate dimeglumine , relative to gadopentetate dimeglumine , when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease Purpose : To prospect ively determine the accuracy of 1.5 Tesla ( T ) and 3 T magnetic resonance angiography ( MRA ) versus digital subtraction angiography ( DSA ) in the depiction of infrageniculate arteries in patients with symptomatic peripheral arterial disease . Patients and Methods : A prospect i ve 1.5 T , 3 T MRA , and DSA comparison was used to evaluate 360 vessel segments in 10 patients ( 15 limbs ) with chronic symptomatic peripheral arterial disease . Selective DSA was performed within 30 days before both MRAs . The accuracy of 1.5 T and 3 T MRA was compared with DSA as the st and ard of reference by consensus agreement of 2 experienced readers . Signal-to-noise ratios ( SNR ) and signal-difference-to-noise ratios ( SDNRs ) were quantified . Results : No significant difference in overall image quality , sufficiency for diagnosis , depiction of arterial anatomy , motion artifacts , and venous overlap was found comparing 1.5 T with 3 T MRA ( P > 0.05 by Wilcoxon signed rank and as by Cohen k test ) . Overall sensitivity of 1.5 and 3 T MRA for detection of significant arterial stenosis was 79 % and 82 % , and specificity was 87 % and 87 % for both modalities , respectively . Interobserver agreement was excellent k > 0.8 , P < 0.05 ) for 1.5 T as well as for 3 T MRA . SNR and SDNR were significantly increased using the 3 T system ( average increase : 36.5 % , P < 0.032 by t test , and 38.5 % , P < 0.037 respectively ) . Conclusions : Despite marked improvement of SDNR , 3 T MRA does not yet provide a significantly higher accuracy in diagnostic imaging of atherosclerotic lesions below the knee joint as compared with 1.5 T MRA OBJECTIVE The objective of our study was to prospect ively evaluate the diagnostic accuracy of intraarterial ( i.a . ) and i.v . MR angiography ( MRA ) of the infrainguinal arteries in comparison with the reference st and ard selective digital subtraction angiography ( DSA ) . SUBJECTS AND METHODS Twenty consecutive patients with symptomatic peripheral arterial occlusive disease ( PAOD ) underwent i.v . MRA and i.a . MRA of the infrainguinal arteries and DSA , which served as the reference st and ard . For i.v . MRA , 27 mL of gadodiamide was injected through a peripheral arm vein ; for i.a . MRA , 30 mL of diluted contrast agent ( 5 mL of gadodiamide in 55 mL of 0.9 % saline solution ) was twice injected in the superficial femoral artery with a flow rate of 2.5 mL/s through a 5-French sheath that was placed on the occasion of DSA before vascular intervention . A 3D gradient-echo sequence was performed using a dedicated coil system on a 1.5-T MR scanner . Three independent blinded observers localized and quantitatively grade d stenoses on i.v . MRA and i.a . MRA . The overall impression of image quality of i.v . MRA and i.a . MRA was documented using a 4-point scale ( 1 , excellent ; 4 , poor ) . Interobserver agreement was calculated . RESULTS The mean sensitivity and mean specificity for the detection of stenoses > or= 50 % of the upper leg arteries ( i.e. , superficial femoral artery and popliteal artery ) were 85.5 % and 83.3 % for i.a . MRA and 82.2 % and 86.7 % for i.v . MRA , respectively . The mean sensitivity and mean specificity for the detection of stenoses > or= 50 % of the lower leg arteries ( i.e. , proximal anterior tibial artery , tibiofibular trunk , proximal posterior tibial artery , and proximal peroneal artery ) were 91.7 % and 75.0 % for i.a . MRA , respectively , and 87.5 % each for i.v . MRA . the diagnostic quality of i.a . MRA images and i.v . MRA images was assessed as excellent or good . CONCLUSION i.a . MRA provides sensitivity and specificity for the detection of hemodynamically significant stenoses of the infrainguinal arteries comparable to i.v . MRA and therefore is a good diagnostic tool especially for MR-guided vascular interventions PURPOSE To prospect ively determine the diagnostic performance of a combination of st and ard bolus-chase magnetic resonance ( MR ) angiography and MR angiography with time-resolved imaging of contrast kinetics ( TRICKS ) for depicting severity of peripheral vascular disease of the lower extremity , including the pedal arteries , in diabetic patients with digital subtraction angiography ( DSA ) as the reference st and ard . MATERIAL S AND METHODS An ethical committee approved this study ; written informed consent was obtained from patients . St and ard three-station and TRICKS MR angiography of the calf and foot were performed in 31 consecutive diabetic patients ( 23 men , eight women ; mean age , 67 years ; range , 43 - 81 years ) . Two readers separately assessed images of arterial segments as diagnostic or nondiagnostic and grade d stenosis . Results were compared with those at DSA when the corresponding arterial segments were considered diagnostic at DSA . Wilcoxon signed rank test was used to determine if a significant difference between imaging techniques existed , and kappa statistics were used to determine interobserver agreement . RESULTS The difference between st and ard MR angiography and DSA regarding the number of diagnostic segments in the thigh was not significant ( P = .50 ) . A significantly higher number of calf and foot segments was considered diagnostic at TRICKS MR angiography than at st and ard MR angiography ( P < .025 ) . Sixteen of 26 segments in the foot that were considered nondiagnostic at DSA were considered diagnostic at TRICKS MR angiography . Average sensitivity of st and ard MR angiography for depicting hemodynamically significant arterial stenosis was 84 % ( reader 1 ) and 83 % ( reader 2 ) in the thigh and 78 % ( reader 1 ) and 80 % ( reader 2 ) in the calf . For both readers , average specificity was 97 % in the thigh and 90 % in the calf . Sensitivity and specificity of TRICKS MR angiography in the calf and foot were improved compared with those at st and ard MR angiography . CONCLUSION TRICKS MR angiography of the distal calf and pedal vessels is superior to st and ard MR angiography regarding the number of diagnostic segments and assessment of the degree of luminal narrowing Purpose : To evaluate and compare the diagnostic accuracy of duplex ultrasound ( US ) and MR angiography ( MRA ) at 1.0 T in aortoiliac arterial disease using digital subtraction angiography ( DSA ) as the reference st and ard . In addition , a comparison of the 2D time-of flight ( TOF ) and 3D contrast-enhanced MRA ( CE MRA ) techniques was performed . Material and Methods : Prospect ively , 39 patients with symptoms of lower-extremity arterial occlusive disease were examined using US , TOF MRA , CE MRA and DSA . Significant lesions ( stenosis ≥50 % ) and occlusions were evaluated blindly for each method . Results : For all segments , the sensitivity for US , TOF MRA and CE MRA with regard to significant lesions was 0.72 , 0.81 and 0.81 , respectively , and the specificity for each was 0.97 , 0.91 and 0.92 , respectively . For significant lesions above the inguinal ligament the corresponding sensitivity was 0.84 , 0.89 and 0.94 and the specificity 0.93 , 0.82 and 0.73 , respectively . The specificity was higher when the two MRA methods were combined . TOF MRA over grade d 7 segments as occluded . In most cases , the length of the occlusions was correctly determined on CE MRA , overestimated on TOF MRA and uncertain on US . Conclusion : Neither US nor MRA were sufficiently accurate to fully replace angiography . MRA was preferable to US as a non-invasive test when vascular intervention was contemplated . Although CE MRA was superior to TOF MRA , the most accurate results were achieved when the two methods were combined PURPOSE To evaluate the efficacy and safety of 0.1 mmol/kg gadodiamide administration for contrast-enhanced magnetic resonance angiography ( CE-MRA ) in detecting hemodynamically relevant main stenosis ( ie , > or = 50 % or occlusion ) of aortoiliac arteries . MATERIAL S AND METHODS In a multicenter , phase 3 , controlled study , patients with suspected or proven peripheral arterial occlusive disease ( PAOD ) underwent CE-MRA with administration of gadodiamide . Intraarterial digital subtraction angiography ( IA-DSA ) was used as the reference . The study was approved by all Institutional Review Boards or Institutional Ethic Committees prior to commencement of patient recruitment and written informed consent was obtained from all patients . RESULTS Independent readers rated 25%-45 % of CE-MRA images as excellent compared with 0.3%-6 % of noncontrast MRA images . Mean imaging acquisition time for CE-MRA was < 1 minute ( 0.7 + /- 1.9 minutes ) versus 10 minutes ( 10.8 + /- 3.0 ) for noncontrast MRA . Sensitivity , specificity , and accuracy of CE-MRA were superior compared with those of noncontrast MRA in detecting significant arterial stenoses . Compared with IA-DSA , the sensitivity of CE-MRA ranged from 80%-88 % and the specificity from 73 % to 92 % for the three blinded readers , at the patient level . CONCLUSION Diagnostic results with CE-MRA were superior and more consistent compared with noncontrast MRA for detecting hemodynamically relevant main stenoses in patients with suspected or proven PAOD and compared favorably with IA-DSA as a reference st and ard OBJECTIVE The purpose of our study was to evaluate the diagnostic accuracy of hybrid MR angiography by comparison with digital subtraction angiography ( DSA ) in diabetic patients with critical limb ischemia . SUBJECTS AND METHODS Thirty-one patients prospect ively underwent both hybrid MR angiography and DSA . The hybrid MR angiography study consisted of high-resolution MR angiography of a single calf and foot using a contrast-enhanced 3D gradient-echo volumetric interpolated breath-hold examination with surface coils , followed by three-station bolus chase MR angiography with a dedicated peripheral vascular coil . Two blinded review ers separately analyzed maximum-intensity-projection hybrid MR angiograms and DSA images . The peripheral vessels were divided into 10 anatomic segments for review . The status of each segment was grade d as normal , stenosis less than 50 % in diameter , stenosis greater than 50 % , or occluded . The sensitivity and specificity of hybrid MR angiography were determined using DSA as the gold st and ard . Treatment options were considered separately from the results of each examination . RESULTS Among 310 analyzed segments , the sensitivities of hybrid MR angiography for stenosis and occlusion were , respectively , 95 % and 95 % for review er 1 and 96 % and 90 % for review er 2 . The specificities of hybrid MR angiography for stenosis and occlusion were , respectively , 98 % and 98 % for review er 1 and 98 % and 99 % for review er 2 . In 25 patients ( 81 % ) , the quality of bolus chase MR angiography images was insufficient to assess runoff arteries . All treatments proposed on the basis of DSA findings were endorsed by hybrid MR angiography findings . Eleven more treatments were formulated on the basis of hybrid MR angiography findings . Of these , four were due to overestimation of stenosis on MR angiography and seven were due to the detection of patent infrageniculate arteries on hybrid MR angiography that were not detected on DSA . CONCLUSION Hybrid MR angiography depicts runoff arteries not seen on DSA . Hybrid MR angiography may be useful for treatment planning in selected diabetic patients with critical limb ischemia OBJECTIVE The purpose of this study was to evaluate the accuracy of CT angiography ( CTA ) with a single helical acquisition for assessment of stenoses and occlusions of the iliac arteries . SUBJECTS AND METHODS In our prospect i ve study , intraarterial digital subtraction angiography and IV CTA were performed from the suprarenal aorta to below the femoral bifurcation in 30 patients with vascular occlusive disease . Maximum-intensity-projection images in multiple views were also obtained . The accuracy of CTA with and without analysis of axial images was determined . RESULTS Sensitivity and specificity of CTA were 100 % for iliac artery occlusions with a confidence interval 85 - 100 % and 97 - 100 % , respectively . When axial scans were interpreted , 14 of 15 high- grade ( > 75 % ) stenoses were recognized . Sensitivity and specificity of CTA were 93 % ( range , 68 - 100 % ) and 99 % ( range , 97 - 100 % ) , respectively . When maximum intensity projections alone were analyzed , sensitivity for the diagnosis of 15 high- grade stenoses was only 53 % ( range , 27 - 79 % ) because calcified plaques obscured six stenoses . CONCLUSIONS CTA accurately reveals iliac artery occlusions . Observers of CT angiograms may overlook short stenoses in rare instances . Calcified plaques limit the use of maximum-intensity-projection images A sensitivity-encoded magnetic resonance ( MR ) angiography protocol was developed in which imaging times in the pelvic and upper-leg positions were reduced and isotropic su bmi llimeter voxel volumes were acquired in the lower-leg position . To achieve this , sensitivity encoding and r and om central -k-space segmentation in a centric filling order were applied . Results with this technique were compared with those with midstream aortic digital subtraction angiography ( DSA ) ( as the reference st and ard ) and conventional MR angiography in 15 patients with peripheral vascular disease . The results show that sensitivity-encoded MR angiography demonstrates increased diagnostic accuracy in comparison to that with conventional MR angiography and depicts more open infragenual arterial segments compared with both midstream aortic DSA and conventional MR angiography PURPOSE To compare the diagnostic accuracy of gadobenate dimeglumine (Gd-BOPTA)-enhanced versus gadoterate meglumine (Gd-DOTA)-enhanced magnetic resonance ( MR ) angiography in patients with peripheral arterial occlusive disease ( PAOD ) . MATERIAL S AND METHODS Fifty-six patients underwent MR angiography enhanced with either Gd-DOTA ( 28 patients ) or Gd-BOPTA ( 28 patients ) . All arterial segments from the renal arteries to the distal run-off vessels were evaluated for disease severity . The sensitivity , specificity , and accuracy of MR angiography enhanced with both agents separately were evaluated with a paired t test ; digital subtraction angiography was the reference st and ard . Interobserver variability was assessed by using the Cohen test . RESULTS Diagnostic MR angiograms were obtained in all 56 patients . Overall , sensitivity and specificity of Gd-DOTA-enhanced MR angiography were 96 % and 93 % , respectively , for observer 1 and 96 % and 85 % , respectively , for observer 2 ( kappa = 0.82 ) . Corresponding values for Gd-BOPTA-enhanced MR angiography were 94 % and 93 % , respectively , for observer 1 and 94 % and 89 % , respectively , for observer 2 ( kappa = 0.78 ) . No consistent differences between the two contrast material s in assessment of PAOD in the renal to popliteal arteries were observed . For assessment below the knee , specificity was slightly higher in the Gd-BOPTA group-91 % and 84 % for observers 1 and 2 , respectively-than in the Gd-DOTA group-89 % and 77 % , respectively ( P < .01 ) . The number of nonassessable below-the-knee segments was significantly lower in the Gd-BOPTA group : nine of 299 segments versus 25 of 312 segments in the Gd-DOTA group ( P < .01 ) . CONCLUSION At MR angiography of the distal run-off vessels , Gd-BOPTA yielded higher specificity and a significantly smaller number of nonassessable segments than Gd-DOTA . The diagnostic accuracy of the two gadolinium chelates at peripheral MR angiography was comparable in the renal to popliteal arteries OBJECTIVE Our objective was to determine whether multidetector CT ( MDCT ) angiography is an accurate and reliable method of revealing atheroocclusive disease of the aortoiliac system and the lower extremities compared with digital subtraction angiography ( DSA ) . SUBJECTS AND METHODS Forty-one patients with ischemic legs underwent both MDCT angiography and DSA of the aortoiliac system and the legs . The arterial supply of the legs was divided into 35 segments . Three independent observers rated each segment according to the maximal degree of arterial stenosis . Consensus interpretation was used to calculate the sensitivity and specificity of MDCT angiography in showing arterial occlusions and stenoses of at least 75 % . Intertechnique agreement was measured for each anatomic segment , and interobserver agreement was calculated for both techniques . Agreement was quantified using the kappa statistic . RESULTS The sensitivity and specificity of MDCT angiography for depicting arterial occlusions and stenoses of at least 75 % were 88.6 % and 97.7 % , and 92.2 % and 96.8 % , respectively . Substantial intertechnique agreement ( kappa > 0.4 ) was present in 102 ( 97.1 % ) of 105 arterial segments . Substantial interobserver agreement was present in 104 ( 99.0 % ) of 105 comparisons for both MDCT angiography and DSA with an average kappa value of 0.84 for CT and 0.78 for DSA . MDCT angiography showed more patent segments than DSA ( 1192 vs 1091 ) . All nine segments seen on DSA and not seen on MDCT angiography were in the calves . Of 110 segments seen on MDCT angiography and not seen on DSA , 100 ( 90.9 % ) were in the calves . CONCLUSION MDCT angiography was accurate in showing arterial atheroocclusive disease with reliability similar to DSA . MDCT angiography showed more vascular segments than DSA , particularly within calf vessels |
13,009 | 30,348,165 | The COM-B model provided the framework for underst and ing the complexity of chlamydia testing behaviour .
While we can not at this juncture state which component represents the most salient influence on chlamydia testing , across all three levels , multiple barriers and facilitators were identified relating psychological capability and physical and social opportunity . | Background Chlamydia is a major public health concern , with high economic and social costs .
In 2016 , there were over 200,000 chlamydia diagnoses made in Engl and .
The highest prevalence rates are found among young people .
Although annual testing for sexually active young people is recommended , many do not receive testing .
General practice is one ideal setting for testing , yet attempts to increase testing in this setting have been disappointing .
The Capability , Opportunity , and Motivation Model of Behaviour ( COM-B model ) may help improve underst and ing of the underpinnings of chlamydia testing .
The aim of this systematic review was to ( 1 ) identify barriers and facilitators to chlamydia testing for young people and primary care practitioners in general practice and ( 2 ) map facilitators and barriers onto the COM-B model . | Objectives Rates of sexually transmitted infections ( STIs ) in UK young people remain high in men and women . However , the National Chlamydia Screening Programme has had limited success in reaching men . The authors explored the acceptability of various medical , recreational and sports venues as setting s to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport . Methods A stratified r and om probability survey of 411 ( weighted n=632 ) men in Great Britain aged 18–35 years using computer-assisted personal and self-interviews . Results Young men engaged well with healthcare with 93.5 % registered with , and 75.3 % having seen , a general practitioner in the last year . 28.7 % and 19.8 % had previously screened for STIs and HIV , respectively . Willingness to access self-collected tests for STIs ( 85.1 % ) and HIV ( 86.9 % ) was high . The most acceptable pick-up points for testing kits were general practice 79.9 % , GUM 66.8 % and pharmacy 65.4 % . There was a low acceptability of sport venues as pick-up points in men as a whole ( 11.7 % ) , but this was greater among those who participated in sport ( 53.9 % ) . Conclusions Healthcare setting s were the most acceptable places for accessing STI and HIV self-testing kits . Although young men frequently access general practice , currently little STI screening occurs in this setting . There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice . While non- clinical setting s are acceptable to a minority of men , more research is needed to underst and how these venues could be used most effectively BACKGROUND Opportunistic screening for genital chlamydia infection is being introduced in Engl and , but evidence for the effectiveness of this approach is lacking . There are insufficient data about young peoples ' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population -based approach . AIM To estimate use of primary care services by young men and women ; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach . DESIGN OF STUDY Population based cross-sectional study . SETTING Twenty-seven general practice s around Bristol and Birmingham . METHOD A r and om sample of patients aged 16 - 24 years were posted a chlamydia screening pack . We collected details of face-to-face consultations from general practice records . Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening . RESULTS Of 12 973 eligible patients , an estimated 60.4 % ( 95 % confidence interval [ CI ] = 58.3 to 62.5 % ) of men and 75.3 % ( 73.7 to 76.9 % ) of women aged 16 - 24 years attended their practice at least once in a 1-year period . During this period , an estimated 21.3 % of patients would not attend their general practice but would be reached by postal screening , 9.2 % would not receive a postal invitation but would attend their practice , and 11.8 % would be missed by both methods . CONCLUSIONS Opportunistic and population -based approaches to chlamydia screening would both fail to contact a substantial minority of the target group , if used alone . A pragmatic approach combining both strategies might achieve higher coverage OBJECTIVE To determine whether asking general practitioners to offer chlamydia screening at the same time as Pap screening increases chlamydia screening rates . DESIGN A pragmatic cluster r and omised controlled trial . PARTICIPANTS AND SETTING Doctors from 31 general practice s in the Australian Capital Territory performing more than 15 Pap smear screens per year , and all women aged 16 - 39 years attending those practitioners between 1 November 2004 and 31 October 2005 . INTERVENTION Doctors in the intervention practice s were asked to routinely offer combined chlamydia and Pap screening to eligible women ; doctors in the control practice s were asked to implement screening guidelines based on a risk assessment of the individual patient ( ie , usual practice ) . MAIN OUTCOME MEASURE Chlamydia screening rate per visit . RESULTS There were 26 876 visits by eligible women during the study period : 16 082 to intervention practice s and 10 794 to control practice s. Chlamydia screening occurred during 6.9 % ( 95 % CI , 6.5%-7.3 % ) of visits to intervention practice s and 4.5 % ( 95 % CI , 4.1%-4.9 % ) of visits to control practice s. After controlling for clustering and potential confounders , there were twofold greater odds of chlamydia screening occurring during a visit by an eligible woman to an intervention practice than to a control practice ( adjusted odds ratio , 2.1 [ 95 % CI , 1.3 - 3.4 ] ) . CONCLUSION Combining chlamydia and Pap screening increases the rate of chlamydia screening in general practice . Implementing this approach would require little additional infrastructure support in setting s where a cervical screening program already exists Background Financial incentives have been used for many years internationally to improve quality of care in general practice . The aim of this pilot study was to determine if offering general practitioners ( GP ) a small incentive payment per test would increase chlamydia testing in women aged 16 to 24 years , attending general practice . Methods General practice clinics ( n = 12 ) across Victoria , Australia , were cluster r and omized to receive either a $ AUD5 payment per chlamydia test or no payment for testing 16 to 24 year old women for chlamydia . Data were collected on the number of chlamydia tests and patient consultations undertaken by each GP over two time periods : 12 month pre-trial and 6 month trial period . The impact of the intervention was assessed using a mixed effects logistic regression model , accommodating for clustering at GP level . Results Testing increased from 6.2 % ( 95 % CI : 4.2 , 8.4 ) to 8.8 % ( 95 % CI : 4.8 , 13.0 ) ( p = 0.1 ) in the control group and from 11.5 % ( 95 % CI : 4.6 , 18.5 ) to 13.4 % ( 95 % CI : 9.5 , 17.5 ) ( p = 0.4 ) in the intervention group . Overall , the intervention did not result in a significant increase in chlamydia testing in general practice . The odds ratio for an increase in testing in the intervention group compared to the control group was 0.9 ( 95 % CI : 0.6 , 1.2 ) . Major barriers to increased chlamydia testing reported by GPs included a lack of time , difficulty in remembering to offer testing and a lack of patient awareness around testing . Conclusions A small financial incentive alone did not increase chlamydia testing among young women attending general practice . It is possible small incentive payments in conjunction with reminder and feedback systems may be effective , as may higher financial incentive payments . Further research is required to determine if financial incentives can increase testing in Australian general practice , the type and level of financial scheme required and whether incentives needs to be part of a multi-faceted package . Trial Registration Australian New Zeal and Clinical Trial Registry ACTRN12608000499381 Background Chlamydia infection is a significant public health issue for young people ; however , testing rates in Australian general practice are low . Practice nurses ( PNs ) could have an important role in contributing to increasing chlamydia testing rates . The Australian Chlamydia Control Effectiveness Pilot ( ACCEPt ) , a large cluster r and omised control trial of annual testing for 16 to 29 year olds in general practice , is the first to investigate the role of PNs in maximising testing rates . In order to assess the scope for PN involvement , we aim ed to explore PN ’s views in relation to involvement in chlamydia testing in general practice . Methods Semi structured interviews were conducted between June 2011 and April 2012 with a purposive sample of 23 PNs participating in ACCEPt . Interview data was thematically analysed using a conventional content analysis approach . Results The participants in our study supported an increased role for PNs in chlamydia testing and identified a number of patient benefits from this involvement , such as an improved service with greater access to testing and patients feeling more comfortable engaging with a nurse rather than a doctor . An alleviation of doctors ’ workloads and expansion of the nurse ’s role were also identified as benefits at a clinic level . Time and workload constraints were commonly considered barriers to chlamydia testing , along with concerns around privacy in the “ small town ” rural setting s of the general practice s. Some felt negative GP attitudes as well as issues with funding for PNs ’ work could also be barriers . The provision of training and education , streamlining chlamydia testing pathways in clinics and changes to pathology ordering processes would facilitate nurse involvement in chlamydia testing . Conclusion This study suggests that PNs could take a role in increasing chlamydia testing in general practice and that their involvement may result in possible benefits for patients , doctors , PNs and the community . Strategies to overcome identified barriers and facilitate their involvement must be further explored BACKGROUND Opportunistic testing and screening for genital chlamydia infection in sexually active women under the age of 25 years can lead to a reduction in chlamydia infection and its related morbidity . AIMS To explore the barriers to testing for genital chlamydial infection in primary care . DESIGN OF STUDY Qualitative study with focus groups . SETTING Rural and urban general practice in Southwest Engl and . METHODS Focus groups were held with r and omly selected high- and lowtesting general practice s in Herefordshire , Gloucestershire and Avon . The high- and low-testing practice s did not differ in their age/sex make-up , or by deprivation indices . Open questions were asked about the management of genitourinary symptoms and opportunistic testing for chlamydia . Data were collected and analysed concurrently until saturation occurred . RESULTS Although staff from high test rate practice s were much more aware of the evidence for opportunistic chlamydia testing and screening , none of the practice s were happy to discuss chlamydia in a consultation unrelated to sexual health . The greatest barriers to opportunistic chlamydia testing and screening were lack of knowledge of the benefits of testing , when and how to take specimens , lack of time , worries about discussing sexual health , and lack of guidance . Healthcare staff stated that any increased testing should be accompanied by clear , concise primary care trust guidance on when and how to test , including how to obtain informed consent and perform contact tracing . Staff felt that testing could be undertaken at family planning clinics or with cervical smears if patients received information before the consultation . Alternatively , in larger practice s specific chlamydia clinics could be held . CONCLUSION The Department of Health needs to be aware of the extreme pressures that primary care staff are under , and the potential barriers to any screening implementation . Efforts to increase chlamydia screening in this setting should be accompanied by clear guidance and education . Any chlamydia clinics or increased testing must have appropriate financial and staff re sources . Genitourinary medicine ( GUM ) clinics , or level three practice s with GUM expertise , will need to be increased in parallel with testing in primary care to provide appropriate contact tracing and follow-up Study objective : To assess whether opportunistic and postal screening strategies for Chlamydia trachomatis can be compared with usual care in a r and omised trial in general practice . Design : Feasibility study for a r and omised controlled trial . Setting : Three West of Scotl and general medical practice s : one rural , one urban/deprived , and one urban/affluent . Participants : 600 women aged 16–30 years , 200 from each of three participating practice s selected at r and om from a sample of West of Scotl and practice s that had expressed interest in the study . The women could opt out of the study . Those who did not were r and omly assigned to one of three groups : postal screening , opportunistic screening , or usual care . Results : 38 % ( 85 of 221 ) of the approached practice s expressed interest in the study . Data were collected successfully from the three participating practice s. There were considerable workload implication s for staff . Altogether 124 of the 600 women opted out of the study . During the four month study period , 55 % ( 81 of 146 ) of the control group attended their practice but none was offered screening . Some 59 % ( 80 of 136 ) women in the opportunistic group attended their practice of whom 55 % ( 44 of 80 ) were offered screening . Of those , 64 % ( 28 of 44 ) accepted , representing 21 % of the opportunistic group . Forty eight per cent ( 59 of 124 ) of the postal group returned sample s. Conclusion : A r and omised controlled trial comparing postal and opportunistic screening for chlamydial infection in general practice is feasible , although re source intensive . There may be problems with generalising from screening trials in which patients may opt out from the offer of screening Background Australia is developing a chlamydia screening program . This study aim ed to determine the attitudes of young women to the introduction of chlamydia screening in Australian General Practice . Methods In-depth face-to-face interviews with 24 young women from across Victoria , Australia , attending a r and omly selected sample of general practice s. Results Young women reported that they would accept age-based screening for chlamydia in general practice , during both sexual-health and non-sexual-health related consultations . Trust in their general practitioner ( GP ) was reported to be a major factor in the acceptability of chlamydia screening . The women felt chlamydia screening should be offered to all young women rather than targeted at " high risk " women based on sexual history and they particularly emphasised the importance of normalising chlamydia screening . The women reported that they did not want to be asked to provide a sexual history as part of being asked to have a chlamydia test . Some reported that they would lie if asked how many partners they had had Conclusion Women do not want a sexual history taken when being asked to have a chlamydia test while attending a general practitioner . They prefer the offer of chlamydia screening to be based on age rather than assessment of sexual risk . Chlamydia screening needs to be normalised and destigmatised Background Chlamydia trachomatis ( chlamydia ) is the most commonly diagnosed sexually transmitted infection ( STI ) in Engl and ; approximately 70 % of diagnoses are in sexually active young adults aged under 25 . To facilitate opportunistic chlamydia screening in general practice , a complex intervention , based on a previously successful Chlamydia Intervention R and omised Trial ( CIRT ) , was piloted in Engl and . The modified intervention ( 3Cs and HIV ) aim ed to encourage general practice staff to routinely offer chlamydia testing to all 15–24 year olds regardless of the type of consultation . However , when the 3Cs ( chlamydia screening , signposting to contraceptive services , free condoms ) and HIV was offered to a large number of general practitioner ( GP ) surgeries across Engl and , chlamydia screening was not significantly increased . This qualitative evaluation addresses the following aims : a)Explore why the modified intervention did not increase screening across all general practice s.b)Suggest recommendations for future intervention implementation . Methods Phone interviews were carried out with 26 practice staff , at least 5 months after their initial educational workshop , exploring their opinions on the workshop and intervention implementation in the real world setting . Interview transcripts were thematically analysed and further examined using the fidelity of implementation model . Results Participants who attended had a positive attitude towards the workshops , but attendee numbers were low . Often , the intervention content , as detailed in the educational workshops , was not adhered to : practice staff were unaware of any on-going trainer support ; computer prompts were only added to the female contraception template ; patients were not encouraged to complete the test immediately ; complete chlamydia kits were not always readily available to the clinicians ; and videos and posters were not utilised . Staff reported that financial incentives , themselves , were not a motivator ; competing priorities and time were identified as major barriers . Conclusion Not adhering to the exact intervention model may explain the lack of significant increases in chlamydia screening . To increase fidelity of implementation outside of R and omised Controlled Trial ( RCT ) conditions , and consequently , improve likelihood of increased screening , future public health interventions in general practice s need to have : more specific action planning within the educational workshop ; computer prompts added to systems and used ; all staff attending the workshop ; and on-going practice staff support with feedback of progress on screening and diagnosis rates fed back to all staff Background Chlamydia notifications continue to rise in young people in many countries and regular chlamydia testing is an important prevention strategy . Although there have been initiatives to increase testing in primary care , none have specifically investigated the role of practice nurses ( PNs ) in maximising testing rates . PNs have previously expressed a willingness to be involved , but noted lack of support from general practitioners ( GPs ) as a barrier . We sought GPs ’ attitudes and opinions on PNs taking an exp and ed role in chlamydia testing and partner notification . Methods In the context of a cluster r and omised trial in mostly rural towns in 4 Australian states , semi structured interviews were conducted with 44 GPs between March 2011 and July 2012 . Data relating to PN involvement in chlamydia testing were thematically analysed using a conventional content analysis approach . Results The majority of GPs interviewed felt that a role for PNs in chlamydia testing was appropriate . GPs felt that PNs had more time for patient education and advice , that patients would find PNs easier to talk to and less intimidating than GPs , and that GPs themselves could benefit through a reduction in their workload . Although GPs felt that PNs could be utilised more effectively for preventative health activities such as chlamydia testing , many raised concerns about how these activities would be renumerated whilst some felt that existing workload pressures for PNs could make it difficult for them to exp and their role . Whilst some rural GPs recognised that PNs might be well placed to conduct partner notification , they also recognised that issues of patient privacy and confidentiality related to living in a “ small town ” was also a concern . Conclusion This is the first qualitative study to explore GPs ’ views around an increased role for PNs in chlamydia testing . Despite the concerns raised by PNs , these findings suggest that GPs support the concept and recognise that PNs are suited to the role . However issues raised , such as funding and remuneration may act as barriers that will need to be addressed before PNs are supported to make a contribution to increasing chlamydia testing rates in general practice Background ACCEPt , a large cluster r and omized control trial , aims to determine if annual testing for 16 to 29 year olds in general practice can reduce chlamydia prevalence . ACCEPt is the first trial investigating the potential role of practice nurses ( PN ) in chlamydia testing . To inform the design of the ACCEPt intervention , we aim ed to determine the chlamydia knowledge , attitudes , and testing practice s of participating general practitioners ( GPs ) and PNs . Methods GPs and PNs from 143 clinics recruited from 52 areas in 4 Australian states were asked to complete a survey at time of recruitment . Responses of PNs and GPs were compared using conditional logistic regression to account for possible intra cluster correlation within clinics . Results Of the PNs and GPs enrolled in ACCEPt , 81 % and 72 % completed the question naire respectively . Less than a third of PNs ( 23 % ) and GPs ( 32 % ) correctly identified the two age groups with highest infection rates in women and only 16 % vs 17 % the correct age groups in men . More PNs than GPs would offer testing opportunistically to asymptomatic patients aged ≤25 years ; women having a pap smear ( 84 % vs 55 % , P<0.01 ) ; antenatal checkup ( 83 % vs 44 % , P<0.01 ) and Aboriginal men with a sore throat ( 79 % vs 33 % , P<0.01 ) , but also to patients outside of the guideline age group at the time of the survey ; 26 year old males presenting for a medical check ( 78 % vs 30 % , P = < 0.01 ) and 33 year old females presenting for a pill prescription ( 83 % vs 55 % , P<0.01 ) . More PNs than GPs knew that retesting was recommended after chlamydia treatment ( 93 % vs 87 % , P=0.027 ) ; and the recommended timeframe was 3 months ( 66 % vs 26 % , P<0.01 ) . A high proportion of PNs ( 90 % ) agreed that they could conduct chlamydia testing in general practice , with 79 % wanting greater involvement and 89 % further training . Conclusions Our survey reveals gaps in chlamydia knowledge and management among GPs and PNs that may be contributing to low testing rates in general practice . The ACCEPt intervention is well targeted to address these and support clinicians in increasing testing rates . PNs could have a role in increasing chlamydia testing Objectives : To explore the reasons for the 40-fold variation in diagnostic testing for genital Chlamydia trachomatis by general practice s. Methods : A qualitative study with focus groups . We r and omly selected urban and rural high and low testing practice s served by Bristol , Hereford , and Gloucester microbiology laboratories . Open questions were asked about the investigation of C trachomatis in men and women in different clinical context s. Results : The high and low testing practice s did not differ in their age/sex make-up or by deprivation indices . There were major differences between high and low chlamydia testing practice s. Low testing practice s knew very little about the epidemiology and presentation of genital chlamydia infection and did not consider it in their differential diagnosis of genitourinary symptoms until patients had consulted several times . Low testers were less aware that chlamydia was usually asymptomatic , thought it was an inner city problem , and had poor knowledge of how to take diagnostic specimens . High testing practice s either had a general practitioner with an interest in sexual health or a practice nurse who had completed specialist training in family planning . High testing practice s were more cognizant of the symptoms and signs of chlamydia and always considered it in their differential diagnosis of genitourinary symptoms , including patients attending family planning clinics . Conclusions : Any programme to increase chlamydia testing in primary care must be accompanied by an education and awareness programme especially targeted at low testing practice s. This will need to include information about the benefits of testing and who , when , and how to test Objective To determine the needs of primary healthcare general practice ( GP ) staff , stakeholders and trainers to inform the adaptation of a locally successful complex intervention ( Chlamydia Intervention R and omised Trial ( CIRT ) ) aim ed at increasing chlamydia testing within primary healthcare within South West Engl and to three EU countries ( Estonia , France and Sweden ) and throughout Engl and . Design Qualitative interviews . Setting European primary healthcare in Engl and , France , Sweden and Estonia with a range of chlamydia screening provision in 2013 . Participants 45 GP staff , 13 trainers and 18 stakeholders . Interviews The iterative interview schedule explored participants ’ personal attitudes , subjective norms and perceived behavioural controls around provision of chlamydia testing , sexual health services and training in general practice . Research ers used a common thematic analysis . Results Findings were similar across all countries . Most participants agreed that chlamydia testing and sexual health services should be offered in general practice . There was no culture of GP staff routinely offering opportunistic chlamydia testing or sexual health advice , and due to other priorities , participants reported this would be challenging . All participants indicated that the CIRT workshop covering chlamydia testing and sexual health would be useful if practice based , included all practice staff and action planning , and was adequately re source d. Participants suggested minor adaptations to CIRT to suit their country ’s health services . Conclusions A common complex intervention can be adapted for use across Europe , despite varied sexual health provision . The intervention ( ChlamydiA Testing Training in Europe ( CATTE ) ) should comprise : a staff workshop covering sexual health and chlamydia testing rates and procedures , action planning and patient material s and staff reminders via computer prompts , emails or newsletters , with testing feedback through practice champions . CATTE material s are available at : www.STItraining.eu Background : Chlamydia notifications are increasing in Australia , and the use of a computer alert prompting general practitioners to test young women is a potential way to increase opportunistic chlamydia testing . The aim of this trial was to determine the effectiveness of a computer alert in general practice on chlamydia testing in young women . Methods : In 2006 , clinics ( n = 68 ) in Melbourne , Australia were cluster r and omized into 2 groups : the intervention group received a computerized alert advising the general practitioner to discuss chlamydia testing with their patient which popped up when the medical record of a 16- to 24-year-old woman was opened ; the control group received no alert . The outcome was whether or not that patient received a chlamydia test at the level of a single consultation with an eligible patient . A mixed effects logistic regression model adjusting for clustering was used to assess the impact of the alert on the proportion of women tested for chlamydia during the trial period . Results : Testing increased from 8.3 % ( 95 % confidence interval ( CI ) : 6.8 , 9.8 ) to 12.2 % ( 95 % CI : 9.1 , 15.3 ) ( P < 0.01 ) in the intervention group , and from 8.8 % ( 95 % CI : 6.8 , 10.7 ) to 10.6 % ( 95 % CI : 8.5 , 12.7 ) ( P < 0.01 ) in the control group . Overall , the intervention group had a 27 % ( OR = 1.3 ; 95 % CI : 1.1 , 1.4 ) greater increase in testing . Conclusion : The results of this study suggest that alerts alone may not be sufficient to get chlamydia testing levels up sufficiently high enough to have an impact on the burden of chlamydia in the population but that they could be included as part of a more complex intervention Abstract Objectives : To introduce a psychological model of behaviour ; the COM-B model and describe how this has been used in combination with the behaviour change wheel ( BCW ) in developing an intervention which aims to promote regular , long-term use of hearing aids by adults with acquired hearing loss . Design : Qualitative structured interview study using the COM-B model to identify the determinants of behavioural planning on the part of audiologists ; a potentially important factor in encouraging long-term hearing-aid use . Study sample : Ten audiologists drawn from a r and om sample of five English audiology departments . Results : The analysis suggests that behavioural planning might be more likely to occur if audiologists ’ psychological capability , physical and social opportunity , and reflective and automatic motivation were addressed . This analysis forms the basis of an intervention design , using the BCW , to encourage behavioural planning by audiologists and subsequent hearing-aid use by people with hearing loss . Conclusions : The COM-B model and BCW can be applied successfully in the context of audiology to analyse the behaviour of both people with hearing loss and professionals working with them , supplying information that is being used in intervention design . The effectiveness of the intervention will be tested in a clinical trial R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community |
13,010 | 31,633,805 | Regardless of how people are enrolled , sensitivity is higher in in patients and those with lower CD4 cell , but a concomitant lower specificity .
As a simple point‐of‐care test that does not depend upon sputum evaluation , LF‐LAM may assist with the diagnosis of tuberculosis , particularly when a sputum specimen can not be produced | Background The lateral flow urine lipoarabinomannan ( LF‐LAM ) assay Alere Determine ™ TB LAM Ag is recommended by the World Health Organization ( WHO ) to help detect active tuberculosis in HIV‐positive people with severe HIV disease .
This review up date asks the question , " does new evidence justify the use of LF‐LAM in a broader group of people ? ” ,
and is part of the WHO process for updating guidance on the use of LF‐LAM .
Objectives To assess the accuracy of LF‐LAM for the diagnosis of active tuberculosis among HIV‐positive adults with signs and symptoms of tuberculosis ( symptomatic participants ) and among HIV‐positive adults irrespective of signs and symptoms of tuberculosis ( unselected participants not assessed for tuberculosis signs and symptoms ) .
The proposed role for LF‐LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis . | Background Hospitals in sub-Saharan Africa are inun date d with HIV-infected patients and tuberculosis ( TB ) is the commonest opportunistic infection in this sub-group . Up to one third of TB-HIV co-infected patients fail to produce a sputum sample ( sputum scarce ) and diagnosis is thus often delayed or missed . We investigated the sensitivity of urine-based methods ( Xpert MTB/RIF , LAM strip test and LAM ELISA ) in such patients . Methodology /Principal Findings 281 HIV-infected hospitalised patients with clinical ly suspected TB provided a spot urine sample . The reference st and ard was culture positivity for Mycobacterium tuberculosis on ≥1 sputum or extra-pulmonary sample . MTB/RIF was performed using 1 ml of both unprocessed and , when possible , concentrated urine . Each unconcentrated urine sample was also tested using the Clearview LAM ELISA and Alere LAM strip test . 42 % ( 116/242 ) of patients had culture-proven TB . 18 % ( 20/54 ) were sputum scarce . In sputum-scarce patients , the sensitivity of urine MTB/RIF and LAM ELISA was 40 % ( 95%CI : 22–61 ) and 60 % ( 95%CI : 39–78 ) , respectively . Urine MTB/RIF specificity was 98 % ( 95%CI : 95–100 ) . Combined sensitivity of urine LAM ELISA and MTB/RIF was better than MTB/RIF alone [ MTB/RIF and LAM : 70 % ( 95%CI : 48–85 ) vs. MTB/RIF : 40 % ( 95%CI : 22–61 ) , p = 0.03 ] . Significant predictors of urine MTB/RIF positivity were CD4<50 cells/ml ( p = 0.001 ) , elevated protein-to-creatinine ratio ( p<0.001 ) and LAM ELISA positivity ( p<0.001 ) . Urine centrifugation and pelleting significantly increased the sensitivity of MTB/RIF over unprocessed urine in paired sample s [ 42 % ( 95%CI : 26–58 ) vs. 8 % ( 95%CI : 0–16 ) , p<0.001 ] . Urine MTB/RIF-generated CT values correlated poorly with markers of bacillary burden ( smear grade and time-to-positivity ) . Conclusions / Significance This preliminary study indicates that urine-based MTB/RIF , alone or in combination with LAM antigen detection , may potentially aid the diagnosis of TB in HIV-infected patients with advanced immunosuppression when sputum-based diagnosis is not possible . Concentration of urine prior to MTB/RIF-testing significantly improves sensitivity Background Although antiretroviral therapy ( ART ) is known to be associated with time-dependent reductions in tuberculosis ( TB ) incidence , the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies . We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery . We compared these rates with those of HIV-uninfected individuals living in the same community . Methodology /Principal Findings Prospect ively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed . 1544 patients with a median follow-up of 5.0 years ( IQR 2.4–5.8 ) were included in the analysis . 484 episodes of incident TB ( 73.6 % culture-confirmed ) were diagnosed in 424 patients during 6506 person-years ( PYs ) of follow-up . The TB incidence rate during the first year of ART was 12.4 ( 95 % CI 10.8–14.4 ) cases/100PYs and decreased to 4.92 ( 95 % CI 3.64–8.62 ) cases/100PYs between 5 and 8 years of ART . During person-time accrued within CD4 cell strata 0–100 , 101–200 , 201–300 , 301–400 , 401–500 , 501–700 and ≥700 cells/µL , TB incidence rates ( 95 % CI ) were 25.5 ( 21.6–30.3 ) , 11.2 ( 9.4–13.5 ) , 7.9 ( 6.4–9.7 ) , 5.0 ( 3.9–6.6 ) , 5.1 ( 3.8–6.8 ) , 4.1 ( 3.1–5.4 ) and 2.7 ( 1.7–4.5 ) cases/100PYs , respectively . Overall , 75 % ( 95 % CI 70.9–78.8 ) of TB episodes were recurrent cases . Up date d CD4 cell count and viral load measurements were independently associated with long-term TB risk . TB rates during person-time accrued in the highest CD4 cell count stratum ( > 700 cells/µL ) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community ( 2.7 versus 0.62 cases/100PYs ; 95%CI 0.58–0.65 ) . Conclusions / Significance TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected population s regardless of duration of ART or attainment of CD4 cell counts exceeding 700 Background Detection of lipoarabinomannan ( LAM ) , a Mycobacterium tuberculosis ( Mtb ) cell wall antigen , is a potentially attractive diagnostic . However , the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical population s. We therefore explored pathogen and host factors potentially impacting LAM detection . Methods LAM-ELISA assay testing , sputum smear and culture status , HIV status , CD4 cell count , proteinuria and TB outcomes were prospect ively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic . Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism ( RFLP ) and urines were tested for mycobacteriuria by Xpert ® MTB/RIF assay . Results 32/199 ( 16.1 % ) of patients tested LAM-ELISA positive . Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks . LAM was associated with positive sputum smear and culture status , HIV infection and low CD4 cell counts but not proteinuria , RFLP strain or TB treatment outcome . The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200 , 100 - 199 , 50 - 99 , and < 50 cells/μl , was 15.2 % , 32 % , 42.9 % , and 69.2 % respectively . Mycobacteriuria was found in 15/32 ( 46.9 % ) of LAM positive patients and in none of the LAM negative controls . Conclusions Urinary LAM was related to host immune factors , was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment . The strong association of urine LAM with mycobacteriuria is a new finding , indicating frequent TB involvement of the renal tract in advanced HIV infection Background A rapid diagnostic test for active tuberculosis ( TB ) at the clinical point-of-care could expedite case detection and accelerate TB treatment initiation . We assessed the diagnostic accuracy of a rapid urine lipoarabinomannan ( LAM ) test for TB screening among HIV-infected adults in a TB-endemic setting . Methods We prospect ively enrolled newly-diagnosed HIV-infected adults ( ≥18 years ) at 4 outpatient clinics in Durban from Oct 2011-May 2012 , excluding those on TB therapy . A physician evaluated all participants and offered CD4 cell count testing . Trained study nurses collected a sputum sample for acid-fast bacilli smear microscopy ( AFB ) and mycobacterial culture , and performed urine LAM testing using Determine ™ TB LAM in the clinic . The presence of a b and regardless of intensity on the urine LAM test was considered positive . We defined as the gold st and ard for active pulmonary TB a positive sputum culture for Mycobacterium tuberculosis . Diagnostic accuracy of urine LAM was assessed , alone and in combination with smear microscopy , and stratified by CD4 cell count . Results Among 342 newly-diagnosed HIV-infected participants , 190 ( 56 % ) were male , mean age was 35.6 years , and median CD4 was 182/mm3 . Sixty participants had culture-positive pulmonary TB , result ing in an estimated prevalence of 17.5 % ( 95 % CI 13.7 - 22.0 % ) . Forty-five ( 13.2 % ) participants were urine LAM positive . Mean time from urine specimen collection to LAM test result was 40 minutes ( 95 % CI 34–46 minutes ) . Urine LAM test sensitivity was 28.3 % ( 95 % CI 17.5 - 41.4 ) overall , and 37.5 % ( 95 % CI 21.1 - 56.3 ) for those with CD4 count < 100/mm3 , while specificity was 90.1 % ( 95 % CI 86.0 - 93.3 ) overall , and 86.9 % ( 95 % CI 75.8 - 94.2 ) for those with CD4 < 100/mm3 . When combined with sputum AFB ( either test positive ) , sensitivity increased to 38.3 % ( 95 % CI 26.0 - 51.8 ) , but specificity decreased to 85.8 % ( 95 % CI 81.1 - 89.7 ) . Conclusions In this prospect i ve , clinic-based study with trained nurses , a rapid urine LAM test had low sensitivity for TB screening among newly-diagnosed HIV-infected adults , but improved sensitivity when combined with sputum smear microscopy Background Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal . Data about the value of new diagnostic technologies are limited , particularly , in high burden setting s. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein ( IP-10 ) as a promising diagnostic marker ; however , its diagnostic utility in a day-to-day clinical setting is unclear . Detection of LAM antigen has not previously been evaluated in pleural fluid . Methods We investigated the comparative diagnostic utility of established ( adenosine deaminase [ ADA ] ) , more recent ( st and ardized nucleic-acid-amplification-test [ NAAT ] ) and newer technologies ( a st and ardized LAM mycobacterial antigen-detection assay and IP-10 levels ) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects . All consenting participants underwent pleural biopsy unless contra-indicated or refused . The reference st and ard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis . Principal Findings Of 74 evaluable subjects 48 , 7 and 19 had definite , probable and non-TB , respectively . IP-10 levels were significantly higher in TB vs non-TB participants ( p<0.0001 ) . The respective outcomes [ sensitivity , specificity , PPV , NPV % ] for the different diagnostic modalities were : ADA at the 30 IU/L cut-point [ 96 ; 69 ; 90 ; 85 ] , NAAT [ 6 ; 93 ; 67 ; 28 ] , IP-10 at the 28,170 pg/ml ROC-derived cut-point [ 80 ; 82 ; 91 ; 64 ] , and IP-10 at the 4035 pg/ml cut-point [ 100 ; 53 ; 83 ; 100 ] . Thus IP-10 , using the ROC-derived cut-point , missed ∼20 % of TB cases and mis-diagnosed ∼20 % of non-TB cases . By contrast , when a lower cut-point was used a negative test excluded TB . The NAAT had a poor sensitivity but high specificity . LAM antigen-detection was not diagnostically useful . Conclusion Although IP-10 , like ADA , has sub-optimal specificity , it may be a clinical ly useful rule-out test for tuberculous pleural effusions . Larger multi-centric studies are now required to confirm our findings Background Reducing mortality from HIV-associated tuberculosis ( TB ) requires diagnostic tools that are rapid and have high sensitivity among patients with poor prognosis . We determined the relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays . Methods Consecutive ambulatory patients enrolling for antiretroviral treatment in South Africa were screened for TB regardless of symptoms using diagnostic assays prospect ively applied to sputum ( fluorescence smear microscopy , Xpert MTB/RIF and liquid culture ( reference st and ard ) ) and retrospectively applied to stored urine sample s ( Determine TB-LAM and Xpert MTB/RIF ) . Assay sensitivities were calculated stratified according to pre-defined indices of disease severity : CD4 count , symptom intensity , serum C-reactive protein ( CRP ) , hemoglobin concentration and vital status at 90 days . Results Sputum culture-positive TB was diagnosed in 15 % ( 89/602 ) of patients screened and data from 86 patients were analyzed ( median CD4 count , 131 cells/μL ) including 6 ( 7 % ) who died . The sensitivity of sputum microscopy was 26.7 % overall and varied relatively little with disease severity . In marked contrast , the sensitivities of urine-based and sputum-based diagnosis using Determine TB-LAM and Xpert MTB/RIF assays were substantially greater in sub-groups with poorer prognosis . Rapid diagnosis from sputum and /or urine sample s was possible in > 80 % of patients in sub-groups with poor prognosis as defined by either CD4 counts < 100 cells/μL , advanced symptoms , CRP concentrations > 200 mg/L or hemoglobin < 8.0 g/dl . Retrospective testing of urine sample s with Determine TB-LAM correctly identified all those with TB who died . Conclusions The sensitivities of Xpert MTB/RIF and Determine TB-LAM for HIV-associated TB were highest among HIV-infected patients with the most advanced disease and poorest prognostic characteristics . These data provide strong justification for large-scale intervention studies that assess the impact on survival of screening using these new sputum-based and urine-based diagnostic approaches Background : Tuberculosis ( TB ) causes substantial morbidity and mortality in HIV-infected children . Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging . Rapid diagnostic tools using easily obtained specimens are urgently needed . Methods : Hospitalized , HIV-infected children aged 12 years or less enrolled in a r and omized controlled trial ( NCT02063880 ) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation . At enrollment , sputum or gastric aspirates were collected for TB culture and Xpert , stool for Xpert , and urine for lipoarabinomannan ( LAM ) . When possible , a second sputum/gastric aspirate for culture was obtained . Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture . Results : Among 165 HIV-infected children , median age was 24 months [ interquartile range ( IQR ) 13–58 ] , median CD4+% was 14.3 ( IQR 8.9–22.0 % ) , and 114 ( 69.5 % ) had severe immunosuppression . Thirteen ( 7.9 % ) children had confirmed TB ( positive culture and /or Xpert ) . Sputum/gastric aspirate Xpert , stool Xpert , and urine LAM sensitivities were 60 % [ 95 % confidence interval ( CI ) 26–88 % ] , 63 % ( 95 % CI 25–92 % ) , and 43 % ( 95 % CI 10–82 % ) , respectively . Specificity was 98 % ( 95 % CI 94–100 % ) for sputum/gastric aspirate Xpert , 99 % ( 95 % CI 95–100 % ) for stool Xpert , and 91 % ( 95 % CI 84–95 % ) for urine LAM . Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [ 80 % ( 95 % CI 28–100 ) and 60 % ( 95 % Cl 15–95 % ) ] . Conclusion : Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB . Urine LAM had lower sensitivity and specificity , but increased among children with severe immunosuppression . Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible sample Background Up to one third of HIV-infected individuals with suspected TB are sputum-scarce . The Alere Determine ™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression . However , how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear . Methods This study represents a post hoc sub-group analysis of data from a r and omized multi-center parent study . The study population consisted of hospitalized HIV-infected patients with suspected TB who were unable to produce sputum and who underwent urine LAM testing . The diagnostic utility of urine LAM for TB in this group was compared to the performance of urine LAM in patients who did produce a sputum sample in the parent study . Results There were a total of 187 and 2341 patients in the sputum-scarce and sputum-producing cohorts , respectively . 80 of the sputum-scarce patients underwent testing with urine LAM . In comparison to those who did produce sputum , sputum-scarce patients had a younger age , a lower Karnofsky performance score , and a lower weight and BMI at admission . A greater proportion of sputum-scarce patients were urine LAM positive , compared to those who were able to produce sputum ( 31 % vs. 21 % , p = 0.04 ) . A higher proportion of sputum-scarce patients died within 8 weeks of admission ( 32 % vs. 24 % , p = 0.013 ) . We inferred that 19 % of HIV-infected sputum-scarce patients suspected of TB were diagnosed with tuberculosis by urine LAM testing , with an estimated positive predictive value of 63 % ( 95 % CI 43–82 % ) . Conclusions Urine LAM testing can effectively identify tuberculosis in HIV-infected patients who are at a higher risk of mortality yet are unable to generate a sputum sample for diagnostic testing . Our findings support the use of urine LAM testing in sputum-scarce hospitalized HIV-infected patients , and its incorporation into diagnostic algorithms for this patient population BACKGROUND HIV-associated tuberculosis is difficult to diagnose and results in high mortality . Frequent extra-pulmonary presentation , inability to obtain sputum , and paucibacillary sample s limits the usefulness of nucleic-acid amplification tests and smear microscopy . We therefore assessed a urine-based , lateral flow , point-of-care , lipoarabinomannan assay ( LAM ) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality . METHODS We did a pragmatic , r and omised , parallel-group , multicentre trial in ten hospitals in Africa -- four in South Africa , two in Tanzania , two in Zambia , and two in Zimbabwe . Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis ( fever , cough , night sweats , or self-reported weightloss ) and illness severity necessitating admission to hospital . Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment . We r and omly assigned patients ( 1:1 ) to either LAM plus routine diagnostic tests for tuberculosis ( smear microscopy , Xpert-MTB/RIF , and culture ; LAM group ) or routine diagnostic tests alone ( no LAM group ) using computer-generated allocation lists in blocks of ten . All patients were asked to provide a urine sample of at least 30 mL at enrolment , and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test ( Alere , USA ) at the bedside on enrolment . On the basis of a positive test result , the nurses made a recommendation for initiating anti-tuberculosis treatment . The attending physician made an independent decision about whether to start treatment or not . Neither patients nor health-care workers were masked to group allocation and test results . The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population ( those who received their allocated intervention ) . This trial is registered with Clinical Trials.gov , number NCT01770730 . FINDINGS Between Jan 1 , 2013 , and Oct 2 , 2014 , we screened 8728 patients and r and omly assigned 2659 to treatment ( 1336 to LAM , 1323 to no LAM ) . 108 patients did not receive their allocated treatment , mainly because they did not meet the inclusion criteria , and 23 were excluded from analysis , leaving 2528 in the final modified intention-to-treat analysis ( 1257 in the LAM group , 1271 in the no LAM group ) . Overall all-cause 8-week mortality occurred in 578 ( 23 % ) patients , 261 ( 21 % ) in LAM and 317 ( 25 % ) in no LAM , an absolute reduction of 4 % ( 95 % CI 1 - 7 ) . The risk ratio adjusted for country was 0·83 ( 95 % CI 0·73 - 0·96 ) , p=0·012 , with a relative risk reduction of 17 % ( 95 % CI 4 - 28 ) . With the time-to-event analysis , there were 159 deaths per 100 person-years in LAM and 196 per 100 person-years in no LAM ( hazard ratio adjusted for country 0·82 [ 95 % CI 0·70 - 0·96 ] , p=0·015 ) . No adverse events were associated with LAM testing . INTERPRETATION Bedside LAM-guided initiation of anti-tuberculosis treatment in HIV-positive hospital in patients with suspected tuberculosis was associated with reduced 8-week mortality . The implementation of LAM testing is likely to offer the greatest benefit in hospitals where diagnostic re sources are most scarce and where patients present with severe illness , advanced immunosuppression , and an inability to self-expectorate sputum . FUNDING European Developing Clinical Trials Partnership , the South African Medical Research Council , and the South African National Research Foundation Background Mortality in hospitalized , febrile patients in Sub-Saharan Africa is high due to HIV-infected , severely immunosuppressed patients with opportunistic co-infection , particularly disseminated tuberculosis ( TB ) and cryptococcal disease . We sought to determine if a positive lateral flow assay ( LFA ) result for urine lipoarabinomannan ( LAM ) and cryptococcal antigenuria was associated with mortality . Methods 351 hospitalized , HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospect ively enrolled at Mulago National Referral Hospital in Ug and a as part of a prospect i ve accuracy evaluation of the lateral flow Determine TB LAM test . Stored frozen urine was retrospectively tested for cryptococcal antigen ( CRAG ) using the LFA . We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation . Results The median CD4 of the participants was 57 ( IQR : 14–179 ) cells/µl and 41 % ( 145 ) were microbiologically confirmed TB cases . LAM LFA was positive in 38 % ( 134 ) , 7 % ( 25 ) were CRAG positive , and 43 % ( 151 ) were positive for either test in urine . Overall , 21 % ( 75 ) died within the first 2 months , and a total of 32 % ( 114 ) were confirmed dead by 6 months . At 2 months , 30 % of LAM or CRAG positive patients were confirmed dead compared to 15.0 % of those who were negative . In an adjusted model , LAM or CRAG positive results were associated with an increased risk of death ( RRR 2.29 , 95 % CI : 1.29 , 4.05 ; P = 0.005 ) . Conclusions In hospitalized HIV-infected patients , LAM or CRAG LFA positivity was associated with subsequent death within 2 months . Further studies are warranted to examine the impact of POC diagnostic ‘ test and treat ’ approach on patient-centered outcomes Background Upon initiation of antiretroviral therapy ( ART ) , 15.7 % [ 95 % confidence interval ( CI ) : 9.7 % to 24.5 % ] of tuberculosis (TB)-HIV – coinfected individuals experience paradoxical worsening of their clinical status with exuberant inflammation consistent with immune reconstitution inflammatory syndrome ( IRIS ) . We investigated whether a positive urinary TB lipoarabinomannan ( LAM ) antigen enzyme-linked immunosorbent assay test before ART initiation was associated with development of paradoxical TB-IRIS . Methods In a prospect i ve observational cohort in Mulago Hospital , Kampala , Ug and a , we measured pre-ART urinary LAM concentrations in HIV-infected patients on TB treatment . Patients who developed TB-IRIS ( according to the International Network for the Study of HIV-associated IRIS case definition ) were compared with patients who remained IRIS free for at least 3 months . Results Twenty-six individuals with TB-IRIS and 64 without IRIS were included in the analysis . The median time to TB-IRIS was 14 days ( interquartile range : 11–14 days ) . Univariate analysis showed that a positive pre-ART urinary LAM test [ OR : 4.6 ( 95 % CI : 1.5 to 13.8 ) , P = 0.006 ] and a CD4 count < 50 cells/mL [ OR : 21 ( 95 % CI : 2.6 to 169.4 ) , P = 0.004 ] were associated with an increased risk of TB-IRIS . In multivariate analysis , only a baseline CD4 T-cell count < 50 cells/mL was predictive of IRIS ( P < 0.004 ) . Sensitivity and specificity of a positive pre-ART urinary LAM test to diagnose IRIS were 80.8 % ( 95 % CI : 60.6 to 93.4 ) and 52.4 % ( 95 % CI : 39.4 to 65.1 ) , respectively . Conclusions If CD4 T-cell count testing is available , a pre – highly active antiretroviral therapy urinary LAM test has no added value to predict TB-IRIS . When CD4 T-cell count is not available , a positive LAM test could identify patients at increased risk of TB-IRIS Background The commercially available urine LAM strip test , a point-of-care tuberculosis ( TB ) assay , requires evaluation in a primary care setting where it is most needed . There is currently inadequate data to guide implementation in TB and HIV-endemic setting s. Methods Adult HIV-infected out patients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa , Zambia and Tanzania underwent diagnostic evaluation [ sputum smear microscopy , Xpert-MTB/RIF , and culture ( reference st and ard ) ] as part of a prospect i ve parent study . Urine LAM testing ( grade -2 cut-point ) was performed on archived sample s. Performance characteristics of LAM alone or in combination with sputum — based diagnostics were evaluated . Potential impact on 2 and 6-month morbidity ( TBscore ) , patient dropout rates , and prognosis ( death/ loss to follow-up ) were evaluated . Results Among 583 participants with suspected TB that were HIV-infected or refused testing , the overall LAM sensitivity ( 95 % CI ; n/N ) and in the CD4 ≤ 100 cells/mm3 sub-group was 22.7 % ( 16.6 - 28.7 ; 41/181 ) and 30.4 % ( 17.1 - 43.7 ; 14/46 ) , respectively . Overall specificity was 93.0 % ( 90.5 - 95.6 ; 361/388 ) . Amongst culture-positive TB cases , adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [ 78.2 % ( 69.8 - 86.7 ; 72/92 ) versus 76.1 % ( 67.4 - 84.8 ; 70/92 ) , p = 0.7 ] or smear-microscopy [ 56.2 % ( 45.9 - 66.5 ; 50/89 ) versus 43.8 % ( 33.5 - 54.1 ; 39/89 ) , p = 0.1 ) . Clinic-based LAM , as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing , would neither have decreased patient dropout , nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available . LAM positivity was associated with 6-month lost-to-follow-up/death ( AOR 4.4 ; p = 0.002 ) but not TBscore ( at baseline or change in TBscore 2-months post-treatment ) ( p = 0.17 ) . Conclusions In African HIV-TB co-infected out patients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts , and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy . In primary care clinics with chest radiography and where empiric TB treatment is common , LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout , however , the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan ( LAM ) into the urine , the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay , in children with suspected tuberculosis ( TB ) in a high TB/HIV-prevalence setting . In a prospect i ve study , 132 children with suspected active TB were assigned to diagnostic subgroups . Urine sample s were subjected to testing by both assays to ascertain sensitivity and specificity . Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation . 18 ( 13.6 % ) children had culture-confirmed pulmonary TB . The assays ' sensitivity was higher in HIV-positive versus HIV-negative children : 70 % ( 95 % confidence interval 35–93 % ) versus 13 % ( 0–53 % ) for MTB-LAM-ELISA and 50 % ( 19–81 % ) versus 0 % ( 0–37 % ) for Determine TB-LAM . In 35 ( 27 % ) children with excluded active TB , both assays showed a specificity of 97.1 % ( 85–100 % ) . Proteinuria and low body mass index were independently associated with LAM positivity . In most patients , LAM excretion declined to zero during or at conclusion of antituberculous treatment . HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality . Using LAM as a rule-in and treatment-monitoring tool may also show further potential . Urine lipoarabinomannan assays show reasonable sensitivity in HIV+ but not HIV− TB-infected children Objective To determine if urinary lipoarabinomannan ( LAM ) may serve as a biomarker to monitor antituberculosis ( TB ) therapy response , and whether LAM results before and after treatment are predictive of patient outcomes . Design Prospect i ve cohort . Setting Outpatient referral clinic and tertiary hospital in South Africa . Participants Adults ( ≥18 years ) with ≥2 TB-related symptoms ( cough , fever , weight loss , night sweats ) for ≥2 weeks being initiated on anti-TB therapy . Interventions On enrolment , we obtained urine and nebulised sputum specimens , offered HIV testing and started participants on anti-TB therapy for ≥6 months . We collected urine sample s after the 2-month intensive treatment phase and at the completion of anti-TB therapy . Positive LAM results were grade d from 1 ( low ) to 5 ( high ) . Participants were followed for > 3 years . Outcome measures The primary outcome was change in urine LAM results during anti-TB therapy . The secondary outcome was all-cause mortality . Results Among 90 participants , 57 ( 63 % ) had culture-confirmed pulmonary TB . Among the 88 participants tested , 82 ( 93 % ) were HIV-infected with median CD4 168/mm3 ( IQR 89–256/mm3 ) . During anti-TB therapy , the percentage of LAM-positive participants decreased from baseline to 2 months ( 32 % to 16 % ) , and from baseline to 6-months ( 32 % to 10 % ) ( p values < 0.005 ) . In multivariate longitudinal analyses , urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB ( p<0.0001 ) , and had no change in sputum culture-negative participants . At the 2-month visit , participants with positive laboratory-based LAM or rapid LAM with ≥2 + grade had a significantly greater risk of mortality . In analyses adjusted for age , sex , baseline Karnofsky score and HIV status , participants with a rapid LAM ≥2 + grade after 2 months of anti-TB therapy had a 5.6-fold ( 95 % CI 1.2 to 25.2 ) greater risk of mortality . Conclusions Rapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions Background The inherent risk of developing tuberculosis ( TB ) in HIV- infected individuals is further enhanced by hypovitaminosis D. Interventions that offset HIV-associated immune deterioration potentially arrest disease progression and incidence of opportunistic infections including TB . Despite conflicting reports on association between vitamin D deficiency ( VDD ) and risk of TB , vitamin D ( VD ) supplementation remains a promising intervention . Methods We conducted a comparative cross-sectional study on 145 HIV+/pulmonary TB+ ( PTB ) and 139 HIV+/PTB− hospitalised patients to investigate association of vitamin D status and risk of PTB . Stratified r and om sampling was used to select archived serum specimens from participants enrolled in a r and omised controlled trial ( RCT ) conducted to investigate the impact of using a point-of-care urine lipoarabinomannan strip test for TB diagnosis . PTB status was confirmed using sputum smear microscopy , culture or GeneXpert MTB/RIF . Serum 25-hydroxyvitamin D [ 25(OH ) D ] concentrations were assayed by competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment . Effect of VD status on duration of hospital stay and patient outcomes on follow up at 8 weeks were also investigated . Median serum 25(OH ) D concentrations were compared using Mann-Whitney test and covariates of serum VD status were assessed using logistic regression analysis . Results Overall VDD prevalence in the cohort was 40.9 % ( 95 % CI : 35.1–46.8 ) . Median serum 25(OH)D concentrations were significantly higher in HIV+/PTB+ group ( 25.3 ng/ml , IQR:18.0–33.7 ) compared to the HIV+/PTB− group ( 20.4 ng/ml , IQR:14.6–26.9 ) , p = 0.0003 . Patients with serum 25(OH ) D concentration ≥ 30 ng/ml were 1.9 times more likely to be PTB+ compared to those with serum 25(OH ) D concentrations < 30 ng/ml ( odds ratio ( OR ) 1.91 ; 95 % CI 1.1–3.2 ) . PTB-related death was associated with higher odds of having 25(OH ) D levels≥30 ng/ml . Age , gender , CD4 + count , combination antiretroviral therapy ( cART ) status , efavirenz based cART regimen and length of hospital stay were not associated with vitamin D status . Conclusions The finding of an association between higher serum 25(OH ) D concentrations and active PTB and TB-related mortality among hospitalised HIV-infected patients in the present study is at variance with the commonly reported association of hypovitaminosis and susceptibility to TB . Our findings though , are in concordance with a small pool of reports from other setting Background HIV-associated tuberculosis ( TB ) co-infection remains an enormous burden to international public health . Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB . Determine TB-LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission . However , it remains unclear if this approach can impact clinical outcomes . The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current , sputum-based screening . Methods The trial is a pragmatic , individually r and omised , multi-country ( Malawi and South Africa ) clinical trial with two study arms ( 1:1 recruitment ) . Unselected HIV-positive patients admitted to medical wards , irrespective of presentation , meeting the inclusion criteria and giving consent will be r and omized to screening for TB using either : ( i ) ‘ st and ard of care’- testing of sputum using the Xpert MTB/RIF assay ( Xpert ) or ( ii ) ‘ intervention’- testing of sputum using Xpert and testing of urine using ( a ) Determine TB-LAM lateral-flow assay and ( b ) Xpert following concentration of urine by centrifugation . Patients will be excluded if they have received TB treatment in the previous 12 months , if they have received isoniazid preventive therapy in the last 6 months , if they are aged < 18 years or they live outside the pre-specified geographical area . Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment . Both the study and routine medical team will be masked to study arm allocation . 1300 patients will be enrolled per arm ( equal numbers at the two trial sites ) . The primary endpoint is all-cause mortality at 56 days . An economic analysis will be conducted to project long-term outcomes for shorter-term trial data , including cost-effectiveness . Discussion This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB , which could feasibly be scaled up in high-burden setting s if shown to be efficacious and cost-effective . We discuss the challenges of design ing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes . We also elaborate on the practical and ethical issues of ‘ testing a test ’ in general . Trial registration IS RCT N Registry ( IS RCT N71603869 ) prospect ively registered 08 May 2015 ; the South African National Controlled Trials Registry ( DOH-27 - 1015 - 5185 ) prospect ively registered October 2015 OBJECTIVE To evaluate a commercially available antigen capture enzyme-linked immunosorbent assay ( ELISA ) based on detecting lipoarabinomannan ( LAM ) in urine for the diagnosis of tuberculosis ( TB ) . DESIGN Consenting TB suspects and registering TB patients prospect ively recruited from three hospitals were asked for two sputum specimens for microscopy and culture , urine for LAM testing and blood for human immunodeficiency virus ( HIV ) testing , with radiological and clinical follow-up for 2 months . RESULTS Of 427 participants , complete data were available from 397 ( 307 adult and 23 adolescent TB suspects , and 67 registering TB patients ) . HIV prevalence was 77 % . TB was diagnosed in 195 ( 49 % ) , including 161 culture-positive patients , and confidently excluded in 114 ( 29 % ) participants . LAM ELISA sensitivity was 44 % ( 95%CI 36 - 52 ) for culture-confirmed TB ( 52 % in smear-positive patients ) . Specificity was 89 % ( 95%CI 81 - 94 ) . Sensitivity was significantly higher in HIV-related TB ( 52 % , 95%CI 43 - 62 , P < 0.001 ) compared to HIV-negative TB ( 21 % , 95%CI 9 - 37 ) . Sensitivity in smear-negative patients was low ( 28 % , 95%CI 13 - 43 ) for combined HIV-positive and -negative patients . CONCLUSION Our findings confirm greater sensitivity of urine LAM detection for HIV-related TB . However , both sensitivity and specificity were suboptimal , suggesting that this version can not confirm or exclude TB in either HIV-infected or non-infected patients Background In Africa , tuberculous meningitis ( TBM ) is an important opportunistic infection in HIV-positive patients . Current diagnostic tools for TBM perform sub-optimally . In particular , the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in re source -poor setting s. Methods We evaluated the performance outcome of a novel st and ardized lipoarabinomannan ( LAM ) antigen-detection assay , using archived cerebrospinal fluid sample s , in 50 African TBM suspects of whom 68 % were HIV-positive . Results Of the 50 participants 14 , 23 and 13 patients had definite , probable and non-TBM , respectively . In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded . The test sensitivities and specificities were as follows : LAM assay 64 % and 69 % ( cut-point 0.22 ) , smear microscopy 0 % and 100 % and PCR 93 % and 77 % , respectively . Conclusion In this preliminary proof-of-concept study , a rapid diagnosis of TBM could be achieved using LAM antigen detection . Although specificity was sub-optimal , the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up . As PCR is largely unavailable , the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence setting s. These preliminary results justify further enquiry and prospect i ve studies are now required to definitively establish the place of this technology for the diagnosis of TBM Background The urine lipoarabinomannan ( LAM ) strip test has been suggested as a new point-of-care test for active tuberculosis ( TB ) among human immunodeficiency virus ( HIV ) infected individuals . It has been question ed if infections with nontuberculous mycobacteria ( NTM ) affect assay specificity . We set forth to investigate if the test detects LAM in urine from a Danish cystic fibrosis ( CF ) population characterized by a high NTM prevalence and negligible TB exposure . Method Patients followed at the Copenhagen CF Center were comprehensively screened for pulmonary NTM infection between May 2012 and December 2013 . Urine sample s were tested for LAM using the 2013 Determine ™ TB LAM Ag strip test . Results Three-hundred and six patients had a total of 3,322 respiratory sample s cultured for NTM and 198 had urine collected ( 65 % ) . A total of 23/198 ( 12 % ) had active pulmonary NTM infection . None had active TB . The TB-LAM test had an overall positive rate of 2.5 % applying a grade 2 cut-point as positivity threshold , increasing to 10.6 % ( 21/198 ) if a grade 1 cut-point was applied . Among patients with NTM infection 2/23 ( 8.7 % ) had a positive LAM test result at the grade 2 cut-point and 9/23 ( 39.1 % ) at the grade 1 cut -point . Test specificity for NTM diagnosis was 98.3 % and 93.1 for grade 2 and 1 cut-point respectively . Conclusions This is the first study to assess urine LAM detection in patients with confirmed NTM infection . The study demonstrated low cross-reactivity due to NTM infection when using the recommended grade 2 cut-point as positivity threshold . This is reassuring in regards to interpretation of the LAM test for TB diagnosis in a TB prevalent setting . The test was not found suitable for NTM detection among patients with CF Background The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals . New TB diagnostics such as urine TB lipoarabinomannan ( LAM ) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB . We sought to determine predictors for MTB culture-positivity among these patients . Methods This study was nested into a prospect i ve evaluation of HIV-infected out patients and in patients clinical ly suspected to have TB who were screened by smear-microscopy on two spot sputum sample s. Data on socio-demographics , clinical symptoms , antiretroviral therapy , CXR , CD4 count , mycobacterial sputum and blood cultures and TB-LAM were collected . Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity . Results Of the 418 smear-negative participants [ female , 64 % ; median age ( IQR ) 32 ( 28 - 39 ) years , median CD4 106 ( IQR 22 - 298 ) cells/mm3 ] , 96/418 ( 23 % ) were sputum and / or blood culture-positive for Mycobacterium tuberculosis ( MTB ) complex . Abnormal CXR ( aOR 3.68 , 95 % CI 1.76- 7.71 , p=0.001 ) and positive urine TB-LAM ( aOR 6.21 , 95 % CI 3.14 - 12.27 , p < 0.001 ) were significantly associated with MTB culture-positivity . Previous TB treatment ( aOR 0.41 , 95 % CI 0.17 - 0.99 , p=0.049 ) reduced the likelihood of a positive MTB culture . A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity . A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50 % and 86.1 % respectively overall , and 70.8 % and 84.1 % respectively among those with CD4<100 cells/mm3 . Conclusions A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture . Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted Background Determine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients . We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs , sputum smear-microscopy , chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB ( PTB ) . Methods Prospect i ve observational cohort of ambulatory ( either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2 ) and hospitalized symptomatic HIV-positive adults in Kenya . Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients ( positive Xpert or MTB culture ) diagnosed by the algorithm with LAM compared to the algorithm without LAM . The multivariable mortality model was adjusted for age , sex , clinical severity , BMI , CD4 , ART initiation , LAM result and TB confirmation . Results Among 474 patients included , 44.1 % were severely ill , 69.6 % had CD4<200cells/μl , 59.9 % had initiated ART , 23.2 % could not produce sputum . LAM , smear-microscopy , Xpert and culture in sputum were positive in 39.0 % ( 185/474 ) , 21.6 % ( 76/352 ) , 29.1 % ( 102/350 ) and 39.7 % ( 92/232 ) of the patients tested , respectively . Of 156 patients with confirmed TB , 65.4 % were LAM positive . Of those classified as non-TB , 84.0 % were LAM negative . Adding LAM increased the diagnostic yield of the algorithms by 36.6 % , from 47.4 % ( 95%CI:39.4–55.6 ) to 84.0 % ( 95%CI:77.3–89.4 % ) , when using clinical signs and X-ray ; by 19.9 % , from 62.2 % ( 95%CI:54.1–69.8 ) to 82.1 % ( 95%CI:75.1–87.7 ) , when using clinical signs and microscopy ; and by 13.4 % , from 74.4 % ( 95%CI:66.8–81.0 ) to 87.8 % ( 95%CI:81.6–92.5 ) , when using clinical signs and Xpert . LAM positive patients had an increased risk of 2-months mortality ( aOR:2.7 ; 95%CI:1.5–4.9 ) . Conclusion LAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory ( severely ill or CD4<200cells/μl ) or hospitalized . LAM allows same day treatment initiation in patients at higher risk of death and in those not able to produce sputum Background In Zimbabwe , sputum smear microscopy ( SSM ) is the routinely used TB diagnostic tool in hospitalised HIV-infected patients . However , SSM has poor sensitivity in HIV-infected patients . We compared performance of urine lipoarabinomannan strip test ( LAM ) and SSM among hospitalized HIV-infected patients with suspected TB . Methods Hospitalized HIV-infected patients with suspected TB were r and omized to LAM plus SSM or SSM alone groups as part of a larger multi-country parent study . Here we present a comparison of LAM versus SSM performance from the Zimbabwe study site . LAM analyses ( grade 2 cut-off ) were conducted using ( i ) a microbiological reference st and ard ( MRS ; culture positivity for M.tb and design ated definite TB ) and ( ii ) a composite reference st and ard ( CRS ; definite TB plus probable TB i.e. patients with clinical TB excluded from the culture negative group ) . CRS constituted the primary analysis . Results 82/457 ( 18 % ) of the patients r and omized to the LAM group were M.tuberculosis culture positive . Using CRS , sensitivity ( % , 95 % CI ) of LAM was significantly higher than SSM [ 49.2 ( 42.1 - 56.4 ) versus 29.4(23.2 - 36.3 ) ; p < 0.001 ] . Specificity and PPV were 98.1 % , and 95.8 % , respectively . By contrast , using MRS , LAM sensitivity was similar to SSM and specificity was significantly lower , however , the combined sensitivity of LAM and SSM was significantly higher than that of SSM alone , p = 0.009 . Using CRS , LAM sensitivity ( % , CI ) was CD4 count dependent [ 60.6(50.7 - 69.8 ) at ≤50 cells/μL ; 40.0(22.7 - 59.4 ) at 51 - 100 cells/μL , and 32.8(21.0 - 46.3 ) at > 100 cells/μL. The combined sensitivity of LAM and SSM was higher than SSM alone being highest at CD4 counts < 50 cells/μL [ 67.6(57.9 - 76.3 ) ; p = < 0.001 ] . Specificity of LAM or SSM alone , or of combined LAM and SSM was > 97 % in all the 3 CD4 strata . Conclusion Among hospitalized HIV-infected patients with suspected TB , the sensitivity of LAM is significantly higher than that of SSM , especially at low CD4 counts . LAM and SSM are complimentary tests for diagnosis of TB in HIV-infected patients . We recommend a combination of LAM and SSM for TB diagnosis in HIV-infected patients with low CD4 counts in HIV/TB co-endemic countries , where alternative methods are unavailable Background Diagnosis of tuberculosis is difficult among pregnant women because the signs and symptoms of the disease , such as fatigue , shortness of breath , sweating , cough , and mild fever are similar to some manifestations of pregnancy . It is particularly challenging among HIV-infected women as symptoms are often masked or atypical . Currently , WHO recommends a st and ard four-symptom screening tool for pregnant and lactating women . There is evidence from South Africa that this screening tool ( which , despite complex symptomology in this population , recommends identification of patients with weight loss , fever , current cough and night sweats ) , may be missing true active TB cases . However there exist several laboratory and clinical procedures that have the potential to improve the sensitivity and specificity of this screening tool . Methods This study will evaluate the sensitivity and specificity of the current TB screening tool for pregnant and lactating women , both HIV positive and negative . We will also assess several different enhanced screening algorithm using LAM , IGRA , TST and chest radiography and clinical /laboratory procedures and tests . The study will use a cross-sectional analytical study design involving pregnant and lactating women up to six months post-delivery attending antenatal or postnatal care , respectively in one of three selected public health units in Swazil and . Participants will be consecutively enrolled and will be in one of four groups of interest : HIV infected pregnant women , non-HIV infected pregnant women , HIV infected lactating women and non-HIV infected lactating women . Discussion We expect in conducting all procedures on all participants regardless of result of the symptom screening we may experience a high refusal rate . However , this risk will be mitigated by the long data collection period of five or more months Background Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis ( TB ) mortality . We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan ( LAM ) test for pulmonary TB and assessed the effect of a two- sample strategy . Methods HIV-infected adults eligible for antiretroviral therapy were prospect ively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months . We applied the LAM test on urine collected as a spot and early morning sample . Diagnostic accuracy was analysed for a microbiological TB reference st and ard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference st and ard including clinical follow-up data . Performance of sputum smear microscopy was included for comparison . Results Of 469 patients investigated for TB , the LAM test correctly identified 24/55 ( 44 % ) of microbiologically confirmed TB cases . Sensitivity of the LAM test was positively associated with hospitalisation ( 67 % ) , Modified Early Warning Score > 4 ( 57 % ) and subsequent death ( 71 % ) . LAM test specificity was 95 % increasing to 98 % for the composite reference st and ard . A two- sample LAM test strategy did not improve test performance . Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 ( 56 % ) that increased to 35/55 ( 64 % ) when the LAM test was added . Surprisingly , nontuberculous mycobacteria were cultured in 34/469 ( 7 % ) and associated with a positive LAM test ( p = 0.008 ) . Conclusions LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two- sample strategy . A rigorous sputum microscopy strategy had superior sensitivity , but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients Lack of point-of-care tests for tuberculosis ( TB ) result in diagnostic delay , and increased mortality and healthcare-related costs . The urine DetermineTM TB-LAM point-of-care strip-test was evaluated in 335 prospect ively-recruited hospitalised patients with suspected TB-HIV co-infection ( group 1 ) and from 88 HIV-infected hospitalised patients with non-TB diagnoses ( group 2 ) . Cut-off point-specific analyses were performed using : 1 ) a microbiological reference st and ard ( culture positive versus negative ) ; and 2 ) a composite reference st and ard ( exclusion of patients with clinical -TB from the culture-negative group ) . Using the microbiological reference and the manufacturer-recommended grade -1 cut-off point , LAM sensitivity and specificity was 66 % ( 95 % CI 57–74 % ) . By contrast , using the composite reference sensitivity was 60 % ( 95 % CI 53–67 % ) and specificity improved to 96 % ( 95 % CI 89–100 % ) ( p=0.001 ) . The same pattern was seen when the grade -2 cut-off point was used ( specificity 75 % versus 96 % ; p=0.01 ) . In group two patients specificity was poor using the grade -1 cut-off point , but improved significantly when the grade -2 cut-off point was used ( 90 % versus 99 % ; p=0.009 ) . The grade -2 cut-off point also offered superior inter-reader reliability ( p=0.002 ) . Sensitivity was highest in those with a CD4 < 200 cells per mL. LAM combined with smear-microscopy was able to rule-in TB in 71 % of Mycobacterium tuberculosis culture-positive patients . This preliminary study indicates that the LAM strip-test may be a potentially useful rapid rule-in test for TB in hospitalised patients with advanced immunosuppression . The grade 2 , but not the manufacturer-recommended grade 1 cut-off point , offered superior rule-in utility and inter-reader reliability . Larger studies to evaluate cut-off points and diagnostic accuracy are urgently required Background Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression . However , sensitivity remains suboptimal . We therefore examined the incremental diagnostic sensitivity of early morning urine ( EMU ) versus r and om urine sampling using the Determine ® lateral flow lipoarabinomannan assay ( LF-LAM ) in HIV-TB co-infected patients . Methods Consenting HIV-infected in patients , screened as part of a larger prospect i ve r and omized controlled trial , that were treated for TB , and could donate matched r and om and EMU sample s were included . Thus paired sample were collected from the same patient , LF-LAM was grade d using the pre-January 2014 , with grade 1 and 2 manufacturer- design ated cut-points ( the latter design ated grade 1 after January 2014 ) . Single sputum Xpert-MTB/RIF and /or TB culture positivity served as the reference st and ard ( definite TB ) . Those treated for TB but not meeting this st and ard were design ated probable TB . Results 123 HIV-infected patients commenced anti-TB treatment and provided matched r and om and EMU sample s. 33 % ( 41/123 ) and 67 % ( 82/123 ) had definite and probable TB , respectively . Amongst those with definite TB LF-LAM sensitivity ( 95%CI ) , using the grade 2 cut-point , increased from 12 % ( 5–24 ; 5/43 ) to 39 % ( 26–54 ; 16/41 ) with r and om versus EMU , respectively ( p = 0.005 ) . Similarly , amongst probable TB , LF-LAM sensitivity increased from 10 % ( 5–17 ; 8/83 ) to 24 % ( 16–34 ; 20/82 ) ( p = 0.001 ) . LF-LAM specificity was not determined . Conclusion This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients . These data have implication s for clinical practice This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence BACKGROUND Inadequate case detection results in high levels of undiagnosed tuberculosis in sub-Saharan Africa . Data for the effect of new diagnostic tools when used for community-based intensified case finding are not available , so we investigated whether the use of sputum Xpert-MTB/RIF and the Determine TB LAM urine test in two African communities could be effective . METHODS In a pragmatic , r and omised , parallel-group trial with individual r and omisation stratified by country , we compared sputum Xpert-MTB/RIF , and if HIV-infected , the Determine TB LAM urine test ( novel diagnostic group ) , with laboratory-based sputum smear microscopy ( routine diagnostic group ) for intensified case finding in communities with high tuberculosis and HIV prevalence in Cape Town , South Africa , and Harare , Zimbabwe . Participants were r and omly assigned ( 1:1 ) to these groups with computer-generated allocation lists , using culture as the reference st and ard . In Cape Town , participants were r and omised and tested at an Xpert-equipped mobile van , while in Harare , participants were driven to a local clinic where the same diagnostic tests were done . The primary endpoint was the proportion of culture-positive tuberculosis cases initiating tuberculosis treatment in each study group at 60 days . This trial is registered at Clinical Trials.gov , number NCT01990274 . FINDINGS Between Oct 18 , 2013 , and March 31 , 2015 , 2261 individuals were screened and 875 ( 39 % ) of these met the criteria for diagnostic testing . 439 participants were r and omly assigned to the novel group and 436 to the routine group . 74 ( 9 % ) of 875 participants had confirmed tuberculosis . If late culture-based treatment initiation was excluded , more patients with culture-positive tuberculosis were initiated on treatment in the novel group at 60 days ( 36 [ 86 % ] of 42 in the novel group vs 18 [ 56 % ] of 32 in the routine group ) . Thus the difference in the proportion initiating treatment between groups was 29 % ( 95 % CI 9 - 50 , p=0·0047 ) and 53 % more patients initiated therapy in the novel diagnostic group than in the routine diagnostic group . One culture-positive patient was treated based only on a positive LAM test . INTERPRETATION Compared with traditional tools , Xpert-MTB/RIF for community-based intensified case finding in HIV and tuberculosis-endemic setting s increased the proportion of patients initiating treatment . By contrast , urine LAM testing was not found to be useful for intensive case finding in this setting . FUNDING European and Developing Countries Clinical Trials Partnership and South African Medical Research Council Objective : In setting s of high HIV prevalence , tuberculosis control and patient management are hindered by lack of accurate , rapid tuberculosis diagnostic tests that can be performed at point-of-care . The Determine TB LAM Ag ( TB LAM ) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan ( LAM ) in urine . Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis . Design : Prospect i ve diagnostic accuracy study . Setting : Hospital and outpatient setting s in Ug and a and South Africa . Participants : HIV-infected adults with tuberculosis symptoms and /or signs . Methods : Participants provided a fresh urine specimen for TB LAM testing , blood for mycobacterial culture , and 2 respiratory specimens for smear microscopy and mycobacterial culture . Main Outcome Measures : For the TB LAM test , sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis . Results : A total of 1013 participants were enrolled . Among culture-positive tuberculosis patients , the TB LAM test identified 136/367 ( 37.1 % ) overall and 116/196 ( 59.2 % ) in the group with CD4 ⩽100 cells per cubic millimeter . The test was specific in 559/573 ( 97.6 % ) patients without tuberculosis . Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 ( 53.7 % ) overall and 133/196 ( 67.9 % ) among those with CD4 ⩽100 . CD4 ⩽50 [ adjusted odds ratio ( AOR ) , 6.2 ; P < 0.001 ] or 51–100 ( AOR , 7.1 ; P < 0.001 ) , mycobacteremia ( AOR , 6.1 ; P < 0.01 ) and hospitalization ( AOR , 2.6 ; P = 0.03 ) were independently associated with a positive TB LAM test . Conclusions : In HIV-positive adults with CD4 ⩽100 , the TB LAM urine test detected over half of culture-positive tuberculosis patients , in < 30 minutes and without the need for equipment or reagents SETTING Urine antigen testing is an attractive strategy for the diagnosis of active tuberculosis ( TB ) , but accuracy data are scarce . OBJECTIVE To prospect ively evaluate the diagnostic performance of commercial urinary lipoarabinomannan ( LAM ) antigen testing for active TB among pulmonary and extra-pulmonary TB suspects . DESIGN Prospect i ve blinded evaluation of 200 adult TB suspects at a tertiary referral hospital in India . Reference st and ards included culture and clinical diagnosis . RESULTS Patients were 61 % male ( mean age 40.4 years ) : 8.5 % were human immunodeficiency virus ( HIV ) infected and 47 of 200 ( 23.5 % ) were culture-positive for TB . Compared to positivity on either Löwenstein-Jensen ( LJ ) or BACTEC cultures , LAM sensitivity was 17.8 % ( 95%CI 8.5 - 32.6 ) , while specificity was 87.7 % ( 95%CI 81.3 - 92.3 ) . Compared to positivity on both LJ and BACTEC , LAM sensitivity was 5.8 % ( 95%CI 12.5 - 44.9 ) , with a specificity of 88.8 % ( 95%CI 82.7 - 92.9 ) . Compared to the clinical diagnosis , LAM sensitivity was 20.0 % ( 95%CI 1.1 - 70.1 ) , with a specificity of 83.3 % ( 95%CI 50.9 - 97.0 ) . HIV and smear status did not influence test accuracy . CONCLUSION In its current form , LAM is insensitive for the diagnosis of active TB , although its specificity is adequate Background : Xpert MTB/RIF ( ‘ Xpert ’ ) and urinary lipoarabinomannan ( LAM ) assays offer rapid tuberculosis ( TB ) diagnosis , but have suboptimal sensitivity when used individually in HIV-positive patients . The yield of these tests used in combination for the diagnosis of active TB among HIV-infected TB suspects is unknown . Design : Study of comparative diagnostic accuracy nested into a prospect i ve study of HIV-infected individuals with signs and /or symptoms of TB in Ug and a. Methods : Xpert testing of archived sputum was conducted for culture-confirmed TB cases and TB suspects in whom a diagnosis of TB was excluded . Additional testing included sputum smear microscopy , sputum culture ( solid and liquid media ) , mycobacterial blood culture , and urinary testing for LAM using a lateral flow test ( ‘ LF-LAM ’ ) and an enzyme-linked immunosorbance assay ( ‘ ELISA-LAM ’ ) . Results : Among 103 participants with culture-confirmed TB , sensitivity of Xpert was 76 % ( 95 % confidence interval , CI 0.66–0.84 ) , and was superior to that of LF-LAM ( 49 % , 95 % CI 0.39–0.59 , P < 0.001 ) . Specificity was greater than 97 % for both tests among 105 individuals without TB . The combination of smear microscopy and LF-LAM identified 67 % ( 95 % CI 0.57–0.76 ) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone ( P = 0.15 ) . The sensitivity of the combination of Xpert and LF-LAM was 85 % ( 88/103 95 % CI 0.77–0.92 ) , which was superior to either test alone ( P < 0.05 ) and approached sensitivity of sputum liquid culture testing ( 94 % , 95 % CI 0.88–0.98 , P = 0.17 ) . Conclusion : Sputum Xpert and urinary LAM assays were complementary for the diagnosis of active TB in HIV-infected patients , and sensitivity of the combination of these tests was superior to that of either test alone OBJECTIVE To assess the diagnostic performance of urine lipoarabinomannan ( LAM ) detection for TB screening in HIV-positive adults in Ethiopia . METHODS Testing for LAM was performed using the Determine TB-LAM lateral flow assay on urine sample s from participants in a prospect i ve cohort with baseline bacteriological categorisation for active TB in sputum . Characteristics of TB patients with regard to LAM status were determined . Participants were followed for 6 months to evaluate survival , retention in care and incident TB . RESULTS Positive LAM results were found in 78/757 participants . Among 128 subjects with definite ( confirmed by culture and /or Xpert MTB/RIF ) TB , 33 were LAM-positive ( 25.8 % ) ; the respective figure for clinical ly diagnosed cases was 2/20 ( 10 % ) . Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period , whereas 38 remained in care without clinical signs of TB . The overall sensitivity , specificity , positive predictive value ( PPV ) and negative predictive value ( NPV ) were 25.8 % , 92.9 % , 42.3 % and 86.0 % , respectively . Among TB patients , LAM positivity was associated with higher WHO clinical stage , lower body mass index ( BMI ) , CD4 cell and haemoglobin levels , and with increased mortality . A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 ( 38.2 % ) of definite TB cases ; among those with CD4 count ≤100 cells/mm3 , this proportion was 66.7 % . CONCLUSIONS The performance of urine LAM testing for TB detection was poor in this population . However , this was improved among subjects with CD4 count ≤100 cells/mm3 . In combination with sputum microscopy urine , LAM could be considered for targeted TB screening in this subgroup Summary Background Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection , but have not been assessed in children . We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children . Methods We prospect ively recruited children ( aged ≤15 years ) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa , between March 1 , 2009 , and April 30 , 2012 . We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA , with mycobacterial culture of two induced sputum sample s as the reference st and ard . Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid . Findings 535 children ( median age 42·5 months , IQR 19·1–66·3 ) had urine and two induced specimens available for testing . 89 ( 17 % ) had culture-confirmed tuberculosis and 106 ( 20 % ) had HIV . The lateral flow lipoarabinomannan test showed poor accuracy against the reference st and ard , with sensitivity of 48·3 % ( 95 % CI 37·6–59·2 ) , specificity of 60·8 % ( 56·1–65·3 ) , and an area under the receiver operating characteristic curve of 0·53 ( 0·46–0·60 ) for children without HIV and 0·64 ( 0·51–0·76 ) for children with HIV . ELISA had poor sensitivity in children without HIV ( sensitivity 3·0 % , 95 % CI 0·4–10·5 ) and children with HIV ( 0 % , 0·0–14·3 ) ; overall specificity was 95·7 % ( 93·4–97·4 ) . Interpretation Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population . Funding US National Institutes of Health , the National Health Laboratory Services Research Trust , the Medical Research Council of South Africa , and the Wellcome Trust A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum sample s and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City . The test had a sensitivity of 88 % in patients with sputum-smear-positive active pulmonary tuberculosis . The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67 % . Less favorable results were obtained for patients with AIDS and tuberculosis , with a sensitivity of 57 % . The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100 % . The positive predictive value was 100 % , and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97 % . The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis Summary Background Current diagnostics for HIV-associated tuberculosis are suboptimal , with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally . Urine-based assays have a good diagnostic yield ; therefore , we aim ed to assess whether urine-based screening in HIV-positive in patients for tuberculosis improved outcomes . Methods We did a pragmatic , multicentre , double-blind , r and omised controlled trial in two hospitals in Malawi and South Africa . We included HIV-positive medical in patients aged 18 years or more who were not taking tuberculosis treatment . We r and omly assigned patients ( 1:1 ) , using a computer-generated list of r and om block size stratified by site , to either the st and ard-of-care or the intervention screening group , irrespective of symptoms or clinical presentation . Attending clinicians made decisions about care ; and patients , clinicians , and the study team were masked to the group allocation . In both groups , sputum was tested using the Xpert MTB/RIF assay ( Xpert ; Cepheid , Sunnyvale , CA , USA ) . In the st and ard-of-care group , urine sample s were not tested for tuberculosis . In the intervention group , urine was tested with the Alere Determine TB-LAM Ag ( TB-LAM ; Alere , Waltham , MA , USA ) , and Xpert assays . The primary outcome was all-cause 56-day mortality . Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count , haemoglobin , clinical suspicion for tuberculosis ; and by study site and calendar time . We used an intention-to-treat principle for our analyses . This trial is registered with the IS RCT N registry , number IS RCT N71603869 . Findings Between Oct 26 , 2015 , and Sept 19 , 2017 , we screened 4788 HIV-positive adults , of which 2600 ( 54 % ) were r and omly assigned to the study groups ( n=1300 for each group ) . 13 patients were excluded after r and omisation from analysis in each group , leaving 2574 in the final intention-to-treat analysis ( n=1287 in each group ) . At admission , 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per μL ( IQR 79–436 ) . Mortality at 56 days was reported for 272 ( 21 % ) of 1287 patients in the st and ard-of-care group and 235 ( 18 % ) of 1287 in the intervention group ( adjusted risk reduction [ aRD ] −2·8 % , 95 % CI −5·8 to 0·3 ; p=0·074 ) . In three of the 12 prespecified , but underpowered subgroups , mortality was lower in the intervention group than in the st and ard-of-care group for CD4 counts less than 100 cells per μL ( aRD −7·1 % , 95 % CI −13·7 to −0·4 ; p=0.036 ) , severe anaemia ( −9·0 % , −16·6 to −1·3 ; p=0·021 ) , and patients with clinical ly suspected tuberculosis ( −5·7 % , −10·9 to −0·5 ; p=0·033 ) ; with no difference by site or calendar period . Adverse events were similar in both groups . Interpretation Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive in patients , but might benefit some high-risk subgroups . Implementation could contribute towards global targets to reduce tuberculosis mortality . Funding Joint Global Health Trials Scheme of the Medical Research Council , the UK Department for International Development , and the Wellcome Trust Background : Tuberculosis is a major cause of mortality among HIV-infected in patients , and the World Health Organization ( WHO ) recommends an algorithm to improve diagnosis . The urine lateral flow lipoarabinomannan ( LAM ) and sputum Xpert MTB/RIF tests are promising tools , but the optimal diagnostic algorithm is unclear . Methods : This prospect i ve cohort study enrolled HIV-positive in patients with cough and WHO danger signs . The Xpert MTB/RIF test and mycobacterial culture were performed on sputum using sputum induction when necessary , and the LAM test was performed on stored urine . Tuberculosis was diagnosed by culture from any site . The diagnostic accuracy and costs of testing were determined for single and combined tests . Results : Tuberculosis was confirmed in 169 of 332 patients ( 50.9 % ) . The yield of LAM , Xpert MTB/RIF on spontaneous sputum ( Xpert Spot ) , and Xpert MTB/RIF on spontaneous or induced sputum ( Xpert SI ) was 35.5 % , 23.1 % , and 90.5 % , respectively . When LAM was placed before Xpert Spot and Xpert SI in an algorithm , the yield was 50.9 % and 92.3 % , respectively . Adding culture to Xpert MTB/RIF only increased the yield by 1.2 % and 2.7 % , respectively . Use of the LAM test reduced costs . Conclusions : Sputum induction is important to increase the yield of Xpert MTB/RIF for seriously ill patients with HIV and cough . LAM testing has little effect on yield when sputum induction is available , but reduces costs and may have other benefits BACKGROUND Testing urine improves the number of tuberculosis diagnoses made among patients in hospital with HIV . In conjunction with the two-country r and omised Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa ( STAMP ) trial , we used a microsimulation model to estimate the effects on clinical outcomes and the cost-effectiveness of adding urine-based tuberculosis screening to sputum screening for hospitalised patients with HIV . METHODS We compared two tuberculosis screening strategies used irrespective of symptoms among hospitalised patients with HIV in Malawi and South Africa : a GeneXpert assay ( Cepheid , Sunnyvale , CA , USA ) for Mycobacterium tuberculosis and rifampicin resistance ( Xpert ) in sputum sample s ( st and ard of care ) versus sputum Xpert combined with a lateral flow assay for M tuberculosis lipoarabinomannan in urine ( Determine TB-LAM Ag test , Abbott , Waltham , MA , USA [ formerly Alere ] ; TB-LAM ) and concentrated urine Xpert ( intervention ) . A cohort of simulated patients was modelled using selected characteristics of participants , tuberculosis diagnostic yields , and use of hospital re sources in the STAMP trial . We calibrated 2-month model outputs to the STAMP trial results and projected clinical and economic outcomes at 2 years , 5 years , and over a lifetime . We judged the intervention to be cost-effective if the incremental cost-effectiveness ratio ( ICER ) was less than US$ 750/year of life saved ( YLS ) in Malawi and $ 940/YLS in South Africa . A modified intervention of adding only TB-LAM to the st and ard of care was also evaluated . We did a budget impact analysis of countrywide implementation of the intervention . FINDINGS The intervention increased life expectancy by 0·5 - 1·2 years and was cost-effective , with an ICER of $ 450/YLS in Malawi and $ 840/YLS in South Africa . The ICERs decreased over time . At lifetime horizon , the intervention remained cost-effective under nearly all modelled assumptions . The modified intervention was at least as cost-effective as the intervention ( ICERs $ 420/YLS in Malawi and $ 810/YLS in South Africa ) . Over 5 years , the intervention would save around 51 000 years of life in Malawi and around 171 000 years of life in South Africa . Health-care expenditure for screened individuals was estimated to increase by $ 37 million ( 10·8 % ) and $ 261 million ( 2·8 % ) , respectively . INTERPRETATION Urine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in re source -limited setting s. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert , making a compelling case for exp and ing its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis . FUNDING UK Medical Research Council , UK Department for International Development , Wellcome Trust , US National Institutes of Health , Royal College of Physicians , Massachusetts General Hospital Summary Background Most tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment . The only commercially available tuberculosis point-of-care test ( Alere Determine TB LAM Ag [ AlereLAM ] ) has suboptimal sensitivity , which restricts its use in clinical practice . The novel Fujifilm SILVAMP TB LAM ( FujiLAM ) assay has been developed to improve the sensitivity of AlereLAM . We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital in patients with HIV compared with the AlereLAM assay . Methods For this diagnostic accuracy study , we assessed biobanked urine sample s obtained from the FIND Specimen Bank and the University of Cape Town Biobank , which had been collected from hospital in patients ( aged ≥18 years ) with HIV during three independent prospect i ve cohort studies done at two South African hospitals . Urine sample s were tested using FujiLAM and AlereLAM assays . The conduct and reporting of each test was done blind to other test results . The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM , against microbiological and composite reference st and ards ( including clinical diagnoses ) . Findings Between April 18 , 2018 , and May 3 , 2018 , urine sample s from 968 hospital in patients with HIV were evaluated . The prevalence of microbiologically-confirmed tuberculosis was 62 % and the median CD4 count was 86 cells per μL. Using the microbiological reference st and ard , the estimated sensitivity of FujiLAM was 70·4 % ( 95 % CI 53·0 to 83·1 ) compared with 42·3 % ( 31·7 to 51·8 ) for AlereLAM ( difference 28·1 % ) and the estimated specificity of FujiLAM was 90·8 % ( 86·0 to 94·4 ) and 95·0 % ( 87·7–98·8 ) for AlereLAM ( difference −4·2 % ) . Against the composite reference st and ard , the specificity of both assays was higher ( 95·7 % [ 92·0 to 98·0 ] for FujiLAM vs 98·2 % [ 95·7 to 99·6 ] for AlereLAM ; difference −2·5 % ) , but the sensitivity of both assays was lower ( 64·9 % [ 50·1 to 76·7 ] for FujiLAM vs 38·2 % [ 28·1 to 47·3 ] for AlereLAM ; difference 26·7 % ) . Interpretation In comparison to AlereLAM , FujiLAM offers superior diagnostic sensitivity , while maintaining specificity , and could transform rapid point-of-care tuberculosis diagnosis for hospital in patients with HIV . The applicability of FujiLAM for setting s of intended use requires prospect i ve assessment . Funding Global Health Innovative Technology Fund , UK Department for International Development , Dutch Ministry of Foreign Affairs , Bill & Melinda Gates Foundation , German Federal Ministry of Education and Research , Australian Department of Foreign Affairs and Trade , Wellcome Trust , Department of Science and Technology and National Research Foundation of South Africa , and South African Medical Research Council Objective : To assess the diagnostic accuracy of the urine lipoarabinomannan ( LAM ) test among ambulatory HIV-infected persons . Design : Cross-sectional . Methods : HIV-infected persons consecutively presenting to the HIV Clinic at Tembisa Main Clinic in Ekhuruleni , South Africa , were screened for symptoms of tuberculosis ( TB ) and asked to provide sputum and blood sample s for smears for acid-fast bacilli and mycobacterial culture and a urine specimen for a LAM enzyme-linked immunosorbent assay . Fine needle aspirates were obtained from participants with enlarged lymph nodes and sent for histopathology . Nonpregnant participants underwent chest x-ray . Results : Four hundred twenty-two HIV-infected participants were enrolled with median age 37 years ( interquartile range : 31 - 44 years ) , median CD4 + T-cell count 215 cells per microliter ( interquartile range : 107 - 347 cells/μL ) , and 212 ( 50 % ) receiving antiretroviral therapy . Thirty ( 7 % ) had active TB : 18 with only pulmonary TB , 5 with only extrapulmonary TB , and 7 with both pulmonary TB and extrapulmonary TB . Twenty-seven percent [ 95 % confidence interval ( CI ) : 12 % to 48 % ] of TB cases were sputum acid-fast bacilli positive . The sensitivity and specificity of the urine LAM compared with the gold st and ard of positive bacteriology or histopathology were 32 % ( 95 % CI : 16 % to 52 % ) and 98 % ( 95 % CI : 96 % to 99 % ) , respectively . Urine LAM had higher sensitivity in TB cases with higher bacillary burdens , though these differences were not statistically significant . Conclusions : The sensitivity of urine LAM testing is inadequate to replace mycobacterial culture . In contrast to prior research on the urine LAM , this study was conducted among less sick , ambulatory HIV-infected patients presenting for routine care |
13,011 | 23,235,577 | We found moderate- quality evidence that nutritional supplementation promotes significant weight gain among patients with COPD , especially if malnourished .
Nourished patients may not respond to the same degree to supplemental feeding .
We also found a significant change from baseline in fat-free mass index/fat-free mass , fat mass/fat mass index , MAMC ( as a measure of lean body mass ) , six-minute walk test and a significant improvement in skinfold thickness ( as measure of fat mass , end score ) for all patients . | BACKGROUND Individuals with chronic obstructive pulmonary disease ( COPD ) and low body weight have impaired pulmonary status , reduced diaphragmatic mass , lower exercise capacity and higher mortality than those who are adequately nourished .
Nutritional support may be useful for their comprehensive care .
OBJECTIVES To assess the impact of nutritional support on anthropometric measures , pulmonary function , respiratory and peripheral muscles strength , endurance , functional exercise capacity and health-related quality of life ( HRQoL ) in COPD .If benefit is demonstrated , to perform subgroup analysis to identify treatment regimens and sub population s that demonstrate the greatest benefits . | The inflammatory cytokines , tumor necrosis factor-alpha ( TNF-alpha ) and interleukin-1-beta ( IL-1 beta ) , have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans . We hypothesized that these inflammatory cytokines might contribute to the weight-losing process in patients with chronic obstructive pulmonary disease ( COPD ) . COPD patients were identified prospect ively as " weight losers " ( WL ; n = 10 ) if they reported > 5 % weight loss during the preceding year or as " weight stable " ( WS ; n = 10 ) if their body weight fluctuated < or = 5 % . Age-matched healthy volunteers were selected as the control group ( C ; n = 13 ) . Monocytes were isolated from a peripheral blood sample , cultured , and exposed to lipopolysaccharide ( LPS ) . The concentration of TNF-alpha and IL-1 beta in the monocyte supernatant was measured using a four layer enhanced ELISA . No significant difference in LPS-stimulated IL-1 beta production was found in the three study population s. However , LPS-stimulated TNF-alpha production ( mean [ range ] ng/ml ) by monocytes was significantly higher in the WL COPD patients ( 20.2 [ 6.3 to 44.8 ] ) , compared with WS patients ( 6.9 [ 1.5 to 16.6 ] ) , and C subjects ( 5.7 [ 0 to 61.8 ] ) . This difference was not maintained at 6 mo follow-up in the absence of ongoing weight loss . Definition of a causal relationship between TNF-alpha production and weight loss will require further underst and ing of the relationship between energy metabolism and TNF-alpha production in these patients The impact of oral nutritional supplementation during an acute exacerbation of COPD on functional status was assessed through measuring change in lung function , strength testing , and general well-being . Subjects hospitalized for an acute exacerbation of COPD ( n = 33 ) were r and omized to extra nutritional support or the regular hospital care . They consumed an additional 10 kcal/kg/d . Outcome measures were measured at 2 wk as change scores . Forced vital capacity ( % predicted ) improved in the treatment group as compared with the control group ( + 8.7 % versus -3.5 % , p = 0.015 ) , and change in FEV1 was in the same direction but not significantly different ( p = 0.099 ) . There were no changes in h and grip strength or respiratory muscle strength , but there was a trend towards more improvement in the general well-being score ( + 11.96 versus -10.25 , p = 0.066 ) . Almost all subjects were in negative nitrogen balance , indicating muscle wasting . The degree of muscle wasting was strongly correlated with the dose of corticosteroids ( r = 0.73 , p < 0.005 ) . In conclusion , it is difficult to prevent important muscle wasting in patients with COPD treated with corticosteroids , but some small gains were observed with increased dietary intake Background In chronic respiratory failure ( CRF ) , body composition strongly predicts survival . Methods A prospect i ve r and omised controlled trial was undertaken in malnourished patients with CRF to evaluate the effects of 3 months of home rehabilitation on body functioning and composition . 122 patients with CRF on long-term oxygen therapy and /or non-invasive ventilation ( mean ( SD ) age 66 ( 10 ) years , 91 men ) were included from eight respiratory units ; 62 were assigned to home health education ( controls ) and 60 to multimodal nutritional rehabilitation combining health education , oral nutritional supplements , exercise and oral testosterone for 90 days . The primary endpoint was exercise tolerance assessed by the 6-min walking test ( 6MWT ) . Secondary endpoints were body composition , quality of life after 3 months and 15-month survival . Results Mean ( SD ) baseline arterial oxygen tension was 7.7 ( 1.2 ) kPa , forced expiratory volume in 1 s 31 (13)% predicted , body mass index ( BMI ) 21.5 ( 3.9 ) kg/m2 and fat-free mass index ( FFMI ) 15.5 ( 2.4 ) kg/m2 . The intervention had no significant effect on 6MWT . Improvements ( treatment effect ) were seen in BMI ( + 0.56 kg/m2 , 95 % CI 0.18 to 0.95 , p=0.004 ) , FFMI ( + 0.60 kg/m2 , 95 % CI 0.15 to 1.05 , p=0.01 ) , haemoglobin ( + 9.1 g/l , 95 % CI 2.5 to 15.7 , p=0.008 ) , peak workload ( + 7.2 W , 95 % CI 3.7 to 10.6 , p<0.001 ) , quadriceps isometric force ( + 28.3 N , 95 % CI 7.2 to 49.3 , p=0.009 ) , endurance time ( + 5.9 min , 95 % CI 3.1 to 8.8 , p<0.001 ) and , in women , Chronic Respiratory Question naire ( + 16.5 units , 95 % CI 5.3 to 27.7 , p=0.006 ) . In a multivariate Cox analysis , only rehabilitation in a per- protocol analysis predicted survival ( HR 0.27 , 95 % CI 0.07 to 0.95 , p=0.042 ) . Conclusions Multimodal nutritional rehabilitation aim ed at improving body composition increased exercise tolerance , quality of life in women and survival in compliant patients , supporting its incorporation in the treatment of malnourished patients with CRF . Clinical Trial number NCT00230984 It has been reported that malnutrition is common in stable chronic obstructive pulmonary disease ( COPD ) patients . In order to observe the effects of Megestrol Acetate ( MA ) on nutritional status , respiratory muscle strength and immunological parameters in stable COPD patients , 31 stable COPD patients were divided into two groups at r and om -- a treatment group of 16 cases and a control group of 15 cases . Before and after treatment all parameters were recorded , including food and energy intake , body weight , triceps skinfolds ( TSF ) , pre-albumin , transferrin , albumin . Lung function , respiratory muscle and h and grip strength were examined and immunological parameters also determined . After taking MA 160 mg/day orally for two weeks , the treatment group got benefits as follows : heat energy and protein intake increased fro 6977.9 + /- 1136 kJ/d and 44.65 + /- 13.75 g/d to 9854.0 + /- 2355.3 kJ/d and 84.80 + /- 20.23 g/d respectively . With the increase of daily energy and protein intake , body weight increased from 48.27 + /- 8.61 kg to 50.34 + /- 8.76 kg , TSF from 11.75 + /- 4.50 mm to 15.06 + /- 4.73 mm , serum pre-albumin from 306.6 + /- 33.7 mg/L to 332.6 + /- 1 mg/L , transferrin from 3.09 + /- 0.21 g/L to 3.46 + /- 0.32 g/L , albumin from 38.00 + /- 1.73 g/L to 42.64 + /- 3.36 g/L , MIP from 4.77 + /- 2.14 kPa ( 1 kPa = 7.5 mmHg ) to 6.31 + /- 2.87 kPa , MEP from 6.21 + /- 2.90 kPa to 7.20 + /- 3.67 kPa and 6 minutes walking distance from 280.2 + /- 76.4 m to 370.6 + /- 81.5 m. H and grip strength also improved . Blood lymphocyte transformation rate elevated too . ( The changes of all these parameters indicated above were statistically significant , P < 0.01 ) . However , parameters of lung function , blood gas analysis , serum immunoglobulin and complement 3 did not change significantly . In 15 control patients all the parameters did not change significantly . There were few side effects ; only one case complained of nausea and vomiting . It was shown that MA can stimulate appetite and increase dietintake , improve nutritional status , elevate respiratory muscle strength , and enhance immunity . MA is a safe and effective drug which exerts a beneficial influence on stable COPD The purpose of this study was to determine whether a single large liquid carbohydrate ( CHO ) load ( 920 calories ) affects walking performance in patients with chronic air-flow obstruction ( CAO ) . Walking performance was measured using the 12-min walking test . Fifteen patients with stable CAO ( FEV1 , 1.30 + /- 0.41 L ; FVC , 3.26 + /- 0.46 L ) underwent 12-min walking tests 40 min after ingestion of either CHO or placebo on consecutive days in r and omized double-blind fashion . Three practice walks were performed on a preliminary day in order to eliminate learning effects . Resting measurements of ventilation ( VE ) and carbon dioxide output ( VCO2 ) were obtained prior to each walking test . Carbohydrate significantly increased both VCO2 ( from 0.288 + /- 0.060 to 0.372 + /- 0.057 L/min , p less than 0.001 ) and VE ( from 15.2 + /- 3.5 to 18.5 + /- 3.1 L/min , p less than 0.001 ) at rest . The total 12-minute walking distance decreased from 894 + /- 199 to 847 + /- 191 m following CHO ( p less than 0.005 ) . This distance decreased in 14 of the 15 study patients . The decrease in walking distance ranged from 1.5 to 168 m ( 0.2 to 15.2 % ) . From this study we conclude that a large liquid carbohydrate load adversely affects walking performance in patients with CAO . This potential impairment of functional capacity should be considered when caloric intake is increased in attempts to improve nutritional status in this patient population A body weight lower than 90 % of the optional value has an unfavorable influence on the prognosis of chronic obstructive pulmonary disease ( COPD ) . Short term studies of up to three months duration have shown improved function of respiratory muscle exercise tolerance and immunologic parameters by an increased caloric intake of 45 kcal/kg body weight . In a r and omized trial of twelve months 14 of 30 patients with an average FEV1 of 0.8 l were instructed to take a high calorie diet . For simplicity a part of the calories were administered as Fresubin , a fluid nutrient formula . Although a weight gain of 7 kg ( p = 0.003 ) was obtained the difference to the control group was statistically not significant ( p = 0.08 ) . The same was true for skin fold thickness ( 12.4 vs 5.7 mm ) , change of ventilatory parameters and the 6 minute walking distance ( -33 vs -86 m ) . Subjective improvement was , however , impressive in all patients with dietary intervention , explainable probably by increased attention . Dietary counselling for increased intake of calories , vitamins and also calcium is thus very important in the treatment of patients with COPD The study aim ed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease ( COPD ) management in patients with COPD . We conducted a cost-effectiveness analysis alongside a 2-yr r and omised controlled trial , in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care . The INTERCOM programme consisted of exercise training , education , nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses . All-cause re source use during 2 yrs was obtained by self-report and from hospital and pharmacy records . Health outcomes were the St George 's Respiratory Question naire ( SGRQ ) , exacerbations and quality -adjusted life years ( QALYs ) . The INTERCOM group had 30 % ( 95 % CI 3–56 % ) more patients with a clinical ly relevant improvement in SGRQ total score , 0.08 ( 95 % CI -0.01–0.18 ) more QALYs per patient , but a higher mean number of exacerbations , 0.84 ( 95 % CI -0.07–1.78 ) . Mean total 2-yr costs were € 2,751 ( 95 % CI -€632–€6,372 ) higher for INTERCOM than for usual care , which result ed in an incremental cost-effectiveness ratio of € 9,078 per additional patient with a relevant improvement in SGRQ or € 32,425 per QALY . INTERCOM significantly improved disease-specific quality of life , but did not affect exacerbation rate . The cost per QALY ratio was moderate , but within the range of that generally considered to be acceptable Background : The effectiveness of pulmonary rehabilitation in advanced COPD is well established , but few data are available in less advanced disease . Methods : In a 2 year r and omised controlled trial , 199 patients with an average moderate airflow obstruction but impaired exercise capacity ( mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) 60 (16)% , peak work load ( Wmax ) < 70 % ) were r and omised to the INTERdisciplinary COMmunity-based COPD management programme ( INTERCOM ) or usual care . Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase . Outcomes ( 4 , 12 , 24 months ) : health-related quality of life ( St George ’s Respiratory Question naire ( SGRQ ) ) , exacerbation frequency , MRC dyspnoea score , cycle endurance time ( CET ) , 6-minute walking distance ( 6MWD ) , skeletal muscle strength and patients ’ and caregivers ’ perceived effectiveness . Results : Between-group comparison after 4 months revealed the following mean ( SE ) significant differences in favour of INTERCOM : SGRQ total score 4.06 ( 1.39 ) , p = 0.004 ; activity and impact subscores , p<0.01 ; MRC score 0.33 ( 0.13 ) , p = 0.01 ; Wmax 6.0 ( 2.3 ) Watt , p = 0.02 ; CET 221 ( 104 ) s , p = 0.04 ; 6MWD 13 ( 6 ) m , p = 0.02 ; h and grip force 4.3 ( 1.5 ) lb , p<0.01 ; and fat-free mass index 0.34 ( 0.13 ) kg/m2 , p = 0.01 . Between-group differences over 2 years were as follows : SGRQ 2.60 ( 1.3 ) , p = 0.04 ; MRC score 0.21 ( 0.10 ) , p = 0.048 ; CET 253 ( 104 ) s , p = 0.0156 ; 6MWD 18 ( 8) m , p = 0.0155 . Exacerbation frequency was not different ( RR 1.29 ( 95 % CI 0.89 to 1.87 ) ) . Patients ’ and caregivers ’ perceived effectiveness significantly favoured the INTERCOM programme ( p<0.01 ) . Conclusions : This study shows that a multidisciplinary community-based disease management programme is also effective in patients with COPD with exercise impairment but less advanced airflow obstruction . Trial registration number : RATIONALE Nutritional depletion is a common problem in chronic obstructive pulmonary disease ( COPD ) patients . It is caused , to a large extent , by an imbalance between low-energy intake and high-energy requirements . This problem adversely affects morbidity and mortality . However , the use of nutritional supplements to reach their energy necessities requires optimisation between positive and adverse effects on outcome before being used systematic ally as part of their comprehensive care . PURPOSE The aim of our study was to investigate the effects of oral nutritional repletion on quality of life in stable COPD patients . METHODS Prospect i ve , r and omised and multi-centre study . Stable COPD patients with a body mass index 22 , a fat-free mass index 16 , and /or a recent involuntary weight loss ( 5 % during last month , or 10 % during the last 3 months ) were studied . Exclusion criteria were to present signs of an airway infection , to have a cardiovascular , neurological , or endocrine disease , to be treated with oral steroids , immunosuppressors or oxygen therapy at home , and to receive nutritional supplements . During 12 weeks , patients were encouraged to ingest a total daily defined energy intake . R and omly , in patients from group A the total daily energy load was Resting Energy Expenditure (REE)x1.7 , and those from group B , REE x1.3 . Total daily energy intake was achieved with regular food plus , if necessary , oral nutritional supplement rich in proteins ( with 50 % of whey protein ) , with predominance of carbohydrates over fat , and enriched in antioxidants . Primary end-point variable was quality of life . Secondary end-point outcomes included body weight , body composition , lung function , h and grip strength , and compliance with the energy intake previously planned . Data were treated with a SAS System . Student 's test , Wilcoxon 's rank sum test , and Mann-Whitney 's test were used . RESULTS At baseline both groups of patients were comparable . All patients needed oral nutritional supplements to achieve total daily defined energy intake . After 12 weeks of follow-up , patients in both groups significantly increased energy intake . Patients in group A increased body weight ( P=0.001 ) , triceps skin fold thickness ( P=0.009 ) and body fat mass ( P=0.02 ) , and decreased body fat-free mass index ( P=0.02 ) . In this group a marked increase in airflow limitation was observed . A tendency to increase body weight and h and grip strength , and to decrease airflow limitation was observed in patients from group B. Furthermore , patients in the later group showed a significant improvement in the feeling of control over the disease ( P=0.007 ) and a tendency to better the other criteria in a quality of life scale . CONCLUSIONS According to our results , total daily energy intake of REE x 1.3 is preferable to REE x 1.7 in mild stable COPD patients . The administration of oral nutritional supplements , rich in proteins ( with 50 % of whey protein ) , with predominance of carbohydrates over fat , and enriched in antioxidants , to achieve total daily defined energy intake in patients in group B was followed by a significant improvement of one criteria ( mastery ) among many others in a quality of life scale UNLABELLED Dietary intervention studies in COPD patients often are short-term inpatient studies where a certain amount of extra energy is guaranteed . The aim of this study was to evaluate the effect of an 1 year individual multifaceted dietary intervention during multidisciplinary rehabilitation . Eighty-seven patients with severe COPD , not dem and ing oxygen therapy were included , 24 of them served as controls . A dietary history interview was performed at baseline and at study end . Dietary advice given were based on results from the dietary history and socio-economic status . The intervention group was divided into three parts ; NW : normal weight ( dietary advice given aim ing to weight maintenance ) , OW : overweight ( weight-reducing advice ) and UW : underweight ( dietary advise based on an energy- and protein-rich diet ) . RESULTS UW-group : Eighty-one per cent of the patients gained weight or kept a stable weight . OW-group : Fifty-seven per cent lost more than 2 kg NW-group : Seventy-six per cent kept a stable weight or gained weight . Increased dietary intake from baseline was seen for energy protein , carbohydrates and certain micronutrients ( P < 0.05 ) in the UW group . Six minutes walking distance increased by approximately 20 m in both NW ( P < 0.05 ) and UW patients . To conclude , slight , but uniform , indications of positive effects of dietary intervention during multidisciplinary rehabilitation was seen . Dietary intervention in underweight COPD patients might be a prerequisite for physical training The prevalence and features of malnutrition in COPD patients have been studied extensively in stable conditions but are poorly defined in the presence of acute respiratory failure ( ARF ) . Nutritional status was prospect ively assessed , on hospital admission , in 50 consecutive COPD patients presenting with ARF , 27 of them requiring mechanical ventilation ( MV ) . Malnutrition , defined on a multiparameter nutritional index , was observed in 60 percent ( 30/50 ) of all patients , and in 39 percent ( 13/33 ) of those whose body weight was equal to or above 90 percent ideal body weight ( IBW ) . Malnutrition was more frequent in those patients who required MV than in those who did not ( 74 percent vs 43 percent , p < 0.05 ) . Subcutaneous fat stores were decreased ( triceps skinfold thickness [ TSF ] < 80 percent pred ) in 68 percent of patients , and markedly depleted ( TSF < 60 percent pred ) in 52 percent of them . The indices of lean body mass , ie , mid-arm muscle circumference ( MAMC ) and creatinine height index ( CHI ) were decreased in , respectively , 42 percent and 71 percent of patients , but MAMC was severely depressed ( < 60 percent pred ) in only 6 percent of them . A severe decrease of prealbumin ( < 100 mg/L ) , retinol-binding-protein ( < 20 mg/L ) , and albumin ( < 20 g/L ) serum concentrations was observed in , respectively , 22 percent , 28 percent , and 4 percent of patients . These results suggest that an assessment of nutritional status using a multiparameter approach should be systematic ally performed in COPD patients with ARF , especially in those requiring MV , as malnutrition may have deleterious effects on weaning off MV STATE OF THE ART The IRAD2 trial is evaluating a 3-month home intervention which includes education , oral supplements , exercise and and rogenic steroids in undernourished patients with chronic respiratory failure . The main objective is to increase the six-minute walking distance by more than 50 m with an improvement in health-related quality -of-life . Secondary end-points include a reduction in exacerbation rates by 25 % , a reduction in health-related costs and an increase in survival during the year following intervention . MATERIAL AND METHODS This interventional , multi-centre , prospect i ve , two-armed parallel , controlled trial is being conducted in 200 patients . In both groups , " Control " and " Rehabilitation " , 7 home visits are scheduled during the 3-month intervention for education purpose . In the " Rehabilitation " group , patients will receive 160 mg/d of oral testosterone undecanoate in men , 80 mg/d in women , oral dietary supplements ( 563 kcal/d ) and exercises on an ergometric bicycle 3 to 5 times a week . EXPECTED RESULTS In the event of significant responses to intervention , this trial would vali date a comprehensive and global home-care for undernourished patients with chronic respiratory failure combining therapeutic education , oral supplements , and rogenic substitution and physical activity AIM Aim of the study was to investigate whether or not oral supplementation of essential amino acids ( EAAs ) may improve body composition , muscle metabolism , physical activity , cognitive function , and health status in a population of subjects with severe chronic obstructive pulmonary disease ( COPD ) and sarcopenia . METHODS Thirty-two patients ( 25 males ) ( FEV1/FVC < 40 % predicted ) , age 75 + /- 7 years , were r and omised ( n = 16 in both groups ) to receive 4 gr/bid EAAs or placebo according to a double-blind design . When entered the study ( T0 ) , after four ( T4 ) , and after twelve ( T12 ) weeks of treatments , body weight , fat free-mass ( FFM ) , plasma lactate concentration ( micromol/l ) , arterial PaCO2 and PaO2 , physical activity ( n degree steps/day ) , cognitive function ( Mini Mental State Examination ; MMSE ) , health status ( St. George 's Respiratory Question naire ; SGRQ ) were measured . RESULTS EAAs supplemented , but not patients assuming placebo , progressively improved all baseline variables overtime . In particular , at T12 of EAAs supplementation , body weight ( BW ) increased by 6 Kg ( p = 0.002 ) , FFM by 3.6 Kg ( p = 0.05 ) , plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l ( p = 0.023 ) , PaO2 increased by 4.6 mmHg ( p = 0.01 ) , physical activity increased by 80 % ( p = 0.01 ) . Moreover , the score for cognitive dysfunction improved from 19.1 scores to 20.8 ( p = 0.011 ) , while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance . CONCLUSIONS . A three-month EAAs supplementation may have comprehensive effects on nutritional status ; muscle energy metabolism ; blood oxygen tension , physical autonomy ; cognitive function , and perception of health status in patients with severe COPD and secondary sarcopenia Twenty five patients with advanced chronic obstructive pulmonary disease ( COPD ) having malnutrition were r and omly assigned to parenteral nutrition ( PN ) group ( 12 cases ) and control group ( 13 cases ) . Patients in the PN group received 10 % Intralipid and 5 % Nutrisol-S. Body weight , blood lymphocyte , serum albumin , transferrin , prealbumin , fibronectin and serum free fatty acids ( FFA ) and serum free amino acids ( AA ) were monitored . The results showed that parenteral nutritional support for 10 - 20 days improved the nutritional status , significantly increased the body weight and the serum albumin , prealbumin , fibronectin , transferrin ( P < 0.05 or P < 0.01 ) and some kinds of serum free amino acids : PaCO2 also decreased . Serum FFA remained under the normal level whether nutritional support was given ( P < 0.01 ) . It is suggested that nutritional support may promote synthesis of protein in COPD patients with malnutrition . Intralipid infusion would preserve nitrogen and diminish the carbohydrate metabolism and might be beneficial to correct the hypercapnea in COPD We have measured caloric intake , energy expenditure , and the thermogenic effect of food in ten patients with stable COPD who had a history of involuntary weight loss over several years and were malnourished ( < 85 percent ideal body weight ) . Each patient completed a 7-day food record . Indirect calorimetry was performed in the resting postabsorptive state . After placement of a nasoenteric tube , patients were r and omly assigned to be refed or sham-fed ( mean + /- SD , 16 + /- 3 days ) , following which , metabolic measurements were repeated . Indirect calorimetry was also performed before and after a large meal in each patient . Home caloric intake was 135 + /- 23 percent of resting energy expenditure . Resting energy expenditure was 94 + /- 16 percent of that predicted by the Harris-Benedict equation and did not change significantly during inpatient refeeding . Refeeding result ed in weight gain ( 2.4 + /- 1.9 kg , p < 0.02 ) . A large meal caused substantial increases in energy expenditure ( 24 + /- 18 percent ) , carbon dioxide production ( 39 + /- 18 percent ) , and oxygen consumption ( 23 + /- 16 percent ) . We conclude that stable malnourished COPD patients consume adequate calories to meet average energy requirements and are not hypermetabolic . Inpatient refeeding by nocturnal nasoenteric infusion is well tolerated and results in weight gain , but the thermogenic effect of a large meal poses a considerable metabolic and ventilatory load that could precipitate acute respiratory failure OBJECTIVE One of the goals in treating patients with chronic obstructive pulmonary disease ( COPD ) who suffer from hypoxemia , hypercapnia , and malnutrition is to correct the malnutrition without increasing the respiratory quotient and minimize the production of carbon dioxide . This 3-wk study evaluated the efficacy of feeding a high-fat , low-carbohydrate ( CHO ) nutritional supplement as opposed to a high-carbohydrate diet in COPD patients on parameters of pulmonary function . S METHODS : Sixty COPD patients with low body weight ( < 90 % ideal body weight ) were r and omized to the control group , which received dietary counseling for a high-CHO diet ( 15 % protein , 20 % to 30 % fat , and 60 % to 70 % CHO ) , or the experimental group , which received two to three cans ( 237 mL/can ) of a high-fat , low-CHO oral supplement ( 16.7 % protein , 55.1 % fat , and 28.2 % CHO ) in the evening as part of the diet . Measurements of lung function ( forced expiratory volume in 1 s or volume of air exhaled in 1 s of maximal expiration , minute ventilation , oxygen consumption per unit time , carbon dioxide production in unit time , and respiratory quotient ) and blood gases ( pH , arterial carbon dioxide tension , and arterial oxygen tension ) were taken at baseline and after 3 wk . RESULTS Lung function measurements decreased significantly and forced expiratory volume increased significantly in the experimental group . CONCLUSION This study demonstrates that pulmonary function in COPD patients can be significantly improved with a high-fat , low-CHO oral supplement as compared with the traditional high-CHO diet STUDY OBJECTIVES Skeletal muscle weakness commonly occurs in patients with COPD . Long-term use of systemic glucocorticosteroids further contributes to muscle weakness . Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning , possibly mediated by increasing erythropoietic function . PATIENTS AND METHODS We r and omly assigned 63 male patients with COPD to receive on days 1 , 15 , 29 , and 43 a deep IM injection of 50 mg of n and rolone decanoate ( ND ) [ Deca-Durabolin ; N.V. Organon ; Oss , The Netherl and s ] in 1 mL of arachis oil , or 1 mL of arachis oil alone ( placebo ) in a double-blind design . All patients participated in a st and ardized pulmonary rehabilitation program . Outcome measures were body composition by deuterium and bromide dilution , respiratory and peripheral muscle function , incremental exercise testing , and health status by the St. George 's Respiratory Question naire . RESULTS Treatment with ND relative to placebo result ed in higher increases in fat-free mass ( FFM ; mean , 1.7 kg [ SD , 2.5 ] vs 0.3 kg [ SD , 1.9 ] ; p = 0.015 ) owing to a rise in intracellular mass ( mean , 1.8 kg [ SD , 3.1 ] vs - 0.5 kg [ SD , 3.1 ] ; p = 0.002 ) . Muscle function , exercise capacity , and health status improved in both groups to the same extent . Only after ND were increases in erythropoietic parameters seen ( erythropoietin : mean , 2.08 U/L [ SD , 5.56 ] , p = 0.067 ; hemoglobin : mean , 0.29 mmol/L [ SD , 0.73 ] , p = 0.055 ) . In the total group , the changes in maximal inspiratory mouth pressure ( PImax ) and peak workload were positively correlated with the change in hemoglobin ( r = 0.30 , p = 0.032 , and r = 0.34 , p = 0.016 , respectively ) , whereas the change in isokinetic leg work was correlated with the change in erythropoietin ( r = 0.38 , p = 0.013 ) . In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids ( 31 of 63 patients ; mean , 7.5 mg/24 h [ SD , 2.4 ] ) , greater improvements in PImax ( mean , 6.0 cm H(2)O [ SD , 8.82 ] vs - 2.18 cm H(2)O [ SD , 11.08 ] , p = 0.046 ) , and peak workload ( mean , 20.47 W [ SD , 19.82 ] vs 4.80 W [ SD , 7.74 ] , p = 0.023 ) were seen after 8 weeks of treatment with ND vs placebo . CONCLUSIONS In conclusion , a short-term course of ND had an overall positive effect relative to placebo on FFM without exp and ing extracellular water in patients with COPD . In the total group , the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters . The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity , which could be restored by ND treatment RATIONALE Limited data are available on effectiveness and costs of nutritional rehabilitation for patients with COPD in community care . METHODS In a 2-year RCT , 199 COPD patients ( FEV(1)%pred . 60 % [ SD 16 % ] ) and impaired exercise capacity were r and omized to the interdisciplinary community-based COPD management program ( INTERCOM ) or usual care ( UC ) . A prescheduled subgroup analysis was performed on 39 of 199 patients who were muscle wasted and received UC or nutritional therapy in combination with exercise training . Body composition , muscle strength , and exercise capacity were assessed at baseline and 4 , 12 , and 24 months . RESULTS Between group differences after 4 months in favor of the intervention group : fat free mass index ( FFMI 0.9 kg/m(2 ) [ SE = 0.2 , P < .001 ] ) , body mass index ( BMI 1.0 kg/m(2 ) [ SE = 0.4 , P = .009 ] ) , maximum inspiratory mouth pressure ( Pimax 1.4 kPa [ SE = 0.5 , P = .011 ] ) , quadriceps average power ( QAP 13.1 Watt [ SE=5.8 , P = .036 ] ) , 6-minute walking distance ( 6MWD 27 m , [ SE = 11.5 , P = .028 ] ) , cycle endurance time ( CET 525 seconds [ SE=195 , P = .013 ] ) , and peak exercise capacity ( Wmax 12 Watt [ SE = 5 , P = .036 ] ) . Between group difference over 24 months in favor of the intervention group : Pimax 1.7 kPa ( SE = 0.53 , P = .004 ) , QAP 19 Watt ( SE = 6 , P = .005 ) , 6MWD 57 ( SE = 19 , P = .006 ) , and CET 485 seconds ( SE = 159 , P = .006 ) . After 4 months total costs were Euro 1501 higher in the intervention group than in the UC group ( P < .05 ) , but not significantly different after 24 months . Hospital admission costs were significantly lower in the intervention group -euro 4724 ( 95 % CI -7704 , -1734 ) . CONCLUSION This study in muscle-wasted COPD patients with moderate airflow obstruction shows a prolonged positive response to nutritional support integrated in a community-based rehabilitation program |
13,012 | 26,121,659 | There was no difference in antenatal , obstetric and neonatal outcome or morbidity in screened versus control groups .
Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality .
There is little information on long-term substantive outcomes such as neurodevelopment .
There is a lack of data on maternal psychological effects .
Based on existing evidence , routine late pregnancy ultrasound in low-risk or unselected population s does not confer benefit on mother or baby .
There was no difference in the primary outcomes of perinatal mortality , preterm birth less than 37 weeks , caesarean section rates , and induction of labour rates if ultrasound in late pregnancy was performed routinely versus not performed routinely . | BACKGROUND Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications .
However , the value of routine late pregnancy ultrasound screening in unselected population s is controversial .
The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk , which would not necessarily have been detected by other means such as clinical examination , and for which subsequent management would improve perinatal outcome .
OBJECTIVES To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound , defined as greater than 24 weeks ' gestation , in women with either unselected or low-risk pregnancies . | In a study of 2000 unselected pregnant women the development of a mature placental appearance ( grade 3 ) on ultrasonography by 34 - 36 weeks ' gestation , observed in 15 % of cases , was associated with maternal smoking , low parity , low maternal age , and being white . These women had an increased risk of problems during labour and their babies had an increased risk of low birth weight , poor condition at birth , and perinatal death . The women were r and omly allocated to two groups : in one group the result of the placental grading was reported to the clinician responsible for care ; in the second the result was noted but not reported . There was a significant decrease in the risk of perinatal death in the group where the grading was known . This reduction was responsible for a difference in the principal outcome index , a heterogeneous group of measures of mortality and morbidity , but this difference was not significant . This study alone does not justify routine late scanning , and further , larger trials are required . Nevertheless , the results do provide a basis for the reporting of placental grading when ultrasound examination is performed during the third trimester Background In high-re source setting s , obstetric ultrasound is a st and ard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care . Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-re source setting s is unknown . Methods / Design This multi-country cluster r and omized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss , stillbirth and neonatal mortality in low-re source community setting s. The trial will utilize an existing research infrastructure , the Global Network for Women ’s and Children ’s Health Research with sites in Pakistan , Kenya , Zambia , Democratic Republic of Congo and Guatemala . A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population -based rates of maternal mortality and morbidity , stillbirth , neonatal mortality and morbidity , and health care utilization for study clusters . A total of 58 study clusters each with a health center and about 500 births per year will be r and omized ( 29 intervention and 29 control ) . The intervention includes training of health workers ( e.g. , nurses , midwives , clinical officers ) to perform ultrasound examinations during antenatal care , generally at 18–22 and at 32–36 weeks for each subject . Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care . Finally , the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities . Discussion In summary , our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural , low-re source setting s. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately . Trial registration Clinical trials.gov ( NCT # 01990625 OBJECTIVE --To examine any associations between routine ultrasonography in utero and subsequent brain development as indicated by non-right h and edness at primary school age and neurological development during childhood . DESIGN --Follow up of 8 and 9 year old children of women who took part in two r and omised , controlled trials of routine ultrasonography during pregnancy . SETTING --Clinics of 60 general practitioners in Norway during 1979 - 81 . Maternal and child health centres . SUBJECTS--2161 ( 89 % ) of 2428 eligible singletons were followed up , partly through a question naire to their parents and partly through information from health centres . MAIN OUTCOME MEASURES --The dominant h and of the child was assessed by 10 questions . Deficits in attention , motor control , and perception were evaluated by five questions . Impaired neurological development during the first year of life was assessed by an abbreviated version of the Denver developmental screening test . RESULTS --The odds of non-right h and edness were higher among children who had been screened in utero than among control children ( odds ratio 1.32 ; 95 % confidence interval 1.02 to 1.71 ) . No clear differences were found between the groups with regard to deficits in attention , motor control , and perception or neurological development during the first year of life . CONCLUSION --Our data suggest a possible association between routine ultrasonography in utero and subsequent non-right h and edness , whereas no association with impaired neurological development was found . As the question on non-right h and edness was one of six initial hypotheses , the observed results may be due to chance . None the less , the results suggest that the hypothesis may have some merit and should be tested in future studies The objective of this study was to evaluate and characterise by study of newborn biometry a possible effect on birthweight which we observed previously in a r and omised controlled trial of multiple prenatal ultrasound examinations . A total of 2743 women with single pregnancies had been allocated at r and om to either a protocol of ultrasound imaging and continuous wave Doppler studies at 18 , 24 , 28 , 34 and 38 weeks gestation ( intensive group ) , or to a protocol of a single imaging examination at 18 weeks and further imaging scans only as clinical ly indicated ( regular group ) . When compared with those in the regular group , and adjusted for other confounding variables , normally formed babies of term gestational age in the intensive group tended to be shorter when measured at birth ( P = 0.123 ) and on day 2 - 3 of age ( P = 0.068 ) . There were statistically insignificant reductions in the circumferences of the chest , abdomen and mid-arm ; and in the skinfold thicknesses of the triceps , parascapular and subscapular regions . Principal component analysis showed a trend for a reduction for the skeletal component ( P = 0.085 ) but not for the soft tissue component ( P = 0.332 ) . Comparison of the neonatal biometry in the two groups is not conclusive , but the differential effects on the various growth parameters suggest that if multiple scans do indeed restrict fetal growth , the mechanism is more likely to be an effect on bone growth rather than a reduction in nutrient supply from the placenta The study was performed to investigate any associations between routine ultrasonography during pregnancy and subsequent reduced vision and /or hearing among children . A follow-up was carried out of primary school children born to women who took part in two r and omized , controlled trials of routine ultrasonography during pregnancy . Of 2428 eligible singletons , 2161 ( 89 % ) were followed up with a parental question naire and with information from maternal and child health centers . Parents assessed vision and hearing in their children and reported their observations in question naires . At the age of 7 years , the children were also screened with bilateral visual acuity tests and pure tone audiometry at public maternal and child health centers . No significant differences between ultrasound-screened children and their controls were found in the parental assessment of vision or hearing . The objective tests did not show any significant differences between children in the two groups with regard to visual acuity or hearing . The risk of reduced vision or hearing was no greater for children of mothers who had been offered routine ultrasonography during pregnancy than for those whose mothers had not received that offer Abstract Despite widespread application of ultrasound imaging and Doppler blood flow studies , the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials . From 2834 women with single pregnancies at 16 - 20 weeks gestation , 1415 were selected at r and om to receive ultrasound imaging and continuous-wave Doppler flow studies at 18 , 24 , 28 , 34 , and 38 weeks gestation ( the intensive group ) and 1419 to receive single ultrasound imaging at 18 weeks ( the regular group ) . Outcome data was obtained from 99 % of women who entered the study . The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group , when expressed both as birthweight 342 : To compare detection rates of small‐for‐gestational‐age fetuses , large‐for‐gestational‐age fetuses , congenital anomalies and adverse perinatal outcomes in pregnancies r and omized to third‐trimester routine ultrasound or ultrasound on clinical indication Objective To compare the effects of four methods of analysis on the results of r and omised controlled trials that recruit women with multiple pregnancies and measure outcomes on their babies OBJECTIVES This r and omized clinical trial of 15,530 women was design ed to test the hypothesis that screening ultrasonography in low-risk pregnancies would improve perinatal outcome . A secondary hypothesis addressed in this article was that screening ultrasonography would have a favorable impact on maternal management or outcome . STUDY DESIGN Pregnant women without a specific indication for ultrasonographic examination in early pregnancy were r and omly assigned to have either two screening sonograms or conventional obstetric care . Pregnancy interventions and maternal outcomes were compared in the two groups . RESULTS No significant differences were found in maternal outcomes . Use of ultrasonography was markedly higher in the screened group . The rates of induced abortion , amniocentesis , tests of fetal well-being , external version , induction , and cesarean section and the distribution of total hospital days were similar in the two groups . Use of tocolytics and the rate of post date pregnancy were both slightly lower in the screened group . CONCLUSION Screening ultrasonography result ed in no clinical ly significant benefit A total of 745 Caucacian women were allocated at r and om between two groups , A and B , at the first antenatal visit . At the completion of the study , 341 patients in group A underwent a single ultrasonic measurement of fetal chest area between 32 and 36 weeks of gestation . The medical staff was not informed of these results . Three hundred and sixty‐four patients in group B acted as controls OBJECTIVE To evaluate the effect of introducing two biophysical ultrasound examinations in a low-risk antenatal population . METHODS Scans were performed at 30–32 weeks ' gestation and 36–37 weeks ' gestation . Scans assessed placental maturity , amniotic fluid volume , and estimated fetal weight . One thous and nine hundred ninety-eight low-risk patients were r and omized at 30 weeks ' gestation to a control group receiving st and ard antenatal care , or to the study group who also received an ultrasound scan . Outcome measures were frequency of small for date s ( less than 10th percentile at birth ) , intervention rates , and admissions to neonatal intensive care . RESULTS The proportion of infants assessed as small for date s at birth in the study group was 6.9 % ( 69 of 994 ) compared with 10.4 % ( 104 of 999 ) in the control group ( P = 008 ) . The rates of intervention in the study and control groups were 31.3 % ( 313 of 999 ) and 16.9 % ( 169 of 999 ) , respectively ( P < .001 ) . Twenty-eight ( 2.8 % ) neonates in the study group were admitted to the neonatal unit compared with 34 ( 3.4 % ) in the control group ( P = .532 ) . CONCLUSION Introduction of an ultrasound scan at 30–32 weeks ' and 36–37 weeks ' gestation may reduce the risk of a growth-restricted infant and increases antenatal interventions . Rates of admission to a neonatal unit are not significantly affected Summary : In this study 3 different methods of screening for birth‐weight < 10th percentile in pregnancy were evaluated both indivually and in combination ; 1,135 women with singleton pregnancies were studied . Measurements of symphysiofundal height by tape measure , and amniotic fluid index and fetal abdominal circumference by ultrasound imaging , were made at 18 , 24 , 28 , 34 and 38 weeks . At none of these gestational ages did amniotic fluid index perform well as a screening test for birth‐weight < 10th percentile . Combining the tests , using symphysiofundal height to select a group at high risk who then had a fetal abdominal circumference measurement , reduced the false positive rate but significantly decreased the percentage of infants diagnosed . The results of this study confirm that the most appropriate antenatal diagnostic test for birth‐weight < 10th percentile is ultrasound measurement of fetal abdominal circumference . Selecting pregnancies at risk by clinical measurement of symphysiofundal height will provide a lower false positive rate than a policy of performing ultrasound on all pregnancies during the third trimester , but will also reduce the sensitivity Most fetuses in developed countries are exposed in utero to diagnostic ultrasound examination . Many pregnant women express concern about whether the procedure harms the fetus . Since most routine ultrasound examinations are done at weeks 16 - 22 , when the fetal brain is developing rapidly , effects on neuronal migration are possible . We have sought an association between routine ultrasonography in utero and reading and writing skills among children in primary school . At the age of 8 or 9 years , children of women who had taken part in two r and omised , controlled trials of routine ultrasonography during pregnancy were followed-up . The women had attended the clinics of 60 general practitioners in central Norway during 1979 - 81 . The analysis of outcome was by intention to treat : 92 % of the " screened " group had been exposed to ultrasound screening at weeks 16 - 22 , and 95 % of controls had not been so exposed , but there was some overlap . 2428 singletons were eligible for follow-up , and the school performance of 2011 children ( 83 % ) was assessed by their teachers on a scale of 1 - 7 ; the teachers were unaware of ultrasound exposure status . A subgroup of 603 children underwent specific tests for dyslexia . There were no statistically significant differences between children screened with ultrasound and controls in the teacher-reported school performance ( scores for reading , spelling , arithmetic , or overall performance ) . Results from the dyslexia test sample showed no differences between screened children and controls in reading , spelling , and intelligence scores , or in discrepancy scores between intelligence and reading or spelling . The test results classified 21 of the 309 screened children ( 7 % [ 95 % confidence interval 3 - 10 % ] ) and 26 of the 294 controls ( 9 % [ 4 - 12 % ] ) as dyslexic . The risk of having poor skills in reading and writing was no greater for children whose mothers had been offered routine ultrasonography than for those whose mothers had not been offered the procedure OBJECTIVES Through comprehensive ophthalmic examination of adult offspring we sought to determine the impact of multiple prenatal ultrasound scans on ocular development . METHODS 2743 pregnant women recruited to the Western Australian Pregnancy ( Raine ) Cohort study during 1989 - 1991 were r and omized to receive at King Edward Memorial Hospital , Western Australia either multiple prenatal ultrasound scans and Doppler flow studies ( intensive group ) or a single ultrasound scan at 18 weeks ' gestation . Neonatal birth weight of the offspring and other physical measurements were collected prospect ively . At age 20 years , participants underwent a comprehensive ophthalmic examination including measurement of ocular biometry and visual acuity . RESULTS Complete data were available for 1134 adult offspring participants . The mothers of 563 of these had been r and omized to receive multiple prenatal ultrasound scans . The mean age of participants at follow-up was 20.0 years . There was no statistically significant difference between the two groups with regard to ocular biometric or visual outcomes , except for slightly higher intraocular pressure identified in individuals exposed to multiple ultrasound scans ( P = 0.034 ) . Although infants in the intensive-ultrasound arm were more likely to have birth weights in the lower quartiles , this was not reflected in adult eye development . Axial length , lens thickness , corneal curvature and thickness and optic cup to disc ratio ( a risk factor for glaucomatous optic neuropathy ) were not significantly influenced by the more frequent ultrasound protocol . CONCLUSIONS Prior to this study , there was a paucity of safety data for ultrasound with regard to eye development . We found that frequent in-utero exposure to ultrasound , including B-mode imaging and the use of spectral Doppler mode from 18 weeks ' gestation , had no significant impact on visual outcomes or ocular biometry OBJECTIVE To determine the relative accuracy of clinical and sonographic birth weight estimation among term parturients ( > or = 37 weeks ) and to assess the performance of the two techniques in identifying newborns with weights of < 2,500 g vs. > or = 2,500 g or < 2,500 g vs. at least 4,000 g. STUDY DESIGN The sample size for this r and omized clinical trial was based on the assumption that 50 % of clinical predictions are within 10 % of birth weight . Thus , 700 parturients were necessary to show a difference of 10 % with sonographic estimates ( alpha = .05 , beta = .02 ) . Inclusion criteria were singletons with a reliable gestational age of > or = 37 weeks , admitted for delivery and with no known fetal anomalies . Physicians who were unaware of previous sonographic estimates obtained the estimates . Student t and chi 2 tests were used ; relative risk ( RR ) and 95 % confidence intervals ( CIs ) were calculated . Receiver-operating characteristic ( ROC ) curves were constructed to compare the two techniques ' ability to differentiate between abnormal ( birth weight < 2,500 g and > 4,000 g ) and normal ( 2,500 - 3,999 g ) . P < .05 was considered significant . RESULTS Over 30 months , 758 term parturients were recruited ; of them , 391 had clinical estimates and 367 , sonographic . The two groups were similar in gestational age , prepregnancy and intrapartum body mass index , station of the presenting part , actual birth weight and frequency of newborns with weights < 2,500 g or > or = 4,000 g. Predictions based on clinical examination were significantly more likely to be within 10 % of actual weight ( 58 % ) than those derived from ultrasound examination ( 32 % ; P < .0001 ; RR , 1.65 ; 95 % CI , 1.43 , 1.69 ) . The areas under the ROC curves indicated that both techniques had a similar ability to differentiate normally and abnormally grown fetuses ( P > .05 ) . CONCLUSION Among term parturients , clinical estimates had significantly higher accuracy than ones derived sonographically An existing r and omised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype . From 2,834 single pregnancies , 1,415 were selected at r and om to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy ( Intensive ) and 1,419 to receive a single imaging scan at 18 weeks ( Regular ) , with further scans only as indicated on clinical grounds . There was no significant difference in the rate of Autism Spectrum Disorder between the Regular ( 9/1,125 , 0.8 % ) and Intensive ( 7/1,167 , 0.6 % ) groups , nor a difference between groups in the level of autistic-like traits in early adulthood . There is no clear link between the frequency and timing of prenatal ultrasound scans and the autism phenotype BACKGROUND Despite the widespread use of prenatal ultrasound studies , there are no published data from r and omised controlled trials describing childhood outcomes that might be influenced by repeated ultrasound exposures . We previously undertook a r and omised controlled trial to assess the effects of multiple studies on pregnancy and childhood outcomes and reported that those pregnancies allocated to receive multiple examinations had an unexplained and significant increase in the proportion of growth restricted newborns . Our aim was to investigate the possible effects of multiple prenatal ultrasound scans on growth and development in childhood . Here , we provide follow-up data of the childrens ' development . METHODS Physical and developmental assessment s were done on children whose pregnant mothers had been allocated at r and om to a protocol of five studies of ultrasound imaging and umbilical artery Doppler flow velocity waveform between 18 and 38 weeks ' gestation ( intensive group n=1490 ) or a single imaging study at 18 weeks ' gestation ( regular group n=1477 ) . We used generalised logistic and linear regression models to assess the group differences in developmental and growth outcomes over time . Primary data analysis was done by intention-to-treat . FINDINGS Examinations were done at 1 , 2 , 3 , 5 , and 8 years of age on children born without congenital abnormalities and from singleton pregnancies ( intensive group n=1362 , regular group n=1352 ) . The follow-up rate at 1 year was 85 % ( 2310/2714 ) and at 8 years was 75 % ( 2042/2714 ) . By 1 year of age and thereafter , physical sizes were similar in the two groups . There were no significant differences indicating deleterious effects of multiple ultrasound studies at any age as measured by st and ard tests of childhood speech , language , behaviour , and neurological development . INTERPRETATION Exposure to multiple prenatal ultrasound examinations from 18 weeks ' gestation onwards might be associated with a small effect on fetal growth but is followed in childhood by growth and measures of developmental outcome similar to those in children who had received a single prenatal scan Summary : Poor fetal growth is an important cause of perinatal mortality and morbidity . Based on the hypothesis that early diagnosis of fetal growth problems leads to more appropriate management and therefore , improved outcome , a r and omized controlled trial of ultrasound measurement was performed on 1,528 women booked though a hospital antenatal clinic This compared a number of perinatal outcomes between the group who had a routine 2‐stage examination ( early dating and 34‐week scan ) and a group who had only a dating scan and then additional scans as generated by their clinical situations . No significant differences could be found between the groups when these perinatal outcomes were considered . These results mirror previously published r and omized controlled trials . Selection of women for third trimester ultrasound examination for suspected fetal growth problems should be based on careful clinical assessment and should not be routine In the hope of reducing perinatal risks associated with retardation of intrauterine growth a previously described two stage ultrasound screening schedule was evaluated by a controlled trial in 877 women with low risk single pregnancies . The two stages of ultrasound examination were an assessment of gestational age during early pregnancy followed by measurement of length from crown to rump and area of trunk at between 34 and 36 weeks ' gestation . The product of crown to rump length and trunk area was calculated . The sensitivity of this schedule in identifying in advance 94 % of babies who were small for date s at birth , with 90 % specificity , and the speed and simplicity of measurement confirmed the accuracy and feasibility of two stage ultrasonography as a screening procedure . The controlled trial did not , however , show any benefit from its routine application in these low risk pregnancies OBJECTIVE To evaluate the possible benefits of the routine use of ultrasound screening in pregnancy . DESIGN A r and omized controlled trial was design ed to detect a 50 % difference in the incidence of induction for apparent post-term pregnancies between women who were screened with ultrasound and unscreened women . A total of 1628 pregnant women from the general population were included . Eight hundred and twenty-five were allocated to an ultrasound examination at the 18th and 32nd week of pregnancy in addition to receiving routine antenatal care . The remaining 803 women received st and ard antenatal care , but could only be referred for ultrasound examination on clinical indication . RESULTS The incidence of induced labor due to apparent post-term pregnancies was approximately 70 % lower in the ultrasound-screened group . Inductions from all causes were also less frequent among ultrasound-screened women . There were six perinatal deaths among the screened and seven among the controls after excluding three lethal malformations among the controls . There was no difference in Apgar score after 1 min , but the proportion with Apgar score less than 8 after 5 min was lower among the screened group ( P = 0.04 ) . The need for positive pressure ventilation for more than 1 min was lower among the screened group ( P = 0.02 ) . Birth weight was slightly higher in the screened group ( 39 g ) , but the difference was not statistically significant . Among the controls three pairs of twins remained undiagnosed until the mothers were admitted to the hospital in labor at between 36 and 38 weeks gestation . CONCLUSION These results suggest that for women who were screened with ultrasound , obstetricians were less likely to induce labor due to apparent post-term pregnancy , than for women who were not screened . All 10 pairs of twins in the screened group were diagnosed at the routine examination . These data also suggest that perinatal morbidity might be slightly lower in the screened group OBJECTIVE The objective of this r and omized clinical trial was to test the hypothesis that ultrasonographic screening would significantly alter perinatal outcome as a result of the antenatal detection of fetal congenital malformations . STUDY DESIGN Pregnant women without a specific indication for ultrasonography were r and omly assigned to have either two screening sonograms ( 15 to 22 weeks and 31 to 35 weeks ) or conventional obstetric care with ultrasonography used only as determined by the clinical judgment of the patient 's physician . The frequency of birth defect detection in the screened and control population s was compared , as was the impact of discovery on pregnancy outcome . RESULTS Major congenital malformations occurred in 2.3 % of the 15,281 fetuses and infants in this study . Antenatal ultrasonography detected 35 % of the anomalous fetuses in the screened group versus only 11 % in the control population ( relative detection rate 3.1 ; 95 % confidence interval 2.0 to 5.1 ) . Ultrasonography screening did not , however , significantly influence the management or outcome of pregnancies complicated by congenital malformations . Specifically , only 9 abortions were performed for anomalies among 7685 fetuses in the screened group whereas 4 pregnancies were terminated for fetal anomalies detected among 7596 control subjects . Ultrasonography screening also had no significant impact on survival rates among infants with potentially treatable , life-threatening anomalies despite the opportunity to take pre caution ary measures such as delivery in a tertiary center . CONCLUSIONS Ultrasonography screening in a low-risk pregnant population had no significant impact on the frequency of abortion for fetal anomalies . Survival rates for anomalous fetuses were also unaffected by screening Summary . A total of 2771 pregnant women with gestational age esti‐mated by ultrasound measurement of the fetal biparietal diameter ( BPD ) before the 22nd week of gestation were re‐examined by ultrasound in the 32nd and 37th week of pregnancy at which time the fetal BPD and abdominal diameter ( AD ) were measured . An additional examination was performed at 34 weeks if the fetal weight in the 32nd week was estimated to be less than 95 % of the expected mean weight . Light‐for‐gestational age ( LGA ) was suspected if the estimated birth‐weight was less than 85 % of the expected mean birthweight . This applied to 186 uncomplicated pregnancies in which there was no clinical suspicion of poor intrauterine growth . These pregnancies were r and omly allocated to a treatment group ( AD and estimated weight reported ) or to a control group ( AD and estimated weight withheld ) . Induction of labour was significantly more common in the treatment group ( 41 % ) than in the control group ( 15 % ) . No statistically significant difference was found in the use of instrumental vaginal delivery or caesarean section . There was a Suggestion of marginal benefit in terms of neonatal morbidity but this was not statistically significant The study was performed to investigate any associations between routine ultrasonography during pregnancy and subsequent growth during childhood . A follow-up was carried out of children born to women who took part in two r and omized , controlled trials of ultrasonic screening during pregnancy . From a total of 2428 eligible children , 2140 ( 88 % ) were followed up with measurements of growth at Norwegian maternal and child health centers . The body weight and height were recorded at birth and at 3 , 6 and 12 months of age ; and subsequently at 2 , 4 and 7 years of age . A repeated- measures analysis of growth was carried out , stratified by maternal smoking in a sub sample of 1201 children . No significant differences between ultrasound-screened children , and their controls , were found in mean body weight , or height , at birth and at all the subsequent visits to the health centers . However , the repeated- measures analysis of variance in the sub sample indicated that growth from birth to 7 years of age differed significantly ( p = 0.02 ) between screened and control children of mothers who reported smoking at the first antenatal visit . We conclude that children who were routinely exposed to ultrasonography in utero showed no statistically significant differences in growth during childhood compared to control children The study included 3311 pregnant women : 1570 in the screened group and 1741 in the unscreened group . In the screened group , ultrasound was offered routinely in the 32nd and 37th week of pregnancy , at which time the fetal biparietal diameter ( BPD ) and the abdominal mean diameter ( AD ) were measured . If , after the first ultrasound examination , the estimated weight was less than 85 % of the expected mean birthweight , a finding of light for gestational age ( LGA ) was suspected and the ultrasound examination was repeated in the 34th week . In the screened group 6.5 % of the women were at risk at the final ultrasound examination ( the sensitivity was 38 % ) and the predictive values of abnormal and normal weight deviation were 60 % and 93 % , with a specificity of 97 % and a relative risk of 9 . Ultrasound was offered to the unscreened group only in cases of clinical concern ( 23 % of the women ) . In the unscreened group 34 % of the 158 LGA infants had ultrasound performed before delivery because of clinical concern . By including pregnancies induced before ultrasound could be performed , 45 % of the LGA infants in the unscreened group were suspected before delivery . No significant difference between the rate of induction , instrumental deliveries and caesarean sections was found between the two groups . No benefit in terms of decreased incidence of infants with low Apgar score and acidosis was achieved 510 of 1009 pregnant women in the Trondheim area ( Norway ) were r and omly selected for ultrasound examination at the 19th and 32nd weeks of pregnancy in addition to routine antenatal care . Among the screened women , twins were diagnosed earlier and there were slightly fewer post-term inductions ( 2.8 % versus 4.0 % ) and fewer low-weight births ( 2.2 % versus 3.6 % less than 2500 g ) , but none of these differences was statistically significant . There were no differences in the condition of the newborn . Small-for-gestational-age births were more often diagnosed antenatally in the screened group and the mothers received more active treatment . During pregnancy , screened women were admitted to hospital more often than unscreened women ( 15.5 % versus 9.2 % ) . The study revealed no adverse short-term biological effects from ultrasound . The cost of the screening programme , including associated costs such as extra hospital admissions , was about US$ 250 per pregnancy |
13,013 | 28,099,689 | Up-to- date evidence of very low to moderate quality , with insufficient sample power per outcome , does not clearly support the use of procalcitonin-guided antimicrobial therapy to minimize mortality , mechanical ventilation , clinical severity , reinfection or duration of antimicrobial therapy of patients with septic conditions | BACKGROUND Serum procalcitonin ( PCT ) evaluation has been proposed for early diagnosis and accurate staging and to guide decisions regarding patients with sepsis , severe sepsis and septic shock , with possible reduction in mortality .
OBJECTIVES To assess the effectiveness and safety of serum PCT evaluation for reducing mortality and duration of antimicrobial therapy in adults with sepsis , severe sepsis or septic shock . | OBJECTIVE : To identify the independent variables associated with death within 4 days after the first sepsis-induced organ dysfunction . METHODS : In this prospect i ve observational study , severe sepsis and septic shock patients were classified into 3 groups : Group 1 , survivors ; Group 2 , late non-survivors ; and Group 3 , early non-survivors . Early death was defined as death occurring within 4 days after the first sepsis-induced organ dysfunction . Demographic , clinical and laboratory data were collected and su bmi tted to univariate and multinomial analyses . RESULTS : The study included 414 patients : 218 ( 52.7 % ) in Group 1 , 165 ( 39.8 % ) in Group 2 , and 31 ( 7.5 % ) in Group 3 . A multinomial logistic regression analysis showed that age , Acute Physiology and Chronic Health Evaluation II score , Sepsis-related Organ Failure Assessment score after the first 24 hours , nosocomial infection , hepatic dysfunction , and the time elapsed between the onset of organ dysfunction and the sepsis diagnosis were associated with early mortality . In contrast , Black race and a source of infection other than the urinary tract were associated with late death . Among the non-survivors , early death was associated with Acute Physiology and Chronic Health Evaluation II score , chronic renal failure , hepatic dysfunction Sepsis-related Organ Failure Assessment score after 24 hours , and the duration of organ dysfunction . CONCLUSION : Factors related to patients ' intrinsic characteristics and disease severity as well as the promptness of sepsis recognition are associated with early death among severe septic patients BACKGROUND Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units . We aim ed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting . METHODS In this multicentre , prospect i ve , parallel-group , open-label trial , we used an independent , computer-generated r and omisation sequence to r and omly assign patients in a 1:1 ratio to procalcitonin ( n=311 patients ) or control ( n=319 ) groups ; investigators were masked to assignment before , but not after , r and omisation . For the procalcitonin group , antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations ; the control group received antibiotics according to present guidelines . Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician . Patients were expected to stay in the intensive care unit for more than 3 days , had suspected bacterial infections , and were aged 18 years or older . Primary endpoints were mortality at days 28 and 60 ( non-inferiority analysis ) , and number of days without antibiotics by day 28 ( superiority analysis ) . Analyses were by intention to treat . The margin of non-inferiority was 10 % . This trial is registered with Clinical Trials.gov , number NCT00472667 . FINDINGS Nine patients were excluded from the study ; 307 patients in the procalcitonin group and 314 in the control group were included in analyses . Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 ( 21.2 % [ 65/307 ] vs 20.4 % [ 64/314 ] ; absolute difference 0.8 % , 90 % CI -4.6 to 6.2 ) and day 60 ( 30.0 % [ 92/307 ] vs 26.1 % [ 82/314 ] ; 3.8 % , -2.1 to 9.7 ) . Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group ( 14.3 days [ SD 9.1 ] vs 11.6 days [ SD 8.2 ] ; absolute difference 2.7 days , 95 % CI 1.4 to 4.1 , p<0.0001 ) . INTERPRETATION A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes . FUNDING Assistance Publique-Hôpitaux de Paris , France , and Brahms , Germany This prospect i ve , multicenter , epidemiological study was carried out in 99 Italian ICUs , distributed throughout the country , from April 1993 to March 1994 . In the study , we applied the new ACCP/SCCM classification system for sepsis ( SIRS , sepsis , severe sepsis and septic shock ) and determined the prevalence , incidence , evolution and outcome of these categories in critically ill patients . The preliminary analysis of 1101 patients showed that on admission SIRS accounted for about half of the diagnoses ( 52 % ) with sepsis , severe sepsis and septic shock accounting for 4.5 % , 2.1 % and 3 % of patients , respectively . Patients with severe sepsis or septic shock more frequently had high SAPS scores than patients without sepsis . Mortality rates were similar in patients with SIRS ( 26.5 % ) and without SIRS or infection ( 24 % ) , but rose to 36 % in patients with sepsis , to 52 % in those with severe sepsis and to 81.8 % in those with septic shock . Sepsis , severe sepsis and septic shock were more common in patients with medical diagnoses , and neither severe sepsis nor septic shock was observed in trauma patients . With respect to evolution , the incidence of septic shock was progressively higher in patients admitted with more severe “ sepsis-related ” diagnoses , while only a trivial difference in rates of incidence was observed between SIRS patients and those admitted without SIRS or any septic disorder ( nil ) . The breakdown of the various ACCP/SCCM “ sepsis-related ” diagnoses at any time during the study was : SIRS in 58 % of the population , sepsis in 16.3 % , severe sepsis in 5.5 % and septic shock in 6.1 % . It seems reasonable to expect from the final evaluation of our study answers to the questions raised by the ACCP/SCCM Consensus Conference about the correlations between “ sepsis-related ” diagnosis , severity score , organ dysfunction score and outcome Objectives To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients . Design Secondary analysis from a r and omised antibiotic strategy trial ( the Procalcitonin And Survival Study ) . The r and omised arms were conserved from the primary trial for the main analysis . Setting Nine mixed surgical/medical intensive care units across Denmark . Participants 1200 adult intensive care patients , 18 + years , expected to stay + 24 h. Exclusion criteria : bilirubin > 40 mg/dl , triglycerides > 1000 mg/dl , increased risk from blood sampling , pregnant/breast feeding and psychiatric patients . Interventions Patients were r and omised to guideline -based therapy ( ‘ st and ard-exposure ’ arm ) or to guideline -based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements ( ‘ high-exposure ’ arm ) . Main outcome measures Primary end point : estimated glomerular filtration rate ( eGFR ) < 60 ml/min/1.73 m2 . Secondary end points : ( 1 ) delta eGFR after starting/stopping a drug and ( 2 ) RIFLE criterion Risk ‘ R ’ , Injury ‘ I ’ and Failure ‘ F ’ . Analysis was by intention to treat . Results 28-day mortality was 31.8 % and comparable ( Jensen et al , Crit Care Med 2011 ) . A total of 3672/7634 ( 48.1 % ) study days during follow-up in the high-exposure versus 3016/6949 ( 43.4 % ) in the ‘ st and ard-exposure arm were spent with eGFR < 60 ml/min/1.73 m2 , p<0.001 . In a multiple effects model , 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used : 1.0 ml/min/1.73 m2/24 h while exposed to this drug ( 95 % CI 0.7 to 1.3 ml/min/1.73 m2/24 h ) vs meropenem : 2.9 ml/min/1.73 m2/24 h ( 2.5 to 3.3 ml/min/1.73 m2/24 h ) ) ; after discontinuing piperacillin/tazobactam , the renal recovery rate increased : 2.7 ml/min/1.73 m2/24 h ( 2.3 to 3.1 ml/min/1.73 m2 /24 h ) ) . eGFR < 60 ml/min/1.73 m2 in the two groups at entry and at last day of follow-up was 57 % versus 55 % and 41 % versus 39 % , respectively . Conclusions Piperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients . This nephrotoxicity was not observed when using other beta-lactam antibiotics . Trial registration Clinical Trials.gov identifier : NCT00271752 Objective : For patients in intensive care units , sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis . The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation , guided by daily measurements of the biomarker procalcitonin , could reduce the time to appropriate therapy , thus improving survival . Design : R and omized controlled open-label trial . Setting : Nine multidisciplinary intensive care units across Denmark . Patients : A total of 1,200 critically ill patients were included after meeting the following eligibility requirements : expected intensive care unit stay of ≥24 hrs , nonpregnant , judged to not be harmed by blood sampling , bilirubin < 40 mg/dL , and triglycerides < 1000 mg/dL ( not suspensive ) . Interventions : Patients were r and omized either to the “ st and ard-of-care-only arm , ” receiving treatment according to the current international guidelines and blinded to procalcitonin levels , or to the “ procalcitonin arm , ” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements . Measurements and Main Results : The primary end point was death from any cause at day 28 ; this occurred for 31.5 % ( 190 of 604 ) patients in the procalcitonin arm and for 32.0 % ( 191 of 596 ) patients in the st and ard-of-care-only arm ( absolute risk reduction , 0.6 % ; 95 % confidence interval [ CI ] −4.7 % to 5.9 % ) . Length of stay in the intensive care unit was increased by one day ( p = .004 ) in the procalcitonin arm , the rate of mechanical ventilation per day in the intensive care unit increased 4.9 % ( 95 % CI , 3.0–6.7 % ) , and the relative risk of days with estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 1.21 ( 95 % CI , 1.15–1.27 ) . Conclusions : Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit . The procalcitonin strategy like the one used in this trial can not be recommended IMPORTANCE High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress . Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis , but effect on outcome is unclear . OBJECTIVE To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality . DESIGN , SETTING , AND PARTICIPANTS The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis ( SISPCT ) , a multicenter , r and omized , clinical , 2 × 2 factorial trial performed in 33 intensive care units in Germany , was conducted from November 6 , 2009 , to June 6 , 2013 , including a 90-day follow-up period . INTERVENTIONS Patients were r and omly assigned to receive an initial intravenous loading dose of sodium selenite , 1000 µg , followed by a continuous intravenous infusion of sodium selenite , 1000 µg , daily until discharge from the intensive care unit , but not longer than 21 days , or placebo . Patients also were r and omized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance . MAIN OUTCOMES AND MEASURES The primary end point was 28-day mortality . Secondary outcomes included 90-day all-cause mortality , intervention-free days , antimicrobial costs , antimicrobial-free days , and secondary infections . RESULTS Of 8174 eligible patients , 1089 patients ( 13.3 % ) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite ( 543 patients [ 49.9 % ] ) with placebo ( 546 [ 50.1 % ] ) and procalcitonin guidance ( 552 [ 50.7 % ] ) vs no procalcitonin guidance ( 537 [ 49.3 % ] ) . The 28-day mortality rate was 28.3 % ( 95 % CI , 24.5%-32.3 % ) in the sodium selenite group and 25.5 % ( 95 % CI , 21.8%-29.4 % ) ( P = .30 ) in the placebo group . There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance ( 25.6 % [ 95 % CI , 22.0%-29.5 % ] ) vs no procalcitonin guidance ( 28.2 % [ 95 % CI , 24.4%-32.2 % ] ) ( P = .34 ) . Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5 % reduction of antimicrobial exposure . CONCLUSIONS AND RELEVANCE Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis . These findings do not support administration of high-dose sodium selenite in these patients ; the application of a procalcitonin-guided algorithm needs further evaluation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00832039 Background Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications . Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation . Therefore , many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven . With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis . Methods / Design The study is design ed as r and omized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment . Term and near-term infants ( gestational age ≥ 34 0/7 weeks ) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included . The duration of antibiotic therapy in the st and ard group is based on the attending physician 's assessment of the likelihood of infection ( infection unlikely , possible , probable or proven ) . In the Procalcitonin group , if infection is considered to be unlikely or possible , antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range . Co- primary outcome measures are the duration of antibiotic therapy ( superiority aspect of the trial ) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and /or death in the first month of life ( safety of study intervention , non-inferiority aspect of the trial ) . The number of infants to be included equals 800 per arm . With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety , i.e. excluding a disadvantage difference larger than 2 % for the experimental arm , will both be greater than 80 % . Discussion Benefit of the study is a possible limitation of unnecessary use of antibiotics . The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early , result ing in the development of a neonatal infection with its morbidity and mortality . Trial registration This trial is registered in the U.S. National Institutes of Health 's register , located at http://www . clinical trials.gov . ( NCT00854932 ) Purpose To quantify the effects of minor variations in the definition and measurement of systemic inflammatory response syndrome ( SIRS ) criteria and organ failure on the observed incidences of sepsis , severe sepsis and septic shock . Methods We conducted a prospect i ve , observational study in a tertiary intensive care unit in The Netherl and s between January 2009 and October 2010 . A total of 1,072 consecutive adults were included . We determined the upper and lower limits of the measured incidence of sepsis by evaluating the influence of the use of an automated versus a manual method of data collection , and variations in the number of SIRS criteria , concurrency of SIRS criteria , and duration of abnormal values required to make a particular diagnosis . Results The measured incidence of SIRS varied from 49 % ( most restrictive setting ) to 99 % ( most liberal setting ) . Subsequently , the incidences of sepsis , severe sepsis and septic shock ranged from 22 to 31 % , from 6 to 27 % and from 4 to 9 % for the most restrictive versus the most liberal measurement setting s , respectively . In non-infected patients , 39–98 % of patients had SIRS , whereas still 17–6 % of patients without SIRS had an infection . Conclusions The apparent incidence of sepsis heavily depends on minor variations in the definition of SIRS and mode of data recording . As a consequence , the current consensus criteria do not ensure uniform recruitment of patients into sepsis trials Introduction Consistent data about the incidence and outcome of sepsis in Latin American intensive care units ( ICUs ) , including Brazil , are lacking . This study was design ed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs . We also assessed the association between the Consensus Conference criteria and outcome Methods This is a multicenter observational cohort study performed in five private and public , mixed ICUs from two different regions of Brazil . We prospect ively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002 , until their discharge , 28th day of stay , or death . For all patients we collected the following data at ICU admission : age , gender , hospital and ICU admission diagnosis , APACHE II score , and associated underlying diseases . During the following days , we looked for systemic inflammatory response syndrome ( SIRS ) , sepsis , severe sepsis , and septic shock criteria , as well as recording the sequential organ failure assessment score . Infection was diagnosed according to CDC criteria for nosocomial infection , and for community-acquired infection , clinical , radiological and microbiological parameters were used . Results For the whole cohort , median age was 65.2 years ( 49–76 ) , median length of stay was 2 days ( 1–6 ) , and the overall 28-day mortality rate was 21.8 % . Considering 1383 patients , the incidence density rates for sepsis , severe sepsis and septic shock were 61.4 , 35.6 and 30.0 per 1000 patient-days , respectively . The mortality rate of patients with SIRS , sepsis , severe sepsis and septic shock increased progressively from 24.3 % to 34.7 % , 47.3 % and 52.2 % , respectively . For patients with SIRS without infection the mortality rate was 11.3 % . The main source of infection was lung/respiratory tract . Conclusion Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs , with an incidence density about 57 per 1000 patient-days . Moreover , there was a close association between ACCP/SCCM categories and mortality rate Introduction The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment . Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting . Until recently , no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction ; however , over the past years , procalcitonin ( PCT ) is the first among a large array of inflammatory variables that offers this possibility . The present study aim ed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients . Methods All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible . Patients were r and omly assigned to either a PCT-guided ( study group ) or a st and ard ( control group ) antibiotic regimen . Antibiotic therapy in the PCT-guided group was discontinued , if clinical signs and symptoms of infection improved and PCT decreased to < 1 ng/ml or the PCT value was > 1 ng/ml , but had dropped to 25 to 35 % of the initial value over three days . In the control group antibiotic treatment was applied as st and ard regimen over eight days . Results A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high- grade suspected infections were enrolled in this study . In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly . The control group comprised 53 patients with a st and ardized duration of antibiotic therapy over eight days . Demographic and clinical data were comparable in both groups . However , in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls ( 5.9 + /- 1.7 versus 7.9 + /- 0.5 days , P < 0.001 ) without negative effects on clinical outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine . Annotation Results were previously published in German in Anaesthesist 2008 ; 57 : 571–577 ( PMID : 18463831).Trial registration IS RCT Introduction Severe sepsis is associated with high levels of morbidity and mortality , placing a high burden on healthcare re sources . We aim ed to study outcomes in the five years after severe sepsis . Methods This was a cohort study using data from a prospect i ve audit in 26 adult ICUs in Scotl and . Mortality was measured using clinical data bases and quality of life using Short Form 36 ( SF-36 ) at 3.5 and 5 years after severe sepsis . Results A total of 439 patients were recruited with a 58 % mortality at 3.5 years and 61 % mortality at 5 years . A total of 85 and 67 patients responded at 3.5 and 5 years follow-up , respectively . SF-36 physical component score ( PCS ) was low compared to population controls at 3.5 years ( mean 41.8 ( SD 11.8 ) ) and at 5 years ( mean 44.8 ( SD 12.7 ) ) . SF-36 mental component score ( MCS ) was slightly lower than population controls at 3.5 years ( mean 47.7 ( SD 14.6 ) ) and at 5 years after severe sepsis ( mean 48.8 ( SD 12.6 ) ) . The majority of patients were satisfied with their current quality of life ( QOL ) ( 80 % ) and all patients would be willing to be treated in an ICU again if they become critically ill despite many having unpleasant memories ( 19 % ) and recall ( 29 % ) of ICU events . Conclusions Patients with severe sepsis have a high ongoing mortality after severe sepsis . They also have a significantly lower physical QOL compared to population norms but mental QOL scores were only slightly below population norms up to five years after severe sepsis . All survivors would be willing to be treated in an ICU again if critically ill . Mortality and QOL outcomes were broadly similar to other critically ill cohorts throughout the five years of follow-up Objective : We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis . Design : R and omized open clinical trial . Setting : Two university hospitals in Brazil . Patients : Patients with severe sepsis or septic shock . Interventions : Patients were r and omized in two groups : the procalcitonin group and the C-reactive protein group . Antibiotic therapy was discontinued following a protocol based on serum levels of these markers , according to the allocation group . The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25 % shorter than in the C-reactive protein group . For both groups , at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and /or bacteremia at inclusion , and patients with evident resolution of the infectious process had antibiotics stopped after 7 days , despite biomarkers levels . Measurements and Main Results : Ninety-four patients were r and omized : 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group . The mean age was 59.8 ( SD , 16.8 ) years . The median duration of antibiotic therapy for the first episode of infection was 7.0 ( Q1–Q3 , 6.0–8.5 ) days in the procalcitonin group and 6.0 ( Q1–Q3 , 5.0–7.0 ) days in the C-reactive protein group ( p = 0.13 ) , with a hazard ratio of 1.206 ( 95 % CI , 0.774–1.3 ; p = 0.13 ) . Overall , protocol overruling occurred in only 13 ( 13.8 % ) patients . Twenty-one patients died in each group ( p = 0.836 ) . Conclusions : C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients , causing no apparent Objective Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen . We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis . Design This multicentre , r and omised , controlled , single-blind trial was performed in two parallel groups . Setting Eight intensive care units in France . Participants Adults with the phenotype of severe sepsis and no overt source of infection , negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission . Intervention The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians ’ clinical judgement without reference to procalcitonin values in the control arm . Main outcome measure The primary outcome was the proportion of patients on antibiotics on day 5 postr and omisation . Results Over a 3-year period , 62/1250 screened patients were eligible for the study , of whom 31 were r and omised to each arm ; 4 later withdrew their consent . At day 5 , 18/27 ( 67 % ) survivors were on antibiotics in the experimental arm , versus 21/26 ( 81 % ) controls ( p=0.24 ; relative risk=0.83 , 95 % CI : 0.60 to 1.14 ) . Only 8/58 patients ( 13 % ) had baseline procalcitonin < 0.25 µg/l ; in these patients , physician complied poorly with the algorithm . Conclusions In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen , the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure . However , the premature termination of the trial may not allow definitive conclusions Clinicians , patients , governments , third-party payers , and the public take for granted that diagnostic tests are accurate , safe and effective . However , we may be seriously misled if we are relying on robust study design to ensure accurate , safe , and effective diagnostic tests . Properly conducted , r and omized controlled trials are the gold st and ard for assessing the effectiveness and safety of interventions , yet are rarely conducted in the assessment of diagnostic tests . Instead , diagnostic cohort studies are commonly performed to assess the characteristics of a diagnostic test including sensitivity and specificity . While diagnostic cohort studies can inform us about the relative accuracy of an experimental diagnostic intervention compared to a reference st and ard , they do not inform us about whether the differences in accuracy are clinical ly important , or the degree of clinical importance ( in other words , the impact on patient outcomes ) . In this commentary we provide the advantages of the diagnostic r and omized controlled trial and suggest a greater awareness and uptake in their conduct . Doing so will better ensure that patients are offered diagnostic procedures that will make a clinical difference Background Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients . Several antimicrobials have been implicated , although experimental evidence to demonstrate causality is limited . We report , using a r and omized trial , the potential of antimicrobials to induce thrombocytopenia . Methods R and omized trial allocated patients to antimicrobial treatment according to st and ard- of-care ( SOC group ) or drug-escalation in case of procalcitonin increases ( high-exposure group ) . Patients were followed until death or day 28 . Thrombocytopenia defined as absolute ( platelet count ≤100x109/L ) or relative ( ≥20 % decrease in platelet count ) . Analyses were performed in the two r and omized groups and as a merged cohort . Results Of the 1147 patients with platelet data available , 18 % had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17 % developed this complication during follow-up ; 57 % developed relative thrombocytopenia during follow-up . Absolute and relative thrombocytopenia day 1 - 4 was associated with increased mortality ( HR : 1.67 [ 95 % CI : 1.30 to 2.14 ] ; 1.71 [ 95 % CI : 1.30 to 2.30 ] , P<0.0001 , respectively ) . Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam , meropenem and ciprofloxacin compared with the SOC group , whereas cefuroxime was used more frequently in the SOC group ( p<0.05 ) . Risk of absolute and relative thrombocytopenia ( RR : 0.9 [ 0.7 - 1.3 ] , p=0.7439 ; 1.2 [ 1.0 - 1.4 ] , p=0.06 ; respectively ) , as well as absolute platelet count ( daily difference , high-exposure vs. SOC -1.7 [ -3.8 - 0.5 ] , p=0.14 ) was comparable between groups . In observational analyses , use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia ( vs. cefuroxime , RR : 2.08 [ 1.48 - 2.92 ] ; 1.44 [ 1.10 - 1.89 ] , respectively ) , however only ciprofloxacin were associated with a reduction in absolute platelet count ( p=0.0005 ) . Conclusion High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients . However , single use of ciprofloxacin , and less so piperacillin/tazobactam , may contribute to a lower platelet count . Trial Registration Clinical Trials.gov NCT00271752 http:// clinical Introduction The aims of this study were to assess the reliability of circulating cell-free DNA ( cf-DNA ) concentrations , compared with C-reactive protein ( CRP ) , procalcitonin ( PCT ) and eosinophil count , in the diagnosis of infections in patients with systemic inflammatory response syndrome ( SIRS ) and their prognostic values in a cohort of critically ill patients . Methods We conducted a prospect i ve cohort study in a medical-surgical intensive care unit of a university hospital . Eosinophil count and concentrations of cf-DNA , CRP , and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit ( ICU ) and a second determination 24 hours later . DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene . Results One hundred and sixty consecutive patients were included : 43 SIRS without sepsis and 117 with sepsis . Levels of CRP and PCT , but not cf-DNA or eosinophil count , were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2 . PCT on day 1 achieves the best area under the curve ( AUC ) for sepsis diagnosis ( 0.87 ; 95 % confidence interval = 0.81 - 0.94 ) . Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score . PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers . Conclusions Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS . PCT is of value especially for infection identification in patients with SIRS at admission to the ICU Febrile neutropenia ( FN ) requires immediate use of antibiotics ( ATB ) , and procalcitonin ( PCT ) is proven to be useful in guiding antibiotic therapy in different setting s. This study investigated the use of PCT as a guide for the duration of ATB in FN . A r and omized controlled trial was carried out from January – December 2010 . A total of 62 hematological adult patients with FN were r and omized , in 1:1 ratio , into two groups : ( 1 ) PCT group : length of ATB guided by institutional protocol plus PCT dynamics , and ( 2 ) control group : duration of ATB in accordance with institutional protocol . There was no difference between groups regarding the use of ATB for the first episode of fever ( HR 1.14 , 95 % CI 0.66–1.95 , p = 0.641 ) , with equivalent median duration of ATB therapy ( PCT group 9.0 days and control group 8.0 days , p = 0.67 ) , and median number of days without ATB ( 0 days , IQR 0–2 days for both groups , p = 0.96 ) . We observed no difference in clinical cure rate ( p = 0.68 ) , infection relapse ( p = 1.0 ) , superinfection ( p = 0.85 ) , length of hospitalization ( p = 0.64 ) , and mortality at 28 days ( p = 0.39 ) and at 90 days ( p = 0.72 ) . Considering the cut-off of 0.5 ng/ml , PCT was correlated with bacteremia ( sensitivity of 51.9 % and specificity of 76.5 % ) . In this r and omized controlled trial , adding a PCT-guided protocol to the st and ard recommendations did not reduce the use of antibiotics in febrile neutropenia , although no apparent harm was caused . PCT proved to be a marker of bacteremia in this setting PURPOSE In Brazil , sepsis has a high mortality ; and early recognition is essential in outcome . The aim of the study was to evaluate physicians ' knowledge about systemic inflammatory response syndrome ( SIRS ) , sepsis , severe sepsis , and septic shock concepts . METHODS This was a prospect i ve , observational study performed in 21 hospitals in Brazil , which enrolled physicians working in the participant institutions . A previously vali date d question naire was applied to physicians including 5 clinical cases . RESULTS Twenty-one Brazilian institutions enrolled 917 physicians . The percentage of physicians correctly recognizing SIRS , infection , sepsis , severe sepsis , and septic shock was 78.2 % , 92.6 % , 27.3 % , 56.7 % , and 81.0 % , respectively . Intensivists performed better in all diagnoses . There was a significantly higher rate of correct answers for SIRS ( P < .001 ) , sepsis ( P = .001 ) , and severe sepsis ( P = .032 ) among physicians from university hospitals as compared with those from public hospitals . A mean global score of 3.36 ± 1.08 was found , with better performance for residents ( P = .012 ) and intensivists ( P < .001 ) ; but no difference was found for emergency physicians ( P = .875 ) . CONCLUSION The prompt recognition of sepsis and its severity is not satisfactory . This difference is probably due to the difficulty in the recognition of organ dysfunction , which hampers early identification of septic patients INTRODUCTION Procalcitonin ( PCT ) is a thyroid gl and prohormone , and its serum concentration is elevated in systemic bacterial infections . The diagnostic cut-off value of PCT in patients early after cardiac surgery remains unclear . OBJECTIVE We investigated whether procalcitonin-guidance could reduce antibiotic usage safely . METHODS The prospect i ve study included 205 patients who underwent open heart surgery . The patients were r and omly assigned for procalcitonin-guided antibiotic treatment ( PCT-group ; n = 102 ) or st and ard care ( st and ard group ; n = 103 ) . On the basis of serum procalcitonin concentrations , usage of antibiotics was encouraged ( PCT > or = 0.5 ng/mL ) or discouraged . RESULTS A relative risk of antibiotic exposure in the st and ard group compared with the PCT-group was 3.81 ( 95 % CI = 2.03 - 7.17 ; p < 0.0001 ) . The mean cost of antibiotics per patient in procalcitonin group was Euro 193.3 + /- 636.6 vs. Euro 372.1 + /- 841.1 ( p = 0.206 ) in the st and ard group , while the mean cost per hospital day was Euro 8.0 + /- 18.4 vs. Euro 17.8 + /- 36.3 ( p = 0.028 ) . We found that non-infectious complications occurred in 40/102 vs. 41/103 ( p = 0.592 ) while infections appeared in 5/102 vs. 22/103 ( p = 0.001 ) cases . A statistically significant difference was observed in the treatment of urinary infections between PCT-group and st and ard group ; 1/102 vs. 9/103 ( p = 0.016 ) . In the PCT-group , the ICU stay was 5.74 + /- 11.49 days and in the st and ard group 6.97 + /- 11.61 ( p = 0.812 ) . The hospital stay was 12.08 + /- 11.28 vs. 12.93 + /- 10.73 ( p > 0.05 ) days , respectively . Mortality rates were equal in both groups of patients ( p = 0.537 ) . CONCLUSION Procalcitonin-guided antibiotic treatment is safe and can significantly reduce the cost of postoperative care . Additionally , the antibiotic use during immediate postoperative course should be timely controlled and limited to documented bacterial infections Objectives : To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients . Design : Single-center , prospect i ve , r and omized controlled study . Setting : Five intensive care units from a tertiary teaching hospital . Patients : All consecutive adult patients hospitalized for > 48 hrs in the intensive care unit during a 9-month period . Interventions : Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay . The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification . Patients were r and omized into two groups : one using the procalcitonin results ( procalcitonin group ) and one being blinded to the procalcitonin results ( control group ) . The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach . Secondary end points included : a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist . Measurements and Main Results : There were 258 patients in the procalcitonin group and 251 patients in the control group . A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection . This , however , did not result in a reduction of antibiotic consumption . The treatment days represented 62.6 ± 34.4 % and 57.7 ± 34.4 % of the intensive care unit stays in the procalcitonin and control groups , respectively ( p = .11 ) . According to the infectious-disease specialist , 33.8 % of the cases in which no infection was confirmed , had a procalcitonin value > 1µg/L and 14.9 % of the cases with confirmed infection had procalcitonin levels < 0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection , upon initiation of antibiotic treatment was low , as confirmed by the receiving operating curve analysis ( area under the curve = 0.69 ) . Finally , procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician . Conclusions : Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aim ing at decreasing the antibiotic consumption in intensive care unit patients BACKGROUND / AIMS In surgical sepsis , the rapid identification of source of infection at an early stage after surgery or serious trauma is crucial for favorable outcome . The discrimination between local and generalized infection is critical for correct treatment . METHODOLOGY In a r and omized , controlled , single-centre study we investigated 72 patients with severe sepsis after major abdominal surgery or surgery for multiple trauma . Patients were divided in 2 groups : in the first group ( PCT , n=38 ) , more important role in the treatment decision was given to PCT level ( severe sepsis with PCT > 2 ng/mL signalled bacteremia and pushed us to change antibiotics and intravascular devices , severe sepsis with PCT < or = 2 ng/mL prompted use of ultrasonography and /or CT , followed by repeated surgery in patients with localized infection ) . The control group ( CON , n=34 ) was treated by st and ard evaluation of all parameters by consultant surgeon . We investigated 28-day all-cause mortality , sepsis-related complications , the duration of stay in the intensive care unit , and ventilated days . RESULTS The hospital mortality was in PCT group 26 % and 38 % in control group ( p = 0.28 ) . Average SOFA score was 7.9 + /- 2.8 in PCT group vs. 9.3 + /- 3.3 ( p = 0.06 ) . The decline of ICU days ( 16.1 + /- 6.9 vs. 19.4 + /- 8.9 ; p = 0.09 ) and ventilated days ( 10.3 + /- 7.8 vs. 13.9 + /- 9.4 ; p = 0.08 ) in PCT group was observed , but the difference was not significant . CONCLUSIONS We observed a clear tendency to decrease extent of multiple organ dysfunction syndrome in patients , in which therapeutic decision was made earlier using procalcitonin as an additional marker separating local infection from generalized one Objective : To study long-term mortality , quality of life ( QOL ) , quality -adjusted life years ( QALYs ) , and costs per QALY in an unselected intensive care unit ( ICU ) patient population with severe sepsis . Design : Prospect i ve observational cohort study . Setting : Twenty-four ICUs in Finl and . Patients : A total of 470 adult patients with severe sepsis who were treated in ICUs between November 1 , 2004 and February 28 , 2005 . The QOL before critical illness was assessed in 252 patients and QOL after severe sepsis in 156 patients ( 58 % of the patients surviving in April 30 , 2006 ) . Ninety-eight patients responded to both question naires . QOL was assessed by a generic EuroQol-5D ( EQ-5D ) measurement with summary index ( EQsum ) and visual analogue scale ( VAS ) . Measurements and Main Results : The 2-year mortality after severe sepsis was 44.9 % ( 211 of 470 ) . The median response time for QOL assessment after severe sepsis was 17 months ( interquartile range [ IQR ] 16–18 ) . The median EQsum ( 75 , IQR 56–92 ) and EQ VAS ( 66 , IQR 50–80 ) were lower after severe sepsis than age- and sex-adjusted reference values ( p < 0.001 and p < 0.001 ) . The decrease between the mean EQsum reference value and that of severe sepsis patients was 12 ( 95 % confidence interval [ CI ] , 9–16 ) . The difference between the mean EQ VAS reference values and the mean EQ VAS was 8 ( 95 % CI , 5–11 ) . The mean calculated QALYs after severe sepsis were 10.9 ( 95 % CI , 9.7–12.1 ) and the calculated cost for one QALY was only 2139 & OV0556 ; for all survivors and nonsurvivors . Conclusions : Two-year mortality after severe sepsis was high ( 44.9 % ) and the QOL was lower after severe sepsis than before critical illness as assessed by EQ-5D . However , the mean QALYs for the surviving patients were reasonable and the cost for one QALY was reasonably low , which makes intensive care in patients with severe sepsis cost effective Abstract Objectives : To determine the diagnostic values of plasma C-reactive protein ( CRP ) , procalcitonin ( PCT ) , and interleukin-6 ( IL-6 ) using an electrochemiluminescence immunoassay ( ECLIA ) method ( Roche Diagnostics GmbH , Mannheim , Germany ) to identify severe sepsis in an emergency room ( ER ) setting . Methods : This was a single-centre prospect i ve follow-up study of 539 consecutive adult patients admitted to the ER with suspected infection . Blood sample s were taken concurrently with blood cultures at admission . Patients were divided into 5 groups on the basis of systemic inflammatory response syndrome ( SIRS ) criteria , documentation of bacterial infection , and organ dysfunction . Fifty-nine patients with no SIRS or bacterial infection , 68 patients with bacterial infection but no SIRS , 54 patients with SIRS but no bacterial infection , 309 patients with sepsis ( SIRS and bacterial infection ) , and 49 patients with severe sepsis ( sepsis and organ failure ) were evaluated . Results : In a logistic regression model , the odds ratio ( OR ) for PCT was 1.58 ( 95 % confidence interval ( CI ) 1.37–1.82 , p < 0.0001 ) , for IL-6 was 1.54 ( 95 % CI 1.32–1.80 , p < 0.0001 ) , and for CRP was 1.33 ( 95 % CI 1.01–1.75 , p = 0.045 ) . The area under the curve ( AUC ) was 0.77 ( 95 % CI 0.71–0.84 ) for PCT , 0.72 ( 95 % CI 0.64–0.80 ) for IL-6 , and 0.60 ( 95 % CI 0.51–0.69 ) for CRP . PCT emerged as the best marker for severe sepsis , but the difference in AUC was not significant between PCT and IL-6 . In multivariate logistic regression analysis , after adjusting for confounders , PCT and IL-6 remained significant independent predictors of severe sepsis . Conclusions : PCT and IL-6 proved superior to CRP in detecting patients with severe sepsis . The findings thus support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis . The automatic ECLIA method allows even night-shift measurements AIMS 1 ) To assess the prognostic value of levels on admission and serial measurements of lipopolysaccharide binding protein ( LBP ) and procalcitonin ( PCT ) in relation to in-hospital mortality ; and 2 ) to determine whether the addition of these parameters to severity scores ( APACHE II and SOFA ) is able to improve prognostic accuracy . DESIGN A single-center , prospect i ve observational study was carried out . SETTING Intensive Care unit of a university hospital . PATIENTS One hundred severe sepsis and septic shock patients were included . DATA COLLECTED Demographic data , APACHE II and SOFA scores , PCT and LBP levels on admission and after 48 hours , and in-hospital mortality . RESULTS The best area under the curve for predicting in-hospital mortality corresponded to APACHE II on admission and SOFA after 48 h ( AUC ROC : 0.75 for both ) . PCT and LBP levels on admission and LBP clearance were not statistically different between in-hospital survivors and non-survivors . Only PCT clearance was higher among in-hospital survivors than in non-survivors ( AUC ROC : 0.66 ) . The combination of severity scores and PCT clearance did not result in superior areas under the curve . CONCLUSIONS LBP and PCT levels on admission and LBP clearance showed no prognostic value in severe sepsis and septic shock patients . Only PCT clearance was predictive of in-hospital mortality . The prognostic accuracy was significantly better for APACHE on admission and SOFA after 48 h than for any of the analyzed biomarkers , and the addition of PCT clearance did not improve their prognostic value The empiric antibiotic therapy can result in antibiotic overuse , development of bacterial resistance and increasing costs in critically ill patients . The aim of the present study was to evaluate the effect of procalcitonin ( PCT ) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit ( ICU ) with systemic inflammatory response syndrome ( SIRS ) . A total of 60 patients were enrolled in this study and r and omly divided into two groups , cases that underwent antibiotic treatment based on serum level of PCT as PCT group ( n=30 ) and patients who undergoing antibiotic empiric therapy as control group ( n=30 ) . Our primary endpoint was the use of antibiotic treatment . Additional endpoints were changed in clinical status and early mortality . Antibiotics use was lower in PCT group compared to control group ( P=0.03 ) . Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ ( P=0.88 ) . Patients in PCT group had a significantly shorter median ICU stay , four days versus six days ( P=0.01 ) . However , hospital stay was not statistically significant different between two groups , 20 days versus 22 days ( P=0.23 ) . Early mortality was similar between two groups . PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay , and we found no differences in clinical outcomes and early mortality rates between the two studied groups OBJECTIVE To investigate the significance of dynamic monitoring of procalcitonin ( PCT ) in guiding the use of antibiotics for treating patients with sepsis in intensive care unit ( ICU ) . METHODS Eighty-two patients with sepsis from January 2012 to June 2013 hospitalized in ICU of First Hospital of Jilin University were enrolled , and they were r and omly divided into regular antibiotic therapy group ( RAT group , n=40 ) and PCT monitoring in guiding the use of antibiotics group ( PCT group , n=42 ) . Patients in RAT group were treated according to principle of antibiotics usage , while in PCT group patients ' PCT value was observed everyday . When no active symptoms of infection were shown , and acute physiology and chronic health evaluation II ( APACHEII ) scores declined , PCT value decreased over 90 % or PCT value lower than 0.25 μg/L time point were selected as drug withdrawal indication . The general status of the patient , antimicrobial drug use time , and prognosis were compared between the two groups , and Kaplan-Meier method was used for survival curve analysis . Variance analysis was used for repeating measurement to observe dynamic serum PCT level of the two groups of patients for survival and death during 7 days . RESULTS Mann-Whitney U test or χ(2 ) test showed that there were no statistical significance in age , gender , APACHEII score , blood culture positive rate , sputum culture positive rate , cardiac insufficiency , renal failure , respiratory failure , and ventilator and hemofiltration usage ( all P>0.05 ) . Log Rank test results showed that the time of antimicrobial drug usage was significantly reduced in PCT group than that in RAT group [ days : 8.1±0.3 , 95 % confidence interval ( 95%CI 8.3 - 9.7 ) vs. 9.3±0.3 ( 95%CI 8.7 - 10.1 ) , P=0.013 ] . Kaplan-Meier univariate survival curves showed that the speed of curve declination in PCT group was faster significantly than that in RAT group , suggesting that the time of using antimicrobial drug was shortened . There was no significant difference in length of hospital stay , ICU stay time , number of death in 28 days , number of cases of recurrence in 28 days and clinical cure rate between two groups ( all P>0.05 ) . PCT level in non-survivors in both groups was significantly higher than that in the survivors , exceeding more than 10 μg/L in the early and late stages of treatment . CONCLUSIONS Dynamic monitoring of PCT can effectively reduce antimicrobial drug use in ICU patients with sepsis , but there is no significant difference in patients ' prognosis Background The aim of this study was to evaluate the clinical usefulness of a semiquantitative procalcitonin kit for assessing severity of sepsis and early determination of mortality in affected patients . Methods This was a prospect i ve , observational study including 206 septic patients enrolled between June 2008 and August 2009 . Disseminated intravascular coagulation ( DIC ) , Sequential Organ Failure Assessment ( SOFA ) , Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores were measured , along with semiquantitative procalcitonin concentrations . Patients were divided into three groups based on their semiquantitative procalcitonin concentrations ( group A , < 2 ng/mL ; group B ≥ 2 ng/mL < 10 ng/mL ; group C ≥ 10 ng/mL ) . Results A significant difference in DIC , SOFA , and APACHE II scores was found between group A and group C and between group B and group C ( P < 0.01 ) . Patients with severe sepsis and septic shock had significantly higher procalcitonin concentrations than did patients with less severe disease . The rate of patients with septic shock with high procalcitonin concentrations showed an upward trend . There was a significant ( P < 0.01 ) difference between the three groups with regard to numbers of patients and rates of severe sepsis , septic shock , DIC , and mortality . Conclusion Semiquantitative procalcitonin concentration testing can be helpful for early assessment of disease severity in patients with sepsis . Furthermore , it may also help in predicting early mortality in septic patients . Based on the level of semiquantitative procalcitonin measured in patients with suspected sepsis , a timely decision can be reliably made to transfer them to a tertiary hospital with an intensive care unit for optimal care Background : Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific . Early antibiotic therapy is crucial for treatment success . Objective : To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis . Methods : This single-center , prospect i ve , r and omized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children ’s Hospital of Lucerne , Switzerl and , between June 1 , 2005 and December 31 , 2006 . All term and near-term infants ( gestational age ≧34 weeks ) with suspected early-onset sepsis were r and omly assigned either to st and ard treatment based on conventional laboratory parameters ( st and ard group ) or to PCT-guided treatment ( PCT group ) . Minimum duration of antibiotic therapy was 48–72 h in the st and ard group , whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values . Results : 121 newborns were r and omly assigned either to the st and ard group ( n = 61 ) or the PCT group ( n = 60 ) . The two groups were similar for baseline demographics , risk factors for early-onset sepsis , likelihood of infection as assessed by the attending physician and early conventional laboratory findings . There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the st and ard group ( 82 % ) and the PCT group ( 55 % ) ( absolute risk reduction 27 % ; odds ratio 0.27 ( 95 % CI 0.12–0.62 ) , p = 0.002 ) . On average , PCT-guided decision-making result ed in a shortening of 22.4 h of antibiotic therapy . Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events . Conclusion : Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis . Before this PCT-guided strategy can be recommended , its safety has to be confirmed in a larger cohort of neonates Background Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine . The biochemical variable procalcitonin ( PCT ) is known to indicate systemically relevant bacterial infections with high accuracy . In the present study , we aim ed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis . Patients and methods Patients were r and omly assigned to a PCT-guided or a control group requiring antibiotic treatment . All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum . In the PCT-guided group , antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either < 1 ng/ml or decreased to < 35 % of the initial concentration within three consecutive days . In the control group , antibiotic treatment was directed by empirical rules . Results The PCT-guided group ( n = 14 patients ) and the control group ( n = 13 patients ) did not differ in terms of biological variables , underlying diseases , and overall disease severity . PCT guidance led to a significant reduction of antibiotic treatment from 6.6 ± 1.1 days ( mean ± SD ) compared with 8.3 ± 0.7 days in control patients ( p < 0.001 ) along with a reduction of antibiotic treatment costs of 17.8 % ( p < 0.01 ) without any adverse effects on outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine RATIONALE The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse , increasing the risk of developing bacterial resistance . OBJECTIVES To test the hypothesis that an algorithm based on serial measurements of procalcitonin ( PCT ) allows reduction in the duration of antibiotic therapy compared with empirical rules , and does not result in more adverse outcomes in patients with severe sepsis and septic shock . METHODS In patients r and omly assigned to the intervention group , antibiotics were stopped when PCT levels had decreased 90 % or more from the initial value ( if clinicians agreed ) but not before Day 3 ( if baseline PCT levels were < 1 microg/L ) or Day 5 ( if baseline PCT levels were > /=1 microg/L ) . In control patients , clinicians decided on the duration of antibiotic therapy based on empirical rules . MEASUREMENTS AND MAIN RESULTS Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects ( intention-to-treat , n = 79 , P = 0.15 ) . In patients in whom a decision could be taken based on serial PCT measurements , PCT guidance result ed in a 4-day reduction in the duration of antibiotic therapy ( per protocol , n = 68 , P = 0.003 ) and a smaller overall antibiotic exposure ( P = 0.0002 ) . A similar mortality and recurrence of the primary infection were observed in PCT and control groups . A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group ( P = 0.03 ) . CONCLUSIONS Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm Biomarkers such as procalcitonin ( PCT ) have been studied to guide duration of antibiotic therapy . We aim ed to assess whether a decrease in PCT levels could be used to reduce the duration of antibiotic therapy in intensive care unit ( ICU ) patients with a proven infection without risking a worse outcome . We assessed 265 patients with suspected sepsis , severe sepsis , or septic shock in our ICU . Of those , we r and omized 81 patients with a proven bacterial infection into 2 groups : an intervention group in which the duration of the antibiotic therapy was guided by a PCT protocol and a control group in which there was no PCT guidance . In the per- protocol analysis , the median antibiotic duration was 9 days in the PCT group ( n = 20 ) versus 13 days in the non-PCT group ( n = 31 ) , P = 0.008 . This study demonstrates that PCT can be a useful tool for limiting antimicrobial therapy in ICU patients with documented bacterial infection Objectives Procalcitonin ( PCT ) has been described as an early , discriminating marker of bacteria-associated sepsis in patients . However , little is known of its source and actions , in part because no appropriate animal models have been available . We tested the hypothesis that plasma PCT increases during various pathophysiological conditions , such as hemorrhagic shock and sepsis , which differ with regard to the degree of associated endotoxemia . We further hypothesized that in sepsis , PCT would be significantly different in survivors vs. nonsurvivors . Design Prospect i ve , blinded analysis of previously collected plasma of experimental animals . Setting Independent nonprofit research laboratory in a trauma hospital and a contract research institute . SubjectsA total of 22 male baboons ( 17.5–31 kg ) . Interventions Hemorrhagic-traumatic shock was induced by hemorrhage for up to 3 hrs , reperfusion with shed blood and infusion of cobra venom factor ( n = 7 ) . By using a similar experimental setup , severe hyperdynamic sepsis was induced ( n = 15 ) by intravenous infusion of live Escherichia coli ( 2 × 109 colony-forming units/kg ) over 2 hrs , followed by antibiotic therapy ( gentamicin 4 mg/kg twice a day ) . Measurements and Main Results Plasma PCT at baseline was barely detectable , but levels increased significantly ( p < .05 ) to 2 ± 1.8 pg/mL 2 hrs after the start of reperfusion in the shock group , and to 987 ± 230 pg/mL at 4 hrs after E. coli in the sepsis group . Levels were maximal between 6 and 32 hrs and had returned nearly to baseline levels at 72 hrs . Interleukin-6 levels paralleled the course of PCT measurements , whereas a significant increase in neopterin was seen at 24 hrs . PCT levels were approximately three times higher in the sepsis group than in the shock group , corresponding to endotoxin levels ( at the end of hemorrhage , 286 ± 144 pg/mL vs. 3576 ± 979 pg/mL at the end of E. coli infusion;p = .003 ) . PCT levels were significantly different at 24 hrs between survivors ( 2360 ± 620 pg/mL ) and nonsurvivors ( 4776 ± 563 pg/mL ) in the sepsis group ( p = .032 ) , as were interleukin-6 ( 1562 ± 267 vs. 4903 ± 608 pg/mL;p = .01 ) and neopterin/creatinine ratio ( 0.400 ± 0.038 vs. 0.508 ± 0.037;p = .032 ) . Conclusions PCT is detectable in the baboon as in humans , both in hemorrhagic shock and sepsis . PCT levels are significantly higher in sepsis than in hemorrhage , a finding that is probably related to the differences in endotoxin . The baboon can be used for the study of PCT kinetics in both models ; PCT kinetics are clearly different from other markers of sepsis , either IL-6 or neopterin , in both models . There are significant differences between survivors and nonsurvivors in the sepsis model BACKGROUND In critically ill patients , antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance . Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration , but data about safety of this reduction are scarce . We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units ( ICUs ) in a health-care system with a comparatively low use of antibiotics . METHODS We did a prospect i ve , multicentre , r and omised , controlled , open-label intervention trial in 15 hospitals in the Netherl and s. Critically ill patients aged at least 18 years , admitted to the ICU , and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate . Patients who received antibiotics for presumed infection were r and omly assigned ( 1:1 ) , using a computer-generated list , and stratified ( according to treatment centre , whether infection was acquired before or during ICU stay , and dependent on severity of infection [ ie , sepsis , severe sepsis , or septic shock ] ) to receive either procalcitonin-guided or st and ard-of-care antibiotic discontinuation . Both patients and investigators were aware of group assignment . In the procalcitonin-guided group , a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80 % or more of its peak value or to 0·5 μg/L or lower . In the st and ard-of-care group , patients were treated according to local antibiotic protocol s. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment . All analyses were done by intention to treat . Mortality analyses were completed for all patients ( intention to treat ) and for patients in whom antibiotics were stopped while being on the ICU ( per- protocol analysis ) . Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules ( per- protocol analysis ) . The study is registered with Clinical Trials.gov , number NCT01139489 , and was completed in August , 2014 . FINDINGS Between Sept 18 , 2009 , and July 1 , 2013 , 1575 of the 4507 patients assessed for eligibility were r and omly assigned to the procalcitonin-guided group ( 761 ) or to st and ard-of-care ( 785 ) . In 538 patients ( 71 % ) in the procalcitonin-guided group antibiotics were discontinued in the ICU . Median consumption of antibiotics was 7·5 daily defined doses ( IQR 4·0 - 12·7 ) in the procalcitonin-guided group versus 9·3 daily defined doses ( 5·0 - 16·6 ) in the st and ard-of-care group ( between-group absolute difference 2·69 , 95 % CI 1·26 - 4·12 , p<0·0001 ) . Median duration of treatment was 5 days ( 3 - 9 ) in the procalcitonin-guided group and 7 days ( 4 - 11 ) in the st and ard-of-care group ( between-group absolute difference 1·22 , 0·65 - 1·78 , p<0·0001 ) . Mortality at 28 days was 149 ( 20 % ) of 761 patients in the procalcitonin-guided group and 196 ( 25 % ) of 785 patients in the st and ard-of-care group ( between-group absolute difference 5·4 % , 95 % CI 1·2 - 9·5 , p=0·0122 ) according to the intention-to-treat analysis , and 107 ( 20 % ) of 538 patients in the procalcitonin-guided group versus 121 ( 27 % ) of 457 patients in the st and ard-of-care group ( between-group absolute difference 6·6 % , 1·3 - 11·9 , p=0·0154 ) in the per- protocol analysis . 1-year mortality in the per- protocol analysis was 191 ( 36 % ) of 538 patients in the procalcitonin-guided and 196 ( 43 % ) of 457 patients in the st and ard-of-care groups ( between-group absolute difference 7·4 , 1·3 - 13·8 , p=0·0188 ) . INTERPRETATION Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection . This reduction was associated with a significant decrease in mortality . Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial , leading to more adequate diagnosis and treatment , the cornerstones of antibiotic stewardship . FUNDING Thermo Fisher Scientific Purpose Timely knowledge of the bacterial etiology and localization of infection are important for empirical antibiotic therapy . Thus , the goal of this study was to evaluate routinely used biomarkers together with novel laboratory parameters in the diagnosis of infection . Methods In this prospect i ve study , 54 adult patients with bacterial infections admitted to the Department of Infectious Diseases were included . For comparison , 27 patients with viral infections were enrolled . In these patients , white blood cell ( WBC ) counts , differential blood counts , serum levels of procalcitonin ( PCT ) , IL-1β , IL-6 , IL-8 , IL-10 , IL-12 , TNF-α , IFN-γ , soluble CD14 ( sCD14 ) , heparin-binding protein ( HBP ) , cortisol ( Cort ) , and monocyte surface expression of TLR2 , TLR4 , HLA-DR , and CD14 were analyzed . Also , these biomarkers were evaluated in 21 patients with acute community-acquired bacterial pneumonia ( CABP ) , as well as in 21 patients with pyelonephritis and urosepsis . Results The highest sensitivity and specificity ( expressed as the area under the curve [ AUC ] ) for bacterial infection were observed in serum concentration of PCT ( 0.952 ) , neutrophil and lymphocyte counts ( 0.852 and 0.841 , respectively ) , and serum levels of HBP ( 0.837 ) , IL-6 ( 0.830 ) , and Cort ( 0.817 ) . In addition , the serum levels of IFN-γ and Cort were significantly higher and IL-8 levels were lower in CABP when compared to pyelonephritis or urosepsis . Conclusions From the novel potential biomarkers , only PCT demonstrated superiority over the routine parameters in the differentiation of bacterial from viral infections . However , some of the novel parameters should be further evaluated in larger and better characterized cohorts of patients in order to find their clinical applications RATIONALE The role of procalcitonin ( PCT ) , a widely used sepsis biomarker , in critically ill patients with sepsis is undetermined . OBJECTIVES To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality . METHODS This was a multicenter ( 11 Australian intensive care units [ ICUs ] ) , prospect i ve , single-blind , r and omized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours . The primary outcome was the cumulative number of antibiotics treatment days at Day 28 . MEASUREMENTS AND MAIN RESULTS PCT was measured daily while in the ICU . A PCT algorithm , including 0.1 ng/ml cut-off , determined antibiotic cessation . Published guidelines and antimicrobial stewardship were used in all patients . Primary analysis included 196 ( PCT ) versus 198 st and ard care patients . Ninety-three patients in each group had septic shock . The overall median ( interquartile range ) number of antibiotic treatment days were 9 ( 6 - 21 ) versus 11 ( 6 - 22 ) , P = 0.58 ; in patients with positive pulmonary culture , 11 ( 7 - 27 ) versus 15 ( 8 - 27 ) , P = 0.33 ; and in patients with septic shock , 9 ( 6 - 22 ) versus 11 ( 6 - 24 ) , P = 0.64 ; with an overall 90-day all-cause mortality of 35 ( 18 % ) versus 31 ( 16 % ) , P = 0.54 in the PCT versus st and ard care , respectively . Using logistic regression , adjusted for age , ventilation status , and positive culture , the decline rate in log(PCT ) over the first 72 hours independently predicted hospital and 90-day mortality ( odds ratio [ 95 % confidence interval ] , 2.76 [ 1.10 - 6.96 ] , P = 0.03 ; 3.20 [ 1.30 - 7.89 ] , P = 0.01 , respectively ) . CONCLUSIONS In critically ill adults with undifferentiated infections , a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25 % reduction in duration of antibiotic treatment . Clinical trial registered with http://www.anzctr.org.au ( ACTRN12610000809033 ) |
13,014 | 26,833,453 | The present results indicate preliminary evidence of how the motivational processes do not differ between individuals with SMI and the general population , and that they are independent of diagnosis , medication , age , gender , and body mass index .
Results from the current systematic review can give some tentative guidance on how to facilitate motivation for physical activity within mental health-care . | Individuals with severe mental illness ( SMI ) are less physically active than the general population .
One important barrier contributing to this inactivity is lack of motivation .
The aim of this paper is to systematic ally review all cross-sectional literature on motivation for physical activity among people with SMI and to use the results as basis for guidance on how mental health nurses can facilitate motivation for physical activity . | Background The existing literature on weight management interventions targeting physical activity and healthy eating in mental health care appears to provide only limited evidence . The aim of the study was to examine the effectiveness of a 10-week health promotion intervention , followed by a 6-month follow-up period in individuals with mental disorders living in sheltered housing in the Fl and ers region ( Belgium ) . Methods The study had a cluster preference r and omized controlled design . Twenty-five sheltered housing organisations agreed to participate ( 16 in the intervention group , nine in the control group ) . In the intervention group , 225 individuals agreed to participate , while in the control group 99 individuals entered into the study . The main outcomes were changes in body weight , Body Mass Index , waist circumference and fat mass . Secondary outcomes consisted of changes in physical activity levels , eating habits , health-related quality of life and psychiatric symptom severity . Results A significant difference was found between the intervention group and the control group regarding body weight ( −0.35 vs. + 0.22 kg ; p=0.04 ) , Body Mass Index ( −0.12 vs. + 0.08 kg/m2 ; p=0.04 ) , waist circumference ( −0.29 vs. + 0.55 cm ; p<0.01 ) , and fat mass ( −0.99 vs. −0.12 % ; p<0.01 ) . The decrease in these outcomes in the intervention group disappeared during the follow up period , except for fat mass . Within the intervention group , a larger decrease in the primary outcomes was found in the participants who completed the intervention . No significant differences between the two groups in changes in the secondary outcomes were found , except for the pedometer-determined steps/day . In the intervention group , the mean number of daily steps increased , while it decreased in the control group . Conclusions The study demonstrated that small significant improvements in the primary outcomes are possible in individuals with mental disorders . Integration of health promotion activities targeting physical activity and healthy eating into daily care are , however , necessary to maintain the promising results .Trial registration This study is registered at Clinical Trials.gov BACKGROUND : Persons with schizophrenia spectrum disorders ( SSDs ) contend with multiple barriers to exercise . Interventions are needed to enhance attitudes theoretically linked to exercise behavior . OBJECTIVE : To examine the effect of Walk , Address Sensations , Learn About Exercise , Cue Exercise for SSDs ( WALC-S ) intervention on exercise self-efficacy ( SEE ) and outcome expectations ( OEES ) in 97 out patients with SSDs . DESIGN : Experimental , pre- and posttest . R and omization to experimental ( WALC-S ) or time- and -attention control ( TAC ) after baseline SEE and OEES measures . Measures repeated after WALC-S or TAC . RESULTS : N = 97 , 46 % female , 43 % African American , average age 46.9 years ( SD = 2.0 ) . Mean SEE scores were significantly higher in WALC-S participants after intervention , F(1 , 95 ) = 5.92 , p = .0168 , however , mean OEES scores were significantly higher in control participants after intervention , F(1 , 95 ) = 5.76 , p = .0183 . CONCLUSION : This is the first study to examine SEE and OEES in SSDs . Interventions to enhance exercise attitudes are a critical first step toward the ultimate goal of increasing exercise participation Objective To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care . Design Pragmatic , multicentre , two arm parallel r and omised controlled trial . Setting General practice s in Bristol and Exeter . Participants 361 adults aged 18 - 69 who had recently consulted their general practitioner with symptoms of depression . All those r and omised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more . Interventions In addition to usual care , intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months . The intervention was based on theory and aim ed to provide individually tailored support and encouragement to engage in physical activity . Main outcome measures The primary outcome was self reported symptoms of depression , assessed with the Beck depression inventory at four months post-r and omisation . Secondary outcomes included use of antidepressants and physical activity at the four , eight , and 12 month follow-up points , and symptoms of depression at eight and 12 month follow-up . Results There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group ; adjusted between group difference in mean Beck depression inventory score −0.54 ( 95 % confidence interval −3.06 to 1.99 ; P=0.68 ) . Similarly , there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points . Nor was there evidence that the intervention reduced antidepressant use compared with usual care ( adjusted odds ratio 0.63 , 95 % confidence interval 0.19 to 2.06 ; P=0.44 ) over the duration of the trial . However , participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group ( adjusted odds ratio 2.27 , 95 % confidence interval 1.32 to 3.89 ; P=0.003 ) . Conclusions The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone . Trial registration Current Controlled Trials IS RCT N16900744 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 . ) The purpose of this prospect i ve and observational design study was to assess the feasibility of using a pedometer and step log to explore level of physical activity ( PA ) and to assess motivation to be physically active in adults with schizophrenia . Descriptive statistics were used to analyse data of 7 male and 5 female subjects . Pedometer data indicated that subjects walked an average of 4731.03 ( ±3318.19 ) steps and 5002.58 ( ±3041.03 ) during the first week and second week of the study , respectively . A minimum 30-min walk was recorded on an average of 3.67 ( ±1.82 ) days ( week one ) and 4.5 ( ±1.88 ) days ( week two ) . Step logs , inconsistently maintained by subjects , were not able to be analysed . Examination of the Motives for Physical Activity Measure-Revised ( MPAM-R ) at baseline indicates that exercise fitness and body appearance were subjects ' primary motives for PA participation . Study findings indicate that it is feasible to use a pedometer to monitor the level of PA . However , maintenance of a concurrent step log requires further consideration to determine realistic outcomes . Extrinsically focused motivations for PA in this study sample may predict low PA adherence Primary care is a promising venue to build patient motivation and confidence to increase physical activity ( PA ) . Physician PA counselling has demonstrated some success ; however , maintenance of behaviour change appears to require more intensive interventions . In reality , most physicians do not have the necessary training nor the time for this type of counselling . The purpose of this paper is to outline the rationale , methods , and interventions for the ongoing physical activity counselling ( PAC ) r and omized controlled trial ( RCT ) , which aims to assess the impact of integrating a PA counsellor into a primary care practice . This RCT has 2 arms : ( i ) brief PA counselling ( 2 - 4 min ) from a health care provider and ( ii ) brief PA counselling+intensive PA counselling from a PA counsellor ( 3 months ) . The impact of this intervention is being evaluated using the comprehensive RE- AIM framework . One hundred twenty insufficiently active adult patients , aged 18 to 69 y and recruited during regular primary care visits have been r and omized . Dependent measures include psychological mediators , PA participation , quality of life , and physical and metabolic outcomes . The PAC project represents an innovative , theoretically-based approach to promoting PA in primary care , focusing on psychological mediators of change . We anticipate that key lessons from this study will be useful for shaping future public health interventions , theories , and research |
13,015 | 25,190,307 | Our data show that irrespective of clinical or exercise conditions , LowExBP independently predicts fatal and non-fatal cardiovascular events and all-cause mortality | OBJECTIVE The independent prognostic significance of abnormally low systolic blood pressure ( SBP ) during exercise stress testing ( LowExBP ) across different clinical and exercise conditions is unknown .
We sought by systematic review and meta- analysis to determine the association between cardiovascular/all-cause outcomes and LowExBP across different patient clinical presentations , exercise modes , exercise intensities and categories of LowExBP . | The objective of this study was to demonstrate the causes , optimal definition , and predictive value of exercise-induced hypotension occurring during treadmill testing . This study included all patients referred for clinical reasons to the Long Beach Veterans Administration Medical Center treadmill laboratory and then followed for a 2-year period for cardiac events . The population consisted of 2,036 patients who underwent testing from April 4 , 1984 , to May 7 , 1987 , 131 of whom exhibited exercise-induced hypotension ( 6.4 % ) . We found that exercise-induced hypotension is usually related to myocardial ischemia or myocardial infa rct ion , is best defined as a drop in systolic blood pressure during exercise below the st and ing preexercise value , and indicates a significantly increased risk for cardiac events ( 3.2-fold , p less than 0.005 ) . This increased risk was not found in those having no previous myocardial infa rct ion or no signs or symptoms of ischemia during the exercise test , and the increased risk was also not found in those undergoing a treadmill test within 3 weeks after a myocardial infa rct ion . Exercise-induced hypotension appeared to be reversed by revascularization procedures , but confirmation of a beneficial effect on survival requires a r and omized trial . The clinical importance of this study is that we have demonstrated that a drop in systolic blood pressure below st and ing preexercise values during treadmill testing indicates an increased risk for cardiac events except in certain subsets of patients OBJECTIVES This study was design ed to assess the angiographic and prognostic implication s of an exaggerated systolic blood pressure response to exercise ( " exercise hypertension " ) in adults undergoing evaluation for suspected coronary artery disease . BACKGROUND The clinical implication s of exercise hypertension are unclear . METHODS Subjects for this prospect i ve cohort study were derived from a consecutive sample of 9,608 adults who were referred for treadmill testing and who augmented their systolic blood pressure by at least 10 mm Hg . There were 594 subjects who underwent coronary angiography within 90 days of treadmill testing . Exercise hypertension was defined as a peak exercise systolic blood pressure > or = 210 mm Hg in men and > or = 190 mm Hg in women . Severe angiographic coronary disease was defined as left main coronary artery disease ( > or = 50 % diameter stenosis ) , three-vessel disease ( > or = 70 % diameter stenosis ) or two-vessel disease with > or = 70 % diameter stenosis of the proximal left anterior descending coronary artery . All-cause mortality was assessed during a follow-up period of approximately 2 years . RESULTS Exercise hypertension was present in 196 subjects ( 33 % ) . Severe coronary disease was less common in subjects with exercise hypertension ( 14 % vs. 25 % , odds ratio 0.51 , 95 % confidence interval [ CI ] 0.32 to 0.81 , p = 0.004 ) . Exercise hypertension remained associated with a lower rate of severe coronary disease even after adjusting for rest hypertension , age , gender , exercise capacity and other possible confounders . During the follow-up period , there were 23 deaths ; only 2 occurred in the group with exercise hypertension . After adjusting for severity of coronary disease , exercise hypertension remained associated with a lower mortality rate ( adjusted relative risk 0.20 , 95 % CI 0.05 to 0.84 , p = 0.03 ) . CONCLUSIONS In adults evaluated for coronary artery disease , exercise hypertension is associated with a lower likelihood of angiographically severe disease and a lower adjusted mortality rate Background —Predicting the risk of cardiac and all-cause death in patients with established coronary heart disease is important in counseling the individual and design ing risk-stratified rehabilitation and secondary prevention programs . Cox proportional hazards and Kaplan-Meier survival curves were thus completed on initial assessment data obtained from patients referred to an outpatient cardiac rehabilitation center . Methods and Results —A single-center prospect i ve observational design took peak cardiorespiratory exercise test data for 12 169 male rehabilitation c and i date s aged 55.0±9.6 years ( 7096 myocardial infa rct ions [ MIs ] , 3077 coronary artery bypass grafts [ CABGs ] , and 1996 documented cases of ischemic heart disease [ IHD ] ) . A follow-up of 4 to 29 years ( median , 7.9 ) yielded 107 698 man-years of experience . Entry data were tested for associations with time to cardiac and all-cause death . We recorded 1336 cardiac deaths ( 953 MI , 225 CABG , and 158 IHD ) and 2352 all-cause deaths . A powerful predictor of cardiac and all-cause mortality was measured peak oxygen intake ( & OV0312;o2peak ) . For the overall sample , values of < 15 , 15 to 22 , and > 22 mL/kg per minute yielded respective multivariate adjusted hazard ratios of 1.00 , 0.62 , and 0.39 for cardiac and 1.00 , 0.66 , and 0.45 for all-cause deaths . For the separate diagnostic categories , apart from & OV0312;o2peak , the only other significant predictors of cardiac death common to all 3 were smoking and digoxin , and for all-cause death , age , smoking , digoxin , and diabetes . Conclusions —Exercise capacity , as determined by direct measurement of & OV0312;o2peak , exerts a major long-term influence on prognosis in men after MI , CABG , or IHD and can play a valuable role in risk stratification and counseling Exercise testing helped in diagnosing postinfa rct ion patients in the prethrombolytic era . Over the past decade acute myocardial infa rct ion treatment has changed because of new thrombolytic therapies and consequently , the value of exercise testing is under debate . The GISSI-2 data base allowed us to reevaluate the prognostic role of exercise testing in thrombolysed patients . The exercise test was performed in 6296 patients , on average 28 days after r and omisation . The test was not performed in 3923 patients because of contraindications . The test was judged positive for residual ischaemia in 26 % of the patients , negative in 38 % , and non-diagnostic in 36 % . Among the patients with a positive stress test result , 33 % had symptoms , whereas 67 % had silent myocardial ischaemia . The mortality rate was 7.1 % among patients who did not have an exercise test and 1.7 % [ correction of 7.1 % ] for those with a positive test , 0.9 % for those who had a negative test , and 1.3 % for those who did not have a diagnostic test . In the adjusted analysis , symptomatic induced ischaemia , submaximal positive result , low work capacity , and abnormal systolic blood pressure were independent predictors of 6-month mortality ( relative risks [ RR ] 2.54 , 95 % CI 1.27 - 5.08 , 2.28 , 1.17 - 4.45 , 2.05 , 1.23 - 3.42 , and 1.86 , 1.05 - 3.31 , respectively ) . However , when these factors were tested simultaneously , only symptomatic induced ischaemia and low work capacity were confirmed as independent predictors of mortality ( RR Cox 2.07 , 95 % CI 1.02 - 4.23 and 1.78 , 1.06 - 2.99 , respectively ) . Patients with a normal exercise response have an excellent medium-term prognosis and do not need further investigation . However , more evaluation should be devoted to the patients who can not undergo exercise testing , because the potential to influence outcome appears to be much greater OBJECTIVES The present study was design ed to prospect ively evaluate the prognostic relevance of abnormal blood pressure response to exercise ( ABPR ) , defined as hypotension or failed blood pressure increase ( < 20 mm Hg ) with exercise , in a community-based hypertrophic cardiomyopathy ( HCM ) population representative of the overall disease spectrum . BACKGROUND Abnormal blood pressure response to exercise has been proposed as a marker for hemodynamic instability and increased risk for disease-related mortality in highly selected patient population s with HCM . METHODS The study population comprised 126 patients ( aged 42+/-14 years ) who underwent maximal symptom-limited cycloergometer exercise testing as part of the st and ard evaluation at our institution , and who were followed systematic ally for 4.7+/-3.7 years after testing . RESULTS Of the 126 study patients , 98 ( 78 % ) had a normal blood pressure response during exercise , whereas the other 28 ( 22 % ) had ABPR , including nine with hypotension and 19 with failed blood pressure rise . During the follow-up period , nine patients ( 7 % ) died of HCM-related causes ( three suddenly and six heart failure-related ) , of whom four had ABPR . In those patients aged < or = 50 years , survival analysis after exercise testing showed a significantly increased risk for cardiovascular mortality associated with ABPR compared with a normal exercise response ( p = 0.04 ) , with an odds ratio of 4.5 ( 95 % confidence interval : 1.1 , 20.1 ) . However , ABPR showed low positive predictive accuracy for cardiovascular mortality ( i.e. , 14 % ) , whereas negative predictive accuracy was high ( i.e. , 95 % ) . CONCLUSIONS A hypotensive blood pressure response during exercise occurred in over 20 % of a community-based patient cohort with HCM , and was associated with adverse long-term prognosis in patients < 50 years old . However , the positive predictive accuracy of this blood pressure response is too low to justify modifications of clinical management or to allow identification of the high-risk patient based solely on an abnormal test result . By virtue of its high negative predictive accuracy for HCM-related mortality , the blood pressure response to exercise appears to be most valuable ( in conjunction with the absence of other well recognized risk factors ) as a screening test for the identification of low-risk subsets of patients Objective : Studies on the prognostic importance of the systolic blood pressure ( SBP ) response during exercise report ambiguous results . Most research focuses on younger and middle-aged selected patient groups and rarely includes women . We investigated the prognostic value of SBP response during exercise testing in 75-year-olds . Design : Prospect i ve observational cohort study . Setting : A community-based r and om sample of 75-year-old men and women ( n = 382 ) . Main outcome measures : The prognostic value of SBP change from rest to peak exercise during a symptom-limited cycle test was evaluated for the endpoints all-cause mortality and cardiovascular mortality during long-term follow-up . Results : After a median follow-up of 10.6 years , 140 ( 37 % ) of the participants had died , 64 ( 17 % ) from cardiovascular causes . The all-cause mortalities for exercise SBP changes of ⩽30 mm Hg , 31–55 mm Hg and > 55 mm Hg were 5.1 , 4.2 and 2.6 per 100 person-years , respectively ( logrank 9.6 ; p = 0.008 ) . For every 10 mm Hg increase in SBP during exercise the relative hazard for all-cause mortality was reduced by 13 % ( p = 0.030 ) and for cardiovascular mortality by 26 % ( p = 0.004 ) after adjustment for sex , smoking , waist circumference , total/HDL cholesterol ratio , prevalent ischaemic heart disease , hypertension , diabetes , cardiovascular medication , pre-exercise SBP , exercise capacity , resting left ventricular ejection fraction and left ventricular mass index . Conclusions : Our findings suggest that an augmented SBP response during exercise is associated with an improved long-term survival among community-living 75-year-old individuals The relation of maximal exercise systolic pressure to physical conditioning and to mortality was determined in 641 men with > or = 1 myocardial infa rct ions . Each performed a st and ardized multistage exercise test before r and omized assignment either to an exercise group or a control group and at scheduled periodic intervals over 3 years . This study compares 123 men with maximal exercise systolic pressures ( MESP ) of < or = 140 mm Hg with 518 men whose maximal exercise systolic pressure was > or = 140 mm Hg . At baseline , the 2 groups were comparable for age , entry time since the occurrence of the qualifying cardiac event , and reported use of antihypertensive medications . Men with low MESP used more beta blockers , had lower systolic pressure measurements at rest and by definition at maximal exercise , and lower work capacity than men with higher levels of MESP . Men with low MESP experienced : ( 1 ) no reduction in mortality with exercise conditioning ( p<0.86 ) , and ( 2 ) a significantly higher mortality rate over 3 years ( p<0.003 ) compared with men with higher levels of MESP . The relation of a low MESP to mortality persisted : ( 1 ) whether MESP or work capacity increased from the baseline exercise test to the last performed exercise test , and ( 2 ) whether it was measured at low ( < 6 METs ) or high ( > or = 6 METs ) levels of work capacity . We conclude that low maximal exercise systolic blood pressure is a predictor of mortality and is associated with an ineffective training response in men with myocardial infa rct ion Background The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined . This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography . Methods A total of 204 patients at intermediate risk for cardiac complications prospect ively underwent exercise electrocardiography before noncardiac surgery . Of these , 185 were included in the final evaluation . All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days , daily 12-lead electrocardiogram , and creatine kinase , creatine kinase MB , and troponin-T measurements for 5 days . Cardiac events were defined as cardiac death , myocardial infa rct ion , minor myocardial cell injury , unstable angina pectoris , congestive heart failure , and ventricular tachyarrhythmia . Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis . Results Perioperative cardiac events were observed in 16 patients . There were 6 cases of myocardial infa rct ion and 10 cases of myocardial cell injury . The multivariate correlates of adverse cardiac events were definite coronary artery disease ( odds ratio , 8.8 ; 95 % confidence interval [ CI ] , 1.1–73.1;P = 0.04 ) , major surgery ( odds ratio , 4.7 ; 95 % CI , 1.3–16.3;P = 0.02 ) , reduced left ventricular performance ( odds ratio , 2.0 ; 95 % CI , 1.1–3.8;P = 0.03 ) , and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram ( odds ratio , 5.2 ; 95 % CI , 1.5–18.5;P = 0.01 ) . A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification . Conclusions This prospect i ve study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardio-gram is an independent predictor of perioperative cardiac complications The role of coronary angiography before hospital discharge after myocardial infa rct ion was assessed in 1043 hospital survivors of the alteplase/placebo and the alteplase/PTCA trial of the European Cooperative Study Group . Forty-two of 1043 patients ( 4.0 % ) died after 1 to 489 days after predischarge coronary angiography . In survivors , follow-up ranged from 34 to 1106 days . In a stepwise multivariate regression model ( Cox ) , use of diuretics and /or digitalis , a history of previous infa rct ion and age exceeding 60 years were retained in the model with clinical data only . In addition , inability to perform exercise testing and less than 30 mmHg exercise-induced systolic blood pressure increase were selected by multivariate analysis . Large enzymatic infa rct size , radionuclide left ventricular ejection fraction below 40 % , and multivessel disease were also determinants of mortality after hospital discharge . The risk function , including coronary angiography , performed no better in late mortality prediction than functions based on clinical data and non-invasive testing . Patients without a history of previous infa rct ion , not treated with diuretics and /or digitalis and with a systolic blood pressure increase of 30 mmHg or more during exercise had an excellent survival ( 98.6 % ) in the first year after hospital discharge , irrespective of whether symptoms of recurrent ischaemia occurred . This low risk group formed 47 % of the total patient population and does not benefit from coronary angiography The objective of this report is the development of a population -specific prediction rule based on clinical and exercise test data that would estimate the risk of cardiovascular death in patients selected for cardiac catheterization . Prospect i ve data and follow-up information were obtained from patients who underwent cardiac catheterization soon after clinical assessment and exercise testing . Males ( n = 588 ) referred for evaluation of coronary heart disease from 1984 to 1990 were selected after exclusion of patients with significant valvular heart disease and patients with prior cardiac surgery . Half had a prior myocardial infa rct ion and half complained of typical angina pectoris . All patients performed a treadmill test and were selected for clinical reasons to undergo coronary angiography within 3 months . Over a mean follow-up period of 2.5 years ( + /- 1.4 years ) , there were 39 cardiovascular deaths and 45 nonfatal myocardial infa rct ions . The Cox proportional hazards model demonstrated the following characteristics to be statistically significant independent predictors of time until cardiovascular death : history of congestive heart failure ( hazards ratio of 4 ) , ST depression on the resting ECG ( hazards ratio of 3 ) , and a drop in systolic blood pressure below the resting value during exercise ( hazards ratio of 5 ) . Exercise-induced ST depression was not associated with either death or nonfatal myocardial infa rct ion . A simple score based on one item of clinical information ( history of congestive heart failure ) , a resting ECG finding ( ST depression ) , and an exercise test response ( exertional hypotension ) stratified our patients for 4 years after testing from 75 % with a low risk ( annual cardiac mortality rate of 1 % ) , 17 % with a moderate risk ( annual mortality rate of 7 % ) , and 1 % with a high risk ( annual cardiac mortality rate of 12 % , with a hazards ratio of 20 and 95 % confidence interval from 6 to 70X ) . It was concluded that the variables available from the usual noninvasive workup of patients with known or suspected coronary artery disease enable prediction of risk of cardiovascular death . Three quarters of those usually undergoing cardiac catheterization can be identified by simple noninvasive variables as being at such low risk that invasive intervention is unlikely to improve prognosis |
13,016 | 32,200,443 | Our meta- analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension , particularly in those with diabetes mellitus , following probiotic supplementation .
This effect was associated with treatment duration , dosage , and the age of subject , but was not associated with single or multiple strains usage .
Additionally , probiotic supplement had a beneficial effect in reducing BMI and blood glucose | This meta- analysis and systematic review was conducted to evaluate the effect of probiotics on blood pressure , body mass index ( BMI ) , and blood glucose changes in patients with hypertension . | BACKGROUND Hypercholesterolemia is a major risk factor for cardiovascular disease . Not all patients respond well to traditional cholesterol lowering medications . Probiotics have been evaluated for their cholesterol-lowering effects in humans with variable results . This study was performed to evaluate the efficacy of two probiotics in lowering the serum cholesterol of hypercholesterolemic patients . MATERIAL S AND METHODS A r and omized double-blind controlled trial was conducted comparing placebo to Lactobacillus acidophilus plus Bifidobacterium bifidum in patients diagnosed with hypercholesterolemia . Placebo or probiotic capsules were taken three times daily for six weeks . Pre- and post-treatment total cholesterol ( TC ) , HDL-cholesterol ( HDL-C ) , LDL-cholesterol ( LDL-C ) and triglyceride ( TG ) levels and demographic parameters of the two groups were compared . From a total of 70 participants , 64 completed the assigned treatment ( 31 in probiotics group and 33 in the control group).The two treatment groups were matched for age , sex , weight , height , BMI , waist and hip circumferences , and blood pressure . RESULTS Baseline evaluation revealed no difference between the probiotics group and control group levels of TC , HDL-C , LDL-C and TG . TC levels in the probiotics group decreased during treatment ( 237.2 vs. 212.7 mg/dL , p<0.05 ) . TC and LDL-C levels in the control group increased significantly from their baseline levels during treatment . TC ( 212.7 vs 252.8 mg/dL , p<0.001 ) , HDL-C ( 52.0 vs 59.1 mg/dL , p=0.04 ) and LDL-C ( 153.9 vs 182.1 mg/dL , p<0.01 ) levels in the probiotics group were significantly lower at the end of treatment than the corresponding levels in the control group . CONCLUSION A combination of Lactobacillus acidophilus and Bifidobacterium bifidum decreased serum total cholesterol , LDL-cholesterol and HDL-cholesterol levels in hypercholesterolemic patients over a six week period . There was no effect on serum triglyceride or fasting blood glucose levels BACKGROUND The short-chain fatty acids formed in the human colon by the bacterial fermentation of fiber may have an antiinflammatory effect , may reduce insulin production , and may improve lipid metabolism . We previously showed in hypercholesterolemic patients that supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen . OBJECTIVE We determined the influence of a functional food product containing L. plantarum 299v on lipid profiles , inflammatory markers , and monocyte function in heavy smokers . DESIGN Thirty-six healthy volunteers ( 18 women and 18 men ) aged 35 - 45 y participated in a controlled , r and omized , double-blind trial . The experimental group drank 400 mL/d of a rose-hip drink containing L. plantarum 299v ( 5 x 10(7 ) colony-forming units/mL ) ; the control group consumed the same volume of product without bacteria . The experiment lasted 6 wk and entailed no changes in lifestyle . RESULTS Significant decreases in systolic blood pressure ( P < 0.000 ) , leptin ( P < 0.000 ) , and fibrinogen ( P < 0.001 ) were recorded in the experimental group . No such changes were observed in the control group . Decreases in F(2)-isoprostanes ( 37 % ) and interleukin 6 ( 42 % ) were also noted in the experimental group in comparison with baseline . Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion ( P < 0.001 ) to native and stimulated human umbilical vein endothelial cells . CONCLUSION L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing . However , the effect of multi-strain probiotics in people with type 2 diabetes remains unclear . This study investigated the effect of multi-strain microbial cell preparation — also refers to multi-strain probiotics — on glycemic control and other diabetes-related outcomes in people with type 2 diabetes . Design A r and omized , double-blind , parallel-group , controlled clinical trial . Setting Diabetes clinic of a teaching hospital in Kuala Lumpur , Malaysia . Participants A total of 136 participants with type 2 diabetes , aged 30–70 years , were recruited and r and omly assigned to receive either probiotics ( n = 68 ) or placebo ( n = 68 ) for 12 weeks . Outcomes Primary outcomes were glycemic control-related parameters , and secondary outcomes were anthropomorphic variables , lipid profile , blood pressure and high-sensitivity C-reactive protein . The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract . Statistical analysis Intention-to-treat ( ITT ) analysis was performed on all participants , while per- protocol ( PP ) analysis was performed on those participants who had successfully completed the trial with good compliance rate . Results With respect to primary outcomes , glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p < 0.05 , small effect size of 0.050 ) , while these changes were not significant in ITT analysis . Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis . These changes were significant between groups at both analyses ( p < 0.05 , medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis ) . Secondary outcomes did not change significantly . Probiotics successfully passed through the gastrointestinal tract . Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes Background Gut lactobacilli can affect the metabolic functions of healthy humans . We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA ( Deutsche Sammlung für Mikroorganismen , DSM 21380 ) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension . Methods In this 3-week , r and omized , double-blind , placebo-controlled , parallel pilot study , 25 subjects ingested probiotic cheese and 15 ingested control cheese . Fifty grams of each cheese provided 175 kcal of energy . Blood pressure ( BP ) , anthropometric characteristics , markers of liver and kidney function , metabolic indices ( plasma glucose , lipids , and cholesterol ) , and urine polyamines were measured . Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods . The data were analyzed by t-test for independent sample s and Spearman ’s partial correlation analysis . Results The probiotic L. plantarum TENSIA was present in variable amounts ( 529.6 ± 232.5 gene copies ) in 16/25 ( 64 % ) study subjects . Body mass index ( BMI ) was significantly reduced ( p = 0.031 ) in the probiotic cheese group versus the control cheese group . The changes in BMI were closely associated with the water content of the body ( r = 0.570 , p = 0.0007 ) when adjusted for sex and age . Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI ( r = 0.383 , p = 0.0305 ) and urinary putrescine content ( r = 0.475 , p = 0.006 ) . In patients simultaneously treated with BP-lowering drugs , similar reductions of BP were observed in both groups . A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP ( r = 0.617 , p = 0.0248 ) and a trend toward lower values of morning systolic BP ( r = −0.527 , p = 0.0640 ) at the end of the study after adjusting for BMI , age , and sex . Conclusion In a pilot study of obese hypertensive patients , a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values , recognized symptoms of metabolic syndrome . Trial registration Current Controlled Trials IS RCT Objective : Two tripeptides ( Val-Pro-Pro and Ile-Pro-Pro ) that have inhibitory activities for angiotensin I-converting enzyme are produced in milk fermented with Lactobacillus helveticus . In this study we evaluated the effect and safety of powdered fermented milk with L. helveticus CM4 on subjects with high-normal blood pressure or mild hypertension . Methods : A r and omized , placebo-controlled , double-blind study was conducted using 40 subjects with high-normal blood pressure ( HN group ) and 40 subjects with mild hypertension ( MH group ) . Each subject ingested 6 test tablets ( 12 g ) containing powdered fermented milk with L. helveticus CM4 daily for 4 weeks ( test group ) or the same amount of placebo tablets for 4 weeks ( placebo group ) . Results : During treatment , the decrease in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) in the test group tended to be greater than in the placebo group for both blood pressure groups . At the end of treatment ( week 4 ) , a significant decrease in DBP in the HN group was observed ( i.e. 5.0 mm Hg ( 0.1 , 9.9 ; p = 0.04 ) compared with the placebo group ) . There was no significant change in SBP ( 3.2 mm Hg ( 95 % CI −2.6 , 8.9 ; p = 0.27 ) . In the MH group , SBP decreased by 11.2 mm Hg ( 4.0 , 18.4 ; p = 0.003 ) and there was a statistically non-significant decrease in DBP of 6.5 mm Hg ( −0.1 , 13.0 ; p = 0.055 ) compared with the placebo group . No marked changes were observed in other indexes , including pulse rate , body weight and blood serum variables , and no adverse effects attributed to the treatment was found in each group . Conclusions : Daily ingestion of the tablets containing powdered fermented milk with L. helveticus CM4 in subjects with high-normal blood pressure or mild hypertension reduces elevated blood pressure without any adverse effects BACKGROUND AND AIMS Despite strong mechanistic data , and promising results from in vitro and animal studies , the ability of probiotic bacteria to improve blood pressure and serum lipid concentrations in humans remains uncertain . The aim of this study was to determine the effect of Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp lactis Bb12 , provided in either yoghurt or capsule form , on home blood pressure and serum lipid profile . METHODS AND RESULTS Following a 3-week washout period , 156 overweight men and women over 55 y were r and omized to a 6-week double-blinded , factorial , parallel study . The four intervention groups were : A ) probiotic yoghurt plus probiotic capsules ; B ) probiotic yoghurt plus placebo capsules ; C ) control milk plus probiotic capsules ; and D ) control milk plus placebo capsules . Each probiotic test article provided a minimum L. acidophilus La5 and B. animalis subsp . lactis Bb12 dose of 3.0 × 10⁹ CFU/d . Home blood pressure monitoring , consisting of 7-day bi-daily repeat measurements , were collected at baseline and week 6 . Fasting total cholesterol , low density lipoprotein cholesterol ( LDLC ) , high density lipoprotein cholesterol ( HDLC ) , and serum triglyceride were performed at baseline and week 6 . When compared to control milk , probiotic yoghurt did not significantly alter blood pressure , heart rate or serum lipid concentrations ( P > 0.05 ) . Similarly , when compared to placebo capsules , supplementation with probiotic capsules did not alter blood pressure or concentrations of total cholesterol LDLC , HDLC , or triglycerides ( P > 0.05 ) . CONCLUSIONS The probiotic strains L. acidophilus La5 and B. animalis subsp . lactis Bb12 did not improve cardiovascular risk factors The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease ( CVD ) . An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and /or food matrix properties . The probiotic Lactobacillus plantarum strain TENSIA ® ( DSM 21380 ) is a novel microorganism with antimicrobial and antihypertensive functional properties . The aim of this study was to characterise the functional properties of the probiotic L. plantarum TENSIA and compare its effects on host anthropometric , clinical , and blood biomarkers when consumed with cheese or yoghurt . This study involved two double-blinded r and omised placebo-controlled exploratory trials ( IS RCT N15061552 and IS RCT N79645828 ) of healthy adults over a three-week period . The three-week consumption of probiotic L. plantarum TENSIA in a daily dose of 1 × 1010 cfu in probiotic cheese or a daily dose of 6 × 109 cfu in yoghurt with different content of carbohydrates , proteins , and lipids did not significantly change the body mass index ( BMI ) , plasma glucose and lipid levels , or inflammatory markers in the blood . Reduced lowered systolic and diastolic blood pressure values were detected , regardless of food matrix or baseline values for blood pressure and BMI . In conclusion , our study showed that three-week consumption of the probiotic L. plantarum TENSIA either in cheese or yoghurt lowered diastolic and systolic blood pressure regardless of food matrix and baseline values of blood pressure and BMI , confirming the impact of the functional properties of the probiotic strain in decreasing CVD risk Objectives : To our knowledge , no reports are available indicating the effects of synbiotic bread consumption on nitric oxide ( NO ) , biomarkers of oxidative stress , and liver enzymes among patients with type 2 diabetes mellitus ( T2DM ) . This study was performed to determine the effects of the daily consumption of synbiotic bread on NO , biomarkers of oxidative stress , and liver enzymes in patients with T2DM . Methods : This r and omized , double-blind , placebo-controlled trial was performed among 81 patients with diabetes , aged 35–70 years old . After a 2-week run-in period , patients were r and omly divided into 3 groups : group A ( n = 27 ) received synbiotic bread containing viable and the heat-resistant probiotic Lactobacillus sporogenes ( 1 × 108 CFU ) and 0.07 g inulin per 1 g , group B ( n = 27 ) received probiotic bread containing Lactobacillus sporogenes ( 1 × 108 CFU ) , and group C ( n = 27 ) received control bread for 8 weeks . Patients were asked to consume the synbiotic , probiotic , or control breads 3 times a day in 40 g packages for a total of 120 g/day . Fasting blood sample s were taken at baseline and after an 8-week intervention for quantificationof related markers . Results : After 8 weeks , the consumption of synbiotic bread compared to the probiotic and control breads result ed in a significant rise in plasma NO ( 40.6 ± 34.4 vs 18.5 ± 36.2 and −0.8 ± 24.5 µmol/L , respectively , p < 0.001 ) and a significant reduction in malondialdehyde ( MDA ) levels ( −0.7 ± 0.7 vs 0.6 ± 1.7 and 0.5 ± 1.5 µmol/L , respectively , p = 0.001 ) . We did not find any significant effect of the synbiotic bread consumption on plasma total antioxidant capacity ( TAC ) , plasma glutathione ( GSH ) , catalase , serum liver enzymes , calcium , iron , magnesium levels , and blood pressure compared to the probiotic and control breads . Conclusion : In conclusion , consumption of the synbiotic bread for 8 weeks among patients with T2DM had beneficial effects on plasma NO and MDA levels ; however , it did not affect plasma TAC , GSH , catalase levels , serum liver enzymes , calcium , iron , magnesium levels , and blood pressure Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women . One of the key drivers of cardiovascular risk is endothelial dysfunction ; thus , this is also a crucial point for studies on new therapeutic methods of cardioprotective properties . The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic ® Barrier supplement on functional ( primary endpoint ) and biochemical parameters ( secondary endpoint ) of endothelial dysfunction in obese postmenopausal women in a 12-week r and omized , placebo-controlled clinical trial . A total of 81 obese Caucasian women participated in the trial . The subjects were r and omly assigned to three groups that received a placebo , a low dose ( LD ) ( 2.5 × 109 colony forming units ( CFU ) per day ) , or a high dose ( HD ) ( 1 × 1010 CFU per day ) of lyophilisate powder containing live multispecies probiotic bacteria . The probiotic supplement was administered each day for 12 weeks in two equal portions . A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure , vascular endothelial growth factor , pulse wave analysis systolic pressure , pulse wave analysis pulse pressure , pulse wave analysis augmentation index , pulse wave velocity , interleukin-6 , tumor necrosis factor alpha , and thrombomodulin . Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels . The mean changes in the estimated parameters , compared among the three groups , revealed significant differences in the vascular endothelial growth factor , the pulse wave analysis systolic pressure , the pulse wave analysis augmentation index , the pulse wave velocity , the tumor necrosis factor alpha , and thrombomodulin . The post hoc tests showed significant differences for all parameters between HD and the placebo group , and HD and LD ( besides pulse wave analysis augmentation index ) . We show for the first time that supplementation with multispecies probiotic Ecologic ® Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus ( T2DM ) in animal models and human studies . We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed ( HFD ) rats . In the present study , we first identified another L. reuteri strain , ADR-1 , which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats . We further performed a r and omized , double-blinded , placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens . Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group ( n = 22 ) after 3 months of intake when compared with those in the placebo group ( n = 22 ) . Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 ( n = 24 ) , the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake . There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3 , except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake . With the analysis of fecal microflora , we found that L. reuteri or Bifidobacterium spp . were significantly increased in the ADR-1 and ADR-3 consumption groups , respectively , after 6 months of intake . Interestingly , a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri . We also observed that there was a significantly positive correlation between Bifidobacterium spp . and Lactobacillus spp . in participants with increased levels of fecal L. reuteri . In the ADR-1 intake group , the fecal Lactobacillus spp . level displayed a positive correlation with Bifidobacterium spp . but was negatively correlated with Bacteroidetes . The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes . In conclusion , L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients , and the consumption of different strains of L. reuteri may influence changes in intestinal flora , which may lead to different outcomes after probiotic intake Gut microbiota may influence blood pressure ( BP ) , namely via end products of carbohydrate fermentation . After informed consent , male volunteers were prospect ively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements : ( 1 ) hypertension , ( 2 ) borderline hypertension , and ( 3 ) normotension . Stool , urine and serum sample s were collected in fasting conditions . Gut microbiota was characterized by 16S amplicon sequencing . Metabolomics , including quantification of short-chain fatty acids , was conducted using nuclear magnetic resonance . Two-way ANOVA combined with Tukey post hoc test , as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure , was used . The cohort included 54 males : 38 hypertensive ( including 21 under treatment ) , 7 borderline , and 9 normotensive . No significant difference was observed between groups concerning age , body mass index , smoking habits , and weekly alcohol consumption . The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients ( n=33 ) . This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment . Short-chain fatty acid levels were significantly different among groups , with higher stool levels of acetate , butyrate , and propionate in hypertensive versus normotensive individuals . No difference was observed in serum and urine metabolomes . Correlation between stool metabolome and 24-hour BP levels was evidence d , with R2 reaching 0.9 . Our pilot study based on 24-hour ambulatory BP measurements , 16S amplicon sequencing , and metabolomics supports an association between gut microbiota and BP homeostasis , with changes in stool abundance of short-chain fatty acids Purpose Polycystic ovarian syndrome ( PCOS ) is one of the most common metabolic and endocrine disorders . Functional foods like pomegranate and probiotics are those that are considered to have beneficial effects on metabolic diseases beyond their basic nutritional value . So , we aim ed to evaluate the effect of synbiotic pomegranate juice ( SPJ ) on cardiovascular risk factors on PCOS patients . Methods This was a r and omized , triple-blinded , 8-week trial . Participants were r and omly assigned to receive 300 mL/day of pomegranate juice ( PJ ) , synbiotic beverage ( SB ) , synbiotic pomegranate juice ( SPJ ) , or placebo beverage ( PB ) . Biochemical indices ( lipid profile , Total Antioxidant Capacity ( TAC ) , Malondialdehyde ( MDA ) , high sensitive C-Reactive Protein ( hs-CRP ) ) and blood pressure were assessed before and after the intervention . Results Participants in the PJ , SB , and SPJ groups experienced improvement in their lipid profile , oxidative stress , inflammation , and blood pressure during the time . Compared to placebo , Total Cholesterol ( TC ) was lower in the SB group ( P < 0.01 ) , LDL-c was lower in the SPJ and SB groups ( P < 0.01 ) , and HDL-c was higher in the SPJ and PJ groups ( P < 0.01 ) . With regards to oxidative stress and inflammation , when compared with placebo , MDA was lower in the SPJ , SB , and PJ groups ( P < 0.001 ) , TAC was increased in the SPJ and PJ groups ( P $ $ < $ $ < 0.001 ) , and hs-CRP was decreased in the PJ group ( P = 0.02 ) . Blood pressure ( BP ) was lower in the SPJ and PJ groups compared to placebo ( P < 0.001 ; P < 0.01 , respectively ) . Conclusions Consuming daily SPJ for 8 weeks improved metabolic , oxidative , inflammatory , and BP outcomes in females with PCOS . This trial was registered in the Iranian Registry of Clinical Trials ( I RCT 20170207032439N2 ) |
13,017 | 27,931,252 | We did not find a positive impact of directly advertising PPIR on any other outcomes .
Conclusion To our knowledge , this is the largest ever embedded trial to evaluate a recruitment or PPIR intervention .
Advertising PPIR did not improve enrolment rates or any other outcome .
It is possible that rather than advertising PPIR being the means to improve recruitment , PPIR may have an alternative impact on trials by making them more attractive , acceptable and patient-centred . | Background Patient and public involvement in research ( PPIR ) may improve trial recruitment rates , but it is unclear how .
Where trials use PPIR to improve design and conduct , many do not communicate this clearly to potential participants .
Better communication of PPIR might encourage patient enrolment , as trials may be perceived as more socially valid , relevant and trustworthy .
We aim ed to evaluate the impact on recruitment of directly advertising PPIR to potential trial participants . | Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone Investigators should properly calculate sample sizes before the start of their r and omised trials and adequately describe the details in their published report . In these a-priori calculations , determining the effect size to detect -- eg , event rates in treatment and control groups -- reflects inherently subjective clinical judgments . Furthermore , these judgments greatly affect sample size calculations . We question the br and ing of trials as unethical on the basis of an imprecise sample size calculation process . So-called underpowered trials might be acceptable if investigators use method ological rigor to eliminate bias , properly report to avoid misinterpretation , and always publish results to avert publication bias . Some shift of emphasis from a fixation on sample size to a focus on method ological quality would yield more trials with less bias . Unbiased trials with imprecise results trump no results at all . Clinicians and patients deserve guidance now Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment . We report three controlled trials of interventions to increase recruitment to the Txt2stop trial . Purpose To evaluate : Trial 1 . The impact on registration s of a text message regarding an online registration facility ; Trial 2 . The impact on r and omizations of sending £ 5 with a covering letter to those eligible to join the trial ; Trial 3 . The impact on r and omizations of text messages containing quotes from existing participants . Methods Single blind controlled trials with allocation concealment . Interventions : Trial 1 : A text message regarding our new online registration facility ; Trial 2 : A letter with £ 5 enclosed ; Trial 3 : A series of four text messages containing quotes from participants . The control group in each trial received st and ard Txt2stop procedures . Results Trial 1 : 3.6 % ( 17/470 ) of the intervention group and 1.1 % ( 5/467 ) of the control group registered for the trial , risk difference 2.5 % ( 95 % CI 0.6—4.5 ) . 0 % ( 0/ 470 ) of the intervention group and 0.2 % ( 1/467 ) of the control group registered successfully online , risk difference —0.2 ( 95 % CI —0.6—0.2 ) ; Trial 2 : 4.5 % ( 11/246 ) of the intervention group and 0.4 % ( 1/245 ) of the control group were r and omized into the Txt2stop trial , risk difference 4.0 % ( 95 % CI 1.4—6.7 ) ; Trial 3 : 3.5 % ( 14/405 ) of the intervention group and 0 % ( 0/406 ) of the control group were r and omized into the Txt2stop trial , risk difference 3.5 ( 95 % CI 1.7—5.2 ) . Limitations There were no baseline data available for trial 1 . Allocation of participant IDs in trials 2 and 3 were systematic . Conclusion Sending a text message about an online registration facility increased registration s to Txt2stop , but did not increase online registration s. Sending a £ 5 reimbursement for participants ’ time and sending text messages containing quotes from existing participants increased r and omizations into the Txt2stop trial . Clinical Trials 2010 ; 7 : 265—273 . Background Trials increasingly experience problems in recruiting participants . Underst and ing the causes of poor recruitment is critical to developing solutions . We interviewed people who had declined a trial of an innovative psychological therapy for depression ( REFRAMED ) about their response to the trial invitation , in order to underst and their decision and identify ways to improve recruitment . Methods Of 214 people who declined the trial , 35 ( 16 % ) gave permission to be contacted about a qualitative study to explore their decision . Analysis of transcripts of semi-structured interviews was informed by grounded theory . Results We interviewed 20 informants : 14 women and six men , aged 18 to 77 years . Many interviewees had prior experience of research participation and positive views of the trial . Interviewees ’ decision making resembled a four-stage sequential process ; in each stage they either decided not to participate in the trial or progressed to the next stage . In stage 1 , interviewees assessed the invitation in the context of their experiences and attitudes ; we term those who opted out at this stage ‘ prior decliners ’ as they had an established position of declining trials . In stage 2 , interviewees assessed their own eligibility ; those who judged themselves ineligible and opted out at this stage are termed ‘ self-excluders ’ . In stage 3 , interviewees assessed their need for the trial therapy and potential to benefit ; we term those who decided they did not need the trial therapy and opted out at this stage ‘ treatment decliners ’ . In stage 4 , interviewees deliberated the benefits and costs of trial participation ; those who opted out after judging that disadvantages outweighed advantages are termed ‘ trial decliners ’ . Across all stages , most individuals declined because they judged themselves ineligible or not in need of the trial therapy . While ‘ prior decliners ’ are unlikely to respond to any trial recruitment initiative , the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance . Conclusions To improve recruitment in similar trials , the most successful interventions are likely to address patients ’ assessment s of their eligibility and their potential to benefit from the trial treatment , rather than reducing trial burden . Trial registration International St and ard R and omised Controlled Trial Number : IS RCT N85784627 . Registration date 10 August 2011 It is now well known that st and ard statistical procedures become invali date d when applied to cluster r and omized trials in which the unit of inference is the individual . A result ing consequence is that research ers conducting such trials are faced with a multitude of design choices , including selection of the primary unit of inference , the degree to which clusters should be matched or stratified by prognostic factors at baseline , and decisions related to cluster subsampling . Moreover , application of ethical principles developed for individually r and omized trials may also require modification . We discuss several topics related to these issues , with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided Background The blood pressure rapid intensive lowering and normal treatment for mood and cognition in persistent depression ( BRILiANT mood study ) was devised as a pilot study to investigate the feasibility and safety of intensive blood pressure lowering as treatment for persistent mood and cognitive symptoms in older adults with major depressive disorder and to assess the availability of this population for recruitment . In addition , the relationship between reduced blood pressure and the change in cerebral blood flow and mood was to be investigated . Methods A single centre pilot r and omised controlled trial ( RCT ) , with two parallel groups of intensive or normal treatment for hypertension , recruiting from primary and secondary care and newspaper advert , with an aim of recruiting 66 participants , was observed in this study . At the end of the recruitment period , in order to explore the reasons for failure to recruit to target , surveys were developed and issued to those involved in recruitment . Results Recruitment rates were lower than expected which led to the study being exp and ed to further areas and opened to self-referral via advertisement . However , because of better management of hypertension due to changes in the UK Quality and Outcomes Framework guidelines for blood pressure treatment , few eligible patients were identified and the study closed at the end of the recruitment period , with 13 participants consenting , but 12 failing screening result ing in one recruited participant . Conclusions Overall , the BRILiANT mood study was found not to be feasible , and results suggest that the expected patient population no longer exists . To overcome such recruitment difficulties , a prompt commencement of a study after funding so no relevant care changes occur might help prevent similar problems in future studies . In addition , self-referral , in this case via advertisement in papers , may be a useful tool to increase response rate . When recruiting in primary care , direct access to primary care data bases , in a secure and anonymised way , may enable more effective screening . Ultimately , the BRILiANT mood study was shown not to be feasible ; this was a useful conclusion from this pilot study .Trial Registration IS RCT N 64524251 ; UKCRN Portfolio No : PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population . This study hypothesized that use of an easy-to-read consent statement , when compared with a st and ard consent statement , will result in higher patient comprehension of the clinical treatment protocol , lower patient anxiety , higher patient satisfaction , and higher patient accrual . METHODS A r and omized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups . Institutions were r and omly assigned to administer either an easy-to-read consent statement or the st and ard consent statement to patients being recruited to participate in selected cancer treatment trials . Telephone interviews were conducted with a total of 207 patients to assess study outcomes . RESULTS Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm . Patient comprehension and state anxiety were not affected by the intervention . Accrual rates into the parent studies also did not differ significantly between the two study groups . CONCLUSION Clinical trial informed consent statements can be modified to be easier to read without omitting critical information . Patient anxiety and satisfaction can be affected by the consent document . The generalizability of these study results is limited by the characteristics of the patient sample . Ninety percent of the sample were white women , and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64 , indicating a literacy level at or above the ninth grade Background Patient underst and ing of study information is fundamental to gaining informed consent to take part in a r and omised controlled trial . In order to meet the requirements of research ethics committees , patient information material s can be long and need to communicate complex messages . There is concern that st and ard approaches to providing patient information may deter potential participants from taking part in trials . The Systematic Techniques for Assisting Recruitment to Trials ( MRC-START ) research programme aims to test interventions to improve trial recruitment . The aim of this study was to investigate the effect on recruitment of optimised patient information material s ( with improved readability and ease of comprehension ) compared with st and ard material s. The study was embedded within two primary care trials involving patients with long-term conditions . Methods The Healthlines Study involves two linked trials evaluating a telehealth intervention in patients with depression ( Healthlines Depression ) or raised cardiovascular disease risk ( Healthlines CVD ) . We conducted two trials of a recruitment intervention , embedded within the Healthlines host trials . Patients identified as potentially eligible in each of the Healthlines trials were r and omised to receive either the original patient information material s or optimised versions of these material s. Primary outcomes were the proportion of participants r and omised ( Healthlines Depression ) and the proportion expressing interest in taking part ( Healthlines CVD ) . Results In Healthlines Depression ( n = 1364 ) , 6.3 % of patients receiving the optimised patient information material s were r and omised into the study compared to 4.0 % in those receiving st and ard material s ( OR = 1.63 , 95 % CI = 1.00 to 2.67 ) . In Healthlines CVD ( n = 671 ) 24.0 % of those receiving optimised patient information material s responded positively to the invitation to participate , compared to 21.9 % in those receiving st and ard material s ( OR = 1.12 , 95 % CI = 0.78 to 1.61 ) . Conclusions Evidence from these two embedded trials suggests limited benefits of optimised patient information material s on recruitment rates , which may only be apparent in some patient population s , with no effects on other outcomes . Further embedded trials are needed to provide a more precise estimate of effect , and to explore further how effects vary by trial context , intervention , and patient population .Trial registration Current Controlled Trials : Healthlines Depression ( IS RCT N27508731 ) on 26 June 2012 ; and Healthlines CVD ( IS RCT N14172341 ) on 5 July Background Recruitment and retention of participants are critical to the success of a r and omised controlled trial . Gaining the views of potential trial participants who decline to enter a trial and of trial participants who stop the trial treatment is important and can help to improve study processes . Limited research on these issues has been conducted on healthy individuals recruited for prevention trials in the community . Methods Semi-structured interviews with people who were eligible but had declined to participate in the Aspirin for Asymptomatic Atherosclerosis ( AAA ) trial ( N = 11 ) , and AAA trial participants who had stopped taking the trial medication ( N = 11 ) . A focus group with further participants who had stopped taking the trial medication ( N = 6 ) . ( Total participants N = 28 ) . Results Explanations for declining to participate could be divided into two groups : the first group were characterised by a lack of necessity to participate and a tendency to prioritise other largely mundane problems . The second group 's concern was with a high level of perceived risk from participating . Explanations for stopping trial medication fell into four categories : side effects attributed to the trial medication ; starting on aspirin or medication contraindicating to aspirin ; experiencing an outcome event , and changing one 's mind . Conclusions These results indicate that when planning trials ( especially in preventive medicine ) particular attention should be given to design ing appropriate recruitment material s and processes that fully inform potential recruits of the risks and benefits of participation . Trial registration IS RCT Results Nineteen review s were included . Multimedia interventions offer a platform for learning which can include study -specific information ( e.g. study purpose , risks ) , and generic information ( e.g. confidentiality ) . There was evidence that multimedia interventions improved various outcomes including perceived risk , personal choice and feeling informed . PPI forum members and qualitative experts developed study -specific components involving bespoke themes such as investigator details and benefits of participation , and generic information components including informed consent , r and omisation and confidentiality . Existing video clips of patients discussing their experiences of participation were carefully matched to these components BACKGROUND Patient education in the basic concepts of clinical trials is necessary to promote underst and ing of the informed consent process and enhance patients ' decision-making . It has been suggested that patients ' knowledge and attitudes are improved by being given general written information about clinical trials . OBJECTIVE This pilot study was conducted to determine the effect of a patient education h and book on the knowledge , attitudes , and motivations of pharmacy students regarding clinical trials . METHODS A patient clinical trials h and book was developed at a 7th- grade reading level for the Department of Veterans Affairs Cooperative Studies Program and tested in PharmD students . Students were r and omized to the experimental group ( received h and book ) or the control group ( no h and book ) . They were given 15 to 20 minutes to read the h and book , after which they were asked to respond to a question naire adapted from previous studies . The question naire included 25 true/false questions testing participants ' knowledge of clinical trials , 5 questions on attitudes toward clinical trials scored on a 5-point Likert scale , and 6 questions concerning their motivation toward participation in hypothetical clinical trial scenarios scored on a 5-point Likert scale . The experimental group was also asked to rate the informativeness , helpfulness , and clarity of the h and book on a 5-point Likert scale . RESULTS There were 40 students in the experimental group and 50 in the control group . Knowledge scores were significantly higher in the experimental group compared with the control group ( mean [ SD ] percentage of correct answers , 88.7 % [ 8.0 % ] vs 82.6 % [ 9.0 % ] , respectively ; P < 0.001 ) . Positive attitudes toward clinical trials were also increased in the experimental group compared with the control group ; specifically , participants expressed significantly greater clarity of underst and ing of clinical trials ( mean score , 1.4 [ 0.5 ] vs 0.8 [ 0.6 ] ; P < 0.001 ) and relief associated with knowing about clinical trials ( mean score , 0.8 [ 0.8 ] vs 0.4 [ 0.7 ] ; P = 0.017 ) . There were no between-group differences in students ' motivation to participate in the hypothetical clinical trial scenarios . A high proportion of students ( 95 % ) found the h and book informative , helpful , and underst and able . CONCLUSIONS The patient clinical trials h and book increased knowledge and positive attitudes regarding clinical trials among pharmacy students participating in this study Background Involving service users in planning their care is at the centre of policy initiatives to improve mental health care quality in Engl and . Whilst users value care planning and want to be more involved in their own care , there is substantial empirical evidence that the majority of users are not fully involved in the care planning process . Our aim is to evaluate the effectiveness and cost-effectiveness of training for mental health professionals in improving user involvement with the care planning processes . Methods / Design This is a cluster r and omised controlled trial of community mental health teams in NHS Trusts in Engl and allocated either to a training intervention to improve user and carer involvement in care planning or control ( no training and care planning as usual).We will evaluate the effectiveness of the training intervention using a mixed design , including a ‘ cluster cohort ’ sample , a ‘ cluster cross-sectional ’ sample and process evaluation . Service users will be recruited from the caseloads of care co-ordinators . The primary outcome will be change in self-reported involvement in care planning as measured by the vali date d Health Care Climate Question naire . Secondary outcomes include involvement in care planning , satisfaction with services , medication side-effects , recovery and hope , mental health symptoms , alliance/engagement , well-being and quality of life . Cost- effectiveness will also be measured . A process evaluation informed by implementation theory will be undertaken to assess the extent to which the training was implemented and to gauge sustainability beyond the time-frame of the trial . Discussion It is hoped that the trial will generate data to inform mental health care policy and practice on care planning . Trial Registration NumberIS RCT N16488358 ( 14 May 2014 Background R and omized controlled trials play a central role in evidence -based practice , but recruitment of participants , and retention of them once in the trial , is challenging . Moreover , there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies . As with other healthcare initiatives , the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives , which for recruitment would mean embedding a recruitment trial within an ongoing host trial . Systematic review s indicate that such studies are rare . Embedded trials are largely delivered in an ad hoc way , with interventions almost always developed in isolation and tested in the context of a single host trial , limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to research ers working in different context s. Methods / Design The Systematic Techniques for Assisting Recruitment to Trials ( START ) program is funded by the United Kingdom Medical Research Council ( MRC ) Methodology Research Programme to support the routine adoption of embedded trials to test st and ardized recruitment interventions across ongoing host trials . To achieve this aim , the program involves three interrelated work packages : ( 1 ) methodology - to develop guidelines for the design , analysis and reporting of embedded recruitment studies ; ( 2 ) interventions - to develop effective and useful recruitment interventions ; and ( 3 ) implementation - to recruit host trials and test interventions through embedded studies . Discussion Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or , potentially , other types of intervention linked to trial conduct . It will also increase the evidence base for two types of recruitment intervention . Trial registration The START protocol covers the methodology for embedded trials . Each embedded trial is registered separately or as a sub study of the host trial Purpose . To investigate the reasons behind difficulties in recruiting patients to r and omized controlled trials ( RCTs ) in psychiatry and to examine a data base of RCTs for differences between studies in mental health and other specialities . Methods . A discussion of recent changes in research governance in the UK and Europe followed by an examination of the data base of all trials supported by the Health Technology Assessment programme of the National Institute of Health Research in the UK between 1993 and 2007 to determine if three different measures , ( i ) time between grant approval and study start date , ( ii ) percentage of additional time given to extend recruitment and ( iii ) percentage of planned recruitment achieved , changed over the time period studied and differed between mental health , cancer and other medical disciplines . Findings . Despite attempts in the UK to accelerate the process of clinical trials in recent years , there was a significant increase in the extension time for trials to be completed ( p = 0.038 ) and the percentage of planned recruitment to mental health studies ( 71 % ) was significantly less than for cancer ( 90.3 % ) and other studies ( 86.1 % ) ( p = 0.032 ) . Summary . These results suggest that , despite the priority afforded to the advancement of RCTs in healthcare , such studies are encountering increasing difficulty in recruiting to time and target . We suggest that this difficulty can be attributed , at least in part , to the excessively byzantine regulation and governance processes for health research in the UK , and unnecessary bureaucracy in the current National Health Service system . Mental health studies appear particularly vulnerable to delay and better systems to facilitate recruitment are required urgently for the evidence base to be improved and facilitate new cost-effective interventions Purpose To provide empirical evidence on the impact of on-site initiation visits on the following outcomes : patient recruitment , quantity and quality of data su bmi tted to the trial coordinating office , and patients ' follow-up time . Patients and methods This method ological study was performed as part of a r and omized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer . Centers participating to the trial were r and omized to either receive systematic on-site visits ( Visited group ) , or not ( Non-visited group ) . Results The study was terminated after two years , while the main r and omized trial continued . Of the 135 centers that had expressed an interest in the trial , only 69 r and omized at least one patient ( 35/68 in the Visited group , 34/67 in the Nonvisited group ) . Almost two-thirds of the patients were entered by 17 centers ( 10 in the Visited group , seven in the Non-visited group ) that accrued more than 10 patients each . None of the prespecified outcomes favored the group of centers su bmi tted to on-site initiation visits ( ie , mean number of queries par patient : 6.1 ± 9.7 versus 5.4 ± 6.4 , respectively for the Visited and Non-visited groups ) . Spontaneous transmittal of case report forms , although required by protocol , was low in both r and omized groups ( mean number of pages per patient : 1.5 ± 2.0 versus 2.1 ± 2.3 , respectively ) , with investigators su bmi tting about one-third of the expected forms on time ( 29 % and 39 % , respectively ) . Limitations This study could not evaluate the impact of repeated on-site visits on clinical outcomes . Conclusion Systematic on-site initiation visits did not contribute significantly to this clinical trial This study examined the use of lay advocates ( i.e. , women enrolled in a study who advocate to others ) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale , national prevention study , the Women 's Health Initiative ( WHI ) . We examined whether trained , Hispanic lay advocates ( called Embajadoras ) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures . Fifty-six Hispanic participants in the WHI were r and omized to receive training or no training on advocacy , and continued to meet quarterly for 18 months . Also , 42 Anglo women were assigned to control . All groups received brochures to use for advocating the WHI . The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes . Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls . Embajadoras were also found to distribute significantly more brochures than control groups . Therefore , a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments . Other potential influences on enrollment or referral success could not be determined due to the small sample size . Further study is needed to examine the best methods to encourage enrollment for women referred to the study INTRODUCTION Psychological theory suggests that participants may be more likely to volunteer to join a clinical trial if they perceive places in the trial are a scarce commodity . MATERIAL AND METHODS We conducted a single blind , r and omized controlled trial to test recruitment strategies within the larger txt2stop smoking cessation trial . 1862 people who were eligible for the txt2stop trial but had not yet consented to join were r and omized to receive either A ) a reminder about the txt2stop trial plus a message that there were only 300 places left , or B ) a reminder about the trial only . The outcome was the participant 's consent to join the txt2stop trial 3days after messages were sent . RESULTS Of 895 participants r and omized to the intervention group , 90 ( 10.1 % ) had consented to join the txt2stop trial . Of the 967 participants r and omized to the control group , 67 ( 6.9 % ) had consented to join the txt2stop trial ( OR=1.50 , 95 % CI 1.07 - 2.12 ) . DISCUSSION Scarcity messages were an effective way to increase recruitment into the txt2stop trial and could be relevant to other trials . CONCLUSIONS Communicating scarcity is an effective way to increase trial recruitment AIMS AND OBJECTIVES To discuss the evidence of poor recruitment rates in r and omised clinical trials and relate this to existing recruitment methodology before a novel approach to recruitment is suggested . BACKGROUND Recruitment is crucial to the success of research projects . Effective recruitment leads to effective retention , an increased pool of data and in-time completion of projects . Robust evidence indicates that recruitment remains a challenge in many clinical trials . DESIGN Discursive article . METHODS The complexity of recruitment is m and ated based on the findings from a literature review that summarises common threats to successful recruitment . Nursing theories and models that incorporate recruitment are critically review ed before recruiting , and its planning is related to existing complex intervention methodology . CONCLUSION Threats to sufficient recruitment are inherent in the planning of studies , the recruiting process and triadic relationships between institutions , recruiter and participants . Existing nursing theories and models address important recruitment issues but do not account for all aspects that jeopardise sufficient recruitment . Hence , available frameworks for complex intervention planning and evaluation are useful to guide recruitment and its planning as an umbrella methodology . RELEVANCE TO CLINICAL PRACTICE Using complex intervention methodology for recruitment and its planning enhances a nurse research er 's awareness of the challenges and pitfalls recruitment poses and may translate to improved recruitment rates and overall success of clinical trials Background R and omised controlled trials ( RCTs ) are considered particularly likely to benefit from patient and public involvement ( PPI ) . Decisions made by professional research ers at the outset may go on to have a significant impact on the potential for PPI contributions . Objective To increase knowledge of PPI within the early development of RCTs by systematic ally describing the reported level , nature and acceptability of proposed PPI to the funders . Methods Documentation from the outline application process for all RCTs that received funding from the Health Technology Assessment ( HTA ) Programme 2006–2010 was requested . For each application , data were extracted on trial characteristics , references to PPI in the development of the outline application and funding Board feedback , and plans for PPI in the full application and after the trial was funded . Results 110 applications were eligible with outline applications available for 90 ( 82 % ) . The cohort covered a wide range of interventions and conditions . 54 % ( 49/90 ) provided some information about PPI . 26 ( 28.9 % ) indicated PPI within the development of the outline application itself ; 32 ( 35.6 % ) planned involvement in the full application and 43 ( 48 % ) once the trial was funded . Recruitment at diagnosis and surgical interventions were less likely to describe PPI . Blinded trials and trials in which participants may receive placebo only , more frequently described PPI activity . The HTA commissioning Board feedback rarely referred to PPI . Conclusions Incorporation of PPI within the development of the outline application or specification of plans for future involvement was low . Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research . Comments on PPI by review ers should be directional rather than state that an increase is required . Challenges facing applicants in initiating PPI prior to funding need to be addressed To improve the patient education process in clinical research , three information material s describing general aspects of design and conduct of r and omized clinical trials were developed . The material s varied in length , reading ability level , and reader appeal . Their influence on knowledge about and attitude toward r and omized clinical trials was assessed in a r and omized , parallel group , evaluator-blinded trial among 415 out patients . The patients were r and omized to the following groups : control ( no intervention ) , leaflet , brochure , or booklet . Knowledge was assessed by a 17-item multiple-choice question naire and attitude was assessed by a 32-item Likert question naire at entry and 2 weeks after the intervention . The interventions and the question naires were pilot tested and power calculations were performed . At entry , the mean knowledge score was 7.9 points . At follow-up , the knowledge scores increased by 0.5 for the control , 1.0 for the leaflet , 1.6 for the brochure , and 1.4 for the booklet . The brochure and the booklet improved the knowledge score significantly compared with the control . The general attitude was positive at entry ( mean 71.5 points ) . Only the booklet significantly increased the total attitude score ( 4.8 points ) and the r and omized clinical trials attitude subscale score ( 1.8 points ) . In conclusion , written information significantly improved out patients ' knowledge about and attitude toward r and omized clinical trials . Detailed rather than brief information was more effective . Control Clin Trials 2000;21:223 - Objectives . To assess the usefulness of three sources ( faith-based organizations ( FBOs ) health system and community ) for recruitment of African Americans with type 2 diabetes to a r and omized controlled trial ( RCT ) . Design . African Americans with type 2 diabetes were recruited to a diabetes self-management program at four FBO sites . An observational study of a multifaceted recruitment strategy to enroll subjects in the RCT that evaluated the effectiveness of a diabetes self-management program and the effect of recruitment source on retention after enrollment . Self-administered demographic surveys and weekly class attendance records were collected . Results . Of 184 interested individuals 109 ( 59.2 % ) were enrolled . Of those enrolled 60.6 % recruited through the health system 13.8 % FBOs and 19.2 % the community . The highest yield was achieved through the health system . However for both the intervention ( I ) and control ( C ) groups respectively participants recruited from FBOs ( 85.7 % I ; 62.5 % C ) were more likely to attend four or more sessions than those from the health system ( 75.0 % I ; 43.3 % C ) and community ( 55.6 % I ; 25.0 % C ) . Despite similar class size participants in the intervention group ( 74.5 % ; n = 41 ) were more likely to attend four or more of the seven classes than those in the delayed intervention ( control group ) ( 40.7 % ; n = 22 ) . Conclusions . The findings suggest that African American adults with diabetes can be successfully recruited and retained in a racially targeted RCT conducted in FBOs . Key elements to consider are the use of a multifaceted approach for participant recruitment particularly the benefit of health system physician involvement in recruitment since the highest yield was achieved through health system providers and importance of site location for retention PURPOSE To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials . METHODS Main member institutions of the Cancer and Leukemia Group B ( CALGB ) and its affiliates were r and omly assigned to receive st and ard information ( n = 73 ) or educational intervention ( n = 53 ) . St and ard information included CALGB Web site access and periodic notification about existing trials . The geriatric educational intervention included st and ard information plus : ( 1 ) an educational seminar ; ( 2 ) educational material s ; ( 3 ) a list of available protocol s for use on charts ; ( 4 ) a monthly e-mail and mail reminders for 1 year ; and ( 5 ) a case discussion seminar . The main outcome was percentage of accrual of older persons to phase II and III treatment protocol s after study initiation compared with baseline . RESULTS There were 3,032 patients entered onto trials in the baseline year , and 2,160 and 1,239 during the 2 years postintervention , respectively . Overall percentage of accrual of older patients was 37 % at baseline , and 33 % and 31 % during the first and second years after intervention . There was no improvement in accrual in the intervention versus control arm : 36 % v 32 % in the first year and 31 % v 31 % in the second year . CONCLUSION Accrual of older patients was not increased by this intervention . Reasons for lack of effect include low intervention intensity , high baseline accrual rates , and closure of several high-accruing protocol s during the study . More intense and multifaceted approaches will be needed to change physician ( and patient ) behavior and to increase accrual of older persons to clinical trials BACKGROUND The value of the individual placement and support ( IPS ) programme in helping people with severe mental illness gain open employment is unknown in Europe . Our aim was to assess the effectiveness of IPS , and to examine whether its effect is modified by local labour markets and welfare systems . METHODS 312 patients with severe mental illness were r and omly assigned in six European centres to receive IPS ( n=156 ) or vocational services ( n=156 ) . Patients were followed up for 18 months . The primary outcome was the difference between the proportions of people entering competitive employment in the two groups . The heterogeneity of IPS effectiveness was explored with prospect i ve meta-analyses to establish the effect of local welfare systems and labour markets . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , with the number NCT00461318 . FINDINGS IPS was more effective than vocational services for every vocational outcome , with 85 ( 55 % ) patients assigned to IPS working for at least 1 day compared with 43 ( 28 % ) patients assigned to vocational services ( difference 26.9 % , 95 % CI 16.4 - 37.4 ) . Patients assigned to vocational services were significantly more likely to drop out of the service and to be readmitted to hospital than were those assigned to IPS ( drop-out 70 [ 45 % ] vs 20 [ 13 % ] ; difference -32.1 % [ 95 % CI -41.5 to -22.7 ] ; readmission 42 [ 31 % ] vs 28 [ 20 % ] ; difference -11.2 % [ -21.5 to -0.90 ] ) . Local unemployment rates accounted for a substantial amount of the heterogeneity in IPS effectiveness . INTERPRETATION Our demonstration of the effectiveness of IPS in widely differing labour market and welfare context s confirms this service to be an effective approach for vocational rehabilitation in mental health that deserves investment and further investigation Epidemiology and Psychiatric Sciences / Volume 22 / Issue 04 / December 2013 , pp 321 323 DOI : 10.1017/S2045796013000267 , Published online : 12 June 2013 Link to this article : http://journals.cambridge.org/ abstract _ S2045796013000267 How to cite this article : C.E. Adams ( 2013 ) . Many more reasons behind difculties in recruiting patients to r and omized controlled trials in psychiatry . Epidemiology and Psychiatric Sciences , 22 , pp 321 - 323 doi:10.1017/S2045796013000267 Request Permissions : Click |
13,018 | 23,439,701 | Conclusion : DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis . | Objectives : We performed a systematic review to assess alterations in measures of diffusion tensor imaging ( DTI ) in parkinsonian syndromes , exploring the potential role of DTI in diagnosis and as a c and i date biomarker . | BACKGROUND AND PURPOSE : Previous neuropathologic studies in chronic hydrocephalus have suggested the presence of white matter damage , presumably from mechanical pressure due to ventricular enlargement and metabolic derangement . This study aim ed to investigate the diffusional properties of the CST in patients with iNPH by using DTI and to determine whether this method could be used as a new diagnostic tool to differentiate patients with iNPH from those with AD and PDD and control subjects . MATERIAL S AND METHODS : We enrolled 18 patients with iNPH , 11 patients with AD , 11 patients with PDD , and 19 healthy control subjects . Diffusion tensor metrics of the segmented CST , including FA values , axial eigenvalues , and radial eigenvalues , were evaluated by using tract-specific analysis . The anisotropy color-coding tractography of the CST was visually evaluated . The DTI findings were compared among groups . RESULTS : Tract-specific analysis of the CST showed that FA values and axial eigenvalues were significantly increased ( P < .001 ) , whereas radial eigenvalues were not significantly altered , in patients with iNPH compared with other subjects . The CST tractographic images in patients with iNPH was visually different from those in other subjects ( P < .001 ) . In discriminating patients with iNPH from other subjects , the CST FA values had a sensitivity of 94 % and specificity of 80 % at a cutoff value of 0.59 . CONCLUSIONS : Our results suggest that patients with iNPH have altered microstructures in the CST . Quantitative and visual CST evaluation by using DTI may be useful for differentiating patients with iNPH from patients with AD or PDD or healthy subjects AIM To determine prospect ively if qualitative and quantitative diffusion tensor imaging ( DTI ) metrics of white matter integrity are better than conventional magnetic resonance imaging ( MRI ) metrics for discriminating cerebellar diseases . METHODS Conventional MRI images from 31 consecutive patients with ataxia and 12 controls were interpreted by a neuroradiologist given only a clinical indication of ataxia . An expert ataxologist , blinded to radiological findings , determined the clinical diagnosis , as well as ataxia severity and asymmetry for each patient . For qualitative analysis , a comparison of the cerebellar white matter in ataxic vs. control patients was made by visual inspection of directionally encoded color ( DEC ) images . For quantitative analysis , segmentation of the cerebellar white matter in the inferior , middle , and superior cerebellar peduncles ( ICP , MCP , and SCP ) was attempted using three methods : a region of interest method , a deterministic DTI tractography ( DDT ) method , and a probabilistic DTI tractography ( PDT ) method . A statistical comparison of the average fractional anisotropy ( FA ) in these tracts was made between subject groups , and correlated to clinical diagnosis , severity , and asymmetry . RESULTS Of the 31 consecutive patients with ataxia , the two largest subgroups had a clinical diagnosis of multiple system atrophy ( cerebellar subtype ; MSA-C ) , and spinocerebellar ataxia-1 ( SCA1 ) . Conventional MRI features , such as degree of pontocerebellar atrophy , correlated with ataxia severity , but were neither sensitive nor specific for the ataxia subtypes . PDT was the most accurate and least variable method of the three methods used for determining FA , especially in the ICP . Average FA in all ataxic patients was significantly decreased in the MCP , SCP and ICP and this decrease correlated to disease severity . Asymmetric ataxia correlated to proportionately larger contralateral MCP , ICP and SCP FA values . MCP , ICP , and SCP FA difference values formed distinct clusters that distinguished MSA-C from SCA-1 , and other ataxia syndromes . CONCLUSIONS Qualitative and quantitative reductions in DTI metrics of white matter integrity in the cerebellar peduncles correlated better to clinical features of patients with sporadic and hereditary ataxias than conventional structural MRI measures of pontocerebellar atrophy Background : Preliminary work has shown that diffusion tensor MRI ( DTI ) may contribute to the diagnosis of Parkinson ’s disease ( PD ) . Objectives : We conducted a large , prospect i ve , case control study to determine : ( 1 ) if fractional anisotropy ( FA ) and apparent diffusion coefficient ( ADC ) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls ; and ( 2 ) the predictive value of these parameters and their clinical utility . Methods : DTI imaging was carried out in patients with PD and controls . FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard . The structures studied were : cau date , putamen , globus pallidus , thalamus and substantia nigra . Results : 151 subjects ( 73 PD patients , 41 men , 32 women ; mean age 63.6 years ) and 78 age and sex matched control subjects were studied . The FA value of the substantia nigra in patients with PD was lower compared with controls ( 0.403 vs 0.415 ; p = 0.001 ) . However , no significant differences were demonstrated for FA or ADC values of other structures . Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD ( regression coefficient −0.019 ) . No single FA value had both a high positive and negative predictive power for PD . Conclusions : We demonstrated in a large , prospect i ve , case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls , and correlated inversely with the clinical severity of PD . Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response Objective : To determine whether apparent diffusion coefficient ( ADC ) values and fractional anisotropy ( FA ) values can detect early pathological involvement in multiple system atrophy ( MSA ) , and be used to differentiate MSA-P ( multiple system atrophy if parkinsonian features predominate ) from Parkinson ’s disease ( PD ) . Methods : We compared ADC and FA values in the pons , cerebellum and putamen of 61 subjects ( 20 probable MSA patients , 21 age matched PD patients and 20 age matched healthy controls ) using a 3.0 T magnetic resonance system . Results : ADC values in the pons , cerebellum and putamen were significantly higher , and FA values lower in MSA than in PD or controls . These differences were prominent in MSA lacking dorsolateral putaminal hyperintensity ( DPH ) or hot cross bun ( HCB ) sign . In differentiating MSA-P from PD using FA and ADC values , we obtained equal sensitivity ( 70 % ) and higher specificity ( 100 % ) in the pons than in the putamen and cerebellum . In addition , all patients that had both significant low FA and high ADC values in each of these three areas were MSA-P cases , and those that had both normal FA and ADC values in the pons were all PD cases . Our diagnostic algorithm based on these results accurately diagnosed 90 % of patients with MSA-P. Conclusion : FA and ADC values detected early pathological involvement prior to magnetic resonance signal changes in MSA . In particular , low FA values in the pons showed high specificity in discriminating MSA-P from PD . In addition , combined analysis of both FA and ADC values in all three areas was more useful than only one Introduction Progressive supranuclear palsy ( PSP ) is a neurodegenerative disease featuring parkinsonism , supranuclear ophthalmoplegia , dysphagia , and frontal lobe dysfunction . The corpus callosum which consists of many commissure fibers probably reflects cerebral cortical function . Several previous reports showed atrophy or diffusion abnormalities of anterior corpus callosum in PSP patients , but partitioning method used in these studies was based on data obtained in nonhuman primates . In this study , we performed a diffusion tensor analysis using a new partitioning method for the human corpus callosum . Methods Seven consecutive patients with PSP were compared with 29 age-matched patients with Parkinson ’s Disease ( PD ) and 19 age-matched healthy control subjects . All subjects underwent diffusion tensor magnetic resonance imaging , and the corpus callosum was partitioned into five areas on the mid-sagittal plane according to a recently established topography of human corpus callosum ( CC1—prefrontal area , CC2—premotor and supplementary motor area , CC3—motor area , CC4—sensory area , CC5—parietal , temporal , and occipital area ) . Fractional anisotropy ( FA ) and apparent diffusion coefficient ( ADC ) were measured in each area and differences between groups were analyzed . Results In the PSP group , FA values were significantly decreased in CC1 and CC2 , and ADC values were significantly increased in CC1 and CC2 . Receiver operating characteristic analysis showed excellent reliability of FA and ADC analyses of CC1 for differentiating PSP from PD . Conclusion The anterior corpus callosum corresponding to the prefrontal , premotor , and supplementary motor cortices is affected in PSP patients . This analysis can be an additional test for further confirmation of the diagnosis of PSP |
13,019 | 19,754,633 | Higher usage of website features may be associated with positive weight change , but we do not know what features improve this effect or reduce attrition | The objectives of this systematic review are to evaluate the effectiveness of web-based interventions on weight loss and maintenance and identify which components of web-based interventions are associated with greater weight change and low attrition rates . | CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs Background Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment . This study aims to determine the effectiveness and cost-effectiveness of an Internet-based re source for obesity management . Methods A r and omised controlled trial conducted in a community setting , where obese volunteers ( n = 221 ) were r and omly assigned to Internet group ( n = 111 ) or usual care group ( n = 110 ) . Objective measures of weight and height were obtained . Question naires were used to collect dietary , lifestyle , physical activity and quality of life data . Data were collected at baseline , six months and 12 months . Results Data were collected on 54 ( 49 % ) participants in the Internet group and 77 ( 70 % ) participants in the usual care group at 12 months . Based on analysis conducted on all available data , the Internet group lost 1.3 kg , compared with 1.9 kg weight loss in the usual care group at 12 months , a non-significant difference ( difference = 0.6 kg ; 95 % CI : -1.4 to 2.5 , p = 0.56 ) . No significant differences in change in secondary outcome measures between the two groups at six or 12 months were revealed . Total costs per person per year were higher in the Internet group than the usual care group ( £ 992.40 compared to £ 276.12 ) , primarily due to the fixed costs associated with setting up the website , and QALYs were similar ( 0.78 and 0.77 ) for both groups . Conclusion This trial failed to show any additional benefit of this website in terms of weight loss or secondary outcome measures compared with usual care . High attrition and low compliance limits the results of this research . The results suggest that the Internet-based weight control re source was not a cost-effective tool for weight loss in the obese sample studied . Trail Registration IS RCT N BACKGROUND Several studies have shown that e-mail counseling improves weight loss achieved in self-directed Internet programs . Computer-tailored feedback offers a population -based alternative to human e-mail counseling . METHODS One hundred ninety-two adults , aged 49.2 + /- 9.8 years , having a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of 32.7 + /- 3.5 , were r and omized to 1 of 3 Internet treatment groups : No counseling , computer-automated feedback , or human e-mail counseling . All participants received 1 weight loss group session , coupons for meal replacements , and access to an interactive Web site . The human e-mail counseling and computer-automated feedback groups also had access to an electronic diary and message board . The human e-mail counseling group received weekly e-mail feedback from a counselor , and the computer-automated feedback group received automated , tailored messages . RESULTS Retention was 82 % at 3 months and 80 % at 6 months for all 3 groups . At 3 months , completers in both the computer-automated feedback ( -5.3 + /- 4.2 kg ) and human e-mail counseling ( -6.1 + /- 3.9 kg ) groups had significantly greater weight losses compared with the no counseling group ( -2.8 + /- 3.5 kg ) and these groups did not differ from each other . At 6 months , weight losses were significantly greater in the human e-mail counseling group ( -7.3 + /- 6.2 kg ) than in the computer-automated feedback ( -4.9 + /- 5.9 kg ) or no counseling ( -2.6 + /- 5.7 kg ) groups . Intent-to-treat analyses using single or multiple imputation techniques showed the same pattern of significance . CONCLUSIONS Providing automated computer-tailored feedback in an Internet weight loss program was as effective as human e-mail counseling at 3 months . Further research is needed to improve the efficacy of automated computer-tailored feedback as a population -based weight loss approach Background : Internet-based weight-loss programs appear promising in the short-term but , to data , have not been able to produce the level of weight loss seen in traditional in-person treatment ; thus , novel approaches are necessary . Using a combination of interactive technology and in-person support has been beneficial in other areas of medicine . Purpose : The aim of this study is to compare 12-month weight-loss outcomes of an Internet-only behavioral weight-loss treatment with the same program supplemented with monthly in-person meetings . Methods : One hundred and twenty-three participants were r and omized to an Internet-only ( n=62 ) or an Internet + in-person treatment ( I+IPS ; n=61 ) . All participants then participated in a 12-month behavioral weight-loss program conducted over the Internet . The groups met online weekly for the first 6 months and biweekly for the second half of the intervention . The I+IPS group had access to the same Web site as the Internet-only group but , once a month , attended an in-person meeting in place of an online chat . Assessment s included body weight , program adherence , and social support measures . Results : An intent-to-treat analysis ( n=123 ) revealed there were no significant Group x Time differences ( p=.15 ) in weight loss at either 6 ( −6.8±7.8 vs. −5.1±4.8 , p=.15 ) or 12 months ( −5.1±7.1 kg vs. −3.5±5.1 kg , p=.17 , for Internet-only and I+IPS , respectively ) . Differences between groups for those completing all measures ( n=77 ) also revealed no significant differences at 6 months ( −9.2±7.0 kg vs. −6.9±4.2 kg , p=.08 ) or 12 months ( −8.0±7.5 kg vs. −5.6±5.5 kg , p=.10 for the Internet-only and I+IPS conditions , respectively ) . Conclusions : Supplementation of an Internet weight-loss treatment with monthly in-person meetings did not result in greater weight losses over 12 months . Dynamic , socially supportive , and interactive elements of the Web site may have obviated the need for further interpersonal behavioral counseling OBJECTIVE To investigate the efficacy of an Internet weight maintenance program . RESEARCH METHODS AND PROCEDURES Two hundred fifty-five healthy overweight and obese adults ( mean + /- SD BMI , 31.8 + /- 4.1 kg/m(2 ) ) men ( 18 % ; mean + /- SD age , 45.8 + /- 8.9 yrs ) participated in a 6-month behavioral weight control program conducted over interactive television . Treatment was followed by a 12-month weight maintenance program with three conditions : frequent in-person support ( F-IPS ) , minimal in-person support ( M-IPS ) and internet support ( IS ) . Main outcome measures included body weight , program adherence , and social influence components . RESULTS There were no significant differences among the groups in weight loss ( mean + /- SD ) from baseline to 18 months ( 7.6 + /- 7.3 kg vs. 5.5 + /- 8.9 kg vs. 5.1 + /- 6.5 kg , p = 0.23 for the IS , M-IPS , and F-IPS , respectively ) . DISCUSSION Participants assigned to an internet-based weight maintenance program sustained comparable weight loss over 18 months compared with individuals who continued to meet face-to-face . Therefore , the internet appears to be a viable medium for promoting long-term weight maintenance 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 OBJECTIVE Internet weight loss programs have become widely available as alternatives to st and ard treatment , but few data are available on their efficacy . This study aim ed to investigate the effectiveness of a structured behavioral weight loss website ( VTrim ) vs. a commercial weight loss website ( eDiets.com ) . RESEARCH METHODS AND PROCEDURES A r and omized , controlled trial was conducted from February 2003 to March 2005 , in 124 overweight and obese subjects ages 18 years and older with a BMI of 25 to 39.9 kg/m2 ( mean age , 47 + /- 9 years ; BMI , 32 + /- 3 kg/m2 ; 20 % men ) . Analyses were performed for the 88 subjects who had complete follow-up data . Participants were r and omly assigned to 12-month VTrim ( n = 62 ) or eDiets.com ( n = 62 ) intervention . VTrim participants had access to a therapist-led structured behavioral weight loss program delivered on-line . eDiets.com subjects had access to a self-help commercial on-line weight loss program . Body weight , social support , and use of website components were measured at 0 , 6 , and 12 months . RESULTS Repeated- measures analyses showed that the VTrim group lost significantly more weight than the eDiets.com group at 6 months ( 8.3 + /- 7.9 kg vs. 4.1 + /- 6.2 kg ; p = 0.004 ) and maintained a greater loss at 12 months ( 7.8 + /- 7.5 kg vs. 3.4 + /- 5.8 kg ; p = 0.002 ) . More participants in the VTrim group maintained a 5 % weight loss goal ( 65 % vs. 37.5 % ; p = 0.01 ) at 12 months . DISCUSSION An on-line , therapist-led structured behavioral weight loss website produced greater weight loss than a self-help commercial website . Because commercial sites have great potential public health impact , future research should investigate the feasibility of incorporating a more structured behavioral program into a commercial application OBJECTIVE To assess , in a 1-year r and omized controlled trial , the efficacy of eDiets.com ( a commercial Internet weight loss program ) in improving weight , cardiovascular health , and quality of life . RESEARCH METHODS AND PROCEDURES Participants were 47 women with a mean age of 43.7 + /- 10.2 ( SD ) years and a mean BMI of 33.5 + /- 3.1 kg/m2 . They were r and omly assigned to either : 1 ) eDiets.com , a commercial Internet-based program available to the public ; or 2 ) a weight loss manual ( i.e. , LEARN Program for Weight Control 2000 ) . At baseline , participants in both groups met briefly with a psychologist who instructed them to follow the components of their program as closely as possible . Additional brief visits were provided at weeks 8 , 16 , 26 , and 52 to review their progress . Change in weight was the main outcome measure . RESULTS At week 16 , participants in eDiets.com lost 0.9 + /- 3.2 % of initial weight compared with 3.6 + /- 4.0 % for women assigned to the weight loss manual . At week 52 , losses increased to 1.1 + /- 4.0 % and 4.0 + /- 5.1 % , respectively . Results of a last-observation-carried-forward analysis found that women in the manual group lost significantly ( p < 0.05 ) more weight ( at both times ) than those treated by eDiets.com . ( Results , however , of baseline-carried-forward and completers analyses did not reach statistical significance . ) There were no significant differences between groups in changes in cardiovascular risk factors or quality of life . DISCUSSION This study provides consumers with important information about the probable benefits they can expect from participating in a popular Internet-based weight loss program OBJECTIVE To assess the efficacy of a Web-based tailored behavioral weight management program compared with Web-based information-only weight management material s. RESEARCH METHODS AND PROCEDURES Participants , 2862 eligible overweight and obese ( BMI = 27 to 40 kg/m2 ) members from four regions of Kaiser Permanente 's integrated health care delivery system , were r and omized to receive either a tailored expert system or information-only Web-based weight management material s. Weight change and program satisfaction were assessed by self-report through an Internet-based survey at 3- and 6-month follow-up periods . RESULTS Significantly greater weight loss at follow-up was found among participants assigned to the tailored expert system than among those assigned to the information-only condition . Subjects in the tailored expert system lost a mean of 3 + /- 0.3 % of their baseline weight , whereas subjects in the information-only condition lost a mean of 1.2 + /- 0.4 % ( p < 0.0004 ) . Participants were also more likely to report that the tailored expert system was personally relevant , helpful , and easy to underst and . Notably , 36 % of enrollees were African-American , with enrollment rates higher than the general proportion of African Americans in any of the study regions . DISCUSSION The results of this large , r and omized control trial show the potential benefit of the Web-based tailored expert system for weight management compared with a Web-based information-only weight management program OBJECTIVE The objective was to examine the efficacy of adding a technology-based program to an in-person , behavioral weight loss intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven subjects ( BMI = 33.1+/-2.8 kg/m2 ; age=41.3+/-8.7 years ) participated in a 12-week intervention with r and om assignment to St and ard In-Person Behavioral Weight Control Program ( SBWP ) or Intermittent or Continuous Technology-Based Program ( INT-TECH , CON-TECH ) . SBWP subjects received seven individualized weight loss sessions encouraging dietary and exercise modifications . INT-TECH and CON-TECH subjects received all SBWP components ; additionally , these groups used a SenseWear Pro Armb and ( BodyMedia , Inc. ) to monitor energy expenditure and an Internet-based program to monitor eating behaviors . These features were used by INT-TECH subjects during weeks 1 , 5 , and 9 and CON-TECH subjects weekly throughout the intervention . RESULTS Intent-to-treat analysis revealed weight loss of 4.1+/-2.8 kg , 3.4+/-3.4 kg , and 6.2+/-4.0 kg , for SBWP , INT-TECH , and CON-TECH groups , respectively ( CON-TECH > INT-TECH , p < or=0.05 ) . DISCUSSION These results indicate that the technology-based program needs to be used continuously throughout the intervention period to significantly impact weight loss . Future studies should examine the long-term and independent effect of this technology on weight loss , and for whom this intervention format is most effective 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 CONTEXT Behavioral weight loss interventions achieve short-term success , but re-gain is common . OBJECTIVE To compare 2 weight loss maintenance interventions with a self-directed control group . DESIGN , SETTING , AND PARTICIPANTS Two-phase trial in which 1032 overweight or obese adults ( 38 % African American , 63 % women ) with hypertension , dyslipidemia , or both who had lost at least 4 kg during a 6-month weight loss program ( phase 1 ) were r and omized to a weight-loss maintenance intervention ( phase 2 ) . Enrollment at 4 academic centers occurred August 2003-July 2004 and r and omization , February-December 2004 . Data collection was completed in June 2007 . INTERVENTIONS After the phase 1 weight-loss program , participants were r and omized to one of the following groups for 30 months : monthly personal contact , unlimited access to an interactive technology-based intervention , or self-directed control . Main Outcome Changes in weight from r and omization . RESULTS Mean entry weight was 96.7 kg . During the initial 6-month program , mean weight loss was 8.5 kg . After r and omization , weight regain occurred . Participants in the personal-contact group regained less weight ( 4.0 kg ) than those in the self-directed group ( 5.5 kg ; mean difference at 30 months , -1.5 kg ; 95 % confidence interval [ CI ] , -2.4 to -0.6 kg ; P = .001 ) . At 30 months , weight regain did not differ between the interactive technology-based ( 5.2 kg ) and self-directed groups ( 5.5 kg ; mean difference -0.3 kg ; 95 % CI , -1.2 to 0.6 kg ; P = .51 ) ; however , weight regain was lower in the interactive technology-based than in the self-directed group at 18 months ( mean difference , -1.1 kg ; 95 % CI , -1.9 to -0.4 kg ; P = .003 ) and at 24 months ( mean difference , -0.9 kg ; 95 % CI , -1.7 to -0.02 kg ; P = .04 ) . At 30 months , the difference between the personal-contact and interactive technology-based group was -1.2 kg ( 95 % CI -2.1 to -0.3 ; P = .008 ) . Effects did not differ significantly by sex , race , age , and body mass index subgroups . Overall , 71 % of study participants remained below entry weight . CONCLUSIONS The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level . Monthly brief personal contact provided modest benefit in sustaining weight loss , whereas an interactive technology-based intervention provided early but transient benefit . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00054925 This pilot study examined the acceptability and feasibility of conducting a weight loss maintenance intervention over the Internet . Obese adults participated in a 15-week behavioral weight control intervention and were then r and omly assigned to one of the following three maintenance conditions : ( a ) in-person , therapist-led ( TL ) ; ( b ) Internet , therapist-led ( I ) ; and ( c ) control ( C ) . Both maintenance interventions met biweekly for 22 weeks using the same program content . Results showed that TL participants were more likely to attend their meetings and feel more satisfied with their group assignment . Ho wever , there were no differences between the TL and I groups in overall attrition or number of peer support contacts made . There was also no significant difference in weight loss between the groups . Thus , the Internet may hold promise as a method for maintaining contact with patients to facilitate long-term behavior change OBJECTIVE The purpose of this study was to compare weight regain in a group of perimenopausal women ( 48.0+/-4.4 years old ) , r and omized to a 12-month weight maintenance Internet intervention or to self-directed weight maintenance after a 4-month weight loss treatment . METHODS AND PROCEDURES After a 4-month behavioral weight loss program , 135 women were r and omized to either Internet or self-directed groups . The Internet group ( n=66 ) used a website to gain information and complete logs concerning their weight , diet , and exercise progress over a 12-month follow-up . The 69 self-directed women had no contact with study staff . All women were measured for weight and body composition , and diet intake , and were interviewed using the 7-day physical activity question naires at baseline , 4 months , and 16 months . RESULTS At the end of the 12-month follow-up , the Internet and self-directed groups had regained on average 0.4+/-5.0 kg and 0.6+/-4.0 kg , respectively ( P=0.5 ) . In within-group analyses , Internet diet-log entries were correlated with follow-up weight change ( r=-0.29 ; P<0.05 ) and moderately with change in exercise energy expenditure ( EEE ; r=0.44 ; P<0.01 ) . Follow-up weight change was not correlated with change in dietary intake . DISCUSSION While significant weight loss was maintained over follow-up by both groups of women , Internet use did not surpass self-direction in helping to sustain weight loss . Among Internet users , Internet use was related to weight change and EEE |
13,020 | 22,516,495 | CONCLUSIONS Collaborative care models are effective in achieving clinical ly meaningful improvements in depression outcomes and public health benefits in a wide range of population s , setting s , and organizations . | CONTEXT To improve the quality of depression management , collaborative care models have been developed from the Chronic Care Model over the past 20 years .
Collaborative care is a multicomponent , healthcare system-level intervention that uses case managers to link primary care providers , patients , and mental health specialists .
In addition to case management support , primary care providers receive consultation and decision support from mental health specialists ( i.e. , psychiatrists and psychologists ) .
This collaboration is design ed to ( 1 ) improve routine screening and diagnosis of depressive disorders ; ( 2 ) increase provider use of evidence -based protocol s for the proactive management of diagnosed depressive disorders ; and ( 3 ) improve clinical and community support for active client/patient engagement in treatment goal - setting and self-management . | BACKGROUND Depression is a highly prevalent , often recurring or persistent disorder . The majority of patients are initially seen and treated in primary care . Effective treatments are available , but possibilities for providing adequate follow-up care are often limited in this setting . This study assesses the effectiveness of primary -care-based enhanced treatment modalities on short-term patient outcomes . METHOD In a r and omized controlled trial we evaluated a psycho-educational self-management intervention . We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder , assessed by a structured psychiatric interview . Patients were r and omly assigned to : the Depression Recurrence Prevention ( DRP ) program ( n=112 ) ; a combination of the DRP program with psychiatric consultation ( PC+DRP , n=39 ) ; a combination with brief cognitive behavior therapy ( CBT+DRP , n=44 ) ; and care as usual ( CAU , n=72 ) . Follow-up assessment s were made at 3 months ( response 90 % ) and 6 months ( 85 % ) . RESULTS Patient acceptance of enhanced care was good . The mean duration of the index episode was 11 weeks ( S.D.=9.78 ) and similar in CAU and enhanced care . Recovery rate after 6 months was 67 % overall ; 17 % of all participants remained depressed for the entire 6-month period . CONCLUSION Enhanced care did not result in better short-term outcomes . We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program . Observed depression treatment rates in CAU were high Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies OBJECTIVE To compare liaison psychiatric nursing with usual medical care in the management of older medical in patients who screen positive for depression . DESIGN Pragmatic r and omised controlled trial . SETTING Medical wards of UK district general hospital in rural East Anglia . PARTICIPANTS One hundred and thirty-eight medical in patients aged 65 + screened positive on the 15-item geriatric depression scale ( GDS ) . One hundred and twenty-one out of 138 screen positives entered the trial ( 58/121 fulfilled criteria for depressive disorder at baseline ) . INTERVENTIONS ( i ) A liaison psychiatric nurse assessed participants , formulated a care plan for treatment of their depression , ensured its implementation through liaison with appropriate agencies , and monitored participants ' mood and response to treatment for up to 12 weeks . ( ii ) Usual treatment by hospital and primary care staff . MAIN OUTCOME MEASURES ICD-10 depressive disorder , change in GDS-15 score , quality -adjusted life weeks ( QALWs ) and patient satisfaction rating . RESULTS Eighty-six out of 121 participants completed the 16-week trial . Participants in the intervention group were more satisfied with their care , but no significant differences in depressive disorder , depression rating or QALWs gained were found between groups . However , there was a trend towards improvement in the intervention group and effect sizes were higher in the subgroup with depressive disorder . CONCLUSIONS This study is the first RCT to evaluate liaison psychiatric nursing specifically for depression in older medical in patients ; the findings suggest improvement in mental health and quality of life , but a larger trial is required to provide convincing evidence OBJECTIVE This study evaluated the effectiveness of a structured telephone-based care management program for patients in a prepaid health plan receiving new antidepressant prescriptions from psychiatrists . METHODS Potential participants were identified with computerized medical records and contacted by telephone . Eligible and consenting participants were r and omly assigned to continued usual care ( N=104 ) or to a three-session telephone care management program ( N=103 ) . Care management contacts included assessment of depressive symptoms , medication adherence , and medication side effects with structured feedback to treating psychiatrists . Effectiveness was assessed three and six months after r and omization by blinded telephone assessment s ( depression scale on the Hopkins Symptom Checklist [ SCL ] and patient-rated global improvement ) . Computerized records were used to assess medication adherence and frequency of in-person follow-up visits . RESULTS Compared with usual care , the care management intervention had no significant effect on the mean score of the SCL depression scale at six months , on the probability of 50 percent improvement in depressive symptoms ( 41 percent for care management and 37 percent for usual care ) , or on the probability of patient-rated improvement ( 57 percent for care management and 52 percent for usual care ) . Patients assigned to care management made significantly more medication management visits over six months ( 2.4 visits compared with 2.0 visits ; p=.035 ) , but there were no significant differences in rates of adequate medication treatment . CONCLUSIONS This study found that a low-intensity telephone care management program did not appear to significantly improve clinical outcomes for patients starting antidepressant treatment . Compared with findings from earlier primary care studies , this study found that patients receiving care from a psychiatrist received more intensive treatment , although many still experienced poor outcomes Background and Purpose — Poststroke depression is a prevalent and disabling disorder , yet evidence regarding the effectiveness of treating poststroke depression is inconclusive . Our objective was to determine the effectiveness of the Activate-Initiate-Monitor care management program for the treatment of poststroke depression . Methods — We conducted a prospect i ve , r and omized , outcome -blinded trial in 188 ischemic stroke survivors identified at the time of admission to one of 4 Indianapolis hospitals . Depression screening and enrollment occurred between 1 and 2 months poststroke . The Activate-Initiate-Monitor intervention was a care management program that included Activation of the patient to recognize depression symptoms and accept treatment , Initiation of an antidepressant medication , and Monitoring and adjusting treatment . Usual care subjects received nondepression-related education and were prescribed antidepressants at the discretion of their provider . The primary outcome measure was depression response , defined as a Hamilton Depression Inventory score < 8 ( remission ) or a decrease from baseline of at least 50 % at 12 weeks . Results — Intervention and usual care groups did not differ on any key baseline measures . Both depression response ( 51 % versus 30 % , P=0.005 ) and remission ( 39 % versus 23 % , P=0.01 ) were more likely in the Activate-Initiate-Monitor intervention than in the usual care group . This difference in depression scores was present by 6 weeks and persisted through the 12-week assessment . Serious adverse events did not differ between the 2 groups . Conclusion — The Activate-Initiate-Monitor care management model is significantly more effective than usual care in improving depression outcomes in patients with poststroke depression BACKGROUND Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer , but evidence to guide its management is scarce . We aim ed to assess the efficacy and cost of a nurse-delivered complex intervention that was design ed to treat major depressive disorder in patients who have cancer . METHODS We did a r and omised trial in a regional cancer centre in Scotl and , UK . 200 out patients who had cancer with a prognosis of greater than 6 months and major depressive disorder ( identified by screening ) were eligible and agreed to take part . Their mean age was 56.6 ( SD 11.9 ) years , and 141 ( 71 % ) were women . We r and omly assigned 99 of these participants to usual care , and 101 to usual care plus the intervention , with minimisation for sex , age , diagnosis , and extent of disease . The intervention was delivered by a cancer nurse at the centre over an average of seven sessions . The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale ( range 0 to 4 ) at 3 months after r and omisation . Analysis was by intention to treat . This trial is registered as IS RCT N84767225 . FINDINGS Primary outcome data were missing for four patients . For 196 patients for whom we had data at 3 months , the adjusted difference in mean Symptom Checklist-20 depression score , between those who received the intervention and those who did not , was 0.34 ( 95 % CI 0.13 - 0.55 ) . This treatment effect was sustained at 6 and 12 months . The intervention also improved anxiety and fatigue but not pain or physical functioning . It cost an additional pound sterling 5278 ( US$ 10 556 ) per quality -adjusted life-year gained . INTERPRETATION The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible , acceptable , and potentially cost effective The purpose of this study was to examine the impact of the Unified Psychogeriatric Biopsychosocial Evaluation and Treatment ( UPBEAT ) Program , an interdisciplinary mental health care management program , on the behavioral health symptoms of elderly veterans . Participants , 60 years and older , included 2637 veterans recruited from medical/surgical units who screened positively for significant depressive or anxiety symptoms and /or at-risk alcohol drinking . Participants were r and omized to UPBEAT or to usual care . Primary outcomes were measured at baseline and at 6 , 12 , and 24 months . Participant nonadherence to the protocol was common and is a major limitation . There were no differences between UPBEAT and usual care patients on symptom or functional outcomes at any follow-up point . Exploratory analyses suggested that among participants with more physical health problems , there were greater improvements in depressive symptoms in those assigned to UPBEAT care . Despite a theoretical and practically sound intervention , participation was low and treatment outcomes , while generally good , appeared unaffected by the addition of the program PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P < .01 ) , lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P < .01 ) , and lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P < .01 ) compared with participants in the usual care group at 6 weeks . Compared with the usual care group , the proportion of participants in the intervention group who had 80 % or greater adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P < .01 ) and to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P < .001 ) was greater at 6 weeks . CONCLUSION A pilot , r and omized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources OBJECTIVE To evaluate the effect on depressive symptoms in cardiac patients of patient-specific advice to general practitioners regarding management of comorbid depression . DESIGN AND SETTING A r and omised controlled trial in four general hospitals in Adelaide , South Australia . PARTICIPANTS Patients ( n = 669 ) admitted to cardiology units for a range of cardiovascular conditions who were screened and assessed as being depressed according to the Center for Epidemiological Studies Depression Scale ( CES-D ) . INTERVENTION Inpatient psychiatric review , followed by telephone case conferencing between specialist hospital staff and GPs to provide patient-specific information about the patient 's depression and its management , educational material , and ongoing clinical support . MAIN OUTCOME MEASURES Level of depression severity at 12 months post-hospitalisation . RESULTS On the basis of intention to treat , intervention patients had lower rates of moderate to severe depression ( CES-D > or = 27 ) after 12 months ( 25 % v 35 % , relative risk , 0.72 ; 95 % CI , 0.54 - 0.96 , number needed to treat for benefit , 11 ) . The intervention was most effective in preventing progression from mild depression to moderate to severe depression . The multidisciplinary telephone case conferencing was difficult to implement and , in a post hoc analysis , brief phone advice from a psychiatrist was found to be effective . CONCLUSIONS Screening hospitalised cardiac patients for depression and providing targeted advice to their GPs reduces depression severity 12 months after hospitalisation In a pilot study , 55 low-income Latina patients with breast or cervical cancer and comorbid depression were r and omly assigned to receive collaborative care as part of the Multifaceted Oncology Depression Program or usual care . Relative to patients in the usual care condition , patients receiving collaborative care were more likely to show > or=50 % improvement in depressive symptoms as measured by the Personal Health Question naire ( OR=4.51 , 95 % CI=1.07 - 18.93 ) . Patients in the collaborative care program were also more likely to show improvement in emotional well-being ( increase of 2.15 ) as measured by the Functional Assessment of Cancer Therapy Scale than were those receiving usual care ( decrease of 0.50 ) ( group difference=2.65 , 95 % CI : 0.18 - 5.12 ) . Despite health system , provider , and patient barriers to care , these initial results suggest that patients in public sector oncology clinics can benefit from onsite depression treatment OBJECTIVE To evaluate the impact of primary care group visits ( chronic care clinics ) on the process and outcome of care for diabetic patients . RESEARCH DESIGN AND METHODS We evaluated the intervention in primary care practice s r and omized to intervention and control groups in a large-staff model health maintenance organization ( HMO ) . Patients included diabetic patients > or = 30 years of age in each participating primary care practice , selected at r and om from an automated diabetes registry . Primary care practice s were r and omized within clinics to either a chronic care clinic ( intervention ) group or a usual care ( control ) group . The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor 's practice . Chronic care clinics consisted of st and ardized assessment s ; visits with the primary care physician , nurse , and clinical pharmacist ; and a group education/peer support meeting . We collected self-report question naires from patients and data from administrative systems . The question naires were mailed , and telephoned interviews were conducted for nonrespondents , at baseline and at 12 and 24 months ; we queried the process of care received , the satisfaction with care , and the health status of each patient . Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems . RESULTS In an intention-to-treat analysis at 24 months , the intervention group had received significantly more recommended preventive procedures and helpful patient education . Of five primary health status indicators examined , two ( SF-36 general health and bed disability days ) were significantly better in the intervention group . Compared with control patients , intervention patients had slightly more primary care visits , but significantly fewer specialty and emergency room visits . Among intervention participants , we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes , including patient satisfaction and HbA1c levels . CONCLUSIONS Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes CONTEXT Although guideline -concordant depression treatment is clearly effective , treatment often falls short of evidence -based recommendations . Organized depression care programs significantly improve treatment quality , but employer purchasers have been slow to adopt these programs based on lack of evidence for cost-effectiveness from their perspective . OBJECTIVE To evaluate the effects of a depression outreach-treatment program on workplace outcomes , a concern to employers . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial involving 604 employees covered by a managed behavioral health plan were identified in a 2-stage screening process as having significant depression . Patient treatment allocation was concealed and assessment of depression severity and work performance at months 6 and 12 was blinded . Employees with lifetime bipolar disorder , substance disorder , recent mental health specialty care , or suicidality were excluded . INTERVENTION A telephonic outreach and care management program encouraged workers to enter outpatient treatment ( psychotherapy and /or antidepressant medication ) , monitored treatment quality continuity , and attempted to improve treatment by giving recommendations to providers . Participants reluctant to enter treatment were offered a structured telephone cognitive behavioral psychotherapy . MAIN OUTCOME MEASURES Depression severity ( Quick Inventory of Depressive Symptomatology , QIDS ) and work performance ( World Health Organization Health and Productivity Question naire [ HPQ ] , a vali date d self-report instrument assessing job retention , time missed from work , work performance , and critical workplace incidents ) . RESULTS Combining data across 6- and 12-month assessment s , the intervention group had significantly lower QIDS self-report scores ( relative odds of recovery , 1.4 ; 95 % confidence interval , 1.1 - 2.0 ; P = .009 ) , significantly higher job retention ( relative odds , 1.7 ; 95 % confidence interval , 1.1 - 3.3 ; P = .02 ) , and significantly more hours worked among the intervention ( beta=2.0 ; P=.02 ; equivalent to an annualized effect of 2 weeks of work ) than the usual care groups that were employed . CONCLUSIONS A systematic program to identify depression and promote effective treatment significantly improves not only clinical outcomes but also workplace outcomes . The financial value of the latter to employers in terms of recovered hiring , training , and salary costs suggests that many employers would experience a positive return on investment from outreach and enhanced treatment of depressed workers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00057590 CONTEXT Older adults with social isolation , medical comorbidity , and physical impairment are more likely to be depressed but may be less able to seek appropriate care for depression compared with older adults without these characteristics . OBJECTIVE To determine the effectiveness of a home-based program of detecting and managing minor depression or dysthymia among older adults . DESIGN AND SETTING R and omized controlled trial with recruitment through community senior service agencies in metropolitan Seattle , Wash , from January 2000 to May 2003 . PATIENTS One hundred thirty-eight patients aged 60 years or older with minor depression ( 51.4 % ) or dysthymia ( 48.6 % ) . Patients had a mean of 4.6 ( SD , 2.1 ) chronic medical conditions ; 42 % of the sample belonged to a racial/ethnic minority , 72 % lived alone , 58 % had an annual income of less than 10 000 dollars , and 69 % received a form of home assistance . INTERVENTIONS Patients were r and omly assigned to the Program to Encourage Active , Rewarding Lives for Seniors ( PEARLS ) intervention ( n = 72 ) or usual care ( n = 66 ) . The PEARLS intervention consisted of problem-solving treatment , social and physical activation , and potential recommendations to patients ' physicians regarding antidepressant medications . MAIN OUTCOME MEASURES Assessment s of depression and quality of life at 12 months compared with baseline . RESULTS At 12 months , compared with the usual care group , patients receiving the PEARLS intervention were more likely to have at least a 50 % reduction in depressive symptoms ( 43 % vs 15 % ; odds ratio [ OR ] , 5.21 ; 95 % confidence interval [ CI ] , 2.01 - 13.49 ) , to achieve complete remission from depression ( 36 % vs 12 % ; OR , 4.96 ; 95 % CI , 1.79 - 13.72 ) , and to have greater health-related quality -of-life improvements in functional well-being ( P = .001 ) and emotional well-being ( P = .048 ) . CONCLUSIONS The PEARLS program , a community-integrated , home-based treatment for depression , significantly reduced depressive symptoms and improved health status in chronically medically ill older adults with minor depression and dysthymia BACKGROUND Two instruments commonly used in primary care research to measure depressive severity are the Patient Health Question naire-9 ( PHQ-9 ) and the Hopkins Symptom Checklist-20 ( HSCL-20 ) . However , there is little information regarding the relationship between clinical information derived from these scales . The present study investigates the psychometric properties of the PHQ-9 and HSCL-20 , determines the degree of instrument concordance , and describes the factor structure of the HSCL-20 . METHODS A secondary data analysis from a r and omized controlled trial was performed . A total of 405 primary care patients with major depressive disorder and /or dysthymia were administered the PHQ-9 and the HSCL-20 when recruited for the study . RESULTS Good internal consistency reliability estimates were obtained for both scales ( PHQ-9 alpha=0.803 ; HSCL-20 alpha=0.837 ) . All PHQ-9 inter-item and corrected item-total correlations showed that no item detracted from overall scale functioning . HSCL-20 items assessing overeating , poor appetite , and sexual interest were poorly correlated with other items and with the total scale score . A positive , moderate strength relationship was found between the instruments ( r=0.54 , p<0.0001 ) . Exploratory factor analysis of the HSCL-20 yielded a six-factor structure , which accounted for almost 63 % of the variance in total score . The largest contribution to common variance in the scale was provided by an " anxiety and self-reproach " factor . CONCLUSIONS PHQ-9 and HSCL-20 total scores were moderately correlated . Although the HSCL-20 is utilized as a measure of depression severity , it may lack sufficient specificity to be an accurate reflection of depression status per se OBJECTIVE To determine the clinical effectiveness of a nurse-led mental health liaison service in managing mental health problems in older physically ill in patients . DESIGN R and omised controlled trial . SETTING Four general medical wards in a district general hospital in a northern UK town . PARTICIPANTS 153 medically ill older people ( aged 65 or over ) who scored above the threshold for depression and /or cognitive impairment on a brief screening instrument ( 4-item geriatric depression scale and 6-item orientation-memory-concentration test ) : 77 were r and omised to a nurse-led intervention and 76 to usual care . Included in the analysis were 120 participants who completed 6 - 8 week follow-up assessment s. INTERVENTION Multi-faceted intervention led by a mental health liaison nurse . MAIN OUTCOME MEASURES Scores on the Health of the Nation Outcome Scale 65 + , the geriatric depression scale , and the St and ardised Mini-Mental State Examination . RESULTS No significant differences were found between groups on the total Health of the Nation Outcome Scale 65 + scores ( 11.5 versus 11.5 , adjusted mean difference -0.04 , 95 % CI-1.4 to 1.3 , P = 0.96 ) nor on the St and ardised Mini-Mental State Examination ( 20.3 versus 21.8 , adjusted mean difference -0.4 , 95 % CI-2.1 to 1.3 , P = 0.63 ) . Subjects r and omised to the intervention arm had significantly lower Geriatric Depression Scale scores at 6 - 8 week follow-up than those receiving usual care ( 12.2 versus 14.0 , adjusted mean difference -2.0 , 95 % CI-4.0 to -0.1 , P = 0.043 ) . CONCLUSIONS Nurse-led mental health liaison services which accept all screened cases from acute medical wards are unlikely to be effective in reducing general psychiatric morbidity . Services which focus on the prevention of delirium and target particular patient groups or disorders such as depression are more likely to be effective ABSTRACT A prospect i ve r and omized trial was conducted to examine the effectiveness , feasibility , and degree of implementation of home health care quality improvement interventions when implemented under usual conditions by usual care providers . A total of 311 older adults were r and omized to enhanced usual care ( EUC ) that included routine depression screening and staff training in depression care management for older adults or to the intervention group ( INT ) that included antidepressants and /or psychotherapy treatment plus EUC . Implementing a routine screening protocol using the PHQ-9 and depression care management quality improvements is feasible in diverse home health care organizations and results in consistently better ( but not statistically significant ) depression outcomes in the INT group CONTEXT Depression co-occurring with diabetes mellitus is associated with higher health services costs , suggesting that more effective depression treatment might reduce use of other medical services . OBJECTIVE To evaluate the incremental cost and cost-effectiveness of a systematic depression treatment program among out patients with diabetes . DESIGN R and omized controlled trial comparing systematic depression treatment program with care as usual . SETTING Primary care clinics of group-model prepaid health plan . PATIENTS A 2-stage screening process identified 329 adults with diabetes and current depressive disorder . INTERVENTION Specialized nurses delivered a 12-month , stepped-care depression treatment program beginning with either problem-solving treatment psychotherapy or a structured antidepressant pharmacotherapy program . Subsequent treatment ( combining psychotherapy and medication , adjustments to medication , and specialty referral ) was adjusted according to clinical response . MAIN OUTCOME MEASURES Depressive symptoms were assessed by blinded telephone assessment s at 3 , 6 , 12 , and 24 months . Health service costs were assessed using health plan accounting records . RESULTS Over 24 months , patients assigned to the intervention accumulated a mean of 61 additional days free of depression ( 95 % confidence interval [ CI ] , 11 to 82 days ) and had outpatient health services costs that averaged $ 314 less ( 95 % CI , $ 1007 less to $ 379 more ) compared with patients continuing in usual care . When an additional day free of depression is valued at $ 10 , the net economic benefit of the intervention is $ 952 per patient treated ( 95 % CI , $ 244 to $ 1660 ) . CONCLUSIONS For adults with diabetes , systematic depression treatment significantly increases time free of depression and appears to have significant economic benefits from the health plan perspective . Depression screening and systematic depression treatment should become routine components of diabetes care Abstract OBJECTIVE : To compare collaborative care for treatment of depression in primary care with consult-liaison ( CL ) care . In collaborative care , a mental health team provided a treatment plan to the primary care provider , telephoned patients to support adherence to the plan , review ed treatment results , and suggested modifications to the provider . In CL care , study clinicians informed the primary care provider of the diagnosis and facilitated referrals to psychiatry residents practicing in the primary care clinic . DESIGN : Patients were r and omly assigned to treatment model by clinic firm . SETTING : VA primary care clinic . PARTICIPANTS : One hundred sixty-eight collaborative care and 186 CL patients who met criteria for major depression and /or dysthymia . MEASUREMENTS : Hopkins Symptom Checklist ( SCL-20 ) , Short Form (SF)-36 , Sheehan Disability Scale . MAIN RESULTS : Collaborative care produced greater improvement than CL in depressive symptomatology from baseline to 3 months ( SCL-20 change scores ) , but at 9 months there was no significant difference . The intervention increased the proportion of patients receiving prescriptions and cognitive behavioral therapy . Collaborative care produced significantly greater improvement on the Sheehan at 3 months . A greater proportion of collaborative care patients exhibited an improvement in SF-36 Mental Component Score of 5 points or more from baseline to 9 months . CONCLUSIONS : Collaborative care result ed in more rapid improvement in depression symptomatology , and a more rapid and sustained improvement in mental health status compared to the more st and ard model . Mounting evidence indicates that collaboration between primary care providers and mental health specialists can improve depression treatment and supports the necessary changes in clinic structure and incentives PURPOSE To determine the effectiveness of the Alleviating Depression Among Patients With Cancer ( ADAPt-C ) collaborative care management for major depression or dysthymia . PATIENTS AND METHODS Study patients included 472 low-income , predominantly female Hispanic patients with cancer age > or= 18 years with major depression ( 49 % ) , dysthymia ( 5 % ) , or both ( 46 % ) . Patients were r and omly assigned to intervention ( n = 242 ) or enhanced usual care ( EUC ; n = 230 ) . Intervention patients had access for up to 12 months to a depression clinical specialist ( supervised by a psychiatrist ) who offered education , structured psychotherapy , and maintenance/relapse prevention support . The psychiatrist prescribed antidepressant medications for patients preferring or assessed to require medication . RESULTS At 12 months , 63 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline as assessed by the Patient Health Question naire-9 ( PHQ-9 ) depression scale compared with 50 % of EUC patients ( odds ratio [ OR ] = 1.98 ; 95 % CI , 1.16 to 3.38 ; P = .01 ) . Improvement was also found for 5-point decrease in PHQ-9 score among 72.2 % of intervention patients compared with 59.7 % of EUC patients ( OR = 1.99 ; 95 % CI , 1.14 to 3.50 ; P = .02 ) . Intervention patients also experienced greater rates of depression treatment ( 72.3 % v 10.4 % of EUC patients ; P < .0001 ) and significantly better quality -of-life outcomes , including social/family ( adjusted mean difference between groups , 2.7 ; 95 % CI , 1.22 to 4.17 ; P < .001 ) , emotional ( adjusted mean difference , 1.29 ; 95 % CI , 0.26 to 2.22 ; P = .01 ) , functional ( adjusted mean difference , 1.34 ; 95 % CI , 0.08 to 2.59 ; P = .04 ) , and physical well-being ( adjusted mean difference , 2.79 ; 95 % CI , 0.49 to 5.1 ; P = .02 ) . CONCLUSION ADAPt-C collaborative care is feasible and results in significant reduction in depressive symptoms , improvement in quality of life , and lower pain levels compared with EUC for patients with depressive disorders in a low-income , predominantly Hispanic population in public sector oncology clinics OBJECTIVE The authors developed , implemented , and pilot-tested intervention programs to provide effective care for chronic or recurrent depression . METHODS A total of 104 patients with chronic or recurrent depression were r and omly assigned to one of four groups : continued usual behavioral health care , usual care plus telephone monitoring and care management by a care manager , usual care plus care management plus a peer-led chronic-disease self-management group program , or usual care plus care management plus a professionally led depression psychotherapy group . Outcomes in intent-to-treat analyses were assessed at three , six , nine , and 12 months and included treatment participation rates , Hopkins Symptom Checklist depression scale scores , major depression ( Structured Clinical Interview for DSM-IV ) , Patient-Rated Global Improvement ratings , treatment satisfaction , and adequacy of medication . RESULTS Participation in care management was high in the three intervention groups . Close to 60 % of participants invited to both group interventions attended at least an initial meeting , but a greater number assigned to the care management plus the professionally led group continued participation through the 12-month period . The sample was too small to reliably detect small or moderate differences in clinical outcomes , but various measures consistently favored the care management plus professionally led group . CONCLUSIONS It is feasible to direct additional intervention services to patients with persistent or recurring depression . A larger trial of organized self-management support for chronic depression will be necessary for a definitive evaluation of program effectiveness Background : This study evaluated a multifaceted psychiatric intervention targeted at the complex medically ill identified by means of the INTERMED , an instrument to assess case complexity . Methods : Of 885 rheumatology in patients and diabetes out patients who were assessed for eligibility , 247 were identified as complex ( INTERMED score > 20 ) and r and omized to the intervention ( n = 125 , 84 rheumatology and 41 diabetes patients ) or care as usual ( n = 122 , 78 rheumatology and 44 diabetes patients ) . For the majority of the cases the multifaceted intervention consisted of an intervention conducted by a psychiatric liaison nurse and /or of referral to a liaison psychiatrist , followed by advice to the treating physician or organization of a multidisciplinary case conference . Baseline and follow-up at months 3 , 6 , 9 and 12 measured prevalence of major depression ( Mini-International Neuropsychiatric Interview ) , depressive symptoms ( Center for Epidemiological Studies Depression Rating Scale ) , physical and mental health ( SF-36 ) , quality of life ( EuroQol ) , health care utilization and HbA1c levels ( diabetic patients ) . Results : Prevalence of major depression was reduced from 61 % ( T0 ) to 28 % ( T4 ) in the intervention group and remained stable in care as usual ( 57 % at T0 to 50 % at T4 ) . Compared to care as usual , significant improvement over time was observed in the intervention group with regard to depressive symptoms ( F = 11.9 ; p = 0.001 ) , perception of physical ( F = 5.7 ; p = 0.018 ) and mental health ( F = 3.9 ; p = 0.047 ) and quality of life ( F = 21.8 ; p < 0.001 ) . Effects tended to be stronger in diabetes patients , in patients with baseline major depression and in patients with moderate INTERMED scores . Finally , hospital admissions occurred less often in the intervention group , reaching statistical significance for the period between 6 and 9 months of follow-up ( p = 0.02 ) . Conclusions : The results suggest that a psychiatric intervention targeted for complex medical patients can improve health outcomes BACKGROUND Depression is the most common mental health disorder in people aged over 65 years . Late-life depression is associated with chronic illness and disability . AIM To investigate the feasibility of a collaborative care model for depression in older people in a primary care setting . DESIGN OF STUDY R and omised controlled trial with 16-weeks follow up . SETTING A primary care trust in Manchester . METHOD Participants were 105 people aged 60 years or older who scored 5 or more on the Geriatric Depression Scale ; 53 were r and omly allocated to an intervention group and 52 to a usual care group . The intervention group received care managed by a community psychiatric nurse who delivered an intervention comprising a facilitated self-help programme with close liaison with primary care professionals and old-age psychiatry according to a defined protocol . The usual care group received usual GP care . A nested qualitative study explored the views of the health professionals and patients regarding the acceptability and effectiveness of the intervention . RESULTS The main outcome measure was recovery from depression . Patients in the intervention group were less likely to suffer from major depressive disorder at follow up compared with usual care ( 0.32 , 95 % confidence = interval = 0.11 to 0.93 , P = 0.036 ) . The qualitative component of the study demonstrated the acceptability of the intervention to patients . CONCLUSION A model of collaborative care for older people with depression , used in a primary care setting with a facilitated self-help intervention is more effective than usual GP care . This study demonstrates that the implementation of a collaborative care model is feasible in UK primary care and that the intervention is effective and acceptable to patients M eeting the complex needs of patients with chronic illness or impairment is the single greatest challenge facing organized medical practice . Usual care is not doing the job ; dozens of surveys and audits have revealed that sizable proportions of chronically ill patients are not receiving effective therapy , have poor disease con- trol , and are unhappy with their care ( 1 ) . Results of r and omized trials also show that effective disease management programs can achieve substantially better outcomes than usual care , the control intervention . These trials , along with the ideas and efforts for improvement discussed in this issue , show that we can improve care and outcomes . As the articles suggest , these improvements will not come easily . If we are to improve care for most patients with chronic illness , the evidence strongly suggests that we reshape our ambulatory care systems for this purpose . Pri- mary care practice was largely design ed to provide ready access and care to patients with acute , varied problems , with an emphasis on triage and patient flow ; short appointments ; diagnosis and treatment of symptoms and signs ; reliance on laborato- ry investigations and prescriptions ; brief , didactic patient education ; and patient- initiated follow-up . Patients and families struggling with chronic illness have differ- ent needs , and these needs are unlikely to be met by an acute care organization and culture . They require planned , regular interactions with their caregivers , with a focus on function and prevention of exacerbations and complications . This interac- tion includes systematic assessment s , attention to treatment guidelines , and behav- iorally sophisticated support for the patient 's role as self-manager . These interactions must be linked through time by clinical ly relevant information systems and continu- ing follow-up initiated by the medical practice . Comprehensive System Depression is a serious mental health problem for older adults . This study examined the effectiveness of an Advanced Practice Psychiatric Nurse (APPN)- Primary Care Physician ( PCP ) collaborative model to provide care to homebound elders with depressive symptoms . One hundred seventy nine individuals were screened for depression revealing an incidence of 46 % . Of these , 83 ( 46 % ) were invited to participate in the study based on their depression scores ; 41 ( 49 % ) agreed to participate in the study . Significant improvement in depression scores occurred for those who received treatment . Treatment included pharmacological and psychosocial interventions . As the population over the age of 65 continues to grow , many more older adults will need mental health treatment , and creative methods to provide services to homebound individuals must be explored CONTEXT Depressive symptoms commonly follow coronary artery bypass graft ( CABG ) surgery and are associated with less positive clinical outcomes . OBJECTIVE To test the effectiveness of telephone-delivered collaborative care for post-CABG depression vs usual physician care . DESIGN , SETTING , AND PARTICIPANTS Single-blind effectiveness trial at 7 university-based and community hospitals in or near Pittsburgh , Pennsylvania . Participants were 302 post-CABG patients with depression ( 150 , intervention ; 152 , usual care ) and a comparison group of 151 r and omly sample d post-CABG patients without depression recruited between March 2004 and September 2007 and observed as out patients until June 2008 . INTERVENTION Eight months of telephone-delivered collaborative care provided by nurses working with patients ' primary care physicians and supervised by a psychiatrist and primary care physician from this study . MAIN OUTCOME MEASURES Mental health-related quality of life ( HRQL ) measured by the Short Form-36 Mental Component Summary ( SF-36 MCS ) at 8-month follow-up ; secondary outcome measures included assessment of mood symptoms ( Hamilton Rating Scale for Depression [ HRS-D ] ) , physical HRQL ( SF-36 PCS ) , and functional status ( Duke Activity Status Index [ DASI ] ) ; and hospital readmissions . RESULTS The intervention patients reported greater improvements in mental HRQL ( all P < or = .02 ) ( SF-36 MCS : Delta , 3.2 points ; 95 % confidence interval [ CI ] , 0.5 - 6.0 ) , physical functioning ( DASI : Delta , 4.6 points ; 95 % CI , 1.9 - 7.3 ) , and mood symptoms ( HRS-D : Delta , 3.1 points ; 95 % CI , 1.3 - 4.9 ) ; and were more likely to report a 50 % or greater decline in HRS-D score from baseline ( 50.0 % vs 29.6 % ; number needed to treat , 4.9 [ 95 % CI , 3.2 - 10.4 ] ) than usual care patients ( P < .001 ) . Men with depression were particularly likely to benefit from the intervention ( SF-36 MCS : Delta , 5.7 points ; 95 % CI , 2.2 - 9.2 ; P = .001 ) . However , the mean HRQL and physical functioning of intervention patients did not reach that of the nondepressed comparison group . CONCLUSION Compared with usual care , telephone-delivered collaborative care for treatment of post-CABG depression result ed in improved HRQL , physical functioning , and mood symptoms at 8-month follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00091962 OBJECTIVE To examine 9-year outcomes of implementation of short-term quality improvement ( QI ) programs for depression in primary care . DATA SOURCES Depressed primary care patients from six U.S. health care organizations . STUDY DESIGN Group-level , r and omized controlled trial . DATA COLLECTION Patients were r and omly assigned to short-term QI programs supporting education and re sources for medication management ( QI-Meds ) or access to evidence -based psychotherapy ( QI-Therapy ) ; and usual care ( UC ) . Of 1,088 eligible patients , 805 ( 74 percent ) completed 9-year follow-up ; results were extrapolated to 1,269 initially enrolled and living . Outcomes were psychological well-being ( Mental Health Inventory , five-item version [ MHI5 ] ) , unmet need , services use , and intermediate outcomes . PRINCIPAL FINDINGS At 9 years , there were no overall intervention status effects on MHI5 or unmet need ( largest F (2,41)=2.34 , p=.11 ) , but relative to UC , QI-Meds worsened MHI5 , reduced effectiveness of coping and among whites lowered tangible social support ( smallest t(42)=2.02 , p=.05 ) . The interventions reduced outpatient visits and increased perceived barriers to care among whites , but reduced attitudinal barriers due to racial discrimination and other factors among minorities ( smallest F (2,41)=3.89 , p=.03 ) . CONCLUSIONS Main intervention effects were over but the results suggest some unintended negative consequences at 9 years particularly for the medication-re source intervention and shifts to greater perceived barriers among whites yet reduced attitudinal barriers among minorities |
13,021 | 28,360,513 | The nonpharmacological interventions seem to be an efficient , inexpensive , and easy tool for family caregivers .
CONCLUSION Sensory stimulation interventions are inexpensive and practical for dementia caregivers ; however , only bright light therapy seems to be useful to reduce sleeping problems in dementia . | OBJECTIVE The current review aims to evaluate the sensory stimulation interventions in terms of reducing sleeping disturbances in patients with dementia .
Moreover , sleeping disorders increase caregivers ' distress and may lead to hospitalization . | CONTEXT Cognitive decline , mood , behavioral and sleep disturbances , and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers . Circadian rhythm disturbances have been associated with these symptoms . OBJECTIVE To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system : bright light and melatonin . DESIGN , SETTING , AND PARTICIPANTS A long-term , double-blind , placebo-controlled , 2 x 2 factorial r and omized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherl and s ; mean ( SD ) age , 85.8 ( 5.5 ) years ; 90 % were female and 87 % had dementia . INTERVENTIONS R and om assignment by facility to long-term daily treatment with whole-day bright ( + /- 1000 lux ) or dim ( + /- 300 lux ) light and by participant to evening melatonin ( 2.5 mg ) or placebo for a mean ( SD ) of 15 ( 12 ) months ( maximum period of 3.5 years ) . MAIN OUTCOME MEASURES St and ardized scales for cognitive and noncognitive symptoms , limitations of activities of daily living , and adverse effects assessed every 6 months . RESULTS Light attenuated cognitive deterioration by a mean of 0.9 points ( 95 % confidence interval [ CI ] , 0.04 - 1.71 ) on the Mini-Mental State Examination or a relative 5 % . Light also ameliorated depressive symptoms by 1.5 points ( 95 % CI , 0.24 - 2.70 ) on the Cornell Scale for Depression in Dementia or a relative 19 % , and attenuated the increase in functional limitations over time by 1.8 points per year ( 95 % CI , 0.61 - 2.92 ) on the nurse-informant activities of daily living scale or a relative 53 % difference . Melatonin shortened sleep onset latency by 8.2 minutes ( 95 % CI , 1.08 - 15.38 ) or 19 % and increased sleep duration by 27 minutes ( 95 % CI , 9 - 46 ) or 6 % . However , melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale , both for positive affect ( -0.5 points ; 95 % CI , -0.10 to -1.00 ) and negative affect ( 0.8 points ; 95 % CI , 0.20 - 1.44 ) . Melatonin also increased withdrawn behavior by 1.02 points ( 95 % CI , 0.18 - 1.86 ) on the Multi Observational Scale for Elderly Subjects scale , although this effect was not seen if given in combination with light . Combined treatment also attenuated aggressive behavior by 3.9 points ( 95 % CI , 0.88 - 6.92 ) on the Cohen-Mansfield Agitation Index or 9 % , increased sleep efficiency by 3.5 % ( 95 % CI , 0.8%-6.1 % ) , and improved nocturnal restlessness by 1.00 minute per hour each year ( 95 % CI , 0.26 - 1.78 ) or 9 % ( treatment x time effect ) . CONCLUSIONS Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia . To counteract the adverse effect of melatonin on mood , it is recommended only in combination with light . TRIAL REGISTRATION controlled-trials.com/is rct n Identifier : IS RCT N93133646 OBJECTIVES Patients with Alzheimer dementia often display both agitated behavior and poor sleep . Given that the disease is often associated with low endogenous levels of melatonin , exogenous melatonin administration may lead to improvements in sleep and agitation . DESIGN R and omized , placebo-controlled study . SETTING Nursing homes in San Diego , CA , metropolitan area . PARTICIPANTS Subjects were patients with probable Alzheimer disease . INTERVENTION Melatonin ( 8.5 mg immediate release and 1.5 mg sustained release ) ( N = 24 ) or placebo ( N = 17 ) administered at 10:00 P.M. for 10 consecutive nights . The protocol consisted of baseline ( 3 days ) , treatment ( 10 days ) , and posttreatment ( 5 days ) phases . MEASUREMENTS Sleep was measured continuously using actigraphy . Agitation was rated using both the Agitated Behavior Rating Scale and the Cohen-Mansfield Agitation Inventory . Treatment effects were examined both across the 24-hr day and separately by nursing shift . RESULTS There were no significant effects of melatonin , compared with placebo , on sleep , circadian rhythms , or agitation . CONCLUSION : This study failed to find a beneficial effect of exogenous melatonin , consistent with a number of other studies . The lack of efficacy may be related to the absence of a true treatment effect or to the superphysiologic dose of melatonin used We investigated whether low intensity dawn-dusk simulation ( DDS ) , a ' naturalistic ' form of light therapy design ed to embed sleep in its accustomed phase , could improve the disturbed circadian rest-activity cycle , nocturnal sleep and and /or cognitive functions in dementia . A protocol of 3 weeks each of baseline , treatment and follow-up was completed by 13 patients ( 85yr old+/-5yr , MMSE 14+/-5 ; n=9 DDS versus n=4 ' placebo ' dim red light ) who wore an activity/lux monitor throughout . There were no significant changes in clinical or cognitive status , nor modification of circadian stability or amplitude characteristics of the rest-activity cycle . However , two aspects of sleep responded to DDS but not to dim red light . The main sleep episode was 1:14h earlier during treatment ( p=0.03 ) compared with before and after DDS . With respect to actimetry-determined sleep variables , the DDS group tended to have shortened ' sleep latency ' , longer ' sleep duration ' , more nocturnal immobility and less nocturnal activity than the dim red group ( p<0.1 ) . In parallel , nighttime light exposure tended to be reduced ( p=0.07 ) . These promising findings -after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light . Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia , and DDS light therapy may provide one of the appropriate means to do so Purpose A link between poor sleep quality and Alzheimer ’s disease ( AD ) has recently been suggested . Since endogenous melatonin levels are already reduced at pre clinical AD stages , it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients . Patients and methods The effects of add-on prolonged-release melatonin ( PRM ) ( 2 mg ) to st and ard therapy on cognitive functioning and sleep were investigated in 80 patients ( men [ 50.7 % ] , women [ 49.3 % ] , average age 75.3 years [ range , 52–85 years ] ) diagnosed with mild to moderate AD , with and without insomnia comorbidity , and receiving st and ard therapy ( acetylcholinesterase inhibitors with or without memantine ) . In this r and omized , double-blind , parallel-group study , patients were treated for 2 weeks with placebo and then r and omized ( 1:1 ) to receive 2 mg of PRM or placebo nightly for 24 weeks , followed by 2 weeks placebo . The AD Assessment Scale – Cognition ( ADAS-Cog ) , Instrumental Activities of Daily Living ( IADL ) , Mini – Mental State Examination ( MMSE ) , sleep , as assessed by the Pittsburgh Sleep Quality Index ( PSQI ) and a daily sleep diary , and safety parameters were measured . Results Patients treated with PRM ( 24 weeks ) had significantly better cognitive performance than those treated with placebo , as measured by the IADL ( P=0.004 ) and MMSE ( P=0.044 ) . Mean ADAS-Cog did not differ between the groups . Sleep efficiency , as measured by the PSQI , component 4 , was also better with PRM ( P=0.017 ) . In the comorbid insomnia ( PSQI ≥6 ) subgroup , PRM treatment result ed in significant and clinical ly meaningful effects versus the placebo , in mean IADL ( P=0.032 ) , MMSE score ( + 1.5 versus −3 points ) ( P=0.0177 ) , and sleep efficiency ( P=0.04 ) . Median ADAS-Cog values ( −3.5 versus + 3 points ) ( P=0.045 ) were significantly better with PRM . Differences were more significant at longer treatment duration . PRM was well tolerated , with an adverse event profile similar to that of placebo . Conclusion Add-on PRM has positive effects on cognitive functioning and sleep maintenance in AD patients compared with placebo , particularly in those with insomnia comorbidity . The results suggest a possible causal link between poor sleep and cognitive decline OBJECTIVES To test the effects of walking , light exposure , and a combination intervention ( walking , light , and sleep education ) on the sleep of persons with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial with blinded assessors . SETTING Independent community living . PARTICIPANTS One hundred thirty-two people with AD and their in-home caregivers . INTERVENTIONS Participants were r and omly assigned to one of three active treatments ( walking , light , combination treatment ) or contact control and received three or six in-home visits . MEASUREMENTS Primary outcomes were participant total wake time based on wrist actigraphy and caregiver ratings of participant sleep quality on the Sleep Disorders Inventory ( SDI ) . Secondary sleep outcomes included additional actigraphic measurements of sleep percentage , number of awakenings , and total sleep time . RESULTS Participants in walking ( P=.05 ) , light ( P=.04 ) , and combination treatment ( P=.01 ) had significantly greater improvements in total wake time at posttest ( effect size 0.51 - 0.63 ) than controls but no significant improvement on the SDI . Moderate effect size improvements in actigraphic sleep percentage were also observed in active treatment participants . There were no significant differences between the active treatment groups and no group differences for any sleep outcomes at 6 months . Participants with better adherence ( 4 d/wk ) to walking and light exposure recommendations had significantly less total wake time ( P=.006 ) and better sleep efficiency ( P=.005 ) at posttest than those with poorer adherence . CONCLUSION Walking , light exposure , and their combination are potentially effective treatments for improving sleep in community-dwelling persons with AD , but consistent adherence to treatment recommendations is required BACKGROUND Agitated behaviors are common in dementia patients residing in chronic care setting s. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances . OBJECTIVE Prior research has suggested that bright light therapy ( BLT ) may reduce agitated behaviors in dementia patients . The aim of this study was to test the efficacy of BLT in a r and omized , controlled , crossover clinical trial . METHOD Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were r and omized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure . Patients were treated in either condition for 4 weeks , followed by 1 week on no treatment , prior to being crossed over to the other condition . RESULTS Eight out of 15 patients completed the entire study . The rest completed at least 2 weeks of study . Patients r and omized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later ( p<0.05 ) . The sleep of patients in the control condition did not improve significantly . There were no other significant differences between baseline and follow-up , nor between BLT and control treated patients on the other outcome measures , which included the Behavioral Pathology in Alzheimer Disease scale ( Behave-AD ) and the Cornell Scale for Depression in Dementia . CONCLUSION Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT . However , BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles OBJECTIVE To assess the impact of massage versus ear acupuncture on behavior and participation in occupational therapy of dementia patients . METHODS We performed a controlled , r and omized longitudinal trial approved by the Bioethics Commission of the University of Extremadura . One hundred twenty elderly subjects with dementia institutionalized in residential homes in Extremadura ( Spain ) received treatment based on massage and ear acupuncture over three months . Behavior alterations , sleep disturbance , and participation in rehabilitation and eating were assessed every month during the three months of intervention , and at one and two months of follow-up after the end of treatment . The assessment was performed through a structured question naire with closed format questions done by an occupational therapist not involved in the study . RESULTS There was a statistically significant positive effect of massage and ear acupuncture ( P < 0.001 ) on measured variables in the third month of intervention , which were maintained at two months after completing the treatment ( P < 0.021 ) , when compared to the control group . CONCLUSION Massage therapy and ear acupuncture can improve behavior and sleep disturbances , and increase the participation in eating and rehabilitation organized in residential homes , in dementia patients Neuropsychiatric behaviors are common in people with Alzheimer 's disease ( AD ) and make both professional and lay caregiving difficult . Light therapy has been somewhat successful in ameliorating disruptive behaviors . This r and omized trial tested the effects of morning or afternoon bright light exposure compared with usual indoor light on the presence , frequency , severity , and occupational disruptiveness of neuropsychiatric behaviors in nursing home residents with AD . Light was administered for 1 hr daily ( Monday-Friday ) for 10 weeks . The Neuropsychiatric Inventory — Nursing Home was used to assess behavior at baseline and end of the intervention . Analyses revealed statistically significant differences between groups on agitation/aggression , depression/dysphoria , aberrant motor behavior , and appetite/eating disorders . The magnitude of change was small and may not represent clinical ly significant findings . Agitation/aggression and nighttime behaviors commonly occurred and were highly correlated with occupational disruptiveness . Interventions that decrease the presence and /or severity of neuropsychiatric behaviors have the potential to significantly decrease caregiver burden The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity ( R-A ) rhythm disorders in patients with vascular dementia ( VD ) and patients with dementia of Alzheimer 's type ( DAT ) . Participants in this study were 12 patients with VD ( M/F = 5/7 ; average age = 81 years ) and 10 patients with DAT ( M/F = 4/6 ; average age = 78 years ) . They were exposed to 2 weeks of bright light ( BL ; 5000 - 8000 lux ) and 2 weeks of dim light ( DL ; 300 lux ) in the morning ( 09:00 - 11:00 ) in a r and omized crossover design in which the 2-week treatment period took place between pretreatment ( 1 week ) and posttreatment ( 1 week ) periods . Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist . The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period , as well as compared with the DL condition in the VD group , but not in the DAT group . These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy BACKGROUND Agitation is common in people with dementia , is distressing to patients and stressful to their carers . Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate . Alternatives to drug treatment for agitation should be sought . The study aim ed to assess the effects of bright light therapy on agitation and sleep in people with dementia . METHODS A single center r and omized controlled trial of bright light therapy versus st and ard light was carried out . The study was completed prior to the m and atory registration of r and omized controls on the clinical trials registry data base and , owing to delays in writing up , retrospective registration was not completed . RESULTS There was limited evidence of reduction in agitation in people on active treatment , sleep was improved and a suggestion of greater efficacy in the winter months . CONCLUSIONS Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated STUDY OBJECTIVES Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock . We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin , alone and in combination with one session of morning bright light exposure . DESIGN R and omized placebo-controlled double-blind circadian protocol . The effects of four conditions , dim light ( ∼1.9 lux , ∼0.6 Watts/m(2))-placebo , dim light-melatonin ( 5 mg ) , bright light ( ∼3000 lux , ∼7 Watts/m(2))-placebo , and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset ( DLMO ) prior to and following treatment under constant routine conditions . Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time . SETTING Sleep and chronobiology laboratory environment free of time cues . PARTICIPANTS Thirty-six healthy participants ( 18 females ) aged 22 ± 4 y ( mean ± SD ) . RESULTS Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone . Bright light alone and melatonin alone induced similar phase advances . CONCLUSION Information from light and melatonin appear to be combined by the human circadian clock . The ability to combine circadian time cues has important implication s for underst and ing fundamental physiological principles of the human circadian timing system . Knowledge of such principles is important for design ing effective counter measures for phase-shifting the human circadian clock to adapt to jet lag , shift work , and for design ing effective treatments for circadian sleep-wakefulness disorders Sleep in the nursing home environment is extremely fragmented , possibly in part as a result of decreased light exposure . This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer 's disease . Results showed that both morning and evening bright light result ed in more consoli date d sleep at night , as measured with wrist actigraphy . Evening light also increased the quality of the circadian activity rhythm , as measured by a 5-parameter extended cosine model ( amplitude , acrophase , nadir , slope of the curve , and relative width of the peak and trough ) . Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia . It would behoove nursing homes to consider increasing ambient light in multi purpose rooms where patients often spend much of their days |
13,022 | 23,185,429 | Moderate quality evidence suggests that RTW coordination results in small relative , but likely important absolute benefits in the likelihood of disabled or sick-listed patients returning to work , and associated small improvements in function and pain . | BACKGROUND The dramatic rise in chronically ill patients on permanent disability benefits threatens the sustainability of social security in high-income countries .
Social insurance organizations have started to invest in promising , but costly return to work ( RTW ) coordination programmes .
The benefit , however , remains uncertain .
We conducted a systematic review to determine the long-term effectiveness of RTW coordination compared to usual practice in patients at risk for long-term disability . | Introduction Return to work ( RTW ) of employees on sick leave for common mental disorders may require a multidisciplinary approach . This article aims to assess time to RTW after a psychiatric consultation providing treatment advice to the occupational physician ( OP ) for employees on sick leave for common mental disorders in the occupational health ( OH ) setting , compared to care as usual ( CAU ) . Methods Cluster r and omized clinical trial evaluating patients of 12 OPs receiving consultation by a psychiatrist , compared to CAU delivered by 12 OPs in the control group . 60 patients suffering from common mental disorders and ≥ six weeks sicklisted were included . Follow up three and six months after inclusion . Primary outcome measure was time to RTW . Intention- to-treat multilevel analysis and a survival analysis were performed to evaluate time to RTW in both groups . Results In CAU , referral was the main intervention . Both groups improved in terms of symptom severity and quality of life , but time to RTW was significantly shorter in the psychiatric consultation group . At three months follow up , 58 % of the psychiatric consultation group had full RTW versus 44 % of the control group , a significant finding ( P = 0.0093 ) . Survival analysis showed 68 days earlier RTW after intervention in the psychiatric consultation group ( P = 0.078 ) compared to CAU . Conclusion Psychiatric consultation for employees on sick leave in the OH setting improves time to RTW in patients with common mental disorders as compared to CAU . In further research , focus should be on early intervention in patients with common mental disorders on short sick leave duration . Psychiatric consultation might be particularly promising for improvement of RTW in those patients . Trial registration number IS RCT N : Background Common mental disorders are the most prevalent of all mental disorders , with the highest burden in terms of work absenteeism and utilization of health care services . Evidence -based treatments are available , but recognition and treatment could be improved , especially in the occupational health setting . The situation in this setting has recently changed in the Netherl and s because of new legislation , which has result ed in reduced sickness absence . Severe mental disorder has now become one of the main causes of work absenteeism . Occupational physicians ( OPs ) are expected to take an active role in diagnosis and treatment , and seem to be in need of support for a new approach to h and le cases of more complex mental disorders . Psychiatric consultation can be a collaborative care model to achieve this . Methods / design This is a two-armed cluster-r and omized clinical trial , with r and omization among OPs . Forty OPs in two big companies providing medical care for multiple companies will be r and omized to either the intervention group , i.e. psychiatric consultation embedded in a training programme , or the control group , i.e. only training aim ed at recognition and providing Care As Usual . 60 patients will be included who have been absent from work for 6–52 weeks and who , after screening and a MINI interview , are diagnosed with depressive disorder , anxiety disorder or somatoform disorder based on DSM-IV criteria . Baseline measurements and follow up measurements ( at 3 months and 6 months ) will be assessed with question naires and an interview . The primary outcome measure is level of general functioning according to the SF-20 . Secondary measures are severity of the mental disorder according to the PHQ and the SCL-90 , quality of life ( EQ-D5 ) , measures of Return To Work and cost-effectiveness of the treatment assessed with the TiC-P. Process measures will be adherence to the treatment plan and assessment of the treatment provided by the Psychiatric Consultant ( PC ) in both groups . Discussion In the current study , a psychiatric consultation model that has already proved to be effective in the primary care setting , and aim ed to enhance evidence -based care for patients with work absenteeism and common mental disorder will be evaluated for its efficacy and cost-effectiveness in the occupational health setting OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials 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 Objectives : This prospect i ve cohort study examines number of self-reported days of sickness absence as a risk marker for future disability pension among a representative sample of employees in Denmark 1990 - 2004 . Material and methods : 4177 employees between 18 and 45 years were interviewed using a self-administered question naire in 1990 regarding sickness absence , age , gender , socioeconomic position , health behaviour , and physical and psychosocial work environment . They were followed for 168 months in a national disability pension register . Logistic regression analysis was performed in order to assess risk estimates for levels of absence and future disability pension . Results : During follow-up , a total of 140 persons ( 3.4 % ) received disability pension . Of these , 82 ( 58.6 % ) were women , 58 ( 41.4 % ) were men . There was a 2.5 fold risk of future disability pension for the part of the population reporting more than 6 days of sickness absence per annum at baseline , when taking into account gender , age , socioeconomic position , health behaviour , physical and psychosocial work environment . Conclusion : The findings suggest that information on self-reported days of sickness absence can be used to effectively identify “ at risk ” groups for disability pension BACKGROUND CONTEXT The impact of lumbar spinal surgery is commonly evaluated with three patient-reported outcome measures : Oswestry Disability Index ( ODI ) , the physical component summary ( PCS ) of the Short Form of the Medical Outcomes Study ( SF-36 ) , and pain scales . A minimum clinical ly important difference ( MCID ) is a threshold used to measure the effect of clinical treatments . Variable threshold values have been proposed as MCID for those instruments despite a lack of agreement on the optimal MCID calculation method . PURPOSE This study has three purpose s. First , to illustrate the range of values obtained by common anchor-based and distribution-based methods to calculate MCID . Second , to determine a statistically sound and clinical ly meaningful MCID for ODI , PCS , back pain scale , and leg pain scale in lumbar spine surgery patients . Third , to compare the discriminative ability of two anchors : a global health assessment and a rating of satisfaction with the results of the surgery . STUDY DESIGN This study is a review of prospect ively collected patient-reported outcomes data . PATIENT SAMPLE A total of 454 patients from a large data base of surgeries performed by the Lumbar Spine Study Group with a 1-year follow-up on either ODI or PCS were included in the study . OUTCOME MEASURES Preoperative and 1-year postoperative scores for ODI , PCS , back pain scale , leg pain scale , health transition item ( HTI ) of the SF-36 , and Satisfaction with Results scales . METHODS ODI , SF-36 , and pain scales were administered before and 1 year after spinal surgery . Several c and i date MCID calculation methods were applied to the data and the result ing values were compared . The HTI of the SF-36 was used as the anchor and compared with a second anchor ( Satisfaction with Results scale ) . RESULTS Potential MCID calculations yielded a range of values : fivefold for ODI , PCS , and leg pain , 10-fold for back pain . Threshold values obtained with the two anchors were very similar . CONCLUSIONS The minimum detectable change ( MDC ) appears as a statistically and clinical ly appropriate MCID value . MCID values in this sample were 12.8 points for ODI , 4.9 points for PCS , 1.2 points for back pain , and 1.6 points for leg pain Abstract . When measuring treatment effect in chronic low back pain with multi-item outcome instruments , it is necessary , both for clinical decision-making and research purpose s , to underst and the clinical importance of the outcome scores . The aims of the present study were three-fold . Firstly , it aim ed to estimate the minimal clinical ly important difference of three multi-item outcome instruments ( the Oswestry Disability Index , the General Function Score and the Zung Depression Scale ) and of the visual analogue scale ( VAS ) of back pain . Secondly , it aim ed to estimate the error of measurement of these instruments ; and its third aim was to describe the clinical meaning of score change . The study population consisted of 289 patients treated surgically or non-surgically in a r and omised controlled trial . The minimal clinical ly important difference was estimated with patient global assessment as the external criterion . It was compared with the st and ard error of measurement of the instruments . The individual items of the instruments were compared for score changes related to improvement and deterioration . The st and ard error of measurement of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale was 4 , 6 and 3 units , respectively . The 95 % tolerance interval was 10 , 16 and 8 units , respectively . The minimal clinical ly important difference was 10 , 12 and 8–9 units , respectively , thus not significantly exceeding the tolerance interval . The minimal clinical ly important difference of VAS back pain was 18–19 units , well exceeding the 95 % tolerance interval , which was 15 units . Improvement after treatment for chronic low back pain tends to occur to a greater extent in sleep disturbance , ability to do usual things and psychological irritability , but to a lesser extent in the ability to sit , st and and lift . We conclude that the VAS of back pain is responsive enough to detect the minimal clinical ly important difference , whereas the smallest acceptable score changes of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale may require an increase to exceed the 95 % tolerance interval when used for clinical decision making and for power calculation . Despite improvement after treatment , the ability to sit , st and and lift , remain notable problems STUDY DESIGN An intervention study by the medical advisers of a social security sickness fund on a m and atorily insured patient population after open discectomy for herniated lumbar intervertebral disc . The medical advisers were r and omized into two groups : a control group ( n = 30 ) and an intervention group ( n = 30 ) . OBJECTIVES To compare a rehabilitation-oriented approach in insurance medicine focused primarily on early mobilization and early resumption of professional activities with the usual cl aim -based practice . SUMMARY OF BACKGROUND DATA This study included 710 patients , with a mean age of 39.2 years , who underwent surgery for herniated lumbar disc . METHODS Medical advisers in the rehabilitation-oriented group examined the patients monthly , starting at 6 weeks after the surgical intervention . They used a newly developed protocol to motivate the patients and treating physicians toward social and professional reintegration . RESULTS At 52 weeks , 10.1 % of the patients guided by medical advisers from the rehabilitation-oriented group had not resumed work in contrast to 18.1 % of the patients in the control group . It was statistically proven that this effect also holds during the follow-up period . CONCLUSIONS A rehabilitation-oriented approach by the medical advisers of social security can increase the probability of a return to work for patients after lumbar disc herniation surgery Objective To evaluate the cost effectiveness , cost utility , and cost-benefit of an integrated care programme compared with usual care for sick listed patients with chronic low back pain . Design Economic evaluation alongside a r and omised controlled trial with 12 months ’ follow-up . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) in the Netherl and s , 2005 - 9 . Participants 134 adults aged 18 - 65 sick listed because of chronic low back pain : 66 were r and omised to integrated care and 68 to usual care . Interventions Integrated care consisted of a workplace intervention based on participatory ergonomics , with involvement of a supervisor , and a grade d activity programme based on cognitive behavioural principles . Usual care was provided by general practitioners and occupational physicians according to Dutch guidelines . Main outcome measures The primary outcome was duration until sustainable return to work . The secondary outcome was quality adjusted life years ( QALYs ) , measured using EuroQol . Results Total costs in the integrated care group ( £ 13 165 , SD £ 13 600 ) were significantly lower than in the usual care group ( £ 18 475 , SD £ 13 616 ) . Cost effectiveness planes and acceptability curves showed that integrated care was cost effective compared with usual care for return to work and QALYs gained . The cost-benefit analyses showed that every £ 1 invested in integrated care would return an estimated £ 26 . The net societal benefit of integrated care compared with usual care was £ 5744 . Conclusions Implementation of an integrated care programme for patients sick listed with chronic low back pain has a large potential to significantly reduce societal costs , increase effectiveness of care , improve quality of life , and improve function on a broad scale . Integrated care therefore has large gains for patients and society as well as for employers & NA ; Multidisciplinary programmes using a vocational approach can enhance work return in chronic pain patients , but little is known about the long‐term effects of rehabilitation . The current study examined the patterns of sickness absence 10 years after participation in 3 treatment groups ( physiotherapy , cognitive behavioural therapy , and vocational multidisciplinary rehabilitation ) in comparison to a control group receiving treatment‐as‐usual . Cost‐effectiveness was also assessed . Two hundred fourteen patients participated in a r and omized controlled trial and were followed‐up via register data 10 years after the interventions . On average , persons in multidisciplinary rehabilitation had 42.98 fewer days on sickness absence per year compared to those treated‐as‐usual ( 95 % confidence interval −82.45 to −3.52 , P = 0.03 ) . The corresponding reduction of sickness absence after physiotherapy and cognitive behavioural therapy was not significantly different from the control group . The effect of rehabilitation seems to be more pronounced for disability pension than for sick leave . The economic analyses showed substantial cost savings for individuals in the multidisciplinary group compared to the control group . Intensive multidisciplinary rehabilitation for persistent back and neck pain reduces sickness absence 10 years after intervention and shows greater cost reductions than physiotherapy and cognitive behavioural therapy alone Management of the return-to-work process in cl aim ants with work-related upper extremity disorders often poses challenges to the health care provider , cl aim ant , and employer . Modifying workplace ergonomic risk factors as a component of the workplace accommodation process may improve return-to-work outcomes by reducing recurrent pain and discomfort . The present study is a case-control evaluation of the effects of a 2-day training program for nurse case managers that was design ed to facilitate the implementation of workplace accommodations within a workers ’ compensation health care delivery system . After the training , 101 cl aim ants with compensable upper extremity disorders were r and omly assigned to case mangers with and without training . Overall , 208 accommodations were recommended and 155 of these were implemented ( 75 % ) . Cl aim ants of trained nurses received 1.5 times as many recommendations for accommodations as cl aim ants managed by nurses not trained in the process , and 1.4 times as many accommodations were implemented , although no differences were found between the two groups in implementation rates . Trained nurses were more likely to recommend accommodations addressing workstation layout , computer-related improvements , furnishings , accessories , and lifting/carrying aids , whereas the untrained nurses were more likely to suggest light duty and lifting restrictions . This study indicates that the training was associated with a change in the practice behavior of case managers regarding the workplace accommodation process . More research is needed to identify barriers to implementation and develop more effective approaches to facilitate worksite accommodations in disabled workers with carpal tunnel syndrome and other persistent upper extremity disorders A case manager 's ability to obtain worksite accommodations and engage workers in active problem solving may improve health and return to work outcomes for clients with work related upper extremity disorders ( WRUEDs ) . This study examines the feasibility of a 2 day training seminar to help nurse case managers identify ergonomic risk factors , provide accommodation , and conduct problem solving skills training with workers ' compensation cl aim ants recovering from WRUEDs . Eight procedural steps to this case management approach were identified , translated into a training workshop format , and conveyed to 65 r and omly selected case managers . Results indicate moderate to high self ratings of confidence to perform ergonomic assessment s ( mean = 7.5 of 10 ) and to provide problem solving skills training ( mean = 7.2 of 10 ) after the seminar . This training format was suitable to experienced case managers and generated a moderate to high level of confidence to use this case management approach Aim : A study was undertaken to identify predictors for the transition from long-term sickness absence into disability pension with special emphasis on routinely collected medical information ( e.g. diagnoses on sickness certificates ) and the duration of sickness-absence spells . Methods : The study used a 10 % r and om sample of the Norwegian population of working age ( the KIRUT data base ) . Individuals below 60 years of age , with spells of long-term sickness absence starting in 1990 - 91 , where the medical diagnoses on the sickness certificates were known , were identified . This group ( 4,432 men and 5,645 women ) was followed up for three years after the end of sickness absence with regard to disability pension and working status . Results : In logistic regression the following predictors significantly increased the risk of obtaining disability pension during the first three years after the long-term sickness spell : age , part-time employment , and duration of absence > 197 days . Higher education and having children < 11 years significantly decreased the risk . Having the medical diagnoses ` ` mental problems ' ' and diseases in the nervous system , respiratory system , and circulatory systems indicated high risk ( compared with musculoskeletal disease ) . The diagnostic groups ` ` pregnancy-related disease ' ' and ` ` injuries ' ' implied low risk for disability pension . In separate regressions for both genders the ` ` protective effect ' ' of having small children remained only for women . High risk for sickness absence caused by ` ` mental problems ' ' reached significance only for men . Conclusions and implication s : Several risk factors for transition from long-term sickness absence into disability pension were identified . The finding that spells of sickness absence with duration up to seven months did not imply increased risk of disability during the first three years may have implication s for interventions aim ed at long-term sickness absentees This study was design ed to evaluate the effectiveness of a multidisciplinary rehabilitation programme offered to a general population with 90 days of sick-leave due to non-specific musculoskeletal pain . The results concerning return to work and re-sick-listing during a follow-up period of five years were evaluated for Swedes and immigrants separately . Compared to a control group , the rehabilitation offer result ed in improved work stability after work return among the Swedes . The immigrants , as a group , did not benefit from the programme compared to the controls in primary care Compare the effects of integrated case management and usual care on patient satisfaction in employees with work-related upper extremity disorder ( WRUED ) , and consider the implication s of higher levels of satisfaction . Describe those patient-related and work-related factors that predict the severity of upper limb symptoms and the degree of functional limitation 6 and 12 months after intervention . Enumerate the factors influencing the interval before return to work in employees with WRUED who are managed by traditional or integrated case management . An integrated case management ( ICM ) approach ( ergonomic and problem-solving intervention ) to work-related upper-extremity disorders was examined in relation to patient satisfaction , future symptom severity , function , and return to work ( RTW ) . Federal workers with work-related upper-extremity disorder workers ’ compensation cl aims ( n = 205 ) were r and omly assigned to usual care or ICM intervention . Patient satisfaction was assessed after the 4-month intervention period . Question naires on clinical outcomes and ergonomic exposure were administered at baseline and at 6- and 12-months postintervention . Time from intervention to RTW was obtained from an administrative data base . ICM group assignment was significantly associated with greater patient satisfaction . Regression analyses found higher patient satisfaction levels predicted decreased symptom severity and functional limitations at 6 months and a shorter RTW . At 12 months , predictors of positive outcomes included male gender , lower distress , lower levels of reported ergonomic exposure , and receipt of ICM . Findings highlight the utility of targeting workplace ergonomic and problem solving skills Introduction In Denmark , the magnitude and impact of work disability on the individual worker and society has prompted the development of a new “ coordinated and tailored work rehabilitation ” ( CTWR ) approach . The aim of this study was to compare the effects of CTWR with conventional case management ( CCM ) on return-to-work of workers on sick leave due to musculoskeletal disorders ( MSDs ) . Methods The study was a r and omized controlled trial with economic evaluation undertaken with workers on sick leave for 4–12 weeks due to MSDs . CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan . The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up . Secondary outcomes were work status as well as pain intensity and functional disability , measured at baseline , 3 and 12 months follow-up . The economic evaluation ( intervention costs , productivity loss , and health care utilization costs ) was based on administrative data derived from national registries . Results For the time intervals 0–6 months , 6–12 months , and the entire follow-up period , the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group . The total costs saved in CTWR participants compared to controls were estimated at US $ 1,366 per person at 6 months follow-up and US $ 10,666 per person at 12 months follow-up . Conclusions Workers on sick leave for 4–12 weeks due to MSD who underwent “ CTWR ” by an interdisciplinary team had fewer sickness absence hours than controls . The economic evaluation showed that — in terms of productivity loss — CTWR seems to be cost saving for the society Study Design . A r and omized controlled trial comparing usual care with a program for the coordination of primary health care ( CORE ) for the treatment of subacute low-back pain patients . Objectives . To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community . Summary of Background Data . Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain . The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products . The CORE program was design ed to make the guidelines fit in this complex environment . Methods . One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were r and omized in two groups : usual care ( N=56 ) and the CORE program ( N=54 ) . Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians , and included a complete examination , recommendations for the clinical management , and support to carry out the recommendations . All workers were followed for 6 months . Back pain and functional status were assessed at baseline , 3 months , and 6 months . Results . In the 6-month follow-up , the CORE group returned to work 6.6 days ( st and ard error = 8.9 ) quicker than the control group , a difference that was not statistically significant . However , the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up . This represented nine points on the Oswestry scale ( P = 0.02 ) and 12 points on the Quebec Back Pain Disability Scale ( P = 0.01 ) . The CORE group also used three times less specialized imaging tests of the spine at 3 months ( P < 0.01 ) and exercised twice as much at 6 months ( P < 0.05 ) than the controls . Conclusions . The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community , without delaying the return to work . The CORE intervention for back pain patients ishighly relevant to primary care practice . It is simple in its application , flexible to accommo date physicians ’ and patients ’ preferences in health care , and it is effective on patients ’ clinical outcome |
13,023 | 29,206,852 | Analyses of effectiveness showed that smoking cessation interventions appear to increase short-term and long-term smoking abstinence in individuals with current depression .
Subgroup analyses revealed stronger effects among studies that provided pharmacological treatments than in studies using psychological treatments .
However , the evidence is weak due to the small number of studies .
Smoking abstinence appears to be associated with an improvement in depressive symptoms .
Heterogeneity in protocol s in similar types of treatment also prevent firm conclusions being drawn on the effectiveness of any particular treatment model to optimally manage abstinence among depressed smokers . | null | null |
13,024 | 15,846,748 | Overall , weight loss strategies using dietary , physical activity , or behavioral interventions produced significant improvements in weight among persons with prediabetes and a significant decrease in diabetes incidence . | BACKGROUND Most persons with prediabetes ( impaired glucose tolerance or impaired fasting glucose ) are overweight , and obesity worsens the metabolic and physiologic abnormalities associated with this condition .
Prediabetes is an important risk factor for the development of type 2 diabetes .
OBJECTIVES The objective of this review was to assess the effectiveness of dietary , physical activity , and behavioral weight loss , and weight control interventions for adults with prediabetes . | 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 < 0.01 ) . Subjects adherent to both the 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 Risk factors associated with the progression from impaired glucose tolerance ( IGT ) to NIDDM were examined in data from six prospect i ve studies . IGT and NIDDM were defined in all studies by World Health Organization ( WHO ) criteria , and baseline risk factors were measured at the time of first recognition of IGT . The studies varied in size from 177 to 693 participants with IGT , and included men and women followed from 2 to 27 years after the recognition of IGT . Across the six studies , the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years . Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence , incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels , but increased linearly with increasing 2-h postchallenge glucose quartiles . Incidence rates were higher among the Hispanic , Mexican-American , Pima , and Nauruan population s than among Caucasians . The effect of baseline age on NIDDM incidence rates differed among the studies ; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies . In all studies , estimates of obesity ( including BMI , waist-to-hip ratio , and waist circumference ) were positively associated with NIDDM incidence . BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately , but not in the three studies with the highest NIDDM incidence rates . Sex and family history of diabetes were generally not related to NIDDM progression . This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements . The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention 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 < 0.001 ) . The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p < 0.001 ; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l , p < 0.05 ) were significantly lower in the intervention group after the first year of intervention . Favourable changes were also found 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 < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater 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 Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance ( IGT ) . However , it is unknown whether this is due to improved insulin sensitivity or insulin secretion . We investigated at baseline insulin sensitivity and insulin secretion applying frequently sample d intravenous glucose tolerance test ( FSIGT ) in 87 of 101 obese middle-aged subjects with IGT r and omized into an intervention or a control group in the Finnish Diabetes Prevention Study . FSIGT was repeated after 4 years in 52 people . There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups . The 4-year weight and waist circumference decreases were greater in the intervention than in the control group ( P = 0.043 and P = 0.025 , respectively ) . At 4-year examination , insulin sensitivity ( Si ) tended to be higher in the intervention group ( the difference between the mean values 36 % ; P = 0.067 , and P = 0.136 after adjustment for age , sex , BMI , and baseline Si value ) . There was strong correlation between the 4-year changes in Si and weight ( r = -0.628 and r = -0.710 , for intervention and control groups ; P < 0.001 for both ) . In the entire group , Si improved by 64 % in the highest tertile of weight loss but deteriorated by 24 % in those who gained weight ( lowest tertile ) . Acute insulin response declined significantly in the control group . In conclusion , Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT . Insulin secretion remained constant for years in individuals with IGT who were able to lose weight 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 < 0.001 ) . CONCLUSIONS The NDE was shown to reduce glucose levels in high-risk subjects for type 2 diabetes Background We examined the development of new diabetes mellitus in men aged 45 to 64 years during the West of Scotl and Coronary Prevention Study . Methods and Results Our definition of diabetes mellitus was based on the American Diabetic Association threshold of a blood glucose level of ≥7.0 mmol/L. Subjects who self-reported diabetes at baseline or had a baseline glucose level of ≥7.0 mmol/L were excluded from the analyses . A total of 5974 of the 6595 r and omized subjects were included in the analysis , and 139 subjects became diabetic during the study . The baseline predictors of the transition from normal glucose control to diabetes were studied . In the univariate model , body mass index , log triglyceride , log white blood cell count , systolic blood pressure , total and HDL cholesterol , glucose , and r and omized treatment assignment to pravastatin were significant predictors . In a multivariate model , body mass index , log triglyceride , glucose , and pravastatin therapy were retained as predictors of diabetes in this cohort . Conclusions We concluded that the assignment to pravastatin therapy result ed in a 30 % reduction ( P = 0.042 ) in the hazard of becoming diabetic . By lowering plasma triglyceride levels , pravastatin therapy may favorably influence the development of diabetes , but other explanations , such as the anti-inflammatory properties of this drug in combination with its endothelial effects , can not be excluded with these analyses The majority of the obese persons is characterized by a disturbed glucose tolerance and an increased insulin secretion . The cause of this apparent contradiction lies in the existence of an insulin resistance . In 23 obese persons ( relative weight greater than 120 % according to Möhr and Johnson ) with normal or disturbed glucose tolerance the effect of a diet restriction lasting 4 weeks ( 700 kcal/die ) or of a combined diet training programme on the body weight , serum lipids , state of conditioning ( PWC170 ) and insulin sensitivity in vivo was investigated . The insulin sensitivity was characterized by means of 1 h insulin infusion test . At comparable peripheral steady state insulin levels the relative decrease of the plasma glucose and free fatty acid concentration is a measure of the insulin sensitivity in vivo . In 9 obese persons with disturbed glucose tolerance observations of the course over 1 year are existing . The finding demonstrate that only a combined diet training programme leads to a significant improvement of the insulin sensitivity and prevails a unique dietary treatment . The measure of the improved insulin effectivity directly correlates with the effect of conditioning . The reduction of the body weight obtained is about double as large in a combined diet conditioning treatment as after a unique restriction of the diet ( 18 % or 10 % of the relative weight ) . Triglyceride and cholesterol levels significantly decrease , the HDL-cholesterol increases in tendency . On the other h and , the results are unsatisfactory after one year . The therapy regime is a promising strategy for the reduction of the insulin resistance in adiposity as a preventive medical measure , provided a good cooperation and motivation on the side of the patient is present Context In observational studies , postmenopausal hormone therapy has been associated with lower fasting glucose levels . No prospect i ve , controlled trial has evaluated the effect of postmenopausal hormone therapy on the development of diabetes mellitus . Contribution Among the 2029 women in the Heart and Estrogen/progestin Replacement Study who had coronary disease but no diabetes at baseline , 6.2 % of those receiving 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate and 9.5 % of those receiving placebo developed diabetes . Implication s Recommendations about combination postmenopausal hormone therapy should consider that for every 30 women treated for 4 years , therapy might prevent one case of diabetes . The Editors Several clinical studies have evaluated the effect of postmenopausal hormone therapy on glucose metabolism and have had disparate results . Results from r and omized , controlled trials performed primarily in women without diabetes have found decreased mean fasting glucose or insulin levels among those assigned to hormone therapy ( 1 - 5 ) or no difference between those assigned to hormones and those assigned to placebo ( 6 - 10 ) . Fewer clinical trials have evaluated the effect of postmenopausal hormones on fasting glucose and insulin levels among women with type 2 diabetes mellitus , but again , the results have been mixed ( 11 - 16 ) . Observational studies have more consistently found that postmenopausal women taking hormone therapy have lower fasting glucose or hemoglobin A1c levels than those not taking hormones ( 17 - 24 ) . In addition , some ( 25 , 26 ) but not all ( 24 , 27 ) observational studies have noted a decreased incidence of diabetes among users of postmenopausal hormone therapy . No r and omized , controlled trial has evaluated the long-term effect of hormone therapy on diabetes incidence . To determine the effect of hormone therapy on subsequent diabetes , we analyzed data from the Heart and Estrogen/progestin Replacement Study ( HERS ) , in which 2763 postmenopausal women with documented coronary heart disease ( CHD ) were r and omly assigned to daily estrogen plus progestin therapy or to placebo . We evaluated the effect of hormone therapy on fasting glucose levels and incident diabetes over 4 years of follow-up . Methods Study Setting , Participants , and Design The design , methods , baseline characteristics ( 28 ) , and main findings ( 29 ) of HERS have been published elsewhere . Briefly , HERS was a r and omized , double-blind , placebo-controlled trial performed to evaluate daily doses of 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate for the prevention of coronary events in postmenopausal women with established CHD . The trial enrolled 2763 women at 20 clinical centers in the United States between January 1993 and September 1994 and followed participants for a mean of 4.1 years . To be included in the trial , women had to be younger than 80 years of age and have CHD , as evidence d by previous myocardial infa rct ion , coronary artery bypass graft surgery , mechanical revascularization , or angiographic evidence of coronary stenosis . Women who reported a CHD event within 6 months of r and omization or who had used postmenopausal hormone therapy within 3 months of the initial screening were excluded . Those with serum triglyceride levels of 3.39 mmol/L or greater ( 300 mg/dL ) , fasting blood glucose levels of 16.5 mmol/L or greater ( 300 mg/dL ) , or uncontrolled hypertension ( systolic blood pres sure 200 mg Hg or diastolic blood pressure 105 mm Hg ) were also excluded . Computer-generated r and om numbers were used to specify the allocation sequence . Women were r and omly assigned to the two treatment groups by use of a tamper-proof blocked r and omization stratified by clinical center . Participants , investigators , and staff at the clinical centers ; Wyeth-Ayerst Research ; and those adjudicating study outcomes were blinded to medication assignment . Additional details about sample size calculations , r and omization , and blinding procedures have been published elsewhere ( 29 ) . For our analysis , women were classified as having diabetes at the baseline visit if they reported a physician diagnosis of diabetes , were taking diabetes medication , or had a fasting plasma glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) . Women were classified as having impaired fasting glucose if they had a fasting glucose level of 6.0 to 6.9 mmol/L ( 110 to 125 mg/dL ) at baseline . The remaining women were considered to have normal glucose metabolism . Data Collection At baseline , participants completed a question naire to ascertain age , race or ethnicity , education , smoking habits ( current , former , or never ) , alcohol consumption ( drinks per week ) , and exercise or walking activity . Physical examination variables measured at baseline were body weight , height , waist and hip circumference , and systolic and diastolic blood pressure . At baseline , at year 1 , and at the end-of-trial visit , participants had fasting blood tests for levels of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , and lipoprotein(a ) measured by the Lipoprotein Analytical Laboratory at Johns Hopkins Hospital , Baltimore , Maryl and . Fasting serum glucose level was measured at baseline , at year 1 , and at the end-of-trial visit . Venous blood was obtained in the morning after a 12-hour fast , and SmithKline Beecham Clinical Laboratory , Van Nuys , California , analyzed the sample s using the hexokinase enzymatic method . We determined coefficients of variation by using ChemTrac ( Medical Analysis Systems , Inc. , Camarillo , California ) control . The coefficient of variation for serum glucose level was 1.6 % at a mean value ( SD ) of 4.2 0.05 mmol/L ( 77 1.0 mg/dL ) and 1.1 % at a mean value ( SD ) of 14.6 0.16 mmol/L ( 266 3.0 mg/dL ) . Adherence to study medication was reassessed every 4 months , at each visit . Ascertainment of Outcomes Diabetes incidence was not a secondary end point of the main HERS trial , but blood glucose level was prespecified as a variable that may mediate the effects of hormone therapy on CHD outcomes . We defined incident cases of diabetes by the presence of a fasting glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) at year 1 or at the end-of-trial visit , self-report of new diabetes or a complication directly related to diabetes , or initiation of hypoglycemic medication at any point during follow-up . Self-reported complications included diabetic neuropathy , diabetic retinopathy , diabetic foot ulcer , and diabetic renal disease . Hypoglycemia was considered a complication of diabetes if a participant taking an antidiabetic medication reported it to the study staff as an adverse event . Statistical Analysis To compare fasting glucose levels by treatment assignment at baseline , at year 1 , and at the end-of-trial visit , t-tests were used . In addition , mixed linear models for repeated measures were used to assess treatment effects on fasting glucose level measured at year 1 and at the end-of-trial visit . Since mean values changed little after the year 1 visit , treatment effects were modeled by using the interaction between treatment assignment and an indicator for follow-up compared with baseline . These analyses were repeated after stratification by baseline diabetes status ( diabetes , impaired fasting glucose , or normal glucose metabolism ) . We calculated the number needed to treat for benefit by taking the inverse of the absolute risk reduction of incident diabetes between the treatment groups . The effect of treatment assignment on incident diabetes was assessed by using Cox proportional-hazards models . Primary analyses used unadjusted intention-to-treat models ; in supplementary analyses , we adjusted first for age and then for a range of potential confounders selected a priori , including age ; ethnicity ; education ; current smoking ; alcohol use ; exercise ; body mass index ; waist circumference ; and baseline use of diuretics , -blockers , angiotensin-converting enzyme inhibitors , and statins . In addition to intention-to-treat analyses , we also performed as treated analyses to determine whether the observed effect of hormone therapy on glucose levels and incident diabetes was also seen among women who adhered to the study medication . In these analyses , follow-up was censored at the beginning of the first 2-week period in which participants did not adhere to medication . To minimize potential confounding , these analyses were adjusted for baseline variables that differed between adherent and nonadherent women . We hypothesized that certain characteristics ( body mass index , waist circumference , weight change , smoking , triglyceride level , high-density lipoprotein cholesterol level , hypertension , and certain cardiac medications ) may mediate the effect of hormone therapy on fasting glucose level and diabetes incidence . To test this theory , we added postr and omization values of one or more hypothesized mediators as covariates to Cox regression models for incident diabetes . All analyses were conducted by using SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . A P value less than 0.05 was considered statistically significant . Role of the Funding Sources The funding sources had no role in the design or conduct of this analysis or in the decision to su bmi t the paper for publication . Results Characteristics of women enrolled in HERS did not differ substantially between the hormone therapy group and the placebo group ( Table 1 ) . At the baseline examination , 734 women ( 26.6 % ) were classified as diabetic based on self-report of diagnosis or medication use ( n = 640 [ 87.2 % ] ) or by a fasting serum glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) ( n = 101 [ 13.8 % ] ) . Impaired fasting glucose ( fasting serum glucose level , 6.0 to 6.9 mmol/L [ 110 to 125 mg/dL ] ) was noted in 218 women ( 7.9 % ) , and 1811 women ( 65.5 % ) were classified as nondiabetic ( Table 2 ) . Women with diabetes had higher body mass index , waist circumference , Seventy-six obese women with a mean age of 42.1 years and weight of 106.0 kg were r and omly assigned to one of three treatments : ( a ) very low calorie diet alone ; ( b ) behavior therapy alone ; or their combination ( i.e. combined treatment ) . Weight losses for the three conditions at the end of treatment were 13.1 , 13.0 , and 16.8 kg , respectively , with losses for combined treatment significantly greater than those for the two other conditions . Weight losses 1 year after treatment were 4.7 , 6.6 , and 10.6 kg , respectively . A significantly greater percentage of subjects in the behavior therapy alone ( 36 percent ) and combined treatment conditions ( 32 percent ) maintained their full end-of-treatment weight losses than in the very low calorie diet alone condition ( 5 percent ) . Five years after treatment , a majority of subjects in all three conditions had returned to their pretreatment weight , and 55 percent of the total sample had received additional weight reduction therapy . The short and long term effects of treatment are discussed in terms of their implication s for practice and research The beneficial effects of weight loss in the obese have been widely accepted . Still , there is a lack of controlled studies displaying large maintained weight losses over long periods ( > 4 years ) . We wanted to examine the results of long-st and ing intentional weight loss on the development of diabetes and hypertension in severely obese individuals over an 8-year period . In the ongoing prospect i ve Swedish Obese Subjects ( SOS ) study , 346 patients awaiting gastric surgery were matched with 346 obese control subjects on 18 variables by a computerized matching program . The controls were drawn from a registry consisting of 1508 obese potential controls examined at primary health care centers in Sweden . Of the 692 selected patients ( body mass index 41.2+/-4.7 kg/m(2 ) [ mean+/-SD ] ) , 483 ( 70 % ) were followed for 8 years . No significant weight changes occurred in the obese control group over 8 years . Gastric surgery result ed in a maximum weight loss of -31.1+/-13.6 kg after 1 year . After 8 years , the maintained weight loss was still 20.1+/-15.7 kg ( 16.3+/-12.3 % ) . Whereas this weight reduction had a dramatic effect on the 8-year incidence of diabetes ( odds ratio 0.16 , 95 % CI 0.07 to 0.36 ) , it had no effect on the 8-year incidence of hypertension ( odds ratio 1.01 , 95 % CI 0.61 to 1.67 ) . A differentiated risk factor response was identified : a maintained weight reduction of 16 % strongly counteracted the development of diabetes over 8 years but showed no long-term effect on the incidence of hypertension 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 CONTEXT Type 2 diabetes is a growing clinical and public health problem . Preventive efforts related to lifestyle modification are not always successful ; therefore , alternative prevention strategies need to be studied . OBJECTIVE To investigate the effectiveness of ramipril , an angiotensin-converting enzyme inhibitor , in preventing diabetes among high-risk persons . DESIGN , SETTING , AND PARTICIPANTS The r and omized , controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years . The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999 . INTERVENTION Patients were r and omly assigned to receive ramipril , up to 10 mg/d ( n = 2837 ) , or placebo ( n = 2883 ) . MAIN OUTCOME MEASURE Diagnosis of diabetes determined from self-report at follow-up visits every 6 months , compared between the 2 groups . RESULTS One hundred and two individuals ( 3.6 % ) in the ramipril group developed diabetes compared with 155 ( 5.4 % ) in the placebo group ( relative risk [ RR ] , 0.66 ; 95 % confidence interval [ CI ] , 0.51 - 0.85 , P<.001 ) . Similar results were noted when different diagnostic criteria were used ; in the ramipril group , the RR for diagnosis of diabetes and hemoglobin A(1c ) greater than 110 % was 0.60 ( 95 % CI , 0.43 - 0.85 ) , for initiation of glucose-lowering therapy , 0.56 ( 95 % CI , 0.41 - 0.77 ) , and for both , 0.51 ( 95 % CI , 0.34 - 0.76 ) . These effects were also consistently seen in several subgroups examined . CONCLUSIONS Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals . Because these results have important clinical and public health implication s , this hypothesis requires prospect i ve confirmation BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy BACKGROUND New diagnostic criteria for diabetes based on fasting blood glucose ( FBG ) level were approved by the American Diabetes Association . The impact of using FBG only has not been evaluated thoroughly . The fasting and the 2-hour glucose ( 2h-BG ) criteria were compared with regard to the prediction of mortality . METHODS Existing baseline data on glucose level at fasting and 2 hours after a 75-g oral glucose tolerance test from 10 prospect i ve European cohort studies including 15 388 men and 7126 women aged 30 to 89 years , with a median follow-up of 8.8 years , were analyzed . Hazards ratios for death from all causes , cardiovascular disease , coronary heart disease , and stroke were estimated . RESULTS Multivariate Cox regression analyses showed that the inclusion of FBG did not add significant information on the prediction of 2h-BG alone ( P>.10 for various causes ) , whereas the addition of 2h-BG to FBG criteria significantly improved the prediction ( P<.001 for all causes and P<.005 for cardiovascular disease ) . In a model including FBG and 2h-BG simultaneously , hazards ratios ( 95 % confidence intervals ) in subjects with diabetes on 2h-BG were 1.73 ( 1.45 - 2.06 ) for all causes , 1.40 ( 1.02 - 1.92 ) for cardiovascular disease , 1.56 ( 1.03 - 2.36 ) for coronary heart disease , and 1.29 ( 0.66 - 2.54 ) for stroke mortality , compared with the normal 2h-BG group . Compared with the normal FBG group , the corresponding hazards ratios in subjects with diabetes on FBG were 1.21 ( 1.01 - 1.44 ) , 1.20 ( 0.88 - 1.64 ) , 1.09 ( 0.71 - 1.67 ) , and 1.64 ( 0.88 - 3.07 ) , respectively . The largest number of excess deaths was observed in subjects who had impaired glucose tolerance but normal FBG levels . CONCLUSION The 2h-BG is a better predictor of deaths from all causes and cardiovascular disease than is FBG OBJECTIVE To estimate the effect of intentional weight loss on mortality in overweight individuals with diabetes . RESEARCH DESIGN AND METHODS We performed a prospect i ve analysis with a 12-year mortality follow-up ( 1959 - 1972 ) of 4,970 overweight individuals with diabetes , 40 - 64 years of age , who were enrolled in the American Cancer Society 's Cancer Prevention Study I. Rate ratios ( RRs ) were calculated , comparing overall death rates , and death from cardiovascular disease ( CVD ) or diabetes in individuals with and without reported intentional weight loss . RESULTS Intentional weight loss was reported by 34 % of the cohort . After adjustment for initial BMI , sociodemographic factors , health status , and physical activity , intentional weight loss was associated with a 25 % reduction in total mortality ( RR = 0.75 ; 95 % CI 0.67 - 0.84 ) , and a 28 % reduction in CVD and diabetes mortality ( RR = 0.72 ; 0.63 - 0.82 ) . Intentional weight loss of 20 - 29 lb was associated with the largest reductions in mortality ( approximately 33 % ) . Weight loss > 70 lb was associated with small increases in mortality CONCLUSIONS Intentional weight loss was associated with substantial reductions in mortality in this observational study of overweight individuals with diabetes We tested the hypothesis that the use of a very-low-calorie diet ( VLCD ) in combination with behavior modification would promote long-term glycemic control in obese type 2 diabetic subjects . Thirty-six diabetic subjects were r and omly assigned to a st and ard behavior therapy program or to a behavior therapy program that included an 8-week period of VLCD . The behavior therapy group consumed a balanced diet of 4200 to 6300 J/d throughout the 20-week program . The VLCD group consumed a balanced diet of 4200 to 6300 J for weeks 1 to 4 , followed by a VLCD ( 1680 J/d of lean meat , fish , and fowl ) for weeks 5 to 12 . The VLCD group then gradually reintroduced other foods during weeks 13 to 16 and consumed a balanced diet of 4200 to 6300 J/d for weeks 17 to 20 . Thirty-three of the 36 subjects completed the 20-week program and the 1-year follow-up . Use of the VLCD produced greater decreases in fasting glucose at the end of the 20-week program and at 1-year follow-up and greater long-term reductions in HbA1 . The VLCD group also had greater weight losses at week 20 , but weight losses from pretreatment to 1-year follow-up were similar in the two treatment groups . The improved glycemic control with the VLCD appeared to be due to increased insulin secretion , but further research is needed to confirm this 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<0.001 for both comparisons between the groups ) . The 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<0.001 ) in the intervention group . The reduction in 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 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 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 BACKGROUND The worldwide increase in type 2 diabetes mellitus is becoming a major health concern . We aim ed to assess the effect of acarbose in preventing or delaying conversion of impaired glucose tolerance to type 2 diabetes . METHODS In a multicentre , placebo-controlled r and omised trial , we r and omly allocated patients with impaired glucose tolerance to 100 mg acarbose or placebo three times daily . The primary endpoint was development of diabetes on the basis of a yearly oral glucose tolerance test ( OGTT ) . Analyses were by intention to treat . FINDINGS We r and omly allocated 714 patients with impaired glucose tolerance to acarbose and 715 to placebo . We excluded 61 ( 4 % ) patients because they did not have impaired glucose tolerance or had no postr and omisation data . 211 ( 31 % ) of 682 patients in the acarbose group and 130 ( 19 % ) of 686 on placebo discontinued treatment early . 221 ( 32 % ) patients r and omised to acarbose and 285 ( 42 % ) r and omised to placebo developed diabetes ( relative hazard 0.75 [ 95 % CI 0.63 - 0.90 ] ; p=0.0015 ) . Furthermore , acarbose significantly increased reversion of impaired glucose tolerance to normal glucose tolerance ( p<0.0001 ) . At the end of the study , treatment with placebo for 3 months was associated with an increase in conversion of impaired glucose tolerance to diabetes . The most frequent side-effects to acarbose treatment were flatulence and diarrhoea . INTERPRETATION Acarbose could be used , either as an alternative or in addition to changes in lifestyle , to delay development of type 2 diabetes in patients with impaired glucose tolerance OBJECTIVE To assess the effects of lifestyle intervention on cardiovascular risk factors in general and especially on fibrinolysis . DESIGN R and omized clinical study . SUBJECTS A total of 186 subjects with impaired glucose tolerance and obesity . INTERVENTIONS The intervention programme included a low-fat , high-fibre diet and regular physical exercise . Half of the participants ( n = 93 ) took part in a one-month learning and training session using different behavioural modification techniques and conducted in a full-board wellness centre ( intense intervention group ) . The other half ( n = 93 ) was r and omized a one-hour counselling session with a specially trained nurse ( usual care group ) . Follow-up was carried out after 12 months . MAIN OUTCOME MEASURES Body weight , oxygen consumption , plasminogen activator inhibitor type 1 ( PAI-1 ) activity , tissue plasminogen activator ( tPA ) antigen , fibrinogen and fasting plasma insulin measured at the start of the programme and at follow-up after 1 year . RESULTS The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group . Oxygen consumption in the intense group increased 10 % vs. a 1 % decline in the usual care group . In the intense group , PAI-1 activity decreased 31 % ( -10.1 U mL(-1 ) ) , which was significantly more than in the usual care group ( 12 % ; -3.0 U mL(-1 ) ) . The corresponding reductions in tPA antigen were 14 % ( -1.65 microg L(-1 ) ) and 6 % ( -0.69 microg L(-1 ) ) . CONCLUSIONS The present r and omized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis 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 Selective attrition causes serious threats to the validity of experimental trials . Experimental studies in behavior therapy typically include only data from those who complete an experiment . In this paper , we examine the probability of dropping out of a study contingent upon failure to achieve desired benefits . The data are derived from an experimental trial evaluating the effects of weight loss for patients with Diabetes Mellitus . Seventy-six percent of the original participants completed the intervention and the follow-up assessment s. However , the probability of failing to appear for follow-ups over an 18 month period was examined . The chances of dropping out of the study were significantly higher for those who did not achieve a goal of weight reduction . This selective loss to follow-up results in an overestimate of treatment effectiveness . By failing to acknowledge drop-outs , treatment failures may be systematic ally eliminated from the analyses Background —The Women ’s Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause . Methods and Results —There were 275 premenopausal women r and omized into the assessment only group and 260 women into the intervention group . The mean age of participants at baseline was 47 years , and 92 % of the women were white . The mean LDL cholesterol was 115 mg/dL at baseline , and mean body mass index was 25 kg/m2 . The follow-up through 54 months was excellent . By 54 months , 35 % of the women had become postmenopausal . At the 54-month examination , there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment -only group ( P = 0.009 ) . Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment -only group ( P = 0.000 ) . Triglycerides and glucose also increased significantly more in the assessment -only group than in the intervention group . Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment -only group ( P = 0.000 ) . Conclusions —The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol . The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause . The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers OBJECTIVE The Diabetes Prevention Program ( DPP ) is a 27-center r and omized clinical trial design ed to evaluate the safety and efficacy of interventions that may delay or prevent development of diabetes in people at increased risk for type 2 diabetes . RESEARCH DESIGN AND METHODS Eligibility requirements were age > or = 25 years , BMI > or = 24 kg/m2 ( > or = 22 kg/m2 for Asian-Americans ) , and impaired glucose tolerance plus a fasting plasma glucose of 5.3 - 6.9 mmol/l ( or < or = 6.9 mmol for American Indians ) . R and omization of participants into the DPP over 2.7 years ended in June 1999 . Baseline data for the three treatment groups -- intensive lifestyle modification , st and ard care plus metformin , and st and ard care plus placebo -- are presented for the 3,234 participants who have been r and omized . RESULTS Of all participants , 55 % were Caucasian , 20 % were African-American , 16 % were Hispanic , 5 % were American Indian , and 4 % were Asian-American . Their average age at entry was 51 + /- 10.7 years ( mean + /- SD ) , and 67.7 % were women . Moreover , 16 % were < 40 years of age , and 20 % were > or = 60 years of age . Of the women , 48 % were postmenopausal . Men and women had similar frequencies of history of hypercholesterolemia ( 37 and 33 % , respectively ) or hypertension ( 29 and 26 % , respectively ) . On the basis of fasting lipid determinations , 54 % of men and 40 % of women fit National Cholesterol Education Program criteria for abnormal lipid profiles . More men than women were current or former cigarette smokers or had a history of coronary heart disease . Furthermore , 66 % of men and 71 % of women had a first-degree relative with diabetes . Overall , BMI averaged 34.0 + /- 6.7 kg/m2 at baseline with 57 % of the men and 73 % of women having a BMI > or = 30 kg/m2 . Average fasting plasma glucose ( 6.0 + /- 0.5 mmol/l ) and HbA1c ( 5.9 + /- 0.5 % ) in men were comparable with values in women ( 5.9 + /- 0.4 mmol/l and 5.9 + /- 0.5 % , respectively ) . CONCLUSIONS The DPP has successfully r and omized a large cohort of participants with a wide distribution of age , obesity , and ethnic and racial background s who are at high risk for developing type 2 diabetes . The study will examine the effects of interventions on the development of diabetes OBJECTIVE To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance ( IGT ) . RESEARCH DESIGN AND METHODS This study compared the effects of an American Heart Association ( AHA ) step 2 diet ( < 30 % of total calories as fat , < 7 % saturated fat , 55 % carbohydrate , and < 200 mg cholesterol daily ) plus endurance exercise for 1 h three times a week ( treatment group ) with an AHA step 1 diet ( 30 % of total calories as fat , 10 % saturated fat , 50 % carbohydrate , and < 300 mg cholesterol ) plus stretching exercise three times a week ( control group ) on BMI , body composition ( % fat ) , and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT , 58 of whom completed the study . RESULTS At 6 months , the treatment group showed significantly greater reduction in percent , body fat ( -1.4 + /- 0.4 vs. -0.3 + /- 0.3 % ) ; BMI ( -1.1 + /- 0.2 vs. -0.4 + /- 0.1 kg/m(2 ) ) ; subcutaneous fat by computed tomography at the abdomen ( -29.3 + /- 4.2 vs. -5.7 + /- 5.9 cm(2 ) ) , thigh ( -13.2 + /- 3.6 vs. -3.6 + /- 3.0 cm(2 ) ) , and thorax ( -19.6 + /- 3.6 vs. -8.9 + /- 2.6 cm(2 ) ) ; and skinfold thickness at the bicep ( -2.0 + /- 0.6 vs. 1.1 + /- 0.6 mm ) and tricep ( -3.7 + /- 0.8 vs. -0.9 + /- 0.6 mm ) , which continued despite moving to home-based exercise for the last 18 months . CONCLUSIONS Diet and endurance exercise improved BMI , body composition , and body fat distribution and , thus , may delay or prevent type 2 diabetes in Japanese Americans with IGT 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 AIMS : Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity , diet and physical inactivity . The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance ( IGT ) . METHODS : A total of 102 subjects were studied , r and omised into two groups . Subjects in the intervention group received regular dietary advice , and were stimulated to lose weight and to increase their physical activity . The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity . Before and after the first year , glucose tolerance was measured and several other measurements were done . RESULTS : Body weight loss after 1 y was higher in the intervention group . The 2-h blood glucose concentration decreased 0.8±0.3 mmol/l in the intervention group and increased 0.2±0.3 mmol/l in the control group ( P<0.05 ) . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity . CONCLUSION : A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle , which improve glucose tolerance in subjects with IGT . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT The results of the XENDOS study were presented by Professor Lars Sjöström ( Gothenburg , Sweden ) , on August 26 , 2002 , at the 9th International Congress on Obesity in Sao Paulo , Brazil . XENDOS ( XENical in the prevention of Diabetes in Obese Subjects ) is a multicentre , r and omised , double-blind , placebo-controlled , parallel-group prospect i ve study performed in Sweden over a period of 4 years . The aim of XENDOS was to investigate the use of a weight loss agent ( orlistat , Xenical ) compared with lifestyle changes for the prevention of type 2 diabetes in obese patients ( body mass index > or = 30 kg/m2 ) . Weight loss was greater in the orlistat group ( -6.9 kg ; n = 1.640 ) than in the placebo group ( -4.1 kg ; n = 1.637 ; p < 0.001 ) . Such a difference in weight reduction was sufficient to significantly reduce the cumulative incidence of type 2 diabetes ( 6.2 % versus 9.0 % ; p = 0.0032 ; relative risk reduction of 37.3 % ) . The difference was especially remarkable in obese patients with impaired glucose tolerance ( 21 % of the cohort ) , with a reduction of conversion to diabetes from 28.8 % in the placebo group to 18.8 % in the orlistat group ( p < 0.005 ) and a number needed to treat to avoid one event of 11 only . Significant and sustained reductions in cardiovascular risk factors such as arterial blood pressure and lipid levels were also observed in the orlistat group as compared to the placebo group . XENDOS is the first study demonstrating that an antiobesity agent , like orlistat , is able to reduce the progression to diabetes in obese subjects as compared with lifestyle changes alone Leptin is proposed to be involved in regulation of body weight . Only little information is available on leptin concentrations in individuals with impaired glucose tolerance ( IGT ) . The aim of the present study was to assess the effect of body fat distribution and weight reduction on serum leptin levels in a prospect i ve setting in IGT subjects . Sixty-nine individuals with impaired glucose tolerance aged 45 - 64 years participated in this prospect i ve study . Serum leptin levels were about 300 % higher among females than among males , despite an only 30 % higher fat percentage in females . A close association between degree of obesity and leptin concentrations was observed in both sexes . The correlation coefficient between fat mass and leptin concentration ranged between r = 0.467- 0.817 ( p < 0.001 - 0.01 ) . A close correlation between degree of weight loss and decrease in leptin concentrations was observed in both sexes . A 10.1 kg ( 9.6 % ) decrease in body weight among females was associated with a 32 % decrease in leptin concentrations . The corresponding value among males for an 8.0 kg ( 8.6 % ) decrease was 29 % . Changes in leptin concentrations were best explained by changes in fat mass among both males and females . Body fat distribution was also of importance , especially among females . Gender associated differences in leptin concentrations appear to be largely influenced by gender differences in body fat distribution Type 2 diabetes frequently results from progressive failure of pancreatic beta-cell function in the presence of chronic insulin resistance . We tested whether chronic amelioration of insulin resistance would preserve pancreatic beta-cell function and delay or prevent the onset of type 2 diabetes in high-risk Hispanic women . Women with previous gestational diabetes were r and omized to placebo ( n = 133 ) or the insulin-sensitizing drug troglitazone ( 400 mg/day ; n = 133 ) administered in double-blind fashion . Fasting plasma glucose was measured every 3 months , and oral glucose tolerance tests ( OGTTs ) were performed annually to detect diabetes . Intravenous glucose tolerance tests ( IVGTTs ) were performed at baseline and 3 months later to identify early metabolic changes associated with any protection from diabetes . Women who did not develop diabetes during the trial returned for OGTTs and IVGTTs 8 months after study medications were stopped . During a median follow-up of 30 months on blinded medication , average annual diabetes incidence rates in the 236 women who returned for at least one follow-up visit were 12.1 and 5.4 % in women assigned to placebo and troglitazone , respectively ( P < 0.01 ) . Protection from diabetes in the troglitazone group 1 ) was closely related to the degree of reduction in endogenous insulin requirements 3 months after r and omization , 2 ) persisted 8 months after study medications were stopped , and 3 ) was associated with preservation of beta-cell compensation for insulin resistance . Treatment with troglitazone delayed or prevented the onset of type 2 diabetes in high-risk Hispanic women . The protective effect was associated with the preservation of pancreatic beta-cell function and appeared to be mediated by a reduction in the secretory dem and s placed on beta-cells by chronic insulin resistance Self-referred subjects ( N = 227 ) thought to be at risk of developing non-insulin-dependent diabetes mellitus ( NIDDM ) and with fasting plasma glucose ( FPG ) in the range of 5.5 to 7.7 mmol . L-1 on two consecutive tests 2 weeks apart were r and omized to reinforced or basic healthy-living advice . They were simultaneously allocated either to a sulfonylurea group or a control group in a two-by-two factorial design . A total of 201 subjects in three English and two French centers completed 1 year 's follow-up study . Reinforced advice recommending dietary modification and increased exercise was given every 3 months , and basic advice was given once at the initial visit . Glycemia was monitored by FPG , dietary compliance by body weight and food diaries , and fitness compliance by bicycle ergometer assessment and exercise diaries . Both reinforced and basic advice groups had a significant mean reduction in body weight ( 1.5 kg ) at 3 months , although the weight subsequently returned to baseline . After 1 year , subjects allocated to reinforced advice versus basic advice ( 1 ) reported a lower fat intake ( 34.1 % v 35.8 % , P = .04 ) with no difference in lipid profiles , ( 2 ) had improved fitness as shown by increased calculated maximal oxygen uptake ( [ Vo2max ] 2.39 v 2.18 L.min-1 , P = .007 ) with no change in insulin sensitivity , ( 3 ) showed no change in FPG , glucose tolerance , or hemoglobin A1c ( HbA1c ) , and ( 4 ) showed a greater tendency to withdraw from the study ( 16 % v 7 % , P = .03 ) . In conclusion , reinforced healthy-living advice given to self-referred subjects with increased FPG did not encourage sufficiently pronounced life-style changes for significantly greater effects on body weight and glycemia in a 1-year study than basic healthy-living advice 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 Sulfonylureas stimulate insulin secretion as their predominant contribution toward decreasing blood glucose in diabetic patients . We studied eight gliclazide-treated , non-insulin-dependent diabetic patients on two occasions with a protocol of basal observation for 30 minutes , a 60-minute infusion of r and omized leucine or arginine , and a further 90-minute hyperglycemic clamp . Basal glucose was the same on both occasions ( mean , 7.82 mmol/L for leucine v 7.79 for arginine , P = NS ) , and glucose levels declined to 7.50 and 7.25 mmol/L , respectively , by 30 minutes . After leucine infusion , the decline of glucose continued , but stabilized or reversed with arginine such that by the end of the infusions , glucose levels were 6.63 + /- 0.69 mmol/L for leucine and 7.62 + /- 0.67 for arginine ( P < .02 ) . Arginine caused a sharp increase in insulin secretion ( from 17.8 mU/L to 43.8 mU/L in 6 minutes ) at the onset of the infusion , and thereafter insulin secretion was not significantly different throughout either the amino acid or hyperglycemic clamp periods ( mean , 42.1 v 44.7 mU/L , respectively , P = NS ) . By contrast , the leucine infusion caused little acute change in secretion , but augmented it with time from the basal period ( 17.2 mU/L ) to the end of the infusion ( 29.4 mU/L ) . During the hyperglycemic clamp period , there was significant further augmentation of insulin secretion , increasing to 81.6 + /- 16 mU/L at the end of the study . Leucine significantly augmented insulin secretion compared with arginine ( 81.6 + /- 16 v 54.0 + /- 8.4 mU/L , respectively , P < .002 ) . These data suggest that leucine is a better priming agent for sulfonylurea than arginine . Additive effects on insulin secretion may allow the use of combinations of branched chain amino acids ( BCAAs ) and sulfonylureas to augment insulin secretion in the presence of hyperglycemia Relative changes in body weight and blood pressure over ten years of observation are reported in men recruited for a trial of therapy in relation to the natural history of glucose intolerance . Half were recommended a diet restricting carbohydrate to 120 g daily ( diet group ) and half were recommended to ' limit use of table sugar ' ( no diet ) . In both groups average weight and blood pressure fell over the 12 to 18 months after treatment allocation , the decline being proportionately greater for both variables in the diet group . Subsequently , average weight remained constant up to the end of the ten year study , but blood pressure levels rose , though remaining below baseline levels in the diet group . Statistical analysis of changes in blood pressure and weight between initial ( pre-treatment ) and third follow-up visit measurement indicated that the proportional change in blood pressure was related principally to change in weight , with little relation to initial level of blood pressure . Although a reduction in weight results in a fall in blood pressure , it does not necessarily prevent a subsequent age related increase in blood pressure OBJECTIVE To investigate the effects of insulin resistance ( IR ) and insulin secretion ( IS ) on the development of diabetes mellitus in individuals with impaired glucose tolerance ( IGT ) who underwent lifestyle interventions . METHODS 284 out of 577 individuals with IGT identified by population -based screening in Da Qing , China , who were r and omized to undergo diet change and /or increased physical activity had baseline fasting and 2 h post-load insulin determinations . They were followed for 6 years for the development of diabetes . IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose . The interactions of IR , IS , obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis . RESULTS Both IR and IS were significantly associated with the development of diabetes . Lifestyle interventions were more effective in those with lower IT and higher IS at baseline . Diet plus exercise interventions result ed in significantly lower incidence of diabetes , even after controlling for IR , IS , BMI and 2hrPG . CONCLUSION Both IR and beta-cell function were predictors of diabetes in Chinese with IGT . Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR The Diabetes Prevention Program ( DPP ) is a multicenter r and omized controlled trial design ed to test whether diet and exercise or medication can prevent or delay the onset of type 2 diabetes in persons with impaired glucose tolerance , who are at increased risk of the disease . This paper describes DPP recruitment methods , strategies , performance , and costs . The DPP developed an organizational structure for comprehensive management and continuous monitoring of recruitment efforts . The DPP utilized a variety of recruitment strategies , alone or in combination , and a stepped informed consent procedure leading to r and omization . Study wide and clinic-specific recruitment data were monitored , analyzed , and used to modify recruitment approaches . DPP recruitment was completed slightly ahead of schedule , meeting goals for the proportion of women enrolled and nearly meeting goals for the proportion of racial/ethnic minorities . Clinics varied widely in the recruitment strategies they used , and these strategies also varied by participant age , gender , and race/ethnicity . Staff time devoted to recruitment averaged 86.8 hours per week per clinic , with the majority of effort by staff specifically assigned to recruitment . The number of staff hours required to recruit a participant varied by recruitment strategy . Recruitment cost ( excluding staff cost ) was about 1075 US dollars per r and omized participant . The DPP experience offers lessons for those planning similar efforts : ( 1 ) a method for ongoing assessment and revision of recruitment strategies is valuable ; ( 2 ) a range of recruitment strategies may be useful ; ( 3 ) the most effective methods for recruiting potential subjects may vary according to the gender , age , and race/ethnicity of those individuals ; ( 4 ) recruitment strategies vary in the amount of staff time required to r and omize a participant ; and ( 5 ) a stepped screening may make it easier to identify and recruit volunteers who underst and the requirements of the study OBJECTIVE To determine if weight loss may prevent conversion of impaired glucose tolerance ( IGT ) to diabetes , because weight loss reduces insulin resistance . The prevalence of IGT in the U. S. population is estimated at 11.2 % , more than twice that of diabetes . Furthermore , because an oral glucose tolerance test is needed for its detection , most of these patients are undiagnosed . Screening for IGT would be meaningful if progression to diabetes could be delayed or prevented . RESEARCH DESIGN AND METHODS For an average of 5.8 years ( range 2–10 years ) , 136 individuals with IGT and clinical ly severe obesity ( > 45 kg excess body weight ) were followed . The experimental group included 109 patients with IGT who underwent bariatric surgery for weight loss . The control group was made up of 27 subjects with IGT who did not have bariatric surgery . The criteria of the World Health Organization was used to detect IGT and diabetes in this population . The main outcome measure of this nonr and omized control trial is the incidence density , or number of events ( development of diabetes ) divided by the time of exposure to risk . RESULTS Of the 27 subjects in the control group , 6 developed diabetes during an average of 4.8 ± 2.5 years of postdiagnosis follow-up , yielding a rate of conversion to diabetes of 4.72 cases per 100 person-years . The 109 individuals of the experimental group were followed for an average of 6.2 ± 2.5 years postbariatric surgery . Based on the 95 % confidence interval of the comparison group , we would expect to find that between 22 and 36 subjects in the experimental group developed diabetes over the follow-up period . Only 1 of the 109 experimental-group patients developed diabetes , result ing in a conversion rate of the experimental group of only 0.15 cases per 100 person-years , which is significantly lower ( P < 0.0001 ) than the control group . CONCLUSIONS Weight loss in patients with clinical ly severe obesity prevents the progression of IGT to diabetes by > 30-fold OBJECTIVE The effects of three cognitive-behavioral weight control interventions for adults were compared : diet only , exercise only , and a combination of diet and exercise . This article reports 2-year follow-up data . DESIGN The three interventions were compared in a r and omized , experimental design . SUBJECTS A total of 127 men and women who were at least 14 kg overweight ( according to height-weight tables ) were recruited from an urban community and assigned r and omly to the experimental conditions . INTERVENTION The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight . The exercise component involved training in walking and a home-based program of up to five exercise periods per week . There were 12 weekly instructional sessions , followed by 3 biweekly and 8 monthly meetings . All sessions were led by registered dietitians . OUTCOME MEASURES Changes in body weight . STATISTICAL ANALYSES Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends . RESULTS At 1 year , no significant differences were noted among the three groups . The diet-only group lost 6.8 kg , the exercise-only group lost 2.9 kg , and the combination group lost 8.9 kg ( P=.09 ) . During the second year , the diet-only group regained weight -- reaching 0.9 kg above baseline ; the combination group regained to 2.2 kg below baseline ; and the exercise-only group regained slightly to 2.7 kg below baseline ( P=.36 ) . Repeated measures analysis of variance showed a group-by-time interaction ( P=.001 ) ; data for the dieting groups best fit a U-shaped regain curve ( P=.001 ) . APPLICATIONS The results suggest that dieting is associated with weight loss followed by regain after treatment ends , whereas exercise alone produced smaller weight losses but better maintenance . The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings |
13,025 | 29,147,869 | Conclusion Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all- grade and high- grade hematological adverse events , which seems to be a class-effect , but not of febrile neutropenia compared with hormonal therapy alone | Background The introduction of specific cyclin-dependent kinase 4 and 6 ( CDK4/6 ) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer .
CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect .
Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting . | Background Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 . In the r and omized , open-label , phase II PALOMA-1/TRIO-18 trial , palbociclib in combination with letrozole improved progression-free survival ( PFS ) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive , human epidermal growth factor receptor 2 (HER2)-negative , advanced breast cancer ( 20.2 months versus 10.2 months ; hazard ratio ( HR ) = 0.488 , 95 % confidence interval ( CI ) 0.319–0.748 ; one-sided p = 0.0004 ) . Grade 3–4 neutropenia was the most common adverse event ( AE ) in the palbociclib + letrozole arm . We now present efficacy and safety analyses based on several specific patient and tumor characteristics , and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population . Methods Postmenopausal women ( n = 165 ) with ER+ , HER2-negative , advanced breast cancer who had not received any systemic treatment for their advanced disease were r and omized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone . Treatment continued until disease progression , unacceptable toxicity , consent withdrawal , or death . The primary endpoint was PFS . We now analyze the difference in PFS for the treatment population s by subgroups , including age , histological type , history of prior neoadjuvant/adjuvant systemic treatment , and sites of distant metastasis , using the Kaplan-Meier method . HR and 95 % CI are derived from a Cox proportional hazards regression model . Results A clinical ly meaningful improvement in median PFS and clinical benefit response ( CBR ) rate was seen with palbociclib + letrozole in every subgroup evaluated . Grade 3–4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups . Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3–4 neutropenia over time . Among those who experienced Grade 3–4 neutropenia , 71.7 % had no overlapping infections of any grade and none had overlapping Grade 3–4 infections . Conclusion The magnitude of clinical benefit seen with the addition of palbociclib to letrozole in improving both median PFS and CBR rate is consistent in nearly all subgroups analyzed , and consistent with that seen in the overall study population . The safety profile of the combination treatment in all subgroups was also comparable to that in the overall safety population of the study Purpose Abemaciclib , a cyclin-dependent kinase 4 and 6 inhibitor , demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy . Methods MONARCH 3 is a double-blind , r and omized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive , HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting . Patients received abemaciclib or placebo ( 150 mg twice daily continuous schedule ) plus either 1 mg anastrozole or 2.5 mg letrozole , daily . The primary objective was investigator-assessed progression-free survival . Secondary objectives included response evaluation and safety . A planned interim analysis occurred after 189 events . Results Median progression-free survival was significantly prolonged in the abemaciclib arm ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.72 ; P = .000021 ; median : not reached in the abemaciclib arm , 14.7 months in the placebo arm ) . In patients with measurable disease , the objective response rate was 59 % in the abemaciclib arm and 44 % in the placebo arm ( P = .004 ) . In the abemaciclib arm , diarrhea was the most frequent adverse effect ( 81.3 % ) but was mainly grade 1 ( 44.6 % ) . Comparing abemaciclib and placebo , the most frequent grade 3 or 4 adverse events were neutropenia ( 21.1 % v 1.2 % ) , diarrhea ( 9.5 % v 1.2 % ) , and leukopenia ( 7.6 % v 0.6 % ) . Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy , significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive , HER2-negative advanced breast cancer OBJECTIVES Cyclin D-cyclin-dependent kinase ( CDK ) 4/6-inhibitor of CDK4/6-retinoblastoma ( Rb ) pathway hyperactivation is associated with hormone receptor-positive ( HR+ ) breast cancer ( BC ) . This study assessed the biological activity of ribociclib ( LEE011 ; CDK4/6 inhibitor ) plus letrozole compared with single-agent letrozole in the presurgical setting . MATERIAL S AND METHODS Postmenopausal women ( N = 14 ) with resectable , HR+ , human epidermal growth factor receptor 2-negative ( HER2- ) early BC were r and omized 1:1:1 to receive 2.5 mg/day letrozole alone ( Arm 1 ) , or with 400 or 600 mg/day ribociclib ( Arm 2 or 3 ) . Circulating tumor DNA and tumor biopsies were collected at baseline and , following 14 days of treatment , prior to or during surgery . The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1 . Additional assessment s included safety , pharmacokinetics , and genetic profiling . RESULTS Mean decreases in the Ki67-positive cell fraction from baseline were : Arm 1 69 % ( range 38 - 100 % ; n = 2 ) , Arm 2 96 % ( range 78 - 100 % ; n = 6 ) , Arm 3 92 % ( range 75 - 100 % ; n = 3 ) . Decreased phosphorylated Rb levels and CDK4 , CDK6 , CCND2 , CCND3 , and CCNE1 gene expression were observed following ribociclib treatment . Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data . The ribociclib plus letrozole combination was well tolerated , with no Grade 3/4 adverse events over the treatment . CONCLUSION The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+ , HER2- BC ( NCT01919229 ) Purpose MONARCH 2 ( Clinical Trials.gov identifier : NCT02107703 ) compared the efficacy and safety of abemaciclib , a selective cyclin-dependent kinase 4 and 6 inhibitor , plus fulvestrant with fulvestrant alone in patients with advanced breast cancer ( ABC ) . Patients and Methods MONARCH 2 was a global , double-blind , phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy ( ET ) , ≤ 12 months from the end of adjuvant ET , or while receiving first-line ET for metastatic disease . Patients were r and omly assigned 2:1 to receive abemaciclib or placebo ( 150 mg twice daily ) on a continuous schedule and fulvestrant ( 500 mg , per label ) . The primary end point was investigator-assessed progression-free survival ( PFS ) , and key secondary end points included overall survival , objective response rate ( ORR ) , duration of response , clinical benefit rate , quality of life , and safety . Results Between August 2014 and December 2015 , 669 patients were r and omly assigned to receive abemaciclib plus fulvestrant ( n = 446 ) or placebo plus fulvestrant ( n = 223 ) . Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone ( median , 16.4 v 9.3 months ; hazard ratio , 0.553 ; 95 % CI , 0.449 to 0.681 ; P < .001 ) . In patients with measurable disease , abemaciclib plus fulvestrant achieved an ORR of 48.1 % ( 95 % CI , 42.6 % to 53.6 % ) compared with 21.3 % ( 95 % CI , 15.1 % to 27.6 % ) in the control arm . The most common adverse events in the abemaciclib versus placebo arms were diarrhea ( 86.4 % v 24.7 % ) , neutropenia ( 46.0 % v 4.0 % ) , nausea ( 45.1 % v 22.9 % ) , and fatigue ( 39.9 % v 26.9 % ) . Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective , significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET thous and s of false-positive findings and strain health care re sources . Though reluctant to rule out that a protein biomarker could reveal new pancreatic tumors , Goggins questions whether proteins in general are selective enough to avoid diagnostic overlap with other , noncancerous problems . Such proteins include the initial 28 in the M. D. And erson study , he said , most of which are elevated under multiple setting s. Goggins 's views on biomarker c and i date s lean more toward circulating tumor DNA snippets in blood , or circulating tumor cells , which he said could be more specific to pancreatic cancer . However , Firpo maintains that protein-based panels can be continually improved . " Each biomarker is individually a weak classifier , so our goal is to combine them into stronger classifier panels , " he said . " That approach has mathematical validity , and this latest study shows that we 're making progress , even though we 're not there yet . " According to Taguchi , the next step will be to vali date current results and then investigate the panel in prediagnostic blood sample s , which will help ensure its predic-tive value . professor and pancreatic cancer specialist at Cold Spring Harbor Laboratory in New York , and a program chair at the American Association for Cancer Research conference , agrees that 's the right approach . Emphasizing optimism over pessimism is important , he said . " However , we now need to substantiate the panel on retrospective cases , and perhaps also with a new prospect i ve series from the general population or from patients who are at high risk . " Sources for this story all agreed that the panel is not ready for the clinic . Screening high-risk individuals is now performed exclusively with imaging , as described in P albociclib , the first in a new class of drugs to complete phase II testing , doubled progression-free survival ( PFS ) in women with metastatic estro-gen receptor – positive ( ER + ) and HER2-negative ( HER2 – ) breast cancer when given with st and ard hormone therapy , compared with hormone therapy alone . In the 47-patient r and omized study , those taking palbociclib and the aromatase inhibitor letrozole had a median PFS of 20.2 months , compared with 10.2 months for those taking letrozole alone . Women taking the combination lived a mean of 4 months longer ( 37.5 vs. 33.3 months ) . But increased survival did not reach statistical significance , said at April 's American Association of Cancer Research meeting in San Diego . The Food and Drug Administration design ated palbociclib a breakthrough therapy in April 2013 . Palbociclib targets two cell cycle enzymes , cyclin-dependent Purpose : To identify the dose-limiting toxicity ( DLT ) and maximum tolerated dose ( MTD ) of the first-in-class , oral CDK4/6 inhibitor PD 0332991 administered once daily for 21 of 28 days ( 3/1 schedule ) in patients with retinoblastoma protein (Rb)-positive advanced solid tumors and to describe pharmacokinetic – pharmacodynamic relationships relative to drug effects . Experimental Design : This open-label phase I study ( NCT00141297 ) enrolled patients who received PD 0332991 orally in six dose-escalation cohorts in a st and ard 3 + 3 design . Results : Forty-one patients were enrolled . DLTs were observed in five patients ( 12 % ) overall ; at the 75 , 125 , and 150 mg once daily dose levels . The MTD and recommended phase II dose of PD 0332991 was 125 mg once daily . Neutropenia was the only dose-limiting effect . After cycle 1 , grade 3 neutropenia , anemia , and leukopenia occurred in five ( 12 % ) , three ( 7 % ) , and one ( 2 % ) patient(s ) , respectively . The most common non-hematologic adverse events included fatigue , nausea , and diarrhea . Thirty-seven patients were evaluable for tumor response ; 10 ( 27 % ) had stable disease for ≥4 cycles of whom six derived prolonged benefit ( ≥10 cycles ) . PD 0332991 was slowly absorbed ( median Tmax , 5.5 hours ) , and slowly eliminated ( mean half-life was 25.9 hours ) with a large volume of distribution ( mean , 2,793 L ) . The area under the concentration – time curve increased linearly with dose . Using an Emax model , neutropenia was shown to be proportional to exposure . Conclusions : PD 0332991 warrants phase II testing at 125 mg once daily , at which dose neutropenia was the sole significant toxicity . Clin Cancer Res ; 18(2 ) ; 568–76 . © 2011 AACR INTRODUCTION Effective therapies after failure of treatment with anthracyclines and taxanes are needed for patients with metastatic breast cancer . Dinaciclib ( MK-7965 , formerly SCH727965 ) , a small-molecule cyclin-dependent kinase inhibitor , has demonstrated antitumor activity in phase I studies with solid-tumor patients . This phase II trial was design ed to assess the efficacy and safety of dinaciclib compared with that of capecitabine in women with previously treated advanced breast cancer . PATIENTS AND METHODS Patients were r and omized to receive either dinaciclib at 50 mg/m(2 ) , administered as a 2-hour infusion every 21 days , or 1250 mg/m(2 ) capecitabine , administered orally twice daily in 21-day cycles . RESULTS An unplanned interim analysis showed that the time to disease progression was inferior with dinaciclib treatment compared with capecitabine treatment ; therefore , the trial was stopped after 30 patients were r and omized . Dinaciclib treatment demonstrated antitumor activity in 2 of 7 patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer ( 1 confirmed and 1 unconfirmed partial response ) , as well as acceptable safety and tolerability . Grade 3 or 4 treatment-related adverse events were common and included neutropenia , leukopenia , increase in aspartate aminotransferase , and febrile neutropenia . Population pharmacokinetic model-predicted mean dinaciclib exposure ( area under the concentration-time curve extrapolated to infinity [ AUC[I ] ] ) at 50 mg/m(2 ) was similar to that observed in a previous phase I trial , and no drug accumulation was observed after multiple-dose administration . CONCLUSION Although dinaciclib monotherapy demonstrated some antitumor activity and was generally tolerated , efficacy was not superior to capecitabine . Future studies may be considered to evaluate dinaciclib in select patient population s with metastatic breast cancer and in combination with other agents BACKGROUND Palbociclib ( PD-0332991 ) is an oral , small-molecule inhibitor of cyclin-dependent kinases ( CDKs ) 4 and 6 with pre clinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens . We aim ed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced , oestrogen receptor-positive , HER2-negative breast cancer . METHODS In this open-label , r and omised phase 2 study , postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate . Patients were enrolled in two separate cohorts that accrued sequentially : in cohort 1 , patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone , whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 ( CCND1 ) , loss of p16 ( INK4A or CDKN2A ) , or both . In both cohorts , patients were r and omly assigned 1:1 via an interactive web-based r and omisation system , stratified by disease site and disease-free interval , to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg , given once daily for 3 weeks followed by 1 week off over 28-day cycles . The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population . Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 ( instead of cohort 2 alone ) . The study is ongoing but closed to accrual ; these are the results of the final analysis of progression-free survival . The study is registered with the Clinical Trials.gov , number NCT00721409 . FINDINGS Between Dec 22 , 2009 , and May 12 , 2012 , we r and omly assigned 165 patients , 84 to palbociclib plus letrozole and 81 to letrozole alone . At the time of the final analysis for progression-free survival ( median follow-up 29.6 months [ 95 % CI 27.9 - 36.0 ] for the palbociclib plus letrozole group and 27.9 months [ 25.5 - 31.1 ] for the letrozole group ) , 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group . Median progression-free survival was 10.2 months ( 95 % CI 5.7 - 12.6 ) for the letrozole group and 20.2 months ( 13.8 - 27.5 ) for the palbociclib plus letrozole group ( HR 0.488 , 95 % CI 0.319 - 0.748 ; one-sided p=0.0004 ) . In cohort 1 ( n=66 ) , median progression-free survival was 5.7 months ( 2.6 - 10.5 ) for the letrozole group and 26.1 months ( 11.2-not estimable ) for the palbociclib plus letrozole group ( HR 0.299 , 0.156 - 0.572 ; one-sided p<0.0001 ) ; in cohort 2 ( n=99 ) , median progression-free survival was 11.1 months ( 7.1 - 16.4 ) for the letrozole group and 18.1 months ( 13.1 - 27.5 ) for the palbociclib plus letrozole group ( HR 0.508 , 0.303 - 0.853 ; one-sided p=0.0046 ) . Grade 3 - 4 neutropenia was reported in 45 ( 54 % ) of 83 patients in the palbociclib plus letrozole group versus one ( 1 % ) of 77 patients in the letrozole group , leucopenia in 16 ( 19 % ) versus none , and fatigue in four ( 4 % ) versus one ( 1 % ) . Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism ( three [ 4 % ] patients ) , back pain ( two [ 2 % ] ) , and diarrhoea ( two [ 2 % ] ) . No cases of febrile neutropenia or neutropenia-related infections were reported during the study . 11 ( 13 % ) patients in the palbociclib plus letrozole group and two ( 2 % ) in the letrozole group discontinued the study because of adverse events . INTERPRETATION The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer . A phase 3 trial is currently underway . FUNDING Pfizer |
13,026 | 31,489,762 | One study was a r and omized controlled trial , 14 were pre design s and post design s , and two were longitudinal observational design s. The Group 1 studies demonstrated that ACS care pathways had a positive effect on reducing the length of the hospital stay and the door-to-balloon times .
Implementing ACS care pathway helps to organize care processes and decrease treatment delays as well as improve the patient outcomes without adverse consequences for patients or additional re sources and costs . | BACKGROUND Health care institutions need to construct management strategies for patients diagnosed with acute coronary syndrome ( ACS ) that focus on evidence -based treatments , adherence to treatment guidelines , and organized care .
These help to reduce variations as well as the mortality and morbidity rates , which indicates the critical need for st and ardized care and adherence to evidence -based practice s for patients hospitalized with ACS .
The care pathways translate research and guidelines into clinical practice to close the gap between the guidelines and the clinical practice s. OBJECTIVES This review focuses on identifying the indicators used to evaluate ACS care pathways and their effect on the care process and clinical outcomes . | Objective To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infa rct ion in Sweden and the United Kingdom . Design Population based longitudinal cohort study using nationwide clinical registries . Setting and participants Nationwide registry data comprising all hospitals providing acute myocardial infa rct ion care in Sweden ( SWEDEHEART/RIKS-HIA , n=87 ; 119 786 patients ) and the UK ( NICOR/MINAP , n=242 ; 391 077 patients ) , 2004 - 10 . Main outcome measures Between hospital variation in 30 day mortality of patients admitted with acute myocardial infa rct ion . Results Case mix st and ardised 30 day mortality from acute myocardial infa rct ion was lower in Swedish hospitals ( 8.4 % ) than in UK hospitals ( 9.7 % ) , with less variation between hospitals ( interquartile range 2.6 % v 3.5 % ) . In both countries , hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care . Compared with the highest quarter , hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infa rct ion ( 10.7 % v 6.6 % in Sweden ; 12.7 % v 5.8 % in the UK ) . The adjusted odds ratio comparing the highest with the lowest quarters for hospitals ’ use of primary percutaneous coronary intervention was 0.70 ( 95 % confidence interval 0.62 to 0.79 ) in Sweden and 0.68 ( 0.60 to 0.76 ) in the UK . Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infa rct ion and secondary prevention drugs for all discharged acute myocardial infa rct ion patients were smaller than for reperfusion treatment in both countries . Conclusion Between hospital variation in 30 day mortality for acute myocardial infa rct ion was greater in the UK than in Sweden . This was associated with , and may be partly accounted for by , the higher practice variation in acute myocardial infa rct ion guideline recommended treatment in the UK hospitals . High quality healthcare across all hospitals , especially in the UK , with better use of guideline recommended treatment , may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infa rct ion . Clinical trials registration Clinical trials NCT01359033 UNLABELLED Aim Integrated care pathways ( ICP ) are management technologies which formalise multidisciplinary team-working and enable professionals to examine their roles and responsibilities . ICPs are now being implemented across international healthcare arena , but evidence to support their use is equivocal . The aim of this study was to identify the circumstances in which ICPs are effective , for whom and in what context s. Methods A systematic review of high- quality r and omised controlled trials published between 1980 and 2008 ( March ) evaluating ICP use in child and adult population s in the full range of healthcare setting s. RESULTS 1 For relatively predictable trajectories of care ICPs can be effective in supporting proactive care management and ensuring that patients receive relevant clinical interventions and /or assessment s in a timely manner . This can lead to improvements in service quality and service efficiency without adverse consequences for patients . 2 ICPs are an effective mechanism for promoting adherence to guidelines or treatment protocol s thereby reducing variation in practice . 3 ICPs can be effective in improving documentation of treatment goals , documentation of communication with patients , carers and health professionals . 4 ICPs can be effective in improving physician agreement about treatment options . 5 ICPs can be effective in supporting decision-making when they incorporate a decision-aide . 6 The evidence considered in this review indicates that ICPs may be particularly effective in changing professional behaviours in the desired direction , where there is scope for improvement or where roles are new . 7 Even in context s in which health professionals are already experienced with a particular pathway , ICP use brings additional beneficial effects in directing professional practice in the desired direction . 8 ICPs may be less effective in bringing about service quality and efficiency gains in variable patient trajectories . 9 ICPs may be less effective in bringing about quality improvements in circumstances in which services are already based on best evidence and multidisciplinary working is well established . 10 Depending on their purpose , the benefits of ICPs may be greater for certain patient subgroups than others . 11 We do not know whether the costs of ICP development and implementation are justified by any of their reported benefits . 12 ICPs may need supporting mechanisms to underpin their implementation and ensure their adoption in practice , particularly in circumstances in which ICP use is a significant change in organisational culture . 13 ICP documentation can introduce scope for new kinds of error . Conclusions ICPs are most effective in context s where patient care trajectories are predictable . Their value in setting s in which recovery pathways are more variable is less clear . ICPs are most effective in bringing about behavioural changes where there are identified deficiencies in services ; their value in context s where inter-professional working is well established is less certain . None of the studies review ed included an economic evaluation and thus it is not known whether their benefits justify the costs of their implementation This study was planned in an experimental manner to use the " case management model " for the care of patients with acute myocardial infa rct ion ( MI ) , and to determine the effect of this method on the quality of care , patient and nurse satisfaction , and the patient 's inpatient duration at the hospital . Data for the study were obtained using the Patient Information Form , Acute MI Care Protocol ( Clinical Pathway ) , Care Monitoring Scale and Scoring Form , Acute MI Nursing Care Plan , Patient Education Booklet , and a Patient and Nurse Satisfaction Evaluation Survey . Evaluation results showed that the patient group where the case management model was used had increased quality of care , decreased inpatient stay , and increased satisfaction of the patient and the nurse . Therefore , it was suggested that the case management model be used in healthcare institutions in Turkey , care protocol s for various diagnoses be developed , and nurses should be trained as case managers to increase the quality of care at healthcare institutions A critical or clinical pathway defines the optimal care process , sequencing and timing of interventions by healthcare professionals for a particular diagnosis or procedure . It is a relatively new clinical process improvement tool that has been gaining popularity across hospitals and various healthcare organisations in many parts of the world . It is now slowly gaining momentum and popularity in Asia and Singapore . Clinical pathways are developed through collaborative efforts of clinicians , case managers , nurses , and other allied healthcare professionals with the aim of improving the quality of patient care , while minimising cost to the patient . Clinical pathways have been shown to reduce unnecessary variation in patient care , reduce delays in discharge through more efficient discharge planning , and improve the cost-effectiveness of clinical services . The approach and objectives of clinical pathways are consistent with those of total quality management ( TQM ) and continuous clinical quality improvement ( CQI ) , and is essentially the application of these principles at the patient 's bedside . However , despite the growing popularity of pathways , their impact on clinical outcomes and their clinical effectiveness remains largely untested and unproven through rigorous clinical trials . This paper begins with an overview of the nature of clinical pathways and the analysis of variances from the pathway , their benefits to the healthcare organisation , their application as a tool for CQI activities in direct relation to patient care , and their effectiveness in a variety of healthcare setting s. The paper describes an evaluation of the impact of a clinical pathway on the quality of care for patients admitted for uncomplicated acute myocardial infa rct ion ( AMI ) through an analysis of variances . The author carried out a one year evaluation of a clinical pathway on uncomplicated AMI in Changi General Hospital ( CGH ) to determine its effectiveness and impact on a defined set of outcomes . A before and after nonr and omized study of two groups of patients admitted to the Hospital for uncomplicated AMI was done . A total of 169 patients were managed on the clinical pathway compared to 100 patients in the control ( historical comparison ) group . Outcomes were compared between the two groups of patients . Restriction and matching of study subjects in both groups ensured that the patients selected were comparable in terms of severity of illness . The results showed that the patients on the clinical pathway and the comparison group were similar with respect to demographic variables , prevalence of risk factors and comorbidities . There was a statistically significant reduction in the average length of stay after implementation of the clinical pathway . This was achieved without any adverse effect on short term clinical outcomes such as in-hospital mortality , complication rate and morbidity . There were no significant difference in readmission rates at 6 months after discharge . The paper concludes that clinical pathways , implemented in the context of an acute care general hospital , is able to significantly improve care processes through better collaboration among healthcare professionals and improvements in work systems Objectives : To study the care pathway effect on the percentage of patients with ST-elevation myocardial infa rct ion ( STEMI ) receiving timely coronary reperfusion and the percentage of STEMI patients receiving optimal secondary prevention . Methods : A care pathway was implemented by the Collaborative Model for Achieving Breakthrough Improvement . One pre-intervention and 2 post-intervention audits included all adult STEMI patients admitted within 24 h after onset and eligible for reperfusion . Adjusted ( hospital r and om intercepts and controls for transfer and out-of-office admission ) differences in composite outcomes were analyzed by a multilevel logistic regression . Results : Significant improvements in intervals between the first medical contact ( FMC ) to percutaneous coronary intervention ( PCI ) and between the door to PCI were shown between post-intervention audit II and post-intervention audit I. Secondary prevention significantly deteriorated at post-intervention audit I but improved significantly between both post-intervention audits . Six out of nine outcomes were significantly poorer in the case of transfer . The interval from FMC to PCI was significantly poorer for patients admitted during out-of-office hours . Conclusions : After care pathway implementation , composite outcomes improved for in-hospital STEMI care . Collaborative efforts exploited heterogeneity in performance between hospitals . Iterative and incremental care pathway implementation maximized performance improvement Background While clinical pathways have the potential to improve patient outcomes and reduce healthcare costs , their true impact has been limited by variable implementation strategies and suboptimal research design s. This paper explores a comprehensive set of factors perceived by emergency department staff and administrative leads to influence clinical pathway implementation within the complex and dynamic environments of community emergency department setting s. Methods This descriptive , qualitative study involved emergency health professionals and administrators of 15 community hospitals across Ontario , Canada . As part of our larger cluster r and omized controlled trial , each site was in the preparation phase to implement one of two clinical pathways : pediatric asthma or pediatric vomiting and diarrhea . Data were collected from three sources : ( i ) a mediated group discussion with site champions during the project launch meeting ; ( ii ) a semi-structured site visit of each emergency department ; and ( iii ) key informant interviews with an administrative lead from each hospital . The Theoretical Domains Framework ( TDF ) was used to guide the interviews and thematically analyze the data . Domains within each major theme were then mapped onto the COM-B model — capability , opportunity , and motivation — of the Behaviour Change Wheel . Results Seven discrete themes and 58 subthemes were identified that comprised a set of barriers and enablers relevant to the planned clinical pathway implementation . Within two themes , three distinct levels of impact emerged , namely ( i ) the individual health professional , ( ii ) the emergency department team , and ( iii ) the broader hospital context . The TDF domains occurring most frequently were Memory , Attention and Decision Processes , Environmental Context and Re sources , Behavioural Regulation , and Reinforcement . Mapping these barriers and enablers onto the COM-B model provided an organized perspective on how these issues may be interacting . Several factors were viewed as both negative and positive across different perspectives . Two of the seven themes were limited to one component , while four involved all three components of the COM-B model . Conclusions Using a theory-based approach ensured systematic and comprehensive identification of relevant barriers and enablers to clinical pathway implementation in ED setting s. The COM-B system of the Behaviour Change Wheel provided a useful perspective on how these factors might interact to effect change . Trial registration Clinical Trials.gov , NCT01815710 OBJECTIVE The objective of this study is to measure the impact of a five-step implementation process for an acute myocardial infa rct ion ( AMI ) clinical pathway ( CPW ) on thrombolytic administration in rural emergency departments . DESIGN Cluster r and omised controlled trial . SETTING Six rural Victorian emergency departments participated . INTERVENTION The five-step CPW implementation process comprised ( i ) engaging clinicians ; ( ii ) CPW development ; ( iii ) reminders ; ( iv ) education ; and ( v ) audit and feedback . MAIN OUTCOME MEASURES The impact of the intervention was assessed by measuring the proportion of eligible AMI patients receiving a thrombolytic and time to thrombolysis and electrocardiogram . RESULTS Nine hundred and fifteen medical records were audited , producing a final sample of 108 patients eligible for thrombolysis . There was no significant difference between intervention and control groups for median door-to-needle time ( 29 mins versus 29 mins ; P = 0.632 ) , proportion of those eligible receiving a thrombolytic ( 78 % versus 84 % ; P = 0.739 ) , median time to electrocardiogram ( 7 mins versus 6 mins ; P = 0.669 ) and other outcome measures . Results showed superior outcome measures than other published studies . CONCLUSIONS The lack of impact of the implementation process for a chest pain CPW on thrombolytic delivery or time to electrocardiogram in these rural hospitals can be explained by a ceiling effect in outcome measures but was also compromised by the small sample . Results suggest that quality of AMI treatment in rural emergency departments ( EDs ) is high and does not contribute to the worse mortality rate reported for AMIs in rural areas |
13,027 | 29,271,482 | The effect estimate was 660/1000 women cured/improved with ES compared to 382/1000 with no active treatment ( 95 % CI 538 to 805 women ) ; and for sham treatment , 402/1000 women cured/improved with ES compared to 198/1000 with sham treatment ( 95 % CI 202 to 805 women).Low- quality evidence suggests that there may be no difference in cure or improvement for ES versus PFMT ( RR 0.85 , 95 % CI 0.70 to 1.03 ) , PFMT plus ES versus PFMT alone ( RR 1.10 , 95 % CI 0.95 to 1.28 ) or ES versus vaginal cones ( RR 1.09 , 95 % CI 0.97 to 1.21).Electrical stimulation probably improves incontinence-specific QoL compared to no treatment ( moderate quality evidence ) but there may be little or no difference between electrical stimulation and PFMT ( low quality evidence ) .
It is uncertain whether adding electrical stimulation to PFMT makes any difference in terms of quality of life , compared with PFMT alone ( very low quality evidence ) .
There may be little or no difference between electrical stimulation and vaginal cones in improving incontinence-specific QoL ( low quality evidence ) .
AUTHORS ' CONCLUSIONS The current evidence base indicated that electrical stimulation is probably more effective than no active or sham treatment , but it is not possible to say whether ES is similar to PFMT or other active treatments in effectiveness or not .
Without sufficiently powered trials measuring clinical ly important outcomes , such as subjective assessment of urinary incontinence , we can not draw robust conclusions about the overall effectiveness or cost-effectiveness of electrical stimulation for stress urinary incontinence in women | BACKGROUND Several treatment options are available for stress urinary incontinence ( SUI ) , including pelvic floor muscle training ( PFMT ) , drug therapy and surgery .
Problems exist such as adherence to PFMT regimens , side effects linked to drug therapy and the risks associated with surgery .
We have evaluated an alternative treatment , electrical stimulation ( ES ) with non-implanted devices , which aims to improve pelvic floor muscle function to reduce involuntary urine loss .
OBJECTIVES To assess the effects of electrical stimulation with non-implanted devices , alone or in combination with other treatment , for managing stress urinary incontinence or stress-predominant mixed urinary incontinence in women .
Among the outcomes examined were costs and cost-effectiveness . | CONTEXT Pelvic floor electrical stimulation ( PFES ) has been shown to be effective for stress incontinence . However , its role in a multicomponent behavioral training program has not been defined . OBJECTIVE To determine if PFES increases efficacy of behavioral training for community-dwelling women with stress incontinence . DESIGN AND SETTING Prospect i ve r and omized controlled trial conducted from October 1 , 1995 , through May 1 , 2001 , at a university-based outpatient continence clinic in the United States . PATIENTS Volunteer sample of 200 ambulatory , nondemented , community-dwelling women aged 40 to 78 years with stress or mixed incontinence with stress as the predominant pattern ; stratified by race , type of incontinence ( stress only vs mixed ) , and severity ( frequency of episodes ) . INTERVENTIONS Patients were r and omly assigned to 8 weeks ( 4 visits ) of behavioral training , 8 weeks ( 4 visits ) of the behavioral training plus home PFES , or 8 weeks of self-administered behavioral treatment using a self-help booklet ( control condition ) . MAIN OUTCOME MEASURES Primary outcome was percentage reduction in the number of incontinent episodes as documented in bladder diaries . Secondary outcomes were patient satisfaction and changes in quality of life . RESULTS Intention-to-treat analysis showed that incontinence was reduced a mean of 68.6 % with behavioral training , 71.9 % with behavioral training plus PFES , and 52.5 % with the self-help booklet ( P = .005 ) . In comparison with the self-help booklet , behavioral training ( P = .02 ) and behavioral training plus PFES ( P = .002 ) were significantly more effective , but they were not significantly different from each other ( P = .60 ) . The PFES group had significantly better patient self-perception of outcome ( P<.001 ) and satisfaction with progress ( P = .02 ) . Significant improvements were seen across all 3 groups on the Incontinence Impact Question naire but with no between-group differences . CONCLUSIONS Treatment with PFES did not increase effectiveness of a comprehensive behavioral program for women with stress incontinence . A self-help booklet reduced incontinence and improved quality of life but not as much as the clinic-based programs In a prospect i ve r and omized study the efficiacy of physical therapy in female stress incontinence could be verified . The greatest success rate was achieved by medical gymnastics , whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity . Despite of the good therapeutic success ( 51.5 % ) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found AIMS To evaluate the clinical and cost-effectiveness of electric stimulation plus st and ard pelvic floor muscle training compared to st and ard pelvic floor muscle training alone in women with urinary incontinence and sexual dysfunction . METHODS Single centre two arm parallel group r and omised controlled trial conducted in a Teaching hospital in Engl and . Participants were women presenting with urinary incontinence and sexual dysfunction . The interventions compared were electric stimulation versus st and ard pelvic floor muscle training . OUTCOME MEASURES included Prolapse and Incontinence Sexual function Question naire ( PISQ ) physical function dimension at post-treatment ( primary ) ; other dimensions of PISQ , SF-36 ; EQ-5D , EPAQ , re source use , adverse events and cost-effectiveness ( secondary outcomes ) . RESULTS 114 women were r and omised ( Intervention n=57 ; Control group n=57 ) . 64/114 ( 56 % ) . PARTICIPANTS had valid primary outcome data at follow-up ( Intervention 30 ; Control 34 ) . The mean PISQ-PF dimension scores at follow-up were 33.1 ( SD 5.5 ) and 32.3 ( SD 5.2 ) for the Intervention and Control groups respectively ; with the Control group having a higher ( better ) score . After adjusting for baseline score , BMI , menopausal status , time from r and omisation and baseline oxford scale score the mean difference was -1.0 ( 95 % CI : -4.0 to 1.9 ; P=0.474 ) . There was no differences between the groups in any of the secondary outcomes at follow-up . Within this study , the use of electrical stimulation was cost-effective with very small incremental costs and quality adjusted life years ( QALYs ) . CONCLUSIONS In women presenting with urinary incontinence in conjunction with sexual dysfunction , physiotherapy is beneficial to improve overall sexual function . However no specific form of physiotherapy is beneficial over another . Trial registration IS RCT N09586238 ABSTRACT Objective To determine the efficacy of stress urinary incontinence treatments adding pelvic floor muscle training to vaginal electrical stimulation . Methods Forty-eight women with stress urinary incontinence were r and omized into 2 groups : 24 underwent isolated vaginal electrical stimulation , and 24 vaginal electrical stimulation plus pelvic floor muscle training . History , physical examination , voiding diary , perineum strength test , and urodynamic study were assessed . Comparisons were made for adherence to treatment , muscle strength improvement , urinary symptoms , and degree of satisfaction immediately , 12 and 96 months after treatment . Results Patients ' degree of satisfaction on vaginal electrical stimulation , and on vaginal electrical stimulation plus pelvic floor muscle training immediately , 12 and 96 months post treatment , were , respectively : 88.2 % versus 88.9 % 64.7 % versus 61.1 % and 42.9 % versus 28.6 % ( p>0.05 ) . Conclusion Vaginal electrical stimulation associated to pelvic floor muscle training did not show better results than vaginal electrical stimulation alone OBJECTIVE To evaluate the effects of surface electrical stimulation ( SES ) and to compare them with the effects of the intravaginal electrical stimulation ( IVES ) in women with stress urinary incontinence ( SUI ) . STUDY DESIGN This r and omized controlled study included 48 women aged over 50 years , who complained of SUI evaluated according to two structured questions of King 's Health Question naire ( KHQ ) and who had not previously undergone physical therapy for SUI . The calculation of the sample size estimated a sample of 45 volunteers with a significance level of 5 % and statistical power of 90 % . The women were r and omized to : Surface Electrical Stimulation Group ( SESG ) ( n=15 ) , Intravaginal Electrical Stimulation Group ( IVESG ) ( n=15 ) and Control Group ( CG ) ( n=15 ) . Subjects in the intervention groups were treated with the same parameters of electrical stimulation for 12 sessions . The SESG had four silicone electrodes fixed in the suprapubic and ischial tuberosity regions . The IVES group used an intravaginal electrode . The CG did not receive any treatment during the corresponding time . They were evaluated before and after treatment by a physical therapist who was blind to group allocation . The primary outcomes were urinary leakage , pressure and strength of pelvic floor muscle ( PFM ) contraction . The secondary outcome was quality of life ( QOL ) evaluated by KHQ . Forty-five women completed the study and were included in the analysis . Statistical analysis was performed using the Wilcoxon test for intragroup analysis and Kruskal-Wallis and Mann-Whitney tests for intergroup analysis ( p<0.05 ) . RESULTS There was significant improvement in urinary loss and pressure of contraction in the SESG and IVESG . PFM strength increased only in the IVESG . Intergroup analysis found differences after the treatment in : urinary leakage between the SESG and CG ( p<0.001 ) and the IVESG and CG ( p<0.001 ) . Regarding QOL , there was significant reduction in the incontinence impact , limitations of daily activities , physical limitation , emotion , sleep and disposition and severity domains in the SESG ( all p<0.02 ) and IVESG ( all p<0.04 ) after the treatments . CONCLUSION SES and IVES are important treatments to improve the SUI . Both improved the QOL , urinary leakage , and strength and pressure of PFM contraction PURPOSE To compare the effectiveness of pelvic floor exercises , electrical stimulation , vaginal cones , and no active treatment in women with urodynamic stress urinary incontinence . PATIENTS AND METHODS One hundred eighteen subjects were r and omly selected to recieve pelvic floor exercises ( n=31 ) , ES ( n=30 ) , vaginal cones ( n=27 ) , or no treatment ( untreated control ) ( n=30 ) . Women were evaluated before and after completion of six months of treatment by the pad test , quality of life question naire ( I-QOL ) , urodynamic test , voiding diary , and subjective response . RESULTS In the objective evaluation , we observed a statistically significant reduction in the pad test ( p=0.003 ) , in the number of stress urinary episodes ( p<0.001 ) , and a significant improvement in the quality of life ( p<0.001 ) in subjects who used pelvic floor exercises , electrical stimulation , and vaginal cones compared to the control group . No significant difference was found between groups in the urodynamic parameters . In the subjective evaluation , 58 % , 55 % , and 54 % of women who had used pelvic floor exercises , electrical stimulation , and vaginal cones , respectively , reported being satisfied after treatment . In the control group , only 21 % patients were satisfied with the treatment . CONCLUSION Based on this study , pelvic floor exercises , electrical stimulation , and vaginal cones are equally effective treatments and are far superior to no treatment in women with urodynamic stress urinary incontinence Objective : To evaluate a new pattern of electrical of electrical stimulation as a treatment for stress incontinence . Design : A r and omized , double-blind , controlled trial . Setting : The study took place on three clinical sites . Subjects : Patients ( n= 27 ) with urodynamically proven stress incontinence recruited via consultant referral . Interventions : Patients were r and omly allocated to one of two groups : the new pattern of stimulation or sham stimulation . Main outcome measures : Patients were assessed pre , mid and post treatment using : perineometry , digital assessment and pad testing . The following were only used pre and post treatment : seven-day frequency/ volume chart , SF-36 , the Incontinence Impact Question naire and the Urogenital Distress Inventory . Results : No significant between-group differences were highlighted except when quality of life was assessed with the Urogenital Distress Inventory ( p= 0.01 ) . A significant reduction in scores was observed in the stimulation group ( p= 0.03 ) However , improvements were seen in both the strength and endurance characteristics of the pelvic floor musculature , although these changes were not translated into a reduction in symptoms . Conclusion : Although promising , the improvement in pelvic floor function did not result in a reduction in symptoms in all patients . Further research is required to investigate the effects of the new stimulation in combination with pelvic floor exercises and to compare the new stimulation pattern with existing forms of electrical stimulation Several different methods of enhancing pelvic floor functions have been developed and modified . The aim of this study was to compare the efficacy of a new vaginal cone with conventional FES-Biofeedback therapy for female urinary incontinence , with respect to pelvic floor rehabilitation . One hundred and twenty patients , who required a non-surgical treatment for urinary incontinence , were divided r and omly into two groups ; ( 1 ) the Functional Electrical Stimulation (FES)- Biofeedback group ( or BFB group ) and ( 2 ) the new vaginal cone group ( or cone group ) . For a period of six weeks , two training sessions each week were carried out on the BFB group . The new 150-gram dumbbell-shaped vaginal cone , made of fine ceramic material , was developed domestically . A therapist instructed patients in the cone group upon its use for pelvic floor exercise , and directed the exercise to be repeated at home daily ; these patients had follow-up visits every week . Objective improvements were obvious in both groups . 88.3 % and 91.6 % of the cone and BFB groups showed an improvement after treatment , respectively . There was no significant difference in the improvement or dissatisfaction scores of the two groups . In conclusion , no significant differences in the therapeutic effects were observed between the FES- Biofeedback and the new vaginal cone groups . Considering improvements in the quality of life and objective symptoms , the therapeutic effects of the two techniques showed no significant differences . The new vaginal cone is relatively easy to use at home and aids in pelvic floor muscle exercises . Consequently , the new vaginal cone could be used as an alternative non-surgical treatment modality in female stress urinary incontinence Rehabilitative therapy of the perineum ( FKT , SEF and biofeedback ) represents an efficient method in the treatment of urinary stress incontinence without resorting to a complete uro-genital prolapse , as in patients with urethral instability and /or incontinence . One hundred twenty-one women , 55 with urinary stress incontinence ( USI ) , 20 with urge incontinence ( UI ) and 46 suffering from both types of incontinence , underwent rehabilitative therapy . On each patients the following tests were carried out : an internal test , a urodynamic test ( uroflowmeter , PPU , cystomanometry and pessure/flow study ) , a meter UEC , situated at the bladder neck , anterior and posterior urethra , both clinostatic and orthostatic , urine test with urinoculture and a pap-test . The aim of this study is that of establishing if it is possible a ) to simplify the rehabilitative sitting using only FKT with weekly treatment ; b ) to treat women suffering from urge incontinence or from both types , but with bladder stability ( st and ard cystomanometria ) with FKT and Ditropan ( 1 tablet 3 times daily for weeks therapy ) . One group of patients underwent rehabilitative therapy while another group underwent traditional therapy , for a minimum of 12 sitting , using also electric functional stimulation ( SEF ) . Of 121 women who underwent rehabilitative therapy , 90 ( 74.4 % ) were healed , 30 ( 24.7 % ) improved and one ( 0.9 % ) showed no signs of improvement . Patients treated with FKT , or FKT and made as good if not better grogress than those who attended more sittings and /or underwent SEF . ( ABSTRACT TRUNCATED AT 250 WORDS Sixty-nine female patients with symptoms of stress urinary incontinence were r and omized to treatment with either interferential therapy or weighted vaginal cones . Fifty-four patients completed treatment ( interferential therapy , 30 patients ; weighted vaginal cones , 24 patients ) . Patients were assessed by subjective response , pad testing , continence charts , and the maximum weight of cone that could be held actively and passively . Forty-seven patients were reassessed at 6 months ( 19 cones ; 28 interferential ) , five patients ( 9.26 % ) required surgery , and two patients ( 3.7 % ) could not be reassessed . Subjective response to treatment was good , with 80 % to 90 % of patients cured or improved after treatment . After 6 months , 41.67 % in the cone group and 40 % in the interferential group were subjectively cured , with improvement in 50 % and 30 % , respectively . Of those patients initially referred for treatment , greater than 30 % in each group were cured of symptoms . There was an objective improvement in both groups . In the cone group 50 % had improved after treatment and greater than 60 % had improved at 6 months as assessed by pad testing , while in the interferential group 76 % had improved after treatment and 73 % had improved at 6 months . There was no significant difference in improvement between the two groups in any of the methods of assessment . However , the cones require less supervision by trained staff and can be used at home by the patient . Their use results in a savings in time for the physiotherapy department . The use of the cones is recommended as a cost-effective method of treatment that can be added to the present therapy options available to the physiotherapist Abstract Objective : To compare the effect of pelvic floor exercises , electrical stimulation , vaginal cones , and no treatment for genuine stress incontinence . Design : Stratified , single blind , r and omised controlled trial . Setting : Multicentre . Participants : 107 women with clinical ly and urodynamically proved genuine stress incontinence . Mean ( range ) age was 49.5 ( 24 - 70 ) years , and mean ( range ) duration of symptoms 10.8 ( 1 - 45 ) years . Interventions : Pelvic floor exercise ( n=25 ) comprised 8 - 12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week . The electrical stimulation group ( n=25 ) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day . The vaginal cones group ( n=27 ) used cones for 20 minutes a day . The untreated control group ( n=30 ) was offered the use of a continence guard . Muscle strength was measured by vaginal squeeze pressure once a month . Main outcome measures : Pad test with st and ardised bladder volume , and self report of severity . Results : Improvement in muscle strength was significantly greater ( P=0.03 ) after pelvic floor exercises ( 11.0 cm H2O ( 95 % confidence interval 7.7 to 14.3 ) before v 19.2 cm H2O ( 15.3 to 23.1 ) after ) than either electrical stimulation ( 14.8 cm H2O ( 10.9 to 18.7 ) v 18.6 cm H2O ( 13.3 to 23.9 ) ) or vaginal cones ( 11.8 cm H2O ( 8.5 to 15.1 ) v 15.4 cm H2O ( 11.1 to 19.7 ) ) . Reduction in leakage on pad test was greater in the exercise group ( −30.2 g ; −43.3 to 16.9 ) than in the electrical stimulation group ( −7.4 g ; −20.9 to 6.1 ) and the vaginal cones group ( −14.7 g ; −27.6 to −1.8 ) . On completion of the trial one participant in the control group , 14 in the pelvic floor exercise group , three in the electrical stimulation group , and two in the vaginal cones group no longer considered themselves as having a problem . Conclusion : Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence BACKGROUND Neuromuscular electrical stimulation ( NMES ) is widely treatment for stress urinary incontinence ( SUI ) but there is no consensus in literature regarding the most effective treatment parameters . OBJECTIVE To compare two NMESintra-vaginal protocol s for the treatment of SUI in women . METHODS The study included 20 volunteers with an average age of 55.55±6.51 years and with the clinical diagnosis of SUI . Volunteers were r and omly divided into two groups : group 1 ( G1 ) received NMES with medium-frequency current and group 2 ( G2 ) received NMES with low-frequency current . Functional assessment s of pelvic floor muscles ( PFM ) were performed by perineometry . The severity of signs and symptoms were objective ly evaluated using the 1 hour pad test and subjectively evaluated using a visual analog scale that measured the discomfort caused by the SUI . Shapiro-Wilk test was used to analyze data normality , and the Friedman test was used to analyze nonparametric data . For analysis of symptoms related to SUI the Fisher exact test and the Mann-Whitney test were used . Significance level of 5 % was set for all data analysis . RESULTS No significant differences ( p>0.05 ) were found between groups for any of the variable assessed . The within group analysis of initial and final evaluations ( after NMES ) demonstrated significant differences ( p<0.05 ) in amount of urine lost , the discomfort caused by urinary incontinence and perineal pressure for both treatment groups . CONCLUSION The two NMES protocol s applied were equally effective in the treatment of SUI AIMS To test the null hypothesis that a novel disposable " tampon like " electrostimulation device ( Pelviva ( ® ) ) is no better than unsupervised pelvic floor muscle exercise for treatment of urinary incontinence in women . METHODS Pre/post-intervention assessor blinded , single center RCT . A total of 123 community dwelling self referred women with symptoms of stress , urge , or mixed incontinence were r and omly assigned to one of two 12-week duration treatments : Pelviva ( ® ) used for 30 min a day plus unsupervised pelvic floor muscle exercise or unsupervised exercises alone . Outcome measures included ICIQ-UI ( primary ) , ICIQ FLUTSex and global impression of severity and improvement ( secondary ) completed at recruitment , after 4 weeks of unsupervised exercise and immediately post-treatment . Diary of exercise frequency/type , overall impression , and usage of device was completed mid- and post-treatment . RESULTS Pelviva ( ® ) plus exercise produced significantly better outcome than unsupervised exercise alone : 5 points ( 45 % ) versus 1 point ( 10 % ) for ICIQ-UI ( P = 0.014 ) ; 67 % versus 33 % for leak frequency ( P = 0.005 ) ; 40 % versus 20 % for leak interference with life ( P = 0.018 ) . Incontinence was less bothersome during sex to a greater extent in the Pelviva ( ® ) group ( P = 0.026 ) . Women were enthusiastic about the device , found it comfortable/easy to use and experienced no adverse events . CONCLUSIONS The Pelviva ( ® ) device plus unsupervised exercise is more successful than unsupervised pelvic floor muscle exercise alone in treating urinary incontinence . The device is easy/comfortable to use , there are no apparent adverse incidents , and women can manage their incontinence in the privacy of their own home . The product will be launched 2013 BACKGROUND AND PURPOSE Pelvic floor muscle training ( PFMT ) is an effective therapy for stress urinary incontinence ( SUI ) . There is little and inconsistent data about different strategies of PFMT . Finding the right , patient-oriented treatment decision seems to be essential in order to achieve good results in conservative management of SUI . It was the aim of this prospect i ve r and omized controlled trial ( RCT ) to compare three different strategies using electromyography ( EMG ) biofeedback-assisted PFMT with and without electrical stimulation ( ES ) for treatment of SUI in women capable of voluntarily contracting the pelvic floor when a home-training device with vaginal electrode was used . METHOD Three-arm RCT comparing 1 ) EMG biofeedback-assisted PFMT and conventional ES ; 2 ) EMG biofeedback-assisted PFMT and dynamic ES ; and 3 ) EMG biofeedback-assisted PFMT . Primary outcome measures were quality of life ( King 's Health Question naire ) and degree of suffering ( rated on a visual analogue scale from 1 to 10 ) . Secondary outcome measures were number of pads used , pad weight test , contractility of the pelvic floor measured by digital palpation and intra-vaginal EMG . RESULTS The quality of life significantly increased over the 12-week training . The number of pads used was reduced , the pad weight test and the contractility of the pelvic floor significantly improved . There were no significant differences between the three groups . CONCLUSION This RCT shows significant improvement in patients ' quality of life for conservative therapy of SUI . Differences between the three therapeutic options analyzed could not be found . Additional ES showed no benefit for patients with SUI , capable of voluntary pelvic floor contraction Previous workers have debated the value of maximal perineal stimulation ( MPS ) in the treatment of urinary incontinence in women . In order to assess the efficacy of this simple technique a prospect i ve study was undertaken on 107 consecutive incontinent women . They included those with stress , urge and mixed patterns of leakage . Patients were placed at r and om into treatment and control groups . All underwent clinical assessment , urodynamic study and a single session of pelvic floor re-education with measurement of pelvic contraction and cystoscopy . Those in the treatment group were given MPS using monophasic square wave pulses while under anaesthesia . Independent follow-up assessment was performed 6 and 12 weeks after treatment . Of the 107 patients 94 completed the trial . Forty-five were treated and 49 acted as controls . Analysis of age , parity , duration and severity of incontinence showed that r and omisation had produced comparable results between the treated and the control groups . Sixty per cent of the treatment group and 66 % of the control group had significant symptomatic improvement . Pelvic floor function was re-assessed , using a perineometer , and found to be more efficient , having increased equally in both groups . Both groups of women improved irrespective of the pattern of incontinence . This suggests that MPS does not contribute to the management and that a single physiotherapy session with skillful counselling can produce beneficial results in women with all types of urinary incontinence BACKGROUND Urinary stress incontinence is a common , disruptive and potentially disabling condition in which the subject complains of involuntary leakage on effort or exertion or on sneezing or coughing . AIM This study was performed in order to compare the effects of interferential current and biofeedback applications on incontinence severity in patients with urinary stress incontinence . In addition , pelvic muscle strength and quality of life as important parameters in these subjects were investigated . METHODS In this prospect i ve , r and omised , controlled study , forty women with moderate intensity of urinary stress incontinence as determined by one-hour pad test were included . Pelvic muscle strength was evaluated by a biofeedback device and quality of life was assessed by a 28-itemed question naire . All of the parameters were evaluated before and after the treatments . Twenty cases underwent interferential current therapy , while pelvic floor exercises via biofeedback were applied in the remaining cases . The treatments lasted 15 minutes per session , three times a week for a total of 15 sessions . RESULTS All of the parameters improved after the treatments in each group ( p < 0.05 ) and both treatment modalities seemed to have similar effects on pad test ( 95 % CI : -1.48 - 4.59 ) , pelvic muscle strength ( 95 % CI : -9.29 -1.78 ) and quality of life ( 95 % CI : -11.91 - 5.31 ) outcomes . CONCLUSIONS Physical therapy modalities used in this trial are applied easily and non invasive . Also , when the finding that no adverse effects were observed during the study period is taken into consideration , it can be concluded that both methods can be used effectively in patients with urinary stress incontinence Our objective was to determine the efficacy of functional electrical stimulation as a st and -alone therapy for female stress incontinence . The study was conducted as a prospect i ve , double-blind , r and omized controlled trial using subjective and objective outcome criteria . Patients enrolled in this study had stress incontinence consistent with International Continence Society criteria . Patients with significant pelvic prolapse or detrusor instability were excluded . Patients underwent twice-daily treatment sessions for a total of 3 months . Results were analyzed for confounding variables between the treatment and control groups . Statistical analysis was performed utilizing Fisher 's exact test and the paired t-test . Of the 54 patients enrolled in this study , 44 completed the program . The dropout rate was similar for both the treatment and control groups . There was no statistically significant difference between the treatment and control groups with regard to age , gravity , parity , previous antiincontinence surgery , menopausal status , or previous hysterectomy . Objective success for the treatment group was 15 % and for the control group , 12.5 % ( NS ) . The subjective success for the treatment group was 25 % and for the control group , 29 % ( NS ) . There was no relationship demonstrated between age , parity , previous surgery , hysterectomy , or menopausal status and the successful treatment of genuine stress incontinence with functional electrical stimulation . In this patient population , functional electrical stimulation was no more effective at improving or eliminating the symptoms of genuine stress incontinence than was the daily retention of the control probe OBJECTIVE The objective of this study was to evaluate the effects of surface electrical stimulation in elderly women with stress urinary incontinence ( SUI ) as compared to no treatment . MATERIAL S AND METHODS This r and omized controlled pilot study included women over the age of 60 years , with at least one episode of stress urinary leakage during the previous month . Fourteen women were allocated according to a computer generated r and omization list in two groups : surface electrical stimulation ( SES ) , and control group ( CG ) . The women in the SES group were treated with surface electrical stimulation using four electrodes , during six weeks with two weekly sessions of 20 minutes each . They were evaluated before and after treatment primary outcome , urinary leakage , and secondary outcomes , King 's Health Question naire , pressure perineometry , and subjective satisfaction . RESULTS For the urinary leakage , there was a significant decrease in SES group after treatment ( P=.017 ) . Significant differences were observed between the SES group and CG in the evaluation after treatment ( P<.01 ; effect size : -1,38 ; 95 % confidence interval from 1,18 to 14,14 ) . No significant differences were observed in both groups for the outcome pelvic floor muscle pressure . In the evaluation of quality of life , a significant reduction of score in the gravity domain was observed for the SES group after treatment ( P=.017 ) . CONCLUSION The results of this study showed that surface electrical stimulation in elderly women with SUI can be an effective method for the improvement of urinary leakage PURPOSE The effectiveness of intravaginal electrical stimulation was compared to st and ard therapy in the treatment of genuine stress urinary incontinence and detrusor instability . MATERIAL S AND METHODS A total of 57 women with urinary incontinence was evaluated with video urodynamics and voiding diaries before and after treatment . Of the women 18 with stress urinary incontinence were r and omized to electrical stimulation or Kegel exercise and 38 with detrusor instability were r and omized to anticholinergic therapy or electrical stimulation . RESULTS Of patients using electrical stimulation in the stress urinary incontinence group 66 % improved and 72 % of the patients with detrusor instability treated with electrical stimulation improved . These rates were not statistically significant when compared to traditional therapy . CONCLUSIONS Electrical stimulation is safe and at least as effective as properly performed Kegel and anticholinergic therapy in the treatment of stress urinary incontinence and detrusor instability OBJECTIVE To identify predictors of outcome of a multi-component behavioral training program for urge and stress incontinence in women . METHODS This report is a secondary analysis of data from three prospect i ve , r and omized , clinical trials testing behavioral interventions for urinary incontinence . Participants were a volunteer sample of 258 ambulatory , nondemented , community-dwelling women , aged 40–92 years , with stress , urge , or mixed urinary incontinence . Participants received 8 weeks ( four visits ) of multicomponent behavioral training in each study . The relationship between a number of variables and treatment success were explored by univariate and multivariable logistic regression analyses . RESULTS Successful treatment of predominantly urge incontinence ( 75 % reduction of incontinent episodes as recorded on bladder diary ) was associated with not wearing any form of protection for incontinence ( P = .045 ; 95 % confidence interval [ CI ] .282 , .987 ) . Achieving total continence ( 100 % reduction ) was associated with fewer incontinent episodes at baseline ( P < .001 ; 95 % CI .138 , .557 ) , previous surgery for incontinence ( P = .021 ; 95 % CI 1.169 , 6.543 ) , and lower education level ( P = .022 ; 95 % CI .175 , .871 ) . Successful treatment of predominantly stress incontinence ( 75 % reduction ) was related to not having previous evaluation or treatment for incontinence ( P = .001 ; 95 % CI .026 , .415 ) , and fewer incontinent episodes on baseline bladder diary ( P = .026 ; 95 % CI .210 , .907 ) . Outcomes were not associated with age , race , type of incontinence , or a number of other variables reflecting medical history , obstetric history , medications , pelvic examination , body mass index , urodynamic parameters , or psychological distress . CONCLUSION Aside from indicators of severity and previous treatment , there were few associations between baseline clinical variables and outcome of behavioral treatment OBJECTIVE Our purpose was to determine the efficacy of transvaginal electrical stimulation in treating genuine stress incontinence . STUDY DESIGN This was a multicenter , prospect i ve , r and omized , double-blind , placebo-controlled 15-week trial comparing the use of an active pelvic floor stimulator with a sham device . Thirty-five women used an active unit and 17 control subjects used sham devices . Weekly and daily voiding diaries were recorded throughout the trial . Urodynamic testing , including pad test and subtracted cystometry , was done before and at the end of device use . Pelvic muscle strength was measured at baseline and at the end of the trial . Patients scored their symptoms on visual analog scales and completed quality -of-life question naires before and after therapy . RESULTS Significant improvements from baseline were found in patients using active devices but not in controls . Comparisons of changes from baseline between active-device and control patients showed that active-device patients had significantly greater improvement in weekly ( p = 0.009 ) and daily ( p = 0.04 ) leakage episodes , pad testing ( p = 0.005 ) , and vaginal muscle strength ( p = 0.02 ) when compared with control subjects . Significantly greater improvement was also found for both visual analog scores of urinary incontinence ( p = 0.007 ) and stress incontinence ( p = 0.02 ) , as well as for subjective reporting of frequency of urine loss ( p = 0.002 ) , and urine loss with sneezing , coughing , or laughing ( p = 0.02 ) , when compared with controls . Pad testing showed that stress incontinence was improved by at least 50 % in 62 % of patients using an active device compared with only 19 % of patients using sham devices ( p = 0.01 ) . Voiding diaries showed at least 50 % improvement in 48 % of active-device patients compared with 13 % of women using the sham device ( p = 0.02 ) . No irreversible adverse effects were noted in either group . CONCLUSIONS Transvaginal pelvic floor electrical stimulation was found to be a safe and effective therapy for genuine stress incontinence BACKGROUND Twelve to 55 % of women experience stress urinary incontinence at some time during their lifetime . OBJECTIVE To compare the effectiveness of pelvic floor muscle training with and without electrical stimulation in treatment of stress urinary incontinence . MATERIAL AND METHODS Participants were 24 women , 27 - 73 years of age , diagnosed with stress urinary incontinence . Exclusion criteria were pregnancy and urge urinary incontinence . These participants were r and omly divided into group 1 and 2 . Both groups trained 15 min . twice a day for 9 weeks . Group 2 used simultaneously intermittent electrical stimulation . The pelvic floor muscles were evaluated using the Oxford scale , vaginal palpation , and by electromyogram , ( Myomed 930 , Enraf Nonius ) . The quantity and frequency of urinary incontinence episodes was evaluated using a question naire and a VAS scale before and after the treatment . RESULTS The groups were demographically similar , except group 2 was significantly younger . Both groups had significantly increased pelvic floor muscle strength ( p=0.007 ; p=0.005 respectively ) after the treatment and 70 % of all the women had reduced or no stress urinary incontinence . Group 2 had significantly ( p=0.013 ) better relaxation post treatment . CONCLUSION Pelvic floor muscle training is an effective treatment for stress urinary incontinence , but electrical stimulation gave no additional effect for this patient group . The significantly lower relaxation threshold in group 2 indicates that electrical stimulation could be a possible treatment for symptoms caused by hypertensive pelvic floor muscles OBJECTIVE To compare the efficacy and safety between tension-free vaginal tape obturator technique ( TVT-O ) and TVT-O with biofeedback pelvic floor electrical stimulation on the therapy of female stress urinary incontinence . METHODS In this prospect i ve study , 120 female patients of female stress urinary incontinence were enrolled from January 2012 to December 2013 . The patients were r and omly assigned to two groups , 60 in group A received TVT-O alone , while 60 in group B not only received TVT-O but also received biofeedback pelvic floor electrical stimulation . All the patients were followed up for 12 months to assess the efficacy and safety of the two procedures . Subjective indices [ total volume of urine ( TV ) , the total frequency of urination ( TOV ) , the total leakage of urine events ( TL ) , urinary incontinence related quality of life question naire ( I-QOL ) , International Advisory Committee on urinary incontinence urinary incontinence question naire short form scale ( ICI-Q-SF ) ] and objective indices [ Valsalva leak point pressure ( VLPP ) , maximum flow rate ( MFR ) , residual urine volume (RUV),pad test ] were analyzed . RESULTS Overall , the cure rate was 75 % at 1 year follow-up for group A and 88.33 % for group B ( P<0.05 ) . The effective rate was 16.67 % for group A and 10 % for group B ( P<0.05 ) . The ineffective rate was 8.33 % for group A and 1.67 % for group B ( P<0.05 ) . TV , I-QOL , ICI-Q-SF , VLPP and pad test in group B were superior to group A ( P<0.05 ) . CONCLUSION Pelvic floor electrical stimulation biofeedback therapy could improve the curative effects of TVT-O on the treatment of female stress urinary incontinence OBJECTIVE Our purpose was to determine the objective and subjective efficacy of transvaginal electrical stimulation for treatment of common forms of urinary incontinence in women . STUDY DESIGN A prospect i ve , double-blind , r and omized clinical trial included 121 women with either urinary incontinence caused by detrusor instability or genuine stress incontinence , or both ( mixed incontinence ) . Participants used the assigned device for 8 weeks . Identical preintervention and postintervention assessment included multichannel urodynamic testing , quality -of-life scale , and urinary diaries . RESULTS A total of 121 women completed this study at four North American urogynecology centers . Detrusor instability was cured ( stable on provocative cystometry ) in 49 % of women with detrusor instability who used an active electrical device ( p = 0.0004 , McNemar 's test ) , whereas there was no statistically significant change in the percentage with detrusor instability in the sham device group . There was no statistically significant difference between the preintervention and postintervention rates of genuine stress incontinence for either the active device group or the sham device group . CONCLUSION This form of transvaginal electrical stimulation may be effective for treatment of detrusor overactivity , with or without genuine stress incontinence OBJECTIVE To assess the efficacy of physiotherapeutic treatment modalities in women with proven bladder overactivity . METHODS One hundred and twelve women received ambulatory urodynamics . Based on both urodynamic variables of ambulatory cystometry ( ACM ) and the micturition diary , the Detrusor Activity Index ( DAI ) for each patient was calculated . After r and omization , 68 women with a DAI > or = 0.50 were defined as having proven bladder overactivity . In a single blinded RCT patients were r and omized over four treatment groups , i.e. lower urinary tract exercises ( LUTE ) ; office- and home-based functional electrostimulation ( FES ) ; office-based FES and LUTE ; no treatment . Patients treated received nine treatment sessions , once weekly . The primary outcome variable was the DAI , measured before r and omization and , as soon as possible within a maximum of 14 days after the end of the study period . RESULTS Intention to treat analysis in the group of 68 patients showed a statistically significant decrease of DAI-scores in the FES group ( p=0.032 ) in comparison with no treatment , while this decrease was not statistically significant in the LUTE group ( p=0.105 ) and the LUTE+FES group ( p=0.672 ) . CONCLUSIONS Our conclusion is that , based on the DAI , in the homogeneous set of 68 patients , only FES seemed to be effective OBJECTIVE : Pelvic floor muscle training effectively treats female stress urinary incontinence . However , data on long-term efficacy and adherence are sparse . Our aims were to assess current lower urinary tract symptoms and exercise adherence 15 years after ending organized training . METHODS : Originally , 52 women with urodynamic stress urinary incontinence were r and omly assigned to home or intensive exercise . After 6 months , 60 % in the intensive group were almost or completely continent , compared with 17 % in the home group . Fifteen years later , all original study subjects were invited to complete a postal question naire assessing urinary symptoms ( using vali date d outcome tools ) and current pelvic floor muscle training . RESULTS : Response rate was 90.4 % . There were no differences in any urinary outcomes or satisfaction between the 2 study groups as a whole or when restricted to those without intervening stress urinary incontinence surgery . One half of both groups had stress urinary incontinence surgery during the 15-year follow-up period . Twenty-eight percent performed pelvic floor muscle training at least weekly ; this rate did not differ by original group assignment or operated status . More operated women reported severe incontinence ( P = .03 ) and leakage that interfered with daily life ( P = .04 ) than did nonoperated women . There were no other differences between operated and nonoperated women . CONCLUSION : The marked benefit of intensive pelvic floor muscle training seen short-term was not maintained 15 years later . Long-term adherence to training is low . Urinary symptoms were equally common in both operated and nonoperated women . Further studies are needed to underst and factors associated with long-term effectiveness of stress urinary incontinence treatments . LEVEL OF EVIDENCE : |
13,028 | 22,228,167 | : Cap-assisted colonoscopy is associated with improved detection of colorectal neoplasia and higher cecal intubation rates than st and ard adult colonoscopy | BACKGROUND : Cap-assisted colonoscopy uses a transparent plastic hood attached to the tip of the colonoscope to flatten the semilunar folds and improve mucosal exposure .
Several studies have examined the effect of cap-assisted colonoscopy on polyp detection , but the data are inconsistent .
OBJECTIVE : This study aim ed to evaluate whether cap-assisted colonoscopy improves the yield of colorectal neoplasia detected compared with st and ard colonoscopy . | Context How often does colonoscopy miss adenomas ? Contribution During a multicenter screening trial , experienced colonoscopists performed same-day optical ( OC ) and virtual colonoscopy ( VC ) on 1233 asymptomatic adults . Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps ; 21 of these polyps were adenomas measuring 6 mm or greater . Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge . Virtual colonoscopy missed 14 % of the adenomas that measured 6 mm or greater that were de-tected by OC . Implication s Neither OC nor VC is a perfect test : Each misses 10 % to 14 % of adenomas that measure 6 mm or greater . The Editors Optical colonoscopy ( OC ) is widely accepted as the gold st and ard for detecting colorectal neoplasia ( 1 , 2 ) . However , even in the most experienced h and s , this skilled examination is underst and ably not infallible . Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10 % ( 3 ) . More recently , prospect i ve back-to-back or t and em colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0 % to 6 % ( 4 , 5 ) . However , in addition to evaluating relatively small population s of patients with a high prevalence of polyps , a notable weakness common to these studies was that they used OC as its own reference st and ard . In a large , prospect i ve , multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy ( VC ) in asymptomatic adults ( 6 ) , we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC . By using a reference st and ard other than OC itself for comparison , we could uncover lesions that may be systematic ally missed on repeated colonoscopies . These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused . Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC , and all patients provided written informed consent . We recruited asymptomatic adults who were referred for colorectal cancer screening . Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months ; rectal bleeding , hematochezia , or unintentional weight loss of more than 10 pounds within the past 12 months ; OC within the past 10 years or barium enema within the past 5 years ; personal history of adenomatous polyps , colorectal cancer , or inflammatory bowel disease ; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes . Between May 2002 and June 2003 , 1253 asymptomatic adults enrolled in the study . Eight patients were excluded because of failure to reach the cecum at OC , 6 patients were excluded because of inadequate colonic preparation , and another 6 patients were excluded because of computed tomography ( CT ) system failure . The final study group comprised 1233 asymptomatic adults ( 728 men and 505 women ; mean age , 57.8 years ) who successfully completed same-day VC and OC . Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl . To opacify residual colonic fluid and stool for VC examination , patients also consumed dilute oral contrast as previously described ( 7 ) . Our CT protocol and VC technique have also been detailed previously ( 6 ) . To briefly summarize , we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air . One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system ( Viatronix V3D-Colon , version 1.2 , Viatronix , Inc. , Stony Brook , New York ) . We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving . We measured polyps on the 3-dimensional view and recorded them by segment ( cecum , ascending colon , hepatic flexure , transverse colon , splenic flexure , descending colon , sigmoid colon , or rectum ) . We defined the proximal colon as including the cecum to the splenic flexure . We prospect ively rated diagnostic confidence for each detected lesion on a 3-point scale ( most certain , intermediate , and least certain ) . One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using st and ard commercial video colonoscopes ( Olympus , Inc. , Melville , New York ) . The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection . The colonoscopist measured polyps by using a calibrated linear probe , which is more accurate than either visual or biopsy forceps estimation ( 8) . Our polyp-matching algorithm requires VC and OC agreement according to size ( within a 50 % margin of error ) and location ( within the same or adjacent segment ) . After the colonoscopist evaluated a given segment , a study nurse unblinded the VC results for the previous segment . For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC , the colonoscopist closely reexamined that segment and could review the VC images for guidance . We sent all retrieved polyps for histologic examination . For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC , we retrospectively review ed both the VC and OC images . We recorded polyp characteristics , such as size , morphologic characteristic ( sessile , pedunculated , or flat ) , and location on VC . If the polyp was situated on a colonic fold on VC , we further subcategorized it as being located on the back ( proximal ) side , front ( distal ) side , or edge of the fold . We analyzed both supine and prone VC sets for all cases . The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that , given the relative error in polyp measurement , such polyps found on second-look OC might , in fact , measure 6 mm or greater . This allows for more accurate assessment of the OC miss rate at the 6-mm threshold . We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis . All study participants completed a detailed question naire on their personal and family medical history . For the purpose s of this study , particular attention was given to the question about previous abdominal or pelvic surgery , since adhesions could conceivably result in a more difficult colonoscopic examination . Statistical Analysis Prospect i ve OC performance was compared against the enhanced reference st and ard of second-look OC after segmental unblinding of VC results . We estimated exact binomial 95 % CIs for OC miss rates . We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers . We calculated the 95 % CIs by using Stata software , version 7.0 for Windows ( Stata Corp. , College Station , Texas ) , and performed the chi-square tests by using SAS software , version 8.0 for Windows ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The funding source had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results The performance characteristics of VC from this prospect i ve , multicenter screening trial , using OC as the reference st and ard , have been previously reported ( 6 ) . Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison , which is the focus of this study . We identified 1310 polyps at OC in the 1233 asymptomatic adults ; 511 ( 39.0 % ) of these polyps measured 5 mm or greater ( Figure 1).Of these 511 polyps , 55 ( 10.8 % ) were found only on second-look OC after segmental unblinding of VC results . Twenty-four ( 43.6 % ) of the 55 unblinded lesions were nonadenomatous , including 16 hyperplastic polyps . Of the 31 missed neoplasms , 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size ( 9 ) . Including unblinded lesions , 554 adenomas were detected on OC in this screening sample ; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater . Figure 1 . Polyp flowchart . In 20 patients ( 17 men and 3 women ; mean age , 58.2 years ) , 21 adenomas measuring 6 mm or greater ( range , 6 mm to 17 mm ; mean , 8.1 mm ) were found on OC only after the VC results were unblinded , which represent the lesions of primary interest for this study ( Table ) . The corresponding adenoma miss rate on prospect i ve OC examination was 10.0 % ( 95 % CI , 6.3 % to 14.9 % ) ( 21 of 210 adenomas ) at a 6-mm cutoff . The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6 % of the study sample ( 20 of 1233 patients ) but 11.9 % of patients with adenomas 6 mm or greater ( 20 of 168 patients ) . At 8-mm and 10-mm thresholds , the OC adenoma miss rates by polyp were 10.5 % ( CI , 5.2 % to 18.5 % ) ( 10 of 95 adenomas ) and 11.8 % ( CI , 4.4 % to 23.9 % ) ( 6 of 51 adenomas ) , respectively . The 10 patients with missed adenomas 8 mm or greater represented 12.2 % ( 10 of 82 patients ) of all patients with neoplasms of this size or greater ; the 6 patients with missed adenomas 8 mm or greater represented 12.5 % of all patients with neoplasms 10 mm or greater . Table . Characteristics of Neoplasms Missed at Prospect i ve Colonoscopic Evaluation Seventeen ( 81.0 % ) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas , 3 ( 14.3 % ) were tubulovillous adenomas , and 1 ( 4.8 % ) was an adenocarcinoma . Seven ( 33.3 % ) of the 21 unblinded polyps were classified as advanced lesions ( that is , size 10 mm or high- grade dysplasia , prominent villous component , or focus of malignancy ) . There were 15 sessile lesions , 4 pedunculated lesions , and 2 flat BACKGROUND Clinical dem and for total colonoscopy ( TCS ) is increasing . Improvement of the cecal intubation rate and shortening of the examination time would exp and the capacity for TCS . OBJECTIVE To assess the efficacy of a transparent hood attached to the tip of a colonoscope for cecal intubation in TCS . DESIGN Prospect i ve , r and omized , controlled study . SETTING Single tertiary-referral center . INTERVENTIONS TCS . MAIN OUTCOME MEASUREMENTS Cecal intubation time and rate , complications , patient discomfort , and detection rate of colonic polyps . METHODS Patients who were to undergo screening and /or surveillance TCS for colorectal cancer were invited to participate in the study . Cecal intubation time and rate , complications , patient discomfort , and detection rate of colonic polyps were evaluated . RESULTS A total of 592 patients enrolled in this study were r and omly allocated to the hood group and no-hood group . The mean ( SD ) cecal intubation time in the hood group and the no-hood group was 10.2 + /- 12.5 minutes and 13.4 + /- 15.8 minutes , respectively ( P = .0241 ) . The effect of its use was more prominent in the expert endoscopists group compared with those with moderate experience . The cecal intubation rate and the detection rate of small polyps in the 2 groups were similar . The grade of patient discomfort was significantly lower in the hood group . No complications were encountered with the use of the hood . CONCLUSIONS Use of a transparent hood on the tip of a colonoscope shortened the time required for cecal intubation and decreased patient discomfort ; such use was more effective among experts in shortening the examination time BACKGROUND AND STUDY AIMS In spite of scrupulous inspection during routine colonoscopy , small lesions behind the semilunar folds can be situated in blind spots , where they are easily overlooked . The aim of this study was to evaluate the efficacy of total colonoscopy with a transparent cap in identifying such lesions , in comparison with colonoscopy without the cap . PATIENTS AND METHODS In 24 patients with colorectal polyps , t and em colonoscopic procedures were carried out on the same day in r and om order , first without a transparent cap and then with the cap ( without-to-with ) , or first with the cap and then without the cap ( with-to-without ) . The time required for intubation as far as the cecum , the number of polyps detected , and procedure-related complications were recorded . The frequencies of terminal ileal intubation and retroflexion within the rectum were also recorded . RESULTS Total colonoscopy was carried out in all of the patients without any complications . Colonoscopy with a transparent cap ensured good visual fields during insertion and withdrawal of the colonoscope . There were no significant differences in the intubation time to the cecum or in the frequency of terminal ileal intubation between the two procedures . The miss rate for polyps was 15 % in without-to-with t and em colonoscopies , and zero in with-to-without procedures ( P = 0.0125 ) . The diameter of all the missed polyps except for one lesion ( 8 mm ) was less than 5 mm . Retroflexion within the rectum was more difficult using the colonoscope with the cap ( P < 0.0001 ) , and was successful in only one case using the cap . CONCLUSIONS Total colonoscopy with a transparent cap allows inspection of the blind area of the colonic mucosa behind the semilunar folds , with good visual fields . This method is potentially useful for both screening and diagnostic purpose BACKGROUND & AIMS The miss rate of colonoscopy for neoplasms is poorly understood . The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy . METHODS Two consecutive same day colonoscopies were performed in 183 patients . The patients were r and omized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position . RESULTS The overall miss rate for adenomas was 24 % , 27 % for adenomas < or = 5 mm , 13 % for adenomas 6 - 9 mm , and 6 % for adenomas > or = 1 cm . Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination ( odds ratio , 3.3 ; 95 % confidence interval , 1.69 - 6.46 ) . Right colon adenomas were missed more often ( 27 % ) than left colon adenomas ( 21 % ) , but the difference was not significant . There was evidence of variation in sensitivity between endoscopists , but significant miss rates for small adenomas were found among essentially all endoscopists . CONCLUSIONS Using current colonoscopic technology , there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy . Miss rates are low for adenomas > or = 1 cm . The results suggest the need for improvements in colonoscopic technology OBJECTIVES : Considering the increasing dem and for colonoscopy , auxiliary devices that could facilitate the examination would be useful . A hood attached to the tip of the colonoscope has been reported to be helpful in detecting and removing colorectal polyps . However , its usefulness in aiding scope intubation has not been fully evaluated . METHODS : Patients for colonoscopy between July 2004 and May 2005 in Tokyo University Hospital were enrolled to this r and omized controlled trial , and assigned to colonoscopy with a transparent hood , a short hood , or no hood . Colonoscopies were conducted by trainees without sedation . The evaluated outcomes were cecal intubation rate , trainee intubation rate ( cecal intubation within 15 min ) , cecal intubation time , and polyp detection rate . RESULTS : Enrolled 684 patients were r and omly assigned to transparent hood ( N = 221 ) , short hood ( N = 228 ) , and no hood ( N = 235 ) groups . The overall cecal intubation rate was 95.3 % ( 652/684 ) and did not differ among the groups . The overall trainee intubation rate was 55.1 % ( 377/684 ) and significantly higher in the transparent hood group than in the no hood group for female patients ( 60.7 % vs 37.4 % , P = 0.003 ) . Cecal intubation time was 11.5 , 13.5 , and 14.0 min in the transparent , short , and no hood groups , respectively , and significantly shorter in the transparent hood group than in the no hood group among overall ( P = 0.008 ) , female ( P = 0.001 ) , and old ( P = 0.04 ) patients . Polyp detection rate was higher in the transparent hood group than in the no hood group ( 49.3 % vs 39.1 % , P = 0.04 ) . CONCLUSIONS : The transparent hood was useful in shortening the cecal intubation time especially in difficult cases BACKGROUND : Small adenomas are commonly missed during routine colonoscopy . The aim of this study was to determine whether routine retroflexion in the proximal colon would improve adenoma detection rates . METHODS : One hundred patients underwent colonoscopy from the cecum to the splenic flexure by a gastroenterology fellow , with the removal of all visualized polyps . The cecum was then reintubated and patients were r and omized to a second exam of the proximal colon by an experienced staff physician in either the forward view or a retroflexed view . RESULTS : Two patients were excluded due to a difficult initial cecal intubation . Forty-eight patients were r and omized to forward view and 50 patients were r and omized to a retroflexed view . Retroflexion was successful in the cecum in 60 % , the ascending colon 100 % , and the transverse colon 98 % . The success in retroflexion was determined in part by the type of colonoscope used . If any portion of the retroflexed examination could not be performed , that reexamination was performed in the forward view . The calculated miss rates for all polyps and adenomas among patients r and omized to second examination in the forward view was 36.8 % and 33.3 % , respectively . The calculated miss rate for all polyps and for adenomas among patients r and omized to a second examination in the retroflexed view was 38.1 % and 23.7 % , respectively . There was no difference in miss rates for all polyps or for adenomas ( p = 0.31 ) when the second examination was performed in the forward view versus retroflexed view . CONCLUSIONS : A second examination by retroflexion in the proximal colon did not increase the calculated miss rate relative to that performed by a forward view examination . These results do not support the addition of routine right colon retroflexion to colonoscopy BACKGROUND & AIMS Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain . We conducted a prospect i ve study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy . METHODS Three thous and one hundred twenty-one asymptomatic subjects , age 50 to 75 years , had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs . One thous and one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years . Cohorts were defined by baseline findings . Relative risks for advanced neoplasia within 5.5 years were calculated . Advanced neoplasia was defined as tubular adenoma greater than > or = 10 mm , adenoma with villous histology , adenoma with high- grade dysplasia , or invasive cancer . RESULTS Eight hundred ninety-five ( 76.4 % ) patients with neoplasia and 298 subjects ( 59.5 % ) without neoplasia at baseline had colonoscopy within 5.5 years ; 2.4 % of patients with no neoplasia had interval advanced neoplasia . The relative risk in patients with baseline neoplasia was 1.92 ( 95 % CI : 0.83 - 4.42 ) with 1 or 2 tubular adenomas < 10 mm , 5.01 ( 95 % CI : 2.10 - 11.96 ) with 3 or more tubular adenomas < 10 mm , 6.40 ( 95 % CI : 2.74 - 14.94 ) with tubular adenoma > or = 10 mm , 6.05 ( 95 % CI : 2.48 - 14.71 ) for villous adenoma , and 6.87 ( 95 % CI : 2.61 - 18.07 ) for adenoma with high- grade dysplasia . CONCLUSIONS There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance . Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia BACKGROUND AND AIMS Colonoscopy is an excellent but imperfect modality for colorectal cancer screening and prevention . We studied the effects of a retractable transparent extension device on adenoma detection rate as well as on intubation and withdrawal times . METHODS Colonoscopy with or without the transparent retractable extension ( TRE ) was performed by one endoscopist . A subset of patients with colonic adenomas were r and omized to repeat colonoscopy with or without a TRE device . Adenoma removal was done at the second colonoscopy . The principal outcome parameters were the cecal intubation time , withdrawal time , and the number , size , and location of adenomas detected . RESULTS The study was done in two parts . First , 835 patients underwent colonoscopy with or without the TRE . The patients ' demographic characteristics , the indications for colonoscopy , the cecal intubation time and withdrawal time , and the proportion of patients with adenomas ( 29.0 % vs 24.1 % ) ( P = 0.11 ) were similar between the two techniques . The number of adenomas detected with the TRE was significantly higher than that without the extension ( 205 vs 150 ) ( P = 0.04 ) . Second , 60 patients with adenomas found at colonoscopy without the device were r and omized to repeat colonoscopy within 3 months . Hood-assisted colonoscopy revealed 20 % more adenomas than the initial procedure compared to a 4 % increase without the hood ( P = 0.029 ) . CONCLUSIONS Colonoscopy with a TRE device improved the adenoma detection rate without affecting intubation and withdrawal times Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . OBJECTIVES : Colonoscopy can not be completed in up to 10 % of cases . We postulate that cap-assisted colonoscopy ( CAC ) , by fitting a mucosectomy cap to the tip of a colonoscope , could improve the outcome . METHODS : We conducted a prospect i ve r and omized controlled trial in two regional endoscopy centers . All colonoscopies were performed by experienced colonoscopists . Patients 18 years or older undergoing their first colonoscopy were recruited . Patients were r and omized to the CAC group or to the regular colonoscopy ( RC ) group . The first successful cecal intubation rate , rescue cecal intubation rate , cecal intubation and total colonoscopy times , and polyp detection rate were compared . RESULTS : One thous and patients were enrolled ( mean age 52.6 years , 46 % men ) . There was no statistically significant difference in the first successful cecal intubation rate between CAC and RC groups ( 96.2 % vs. 94.6 % , P=0.23 ) . The cecal intubation and total colonoscopy times were shorter in the CAC group than in the RC group ( 6.0±4.0 min vs. 7.2±4.8 min , P<0.001 ; 14.7±8.6 min vs. 16.7±10.3 min , P=0.001 ) . The adenoma detection rate was significantly lower in the CAC group than in the RC group ( 30.5 % vs. 37.5 % , P=0.018 ) , but there was no significant difference in the detection of advanced lesions . In case of failing cecal intubation , use of CAC as a rescue method could achieve a higher success rate than RC ( 66.7 % vs. 21.1 % , P=0.003 ) . CONCLUSIONS : Among experienced colonoscopists , CAC did not improve the initial cecal intubation rate and had a lower adenoma detection rate . However , it shortened the cecal intubation time and performed better as a rescue method . Its utilization should be reserved for selected cases , especially when initial cecal intubation fails BACKGROUND Failures of adenoma detection diminish the effectiveness of colonoscopy . OBJECTIVE This study investigated the impact of cap-fitted colonoscopy ( CFC ) on the adenoma miss rate at colonoscopy . DESIGN R and omized , t and em colonoscopy study . SETTING University hospital . PATIENTS This study involved patients undergoing elective screening or surveillance colonoscopy . INTERVENTION Patients were r and omized to undergo cap-fitted ( n = 52 ) or regular , high-definition ( n = 48 ) colonoscopy before undergoing a second colonoscopy by the alternate method . During CFC , a plastic cap or hood was attached to the tip of the colonoscope , which was used to flatten haustral folds and improve mucosal exposure . MAIN OUTCOME MEASUREMENTS The primary outcome measure was the miss rate for adenomas between patients who underwent CFC first and patients who underwent regular colonoscopy first . RESULTS A total of 238 adenomas were detected in 67 patients ( 67 % ) , with a combined overall miss rate of 27.7 % , comprising 66 missed adenomas in 38 patients . Patients undergoing initial CFC had a significantly lower miss rate for all adenomas compared with that of patients undergoing regular colonoscopy ( 21 % vs 33 % , P = .039 ) . Miss rates with CFC were significantly lower for adenomas of ≤5 mm ( 22 % vs 35 % ; P = .037 ) . There was no significant difference in per-patient miss rates between the initial CFC group ( 51 % , n = 18 ) and the initial regular colonoscopy group ( 63 % , n = 20 , P = .36 ) . LIMITATIONS Single-center study with two endoscopists . CONCLUSION CFC reduces miss rates for all adenomas and specifically for small adenomas . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00577083 ) AIM To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate . METHODS This study was a prospect i ve r and omized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney . The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate . Consecutive cases of total colonoscopy over a 1-year period were recruited . R and omization into either st and ard colonoscopy ( SC ) or cap-assisted colonoscopy ( CAC ) was performed after consent was obtained . For cases r and omized to CAC , one of the three sizes of cap was used : D-201 - 15004 ( with a diameter of 15.3 mm ) , D-201 - 14304 ( 14.6 mm ) and D-201 - 12704 ( 13.0 mm ) . All of these caps were produced by Olympus Medical Systems , Japan . Independent predictors for faster cecal time and better polyp detection rate were also determined from this study . RESULTS There were 200 cases in each group . There was no significant difference in terms of demographic characteristics between the two groups . CAC , when compared to the SC group , had no significant difference in terms of cecal intubation rate ( 96.0 % vs 97.0 % , P = 0.40 ) and time ( 9.94 + /- 7.05 min vs 10.34 + /- 6.82 min , P = 0.21 ) , or polyp detection rate ( 32.8 % vs 31.3 % , P = 0.75 ) . On the subgroup analysis , there was no significant difference in terms of cecal intubation time by trainees ( 88.1 % vs 84.8 % , P = 0.40 ) , ileal intubation rate ( 82.5 % vs 79.0 % , P = 0.38 ) or total colonoscopy time ( 23.24 + /- 13.95 min vs 22.56 + /- 9.94 min , P = 0.88 ) . On multivariate analysis , the independent determinants of faster cecal time were consultant-performed procedures ( P < 0.001 ) , male patients ( P < 0.001 ) , non-usage of hyoscine ( P < 0.001 ) and better bowel preparation ( P = 0.01 ) . The determinants of better polyp detection rate were older age ( P < 0.001 ) , no history of previous abdominal surgery ( P = 0.04 ) , patients not having esophagogastroduodenoscopy in the same setting ( P = 0.003 ) , trainee-performed procedures ( P = 0.01 ) , usage of hyoscine ( P = 0.01 ) and procedures performed for polyp follow-up ( P = 0.01 ) . The limitations of the study were that it was a single-center experience , no blinding was possible , and there were a large number of endoscopists . CONCLUSION CAC did not significantly different from SC in term of cecal intubation time and polyp detection rate BACKGROUND Although colonoscopy is currently the optimal method for detecting colorectal polyps , some are missed . The Third Eye Retroscope provides an additional retro grade view that may detect polyps behind folds . OBJECTIVE To determine whether the addition of the Third Eye Retroscope to colonoscopy improves the adenoma detection rate . DESIGN Prospect i ve , multicenter , r and omized , controlled trial . SETTING Nine European and U.S. centers . PATIENTS Of 448 enrolled subjects , 395 had data for 2 procedures . INTERVENTIONS Subjects underwent same-day t and em examinations with st and ard colonoscopy ( SC ) and Third Eye colonoscopy ( TEC ) . Subjects were r and omized to SC followed by TEC or TEC followed by SC . MAIN OUTCOME MEASUREMENTS Detection rates for all polyps and adenomas with each method . RESULTS In the per- protocol population , 173 subjects underwent SC and then TEC , and TEC yielded 78 additional polyps ( 48.8 % ) , including 49 adenomas ( 45.8 % ) . In 176 subjects undergoing TEC and then SC , SC yielded 31 additional polyps ( 19.0 % ) , including 26 adenomas ( 22.6 % ) . Net additional detection rates with TEC were 29.8 % for polyps and 23.2 % for adenomas . The relative risk of missing with SC compared with TEC was 2.56 for polyps ( P < .001 ) and 1.92 for adenomas ( P = .029 ) . Mean withdrawal times for SC and TEC were 7.58 and 9.52 minutes , respectively ( P < .001 ) . The median difference in withdrawal times was 1 minute ( P < .001 ) . The mean total procedure times for SC and TEC were 16.97 and 20.87 minutes , respectively ( P < .001 ) . LIMITATIONS Despite r and omization and a large cohort , there was disparity in polyp prevalence between the 2 groups of subjects . CONCLUSION The Third Eye Retroscope increases adenoma detection rate by visualizing areas behind folds . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01044732 . ) PURPOSE : A transparent plastic cap of 17 mm in outer diameter , 15 mm in inner diameter , and 10 mm in length can be easily attached to the tip of a colonoscope . By using the cap , a better view of the lesions hiding at the opposite side of the fold can be obtained . When a flat colonic lesion is found , a submucosal injection of saline solution is performed , the target mucosa is sucked inside the cap , snared under a full endoscopic suction , and resected by an electrical current . This procedure is called endoscopic mucosal resection using transparent cap-fitted endoscope ( EMRC ) . Feasibility of the cap-fitted colonoscope for screening colonoscopic examination and mucosal resection was evaluated . MATERIAL S AND METHODS : One hundred forty patients were r and omly allocated for screening with a normal colonoscope ( NCF ) or that with the cap-fitted colonoscope ( CCF ) . Average time for insertion up to the cecum , patients ' discomfort during insertion expressed in 4 degrees , and average number of lesions found in one patient were compared . Thirty lesions r and omly allocated for mucosal resection with conventional strip biopsy or EMRC were also evaluated . RESULTS : Time consumed for insertion up to the cecum with the CCF ( 12.4±6.6 minutes ) was the same as that with the NCF ( 12.3±5.2 minutes ) , and there was no significant difference in patients ' discomfort ; however , the average number of lesions found in one patient was larger when using the CCF ( 0.86±0.96 ) than when using the NCF ( 0.58±0.81 ) . For mucosal resection , 40 flat or wide-based lesions including 6 mucosal carcinomas were resected with EMRC . We experienced only one pinhole perforation of the ascending colon by heat damage , which was treated successfully by surgery . There was no other major complication or recurrence . CONCLUSION : The cap-fitted endoscope was equal in maneuverability , was excellent in sensitivity in comparison with the regular colonoscope , and was thought to be feasible both in screening and mucosal resection BACKGROUND AND STUDY AIMS Even though colonoscopy was introduced 30 years ago , endoscopists still leave a small percentage of the colonic mucosal surface unexamined because of the limitations of the procedure , so there is still room for technical improvements . The aim of this pilot study was to test the feasibility of attaching a transparent cap to the tip of the colonoscope , partly to gather basic data and experience for planning a larger r and omized study , and partly to evaluate any technical advantages or disadvantages , and also to appraise the patients ' experiences . PATIENTS AND METHODS In 50 consecutive patients examined by a single experienced endoscopist , a prospect i ve pilot study was carried out comparing the use of a colonoscope fitted with a transparent cap ( in half of the colonoscopies ) with the use of an ordinary colonoscope without a cap ( in the remaining 25 patients ) . The following parameters were recorded : indication for colonoscopy , time to reach the cecum , total time for the colonoscopy , findings , diagnosis , type of colonoscopy ( diagnostic or therapeutic , partial or total , ileal intubation ) , the amount of analgesia and sedation given during the endoscopy , and complications . At the end of the examination and also before leaving the hospital , the patients were asked by a nurse to estimate pain experienced during the colonoscopy , using a visual analogue scale . RESULTS The time for the procedure , the ability to perform a complete colonoscopy ( including ileal intubation when it was medically relevant ) , and the complication rate turned out to be similar in both groups . There were no differences between the amounts of analgesia and sedation given during the endoscopy or between the patients ' estimations of the pain experienced . CONCLUSIONS The time to reach the cecum and the total time for the colonoscopy is the same with or without the cap , which is well tolerated by patients . Using the cap greatly facilitates the possibility of finding small polyps behind folds in the colon , because the folds can be straightened , thereby improving the view , although in this small pilot study it could not be proven that the number of polyps found was greater using a cap-fitted colonoscope Background Recently the use of a transparent hood attached to the tip of the colonoscope has been reported to be useful in cecal intubation , especially in difficult colonoscopy cases . However , patient comfort with or without the use of a transparent hood , the type of colonoscope most suitable for this device have not been fully evaluated . Methods A total of 372 patients undergoing routine colonoscopy were evaluated . No sedatives were used as a principle , and patients with prior abdominal surgery were excluded . A single endoscopist performed all the examinations . Four types of colonoscopes were used : CF-230I and CF-Q240AI as a st and ard colonoscope , PCF-240I and PCF-P240AI as a small-caliber colonoscope ( Olympus , Tokyo , Japan ) . A disposable transparent hood was used ( Olympus , Tokyo , Japan ) . Patients were r and omly divided into four groups ; st and ard colonoscope without transparent hood ( 96 patients ) , st and ard colonoscope with transparent hood ( 82 patients ) , small-caliber colonoscope without transparent hood ( 102 patients ) , and small-caliber colonoscope with transparent hood ( 92 patients ) . Cecal intubation time , rate , modified visual analogue scale ( VAS ) of patient ’s pain , and technical difficulty were evaluated among the four groups . Results St and ard colonoscope with the transparent hood showed the shortest cecal intubation time , and lowest modified VAS scale of pain and technical difficulty among the four groups . However there was no significant difference with regard to small-caliber colonoscopes with or without the transparent hood . Conclusions Transparent hood may be a h and y and a cost-effective device for reducing pain and simplifying cecal intubation , especially when using a st and ard adult colonoscope in routine colonoscopy |
13,029 | 28,950,431 | The risks of hypoglycemia and gastrointestinal adverse events were similar between DPP4i/AGI and PCB/AGI .
The addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI achieved better glycemic control without further increasing the risk of weight gain and hypoglycemia | AIMS / INTRODUCTION The combination of dipeptidyl peptidase-4 ( DPP4 ) inhibitors and α-glucosidase inhibitors ( AGIs ) might provide an additive or synergistic glucose-lowering effect , as they have a complementary mode of action .
In the present study , we examined the efficacy and safety of the addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI . | UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones , improving glycemic control in subjects with type 2 diabetes . This twelve-week r and omized , double-masked , placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor , vildagliptin ( 25 mg , bid , n=70 ) VS . placebo ( bid , n=28 ) in previously diet-treated subjects with type 2 diabetes . St and ardized meal tests were performed at baseline and endpoint . The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 + /- 0.2 % ( p=0.0012 ) for the whole cohort ( baseline 8.0 % ) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 % . Fasting glucose and mean pr and ial glucose were reduced by 1.1 + /- 0.4 ( p=0.0043 ) and 1.9 + /- 0.5 mmol/l ( p < 0.0001 ) , respectively . The between-group differences in corrected insulin response at peak glucose and mean pr and ial C-peptide were + 0.06 + /- 0.02 ( p=0.0258 ) and + 0.10 + /- 0.03 nmol/l ( p=0.0031 ) , respectively . Vildagliptin had no effect on fasting lipid levels or body weight . The incidence of adverse events was similar in subjects receiving placebo ( 71.4 % ) and vildagliptin ( 55.7 % ) . CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes . Concomitant improvements in beta-cell function were also observed . Subjects with higher baseline HbA1c levels showed greater response AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo Abstract Objective : To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus ( T2DM ) and inadequate glycemic control on acarbose monotherapy . Research design and methods : This was a multicenter , r and omized , placebo-controlled , double-blind clinical trial . Patients ( N = 381 ) with T2DM and inadequate glycemic control ( glycated hemoglobin [ HbA1c ] ≥ 7.0 % and ≤10.0 % ) on acarbose monotherapy ( at least 50 mg three times daily ) were r and omized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks . Main outcome measures : Changes from baseline in HbA1c and fasting plasma glucose ( FPG ) at Week 24 . Results : The mean baseline HbA1c in r and omized patients was 8.1 % . At Week 24 , the placebo-controlled , least squares mean changes from baseline ( 95 % confidence interval ) in HbA1c and FPG in the sitagliptin group were −0.62 % and −0.8 mmol/L ( p < .001 ) , respectively . At Week 24 , 37.8 % of patients in the sitagliptin group were at HbA1c goal of < 7 % compared with 17.2 % in the placebo group ( p < .001 ) . Sitagliptin was generally well tolerated , and there were no significant between-group differences in prespecified safety parameters ( symptomatic hypoglycemia , diarrhea , abdominal pain , nausea , vomiting ) . A higher incidence of serious adverse events was observed in the sitagliptin group ( 5.2 % ) relative to placebo ( 0.5 % ) ; all but one , in the sitagliptin group , were not considered related to drug . Conclusions : Sitagliptin was generally well tolerated and provided statistically superior and clinical ly meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy . Clinical trials.gov : NCT01177384 Abstract Aims / Introduction Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control . The present multicenter , r and omized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy ( 0.2–0.3 mg three times daily ) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control ( glycated hemoglobin ≥6.9 % and < 10.5 % ) . Material s and Methods The present study had an initial 12‐week , double‐blind treatment period in which patients were r and omized ( 1:1 ) to sitagliptin 50 mg/day ( n = 70 ) or placebo ( n = 63 ) , followed by a 40‐week , open‐label treatment period during which all patients received sitagliptin 50 mg/day , that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria . Results After 12 weeks , treatment with sitagliptin result ed in placebo‐subtracted mean changes from baseline in glycated hemoglobin ( the primary end‐point ) , fasting plasma glucose and 2‐h postmeal glucose of –0.9 % , –22.5 mg/dL and –51.3 mg/dL , respectively ( all , P < 0.001 ) . During the double‐blind period , adverse experiences were reported with similar frequency in both treatment groups , and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low . In the open‐label period , sustained improvements in glycemic parameters were observed with sitagliptin treatment , and sitagliptin was generally well tolerated . Conclusions Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control . This trial was registered with Clinical Trails.gov ( no. NCT00837577 ) Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy BACKGROUND Previous studies reported that administration of first generation alpha-glucosidase inhibitors ( AGIs ) , such as voglibose or acarbose , produced exaggerated and sustained postpr and ial responses of glucagon-like peptide-1 ( GLP-1 ) , an incretin hormone from the enteroinsular axis , in healthy humans . Little is known about the postpr and ial release of GLP-1 after AGI therapy in diabetics . GLP-1 plays a role to mediate satiety . Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger , increase satiation and limit food intake . OBJECTIVES This study was performed to analyse the effect of miglitol , a more potent second generation AGI with fewer gastrointestinal side-effects , on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide ( GIP ) , another incretin hormone , after stimulation by an ordinary meal in obese type-2-diabetic subjects . Miglitol 's subsequent influences on appetite sensations and food intake were also measured . DESIGN In total , 8 obese type-2-diabetic women were r and omized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days ( six doses total ) in a double-blind fashion . On day 3 of each treatment period ( miglitol or placebo ) , measurements of GLP-1 , GIP , insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast . Appetite ratings with visual analogue scales ( VASs ) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch . The number of tuna s and wiches eaten at lunch was used to measure food consumption . RESULTS The plasma GLP-1 , glucose , insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment . Miglitol effectively enhanced postpr and ial GLP-1 release and suppressed plasma GIP secretion . The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects . The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo . The postpr and ial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo . The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period . In the miglitol-treated condition , the average caloric intake at lunch during a 30-min eating period was 12 % lower ( p < 0.05 ) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30 % from the placebo-treated condition . Correspondingly , the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment ; beginning 2 and 3 h , respectively , before the lunch test . CONCLUSIONS Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics . The excessive postpr and ial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake , and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis . Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors . Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 ( GLP-1 ) secretion . We compared the postpr and ial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism , on insulin requirement , on GLP-1 secretion , and on inflammatory and endothelial markers in viscerally obese subjects . Twenty-four viscerally obese subjects with relative insulin resistance participated in this study . Subjects were given a single dose of miglitol ( 50 mg ) , acarbose ( 100 mg ) , or placebo blindly and r and omly before a meal in a crossover design . The meal loads after drug administration were tested 3 times within 2 weeks . We measured glucose , insulin , lipids , lipoprotein lipase , interleukin 6 , intracellular adhesion molecule 1 , vascular cell adhesion molecule 1 , and active GLP-1 at before and various minutes after the meal . Single administration of both alpha-glucosidase inhibitors had several beneficial effects in improving postpr and ial hyperglycemia and reducing postpr and ial insulin requirement approximately 25 % of placebo without adversely affecting lipid profiles . Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol , acarbose , and placebo administrations , miglitol significantly suppressed the increases in triglycerides , remnant-like particle triglycerides , and remnant-like particle cholesterol compared to acarbose and placebo in the early phase . Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose ( P < .01 ) and placebo ( P < .001 ) , and significantly suppressed the postpr and ial increase in interleukin 6 compared to placebo ( P < .01 ) . The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects , in preference to acarbose . Further studies are needed to eluci date the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis AIMS A double-blind r and omised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg , 50 mg , 100 mg and 200 mg all t.i.d . vs placebo t.i.d . in patients with Type 2 diabetes mellitus on diet only . METHODS After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1 % and 10.4 % were r and omised for a 24-week treatment period . RESULTS The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis . In the placebo group the HbA1c level increased by 0.40+/-1.46 % as compared with baseline . The decrease in the mean HbA1c values ( corrected for differences in baseline values ) was significant and dose-dependent for all miglitol groups compared with placebo , being -0.46 % ( 95 % CI : -0.91 % , -0.01 % ) in the 25 mg group , -0.45 % ( 95 % CI : -0.90 % , -0.003 % ) in the 50 mg group , -0.84 % ( 95 % CI : -1.31 % , -0.37 % ) in the 100 mg group and -1.26 % ( 95 % CI : -1.76 % , -0.76 % ) in the 200 mg group . Blood glucose levels following a st and ardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline : in comparison with baseline maximum blood glucose increased by 4 % with placebo and decreased by 7 % , 14 % , 24 % and 33 % with miglitol 25 mg , 50 mg , 100 mg and 200 mg t.i.d . respectively . The same pattern was seen with postpr and ial maximal serum insulin levels which decreased by 8 % under placebo and by 17 % , 26 % , 25 % and 35 % with the 25 mg to 200 mg doses of miglitol . The adverse events reported were mainly of gastrointestinal nature , mostly being flatulence , diarrhoea and abdominal pain and the incidence increased with increasing dose . Although the side effects were not serious , they were troublesome , leading to a considerable drop-out rate increasing with dose . CONCLUSIONS The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postpr and ial glucose and insulin levels in a dose-dependent manner . Gastrointestinal side effects also showed dose-dependency . Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d AIM Acarbose is able to enhance GLP-1 release and delay gastric emptying in normal subjects . The effect of alpha-glucosidase inhibition on GLP-1 has been less evident in Type 2 diabetic patients . The aim of this study was to investigate the possible influence of acarbose on GLP-1 release and gastric emptying in Type 2 diabetic patients after a mixed test meal . PATIENTS AND METHODS Ten Type 2 diabetic patients were tested with 100 mg acarbose or placebo served with a mixed meal that was labelled with 100 mg 13C-octanoic acid . Plasma concentrations of glucose , insulin , C-peptide , glucagon , GLP-1 and GIP were determined over 6 h. Gastric emptying was measured by determining breath 13CO2 using infrared absorptiometry . Statistics repeated- measures anova . RESULTS Gastric emptying rates ( t1/2 : 162 + /- 45 vs. 163 + /- 62 min , P = 0.65 ) and plasma concentrations ( increasing from approximately 12 to approximately 25 pmol/l , P = 0.37 ) and integrated responses of GLP-1 ( P = 0.37 ) were not changed significantly by acarbose treatment . Postpr and ial plasma glucose concentrations ( P < 0.0001 ) and their integrated responses were lowered by acarbose ( by 64 % ; P = 0.016 ) . The plasma concentrations of insulin and C-peptide were reduced ( P = 0.007 and 0.057 , respectively ) by acarbose , while glucagon was not changed ( P = 0.96 ) . GIP plasma concentrations ( increasing with placebo from approximately 10 to approximately 85 pmol/l and with acarbose to approximately 55 pmol/l ( P < 0.0001 ) and their integrated responses were significantly lowered ( by 43 % ) by acarbose ( P = 0.021 ) . After 2 weeks of acarbose treatment ( 50 mg t.i.d . for the first and 100 mg t.i.d . for the second week , n = 6 ) , similar results were found . CONCLUSIONS In hyperglycaemic Type 2 diabetic patients , ingestion of acarbose with a mixed test meal failed to enhance GLP-1 release and did not influence gastric emptying Abstract Objective : To compare the efficacy and safety of alogliptin and placebo as add-on therapy in Japanese patients with type 2 diabetes who experienced inadequate glycemic control on voglibose plus diet/exercise therapy . Research design and methods : During an 8 week screening phase , patients aged ≥20 years were stabilized on voglibose 0.2 mg three times daily plus diet/exercise therapy . Those with HbA1c between ≥6.9 % and < 10.4 % were r and omly assigned to 12 weeks ’ double-blind treatment with once daily alogliptin 12.5 or 25 mg , or placebo . The primary endpoint was the change in HbA1c at 12 weeks from baseline . Patients then entered an open-label , 40 week extension trial ( patients in the placebo group were r and omly allocated to alogliptin 12.5 or 25 mg ) . Clinical trials registration : www . clinical trials.gov ; pivotal trial NCT01263483 ; Long term trial NCT01263509 . Results : Least square mean change in HbA1c after 12 weeks ’ therapy from baseline ( primary endpoint ) was significantly greater in the alogliptin 12.5 mg ( −0.96 % ; P < 0.0001 ) and 25 mg ( −0.93 % ; P < 0.0001 ) groups compared with placebo ( + 0.06 % ) . This was associated with statistically significant improvements in other measures of glycemic control , in particular sustained reductions in fasting plasma glucose and postpr and ial plasma glucose . These benefits were maintained for the duration of the 1 year study and , importantly , they were achieved without detrimental effects on tolerability/safety . In particular , there was no increase in the rate of hypoglycemia and almost no changes in mean body weight . Conclusions : Addition of once daily alogliptin to voglibose monotherapy in Japanese patients with uncontrolled type 2 diabetes produced clinical ly significant improvements in glycemic control , and was well tolerated The alpha-glucosidase inhibitor voglibose ( AO-128 ) was design ed to prevent rapid postpr and ial blood glucose rises in non-insulin-dependent diabetics . We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before , after the 1st dose , and on the 7th day of a 7-day treatment protocol ( 3 daily loads ) . Six parallel groups of 12 volunteers received voglibose ( 0.5 , 1.0 , 2.0 , or 5.0 mg ) or placebo ( two groups ) . Blood was drawn at regular intervals up to 180 min after a st and ardized breakfast to analyze the levels of glucose , insulin , C peptide , gastric inhibitory polypeptide , and glucagon-like peptide 1 ( GLP-1 ) . As expected , after ingestion of voglibose , slight to moderate gastro-intestinal discomfort but no severe side-effects were reported . In a dose-dependent manner , voglibose significantly reduced postpr and ial increases of blood glucose , insulin , and C peptide . At the lower loads ( 0.5 and 1 mg voglibose three times daily ) , these effects were more pronounced after 7 days . The postpr and ial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose . In comparison to the placebo group , this inhibition became also significant for the lower loads after 7 days . Interestingly , GLP-1 , originating from the lower intestines , was increasingly released under voglibose treatment . The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80 % above controls . Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 ( > 90 % above controls ) which was not further increased by 2- or 5-mg loads . We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1 OBJECTIVE To determine the degree to which alpha-glucosidase inhibitors , with their unique mode of action primarily reducing postpr and ial hyperglycemia , offer an additional therapeutic approach in the long-term treatment of type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 1,946 patients ( 63 % men ) who were previously enrolled in the U.K. Prospect i ve Diabetes Study ( UKPDS ) . The patients were r and omized to acarbose ( n = 973 ) , titrating to a maximum dose of 100 mg three times per day , or to matching placebo ( n = 973 ) . Mean + /- SD age was 59 + /- 9 years , body weight 84 + /- 17 kg , diabetes duration 7.6 + /- 2.9 years , median ( interquartile range ) HbA1c 7.9 % ( 6.7 - 9.5 ) , and fasting plasma glucose ( FPG ) 8.7 mmol/l ( 6.8 - 11.1 ) . Fourteen percent of patients were treated with diet alone , 52 % with monotherapy , and 34 % with combined therapy . Patients were monitored in UKPDS clinics every 4 months for 3 years . The main outcome measures were HbA1c , FPG , body weight , compliance with study medication , incidence of side effects , and frequency of major clinical events . RESULTS At 3 years , a lower proportion of patients were taking acarbose compared with placebo ( 39 vs. 58 % , P < 0.0001 ) , the main reasons for noncompliance being flatulence ( 30 vs. 12 % , P < 0.0001 ) and diarrhea ( 16 vs. 8 % , P < 0.05 ) . Analysis by intention to treat showed that patients allocated to acarbose , compared with placebo , had 0.2 % significantly lower median HbA1c at 3 years ( P < 0.001 ) . In patients remaining on their allocated therapy , the HbA1c difference at 3 years ( 309 acarbose , 470 placebo ) was 0.5 % lower median HbA1c ( 8.1 vs. 8.6 % , P < 0.0001 ) . Acarbose appeared to be equally efficacious when given in addition to diet alone ; in addition to monotherapy with a sulfonylurea , metformin , or insulin ; or in combination with more complex treatment regimens . No significant differences were seen in FPG , body weight , incidence of hypoglycemia , or frequency of major clinical events . CONCLUSIONS Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes , irrespective of concomitant therapy for diabetes . Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects BACKGROUND / AIMS Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 ( GLP-1 ) and gastric inhibitory polypeptide ( GIP ) . The present study asked whether vildagliptin accentuates glibenclamide-induced hypoglycemia or affects endogenous secretion of GLP-1 and GIP after an oral glucose tolerance test . METHODS There were 16 healthy male subjects studied on four occasions after an overnight fast in a double-blind , four-way crossover study . In r and om order , vildagliptin ( 100 mg ) or placebo , with and without glibenclamide ( 5 mg ) , was administered 30 min before 75 g oral glucose . Blood was sample d to measure glucose , and total ( sum of active and inactive ) GLP-1 and GIP . Statistical evaluation was done using repeated- measures ANOVA . RESULTS Glibenclamide provoked hypoglycemia ( < or=1.9 mm ) , but this was not accentuated by the simultaneous administration of vildagliptin ( P = 0.25 ) . The integrated incremental responses of total GLP-1 were reduced by vildagliptin by 72 % ( with glibenclamide ) and 48 % ( without glibenclamide ) ( effect of vildagliptin : P < 0.0001 ; glibenclamide : P = 0.31 ; interaction : P = 0.26 ) . Similarly , integrated incremental responses of total GIP were reduced by vildagliptin by 26 and 21 % , with and without glibenclamide , respectively ( vildagliptin : P = 0.017 ; glibenclamide : P = 0.44 ; interaction : P = 0.69 ) . CONCLUSIONS Sulfonylurea-induced hypoglycemia after the oral administration of glibenclamide is not accentuated by the coadministration of vildagliptin . This may be explained by a negative feedback regulation of GLP-1 and GIP secretion that limits the degree to which the active incretin levels are enhanced Background and Objective Gemigliptin is a novel dipeptidyl peptidase-4 ( DPP-4 ) inhibitor used in the treatment of type 2 diabetes mellitus . This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability . Methods A r and omized , open-label , multiple-dose , three-treatment , three-period , three-sequence crossover study was conducted in healthy male subjects . Twenty-seven subjects received gemigliptin ( 50 mg once daily ) , metformin ( 1,000 mg twice a day ) , or both drugs for 7 days per dosing period . Blood sample s were drawn over 24 h on the seventh day of each period for pharmacokinetic and pharmacodynamic evaluations , including plasma DPP-4 activity and total/active glucagon-like peptide-1 ( GLP-1 ) levels . Meal tolerance tests were conducted for pharmacodynamic assessment on the eighth day . Safety and tolerability were evaluated using adverse events , vital signs , ECGs , and clinical laboratory tests . Results Coadministration of gemigliptin and metformin had no significant effect on the pharmacokinetics of gemigliptin or metformin . The inhibition of DPP-4 by gemigliptin was not affected by coadministration with metformin . Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels . The plasma glucagon level was lower in co-therapy than with metformin monotherapy . The coadministration of gemigliptin and metformin was well-tolerated without serious adverse events . Conclusions Coadministration of gemigliptin and metformin showed beneficial anti-diabetic effects without pharmacokinetic drug – drug interactions AIM To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [ haemoglobin A(1c ) ( HbA(1c ) ) 7 - 11 % ] on metformin monotherapy . METHODS Patients ( n = 273 ) on metformin ( > /=1500 mg/day ) were r and omized to receive the addition of once-daily placebo , sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks . The efficacy analysis was based on the all- patients -treated population using an analysis of co-variance with change in HbA(1c ) from baseline as the primary endpoint . RESULTS The mean baseline HbA(1c ) was 7.7 % for the entire cohort . After 18 weeks , both active add-on therapies led to greater improvements in HbA(1c ) from baseline : -0.73 % for sitagliptin ( p < 0.001 vs. placebo ) and -0.79 % for rosiglitazone compared with -0.22 % for placebo . No difference was observed between the sitagliptin and rosiglitazone treatments ( 0.06 % [ 95 % confidence interval ( CI ) : -0.14 to 0.25 ] ) . The proportion of patients achieving an HbA(1c ) < 7 % was greater with sitagliptin ( 55 % ) and rosiglitazone ( 63 % ) compared with placebo ( 38 % ) . Body weight increased from baseline with rosiglitazone ( 1.5 kg ) compared with body weight reduction with sitagliptin ( -0.4 kg ) and placebo ( -0.8 kg ) . The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg ( 95 % CI : 1.3 - 2.5 ) . In a prespecified analysis , the proportion of patients experiencing a greater than 3-kg increase in body weight was 21 % in the rosiglitazone group compared with 2 % in both the sitagliptin and placebo groups . Both active treatments were generally well tolerated , with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo . CONCLUSIONS In this 18-week study , the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy . Treatment with sitagliptin produced similar reductions in HbA(1c ) compared with the addition of rosiglitazone AIM To investigate whether patients taking metformin for type 2 diabetes mellitus ( T2DM ) have improved glycaemic control without compromising tolerability by adding an agent with a complementary mechanism of action vs. uptitrating metformin . METHODS Adults with T2DM and glycated haemoglobin ( HbA1c ) between 7.0 and 10.5 % receiving metformin extended release ( XR ) 1500 mg/day for ≥8 weeks were r and omized to receive saxagliptin 5 mg added to metformin XR 1500 mg ( n = 138 ) or metformin XR uptitrated to 2000 mg/day ( n = 144 ) . Endpoints were change from baseline to week 18 in HbA1c ( primary ) , 120-min postpr and ial glucose ( PPG ) , fasting plasma glucose ( FPG ) and the proportion of patients achieving HbA1c < 7 % . RESULTS At week 18 , the adjusted mean reduction from baseline HbA1c was -0.88 % for saxagliptin + metformin XR and -0.35 % for uptitrated metformin XR ( difference , -0.52 % ; p < 0.0001 ) . For 120-min PPG and FPG , differences in adjusted mean change from baseline between saxagliptin + metformin XR and uptitrated metformin XR were -1.3 mmol/l ( -23.32 mg/dl ) ( p = 0.0013 ) and -0.73 mmol/l ( -13.18 mg/dl ) ( p = 0.0030 ) , respectively . More patients achieved HbA1c < 7.0 % with saxagliptin + metformin XR than with uptitrated metformin XR ( 37.2 vs. 26.1 % ; p = 0.0459 ) . The proportions of patients experiencing any adverse events ( AEs ) were generally similar between groups ; neither group showed any notable difference in hypoglycaemia or gastrointestinal AEs . CONCLUSION Adding saxagliptin to metformin XR provided superior glycaemic control compared with uptitrating metformin XR without the emergence of additional safety concerns CONTEXT Dipeptidyl peptidase-4 inhibitors act by increasing plasma levels of glucagon-like peptide-1 and suppressing excessive glucagon secretion in patients with type 2 diabetes . However , their effects on the glucagon response to hypoglycemia are not established . OBJECTIVE The aim of the study was to assess effects of the dipeptidyl peptidase-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia . DESIGN We conducted a single-center , r and omized , double-blind , placebo-controlled , two-period crossover study of 28-d treatment , with a 4-wk between-period washout . PATIENTS We studied drug-naive patients with type 2 diabetes and baseline glycosylated hemoglobin of 7.5 % or less . INTERVENTION Participants received vildagliptin ( 100 mg/d ) or placebo as out patients . PRIMARY OUTCOME MEASURE(S ) : We measured the following : 1 ) change in plasma glucagon levels during hypoglycemic ( 2.5 mm glucose ) clamp ; and 2 ) incremental ( Delta ) glucagon area under the concentration-time curve from time 0 to 60 min ( AUC(0 - 60 min ) ) during st and ard meal test . Before the study , it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia . RESULTS The mean change in glucagon during hypoglycemic clamp was 46.7 + /- 6.9 ng/liter with vildagliptin treatment and 33.9 + /- 6.7 ng/liter with placebo ; the between-treatment difference was 12.8 + /- 7.0 ng/liter ( P = 0.039 ) , representing a 38 % increase with vildagliptin . In contrast , the mean glucagon DeltaAUC(0 - 60 min ) during meal test with vildagliptin was 512 + /- 163 ng/liter x min vs. 861 + /- 130 ng/liter x min with placebo ; the between-treatment difference was -349 + /- 158 ng/liter x min ( P = 0.019 ) , representing a 41 % decrease with vildagliptin . CONCLUSIONS Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects of hyperglycemia and the stimulatory effects of hypoglycemia . These effects likely contribute to the efficacy of vildagliptin to improve glycemic control as well as to its low hypoglycemic potential AIM To assess changes in circulating incretin levels and body fat compositions with initial combination therapy with α-glucosidase inhibitor and dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes ( T2D ) . METHODS In this multicenter open-label 24-week trial , Japanese over-weight ( BMI ≥ 25 kg/m(2 ) ) patients with T2D not taking medication or taking metformin and /or sulfonylurea were r and omly assigned to receive either 50 mg of miglitol three times a day ( M , n=14 ) , 50 mg of sitagliptin once a day ( S , n=14 ) , or a combination of both ( M+S , n=13 ) . Changes in plasma incretin levels during a meal tolerance test ( MTT ) and body fat composition with impedance method were evaluated . RESULTS During MTT , postpr and ial plasma glucose levels decreased more after M+S than after M or S , and postpr and ial serum insulin levels decreased significantly after M and M+S whereas they increased after S. After M , active gastric inhibitory polypeptide ( aGIP ) decreased significantly at 30 min despite a significant increase at 120 min . After S , aGIP levels increased significantly throughout the MTT . After M+S , aGIP increased significantly at 0 and 120 min despite of significant decrease at 30 min . M+S further enhanced postpr and ial active glucagon-like peptide-1 levels during MTT than S did . Total body fat mass decreased significantly after M and M+S. Visceral fat mass decreased significantly only after M+S. Serum adiponectin increased significantly only after M+S. CONCLUSIONS In over-weight patients with T2D , M+S may have a beneficial effect on adiposity with relation to these different effects on two incretins AIM To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 ( DPP-4 ) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control . METHODS This 24-week , r and omized , placebo-controlled , double-blind , parallel-group study was carried out in 82 centres in 10 countries . Patients with HbA1c levels of 7.0 - 10.0 % on metformin and a maximum of one additional antidiabetes medication , which was discontinued at screening , continued on metformin ≥1500 mg/day for 6 weeks , including a placebo run-in period of 2 weeks , before being r and omized to linagliptin 5 mg once daily ( n = 524 ) or placebo ( n = 177 ) add-on . The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment , evaluated with an analysis of covariance ( ANCOVA ) . RESULTS Mean baseline HbA1c and fasting plasma glucose ( FPG ) were 8.1 % and 9.4 mmol/l , respectively . Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c ( -0.49 vs. 0.15 % ) , FPG ( -0.59 vs. 0.58 mmol/l ) and 2hPPG ( -2.7 vs. 1.0 mmol/l ) ; all p < 0.0001 . Hypoglycaemia was rare , occurring in three patients ( 0.6 % ) treated with linagliptin and five patients ( 2.8 % ) in the placebo group . Body weight did not change significantly from baseline in both groups ( -0.5 kg placebo , -0.4 kg linagliptin ) . CONCLUSIONS The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin result ed in a significant and clinical ly meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia This r and omized , open-label , placebo-controlled , 7-period crossover study assessed dose-response relationships following single oral doses ( 10 - 400 mg ) of vildagliptin in 16 patients with type 2 diabetes mellitus . Plasma levels of parent drug , dipeptidyl peptidase-4 activity , glucose , insulin , and glucagon were measured during 75-g oral glucose tolerance tests performed after an overnight fast , 30 minutes after drug administration . The t(max ) for parent drug was observed between 0.5 and 1.5 hours postdose . Both C(max ) and AUC(0 - 8 h ) increased dose proportionately . Both onset and duration of dipeptidyl peptidase-4 inhibition were dose dependent , but > 90 % inhibition occurred within 45 minutes and was maintained for > /=4 hours after each dose . Glucose excursions and glucagon levels during oral glucose tolerance tests were significantly and similarly decreased after each dose of vildagliptin , and insulin levels were significantly and similarly increased after each dose level . Unlike findings during mixed-meal challenges , vildagliptin increases plasma insulin levels during oral glucose tolerance tests in patients with type 2 diabetes mellitus Although the α-glucosidase inhibitor miglitol ( MG ) has been reported to have anorexigenic effects , the mechanism remains to be eluci date d. The objective of this study was to explore the effects of MG on appetite in relation to concomitant changes in postpr and ial gut hormone levels . This r and omized open-label crossover study included 20 healthy volunteers . The effects of 50 mg MG on glucagon-like peptide-1 ( GLP-1 ) , peptide YY ( PYY ) , and ghrelin levels were assessed in conjunction with a simultaneous determination of appetite scores using visual analogue scales ( VAS ) over 3 h after the ingestion of a 592 kcal test cookie . Additionally , the gastric emptying rate ( GER ) was measured using breath ¹³CO₂ appearance in 10 subjects . 12 subjects were administered 50 mg MG thrice a day for 1 week , and alterations of the gut hormone levels and the VAS scores for appetite were evaluated . MG pre-administration result ed in a significant enhancement of GLP-1 and PYY responses induced by the cookie ingestion . Following MG administration , ghrelin level declined at 1 h , with a persistent suppression during the postpr and ial phase in contrast to the restoration to the basal level without MG . Furthermore , MG pre-administration suppressed appetite and maintained satiety evaluated using a VAS rating with concomitant inhibition of GER after cookie ingestion . One-week administration of MG did not influence either gut hormone levels before a meal or VAS rating during a whole day . These observations suggest that MG exerts an anorexigenic effects with concomitant alterations of gut hormone secretions and gastric emptying after meal ingestion CONTEXT In response to a meal , glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic peptide ( GIP ) are released and modulate glycemic control . Normally these incretins are rapidly de grade d by dipeptidyl peptidase-4 ( DPP-4 ) . DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes . The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test ( OGTT ) were evaluated . OBJECTIVE The objective of the study was to examine the pharmacodynamics , pharmacokinetics , and tolerability of sitagliptin . DESIGN This was a r and omized , double-blind , placebo-controlled , three-period , single-dose crossover study . SETTING The study was conducted at six investigational sites . PATIENTS The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents . INTERVENTIONS Interventions included sitagliptin 25 mg , sitagliptin 200 mg , or placebo . MAIN OUTCOME MEASURES Measurements included plasma DPP-4 activity ; post-OGTT glucose excursion ; active and total incretin GIP levels ; insulin , C-peptide , and glucagon concentrations ; and sitagliptin pharmacokinetics . RESULTS Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h , enhanced active GLP-1 and GIP levels , increased insulin/C-peptide , decreased glucagon , and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin . Sitagliptin was generally well tolerated , with no hypoglycemic events . CONCLUSIONS In this study in patients with type 2 diabetes , near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80 % or greater , corresponding to a plasma sitagliptin concentration of 100 nm or greater , and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT GLP-1 , an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity , is secreted after nutrient ingestion . GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract ( GIT ) ; simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects . In a cross-over study , 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas . Plasma levels of GLP-1 , insulin , C-peptide , glugacon , GIP , glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates . With acarbose , sucrose reached the colon 60 - 90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation ( p = 0.005 ) . After an early GLP-1 increment 15 min after sucrose under both conditions , GLP-1 release was prolonged in the acarbose group ( p = 0.001 ; significant from 210 to 360 min . ) . Initially ( 0 - 150 min ) , glucose ( p = 0.001 ) , insulin ( p = 0.001 ) , and GIP ( p < 0.001 ) were suppressed by acarbose , whereas later there were no significant differences . Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period ( p = 0.02 ) . We conclude that in hyperglycaemic Type 2 diabetic patients , ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release AIMS To evaluate the efficacy and safety of alogliptin added to metformin versus metformin monotherapy in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on metformin ( 500 or 750 mg/day ) + diet/exercise . METHODS In a r and omized , double-blind trial , 288 patients with type 2 diabetes mellitus T2DM received either 12.5 or 25 mg alogliptin once daily + metformin or placebo + metformin for 12 weeks . Thereafter , 276 patients continued on one of the two alogliptin dosages + metformin in an open-label extension for 40 weeks . The primary efficacy endpoint in the r and omized , double-blind phase was the change in HbA1c from baseline ( week 0 ) to the end of treatment ( week 12 ) . The primary endpoint during the long-term extension phase was adverse events . RESULTS After 12 weeks both dosages of alogliptin + metformin produced significantly greater changes from baseline in HbA1c than placebo ( metformin monotherapy : with changes in LS means - 0.55 and - 0.64 % vs. 0.22 % , respectively ; p < 0.0001 ) . Incidences of adverse effects were comparable between groups , with no increases in hypoglycaemia . Over 52 weeks , there were no safety or tolerability concerns with alogliptin when added to metformin . CONCLUSIONS Alogliptin 12.5 and 25 mg once daily was safe and effective when added to metformin ( 500 or 750 mg/day ) in Japanese patients with inadequately controlled type 2 diabetes on metformin alone |
13,030 | 19,077,738 | In conclusion , caffeine ingestion can be an effective ergogenic aid for endurance athletes when taken before and /or during exercise in moderate quantities ( 3 - 6 mg.kg body mass ) .
Abstaining from caffeine at least 7 days before use will give the greatest chance of optimizing the ergogenic effect | Endurance athletes often ingest caffeine because of its reported ergogenic properties .
Although there are a vast number of studies quantifying caffeine 's effects , many research studies measure endurance performance using a time-to-exhaustion test ( subjects exercise at a fixed intensity to volitional exhaustion ) .
Time-to-exhaustion as a performance measure is not ideal because of the high degree of measurement variability between and within subjects .
Also , we are unaware of any endurance sports in which individuals win by going a longer distance or for a longer amount of time than their competitors .
Measuring performance with a time-trial test ( set distance or time with best effort ) has high reproducibility and is more applicable to sport .
Therefore , the purpose of this review was to critically and objective ly evaluate studies that have examined the effect of caffeine on time-trial endurance ( > 5 minutes ) performance . | This study compared the effects of a single and divided dose of caffeine on endurance performance and on postexercise urinary caffeine and plasma paraxanthine concentrations . Nine male cyclists and triathletes cycled for 90 min at 68 % of maximal oxygen uptake , followed by a self-paced time trial ( work equivalent to 80 % of maximal oxygen uptake workload over 30 min ) with three r and omized , balanced , and double-blind interventions : 1 ) placebo 60 min before and 45 min into exercise ( PP ) ; 2 ) single caffeine dose ( 6 mg/kg ) 60 min before exercise and placebo 45 min into exercise ( CP ) ; and 3 ) divided caffeine dose ( 3 mg/kg ) 60 min before and 45 min into exercise ( CC ) . Time trial performance was unchanged with caffeine ingestion ( P = 0.08 ) , but it tended to be faster in the caffeine trials ( CP : 24.2 min and CC : 23.4 min ) compared with placebo ( PP : 28.3 min ) . Postexercise urinary caffeine concentration was significantly lower in CC ( 3.8 micro g/ml ) compared with CP ( 6.8 micro g/ml ) . Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise . In conclusion , dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration The purpose of the present study was to examine the duration of caffeine 's ergogenic effect and whether it differs between users and nonusers of the drug . Twenty-one subjects ( 13 caffeine users and 8 nonusers ) completed six r and omized exercise rides to exhaustion at 80 % of maximal oxygen consumption after ingesting either a placebo or 5 mg/kg of caffeine . Exercise to exhaustion was completed once per week at either 1 , 3 , or 6 h after placebo or drug ingestion . Exercise time to exhaustion differed between users and nonusers with the ergogenic effect being greater and lasting longer in nonusers . For the nonusers , exercise times 1 , 3 , and 6 h after caffeine ingestion were 32.7 + /- 8.4 , 32.1 + /- 8.6 , and 31.7 + /- 12.0 min , respectively , and these values were each significantly greater than the corresponding placebo values of 24.2 + /- 6.4 , 25.8 + /- 9.0 , and 23.2 + /- 7.1 min . For caffeine users , exercise times 1 , 3 , and 6 h after caffeine ingestion were 27.4 + /- 7.2 , 28.1 + /- 7.8 , and 24.5 + /- 7.6 min , respectively . Only exercise times 1 and 3 h after drug ingestion were significantly greater than the respective placebo trials of 23.3 + /- 6.5 , 23.2 + /- 7.1 , and 23.5 + /- 5.7 min . In conclusion , both the duration and magnitude of the ergogenic effect that followed a 5 mg/kg dose of caffeine were greater in the nonusers compared with the users UNLABELLED Both time-to-exhaustion ( TTE ) and time-trial ( TT ) exercise tests are commonly used to assess exercise performance , but no study has directly examined the reliability of comparable tests in the same subjects . PURPOSE To evaluate the reliability of comparable TTE and TT treadmill running tests of high and moderately high exercise intensity in endurance-trained male distance runners , and to vali date Hinckson and Hopkins TT prediction methods using log-log modeling from TTE results . METHODS After familiarization tests , eight endurance-trained male distance runners performed , in a r and omized , counterbalanced order , eight trials consisting of two 5-km TT and two 1500-m TT , and four TTE tests run at a speed equivalent to the average speed attained during both the 5-km and 1500-m TT distances . RESULTS Typical error of the estimate ( TEE ) expressed as a coefficient of variation for the 5-km TT , 5-km TTE , 1500-m TT , and 1500-m TTE were 2.0 , 15.1 , 3.3 , and 13.2 % , respectively . The st and ard error of the estimate for predicted TT running speed using log-log modeling from TTE results was 0.67 % , and the predicted versus criterion reliability of this method revealed TEE values of 1.6 % and 2.5 % for the prediction of 5-km and 1500-m TT , respectively . CONCLUSION The variability of 5-km and 1500-m TT tests was significantly less than for similar TTE treadmill protocol s. Despite the greater variability of the TTE tests , log-log modeling using the TTE test results reliably predicted actual TT performance This study analyzed the effect of caffeine ingestion on performance during a repeated- measures , 100-km , laboratory cycling time trial that included bouts of 1- and 4-km high intensity epochs ( HIE ) . Eight highly trained cyclists participated in 3 separate trials ' placebo ingestion before exercise with a placebo carbohydrate solution and placebo tablets during exercise ( Pl ) , or placebo ingestion before exercise with a 7 % carbohydrate drink and placebo tablets during exercise ( Cho ) , or caffeine tablet ingestion before and during exercise with 7 % carbohydrate ( Caf ) . Placebo ( twice ) or 6 mg.kg(-1 ) caffeine was ingested 60 min prior to starting 1 of the 3 cycling trials , during which subjects ingested either additional placebos or a caffeine maintenance dose of 0.33 mg.kg(-1 ) every 15 min to trial completion . The 100-km time trial consisted of five 1-km HIE after 10 , 32 , 52 , 72 , and 99 km , as well as four 4-km HIE after 20 , 40 , 60 , and 80 km . Subjects were instructed to complete the time trial and all HIE as fast as possible . Plasma ( caffeine ) was significantly higher during Caf ( 0.43 + /- 0.56 and 1.11 + /- 1.78 mM pre vs. post Pl ; and 47.32 + /- 12.01 and 72.43 + /- 29.08 mM pre vs. post Caf ) . Average power , HIE time to completion , and 100-km time to completion were not different between trials . Mean heart rates during both the 1-km HIE ( 184.0 + /- 9.8 Caf ; 177.0 + /- 5.8 Pl ; 177.4 + /- 8.9 Cho ) and 4-km HIE ( 181.7 + /- 5.7 Caf ; 174.3 + /- 7.2 Pl ; 175.6 + /- 7.6 Cho ; p < .05 ) was higher in Caf than in the other groups . No significant differences were found between groups for either EMG amplitude ( IEMG ) or mean power frequency spectrum ( MPFS ) . IEMG activity and performance were not different between groups but were both higher in the 1-km HIE , indicating the absence of peripheral fatigue and the presence of a central ly-regulated pacing strategy that is not altered by caffeine ingestion . Caffeine may be without ergogenic benefit during endurance exercise in which the athlete begins exercise with a defined , predetermined goal measured as speed or distance The ingestion of a combination of caffeine ( C ) and ephedrine ( E ) has been reported to prolong exercise time to exhaustion during cycle ergometry at 85 % VO2max . The present study was undertaken to investigate whether this enhancement would occur in a field setting and if drug ingestion on 1 d would affect performance 1 d later . Two hours after ingesting either a combination of 375 mg of C and 75 mg E ( C+E ) , or a placebo ( P ) , 9 healthy male recreational runners completed six balanced and double-blind trials of the Canadian Forces Warrior Test ( WT ) , a 3.2 km run wearing " fighting order " which weighed about 11 kg . The trials were performed in sets of two runs , i.e. , two runs were done 24 h apart , and these sets were separated by a minimum of 7 d. The sets were : C+E trial on day 1 ( D1 ) , placebo on day 2 ( P2 ) ; placebo first ( P1 ) , C+E second ( D2 ) ; and placebo first ( P3 ) , placebo second ( P4 ) . In addition , 1 wk before the treatment trials the subjects performed a control trial WT . During the WT , heart rates ( HR ) were recorded every minute . Plasma C and E levels immediately before the WT were similar for both C+E trials , but were undetectable for all P trials . Run times ( mean+/-SD ) were 15.3+/-0.6 , 15.4+/-0.9 , 15.5+/-1.2 , 15.4+/-0.9 , 15.4+/-0.9 , 14.8+/-0.7 , and 14.6+/-0.8 min for control , P1 , P2 , P3 , P4 , D1 , D2 trials , respectively . The two C+E trial run times were similar and both were significantly faster ( p < 0.05 ) than control and all placebo trials . HR during the WT was significantly higher ( p < 0.05 ) for the C+E trials compared with the other trials . WT performance was not impaired by C+E ingestion 24 h earlier . In conclusion , performance of the WT was improved by ingestion of BACKGROUND The ingestion of either caffeine ( C ) or ephedrine ( E ) has been shown to improve performance during high-intensity aerobic activity lasting 10 - 20 min , with an additive effect being found when the combination ( C + E ) was ingested . It was the purpose of this study to determine if the addition of E to C would improve performance in activity lasting longer than 20 min . METHODS One and one half hours after ingesting a placebo ( P ) , C ( 4 mg/kg ) , E ( 0.8 mg/kg ) , or C + E , 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg . The trials were performed in a climatic suite at 12 - 13 degrees C , on a treadmill where the speed was regulated by the subject . VO(2 ) , VCO(2 ) , V(E ) , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were measured during the run at 15 and 30 min , and again when the individual reached 9 km . Blood was sample d at 15 and 30 min and again at the end of the run and assayed for lactate , glucose , and catecholamines . RESULTS Run times ( mean + /- SD ) , in minutes , were for C ( 46.0 + /- 2.8 ) , E ( 45.5 + /- 2.9 ) , C + E ( 45.7 + /- 3.3 ) , and P ( 46.8 + /- 3.2 ) . The run times for the E trials ( E and C + E ) were significantly reduced compared with the non-E trials ( C and P ) . Pace was increased for the E trials compared with the non-E trials over the last 5 km of the run . VO(2 ) was not affected by drug ingestion . HR was elevated for the ephedrine trials ( E and C + E ) . RPE remained similar for all trails . Caffeine increased the epinephrine and norepinephrine response associated with exercise and also increased blood lactate , glucose , and glycerol levels . Ephedrine reduced the epinephrine response but increased dopamine and FFA levels . CONCLUSION The previously seen additive nature of E and C was not evident in this study , with the primary ergogenic effect being attributed to The stimulatory effects of acute caffeine intake on choice reaction time , mood state , and visual vigilance are well established . Little research exists , however , on the effects of chronic caffeine ingestion on psychomotor tasks . Therefore , the purpose of this study was to evaluate the effects of 5 days of controlled caffeine intake on cognitive and psychomotor performance . Three groups of 20 healthy males ( age=22+/-3 years , mass=75.4+/-7.9 kg , body fat percentage=11.2+/-5.1 % ) twice completed a battery of cognitive and psychomotor tasks : after 6 days of 3 mg.kg(-1 ) day(-1 ) caffeine equilibration ( Day 6 ) , and after 5 days of experimental ( 0 [ G0 ] , 3 [ G3 ] , or 6 [ G6 ] mg.kg(-1 ) day(-1 ) ) caffeine intake ( Day 11 ) . Groups were r and omized and stratified for age , mass , and body composition ; all procedures were double-blind . Cognitive analyses involved a visual four-choice reaction time test , a mood state question naire , and a visual vigilance task . Experimental chronic caffeine intake did not significantly alter the number of correct responses or the mean latency of response for either the four-choice reaction time or the visual vigilance tasks . The Vigor-Activity subset of the mood state question naire was significantly greater in G3 than G0 or G6 on Day 11 . All other mood constructs were unaffected by caffeine intake . In conclusion , few cognitive and psychomotor differences existed after 5 days of controlled caffeine ingestion between subjects consuming 0 , 3 , or 6 mg.kg(-1 ) day(-1 ) of caffeine , suggesting that chronic caffeine intake ( 1 ) has few perceptible effects on cognitive and psychomotor well-being and ( 2 ) may lead to a tolerance to some aspects of caffeine 's acute effects BACKGROUND Reductions in both cognitive and physical performance occur during periods of sleep loss with sustained operations . It was the purpose of this study to examine the effects of caffeine on activities chosen to simulate the physical challenges that might occur during a military scenario involving a period of sleep loss . METHODS There were 16 subjects ( 26.7 + /- 7.8 yr , 83.8 + /- 11.0 kg ) who completed a double-blind caffeine and placebo trial involving a control day and sleep period followed by 28 h of sleep deprivation . A 400-mg dose of caffeine was administered at 21:30 followed by subsequent 100-mg doses at 03:00 and 05:00 . At 22:00 , subjects began a 2-h forced march followed by a s and bag piling task . A treadmill run to exhaustion at 85 % of maximal aerobic power was performed at 07:00 of the second day of sleep deprivation . RESULTS Caffeine had no effect on the heart rate or oxygen consumption , but rating of perceived exertion ( RPE ) was reduced with caffeine during the forced march . Time to complete the s and bag piling task during set 1 was significantly reduced with caffeine ( 12.9 + /- 1.0 min ) compared with placebo ( 13.8 + /- 1.0 min ) but there was no difference during set 2 and RPE was increased . Time to exhaustion was significantly increased 25 % during the run with caffeine ( 17.0 + /- 4.4 min ) compared with placebo ( 13.5 + /- 3.3 min ) , and caffeine maintained performance at control levels ( 16.9 + /- 4.6 min ) . CONCLUSIONS It was concluded that caffeine is an effective strategy to maintain physical performance during an overnight period of sleep loss at levels comparable to the rested state PURPOSE This study examined the effects of caffeine ( CAF ) on vigilance , marksmanship , and run performance during 27 h of sustained wakefulness in Special Forces personnel . METHODS There were 31 soldiers ( 29.8 + /- 5.4 yr , 86.4 + /- 8.6 kg ) who were divided into placebo ( PLAC , n = 15 ) and CAF ( n = 16 ) groups . A 6.3-km control run was completed on the morning of Day 1 . In the evening of Day 2 , soldiers performed a control observation and reconnaissance vigilance task ( ORVT ) in the field . This 90-min task was repeated twice more between 02:00 and 06:00 on Day 3 during an overnight period of sleep deprivation . Marksmanship was assessed before and after the ORVT . PLAC or 200 mg of CAF gum was administered at 01:45 , 03:45 , and approximately 06:30 on Day 3 . A final 6.3-km run commenced within 30 min of receiving the final dose . RESULTS ORVT was maintained in CAF at control levels of 77 + /- 13 % during the overnight testing . However , values decreased significantly for PLAC from 77 + /- 15 % to 54 + /- 29 % and 51 + /- 31 % during the first and second overnight testing periods , respectively . CAF had no effect on marksmanship but improved 6.3-km run times by 1.2 + /- 1.8 min . Run times slowed for PLAC by 0.9 + /- 0.8 min from approximately 35 min during the control run ; the changes in performance were significant between groups . CONCLUSIONS It was concluded that CAF maintained vigilance and improved running performance during an overnight field operation for Special Forces personnel To investigate the effect of sucrose or caffeine ingestion on the performance of prolonged running , five male distance runners attending senior high school ( 15.6 yrs ) carried out running on a treadmill at an intensity corresponding to the individuals ' 80 % VO2 max until exhaustion . Before and 45 min after exercise , the subjects were given either a placebo ( Con ) , sucrose ( 81 + /- 18 g ) ( Su ) , caffeine ( 384 + /- 13 mg ) ( Caf ) , or sucrose ( 72 + /- 22 g ) plus caffeine ( 396 + /- 29 mg ) ( Su + Caf ) solution . The duration of the exercise was significantly longer in Su , Caf , and Su + Caf than in Con . The duration in four of five subjects was longest in Su + Caf , although it was not significantly different from that in Su or Caf . Carbohydrate ( CHO ) utilization was highest in Su while fat utilization was highest in Caf . The energy supply from both sources was almost the same between Con and Su + Caf . The plasma glucose concentration was higher in Su than in Con . The plasma free fatty acid ( FFA ) level was higher in Caf than in Con . The plasma glucose and lactic acid concentrations were highest in Su + Caf while the plasma FFA level was the same as in Con . In conclusion , ingestion of sucrose , caffeine , or sucrose plus caffeine solution was equally effective in improving endurance during running carried out at an intensity of approximately 80 % VO2 max PURPOSE To investigate the effect of caffeine ingestion on short-term endurance performance in competitive rowers . METHODS In this r and omized double-blind crossover study , eight competitive oarsmen ( peak oxygen uptake [ VO2peak ] 4.7+/-0.4 L x min(-1 ) , mean + /- SD ) performed three familiarization trials of a 2000-m rowing test on an air-braked ergometer , followed by three experimental trials at 3- to 7-d intervals , each 1 h after ingesting caffeine ( 6 or 9 mg x kg(-1 ) body mass ) or placebo . Trials were preceded by a st and ardized warm-up ( 6 min at 225+/-39 W ; 75+/-7.7 % VO2peak ) . RESULTS Urinary caffeine concentration was similar before ingestion ( approximately 1 mg x L(-1 ) ) but rose to 6.2+/-3.6 and 14.5+/-7.0 mg x L(-1 ) for the low and high caffeine doses , respectively . Plasma free fatty acid concentration before exercise was higher after caffeine ingestion ( 0.29+/-0.17 and 0.39+/-0.20 mM for 6 and 9 mg x kg(-1 ) , respectively ) than after placebo ( 0.13+/-0.05 mM ) . Respiratory exchange ratio during the warm-up was also substantially lower with caffeine ( 0.94+/-0.09 and 0.93+/-0.06 for the low and high dose ) than with placebo ( 0.98+/-0.12 ) . Subjects could not distinguish between treatments before or after the exercise test . Both doses of caffeine had a similar ergogenic effect relative to placebo : performance time decreased by a mean of 1.2 % ( 95 % likely range 0.4 - 1.9 % ) ; the corresponding increase in mean power was 2.7 % ( 0.4 - 5.0 % ) . Performance time showed some evidence of individual differences in the effect of caffeine ( SD 0.9 % ; 95 % likely range 1.5 to -0.9 % ) . CONCLUSIONS Ingestion of 6 or 9 mg x kg(-1 ) of caffeine produces a worthwhile enhancement of short-term endurance performance in a controlled laboratory setting A hot and humid environment can be detrimental to race performance . Caffeine , on the other h and , has been shown to be an ergogenic aid for improving endurance performance . To examine the influence of caffeine ingestion on race performance during high heat stress , seven endurance trained competitive road racers aged between 23 and 51 years ( five men , two women ) performed three maximal effort 21-km road races outdoors in hot and humid conditions . The caffeine dose , r and omly assigned in a double-blind fashion , consisted of either 0 , 5 , or 9 mg · kg−1 body mass . During each run , the subjects were allowed to drink waterad libitum at each 5-km point . Blood sample s were obtained immediately before and after each run and analysed for changes in concentrations of Na+ , K+ , glucose , lactate , and hematocrit . Pre and postrun data were also collected for body mass and tympanic membrane temperature . Race times were not significantly different among the races or caffeine doses , with the average times within 1.1 % of each other . In addition , none of the other variables measured varied significantly among the races or caffeine doses . In summary , caffeine intake did not affect race performance . Therefore it was concluded from our study that caffeine is not of ergogenic benefit in endurance races during high heat stress The purpose of this study was to evaluate the potential ergogenic benefit of caffeine in the performance of a 1,500-meter swim . Caffeine ( 6 mg.kg-1 ) or placebo was administered 2 - 1/2 hrs prior to the swim trial in a double-blind crossover design . Caffeine result ed in a significantly lower perceived exertion for 100-m warm-up swims . Subjects swam significantly ( p < 0.05 ) faster with caffeine ( 20:58.8 + /- 0:36.4 , mean + /- SEM ) than without ( 21:21.8 + /- 0:38 ) . Plasma potassium was significantly lower prior to the swim with caffeine , and blood glucose was higher after that swim . Caffeine provides an ergogenic benefit for a 1,500-meter swim , an event that is completed in less than 25 min . Lower plasma potassium concentration prior to exercise and higher blood glucose following the trial suggest that electrolyte balance and glucose availability may be important aspects of the ergogenic effects of caffeine The effect of caffeine on exercise time over a specified distance ( approx . 21 km ) was investigated in well-trained cross-country skiers ( 14 subjects ) both at low ( 300 m above sea level ) and high ( 2900 m above sea level ) altitudes . Each subject participated in two races at both altitudes -- one after caffeine ingestion ( 6 mg/kg body weight ) and one after placebo on a double-blind basis . In each race 50 % of the participants were medicated with caffeine , thereby after normalization ( where the mean time was set at 100 % ) , when the influence of weather and snow conditions were minimized , the difference between the race time with caffeine and placebo could be calculated for each individual and expressed as a percentage of the mean . At low altitudes , after half the distance , the race time with caffeine was decreased 0.94 % of the mean time ( corresponding to approx . 33 s ) as compared to placebo ( P less than 0.05 ) , whereas after the full distance the corresponding decrease was 1.7 % of the mean time ( corresponding to approx . 59 s ) ( 0.05 less than P less than 0.10 ) . At high altitudes , the race time was significantly faster with caffeine than with placebo ( P less than 0.001 ) , both after one and two laps , 2.19 % and 3.18 % of the mean time , respectively ( corresponding to approx . 101 s and 152 s ) . The perceived exertion was similar at low and high altitudes independent of medication . In conclusion , there are indications that caffeine induces an increased performance capacity for cross-country skiers at low altitudes . Furthermore , an even more marked improvement after caffeine as compared to placebo was found at high altitudes OBJECTIVE The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation . METHODS This was a double blind , parallel , r and omized , seven treatment study . The treatment groups were : 50 , 100 , and 200 mg gum , 50 , 100 , and 200 mg capsule , and a placebo . Subjects consisted of 84 ( n=12 per group ) ; healthy , non-smoking , males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were r and omly assigned to the treatment groups . Blood sample s were collected pre-dose and at 5 , 15 , 25 , 35 , 45 , 55 , 65 , 90 min and 2 , 3 , 4 , 6 , 8 , 12 , 16 and 29 h post administration . Plasma caffeine levels were analyzed by a vali date d UV-HPLC method . RESULTS Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0 - 120.0 min for the capsule groups . The Tmax , for the pooled data was significantly lower ( P<0.05 ) for the gum groups as compared with the capsule groups . Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum ( P<0.05 ) . The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1 . Relative bioavailability of the gum formulation after the 50 , 100 and 200 mg dose was 64 , 74 and 77 % , respectively . When normalized to the total drug released from the gum ( 85 % ) , the relative bioavailability of the 50 , 100 and 200 mg dose were 75 , 87 , and 90 % , respectively . No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose . Within each dose level , there were no significant formulation related differences in Cmax . No significant differences were observed in the elimination of caffeine after the gum or capsule . CONCLUSIONS The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa . In addition , for the 100 and 200 mg groups , the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation . These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation , which is advantageous in situations where the rapid reversal of alertness and performance deficits result ing from sleep loss is desirable Gastrointestinal ( GI ) complaints are frequently experienced during running . Sports drinks to prevent dehydration and hypoglycemia during exercise are generally used . The aim was to investigate the effect of 3 different drinks on GI complaints and performance during competitive running in a controlled field study . Ninety-eight well-trained subjects ( 90 M , 8 F , age 41 + /- 8 y ) performed a competitive 18-km run three times within 8 days . The study was a controlled , st and ardized field experiment following a r and omized , crossover design . Three different drinks were compared : water , a sports drink ( CES ) , and a sports drink with added 150 mg/l caffeine ( CAF ) . The incidence of GI complaints and the effect of the drinks on performance was studied . Each subject consumed 4 times 150 ml as follows : at the start , after 4.5 km , 9 km , and 13.5 km . Fluid intake was controlled . Incidence and intensity of GI complaints during the run were determined using a 10 points scale question naire . There were no significant differences in performance between the 3 drinks . Run time ( 18 km , mean + /- SD ) : WAT 1 : 18 : 03 + /- 08 : 30 , CES 1 : 18 : 23 + /- 08 : 47 , CAF 1 : 18 : 03 + /- 08 : 42 . The use of carbohydrate-containing sports drinks led to higher incidences of all types of GI complaints compared to water . Significant differences ( p < 0.05 ) were reached for flatulence ; incidence : WAT 17.9 % , CES 28.6 % , CAF 30.6 % , and reflux ; incidence : WAT 55.7 % , CES 78.6 % , CAF 72.5 % . There were no significant differences in intensity of the GI complaints . Addition of caffeine to CES had no effect on GI complaints , compared to CES alone . We conclude that sports drinks used during an 18-km run in cool environmental conditions do not support the performance better than mineral water . The use of sports drinks during an 18-km run leads to a higher incidence of both upper and lower GI complaints compared to water . Addition of caffeine to the sports drink has no effect on either running performance or GI complaints Eight competitive oarswomen ( age , 22 + /- 3 years ; mass , 64.4 + /- 3.8 kg ) performed three simulated 2,000-m time trials on a rowing ergometer . The trials , which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence , were conducted 1 hour after ingesting caffeine ( 6 or 9 mg á kg-1 body mass ) or placebo . Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo ( 0.67 + /- 0.34 vs. 0.72 + /- 0.36 vs. 0.30 + /- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo , respectively ; p < .05 ) . Performance time improved 0.7 % ( 95 % confidence interval [ CI ] 0 to 1.5 % ) with 6 mg á kg-1 caffeine and 1 . 3 % ( 95 % CI 0.5 to 2.0 % ) with 9 mg á kg-1 caffeine . The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose ( 1.53 + /- 0.52 vs.1.55 + /- 0.62 and 1 . 56 + /- 0.43 min ; p = .02 ) . We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting , primarily by improving the first 500 m of a 2,000-m row & NA ; This double‐blind , within‐subjects experiment examined the effects of ingesting two doses of caffeine on perceptions of leg muscle pain and blood pressure during moderate intensity cycling exercise . Low caffeine consuming college‐aged males ( N=12 ) ingested one of two doses of caffeine ( 5 or 10 mg·kg−1 body weight ) or placebo and 1 h later completed 30 min of moderate intensity cycling exercise ( 60 % Symbol ) . The order of drug administration was counter‐balanced . Resting blood pressure and heart rate were recorded immediately before and 1 h after drug administration . Perceptions of leg muscle pain as well as work rate , blood pressure , heart rate , and oxygen uptake Symbol were recorded during exercise . Caffeine increased resting systolic pressure in a dose‐dependent fashion but these blood pressure effects were not maintained during exercise . Caffeine had a significant linear effect on leg muscle pain ratings [ F(2,22)=14.06 ; P<0.0001 ; & eegr;2=0.56 ] . The mean ( ±SD ) pain intensity scores during exercise after ingesting 10 mg·kg−1 body weight caffeine , 5 mg·kg−1 body weight caffeine , and placebo were 2.1±1.4 , 2.6±1.5 , and 3.5±1.7 , respectively . The results support the conclusion that caffeine ingestion has a dose – response effect on reducing leg muscle pain during exercise and that these effects do not depend on caffeine‐induced increases in systolic blood pressure during exercise . Symbol . No caption available . Symbol . No caption available Abstract The aim of this study was to assess the effect of caffeine ingestion on 8 km run performance using an ecologically valid test protocol . A r and omized double-blind crossover study was conducted involving eight male distance runners . The participants ran an 8 km race 1 h after ingesting a placebo capsule , a caffeine capsule ( 3 mg · kg−1 body mass ) or no supplement . Heart rate was recorded at 5 s intervals throughout the race . Blood lactate concentration and ratings of perceived exertion were recorded after exercise . A repeated- measures analysis of variance ( ANOVA ) identified a significant treatment effect for 8 km performance time ( P < 0.05 ) ; caffeine result ed in a mean improvement of 23.8 s ( 95 % confidence interval [ CI ] = 13.1 to 34.5 s ) in 8 km performance time ( 1.2 % improvement , 95 % CI = 0.7 to 1.8 % ) . In addition , a two-way ( time × condition ) repeated- measures ANOVA identified a significantly higher blood lactate concentration 3 min after exercise during the caffeine trial ( P < 0.05 ) . We conclude that ingestion of 3 mg · kg−1 body mass of caffeine can improve absolute 8 km run performance in an ecologically valid race setting |
13,031 | 32,120,794 | This SR showed that the 10 mg lutein per day for twelve months can lead to improvement of cognitive functions .
Due to the small number of studies , it is difficult to conclude whether astaxanthin would have a positive effect on cognitive functions | BACKGROUND Fruits and vegetables are generally rich in antioxidants such as carotenoids .
Consumption of carotenoids is expected to have benefits on cognitive functions in humans .
However , previous r and omized controlled trials ( RCT ) using carotenoids have reported inconsistent results .
Therefore , this systematic review ( SR ) aim ed to summarize the effect of carotenoid intake on cognitive functions in humans . | Abstract Purpose Epidemiological evidence suggests that chronic consumption of fruit-based flavonoids is associated with cognitive benefits ; however , the acute effects of flavonoid-rich ( FR ) drinks on cognitive function in the immediate postpr and ial period require examination . The objective was to investigate whether consumption of FR orange juice is associated with acute cognitive benefits over 6 h in healthy middle-aged adults . Methods Males aged 30–65 consumed a 240-ml FR orange juice ( 272 mg ) and a calorie-matched placebo in a r and omized , double-blind , counterbalanced order on 2 days separated by a 2-week washout . Cognitive function and subjective mood were assessed at baseline ( prior to drink consumption ) and 2 and 6 h post consumption . The cognitive battery included eight individual cognitive tests . A st and ardized breakfast was consumed prior to the baseline measures , and a st and ardized lunch was consumed 3 h post-drink consumption . Results Change from baseline analysis revealed that performance on tests of executive function and psychomotor speed was significantly better following the FR drink compared to the placebo . The effects of objective cognitive function were supported by significant benefits for subjective alertness following the FR drink relative to the placebo . Conclusions These data demonstrate that consumption of FR orange juice can acutely enhance objective and subjective cognition over the course of 6 h in healthy middle-aged adults Background : High levels of xanthophyll carotenoids lutein ( L ) and zeaxanthin ( Z ) in the central nervous system have been previously correlated with improved cognitive function in community-dwelling older adults . In this study , we tested the effects of supplementing L and Z on older men and women with a range of baseline cognitive abilities . Objective : The purpose of this study was to determine whether or not supplementation with L+Z could improve cognitive function in community-dwelling , older adults . Design : Double-masked , r and omized , placebo-controlled trial . A total of 62 older adults were r and omized into groups receiving either 12 mg L+Z or a visually identical placebo . Data from 51 participants ( M = 73.7 years ) were available for analysis . Retinal L+Z levels ( macular pigment optical density , MPOD ) were measured psychophysically using heterochromatic flicker photometry as a biomarker of cortical L+Z levels . Cognitive function was measured using the CNS Vital Signs computerized test platform . Results : Participants receiving the active L+Z supplement had statistically significant increases in MPOD ( p < 0.03 ) and improvements in complex attention ( p < 0.02 ) and cognitive flexibility domains ( p < 0.04 ) , relative to participants taking the placebo . A trend was also seen for the executive function domain ( p = 0.073 ) . In male participants only , supplementation yielded improved composite memory ( p = 0.04 ) . Conclusions : Supplementation with L+Z improved cognitive function in community-dwelling , older men and women BACKGROUND Prior investigations have reported a link between poor status of antioxidants , folate , and cobalamin result ing in elevated total plasma homocysteine ( tHcy ) and methylmalonic acid ( MMA ) concentrations with an increased risk for reduced cognitive performance . The aim of the study was to evaluate the effect of a 6-month multivitamin supplementation on the cognitive performance of female seniors and to assess cognitive functioning in relation to vitamin status , tHcy , and MMA values at baseline . METHODS The study was performed as a r and omized placebo-controlled double-blind trial . 220 healthy , free-living women ( aged 60 - 91 years ) were included . Blood drawings and cognitive tests were performed at the Institute of Food Science of the University of Hanover , Germany . Vitamin and cognitive status have been evaluated prior to and 6 months after supplementation . Plasma ascorbic acid , serum concentrations of alpha-tocopherol , beta-carotene , and coenzyme Q10 , serum and erythrocyte folate as well as serum cobalamin , serum MMA , and plasma tHcy concentrations were measured . Activity coefficient of erythrocyte alpha aspartic aminotransferase was used as functional index for vitamin B(6 ) status . The cognitive performance was assessed by the Symbol Search test , a subtest of the Wechsler Adult Intelligence Scale ( WAIS-III ) and the pattern-recognition test . Intelligence as assessed by the ' Kurztest für Allgemeine Intelligenz ' ( KAI ) was a further variable . RESULTS No significant differences in pattern-recognition and intelligence score were observed between vitamin and placebo group prior to and after multivitamin supplementation . In the Symbol Search test , the vitamin group exhibited better test results than the placebo group at both measure points . One-way ANOVA showed a marginally significant linear trend between the baseline tHcy concentration and the pattern-recognition score ( P = 0.051 ) in the total sample . Multiple backward regression revealed only a significant influence of the school graduation on baseline cognitive function test results . A general linear model showed that the changes in cognitive function scores could not be explained by the type of treatment or blood parameters . CONCLUSIONS Our data indicate that 6 months supplementation of physiological dosages of antioxidants and B vitamins have no effect on cognitive performance in presumedly healthy and well-nourished female seniors . An intervention period of only 6 months may be too short for improving cognitive performance in well-educated elderly women without dementia Background — Cardiovascular factors are associated with cognitive decline . Antioxidants may be beneficial . Methods and Results — The Women ’s Antioxidant Cardiovascular Study was a trial of vitamin E ( 402 mg every other day ) , beta carotene ( 50 mg every other day ) , and vitamin C ( 500 mg daily ) for the secondary prevention of cardiovascular disease . From 1995 to 1996 , women ≥40 years of age with cardiovascular disease or ≥3 coronary risk factors were r and omized . From 1998 to 1999 , a cognitive function sub study was initiated among 2824 participants ≥65 years of age . With 5 cognitive tests , cognition was assessed by telephone 4 times over 5.4 years . The primary outcome was a global composite score averaging all scores ; repeated- measures analyses were used to examine cognitive change over time . Vitamin E supplementation and beta carotene supplementation were not associated with slower rates of cognitive change ( mean difference in change for vitamin E versus placebo , −0.01 ; 95 % confidence interval , −0.05 to 0.04 ; P=0.78 ; for beta carotene , 0.03 ; 95 % confidence interval , −0.02 to 0.07 ; P=0.28 ) . Although vitamin C supplementation was associated with better performance at the last assessment ( mean difference , 0.13 ; 95 % confidence interval , 0.06 to 0.20 ; P=0.0005 ) , it was not associated with cognitive change over time ( mean difference in change , 0.02 ; 95 % confidence interval , −0.03 to 0.07 ; P=0.39 ) . Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial ( P for interaction=0.009 ) . Conclusions — Antioxidant supplementation did not slow cognitive change among women with preexisting cardiovascular disease or cardiovascular disease risk factors . A possible late effect of vitamin C or beta carotene among those with low dietary intake on cognition warrants further study BACKGROUND There is a biologically plausible rationale whereby the dietary carotenoids lutein ( L ) , zeaxanthin ( Z ) , and meso-zeaxanthin ( MZ ) , which are collectively referred to as macular pigment ( MP ) in the central retina ( macula ) , support the maintenance of cognition via their antioxidant and anti-inflammatory properties . OBJECTIVE To investigate the impact of supplemental L , Z , and MZ on memory , executive function , and verbal fluency among healthy individuals with low MP levels . METHODS In this double-blind , placebo-controlled , r and omized clinical trial , subjects ( n = 91 ; mean±SD age = 45.42±12.40 ; % male = 51.6 ) consumed a daily formulation of 10 mg L , 10 mg MZ , and 2 mg Z ( n = 45 ) or placebo ( n = 46 ) for 12 months . Cognitive domains assessed included verbal and visual learning , immediate and delayed memory , executive function , and verbal fluency . MP and serum carotenoid concentrations of L , Z , and MZ were also measured . RESULTS Following 12-month supplementation , individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group ( paired associated learning [ PAL ] memory score [ rANOVA , p = 0.009 ] ; PAL errors [ rANOVA , p = 0.017 ] ) . Furthermore , the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume ( p = 0.005 ) and observed increases in serum concentrations of L ( p = 0.009 ) . CONCLUSION This r and omized , double-blind , placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L , Z , and MZ in healthy subjects with low MP at baseline . The implication s of these findings for intellectual performance throughout life , and for risk of cognitive decline in later life , warrant further study In this study we tried to confirm the effect of an astaxanthin-rich Haematococcus pluvialis extract on cognitive function in 96 subjects by a r and omised double-blind placebo-controlled study . Healthy middle-aged and elderly subjects who complained of age-related forgetfulness were recruited . Ninety-six subjects were selected from the initial screen , and ingested a capsule containing astaxanthin-rich Haematococcus pluvialis extract , or a placebo capsule for 12 weeks . Somatometry , haematology , urine screens , and CogHealth and Groton Maze Learning Test were performed before and after every 4 weeks of administration . Changes in cognitive performance and the safety of astaxanthin-rich Haematococcus pluvialis extract administration were evaluated . CogHealth battery scores improved in the high-dosage group ( 12 mg astaxanthin/day ) after 12 weeks . Groton Maze Learning Test scores improved earlier in the low-dosage ( 6 mg astaxanthin/day ) and high-dosage groups than in the placebo group . The sample size , however , was small to show a significant difference in cognitive function between the astaxanthin-rich Haematococcus pluvialis extract and placebo groups . No adverse effect on the subjects was observed throughout this study . In conclusion , the results suggested that astaxanthin-rich Haematococcus pluvialis extract improves cognitive function in the healthy aged individuals Lutein and zeaxanthin are major carotenoids in the eye but are also found in post-receptoral visual pathways . It has been hypothesized that these pigments influence the processing of visual signals within and post-retina , and that increasing lutein and zeaxanthin levels within the visual system will lead to increased visual processing speeds . To test this , we measured macular pigment density ( as a biomarker of lutein and zeaxanthin levels in brain ) , critical flicker fusion ( CFF ) thresholds , and visual motor reaction time in young healthy subjects ( n = 92 ) . Changes in these outcome variables were also assessed after four months of supplementation with either placebo ( n = 10 ) , zeaxanthin only ( 20 mg/day ; n = 29 ) or a mixed formulation containing 26 mg/day zeaxanthin , 8 mg/day lutein , and 190 mg/day mixed omega-3 fatty acids ( n = 25 ) . Significant correlations were found between retinal lutein and zeaxanthin ( macular pigment ) and CFF thresholds ( p<0.01 ) and visual motor performance ( overall p<0.01 ) . Supplementation with zeaxanthin and the mixed formulation ( considered together ) produced significant ( p<0.01 ) increases in CFF thresholds ( ∼12 % ) and visual motor reaction time ( ∼10 % ) compared to placebo . In general , increasing macular pigment density through supplementation ( average increase of about 0.09 log units ) result ed in significant improvements in visual processing speed , even when testing young , healthy individuals who tend to be at peak efficiency Background : Past studies have suggested that higher lutein ( L ) and zeaxanthin ( Z ) levels in serum and in the central nervous system ( as quantified by measuring macular pigment optical density , MPOD ) are related to improved cognitive function in older adults . Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults , and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population . Objective : The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young ( age 18–30 ) , healthy adults . Design : A r and omized , double-masked , placebo-controlled trial design was used . Fifty-one young , healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function . Subjects were r and omized into active supplement ( n = 37 ) and placebo groups ( n = 14 ) . MPOD was measured psychophysically using customized heterochromatic flicker photometry . Cognitive function was measured using the CNS Vital Signs testing platform . MPOD and cognitive function were measured every four months for a full year of supplementation . Results : Supplementation increased MPOD significantly over the course of the year , vs. placebo ( p < 0.001 ) . Daily supplementation with L + Z and increases in MPOD result ed in significant improvements in spatial memory ( p < 0.04 ) , reasoning ability ( p < 0.05 ) and complex attention ( p < 0.04 ) , above and beyond improvements due to practice effects . Conclusions : Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young , healthy adults . Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other population Speed of processing is a particularly important characteristic of the visual system . Often a behavioral reaction to a visual stimulus must be faster than the conscious perception of that stimulus , as is the case with many sports ( e.g. , baseball ) . Visual psychophysics provides a relatively simple and precise means of measuring visual processing speed called the temporal contrast sensitivity function ( tCSF ) . Past study has shown that macular pigment ( a collection of xanthophylls , lutein ( L ) , meso-zeaxanthin ( MZ ) and zeaxanthin ( Z ) , found in the retina ) optical density ( MPOD ) is positively correlated with the tCSF . In this study , we found similar correlations when testing 102 young healthy subjects . As a follow-up , we r and omized 69 subjects to receive a placebo ( n=15 ) or one of two L and Z supplements ( n=54 ) . MPOD and tCSF were measured psychophysically at baseline and 4months . Neither MPOD nor tCSF changed for the placebo condition , but both improved significantly as a result of supplementation . These results show that an intervention with L and Z can increase processing speed even in young healthy subjects BACKGROUND The Rotterdam Study previously found that higher dietary intakes of vitamins E and C related to lower risk of dementia and Alzheimer disease ( AD ) over 6 years of follow-up . OBJECTIVE To study consumption of major dietary antioxidants relative to long-term risk of dementia . DESIGN Population -based prospect i ve cohort study . SETTING The Rotterdam Study in the Netherl and s. PARTICIPANTS A total of 5395 participants , 55 years and older , who were free of dementia and provided dietary information at study baseline . MAIN OUTCOME MEASURES Incidence of dementia and AD , based on internationally accepted criteria , relative to dietary intake of vitamin E , vitamin C , beta carotene , and flavonoids . RESULTS During a mean follow-up period of 9.6 years , dementia developed in 465 participants , of whom 365 were diagnosed as having AD . In multivariate models adjusted for age , education , apolipoprotein E epsilon4 genotype , total energy intake , alcohol intake , smoking habits , body mass index , and supplement use , higher intake of vitamin E at study baseline was associated with lower long-term risk of dementia ( P = .02 for trend ) . Compared with participants in the lowest tertile of vitamin E intake , those in the highest tertile were 25 % less likely to develop dementia ( hazard ratio , 0.75 ; 95 % confidence interval , 0.59 - 0.95 with adjustment for potential confounders ) . Dietary intake levels of vitamin C , beta carotene , and flavonoids were not associated with dementia risk after multivariate adjustment ( P > .99 for trend for vitamin C and beta carotene and P = .60 for trend for flavonoids ) . Results were similar when risk for AD was specifically assessed . CONCLUSION Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD Lutein is selectively incorporated into the macula and brain . Lutein levels in the macula ( macular pigment ; MP ) and the brain are related to better cognition . MP density ( MPD ) is a biomarker of brain lutein . Avocados are a bioavailable source of lutein . This study tests the effects of the intake of avocado on cognition . This was a six-month , r and omized , controlled trial . Healthy subjects consumed one avocado ( n = 20 , 0.5 mg/day lutein , AV ) vs. one potato or one cup of chickpeas ( n = 20 , 0 mg/day lutein , C ) . Serum lutein , MPD , and cognition were assessed at zero , three , and six months . Primary analyses were conducted according to intent-to-treat principles , with repeated- measures analysis . At six months , AV increased serum lutein levels by 25 % from baseline ( p = 0.001 ) . C increased by 15 % ( p = 0.030 ) . At six months , there was an increase in MPD from baseline in AV ( p = 0.001 ) and no increase in C. For both groups , there was an improvement in memory and spatial working memory ( p = 0.001 ; p = 0.032 , respectively ) . For AV only there was improved sustained attention ( p = 0.033 ) , and the MPD increase was related to improved working memory and efficiency in approaching a problem ( p = 0.036 ) . Dietary recommendations including avocados may be an effective strategy for cognitive health Macular pigment ( MP ) is comprised of the carotenoids lutein ( L ) , zeaxanthin ( Z ) , and meso-zeaxanthin ( MZ ) , which selectively accumulate at the macula ( central retina ) of the eye and are neuroprotective . These carotenoids are also present in the brain , and evidence suggests a close correlation between retinal and brain concentrations . We investigated the relationship between MP and cognitive function in 4453 adults aged ≥ 50 years as part of The Irish Longitudinal Study on Aging . Macular pigment optical density ( MPOD ) was determined using customized heterochromatic flicker photometry-a quick and noninvasive way of measuring the concentration of the pigment . Lower MPOD was associated with poorer performance on the mini-mental state examination ( p = 0.026 ) and on the Montreal cognitive assessment ( p = 0.016 ) . Individuals with lower MPOD also had poorer prospect i ve memory ( p = 0.011 ) , took longer time to complete a trail-making task ( p = 0.003 ) , and had slower and more variable reaction times on a choice reaction time task ( p = 0.000 and 0.001 ) . These associations were only slightly attenuated following adjustment for physical and mental health . There was no significant association between MPOD and verbal fluency , word recall , visual reasoning , or picture memory . Overall , the findings support the theory that xanthophyll carotenoids impact on cognitive function , underscoring the need for exploration of novel , noninvasive biomarkers for cognitive vulnerability and preventive strategies BACKGROUND Oxidative stress contributes to brain aging . Antioxidant treatment , especially over the long term , might confer cognitive benefits . METHODS We added cognitive testing to the Physicians ' Health Study II ( PHSII ) , a r and omized trial of beta carotene and other vitamin supplements for chronic disease prevention . The PHSII is a continuation of the Physicians ' Health Study ( PHS ) , which had r and omized male participants to low-dose aspirin and beta carotene . Participants include those continuing their original beta carotene assignment from the PHS , begun in 1982 , and newer recruits r and omized as of 1998 . The beta carotene arm ( 50 mg , alternate days ) was terminated ; follow-up is ongoing for the remaining arms . Near the close of the beta carotene arm , we interviewed 5956 participants older than 65 years to assess general cognition , verbal memory , and category fluency . The primary end point was a global score averaging all tests ( using z scores ) ; the secondary end point was a verbal memory score combining results of 4 tests . We compared mean cognition among those assigned to beta carotene vs placebo . We separately examined new recruits and continuing participants . RESULTS Among 1904 newly recruited subjects ( mean treatment duration , 1 year ) , cognition was similar across treatment assignments . Among 4052 continuing participants from the PHS ( mean treatment duration , 18 years ) , the mean global score was significantly higher in the beta carotene group than in the placebo group ( mean difference in z scores , 0.047 st and ard units ; P = .03 ) . On verbal memory , men receiving long-term beta carotene supplementation also performed significantly better than the placebo group ( mean difference in z scores , 0.063 ; P = .007 ) . CONCLUSION We did not find an impact of short-term beta carotene supplementation on cognitive performance , but long-term supplementation may provide cognitive benefits 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 BACKGROUND Antioxidant properties of some vitamins and trace elements may help to prevent cognitive decline . OBJECTIVE The aim of the current study was to estimate the long-term effects of antioxidant nutrient supplementation on the cognitive performance of participants in the Supplementation in Vitamins and Mineral Antioxidants ( SU.VI.MAX ) study 6 y after the end of the trial . DESIGN This study included 4447 French participants aged 45 - 60 y who were enrolled in the SU.VI.MAX study ( 1994 - 2002 ) , which was a double-blind , placebo-controlled , r and omized trial . From 1994 to 2002 , participants received daily vitamin C ( 120 mg ) , β-carotene ( 6 mg ) , vitamin E ( 30 mg ) , selenium ( 100 μg ) , and zinc ( 20 mg ) in combination or as a placebo . In 2007 - 2009 , the cognitive performance of participants was assessed with 4 neuropsychological tests ( 6 tasks ) . Principal components analysis ( PCA ) was performed to identify cognitive-function summary scores . Associations between antioxidant supplementation and cognitive functions , in the full sample and by subgroups , were estimated through ANOVA and expressed as mean differences and 95 % CIs . Subgroup analyses were performed according to baseline characteristics . RESULTS Subjects receiving active antioxidant supplementation had better episodic memory scores ( mean difference : 0.61 ; 95 % CI : 0.02 , 1.20 ) . PCA indicated 2 factors that were interpreted as showing verbal memory and executive functioning . Verbal memory was improved by antioxidant supplementation only in subjects who were nonsmokers or who had low serum vitamin C concentrations at baseline . CONCLUSION This study supports the role of an adequate antioxidant nutrient status in the preservation of verbal memory under certain conditions . This trial was registered at clinical trials.gov as NCT00272428 We used psychophysiological technology to examine the effect of an oral supplement , a combination of lutein , zeaxanthin and blackcurrant extract ( LUT ) , on visual fatigue , within the context of a r and omized , double-blind , placebo-controlled cross-over trial . The LUT supplement and placebo sample s were r and omly assigned to thirteen participants , who took the sample s for two LUT ( and vice versa ) for another 2 week . Each participant completed visual proof reading tasks for 2h during each of four testing sessions . Saccade tests were administered before and after the proof reading task , during which the participants moved their eyes back and forth between two targets positioned in the center of two checkerboards . We recorded EEG , EOG , heart rate , and facial muscle potential/performance during the saccade tests . Blood pressure was measured and subjective fatigue and stress scores were collected before and after the proof reading task . We averaged EEG starting at saccade offset in order to analyze eye fixation related potentials ( EFRP ) . Our results suggested that the proof reading task induced visual fatigue . An analysis of EFRP and other psychophysiological data revealed significant differences between the LUT and placebo conditions . These results suggest that supplementation with LUT could help to reduce symptoms of visual fatigue The present study examined the effects of anti-oxidant vitamin supplementation on mood and cognitive functioning in 205 volunteers ( 110 females , 95 males ; age range : 60 - 80 years ) . In this r and omised , double-blind , placebo-controlled study , the volunteers received either anti-oxidant supplementation ( daily dosage 12mg/d β-carotene , 400 mg/d α-tocopherol and 500mg/d ascorbic acid ) or placebo . The volunteers were followed up for 12 months . Vitamin levels were assessed from plasma sample s. The primary outcome measures were subjective mood , self-reported cognitive failures , and measures of intelligence . These were measured at 4 , 8 and 12 months . There were very few significant differences between the placebo and vitamin groups . Analysis of the effects of changes in vitamin levels on mood and cognition revealed significant effects of changes in vitamin C but not the other anti-oxidants . Increases in vitamin C were associated at 12 months with more positive mood , greater improvements in global assessment s of intellectual functioning and a reduction in everyday errors of memory , attention and action . These effects were greatest for those volunteers who had a more negative mood and lower levels of cognitive function at baseline . Overall , results support earlier findings based on examination of dietary intake BACKGROUND Current hypotheses suggest that intake of fruit and vegetables ( FVs ) protects against age-related cognitive impairment . OBJECTIVE We examined the 13-y association between FV intake and cognitive performance in a sample of French adults . DESIGN A total of 2533 subjects aged 45 - 60 y at baseline , who were part of the Supplementation with Antioxidant Vitamins and Minerals 2 ( SU.VI.MAX 2 ) cohort , were selected . FV intake was estimated at baseline in participants who had completed at least six 24-h dietary records . Cognitive performance was assessed 13 y after baseline and included an evaluation of verbal memory ( RI-48 cued recall , semantic , and phonemic fluency tests ) and executive function ( trail-making and forward and backward digit span tests ) . Principal components analysis was performed to account for correlations in test scores . The relation between cognitive performance and quartiles of FV intake was assessed by multivariate linear regression analyses . RESULTS Intakes of FVs ( P-trend = 0.02 ) , fruit alone ( P-trend = 0.04 ) , vitamin C-rich FVs ( P-trend = 0.03 ) , vitamin C ( P-trend = 0.005 ) , and vitamin E ( P-trend = 0.04 ) were positively associated with verbal memory scores . In contrast , intakes of FVs ( P-trend = 0.006 ) , vegetables alone ( P-trend = 0.03 ) , and β-carotene-rich FVs ( P-trend = 0.02 ) were negatively associated with executive functioning scores . CONCLUSIONS FVs might have a differential effect on cognition according to groups of FVs and type of cognitive function . Further research using sensitive and reliable measures of various types of cognitive function is needed to clarify the effect of individual FV groups and nutrients . This trial is registered at clinical trials.gov as NCT00272428 Participants in the Age-Related Eye Disease Study were r and omly assigned to receive daily antioxidants ( vitamin C , 500 mg ; vitamin E , 400 IU ; beta carotene , 15 mg ) , zinc and copper ( zinc , 80 mg ; cupric oxide , 2 mg ) , antioxidants plus zinc and copper , or placebo . A cognitive battery was administered to 2,166 elderly persons after a median of 6.9 years of treatment . Treatment groups did not differ on any of the six cognitive tests ( p > 0.05 for all ) . These results do not support a beneficial or harmful effect of antioxidants or zinc and copper on cognition in older adults OBJECTIVES The present study constitutes the first r and omized controlled trial to investigate the relation of lutein ( L ) and zeaxanthin ( Z ) to brain function using functional magnetic resonance imaging ( fMRI ) . It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency ( i.e. , reduce activation ) and cognitive performance on a verbal learning task relative to placebo . METHODS A total of 44 community-dwelling older adults ( mean age=72 years ) were r and omly assigned to receive either placebo or L+Z supplementation ( 12 mg/daily ) for 1 year . Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs . Imaging contrasts of blood-oxygen-level-dependent ( BOLD ) signal were created by subtracting active control trials from learning and recall trials . A flexible factorial model was employed to investigate the expected group ( placebo vs. supplement ) by time ( baseline vs. post-intervention ) interaction in pre-specified regions-of-interest . RESULTS L and Z appeared to buffer cognitive decline on the verbal learning task ( Cohen 's d=.84 ) . Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex ( p < .05 , family-wise-error corrected ) . However , these effects were in the direction of increased rather than decreased BOLD signal . Although the omnibus interaction was not significant during recall , within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only . CONCLUSIONS L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion , even if consumed for a discrete period of time in late life . ( JINS , 2018 , 24 , 77 - 90 ) PURPOSE Oxidative and inflammatory processes play a major role in stress-induced neural atrophy . There is a wide body of literature linking oxidative and inflammatory stress with reductions in neurotrophic factors , stress resilience , and cognitive function . Based on their antioxidant and anti-inflammatory capacity , we investigated the effect of the dietary carotenoids lutein and zeaxanthin , along with the zeaxanthin isomer meso-zeaxanthin ( collectively the " macular xanthophylls " [ MXans ] ) on systemic brain-derived neurotrophic factor ( BDNF ) and anti-oxidant capacity ( AOC ) , and the pro-inflammatory cytokines TNF-α , IL-6 , and IL-1β . To investigate higher-order effects , we assessed cognitive performance . METHODS 59 young ( 18 - 25 yrs . ) , healthy subjects participated in a 6-month , double-blind , placebo-controlled trial to evaluate the effects of MXan supplementation on the aforementioned serum parameters and cognitive performance . Subjects were r and omly assigned to one of three groups : placebo , 13 mg , or 27 mg/day total MXans ; all measures were taken at baseline and 6 months . Blood was obtained via fasting blood draw , and MXan concentration in the retina ( termed macular pigment optical density [ MPOD ] ) was measured via customized heterochromatic flicker photometry . Serum BDNF and cytokines were assessed via ELISA . Serum antioxidant capacity ( AOC ) and serum MXan concentrations were quantified via colorimetric microplate assay , and high-performance liquid chromatography , respectively . Cognitive performance was measured via a computer-based assessment tool ( CNS Vital Signs ) . RESULTS BDNF , MPOD , serum MXans , and AOC all increased significantly versus placebo in both treatment groups over the 6-month study period ( p < .05 for all ) . IL-1β decreased significantly versus placebo in both treatment groups ( p = .0036 and p = .006 , respectively ) . For cognitive measures , scores for composite memory , verbal memory , sustained attention , psychomotor speed , and processing speed all improved significantly in treatment groups ( p < .05 for all ) and remained unchanged in the placebo group . Several measures were found to be significantly associated in terms of relational changes over the course of the study . Notably , change in BDNF was related to change in IL-1β ( r = -0.47 ; p < .001 ) and MPOD ( r = 0.44 ; p = .0086 ) . Additionally , changes in serum MXans were strongly related to AOC ( r = 0.79 & 0.61 for lutein and zeaxanthin isomers respectively ; p < .001 ) . For cognitive scores , change in BDNF was correlated to change in composite memory ( r = 0.32 ; p = .014 ) and verbal memory ( r = 0.35 ; p = .007 ) , whereas change in MPOD was correlated with change in both psychomotor speed ( r = 0.38 ; p = .003 ) , and processing speed ( r = 0.35 ; p = .007 ) . Change in serum lutein was found to be significantly correlated to change in verbal memory ( r = 0.41 ; p < .001 ) , composite memory ( r = 0.31 ; p = .009 ) , and sustained attention ( r = 0.28 ; p = .036 ) . Change in serum zeaxanthin isomers was significantly correlated with change in verbal memory ( r = 0.33 ; p = .017 ) . Lastly , change in AOC was significantly associated with verbal memory ( r = 0.34 ; p = .021 ) , composite memory ( r = 0.29 ; p = .03 ) , and sustained attention ( r = 0.35 ; p = .016 ) . No significant relational changes in any cognitive parameter were found for the placebo group . CONCLUSIONS Six months of daily supplementation with at least 13 mg of MXans significantly reduces serum IL-1β , significantly increases serum MXans , BDNF , MPOD , and AOC , and improves several parameters of cognitive performance . Findings suggest that increased systemic antioxidant/anti-inflammatory capacity ( and not necessarily deposition of the carotenoids in neural tissues ) , may explain many of the effects determined in this study . The significant relationship between change in BDNF and IL-1β over the course of the study suggests that regular consumption of MXans interrupts the inflammatory cascade that can lead to reduction of BDNF . Changes in MPOD and BDNF appear to account for enhancement in cognitive parameters that involve speed of processing and complex processing , respectively . IS RCT N Clinical Trial Registration : IS RCT N16156382 Abstract Introduction : Low dietary intake of docosahexaenoic acid ( DHA ) and /or foods rich in lutein may be associated with increased risk of cognitive decline in the elderly . Subjects and methods : The cognitive benefit of DHA and lutein in unimpaired elder women was explored in the context of a 4-month , double-blind , intervention trial of DHA and lutein supplementation for eye health . Forty-nine women ( aged 60–80 years ) were r and omized to receive DHA ( 800 mg/day ; n = 14 ) , lutein ( 12 mg/day ; n = 11 ) , a combination of DHA and lutein ( n = 14 ) or placebo ( n = 10 ) . Subjects underwent cognitive tests measuring verbal fluency , memory , processing speed and accuracy , and self-reports of mood at r and omization and upon completion of the trial . Results : Following supplementation , verbal fluency scores improved significantly in the DHA , lutein , and combined treatment groups ( P < 0.03 ) . Memory scores and rate of learning improved significantly in the combined treatment group ( P < 0.03 ) , who also displayed a trend toward more efficient learning ( P = 0.07 ) . Measures of mental processing speed , accuracy and mood were not affected by supplementation . Conclusions : These exploratory findings suggest that DHA and lutein supplementation may have cognitive benefit for older adults |
13,032 | 32,292,042 | Drinking BRJ may easily increase nitrate intake above the acceptable daily intake , which is known to stimulate the endogenous formation of N-nitroso compounds ( NOC 's ) , a class of compounds that is known to be carcinogenic and that may also induce several other adverse effects . | Beetroot juice ( BRJ ) has become increasingly popular amongst athletes aim ing to improve sport performances .
BRJ contains high concentrations of nitrate , which can be converted into nitric oxide ( NO ) after consumption .
NO has various functions in the human body , including a vasodilatory effect , which reduces blood pressure and increases oxygen- and nutrient delivery to various organs .
These effects indicate that BRJ may have relevant applications in prevention and treatment of cardiovascular disease .
Furthermore , the consumption of BRJ also has an impact on oxygen delivery to skeletal muscles , muscle efficiency , tolerance and endurance and may thus have a positive impact on sports performances . | Abstract This study investigated the influence of dietary inorganic nitrate ( NO 3 − ) supplementation on pulmonary O2 uptake ( V˙O2 ) and muscle deoxyhemoglobin/myoglobin ( i.e. deoxy [ Hb + Mb ] ) kinetics during submaximal cycling exercise . In a r and omized , placebo‐controlled , cross‐over study , eight healthy and physically active male subjects completed two step cycle tests at a work rate equivalent to 50 % of the difference between the gas exchange threshold and peak V˙O2 over separate 4‐day supplementation periods with NO 3 −‐rich ( BR ; providing 8.4 mmol NO 3 −∙day−1 ) and NO 3 −‐depleted ( placebo ; PLA ) beetroot juice . Pulmonary V˙O2 was measured breath‐by‐breath and time‐resolved near‐infrared spectroscopy was utilized to quantify absolute deoxy [ Hb + Mb ] and total [ Hb + Mb ] within the rectus femoris , vastus lateralis , and vastus medialis . There were no significant differences ( P > 0.05 ) in the primary deoxy [ Hb + Mb ] mean response time or amplitude between the PLA and BR trials at each muscle site . BR significantly increased the mean ( three‐site ) end‐exercise deoxy [ Hb + Mb ] ( PLA : 91 ± 9 vs. BR : 95 ± 12 μmol/L , P < 0.05 ) , with a tendency to increase the mean ( three‐site ) area under the curve for total [ Hb + Mb ] responses ( PLA : 3650 ± 1188 vs. BR : 4467 ± 1315 μmol/L sec−1 , P = 0.08 ) . The V˙O2 slow component reduction after BR supplementation ( PLA : 0.27 ± 0.07 vs. BR : 0.23 ± 0.08 L min−1 , P = 0.07 ) correlated inversely with the mean increases in deoxy [ Hb + Mb ] and total [ Hb + Mb ] across the three muscle regions ( r 2 = 0.62 and 0.66 , P < 0.05 ) . Dietary NO 3 − supplementation increased O2 diffusive conductance across locomotor muscles in association with improved V˙O2 dynamics during heavy‐intensity cycling transitions BACKGROUND Dietary inorganic nitrate ( NO3- ) and its reduced forms nitrite ( NO2- ) and nitric oxide ( NO ) , respectively , are of critical importance for host defense in the oral cavity . High concentrations of salivary nitrate are linked to a lower prevalence of caries due to growth inhibition of cariogenic bacteria . OBJECTIVE In-vitro studies suggest that the formation of antimicrobial NO results in an increase of the pH preventing erosion of tooth enamel . The purpose of this study was to prove this effect in-vivo . METHODS In a r and omized clinical study with 46 subjects we investigated whether NO3- rich beetroot juice exhibits a protective effect against caries by an increase of salivary pH. RESULTS Our results show that , in comparison to a placebo group , consumption of beetroot juice that contains 4000 mg/L NO3- results in elevated levels of salivary NO2- , nitrite NO3- , and NO . Furthermore , we determined an increase of the mean pH of saliva from 7.0 to 7.5 , confirming the anti-cariogenic effect of the used NO3 - -rich beetroot juice . CONCLUSIONS Taken together , we have found that NO3 - -rich beetroot juice holds potential effects against dental caries by preventing acidification of human saliva . TRIAL REGISTRATION C-87 - 15 ( Ethics Commissions of Upper Austria ) It is possible that dietary nitrate ( NO3− ) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics . Purpose To investigate the effects of dietary NO3− supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test ( IST ) protocol , which was design ed to reflect typical work patterns during team sports . Methods In a double-blind r and omised crossover study , 16 male team-sport players received NO3−-rich ( BR ; 140 mL day−1 ; 12.8 mmol of NO3− ) , and NO3−-depleted ( PL ; 140 mL day−1 ; 0.08 mmol NO3− ) beetroot juice for 7 days . On day 7 of supplementation , subjects completed the IST ( two 40-min “ halves ” of repeated 2-min blocks consisting of a 6-s “ all-out ” sprint , 100-s active recovery and 20 s of rest ) , on a cycle ergometer during which cognitive tasks were simultaneously performed . Results Total work done during the sprints of the IST was greater in BR ( 123 ± 19 kJ ) compared to PL ( 119 ± 17 kJ ; P < 0.05 ) . Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL ( BR first half : 820 ± 96 vs. second half : 817 ± 86 ms ; PL first half : 824 ± 114 vs. second half : 847 ± 118 ms ; P < 0.05 ) . There was no difference in response accuracy . Conclusions These findings suggest that dietary NO3− enhances repeated sprint performance and may attenuate the decline in cognitive function ( and specifically reaction time ) that may occur during prolonged intermittent exercise The beneficial effects of beetroot juice supplementation ( BJS ) have been tested during cycling , walking , and running . The purpose of the present study was to investigate whether BJS can also improve performance in swimmers . Fourteen moderately trained male master swimmers were recruited and underwent two incremental swimming tests r and omly assigned in a pool during which workload , oxygen uptake ( VO2 ) , carbon dioxide production ( VCO2 ) , pulmonary ventilation ( VE ) , and aerobic energy cost ( AEC ) of swimming were measured . One was a control swimming test ( CSW ) and the other a swimming test after six days of BJS ( 0.5l/day organic beetroot juice containing about 5.5 mmol of NO3− ) . Results show that workload at anaerobic threshold was significantly increased by BJS as compared to the CSW test ( 6.3 ± 1 and 6.7 ± 1.1 kg during the CSW and the BJS test respectively ) . Moreover , AEC was significantly reduced during the BJS test ( 1.9 ± 0.5 during the SW test vs. 1.7 ± 0.3 kcal·kg−1·h−1 during the BJS test ) . The other variables lacked a statistically significant effect with BJS . The present investigation provides evidence that BJS positively affects performance of swimmers as it reduces the AEC and increases the workload at anaerobic threshold Nitrate supplementation appears to be most ergogenic when oxygen availability is restricted and subsequently may be particularly beneficial for swimming performance due to the breath-hold element of this sport . This represents the first investigation of nitrate supplementation and swimming time-trial ( TT ) performance . In a r and omized double-blind repeated- measures crossover study , ten ( 5 male , 5 female ) trained swimmers ingested 140ml nitrate-rich ( ~12.5mmol nitrate ) or nitrate-depleted ( ~0.01mmol nitrate ) beetroot juice . Three hours later , subjects completed a maximal effort swim TT comprising 168 m ( 8 × 21 m lengths ) backstroke . Preexercise fractional exhaled nitric oxide concentration was significantly elevated with nitrate compared with placebo , Mean ( SD ) : 17 ( 9 ) vs. 7 (3)p.p.b . , p = .008 . Nitrate supplementation had a likely trivial effect on overall swim TT performance ( mean difference 1.22s ; 90 % CI -0.18 - 2.6s ; 0.93 % ; p = .144 ; d = 0.13 ; unlikely beneficial ( 22.6 % ) , likely trivial ( 77.2 % ) , most unlikely negative ( 0.2 % ) ) . The effects of nitrate supplementation during the first half of the TT were trivial ( mean difference 0.29s ; 90 % CI -0.94 - 1.5s ; 0.46 % ; p = .678 ; d = 0.05 ) , but there was a possible beneficial effect of nitrate supplementation during the second half of the TT ( mean difference 0.93s ; 90 % CI 0.13 - 1.70s ; 1.36 % ; p = .062 ; d = 0.24 ; possibly beneficial ( 63.5 % ) , possibly trivial ( 36.3 % ) , most unlikely negative ( 0.2 % ) ) . The duration and speed of underwater swimming within the performance did not differ between nitrate and placebo ( both p > .30 ) . Nitrate supplementation increased nitric oxide bioavailability but did not benefit short-distance swimming performance or the underwater phases of the TT . Further investigation into the effects of nitrate supplementation during the second half of performance tests may be warranted A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials The influence of dietary nitrate ( NO3- ) supplementation on indices of maximal sprint and intermittent exercise performance is unclear . PURPOSE To investigate the effects of NO3- supplementation on sprint running performance , and cognitive function and exercise performance during the sport-specific Yo-Yo Intermittent Recovery level 1 test ( IR1 ) . METHODS In a double-blind , r and omized , crossover study , 36 male team-sport players received NO3 - -rich ( BR ; 70 mL·day-1 ; 6.4 mmol of NO3- ) , and NO3 - -depleted ( PL ; 70 mL·day-1 ; 0.04 mmol NO3- ) beetroot juice for 5 days . On day 5 of supplementation , subjects completed a series of maximal 20-m sprints followed by the Yo-Yo IR1 . Cognitive tasks were completed prior to , during and immediately following the Yo-Yo IR1 . RESULTS BR improved sprint split times relative to PL at 20 m ( 1.2 % ; BR 3.98 ± 0.18 vs. PL 4.03 ± 0.19 s ; P < 0.05 ) , 10 m ( 1.6 % ; BR 2.53 ± 0.12 vs. PL 2.57 ± 0.19 s ; P < 0.05 ) and 5 m ( 2.3 % ; BR 1.73 ± 0.09 vs. PL 1.77 ± 0.09 s ; P < 0.05 ) . The distance covered in the Yo-Yo IR1 test improved by 3.9 % ( BR 1422 ± 502 vs. PL 1369 ± 505 m ; P < 0.05 ) . The reaction time to the cognitive tasks was shorter in BR ( 615 ± 98 ms ) than PL ( 645 ± 120 ms ; P < 0.05 ) at rest but not during the Yo-Yo IR1 . There was no difference in response accuracy . CONCLUSIONS Dietary NO3- supplementation enhances maximal sprint and high-intensity intermittent running performance in competitive team sport players . Our findings suggest that NO3- supplementation has the potential to improve performance in single-sprint or multiple-sprint ( team ) sports A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria , and further to vasoprotective NO endogenously . In the present study , two separate r and omly controlled , single-blind , cross-over , postpr and ial studies were performed in normotensive volunteers . Ambulatory blood pressure ( BP ) was measured over a 24 h period following consumption of either four doses of beetroot juice ( BJ ) , 0 , 100 , 250 and 500 g ( n 18 ) , or three bread products , control bread ( 0 g beetroot ) , red beetroot- and white beetroot-enriched breads ( n 14 ) . Total urinary nitrate/nitrite ( NO(x ) ) was measured at baseline , and at 2 , 4 and 24 h post-ingestion . BJ consumption significantly , and in a near dose-dependent manner , lowered systolic BP ( SBP , P < 0·01 ) and diastolic BP ( DBP , P < 0·001 ) over a period of 24 h , compared with water control . Furthermore , bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h ( red beetroot-enriched bread , P < 0·05 ) , with no statistical differences between the varieties . Total urinary NO(x ) significantly increased following the consumption of 100 g ( P < 0·01 ) , 250 g ( P < 0·001 ) and 500 g BJ ( P < 0·001 ) and after red beetroot-enriched bread ingestion ( P < 0·05 ) , but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition . These studies demonstrated significant hypotensive effects of a low dose ( 100 g ) of beetroot which was unaffected by processing or the presence of betacyanins . These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables This study examined the effects of beetroot juice ( BTJ ) on recovery between two repeated-sprint tests . In an independent groups design , 20 male , team-sports players were r and omized to receive either BTJ or a placebo ( PLA ) ( 2 × 250 mL ) for 3 days after an initial repeated sprint test ( 20 × 30 m ; RST1 ) and after a second repeated sprint test ( RST2 ) , performed 72 h later . Maximal isometric voluntary contractions ( MIVC ) , countermovement jumps ( CMJ ) , reactive strength index ( RI ) , pressure-pain threshold ( PPT ) , creatine kinase ( CK ) , C-reactive protein ( hs-CRP ) , protein carbonyls ( PC ) , lipid hydroperoxides ( LOOH ) and the ascorbyl free radical ( A•− ) were measured before , after , and at set times between RST1 and RST2 . CMJ and RI recovered quicker in BTJ compared to PLA after RST1 : at 72 h post , CMJ and RI were 7.6 % and 13.8 % higher in BTJ vs. PLA , respectively ( p < 0.05 ) . PPT was 10.4 % higher in BTJ compared to PLA 24 h post RST2 ( p = 0.012 ) but similar at other time points . No group differences were detected for mean and fastest sprint time or fatigue index . MIVC , or the biochemical markers measured ( p > 0.05 ) . BTJ reduced the decrement in CMJ and RI following and RST but had no effect on sprint performance or oxidative stress INTRODUCTION Dietary nitrate supplementation has received much attention in the literature due to its proposed ergogenic properties . Recently , the ingestion of a single bolus of nitrate-rich beetroot juice ( 500 ml , ~6.2 mmol NO3- ) was reported to improve subsequent time-trial performance . However , this large volume of ingested beetroot juice does not represent a realistic dietary strategy for athletes to follow in a practical , performance-based setting . Therefore , we investigated the impact of ingesting a single bolus of concentrated nitrate-rich beetroot juice ( 140 ml , ~8.7 mmol NO3- ) on subsequent 1-hr time-trial performance in well-trained cyclists . METHODS Using a double-blind , repeated- measures crossover design ( 1-wk washout period ) , 20 trained male cyclists ( 26 ± 1 yr , VO(2peak ) 60 ± 1 ml · kg(-1 ) · min(-1 ) , Wmax 398 ± 7.7 W ) ingested 140 ml of concentrated beetroot juice ( 8.7 mmol NO3- ; BEET ) or a placebo ( nitrate-depleted beetroot juice ; PLAC ) with breakfast 2.5 hr before an ~1-hr cycling time trial ( 1,073 ± 21 kJ ) . Resting blood sample s were collected every 30 min after BEET or PLAC ingestion and immediately after the time trial . RESULTS Plasma nitrite concentration was higher in BEET than PLAC before the onset of the time trial ( 532 ± 32 vs. 271 ± 13 nM , respectively ; p < .001 ) , but subsequent time-trial performance ( 65.5 ± 1.1 vs. 65 ± 1.1 s ) , power output ( 275 ± 7 vs. 278 ± 7 W ) , and heart rate ( 170 ± 2 vs. 170 ± 2 beats/min ) did not differ between BEET and PLAC treatments ( all p > .05 ) . CONCLUSION Ingestion of a single bolus of concentrated ( 140 ml ) beetroot juice ( 8.7 mmol NO3- ) does not improve subsequent 1-hr time-trial performance in well-trained cyclists Background The consumption of beetroot juice on a low nitrate diet may lower blood pressure ( BP ) and therefore reduce the risk of cardiovascular events . However , it is unknown if its inclusion as part of a normal diet has a similar effect on BP . The aim of the study was to conduct a r and omized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP . Method Fifteen women and fifteen men participated in a double-blind , r and omized , placebo-controlled , crossover study . Volunteers were r and omized to receive 500 g of beetroot and apple juice ( BJ ) or a placebo juice ( PL ) . Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor ( ABPM ) . Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities . The identical procedure was repeated 2-wk later with the drink ( BJ or PL ) not consumed on the first visit . Results Overall , there was a trend ( P=0.064 ) to lower systolic blood pressure ( SBP ) at 6-h after drinking BJ relative to PL . Analysis in men only ( n=13 ) after adjustment for baseline differences demonstrated a significant ( P<0.05 ) reduction in SBP of 4 – 5 mmHg at 6-h after drinking BJ . Conclusions Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults . Trial registration anzctr.org.au Recent studies have suggested that dietary inorganic nitrate ( NO3− ) supplementation may improve muscle efficiency and endurance exercise tolerance but possible effects during team sport-specific intense intermittent exercise have not been examined . We hypothesized that NO3− supplementation would enhance high-intensity intermittent exercise performance . Fourteen male recreational team-sport players were assigned in a double-blind , r and omized , crossover design to consume 490 mL of concentrated , nitrate-rich beetroot juice ( BR ) and nitrate-depleted placebo juice ( PL ) over ~30 h preceding the completion of a Yo – Yo intermittent recovery level 1 test ( Yo – Yo IR1 ) . Resting plasma nitrite concentration ( [ NO2− ] ) was ~400 % greater in BR compared to PL . Plasma [ NO2− ] declined by 20 % in PL ( P < 0.05 ) and by 54 % in BR ( P < 0.05 ) from pre-exercise to end-exercise . Performance in the Yo – Yo IR1 was 4.2 % greater ( P < 0.05 ) with BR ( 1,704 ± 304 m ) compared to PL ( 1,636 ± 288 m ) . Blood [ lactate ] was not different between BR and PL , but the mean blood [ glucose ] was lower ( 3.8 ± 0.8 vs. 4.2 ± 1.1 mM , P < 0.05 ) and the rise in plasma [ K+ ] tended to be reduced in BR compared to PL ( P = 0.08 ) . These findings suggest that NO3− supplementation may promote NO production via the nitrate-nitrite-NO pathway and enhance Yo – Yo IR1 test performance , perhaps by facilitating greater muscle glucose uptake or by better maintaining muscle excitability . Dietary NO3− supplementation improves performance during intense intermittent exercise and may be a useful ergogenic aid for team sports players BACKGROUND Dietary nitrate is receiving increased attention due to its reported ergogenic and cardioprotective properties . The extent to which ingestion of various nitrate-rich vegetables increases postpr and ial plasma nitrate and nitrite concentrations and lowers blood pressure is currently unknown . OBJECTIVE We aim ed to assess the impact of ingesting different nitrate-rich vegetables on subsequent plasma nitrate and nitrite concentrations and resting blood pressure in healthy normotensive individuals . METHODS With the use of a semir and omized crossover design , 11 men and 7 women [ mean ± SEM age : 28 ± 1 y ; mean ± SEM body mass index ( BMI , in kg/m(2 ) ) : 23 ± 1 ; exercise : 1 - 10 h/wk ] ingested 4 different beverages , each containing 800 mg ( ∼12.9 mmol ) nitrate : sodium nitrate ( NaNO3 ) , concentrated beetroot juice , a rocket salad beverage , and a spinach beverage . Plasma nitrate and nitrite concentrations and blood pressure were determined before and up to 300 min after beverage ingestion . Data were analyzed using repeated- measures ANOVA . RESULTS Plasma nitrate and nitrite concentrations increased after ingestion of all 4 beverages ( P < 0.001 ) . Peak plasma nitrate concentrations were similar for all treatments ( all values presented as means ± SEMs : NaNO3 : 583 ± 29 μmol/L ; beetroot juice : 597 ± 23 μmol/L ; rocket salad beverage : 584 ± 24 μmol/L ; spinach beverage : 584 ± 23 μmol/L ) . Peak plasma nitrite concentrations were different between treatments ( NaNO3 : 580 ± 58 nmol/L ; beetroot juice : 557 ± 57 nmol/L ; rocket salad beverage : 643 ± 63 nmol/L ; spinach beverage : 980 ± 160 nmol/L ; P = 0.016 ) . When compared with baseline , systolic blood pressure declined 150 min after ingestion of beetroot juice ( from 118 ± 2 to 113 ± 2 mm Hg ; P < 0.001 ) and rocket salad beverage ( from 122 ± 3 to 116 ± 2 mm Hg ; P = 0.007 ) and 300 min after ingestion of spinach beverage ( from 118 ± 2 to 111 ± 3 mm Hg ; P < 0.001 ) , but did not change with NaNO3 Diastolic blood pressure declined 150 min after ingestion of all beverages ( P < 0.05 ) and remained lower at 300 min after ingestion of rocket salad ( P = 0.045 ) and spinach ( P = 0.001 ) beverages . CONCLUSIONS Ingestion of nitrate-rich beetroot juice , rocket salad beverage , and spinach beverage effectively increases plasma nitrate and nitrite concentrations and lowers blood pressure to a greater extent than sodium nitrate . These findings show that nitrate-rich vegetables can be used as dietary nitrate supplements . This trial was registered at clinical trials.gov as NCT02271633 Nitric oxide ( NO ) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle . Dietary nitrate ( NO3(- ) ) intake has been demonstrated to increase NO bioavailability in humans . We therefore hypothesized that acute dietary NO3(- ) intake ( in the form of a concentrated beetroot juice ( BRJ ) supplement ) would improve muscle speed and power in humans . To test this hypothesis , healthy men and women ( n = 12 ; age = 22 - 50 y ) were studied using a r and omized , double-blind , placebo-controlled crossover design . After an overnight fast , subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(- ) . After 2 h , knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer . Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production . No significant changes in breath NO were observed in the placebo trial , whereas breath NO rose by 61 % ( P < 0.001 ; effect size = 1.19 ) after dietary NO3(- ) intake . This was accompanied by a 4 % ( P < 0.01 ; effect size = 0.74 ) increase in peak knee extensor power at the highest angular velocity tested ( i.e. , 6.28 rad/s ) . Calculated maximal knee extensor power was therefore greater ( i.e. , 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg ; P < 0.05 ; effect size = 0.63 ) after dietary NO3(- ) intake , as was the calculated maximal velocity ( i.e. , 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s ; P < 0.05 ; effect size = 0.67 ) . No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s . We conclude that acute dietary NO3(- ) intake increases whole-body NO production and muscle speed and power in healthy men and women Six days of dietary nitrate supplementation in the form of beetroot juice ( ~0.5 L/d ) has been reported to reduce pulmonary oxygen uptake ( VO₂ ) during submaximal exercise and increase tolerance of high-intensity work rates , suggesting that nitrate can be a potent ergogenic aid . Limited data are available regarding the effect of nitrate ingestion on athletic performance , and no study has investigated the potential ergogenic effects of a small-volume , concentrated dose of beetroot juice . The authors tested the hypothesis that 6 d of nitrate ingestion would improve time-trial performance in trained cyclists . Using a double-blind , repeated- measures crossover design , 12 male cyclists ( 31±3 yr , VO2peak=58±2 ml·kg⁻¹·min⁻¹ , maximal power [Wmax]=342±10 W ) ingested 140 ml/d of concentrated beetroot ( ~8 mmol/d nitrate ) juice ( BEET ) or a placebo ( nitrate-depleted beetroot juice ; PLAC ) for 6 d , separated by a 14-d washout . After supplementation on Day 6 , subjects performed 60 min of submaximal cycling ( 2 × 30 min at 45 % and 65 % Wmax , respectively ) , followed by a 10-km time trial . Time-trial performance ( 953±18 vs. 965±18 s , p<.005 ) and power output ( 294±12 vs. 288±12 W , p<.05 ) improved after BEET compared with PLAC supplementation . Submaximal VO₂ was lower after BEET ( 45 % Wmax=1.92±0.06 vs. 2.02±0.09 L/min , 65 % Wmax 2.94±0.12 vs. 3.11±0.12 L/min ) than with PLAC ( main effect , p<.05 ) . Whole-body fuel selection and plasma lactate , glucose , and insulin concentrations did not differ between treatments . Six days of nitrate supplementation reduced VO₂ during submaximal exercise and improved time-trial performance in trained cyclists PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance . However , it is presently unknown whether it may enhance performance during simulated competition . The present study investigated the effects of acute dietary nitrate supplementation on power output ( PO ) , VO2 , and performance during 4- and 16.1-km cycling time trials ( TT ) . METHODS After familiarization , nine club-level competitive male cyclists were assigned in a r and omized , crossover design to consume 0.5 L of beetroot juice ( BR ; containing ∼ 6.2 mmol of nitrate ) or 0.5 L of nitrate-depleted BR ( placebo , PL ; containing ∼ 0.0047 mmol of nitrate ) , ∼ 2.5 h before the completion of a 4- and a 16.1-km TT . RESULTS BR supplementation elevated plasma [ nitrite ] ( PL = 241 ± 125 vs BR = 575 ± 199 nM , P < 0.05 ) . The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance ( P > 0.05 ) , but BR significantly increased mean PO during the 4-km ( PL = 279 ± 51 vs BR = 292 ± 44 W , P < 0.05 ) and 16.1-km TT ( PL = 233 ± 43 vs BR = 247 ± 44 W , P < 0.01 ) . Consequently , BR improved 4-km performance by 2.8 % ( PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min , P < 0.05 ) and 16.1-km performance by 2.7 % ( PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min , P < 0.01 ) . CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy , as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance PURPOSE To determine the effect of [ Formula : see text ] consumption on measures of perception , thermoregulation , and cycling performance in hot conditions . METHODS In a r and omized , double-blind , crossover design , 8 well-trained cyclists ( mean ± SD age 25 ± 8 y , [ Formula : see text ] peak 64 ± 5 mL · kg-1 · min-1 ) performed 2 separate trials in hot ( 35 ° C , 60 % relative humidity ) environments , having ingested either 140 mL [ Formula : see text]-rich beetroot juice ∼8 mmol [ Formula : see text ] ( NIT ) or placebo ( PLA ) daily for 3 d with a 7-d washout period separating trials . Trials consisted of 2 × 10-min bouts at 40 % and 60 % peak power output ( PPO ) to determine physiological and perceptual responses to the heat , followed by a 4-km cycling time trial . RESULTS Basal [ nitrite ] was substantially elevated in NIT ( 2.70 ± 0.98 µM ) vs PLA ( 1.10 ± 0.61 µM ) , result ing in a most likely ( ES = 1.58 ± 0.93 ) increase after 3 d. There was a very likely trivial increase in rectal temperature in NIT at 40 % ( PLA 37.4 ° C ± 0.2 ° C vs NIT 37.5 ° C ± 0.3 ° C , 0.1 ° C ± 0.2 ° C ) and 60 % ( PLA 37.8 ° C ± 0.2 ° C vs NIT 37.9 ° C ± 0.3 ° C , 0.1 ° C ± 0.2 ° C ) PPO . Cycling performance was similar between trials ( PLA 336 ± 45 W vs NIT 337 ± 50 W , CV ± 95%CL ; 0.2 % ± 2.5 % ) . Outcomes for heart rate and perceptual measures were unclear across the majority of time points . CONCLUSIONS Three days of [ Formula : see text ] supplementation result ed in small increases in rectal temperature during low- to moderate-intensity exercise , but this did not appear to influence 4-km cycling time-trial performance in hot climates It has been shown that nitrate supplementation can enhance endurance exercise performance . Recent work suggests that nitrate ingestion can also increase intermittent type exercise performance in recreational athletes . We hypothesized that six days of nitrate supplementation can improve high-intensity intermittent type exercise performance in trained soccer players . Thirty-two male soccer players ( age : 23 ± 1 years , height : 181 ± 1 m , weight : 77 ± 1 kg , playing experience : 15.2 ± 0.5 years , playing in the first team of a 2nd or 3rd Dutch amateur league club ) participated in this r and omized , double-blind cross-over study . All subjects participated in two test days in which high-intensity intermittent running performance was assessed using the Yo-Yo IR1 test . Subjects ingested nitrate-rich ( 140 mL ; ~800 mg nitrate/day ; BR ) or a nitrate-depleted beetroot juice ( PLA ) for six subsequent days , with at least eight days of wash-out between trials . The distance covered during the Yo-Yo IR1 was the primary outcome measure , while heart rate ( HR ) was measured continuously throughout the test , and a single blood and saliva sample were collected just prior to the test . Six days of BR ingestion increased plasma and salivary nitrate and nitrite concentrations in comparison to PLA ( p < 0.001 ) , and enhanced Yo-Yo IR1 test performance by 3.4 ± 1.3 % ( from 1574 ± 47 to 1623 ± 48 m ; p = 0.027 ) . Mean HR was lower in the BR ( 172 ± 2 ) vs. PLA trial ( 175 ± 2 ; p = 0.014 ) . Six days of BR ingestion effectively improves high-intensity intermittent type exercise performance in trained soccer players Aims . To evaluate the possible additive effects of beetroot juice plus caffeine on exercise performance . Methods . In a r and omized , double-blinded study design , fourteen healthy well-trained men aged 22 ± 3 years performed four trials on different occasions following preexercise ingestion of placebo ( PLA ) , PLA plus 5 mg/kg caffeine ( PLA+C ) , beetroot juice providing 8 mmol of nitrate ( BR ) , and beetroot juice plus caffeine ( BR+C ) . Participants cycled at 60 % maximal oxygen uptake ( V˙O2max ) for 30 min followed by a time to exhaustion ( TTE ) trial at 80 % V˙O2max . Saliva was collected before supplement ingestion , before exercise , and after the TTE trial for salivary nitrate , nitrite , and cortisol analysis . Results . In beetroot trials , saliva nitrate and nitrite increased > 10-fold before exercise compared with preingestion ( P ≤ 0.002 ) . TTE in BR+C was 46 % higher than in PLA ( P = 0.096 ) and 18 % and 27 % nonsignificant TTE improvements were observed on BR+C compared with BR and PLA+C alone , respectively . Lower ratings of perceived exertion during TTE were found during 80 % V˙O2max on BR+C compared with PLA and PLA+C ( P < 0.05 for both ) . Conclusions . Acute preexercise beetroot juice coingestion with caffeine likely has additive effects on exercise performance compared with either beetroot or caffeine alone Ingestion of dietary ( inorganic ) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation . In addition , nitrite is a potent vasodilator in humans , an effect thought to underlie the blood pressure – lowering effects of dietary nitrate ( in the form of beetroot juice ) ingestion . Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain . Using a r and omized crossover study design , we show that nitrate supplementation ( KNO3 capsules : 4 versus 12 mmol [ n=6 ] or 24 mmol of KNO3 ( 1488 mg of nitrate ) versus 24 mmol of KCl [ n=20 ] ) or vegetable intake ( 250 mL of beetroot juice [ 5.5 mmol nitrate ] versus 250 mL of water [ n=9 ] ) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers . In addition , post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration , whereby blood pressure is decreased in male volunteers , with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers . Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation . In addition , our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women Human male volunteers were studied in a metabolic facility whilst they were fed r and omized controlled diets . In eight volunteers there was a significant increase in faecal apparent total N:-nitroso compounds ( ATNC ) and nitrite excretion ( P < 0.0001 and P = 0.046 , respectively ) when r and omized doses of meat were increased from 0 to 60 , 240 and 420 g/day over 10 day periods . Mean ( + /- SE ) faecal ATNC levels were 54 + /- 7 microg/day when the diets contained no meat , 52 + /- 11 microg/day when the diets contained 60 g meat/day , 159 + /- 33 microg/day with 240 g meat and 199 + /- 36 microg/day with 420 g meat . Higher concentrations of NOC were associated with longer times of transit in the gut ( r = 0.55 , P = 0.001 ) and low faecal weight ( r = -0.51 , P = 0.004 ) . There was no significant decline in levels in individuals fed 420 g meat for 40 days . The exposures found on the higher meat diets were comparable with other sources of N:-nitroso compounds ( NOC ) , such as tobacco smoke . Many NOC are known large bowel initiators and promotors in colon cancer , inducing G-->A transitions in codons 12 and 13 of K-ras . Endogenous NOC formation , combined with prolonged transit times in the gut , may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk Background : N-nitroso compounds ( NOC ) are found in processed meat and are formed endogenously from intake of nitrite and nitrate . Endogenous NOC formation is antagonized by nitrosation inhibitors in fruit and vegetables ( e.g. , vitamin C ) and promoted by heme in red meat . It has been hypothesized that a diet result ing in high exposure to NOCs increases adult glioma risk . Methods : Using proportional hazards models , we tested this hypothesis among 545,770 participants in the prospect i ve NIH-AARP Diet and Health Study , which assessed dietary intake at baseline ( 1995–1996 ) with a comprehensive food frequency question naire , and at ages 12 to 13 years with an abbreviated food frequency question naire . Results : During follow-up through 2003 , 585 participants were diagnosed with glioma . We found no significant trends in glioma risk for consumption of processed or red meat , nitrate , or vitamin C or E. We found significant positive trends for nitrite intake from plant sources ( hazard ratio for quintile 5 versus quintile 1 , 1.59 ; 95 % confidence interval , 1.20–2.10 ; P for trend = 0.028 ) and , unexpectedly , for fruit and vegetable intake ( hazard ratio , 1.42 ; 95 % confidence interval , 1.08–1.86 ; P for trend = 0.0081 ) . Examination of interactions between dietary intakes ( e.g. , nitrite and vitamin C ) and a limited analysis of diet at ages 12 to 13 years provided no support for the NOC hypothesis . Conclusions : Our results suggest that consumption of processed or red meat , nitrite , or nitrate does not increase adult glioma risk , and that consumption of fruit and vegetables , vitamin C , or vitamin E does not reduce risk . Impact : Our results , in agreement with the only previous prospect i ve analysis , cast doubt on the NOC hypothesis in relation to dietary intake and adult glioma risk . Cancer Epidemiol Biomarkers Prev ; 19(7 ) ; 1709–22 . © 2010 AACR We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide ( NO ) signaling . Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway . Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise , particularly in older adults . Thirteen young ( 25 ± 1 yr ) and 12 older ( 64 ± 2 yr ) adults performed rhythmic forearm exercise at 20 % of maximum voluntary contraction during normoxia and hypoxia ( ∼80 % O2 saturation ) ; both before ( control ) and 3 h after beetroot juice ( BR ) consumption . Forearm vascular conductance ( FVC ; ml·min(-1)·100 mmHg(-1 ) ) was calculated from forearm blood flow ( ml/min ) and blood pressure ( mmHg ) . Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise ( i.e. , % increase compared with respective normoxic exercise trial ) . Plasma nitrite was determined from venous blood sample s obtained before the control trials and each of the exercise trials ( normoxia and hypoxia ) after BR . Consumption of BR increased plasma nitrite in both young and older adults ( P < 0.001 ) . During the control condition , the compensatory vasodilator response to hypoxic exercise was attenuated in older compared with young adults ( 3.8 ± 1.7 % vs. 14.2 ± 1.2 % , P < 0.001 ) . Following BR consumption , compensatory vasodilation did not change in young ( 13.7 ± 3.3 % , P = 0.81 ) adults but was substantially augmented in older adults ( 11.4 ± 2.1 % , P < 0.01 ) . Our data suggest that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise in older but not young adults Acute dietary nitrate ( [ Formula : see text ] ) supplementation reduces resting blood pressure in healthy normotensives . This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation , although nitric oxide also tonically inhibits central sympathetic outflow . We hypothesized that acute dietary [ Formula : see text ] supplementation using beetroot ( BR ) juice would reduce blood pressure and muscle sympathetic nerve activity ( MSNA ) at rest and during exercise . Fourteen participants ( 7 men and 7 women , age : 25 ± 10 yr ) underwent blood pressure and MSNA measurements before and after ( 165 - 180 min ) ingestion of 70ml high-[Formula : see text ] ( ~6.4 mmol [ Formula : see text ] ) BR or [ Formula : see text]-depleted BR placebo ( PL ; ~0.0055 mmol [ Formula : see text ] ) in a double-blind , r and omized , crossover design . Blood pressure and MSNA were also collected during 2 min of static h and grip ( 30 % maximal voluntary contraction ) . The changes in resting MSNA burst frequency ( -3 ± 5 vs. 3 ± 4 bursts/min , P = 0.001 ) and burst incidence ( -4 ± 7 vs. 4 ± 5 bursts/100 heart beats , P = 0.002 ) were lower after BR versus PL , whereas systolic blood pressure ( -1 ± 5 vs. 2 ± 5 mmHg , P = 0.30 ) and diastolic blood pressure ( 4 ± 5 vs. 5 ± 7 mmHg , P = 0.68 ) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95 ) were not different . During static h and grip , the change in MSNA burst incidence ( 1 ± 8 vs. 8 ± 9 bursts/100 heart beats , P = 0.04 ) was lower after BR versus PL , whereas MSNA burst frequency ( 6 ± 6 vs. 11 ± 10 bursts/min , P = 0.11 ) as well as systolic blood pressure ( 11 ± 7 vs. 12 ± 8 mmHg , P = 0.94 ) and diastolic blood pressure ( 11 ± 4 vs. 11 ± 4 mmHg , P = 0.60 ) were not different . Collectively , these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise . Dietary [ Formula : see text ] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical population s . NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation . Here , we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population . These results have applications for targeting central sympathetic overactivation in disease Abstract Dietary nitrate ( NO3− ) is converted to nitrite ( NO2− ) and can be further reduced to the vasodilator nitric oxide ( NO ) amid a low O2 environment . Accordingly , dietary NO3− increases hind limb blood flow in rats during treadmill exercise ; however , the evidence of such an effect in humans is unclear . We tested the hypothesis that acute dietary NO3− ( via beetroot [ BR ] juice ) increases forearm blood flow ( FBF ) via local vasodilation during h and grip exercise in young adults ( n = 11 ; 25 ± 2 years ) . FBF ( Doppler ultrasound ) and blood pressure ( Finapres ) were measured at rest and during grade d h and grip exercise at 5 % , 15 % , and 25 % maximal voluntary contraction ( MVC ) lasting 4 min each . At the highest workload ( 25 % MVC ) , systemic hypoxia ( 80 % SaO2 ) was induced and exercise continued for three additional minutes . Subjects ingested concentrated BR ( 12.6 mmol nitrate ( n = 5 ) or 16.8 mmol nitrate ( n = 6 ) and repeated the exercise bout either 2 ( 12.6 mmol ) or 3 h ( 16.8 mmol ) postconsumption . Compared to control , BR significantly increased FBF at 15 % MVC ( 184 ± 15 vs. 164 ± 15 mL/min ) , 25 % MVC ( 323 ± 27 vs. 286 ± 28 mL/min ) , and 25 % + hypoxia ( 373 ± 39 vs. 343 ± 32 mL/min ) and this was due to increases in vascular conductance ( i.e. , vasodilation ) . The effect of BR on hemodynamics was not different between the two doses of BR ingested . Forearm VO2 was also elevated during exercise at 15 % and 25 % MVC . We conclude that acute increases in circulating NO3− and NO2− via BR increases muscle blood flow during moderate‐ to high‐intensity h and grip exercise via local vasodilation . These findings may have important implication s for aging and diseased population s that demonstrate impaired muscle perfusion and exercise intolerance CONTEXT Beetroot juice is a naturally rich source of inorganic nitrate ( NO(3- ) ) , a compound hypothesized to enhance endurance performance by improving exercise efficiency . PURPOSE To investigate the effect of different doses of beetroot juice on 2000-m ergometer-rowing performance in highly trained athletes . METHODS Ten highly trained male rowers volunteered to participate in a placebo-controlled , double-blinded crossover study . Two hours before undertaking a 2000-m rowing-ergometer test , subjects consumed beetroot juice containing 0 mmol ( placebo ) , 4.2 mmol ( SINGLE ) , or 8.4 mmol ( DOUBLE ) NO(3- ) . Blood sample s were taken before supplement ingestion and immediately before the rowing test for analysis of plasma [ NO(3- ) ] and [ nitrite ( NO(2- ) ) ] . RESULTS The SINGLE dose demonstrated a trivial effect on time to complete 2000 m compared with placebo ( mean difference : 0.2 ± 2.5 s ) . A possibly beneficial effect was found with DOUBLE compared with SINGLE ( mean difference -1.8 ± 2.1 s ) and with placebo ( -1.6 ± 1.6 s ) . Plasma [ NO(2- ) ] and [ NO(3- ) ] demonstrated a dose-response effect , with greater amounts of ingested nitrate leading to substantially higher concentrations ( DOUBLE > SINGLE > placebo ) . There was a moderate but insignificant correlation ( r = -.593 , P = .055 ) between change in plasma [ NO(2- ) ] and performance time . CONCLUSION Compared with nitratedepleted beetroot juice , a high ( 8.4 mmol NO(3- ) ) but not moderate ( 4.2 mmol NO(3- ) ) dose of NO(3- ) in beetroot juice , consumed 2 h before exercise , may improve 2000-m rowing performance in highly trained athletes Increased plasma nitrate concentrations from dietary sources of nitrate have proven to benefit exercise performance . Beetroot ( BR ) contains relatively high levels of nitrate ( NO₃⁻ ) , which increases nitric oxide stores . This study investigated whether dietary nitrate supplementation , in the form of a BR beverage , would improve rowing performance during ergometer repetitions . In a r and omized crossover design , 14 well-trained junior male rowers consumed 500 ml of either BR or placebo ( PL ) daily for 6 d. After supplementation , rowers completed 6 maximal 500-m ergometer repetitions and times were recorded . A 7-d washout period separated the 2 trials . Blood pressure , oxygen saturation , maximum heart rate , urine ( specific gravity , pH , and nitrites ) , and lactates were collected for analysis at baseline and pre- and postperformance . Changes in the mean with 95 % confidence limits were calculated . There was a likely benefit to average repetition time in the BR condition , compared with PL ( 0.4 % , 95 % confidence limits , ± 1.0 % ) . In particular , Repetitions 4 - 6 showed an almost certain benefit in rowing time on BR ( 1.7 % , 95 % CL , ± 1.0 % ) . The underlying mechanism for the observed results remains unknown , as differences observed in rowers ' physiological measures between the 2 conditions were unclear . Conclusively , nitrate supplementation in the form of BR juice result ed in improved maximal rowing-ergometer repetitions , particularly in the later stages of exercise ABSTRACT Objective : To examine the effects of beetroot juice ( BRJ ) on ( i ) in vivo skeletal muscle O2 consumption ( mVO2 ) and microvascular reactivity at rest and ( ii ) muscle performance , muscle oxygenation , and mVO2 during sustained isometric h and grip exercise ( IHG ) . Methods : Sixteen young males consumed , r and omly , a nitrate-rich ( 8.1 mmol BRJnitrate ) or nitrate-depleted ( BRJplacebo ) BRJ . After 2.5 hours , they performed an occlusion-reperfusion maneuver at rest , a 3-minute sustained IHG , and a sustained IHG to exhaustion with arterial occlusion . Changes in muscle oxygenated hemoglobin ( O2Hb ) , deoxygenated hemoglobin ( HHb ) , microvascular red blood cell content ( tHb ) , and mVO2 were measured using near-infrared spectroscopy . Force output was recorded . Results : During occlusion , the O2Hb decline did not differ between BRJnitrate and BRJplacebo ( magnitude : −30.3 ± 1.6 vs. −31.1 ± 1.5 ΔμΜ ; slope : −0.107 ± 0.007 vs. −0.111 ± 0.007 μΜ second−1 ) . During reperfusion , all microvascular reactivity indices were not altered after BRJnitrate ( e.g. , O2Hbslope : 1.584 ± 0.093 vs. 1.556 ± 0.072 μΜ second−1 ) . During the second and third minute of IHG , O2Hb and tHb were higher in BRJnitrate versus BRJplacebo ( p < 0.05 ) , and force output was higher during the third minute ( 10.8 ± 0.7 vs. 9.5 ± 1.2 kg ; p < 0.05 ) ; HHb did not differ between trials . In IHG with arterial occlusion , BRJnitrate prolonged the time to fatigue ( 94.1 ± 5.8 vs. 80.1 ± 3.3 seconds ; p < 0.01 ) , with no effects on O2Hb decline ( O2Hbslope : −0.226 ± 0.015 vs. −0.230 ± 0.026 μΜ s−1 ) and mVO2 ( 14.1 ± 1.0 vs. 14.3 ± 1.6 μmol l−1 minute−1 ) . Conclusion : Acute BRJ ingestion in moderately trained individuals ( i ) did not alter in vivo skeletal muscle microvascular reactivity ( index of microvascular function at rest ) and basal oxidative efficiency , ( ii ) increased muscle oxygenation during IHG ( possibly via enhanced O2 delivery ) , and ( iii ) provided ergogenic benefits during sustained IHG with no effects on muscle oxidative efficiency . The ergogenic effects of BRJ appeared independent of its tissue perfusion benefits Nitrate-rich beetroot juice ( BR ) supplementation has been shown to increase biomarkers of nitric oxide availability with implication s for the physiological responses to exercise . We hypothesized that BR supplementation before and during prolonged moderate-intensity exercise would maintain an elevated plasma nitrite concentration ( [ [ Formula : see text ] ] ) , attenuate the expected progressive increase in V̇o2 over time , and improve performance in a subsequent time trial ( TT ) . In a double-blind , r and omized , crossover design , 12 men completed 2 h of moderate-intensity cycle exercise followed by a 100-kJ TT in three conditions : 1 ) BR before and 1 h into exercise ( BR + BR ) ; 2 ) BR before and placebo ( PL ) 1 h into exercise ( BR + PL ) ; and 3 ) PL before and 1 h into exercise ( PL + PL ) . During the 2-h moderate-intensity exercise bout , plasma [ [ Formula : see text ] ] declined by ~17 % in BR + PL but increased by ~8 % in BR + BR such that , at 2 h , plasma [ [ Formula : see text ] ] was greater in BR + BR than both BR + PL and PL + PL ( P < 0.05 ) . V̇o2 was not different among conditions over the first 90 min of exercise but was lower at 120 min in BR + BR ( 1.73 ± 0.24 l/min ) compared with BR + PL ( 1.80 ± 0.21 l/min ; P = 0.08 ) and PL + PL ( 1.83 ± 0.27 l/min ; P < 0.01 ) . The decline in muscle glycogen concentration over the 2-h exercise bout was attenuated in BR + BR ( ~28 % decline ) compared with BR + PL ( ~44 % decline ) and PL + PL ( ~44 % decline ; n = 9 , P < 0.05 ) . TT performance was not different among conditions ( P > 0.05 ) . BR supplementation before and during prolonged moderate-intensity exercise attenuated the progressive rise in V̇o2 over time and appeared to reduce muscle glycogen depletion but did not enhance subsequent TT performance . NEW & NOTEWORTHY We show for the first time that ingestion of nitrate during exercise preserves elevated plasma [ nitrite ] and negates the progressive rise in O2 uptake during prolonged moderate-intensity exercise Purpose We investigated the influence of inorganic nitrate ( $ $ { \text{NO}}_{3}^ { - } $ $ NO3- ) supplementation on local sweating and cutaneous vascular responses during exercise in hot conditions . Method Eight healthy , young subjects were assigned in a r and omized , double-blind , crossover design to receive $ $ { \text{NO}}_{3}^ { - } $ $ NO3 - -rich beetroot ( BR ) juice ( 140 mL/day , containing ~ 8 mmol of $ $ { \text{NO}}_{3}^ { - } $ $ NO3- ) and $ $ { \text{NO}}_{3}^ { - } $ $ NO3 - -depleted placebo ( PL ) juice ( 140 mL/day , containing ~ 0.003 mmol of $ $ { \text{NO}}_{3}^ { - } $ $ NO3- ) for 3 days . On day 3 of supplementation , subjects cycled at an intensity corresponding to 55 % of $ $ \dot{V}$$V˙O2max for 30 min in hot conditions ( 30 ° C , 50 % relative humidity ) . Chest and forearm sweat rate ( SR ) and skin blood flow ( SkBF ) , were measured continuously . Cutaneous vascular conductance ( CVC ) was calculated by SkBF/mean arterial pressure ( MAP ) . Results Prior to exercise , plasma $ $ { \text{NO}}_{3}^ { - } $ $ NO3- ( 21 ± 6 and 581 ± 161 µM ) and nitrite ( $ $ { \text{NO}}_{2}^ { - } $ $ NO2- , 87 ± 28 and 336 ± 156 nM ) concentrations were higher after BR compared to PL supplementation ( P ≤ 0.011 , n = 6 ) . Oesophageal , mean skin , and mean body temperatures during exercise were not different between conditions . In addition , BR supplementation did not affect SR , SkBF , and CVC during exercise . A lower MAP was found after 30 min of exercise following BR supplementation ( 112 ± 6 and 103 ± 6 mmHg for PL and BR , respectively , P = 0.021 ) . Conclusion These results suggest that inorganic $ $ { \text{NO}}_{3}^ { - } $ $ NO3- supplementation , which increases the potential for O2-independent NO production , does not affect local sweating and cutaneous vascular responses , but attenuates blood pressure in young healthy subjects exercising in a hot environment Reduced partial pressure of oxygen impairs exercise performance at altitude . Acute nitrate supplementation , at sea level , may reduce oxygen cost during submaximal exercise in hypobaric hypoxia . Therefore , we investigated the metabolic response during exercise at altitude following acute nitrate consumption . Ten well-trained ( 61.0 ± 7.4 ml/kg/min ) males ( age 28 ± 7 yr ) completed 3 experimental trials ( T1 , T2 , T3 ) . T1 included baseline demographics , a maximal aerobic capacity test ( VO2max ) and five submaximal intensity cycling determination bouts at an elevation of 1600 m. A 4-day dietary washout , minimizing consumption of nitrate-rich foods , preceded T2 and T3 . In a r and omized , double-blind , placebo-controlled , crossover fashion , subjects consumed either a nitrate-depleted beetroot juice ( PL ) or ~12.8 mmol nitrate rich ( NR ) beverage 2.5 hr before T2 and T3 . Exercise at 3500 m ( T2 and T3 ) via hypobaric hypoxia consisted of a 5-min warm-up ( 25 % of normobaric VO2max ) and four 5-min cycling bouts ( 40 , 50 , 60 , 70 % of normobaric VO2max ) each separated by a 4-min rest period . Cycling RPM and watts for each submaximal bout during T2 and T3 were determined during T1 . Preexercise plasma nitrite was elevated following NR consumption compared with PL ( 1.4 ± 1.2 and 0.7 ± 0.3 uM respectively ; p < .05 ) . There was no difference in oxygen consumption ( -0.5 ± 1.8 , 0.1 ± 1.7 , 0.7 ± 2.1 , and 1.0 ± 3.0 ml/kg/min ) at any intensity ( 40 , 50 , 60 , 70 % of VO2max , respectively ) between NR and PL . Further , respiratory exchange ratio , oxygen saturation , heart rate and rating of perceived exertion were not different at any submaximal intensity between NR and PL either . Blood lactate , however , was reduced following NR consumption compared with PL at 40 and 60 % of VO2max ( p < .0.05 ) . Our findings suggest that acute nitrate supplementation before exercise at 3500 m does not reduce oxygen cost but may reduce blood lactate accumulation at lower intensity workloads Nitrate-rich beetroot juice ( BRJ ) increases plasma nitrite concentrations , lowers the oxygen cost ( V⋅O2 ) of steady-state exercise and improves exercise performance in sedentary and moderately-trained , but rarely in well-trained individuals exercising at sea-level . BRJ supplementation may be more effective in a hypoxic environment , where the reduction of nitrite into nitric oxide ( NO ) is potentiated , such that well-trained and less well-trained individuals may derive a similar ergogenic effect . We conducted a r and omised , counterbalanced , double-blind placebo controlled trial to determine the effects of BRJ on treadmill running performance in moderate normobaric hypoxia ( equivalent to 2500 m altitude ) in participants with a range of aerobic fitness levels . Twelve healthy males ( V⋅O2max ranging from 47.1 to 76.8 ml kg(-1 ) min(-1 ) ) ingested 138 ml concentrated BRJ ( ∼15.2 mmol nitrate ) or a nitrate-deplete placebo ( PLA ) ( ∼0.2 mmol nitrate ) . Three hours later , participants completed steady-state moderate intensity running , and a 1500 m time-trial ( TT ) in a normobaric hypoxic chamber ( FIO2 ∼ 15 % ) . Plasma nitrite concentration was significantly greater following BRJ versus PLA 1 h post supplementation , and remained higher in BRJ throughout the testing session ( p < 0.01 ) . Average V⋅O2 was significantly lower ( BRJ : 18.4 ± 2.0 , PLA : 20.4 ± 12.6 ml kg(-1 ) min(-1 ) ; p = 0.002 ) , whilst arterial oxygen saturation ( SpO2 ) was significantly greater ( BRJ : 88.4 ± 2.7 , PLA : 86.5 ± 3.3 % ; p < 0.001 ) following BRJ . BRJ improved TT performance in all 12 participants by an average of 3.2 % ( BRJ : 331.1 ± 45.3 vs. PL : 341.9 ± 46.1 s ; p < 0.001 ) . There was no apparent relationship between aerobic fitness and the improvement in performance following BRJ ( r(2 ) = 0.05 , p > 0.05 ) . These findings suggests that a high nitrate dose in the form of a BRJ supplement may improve running performance in individuals with a range of aerobic fitness levels conducting moderate and high-intensity exercise in a normobaric hypoxic environment Aging is associated with a vasoconstrictive , pro-coagulant , and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide . Dietary nitrate elicits vasodilatory , anti-coagulant and anti-inflammatory effects in younger individuals , but little is known about whether these benefits are evident in older adults . We investigated the effects of 140 mL of nitrate-rich ( HI-NI ; containing 12.9 mmol nitrate ) versus nitrate-depleted beetroot juice ( LO-NI ; containing ≤0.04 mmol nitrate ) on blood pressure , blood coagulation , vascular inflammation markers , plasma nitrate and nitrite before , and 3 h and 6 h after ingestion in healthy older adults ( five males , seven females , mean age : 64 years , age range : 57–71 years ) in a r and omized , placebo-controlled , crossover study . Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion ( p < 0.05 ) . Systolic , diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only ( p < 0.05 ) . The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake ( p < 0.05 ) , indicating reduced platelet activation . The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake ( p < 0.05 ) , suggesting a shift toward an anti-adhesive granulocyte phenotype . Numbers of blood CD14++CD16 + intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion ( p < 0.05 ) , but the clinical implication s of this response are currently unclear . These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets . Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging We tested the hypothesis that inorganic nitrate ( NO3 ( - ) ) supplementation would improve muscle oxygenation , pulmonary oxygen uptake ( V̇o2 ) kinetics , and exercise tolerance ( Tlim ) to a greater extent when cycling at high compared with low pedal rates . In a r and omized , placebo-controlled cross-over study , seven subjects ( mean ± SD , age 21 ± 2 yr , body mass 86 ± 10 kg ) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3 (-)-rich beetroot juice ( BR ) ( providing 8.4 mmol NO3 (-)/day ) and placebo ( PLA ) . Compared with PLA , plasma nitrite concentration increased 178 % with BR ( P < 0.01 ) . There were no significant differences in muscle oxyhemoglobin concentration ( [ O2Hb ] ) , phase II V̇o2 kinetics , or Tlim between BR and PLA when cycling at 35 rpm ( P > 0.05 ) . However , when cycling at 115 rpm , muscle [ O2Hb ] was higher at baseline and throughout exercise , phase II V̇o2 kinetics was faster ( 47 ± 16 s vs. 61 ± 25 s ; P < 0.05 ) , and Tlim was greater ( 362 ± 137 s vs. 297 ± 79 s ; P < 0.05 ) with BR compared with PLA . These results suggest that short-term BR supplementation can increase muscle oxygenation , expedite the adjustment of oxidative metabolism , and enhance exercise tolerance when cycling at a high , but not a low , pedal cadence in healthy recreationally active subjects . These findings support recent observations that NO3 ( - ) supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers PURPOSE Nitrate supplementation improves endurance exercise and single bouts of high-intensity activity , but its effect on repeated sprints is unclear . This study is the first to investigate the effects of acute dietary nitrate supplementation during a high-intensity intermittent-sprint test to exhaustion . METHODS Team-sport athletes ( 9 male , age 22.3 ± 2.1 y , VO2max 57.4 ± 8.5 mL · kg-1 · min-1 ; 7 female , age 20.7 ± 1.3 y , VO2max 47.2 ± 8.5 mL · kg-1 · min-1 ) were assigned to a double-blind , r and omized , crossover design . Participants consumed 70 mL of concentrated beetroot juice containing a minimum of 0.3 g of nitrate ( NT ) or 70 mL of placebo ( PL ) 2 h before a repeated-sprint protocol involving repeated 8-s sprints with 30-s recovery on a cycle ergometer to exhaustion . RESULTS Fewer sprints ( NT = 13 ± 5 vs PL = 15 ± 6 , P = .005 , d = 0.41 ) and less total work ( NT = 49.2 ± 24.2 kJ vs PL = 57.8 ± 34.0 kJ , P = .027 , d = 0.3 ) were completed in NT relative to PL . However there was no difference in overall mean power output or the mean power output for each individual 8-s sprint . CONCLUSIONS These findings suggest that dietary nitrate is not beneficial for improving repeated-sprint performance , at least when such sprints are near-maximal and frequent in nature . The lack of an effect of nitrate at near-maximal oxygen uptake supports the suggestion that at greater exercise intensities nitrate does not have an ergogenic effect Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide . It has been shown to improve endothelial function , reduce blood pressure and the oxygen cost of sub-maximal exercise , and increase regional perfusion in the brain . The current study assessed the effects of dietary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow ( CBF ) parameters in healthy adults . In this r and omised , double-blind , placebo-controlled , parallel-groups study , 40 healthy adults received either placebo or 450 ml beetroot juice ( ~5.5 mmol nitrate ) . Following a 90 minute drink/absorption period , participants performed a selection of cognitive tasks that activate the frontal cortex for 54 min . Near-Infrared Spectroscopy ( NIRS ) was used to monitor CBF and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated-haemoglobin , in the frontal cortex throughout . The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence . Dietary nitrate modulated the hemodynamic response to task performance , with an initial increase in CBF at the start of the task period , followed by consistent reductions during the least dem and ing of the three tasks utilised . Cognitive performance was improved on the serial 3s subtraction task . These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance , and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function Nitric oxide alters gastric blood flow , improves vascular function , and mediates glucose uptake within the intestines and skeletal muscle . Dietary nitrate , acting as a source of nitric oxide , appears to be a potential low-cost therapy that may help maintain glucose homeostasis . In a r and omized , double-blind , placebo-controlled crossover study , 31 young and older adult participants had a st and ardized breakfast , supplemented with either nitrate-rich beetroot juice ( 11.91 mmol nitrate ) or nitrate-depleted beetroot juice as placebo ( 0.01 mmol nitrate ) . MRI was used to assess apparent diffusion coefficient ( ADC ) , portal vein flux , and velocity . Plasma glucose , incretin , and C-peptide concentrations and blood pressure were assessed . Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo , beetroot juice result ed in a significant elevation in plasma nitrate and plasma nitrite concentration . No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC , or portal vein flux . There was an interaction effect in the young adults between visits for portal vein velocity . Nitrate supplementation did not reduce plasma glucose , active GLP-1 , total GLP-1 , or plasma C-peptide concentrations for the young or older adult cohorts . Despite a significant elevation in plasma nitrite concentration following an acute dose of ( 11.91 mmol ) nitrate , there was no effect on hepatic blood flow , plasma glucose , C-peptide , or incretin concentration in healthy adults INTRODUCTION Dietary nitrate ( NO3- ) supplementation serves as an exogenous source of nitrite ( NO2- ) and nitric oxide ( NO ) through the NO3- - NO2- - NO pathway , and may improve vascular functions during normoxia . The effects of NO3- supplementation in healthy lowl and ers during hypobaric hypoxia are unknown . PURPOSE Determine the effect of acute oral NO3-supplementation via beetroot juice ( BJ ) on endothelial function ( flow mediated dilation ; FMD ) in lowl and ers at 3700 m. METHODS FMD was measured using ultrasound and Doppler in the brachial artery of 11 healthy subjects ( 4 females , age 25 ± 5 yrs ; height 1.8 ± 0.1 m , weight 72 ± 10 kg ) sojourning to high altitude . In a r and omized , double-blinded crossover study design , FMD was measured 3 h after drinking BJ ( 5.0 mmol NO3- ) and placebo ( PL ; 0.003 mmol NO3- ) supplementation at 3700 m , with a 24-h wash out period between tests . FMD was also measured without any BJ supplementation pre-trek at 1370 m , after 5 days at 4200 m and upon return to 1370 m after 4 weeks of altitude exposure ( above 2500 m ) . The altitude exposure was interrupted by a decent to lower altitude where subjects spent two nights at 1370 m before returning to altitude again . RESULTS Ten subjects completed the NO3- supplementation . FMD ( mean ± SD ) pre-trek value was 6.53 ± 2.32 % at 1370 m. At 3700 m FMD was reduced to 3.84 ± 1.31 % ( p < 0.01 ) after PL supplementation but was normalized after receiving BJ ( 5.77 ± 1.14 % ( p = 1.00 ) . Eight of the subjects completed the interrupted 4-week altitude stay , and their FMD was lower at 4200 m ( FMD 3.04 ± 2.22 % ) and at post-altitude exposure to 1370 m ( FMD 3.91 ± 2.58 % ) compared to pre-trek FMD at 1370 m. CONCLUSION Acute dietary NO3-supplementation may abolish altitude-induced reduction in endothelial function , and can serve as a dietary strategy to ensure peripheral vascular function in lowl and subjects entering high altitude environments Abstract This study examined the effect of dietary supplementation with inorganic nitrate ( ) on markers of contractile function in human knee extensors . In a double-blinded , r and omized cross-over design , 18 ( 12 M ) healthy participants undertook four days of supplementation with either nitrate-rich beetroot juice ( NITRATE ; days 1–3 : 525 mg , day 4 : 1050 mg ) or nitrate-depleted beetroot juice ( PLACEBO ) . On the fourth day , isometric knee extension force was assessed during a series of voluntary and electrically evoked ( stimulation ) tests . In addition , muscular fatigue was examined in two separate continuous-stimulation ( 0.8 s tetanus with a 1:1 work : rest ratio for 102.4 s ) fatigue tests , one with and one without blood flow restriction . There were no differences for maximum voluntary contraction , peak twitch force , half-relaxation time and the force – frequency relationship for stimulations up to 100 Hz between the NITRATE and PLACEBO trials . No differences between trials were observed in the non-restricted fatigue test , however NITRATE was found to attenuate the decline in force during the restricted test , such that the force at the 80 s mark ( PLACEBO : 66 ± 11 vs. NITRATE 74 ± 9 % of initial force ; P = .01 ) and 102 s mark ( PLACEBO : 47 ± 8 % vs. NITRATE 55 ± 8 % ; P < .01 ) were significantly higher . These results suggest that four days of supplementation elicits peripheral responses in muscle that attenuate muscular fatigue during exhaustive exercise under hypovolemic conditions . This ergogenic action is likely attributable to improved Ca2 + h and ling in the muscle , or enhanced perfusion during ischemia Little is known about the effect of dietary nitrate on the nitrate/nitrite/nitric oxide cycle in older adults . We examined the effect of a 3-day control diet vs high-nitrate diet , with and without a high-nitrate supplement ( beetroot juice ) , on plasma nitrate and nitrite kinetics and blood pressure using a r and omized 4-period crossover controlled design . We hypothesized that the high-nitrate diet would show higher levels of plasma nitrate/nitrite and lower blood pressure compared with the control diet , which would be potentiated by the supplement . Participants were 8 normotensive older men and women ( 5 female , 3 male , 72.5 ± 4.7 years old ) with no overt disease or medications that affect nitric oxide metabolism . Plasma nitrate and nitrite levels and blood pressure were measured before and hourly for 3 hours after each meal . The mean daily changes in plasma nitrate and nitrite were significantly different from baseline for both control diet + supplement ( P < .001 and P = .017 for nitrate and nitrite , respectively ) and high-nitrate diet + supplement ( P = .001 and P = .002 ) , but not for control diet ( P = .713 and P = .741 ) or high-nitrate diet ( P = .852 and P = .500 ) . Blood pressure decreased from the morning baseline measure to the three 2-hour postmeal follow-up time points for all treatments , but there was no main effect for treatment . In healthy older adults , a high-nitrate supplement consumed at breakfast elevated plasma nitrate and nitrite levels throughout the day . This observation may have practical utility for the timing of intake of a nitrate supplement with physical activity for older adults with vascular dysfunction We investigated the effects of dietary nitrate ( NO3 ( - ) ) supplementation on the concentration of plasma nitrite ( [ NO2 ( - ) ] ) , oxygen uptake ( V̇o2 ) kinetics , and exercise tolerance in normoxia ( N ) and hypoxia ( H ) . In a double-blind , crossover study , 12 healthy subjects completed cycle exercise tests , twice in N ( 20.9 % O2 ) and twice in H ( 13.1 % O2 ) . Subjects ingested either 140 ml/day of NO3 (-)-rich beetroot juice ( 8.4 mmol NO3 ; BR ) or NO3 (-)-depleted beetroot juice ( PL ) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [ NO2 ( - ) ] was significantly elevated in H-BR and N-BR compared with H-PL ( P < 0.01 ) and N-PL ( P < 0.01 ) . The rate of decline in plasma [ NO2 ( - ) ] was greater during severe-intensity exercise in H-BR [ -30 ± 22 nM/min , 95 % confidence interval ( CI ) ; -44 , -16 ] compared with H-PL ( -7 ± 10 nM/min , 95 % CI ; -13 , -1 ; P < 0.01 ) and in N-BR ( -26 ± 19 nM/min , 95 % CI ; -38 , -14 ) compared with N-PL ( -1 ± 6 nM/min , 95 % CI ; -5 , 2 ; P < 0.01 ) . During moderate-intensity exercise , steady-state pulmonary V̇o2 was lower in H-BR ( 1.91 ± 0.28 l/min , 95 % CI ; 1.77 , 2.13 ) compared with H-PL ( 2.05 ± 0.25 l/min , 95 % CI ; 1.93 , 2.26 ; P = 0.02 ) , and V̇o2 kinetics was faster in H-BR ( τ : 24 ± 13 s , 95 % CI ; 15 , 32 ) compared with H-PL ( 31 ± 11 s , 95 % CI ; 23 , 38 ; P = 0.04 ) . NO3 ( - ) supplementation had no significant effect on V̇o2 kinetics during severe-intensity exercise in hypoxia , or during moderate-intensity or severe-intensity exercise in normoxia . Tolerance to severe-intensity exercise was improved by NO3 ( - ) in hypoxia ( H-PL : 197 ± 28 ; 95 % CI ; 173 , 220 vs. H-BR : 214 ± 43 s , 95 % CI ; 177 , 249 ; P = 0.04 ) but not normoxia . The metabolism of NO2 ( - ) during exercise is altered by NO3 ( - ) supplementation , exercise , and to a lesser extent , hypoxia . In hypoxia , NO3 ( - ) supplementation enhances V̇o2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance . These findings may have important implication s for individuals exercising at altitude Nitrate supplementation in the form of beetroot juice has been shown to increase nitric oxide ( NO ) where nitrate can be reduced to nitrite and , subsequently , to NO through both nitric oxide synthase (NOS)-dependent and -independent pathways . We tested the hypothesis that nitrate supplementation would augment the NO component of the cutaneous vasodilatation to local skin heating in young , healthy humans . Participants reported to the lab for pre- and post-supplement local heating protocol s. Nitrate supplementation consisted of one shot ( 70 ml ) of beetroot juice ( 0.45 g nitrate ; 5mM ) for three days . Six participants were equipped with two microdialysis fibers on the ventral forearm and r and omly assigned to lactated Ringer 's ( control ) or continuous infusion of 20mM l-NAME ( NOS inhibitor ) . The control site was subsequently perfused with l-NAME once a plateau in skin blood flow was achieved to quantify NOS-dependent cutaneous vasodilatation . Skin blood flow via laser-Doppler flowmetry ( LDF ) and mean arterial pressure ( MAP ) were measured ; cutaneous vascular conductance ( CVC ) was calculated as LDF/MAP and normalized to % CVCmax . Beetroot juice reduced MAP ( Pre : 90 ± 1 mmHg vs. Post : 83 ± 1 mmHg ) and DBP ( Pre : 74 ± 2 mmHg vs. Post : 62 ± 3 mmHg ) ( P<0.05 ) . The plateau phase of the local heating response at control sites was augmented post-beetroot juice ( 91 ± 5%CVCmax ) compared to pre-beetroot juice ( 79 ± 2%CVCmax ) ( P<0.05 ) . There was no difference in the % NOS-dependent vasodilatation from pre- to post-beetroot juice . These data suggest that nitrate supplementation via beetroot juice can reduce MAP and DBP as well as augment NOS-independent vasodilatation to local heating in the cutaneous vasculature of healthy humans Dietary nitrate supplementation enhances sea level performance and may ameliorate hypoxemia at high altitude . However , nitrate may exacerbate acute mountain sickness ( AMS ) , specifically headache . This study investigated the effect of nitrate supplementation on AMS symptoms and exercise responses with 6-h hypoxia . Twenty recreationally active men [ age , 22 ± 4 yr , maximal oxygen consumption ( V̇o2max ) , 51 ± 6 ml·min-1·kg-1 , means ± SD ] completed this r and omized double-blinded placebo-controlled crossover study . Twelve participants were classified as AMS- on the basis of Environmental Symptoms Question naire [ Acute Cerebral Mountain Sickness score ( AMS-C ) ] < 0.7 in both trials , and five participants were classified as AMS+ on the basis of AMS-C ≥0.7 on placebo . Five days of nitrate supplementation ( 70-ml beetroot juice containing ~6.4 mmol nitrate daily ) increased plasma NO metabolites by 182 µM compared with placebo but did not reduce AMS or improve exercise performance . After 4-h hypoxia [ inspired O2 fraction ( [ Formula : see text ] ) = 0.124 ] , nitrate increased AMS-C and headache severity ( visual analog scale ; whole sample ∆10 [ 1 , 20 ] mm , mean difference [ 95 % confidence interval ] ; P = 0.03 ) compared with placebo . In addition , after 5-h hypoxia , nitrate increased sense of effort during submaximal exercise ( ∆7 [ -1 , 14 ] ; P = 0.07 ) . In AMS- , nitrate did not alter headache or sense of effort . In contrast , in AMS+ , nitrate increased headache severity ( ∆26 [ -3 , 56 ] mm ; P = 0.07 ) , sense of effort ( ∆14 [ 1 , 28 ] ; P = 0.04 ) , oxygen consumption , ventilation , and mean arterial pressure during submaximal exercise . On the next day , in a separate acute hypoxic exercise test ( [ Formula : see text ] = 0.141 ) , nitrate did not improve time to exhaustion at 80 % hypoxic V̇o2max In conclusion , dietary nitrate increases AMS and sense of effort during exercise , particularly in those who experience AMS . Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid in nonacclimatized individuals at altitude . NEW & NOTEWORTHY This is the first study to identify that the popular dietary nitrate supplement ( beetroot ) does not reduce acute mountain sickness ( AMS ) or improve exercise performance during 6-h hypoxia . The consumption of nitrate in those susceptible to AMS exacerbates AMS symptoms ( headache ) and sense of effort and raises oxygen cost , ventilation , and blood pressure during walking exercise in 6-h hypoxia . These data question the suitability of nitrate supplementation during altitude travel in nonacclimatized people Ingestion of vegetables rich in inorganic nitrate has emerged as an effective method , via the formation of a nitrite intermediate , for acutely elevating vascular NO levels . As such a number of beneficial effects of dietary nitrate ingestion have been demonstrated including the suggestion that platelet reactivity is reduced . In this study we investigated whether inorganic nitrate supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen . We conducted two r and omised crossover studies each in 24 ( 12 of each sex ) healthy subjects assessing the acute effects of dietary nitrate ( 250 ml beetroot juice ) or potassium nitrate capsules ( KNO3 , 8 mmol ) vs placebo control on platelet reactivity . Inorganic nitrate ingested either from a dietary source or via supplementation raised circulating nitrate and nitrite levels in both sexes and attenuated ex vivo platelet aggregation responses to ADP and , albeit to a lesser extent , collagen but not epinephrine in male but not female volunteers . These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cGMP levels . In addition , we show that nitrite reduction to NO occurs at the level of the erythrocyte and not the platelet . In summary , our results demonstrate that inorganic nitrate ingestion , whether via the diet or through supplementation , causes a modest decrease in platelet reactivity in healthy males but not females . Our studies provide strong support for further clinical trials investigating the potential of dietary nitrate as an adjunct to current antiplatelet therapies to prevent atherothrombotic complications . Moreover , our observations highlight a previously unknown sexual dimorphism in platelet reactivity to NO and intimate a greater dependence of males on the NO-soluble guanylate cyclase pathway in limiting thrombotic potential Dietary supplementation with beetroot juice ( BR ) has been shown to reduce resting blood pressure and the O(2 ) cost of submaximal exercise and to increase tolerance to high-intensity cycling . We tested the hypothesis that the physiological effects of BR were consequent to its high NO(3)(- ) content per se , and not the presence of other potentially bioactive compounds . We investigated changes in blood pressure , mitochondrial oxidative capacity ( Q(max ) ) , and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO(3)(-)-depleted BR [ placebo ( PL ) ] . After control ( nonsupplemented ) tests , nine healthy , physically active male subjects were assigned in a r and omized , double-blind , crossover design to receive BR ( 0.5 l/day , containing ∼6.2 mmol of NO(3)(- ) ) and PL ( 0.5 l/day , containing ∼0.003 mmol of NO(3)(- ) ) for 6 days . Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Q(max ) ( using (31)P-magnetic resonance spectroscopy ) on day 6 of the supplementation periods . Relative to PL , BR elevated plasma NO(2)(- ) concentration ( 183 ± 119 vs. 373 ± 211 nM , P < 0.05 ) and reduced systolic blood pressure ( 129 ± 9 vs. 124 ± 10 mmHg , P < 0.01 ) . Q(max ) was not different between PL and BR ( 0.93 ± 0.05 and 1.05 ± 0.22 mM/s , respectively ) . The O(2 ) cost of walking ( 0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR , respectively , P < 0.01 ) , moderate-intensity running ( 2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR , respectively , P < 0.01 ) , and severe-intensity running ( end-exercise O(2 ) uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL , respectively , P < 0.01 ) was reduced by BR , and time to exhaustion during severe-intensity running was increased by 15 % ( 7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR , respectively , P < 0.01 ) . In contrast , relative to control , PL supplementation did not alter plasma NO(2)(- ) concentration , blood pressure , or the physiological responses to exercise . These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO(3)(- ) content per se Nitrate-rich beetroot juice is thought to have ergogenic effects , particularly in conditions where oxygen availability is limited . Whether these effects also apply to elite athletes is currently unknown . The aim of this study was to assess the effects of beetroot juice supplementation on dynamic apnea and intermittent sprint performance in elite female water polo players . In a double-blinded , r and omized , crossover manner , the Dutch National female water polo team ( N = 14 ) was subjected to two 6-day supplementation periods ( 1 and 2 ) , with either 140 ml/day of nitrate-rich ( BR ; ∼800 mg/day nitrate ) or nitrate-depleted ( PLA ) beetroot juice . Following blood sampling on Day 6 , the athletes performed a maximal-distance front crawl swimming test without breathing ( dynamic apnea test ) . In addition , intermittent sprint performance was assessed by performing 16 swim sprints of 15 m , in a 4 × 4 block with 30-s recovery between blocks ( intermittent test ) . Distance covered during the dynamic apnea test did not differ between BR ( 49.5 ± 7.8 m ) and PLA ( 46.9 ± 9.1 m , p = .178 ) . However , when correcting for test order , the distance covered was significantly larger in BR versus PLA when BR was ingested in Period 2 ( 50.1 ± 8.5 vs. 42.8 ± 5.7 m , p = .002 ) , whereas no difference was observed when BR was ingested in Period 1 ( 48.8 ± 7.4 vs. 52.3 ± 10.4 m , p = .10 ) . The time to complete the intermittent test was not different between BR and PLA ( 316.0 ± 7.9 vs. 316.3 ± 6.9 s , p = .73 ) . In conclusion , beetroot juice supplementation does not improve intermittent performance in elite female water polo players , but there may be a potential for ergogenic effects during dynamic apnea Abstract Glaister , M , Pattison , JR , Muniz-Pumares , D , Patterson , SD , and Foley , P. Effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . J Strength Cond Res 29(1 ) : 165–174 , 2015—The aim of this study was to examine the acute supplementation effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . Using a r and omized , counterbalanced , double-blind Latin-square design , 14 competitive female cyclists ( age : 31 ± 7 years ; height : 1.69 ± 0.07 m ; body mass : 61.6 ± 6.0 kg ) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer . Approximately 2.5 hours before each trial , subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed ( placebo ) . One hour before each trial , subjects consumed a capsule containing either 5 mg·kg−1 of caffeine or maltodextrin ( placebo ) . There was a significant effect of supplementation on power output ( p = 0.001 ) , with post hoc tests revealing higher power outputs in caffeine ( 205 ± 21 W ) vs. nitrate ( 194 ± 22 W ) and placebo ( 194 ± 25 W ) trials only . Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate ( caffeine : 166 ± 12 b·min−1 vs. placebo : 159 ± 15 b·min−1 ; p = 0.02 ) , blood lactate ( caffeine : 6.54 ± 2.40 mmol·L−1 vs. placebo : 4.50 ± 2.11 mmol·L−1 ; p < 0.001 ) , and respiratory exchange ratio ( caffeine : 0.95 ± 0.04 vs. placebo : 0.91 ± 0.05 ; p = 0.03 ) . There were no effects ( p ≥ 0.05 ) of supplementation on cycling cadence , rating of perceived exertion , , or integrated electromyographic activity . The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance . In contrast , acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation OBJECTIVE There is increasing evidence for a significant effect of processed meat ( PM ) intake on cancer risk . However , refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing . Here , actual data on the intake of PM subcategories is given ; within a food-based approach we considered preservation methods , cooking methods and nutrient content for stratification , in order to address most of the aetiologically relevant hypotheses . DESIGN AND SETTING St and ardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , a prospect i ve cohort study in 27 centres across 10 European countries . SUBJECTS Subjects were 22,924 women and 13,031 men aged 35 - 74 years . RESULTS Except for the so-called ' health-conscious ' cohort in the UK , energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1 ) in women and 18.8 and 88.5 g day(-1 ) in men . Ham , salami-type sausages and heated sausages contributed most to the overall PM intake . The intake of cured ( addition of nitrate/nitrite ) PM was highest in the German , Dutch and northern European EPIC centres , with up to 68.8 g day(-1 ) in men . The same was true for smoked PM ( up to 51.8 g day(-1 ) ) . However , due to the different manufacturing practice , the highest average intake of NaNO2 through PM consumption was found for the Spanish centres ( 5.4 mg day(-1 ) in men ) as compared with German and British centres . Spanish centres also showed the highest intake of NaCl-rich types of PM ; most cholesterol- and iron-rich PM was consumed in central and northern European centres . Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres . CONCLUSIONS We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts . This predisposes EPIC to further investigate the role of PM in cancer aetiology The aim of the current study was to determine the effects of dietary nitrate ingestion on parameters of submaximal and supramaximal exercise and time trial ( TT ) performance in trained kayakers . Eight male kayakers completed four exercise trials consisting of an initial discontinuous grade d exercise test to exhaustion and three performance trials using a kayak ergometer . The performance trials were composed of 15 min of paddling at 60 % of maximum work rate , five 10-s all-out sprints , and a 1 km TT . The second and third trials were preceded by ingestion of either 70 ml nitrate-rich concentrated beetroot juice ( BR ) or tomato juice ( placebo [ PLA ] ) 3 hr before exercise using a r and omized crossover design . Plasma nitrate ( PLA : 33.8 ± 1.9 μM , BR : 152 ± 3.5 μM ) and nitrite ( PLA : 519.8 ± 25.8 , BR : 687.9 ± 20 nM ) were higher following ingestion of BR compared with PLA ( both p < .001 ) . VO2 during steady-state exercise was lower in the BR trial than in the PLA trial ( p = .010 ) . There was no difference in either peak power in the sprints ( p = .590 ) or TT performance between conditions ( PLA : 277 ± 5 s , BR : 276 ± 5 s , p = .539 ) . Despite a reduction in VO2 , BR ingestion appears to have no effect on repeated supramaximal sprint or 1 km TT kayaking performance . A smaller elevation in plasma nitrite following a single dose of nitrate and the individual variability in this response may partly account for these findings PURPOSE Dietary nitrate supplementation positively affects cardiovascular function at rest and energy metabolism during exercise in humans and has recently also been reported to markedly enhance the in vitro contractile properties of mouse fast-twitch muscle . The aim of this study was to investigate the effects of short-term nitrate supplementation on the in vivo contractile properties of the skeletal muscle and voluntary muscle function of humans . METHODS In a double-blind , r and omized , crossover design , 19 healthy untrained men ( 21 ± 3 yr ) ingested a nitrate-rich concentrated beetroot juice ( NIT ; nitrate dosage , approximately 9.7 mmol·d ) and a placebo ( PLA ) for seven consecutive days . After the last supplementation dose , force was recorded while participants completed a series of voluntary and involuntary ( electrically evoked ) unilateral isometric contractions of the knee extensors . RESULTS NIT enhanced the peak force response to low-frequency electrical stimulation , as follows : maximal twitch ( NIT , 149 ± 41 N , vs PLA , 138 ± 37 N ; P = 0.008 ; effect size , r ( ES ) = 0.56 ) and submaximal 1- to 20-Hz contractions ( 5%-10 % , ES = 0.53 - 0.63 ) . Whereas explosive ( rising phase ) force production during the first 50 ms of evoked maximal twitch and octet contractions ( eight electrical impulses at 300 Hz ) was also 3%-15 % greater after NIT compared with that after PLA ( P = 0.023 - 0.048 , ES = 0.52 - 0.59 ) , explosive voluntary force remained similar ( P = 0.510 , ES = 0.16 ) . Maximum voluntary force was also unchanged after NIT ( P = 0.539 , ES = 0.15 ) . CONCLUSIONS These results indicate that 7 d of dietary nitrate supplementation enhanced the in vivo contractile properties of the human skeletal muscle . Specifically , nitrate supplementation improved excitation-contraction coupling at low frequencies of stimulation and enhanced evoked explosive force production but did not affect maximum or explosive voluntary force production in untrained individuals Abstract Purpose : There is an ongoing debate whether highly trained athletes are less responsive to the ergogenic properties of nitrate . We assessed the effects of nitrate supplementation on plasma nitrate and nitrite concentrations and repeated-sprint performance in recreational , competitive and elite sprint athletes . Methods : In a r and omized double-blinded cross-over design , recreational cyclists ( n = 20 ) , national talent speed-skaters ( n = 22 ) and Olympic-level track cyclists ( n = 10 ) underwent two 6-day supplementation periods ; 140 mL/d nitrate-rich ( BR ; ∼800 mg/d ) and nitrate-depleted ( PLA ; ∼0.5 mg/d ) beetroot juice . Blood sample s were collected and three 30-s Wingate tests were performed . Results : Plasma nitrate and nitrite concentrations were higher following BR vs PLA ( P < .001 ) , with no differences between sport levels ( all P > .10 ) . Peak power over the three Wingates was not different between BR and PLA ( 1338 ± 30 vs 1333 ± 30 W ; P = .62 ) , and there was no interaction between treatment ( BR-PLA ) and Wingate number ( 1 - 2 - 3 ; P = .48 ) . Likewise , mean power did not differ between BR and PLA ( P = .86 ) . In contrast , time to peak power improved by ∼2.8 % following BR vs PLA ( P = .007 ) . This improvement in BR vs PLA was not different between Wingate 1 , 2 and 3 . Moreover , the effects of BR vs PLA did not differ between sport levels for any Wingate parameter ( all P > .30 ) . Conclusion : The plasma and repeated-sprint performance responses to beetroot juice supplementation do not differ between recreational , competitive and elite sprint athletes . Beetroot juice supplementation reduces time to reach peak power , which may improve the capacity to accelerate during high-intensity and sprint tasks in recreational as well as elite athletes Beetroot juice ( BR ) has been shown to reduce blood pressure ( BP ) at rest and improve several performance parameters during exercise . However , the effect of BR on BP during submaximal exercise has not been investigated and its effects on VO2max are inconclusive . The purpose of this study was to investigate the effects of BR on VO2max and BP during submaximal exercise . 20 healthy , recreationally trained volunteers ( age 21.8±2.35 years , weight 75.10±10.62 kg , height 177.4±6.39 cm ) participated in this study , which had a double-blind placebo controlled r and omized crossover design . Participants supplemented with either 237 ml servings of placebo or 70 ml BR servings ( nitrate concentration of 6.4 mmol/day ) for 7 days . Participants completed a ramp treadmill protocol to determine VO2max . BP was taken at 70 % max heart rate calculated using the Karvonen method . There was no significant change in VO2max after BR supplementation ( 51.07±6.12 ml/kg/min ) versus placebo ( 50.46±6.06 ml/kg/min ) , t(19)=1.41 , p=0.17 . There was no significant change in either systolic BP after BR supplementation ( 180.65±23.37 mm Hg ) versus placebo ( 177.65±22.07 mm Hg ) , t(19)=0.49 , p=0.63 , or in diastolic BP after BR ( 92.90±18.89 mm Hg ) versus placebo ( 90.75±17.73 mm Hg ) , t(19)=0.51 , p=0.62 . BR did not affect VO2max , nor did it affect BP during submaximal exercise As a nitric oxide precursor , beetroot juice ( BJ ) is known to enhance high-intensity exercise performance ( 80–100 % VO2max ) yet its impacts on higher intensity sprint exercise ( > 100 % VO2max ) remain to be established . This study sought to examine the effects of BJ supplementation on performance and subsequent fatigue during an all-out sprint exercise . Using a r and omized cross-over , double-blind , placebo-controlled design , 15 healthy resistance-trained men ( 22.4 ± 1.6 years ) ingested 70 mL of either BJ or placebo . Three hours later , participants undertook a 30-s all-out Wingate test . Before and after the sprint exercise and at 30 s and 180 s post-exercise , three countermovement jumps ( CMJ ) were performed and blood lactate sample s were obtained . Compared to placebo , BJ consumption improved peak ( placebo vs. BJ , 848 ± 134 vs. 881 ± 135 W ; p = 0.049 ) and mean ( 641 ± 91 vs. 666 ± 100 W ; p = 0.023 ) power output and also reduced the time taken to reach Wpeak in the Wingate test ( 8.9 ± 1.4 vs. 7.3 ± 0.9 s ; p = 0.003 ) . No differences were detected in the fatigue index . In addition , while over time CMJ height and power diminished ( ANOVA p < 0.001 ) and blood lactate levels increased ( ANOVA p < 0.001 ) , no supplementation effect was observed . Our findings indicate that while BJ supplementation improved performance at the 30-s cycling sprint , this improvement was not accompanied by differences in fatigue during or after this type of exercise Background Beetroot juice ( BJ ) is classified as a high-level supplement for improving sports performance . There is some controversy over the benefits of BJ supplementation for endurance exercise performance , especially when referring to well-trained athletes . This study examines the effects of acute BJ supplementation on cardioventilatory responses , exercise economy/efficiency , slow component of oxygen uptake , time trial performance , blood lactate , energy consumption , and carbohydrate and fat oxidation . Methods Twelve well-trained , male triathletes ( aged 21–47 yr ) were assigned in a r and omized , double-blind , crossover design to receive 70 ml of BJ ( 6.5 mmol NO3− ) or placebo ( PL ) . Three hours after taking the supplement , participants completed an endurance test on a cycle ergometer at a constant work rate ( W ) corresponding to first ventilatory threshold ( VT1 ) ( 30 min ) and second ventilatory threshold ( VT2 ) time trial ( ~ 15 min ) . Results Maximal oxygen uptake was 54.78 ± 3.13 mL·min− 1·kg− 1 , and gross efficiency was > 22 % at each load intensity and experimental condition . No significant interaction effect ( supplement*intensity ) was observed on any of the cardioventilatory variables , efficiency/economy , VT2 time trial , energy expenditure , carbohydrate oxidation and fat oxidation ( p > 0.05 ) . Conclusion Our findings do not support an improvement in the variables examined in response to acute BJ supplementation . Probably , higher doses are needed for improving time trial performance in male triathletes during a cycle ergometer test conducted at a load intensity equivalent to the first and second ventilatory threshold Purpose : Dietary nitrate supplementation has been reported to improve performance in kayaking and rowing exercise , which m and ate significant recruitment of the upper-body musculature . Because the effect of dietary nitrate supplementation on swimming performance is unclear , the purpose of this study was to assess the effect of dietary nitrate supplementation on 100-m and 200-m swimming freestyle time-trial ( TT ) performance . Methods : In a double-blind , r and omized crossover design , 10 moderately trained swimmers underwent 2 separate 3-d supplementation periods , with a daily dose of either 140 mL nitrate-rich ( ∼800 mg/d nitrate ) or nitrate-depleted ( PLA ) beetroot juice ( BRJ ) . After blood sampling on day 3 , the swimmers performed both 200-m and 100-m freestyle swimming TTs , with 30 min recovery between trials . Results : Plasma nitrite concentration was greater after BRJ relative to PLA consumption ( 432 [ 203 ] nmol/L , 111 [ 56 ] nmol/L , respectively , P = .001 ) . Systolic blood pressure was lowered after BRJ compared with PLA supplementation ( 114 [ 10 ] , 120 [ 10 ] mm Hg , respectively P = .001 ) , but time to complete the 200-m ( BRJ 152.6 [ 14.1 ] s , PLA 152.5 [ 14.1 ] s ) and 100-m ( BRJ 69.5 [ 7.2 ] s , PLA 69.4 [ 7.4 ] s ) freestyle swimming TTs was not different between BRJ and PLA ( P > .05 ) . Conclusions : Although 3 d of BRJ supplementation increased plasma nitrite concentration and lowered blood pressure , it did not improve 100-m and 200-m swimming TT performance . These results do not support an ergogenic effect of nitrate supplementation in moderately trained swimmers , at least for 100-m and 200-m freestyle swimming performance Purpose Dietary nitrate ( NO3− ) has repeatedly been shown to improve endurance and intermittent , high-intensity events in temperate conditions . However , the ergogenic effects of dietary NO3− on intermittent exercise performance in hot conditions have yet to be investigated . Methods In a r and omised , counterbalanced , double-blind crossover study , 12 recreationally trained males ingested a nitrate-rich beetroot juice shot ( BRJ ) ( 6.2 mmol NO3− ) or a nitrate-depleted placebo ( PLA ) ( < 0.004 mmol NO3− ) 3 h prior to an intermittent sprint test ( IST ) in temperate ( 22 ° C , 35 % RH ) and hot conditions ( 30 ° C , 70 % RH ) . The cycle ergometer IST consisted of twenty maximal 6 s sprints interspersed by 114 s of active recovery . Work done , power output , heart rate and RPE were measured throughout ; tympanic temperature was measured prior to and upon completion . Results There were no significant effects of supplement on sprint performance in either temperate or hot , humid conditions ( p > 0.05 ) . There was a reduced peak ( BRJ : 659 ± 100W vs. PLA : 693 ± 139W ; p = 0.056 ) and mean power ( BRJ : 543 ± 29W vs. PLA : 575 ± 38W ; p = 0.081 ) following BRJ compared to PLA in the hot and humid condition , but this was not statistically significant . There was no effect of supplement on total work done irrespective of environmental condition . However , ~ 75 % of participants experienced performance decreases following BRJ in the hot and humid environment . No differences were observed between trials for tympanic temperature measured at the conclusion of the exercise trial . Conclusion In conclusion , an acute dose of inorganic dietary NO3− does not improve repeated-sprint performance in either temperate , or hot and humid conditions Abstract This study investigated the effects of acute and chronic beetroot juice ( BRJ ) supplementation on submaximal exercise oxygen uptake ( VO 2 ) , time trial ( TT ) performance , and contractile properties of the plantar flexors in females . Study 1 : Using a double blind , r and omized , crossover design , 12 recreationally active females using hormonal contraceptives supplemented acutely ( 2.5 h ) and chronically ( 8 days ) with 280 mL BRJ/d ( ~26 mmoles nitrate [ NO3− ] ) or a NO3−‐free placebo ( PLA ) . On days 1 and 8 , participants cycled for 10 min at 50 % and 70 % VO 2peak and completed a 4 kJ/kg body mass TT . Plasma [ NO3− ] and nitrite ( [ NO2 − ] ) increased significantly following BRJ supplementation versus PLA . There was no effect of BRJ supplementation on VO 2 at 50 % or 70 % VO 2peak , or TT performance . Study 2 : 12 recreationally active females ( n = 7 from Study 1 ) using hormonal contraceptives participated in a baseline visit and were supplemented acutely ( 2.5 h ) and chronically ( 8 days ) with 280 mL BRJ/d . Maximum voluntary strength ( MVC ) of the plantar flexors was assessed and a torque‐frequency curve performed . BRJ had no effect on MVC , voluntary activation , peak twitch torque , time to peak torque , or half relaxation time . Following both acute ( 46.6 ± 4.9 % of 100 Hz torque ) and chronic ( 47.2 ± 4.4 % ) supplementation , 10 Hz torque was significantly greater compared to baseline ( 32.9 ± 2.6 % ) . In summary , BRJ may not be an effective ergogenic aid in recreationally active females as it did not reduce submaximal exercise VO 2 or improve aerobic TT performance despite increasing low frequency torque production PURPOSE Consumption of nitrate-rich beetroot juice can lower blood pressure in peripheral as well as central arteries and may exert additional hemodynamic benefits ( e.g. reduced aortic wave reflections ) . The specific influence of nitrate supplementation on arterial pressures and aortic wave properties in postmenopausal women , a group that experiences accelerated increases in these variables with age , is unknown . Accordingly , the primary aim of this study was to determine the effect of consuming nitrate-rich beetroot juice on resting brachial and aortic blood pressures ( BP ) and pulse wave characteristics in a group of healthy postmenopausal women , in comparison to a true ( nitrate-free beetroot juice ) placebo . METHODS Brachial ( oscillometric cuff ) and radial ( SphygmoCor ) pressures and derived-aortic waveforms were measured during supine rest in thirteen healthy postmenopausal women ( 63 ± 1 yr ) before and 100 min after consumption of 140 ml of either nitrate-rich ( 9.7 mmol , 0.6 gm NO3- ) or nitrate-depleted beetroot juice on r and omized visits approximately 10 days apart ( cross-over design ) . Ten young premenopausal women ( 22 ± 1 yr ) served as a reference ( non-supplemented ) cohort . RESULTS Brachial and derived-aortic variables showed the expected age-associated differences in these women ( all p < 0.05 ) . In post-menopausal women , nitrate supplementation reduced ( p < 0.05 vs. placebo visit ) brachial systolic BP ( BRnitrate -4.9 ± 2.1 mmHg vs BRplacebo + 1.1 ± 1.8 mmHg ) , brachial mean BP ( BRnitrate -4.1 ± 1.7 mmHg vs BRplacebo + 0.9 ± 1.3 mmHg ) , aortic systolic BP ( BRnitrate -6.3 ± 2.0 mmHg vs BRplacebo + 0.5 ± 1.7 mmHg ) and aortic mean BP ( BRnitrate -4.1 ± 1.7 mmHg vs BRplacebo + 0.9 ± 1.3 mmHg ) , and increased pulse pressure amplification ( BRnitrate + 4.6 ± 2.0 % vs BRplacebo + 0.7 ± 2.5 % , p = 0.04 ) , but did not alter aortic pulse wave velocity or any other derived-aortic variables ( e.g. , augmentation pressure or index ) . CONCLUSIONS Dietary nitrate supplementation favorably modifies aortic systolic and mean blood pressure under resting conditions in healthy postmenopausal women . Acute supplementation of nitrate does not , however , appear to restore indices of aortic stiffness in this group . Future work should evaluate chronic , long-term effects of this non-pharmacological supplement Dietary nitrate ( NO3- ) supplementation via beetroot juice ( BR ) is known to improve endurance performance in untrained and moderately trained individuals . However , conflicting results exist in well-trained individuals . Evidence suggests that the effects of NO3- are augmented during conditions of reduced oxygen availability ( e.g. , hypoxia ) , thereby increasing the probability of performance improvements for well-trained athletes in hypoxia vs. normoxia . This r and omized , double-blinded , counterbalanced-crossover study examined the effects of 7 days of BR supplementation with 12.4 mmol NO3- per day on 10-km cycling time trial ( TT ) performance in 12 well-trained cyclists in normoxia ( N ) and normobaric hypoxia ( H ) . Linear mixed models for repeated measures revealed increases in plasma NO3- and NO2- after supplementation with BR ( both p < 0.001 ) . Further , TT performance increased with BR supplementation ( ∼1.6 % , p < 0.05 ) , with no difference between normoxia and hypoxia ( p = 0.92 ) . For respiratory variables there were significant effects of supplementation on VO2 ( p < 0.05 ) and VE ( p < 0.05 ) such that average VO2 and VE during the TT increased with BR , with no difference between normoxia and hypoxia ( p ≥ 0.86 ) . We found no effect of supplementation on heart rate , oxygen saturation or muscle oxygenation during the TT . Our results provide new evidence that chronic high-dose NO3- supplementation improves cycling performance of well-trained cyclists in both normoxia and hypoxia Dietary inorganic nitrate in beetroot can act as a source of nitric oxide and has been reported to lower brachial blood pressure ( BP ) . This study examined the effect of inorganic nitrate in beetroot juice on aortic ( central ) BP acutely and over the subsequent 24-h period . A double blind , r and omized , placebo-controlled crossover trial was performed in fifteen healthy , normotensive men and women ( age 22–40 years ) . Participants were r and omized to receive beetroot juice containing nitrate ( 6.5–7.3 mmol ) or placebo beetroot juice from which nitrate had been removed ( < 0.06 mmol nitrate ) . Effects on aortic systolic BP were measured at 30 min ( primary endpoint ) , 60 min and over a subsequent 24 h period using an ambulatory BP monitor . Carotid-femoral pulse wave velocity ( cfPWV ) was also measured at 30 min . Following a washout period , the procedure was repeated within 7 days with crossover to the opposite arm of the trial . Compared with placebo , ingestion of beetroot juice containing nitrate lowered aortic systolic BP at 30 min by 5.2 ( 1.9–8.5 ) mmHg [ mean ( 95 % confidence interval ) ; p < 0.01 ] . A smaller effect on aortic systolic BP was observed at 60 min . There were minimal effects on brachial BP or cfPWV . Effects on aortic systolic BP were not sustained over the subsequent 24 h and there were no effects on other hemodynamic parameters during ambulatory monitoring . A single dose of beetroot juice containing nitrate lowers aortic BP more effectively than brachial BP in the short term , but the effects are comparatively short-lived and do not persist over the course of the same day Purpose This study investigated the effects of chronic 3-day beetroot juice ( BRJ ) supplementation on maximum oxygen uptake ( VO2max ) , velocity associated with VO2max(vVO2max ) , and peak velocity ( Vpeak ) in recreational runners . Methods Thirteen male recreational runners ( age 28.2 ± 3.0 years , height 176.8 ± 0.1 cm , body mass 74.4 ± 9.5 kg ) performed four tests on a treadmill in a r and omized , double-blind , crossover design : two maximum incremental tests to determine VO2max and vVO2max , and two tests to determine Vpeak . Trials were performed following 3 days of supplementation of NO3−-rich BRJ in natura ( 8.4 mmol NO3− day− 1 ) or BRJ NO3−-depleted placebo ( 0.01 mmol NO3− day− 1 ) , with the last dose being ingested 2 h before each test . During the tests , maximum heart rate ( HRmax ) , maximal rating of perceived exertion ( RPEmax ) , pre- and post-test glucose concentrations ( Glucpre , Glucpost ) , and peak blood lactate concentration were determined . Results VO2max was higher following BRJ vs PLA ( 46.6 ± 6.4 vs 45.1 ± 5.8 mL kg− 1 min− 1 ; P = 0.022 ) , as well as vVO2max ( 14.5 ± 0.8 vs 13.9 ± 1.0 km h− 1P = 0.024 ) and Vpeak ( 15.5 ± 1.1 vs 15.2 ± 1.2 km h− 1P = 0.038 ) , with no differences in the other variables . Conclusion Consumption of NO3−-rich BRJ in natura ( 8.4 mmol NO3− day− 1 ) once per day for 3 days improved VO2max , vVO2max and Vpeak in recreational runners without changing the other analyzed variables ABSTRACT This study evaluated the chronic effects of nitrate ( NO3− ) ingestion over three days , on 40 km TT performance in 11trained cyclists ( VO2max : 60.8 ± 7.4 ml.kg−1.min−1 ; age : 36 ± 9 years ; height : 1.80 ± 0.06 m ; body mass : 87.2 ± 12.0 kg ) . Utilising a double-blind r and omised cross-over design , participants completed three 40 km TT on a Velotron ® ergometer following the ingestion of either a 140 ml of “ BEET It sport ® ” NO3− shot containing 12.8 mmol or 800 mg of NO3− , a placebo drink or nothing ( control ) . Performance , oxygen consumption ( VO2 ) , blood bicarbonate ( HCO3- ) , pH and lactate ( BLa ) and ratings of perceived exertion ( RPE ) were measured every 10 km throughout the TT . The present findings show that NO3− ingestion had no effect on TT performance ( NO3− : 4098.0 ± 209.8 vs. Placebo : 4161.9 ± 263.3 s , p = 0.296 , ES = 0.11 ) , or VO2 ( p = 0.253 , ES = 0.13 ) . Similarly , blood lactate and RPE were also unaffected by the experimental conditions ( p = 0.522 , ES = 0.06 ; p = 0.085 , ES = 0.30 ) respectively . Therefore , these results suggest that a high dose of NO3− over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists Consumption of inorganic nitrate ( NO3(- ) ) is known to enhance endurance exercise performance in recreationally trained subjects . Here we report the effect on a high-intensity performance task in national-level cyclists . The performance test consisted of 2 cycle ergometer time trials of 4 min duration with 75 min between trials . In a r and omized crossover design , 26 cyclists performed the test under the following 4 conditions ( each separated by a 6-day washout ) : consumption of 70 mL of nitrate-rich beetroot juice at 150 min or 75 min before the first time trial , addition of a 35 mL " top-up dose " following the first time trial in the 150 min condition , and consumption of a placebo . A linear mixed model with adjustments for learning effects and athlete fitness ( peak incremental power ) was used to estimate effects on mean power , with probabilistic inferences based on a smallest important effect of 1.0 % . Peak plasma nitrite ( NO2(- ) ) concentration was greatest when nitrate was taken 75 min before the first time trial . Relative to placebo , the mean effect of all 3 nitrate treatments was unclear in the first time trial ( 1.3 % , 90 % confidence limits : ±1.7 % ) , but possibly harmful in the second time trial ( -0.3 % , ±1.6 % ) . Differences between nitrate treatments were unclear , as was the estimate of any consistent individual response to the treatments . Allowing for sampling uncertainty , the effect of nitrate on performance was less than previous studies . Under the conditions of our experiment , nitrate supplementation may be ineffective in facilitating high-intensity exercise in competitive athletes The present study was design ed to provide further insight into the mechanistic basis for the improved exercise tolerance following dietary nitrate supplementation . In a r and omized , double-blind , crossover design , twelve recreationally active males completed a dynamic time-to-exhaustion test of the knee extensors after 5 days of consuming both nitrate-rich ( NITRATE ) and nitrate-depleted beetroot juice ( PLACEBO ) . Participants who improved their time-to-exhaustion following NITRATE performed a time-matched trial corresponding to the PLACEBO exercise duration with another 5 days of dietary nitrate supplementation . This procedure was performed to obtain time-matched exercise trials with ( NITRATEtm ) and without dietary nitrate supplementation ( PLACEBO ) . Neuromuscular tests were performed before and after each time-matched condition . Muscle fatigue was quantified as percentage change in maximal voluntary torque from pre- to post-exercise ( ΔMVT ) . Changes in voluntary activation ( ΔVA ) and quadriceps twitch torque ( ΔPS100 ) were used to quantify central and peripheral factors of muscle fatigue , respectively . Muscle oxygen saturation , quadriceps muscle activity as well as perceptual data ( i.e. , perception of effort and leg muscle pain ) were recorded during exercise . Time-to-exhaustion was improved with NITRATE ( 12:41 ± 07:18 min ) compared to PLACEBO ( 09:03 ± 04:18 min ; P = 0.010 ) . NITRATEtm result ed in both lower ΔMVT and ΔPS100 compared to PLACEBO ( P = 0.002 ; P = 0.001 , respectively ) . ΔVA was not different between conditions ( P = 0.308 ) . NITRATEtm result ed in reduced perception of effort and leg muscle pain . Our findings extend the mechanistic basis for the improved exercise tolerance by showing that dietary nitrate supplementation ( i ) attenuated the development of muscle fatigue by reducing the exercise-induced impairments in contractile muscle function ; and ( ii ) lowered the perception of both effort and leg muscle pain during exercise Aging is often associated with reduced leg blood flow , increased arterial stiffness , and endothelial dysfunction , all of which are related to declining nitric oxide ( NO ) bioavailability . Flow mediated dilatation ( FMD ) and passive leg movement ( PLM ) hyperaemia are two techniques used to measure NO-dependent vascular function . We hypothesised that acute dietary nitrate ( NO3− ) supplementation would improve NO bioavailability , leg FMD , and PLM hyperaemia . Fifteen healthy older men ( 69 ± 4 years ) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice ( 800 mg NO3− ) or placebo ( NO3−-depleted beetroot juice ) in a r and omised , double blind , cross-over design study . Plasma nitrite ( NO2− ) and NO3− , blood pressure ( BP ) , augmentation index ( AIx75 ) , pulse wave velocity ( PWV ) , FMD of the superficial femoral artery , and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3− and placebo . Placebo had no effect but NO3− led to an 8.6-fold increase in plasma NO2− , which was accompanied by an increase in FMD ( NO3− : + 1.18 ± 0.94 % vs. placebo : 0.23 ± 1.13 % , p = 0.002 ) , and a reduction in AIx75 ( NO3− : −8.7 ± 11.6 % vs. placebo : −4.6 ± 5.5 % , p = 0.027 ) . PLM hyperaemia , BP , and PWV were unchanged during both trials . This study showed that a dose of dietary NO3− improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD . These findings provide insight into the specific central and peripheral vascular responses to dietary NO3− supplementation in older adults Consumption of nitrate-rich beetroot juice ( BRJ ) by athletes induces a number of beneficial physiological health effects , which are linked to the formation of nitric oxide ( NO ) from nitrate . However , following a secondary pathway , NO may also lead to the formation of N-nitroso compounds ( NOCs ) , which are known to be carcinogenic in 39 animal species . The extent of the formation of NOCs is modulated by various other dietary factors , such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion . In a r and omized , controlled trial , 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week . A significant increase of urinary apparent total N-nitroso Compounds ( ATNC ) was found after one dose ( 5 to 47 nmol/mmol : p < 0.0001 ) and a further increase was found after seven consecutive doses of BRJ ( 104 nmol/mmol : p < 0.0001 ) . Vitamin C supplementation inhibited ATNC increase after one dose ( 16 compared to 72 nmol/mmol , p < 0.01 ) , but not after seven daily doses . This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs . In order to protect athlete ’s health , it is therefore important to be cautious with chronic use of BRJ to enhance sports performances Abstract Objective : Nitrate (NO3−)-rich beetroot juice ( BR ) is recognized as an ergogenic supplement that improves exercise tolerance during submaximal to maximal intensity exercise in recreational and competitive athletes . A recent study has investigated the effectiveness of BR on exercise performance during supramaximal intensity intermittent exercise ( SIE ) in Olympic-level track cyclists , but studies conducted in elite endurance athletes are scarce . The present study aim ed to determine whether BR supplementation enhances the tolerance to SIE in elite endurance athletes . Methods : Eleven elite endurance athletes ( age : 21.7 ± 3.7 years , maximal oxygen uptake 71.1 ± 5.2 mL·kg−1·min−1 ) performed an SIE test until exhaustion following either a 3-day BR supplementation ( 340 mg/d ) or a placebo ( PL ) supplementation ( < 2.5 mg/d ) in a r and omized , single blind , placebo-controlled , and crossover study . The exercise test consisted of 15-second cycling exercise bouts at 170 % of the maximal aerobic power interspersed with 30-second passive recovery periods . Gas exchange was measured during SIE tests as local muscle O2 delivery and extraction were assessed by near infrared spectroscopy . Results : The number of repetitions completed was not significantly different between BR ( 13.9 ± 4.0 reps ) and PL conditions ( 14.2 ± 4.5 reps ) . BR supplementation did not affect oxygen uptake ( ) during SIE tests ( BR : 3378.5 ± 681.8 mL·min−1 , PL : 3466.1 ± 505.3 mL·min−1 ) . No significant change in the areas under curves was found for local muscle total hemoglobin ( BR : 6816.9 ± 1463.1 arbitrary units ( a.u . ) , PL : 6771.5 ± 3004.5 a.u . ) and deoxygenated hemoglobin ( BR : 6619.7 ± 875.8 a.u . , PL : 6332.7 ± 1336.8 a.u . ) during time-matched work + recovery periods from SIE tests following BR supplementation . Conclusions : BR supplementation does not enhance the tolerance to SIE in elite endurance athletes and affects neither nor local muscle O2 delivery and extraction Dietary nitrate ( NO3- ) supplementation has been shown to reduce resting blood pressure ( BP ) . However , the mechanism(s ) responsible for the reduction in BP has not been identified . Dietary NO3- supplementation may increase nitric oxide ( NO ) bioavailability and NO has been shown to inhibit sympathetic vasoconstriction . Therefore , the purpose of this study was to investigate the hypothesis that acute dietary NO3- supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise . In a double-blind r and omized crossover design , 12 men performed a cold-pressor test ( CPT ) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of NO3- rich beetroot juice ( ~12.9 mmol NO3- ) or a NO3 - -depleted placebo ( ~0.13 mmol NO3- ) . Venous blood was sample d before and 2.5 hours after consumption of beetroot juice to measure total plasma nitrite/nitrate [ NOx ] . BP was measured by Finometer . Leg blood flow ( LBF ) was measured at the femoral artery via Doppler ultrasound and leg vascular conductance ( LVC ) was calculated . Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT . Total plasma [ NOx ] was greater ( p<0.001 ) in the NO3- compared to the placebo condition . However , blood pressure and plasma catecholamines were not different ( p>0.05 ) between NO3- and placebo conditions at rest or during exercise . Sympathetic vasoconstrictor responsiveness ( Δ % LVC ) was not different ( p>0.05 ) between NO3- and placebo conditions at rest or during moderate- and heavy-intensity exercise . These data demonstrate that acute dietary nitrate supplementation does not alter sympathetic vasoconstrictor responsiveness at rest and during exercise in young healthy males Background Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds ( NOCs ) , which are known to be carcinogenic in animals . Humans can be exposed to nitrate via consumption of drinking water and diet , especially green leafy vegetables and cured meat . The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly . Therefore , in the present pilot study , we examined the effect of nitrate from drinking water , and its interaction with the consumption of white and processed red meat , on the endogenous formation of NOCs , taking into account the intake of vitamin C , a nitrosation inhibitor . Methods Twenty healthy subjects were r and omly assigned to two groups consuming either 3.75 g/kg body weight ( maximum 300 g per day ) processed red meat or unprocessed white meat per day for two weeks . Drinking water nitrate levels were kept low during the first week ( < 1.5 mg/L ) , whereas in week 2 , nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight . At baseline , after 1 and 2 weeks , faeces and 24 h urine sample s were collected for analyses of nitrate , apparent total N-nitroso compounds ( ATNC ) , compliance markers , and genotoxic potential in human colonic Caco-2 cells . Results Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types . Furthermore , levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat ( i.e. 1-Methylhistidine levels ) , or unprocessed white meat ( i.e. 3-Methylhistidine ) . ATNC levels significantly increased during the high drinking water nitrate period , which was more pronounced in the processed red meat group . Genotoxicity in Caco-2 cells exposed to faecal water result ed in increased genotoxicity after the interventions , but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat . Furthermore , a positive correlation was found between the ratio of nitrate/vitamin C intake ( including drinking water ) and the level of ATNC in faecal water of subjects in the processed red meat group , but this was not statistically significant . Conclusions Drinking water nitrate significantly contributed to the endogenous formation of NOC , independent of the meat type consumed . This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC.Trial registration Dutch Trialregister : 29707 . Registered 19th of October 2018 . Retrospectively registered The present study examined if an elevated nitrate intake would improve VO(2 ) kinetics , endurance , and repeated sprint capacity in elite endurance athletes . Ten highly trained cyclists ( 72 ± 4 mL O(2 ) /kg/min , mean ± st and ard deviation ) underwent testing for VO(2 ) kinetics ( 3 × 6 min at 298 ± 28 W ) , endurance ( 120 min preload followed by a 400-kcal time trial ) , and repeated sprint capacity ( 6 × 20 s sprints , recovery 100 s ) during two 6-day periods in r and omized order with a daily ingestion of either 0.5 L beetroot ( BR ) juice to increase nitrate levels or a 0.5 L placebo ( PLA ) drink with blackcurrant juice . Plasma NOx ( nitrate + nitrite ) levels were higher ( P < 0.01 ) in BR ( 147 ± 102 and 159 ± 103 μM after 4 and 6 days of beverage intake , respectively ) compared with PLA ( 41 ± 10 and 40 ± 7 μM ) . VO(2 ) kinetics and exercise economy were the same in BR and PLA . Time-trial performance was similar with an average completion time of 18:20 and 18:37 min : s in BR and PLA , respectively , with average power outputs of 290 ± 43 W in BR and 285 ± 44 W in PLA . Peak and mean power during repeated sprinting were similar in BR and PLA . In contrast to observations in moderately trained subjects intake of BR juice had no effect on VO(2 ) kinetics and performance in elite cyclists Beetroot juice ( BR ) has been shown to lower the oxygen cost of exercise in normoxia and may have similar effects in hypoxia . We investigated the effect of BR on steady-state exercise economy and 10-km time trial ( TT ) performance in normoxia and moderate hypoxia ( simulated altitude : ~2500 m ) . Eleven trained male cyclists ( VO 2peak ≥ 60 ml · kg(-1 ) · min(-1 ) ) completed four exercise trials . Two hours before exercise , subjects consumed 70 mL BR ( ~6 mmol nitrate ) or placebo ( nitrate-depleted BR ) in a r and omized , double-blind manner . Subjects then completed a 15-min self-selected cycling warm-up , a 15-min steady-state exercise bout at 50 % maximum power output , and a 10-km time trial ( TT ) in either normoxia or hypoxia . Environmental conditions were r and omized and single-blind . BR supplementation increased plasma nitrate concentration and fraction of exhaled nitric oxide relative to PL ( p < .05 for both comparisons ) . Economy at 50 % power output was similar in hypoxic and normoxic conditions ( p > .05 ) , but mean power output was greater in the normoxic TT relative to the hypoxic TT ( p < .05 ) . BR did not affect economy , steady-state SpO2 , mean power output , or 10-km TT completion time relative to placebo in either normoxia or hypoxia ( p > .05 in all comparisons ) . In conclusion , BR did not lower the oxygen cost of steady-state exercise or improve exercise performance in normoxia or hypoxia in a small sample of well-trained male cyclists INTRODUCTION The purpose of the present study was to assess the effects of acute nitrate ( [ Formula : see text])-rich beetroot juice ( BRJ ) supplementation on peripheral oxygen saturation ( SpO2 ) , heart rate ( HR ) , and pulmonary gas exchange during submaximal static and dynamic apnea . METHODS Nine ( six males and three females ) trained apneists ( age : 39.6 ± 8.2 years , stature : 170.4 ± 11.5 cm , and body mass : 72.0 ± 11.5 kg ) performed three submaximal static apneas at 60 % , 70 % , and 80 % of the participant 's current reported personal best time , followed by three submaximal ( ∼75 % or personal best distance ) dynamic apneas following the consumption of either a 70-ml concentrated BRJ ( 7.7 mmol [ Formula : see text ] ) or a [ Formula : see text]-depleted placebo ( PLA ; 0.1 mmol [ Formula : see text ] ) in double-blind r and omized manner . HR and SpO2 were measured via fingertip pulse oximetry at the nadir , and online gas analysis was used to assess pulmonary oxygen uptake ( [ Formula : see text ] ) during recovery following breath-holds . RESULTS There were no differences ( p < .05 ) among conditions for HR ( PLA = 59 ± 11 bpm and BRJ = 61 ± 12 bpm ) , SpO2 ( PLA = 83 % ± 14 % and BRJ = 84 % ±9 % ) , or [ Formula : see text ] ( PLA = 1.00 ± 0.22 L/min and BRJ = 0.97 ± 0.27 L/min ) . CONCLUSION The consumption of 7.7 mmol of beetroot juice supplementation prior to a series of submaximal static and dynamic apneas did not induce a significant change in SpO2 , HR , and [ Formula : see text ] when compared with placebo . Therefore , there is no apparent physiological response that may benefit free divers as a result of the supplementation PURPOSE Dietary nitrate supplementation with beetroot juice ( BR ) has received widespread attention as an ergogenic aid . However , recent evidence in well-trained cyclists has not consistently reported improved cycling economy or performance . The present study examined the effects of acute and chronic BR supplementation on V˙O2 during submaximal running and 1500-m time trial ( TT ) performance of elite distance runners . METHODS Eight male 1500-m runners ( V˙O2peak , 80 ± 5 mL·kg·min ; 1500-m personal best , 3:56 ± 9 s ) participated in this study . In a r and omized , double-blind , crossover design , subjects supplemented with BR or a nitrate-free BR placebo ( PL ) for 8 d separated by at least 1 wk . On days 1 ( acute ) and 8 ( chronic ) , subjects ingested 210 mL of BR ( 19.5-mmol nitrate ) or PL and completed a submaximal treadmill run and 1500-m TT on an indoor 200-m track . RESULTS Plasma nitrate increased from 37 ± 15 to 615 ± 151 μM ( acute ) and 870 ± 259 μM ( chronic ) after BR supplementation . There were no V˙O2 differences between conditions at 50 % , 65 % , and 80 % V˙O2peak ( acute PL , 4194 ± 90 mL·min ; chronic PL , 4216 ± 95 mL·min ; acute BR , 4192 ± 113 mL·min ; chronic BR , 4299 ± 92 mL·min ) . The 1500-m TT was unaffected by acute or chronic BR supplementation ( acute PL , 4:10.4 min : s ± 2.5 s ; chronic PL , 4:11.4 min : s ± 2.7 s ; acute BR , 4:10.7 min : s ± 1.5 s ; chronic BR , 4:10.5 min : s ± 2.2 s ) . However , two subjects improved their TT performance after acute ( 5.8 and 5.0 s ) and chronic BR supplementation ( 7.0 and 0.5 s ) . CONCLUSIONS Acute and chronic BR supplementation did not reduce running V˙O2 or improve 1500-m TT performance of a group of elite distance runners , but two responders to BR were identified PURPOSE The power asymptote ( critical power [ CP ] ) and curvature constant ( W ' ) of the power- duration relationship dictate the tolerance to severe-intensity exercise . We tested the hypothesis that dietary nitrate supplementation would increase the CP and /or the W ' during cycling exercise . METHODS In a double-blind , r and omized , crossover study , nine recreationally active male subjects supplemented their diet with either nitrate-rich concentrated beetroot juice ( BR ; 2 × 250 mL·d , ∼8.2 mmol·d nitrate ) or a nitrate-depleted BR placebo ( PL ; 2 × 250 mL·d , ∼0.006 mmol·d nitrate ) . In each condition , the subjects completed four separate severe-intensity exercise bouts to exhaustion at 60 % of the difference between the gas exchange threshold and the peak power attained during incremental exercise ( 60 % Δ ) , 70 % Δ , 80 % Δ , and 100 % peak power , and the results were used to establish CP and W ' . RESULTS Nitrate supplementation improved exercise tolerance during exercise at 60 % Δ ( BR , 696 ± 120 vs PL , 593 ± 68 s ; P < 0.05 ) , 70 % Δ ( BR , 452 ± 106 vs PL , 390 ± 86 s ; P < 0.05 ) , and 80 % Δ ( BR , 294 ± 50 vs PL , 263 ± 50 s ; P < 0.05 ) but not 100 % peak power ( BR , 182 ± 37 vs PL , 166 ± 26 s ; P = 0.10 ) . Neither CP ( BR , 221 ± 27 vs PL , 218 ± 26 W ) nor W ' ( BR , 19.3 ± 4.6 vs PL , 17.8 ± 3 kJ ) were significantly altered by BR . CONCLUSION Dietary nitrate supplementation improved endurance during severe-intensity exercise in recreationally active subjects without significantly increasing either the CP or the W ' PURPOSE This study evaluated the change ( Δ ) in plasma volume ( PV ) , nitrate [ NO3- ] , and nitrite [ NO2- ] concentration following changes in posture in the presence and absence of elevated plasma [ NO3- ] and [ NO2- ] METHODS : Fourteen healthy participants completed two trials that were preceded by either supplementation with NO3 - -rich beetroot juice ( BR ; total of ∼31 mmol NO3- ) or no supplementation ( CON ) . Both trials comprised 30 min of lying supine followed by 2 min of st and ing , 2 min of sitting and 5 min of sub-maximal cycling . Measurements of plasma [ NO3- ] and [ NO2- ] were made by gas-phase chemiluminescence and ΔPV was estimated using the Dill and Costill method . RESULTS Plasma [ NO2- ] decreased from baseline ( CON : 120 ± 49 nM , BR : 357 ± 129 nM ) after lying supine for 30 min ( CON 77 ± 30 nM ; BR 231 ± 92 nM , both P < 0.01 ) before increasing during st and ing ( CON 109 ± 42 nM ; BR 297 ± 105 nM , both P < 0.01 ) and sitting ( CON 131 ± 43 nM ; BR 385 ± 125 nM , both P < 0.01 ) . Plasma [ NO2- ] remained elevated following exercise only in CON ( 125 ± 61 nM P = 0.02 ) . Plasma [ NO3- ] was not different between measurement points in either condition ( P > 0.05 ) . PV increased from baseline during the supine phase before decreasing upon st and ing , sitting , and exercise in both trials ( all P<0.05 ) . CONCLUSIONS Changing body posture causes rapid and consistent alterations in plasma [ NO2- ] . Research ers should therefore carefully consider the effect of posture when measuring this variable Dietary nitrate ( NO(3)(- ) ) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults . We investigated whether these effects might also be evident in older adults . In a double-blind , r and omized , crossover study , 12 healthy , older ( 60 - 70 yr ) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice ( BR ; 2 × 70 ml/day , ∼9.6 mmol/day NO(3)(- ) ) or a nitrate-depleted beetroot juice placebo ( PL ; 2 × 70 ml/day , ∼0.01 mmol/day NO(3)(- ) ) . Before and after the intervention periods , resting blood pressure and plasma [ nitrite ] were measured , and subjects completed a battery of physiological and cognitive tests . Nitrate supplementation significantly increased plasma [ nitrite ] and reduced resting systolic ( BR : 115 ± 9 vs. PL : 120 ± 6 mmHg ; P < 0.05 ) and diastolic ( BR : 70 ± 5 vs. PL : 73 ± 5 mmHg ; P < 0.05 ) blood pressure . Nitrate supplementation result ed in a speeding of the Vo(2 ) mean response time ( BR : 25 ± 7 vs. PL : 28 ± 7 s ; P < 0.05 ) in the transition from st and ing rest to treadmill walking , although in contrast to our hypothesis , the O(2 ) cost of exercise remained unchanged . Functional capacity ( 6-min walk test ) , the muscle metabolic response to low-intensity exercise , brain metabolite concentrations , and cognitive function were also not altered . Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2 ) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance . These results may have implication s for the enhancement of cardiovascular health in older age |
13,033 | 26,130,729 | Weight loss for men is best achieved and maintained with the combination of a reducing diet , increased physical activity , and behavior change techniques . | Men are underrepresented in obesity services , suggesting current weight loss service provision is suboptimal .
This systematic review evaluated evidence -based strategies for treating obesity in men . | Background This study assessed the effect of a 1-year internet-based weight loss intervention for men . Methods Four hundred forty-one overweight and obese men were r and omized to intervention or delayed treatment . Participants completed a Web-based assessment of diet and physical activity behaviors and weekly tailored Web modules addressing weight-related behaviors . Results At 12 months compared to controls , intervention men decreased percent of energy from saturated fat and increased grams of fiber and fruit/vegetable servings per 1.000 kcal ( p values < 0.001 ) and walked 16 min more per day ( p < 0.05 ) . No between-group differences in body mass index ( BMI ) , weight , or waist circumference were seen , but among completers , men in the highest tertile of intervention participation had lower weight ( 98.74 vs. 102.37 kg ) , BMI ( 32.38 vs. 33.46 ) , and waist circumference ( 42.17 vs. 43.47 cm ) compared to men who participated less often . Conclusions The intervention improved diet and activity behaviors , but weight loss occurred only for those with the highest adherence This article reports the 12-month follow-up results and process evaluation of the SHED-IT ( Self-Help , Exercise , and Diet using Information Technology ) trial , an Internet-based weight loss program exclusively for men . Sixty-five overweight/obese male staff and students at the University of Newcastle ( Callaghan , Australia ) ( mean ( s.d . ) age = 35.9 ( 11.1 ) years ; BMI = 30.6 ( 2.8 ) ) were r and omly assigned to either ( i ) Internet group ( n = 34 ) or ( ii ) Information only control group ( n = 31 ) . Both received one face-to-face information session and a program booklet . Internet group participants were instructed to use the study website for 3 months . Participants were assessed at baseline , 3- , 6- , and 12-month follow-up for weight , waist circumference , BMI , blood pressure , and resting heart rate . Retention at 3- and 12-months was 85 % and 71 % , respectively . Intention-to-treat ( ITT ) analysis using linear mixed models revealed significant and sustained weight loss of -5.3 kg ( 95 % confidence interval ( CI ) : -7.5 , -3.0 ) at 12 months for the Internet group and -3.1 kg ( 95 % CI : -5.4 , -0.7 ) for the control group with no group difference . A significant time effect was found for all outcomes ( P < 0.001 ) . Per- protocol analysis revealed a significant group-by-time interaction for weight , waist circumference , BMI , and systolic blood pressure . Internet group compliers ( who self-monitored as instructed ) maintained greater weight loss at 12 months ( -8.8 kg ; 95 % CI -11.8 , -5.9 ) than noncompliers ( -1.9 kg ; 95 % CI -4.8 , 1.0 ) and controls ( -3.0 kg ; 95 % CI -5.2 , -0.9 ) . Qualitative analysis by question naire and interview highlighted the acceptability and satisfaction with SHED-IT . Low-dose approaches to weight loss are feasible , acceptable , and can achieve clinical ly important weight loss in men after 1-year follow-up BACKGROUND The prevalence of male obesity is increasing but few men take part in weight loss programmes . We assessed the effect of a weight loss and healthy living programme on weight loss in football ( soccer ) fans . METHODS We did a two-group , pragmatic , r and omised controlled trial of 747 male football fans aged 35 - 65 years with a body-mass index ( BMI ) of 28 kg/m(2 ) or higher from 13 Scottish professional football clubs . Participants were r and omly assigned with SAS ( version 9·2 , block size 2 - 9 ) in a 1:1 ratio , stratified by club , to a weight loss programme delivered by community coaching staff in 12 sessions held every week . The intervention group started a weight loss programme within 3 weeks , and the comparison group were put on a 12 month waiting list . All participants received a weight management booklet . Primary outcome was mean difference in weight loss between groups at 12 months , expressed as absolute weight and a percentage of their baseline weight . Primary outcome assessment was masked . Analyses were based on intention to treat . The trial is registered with Current Controlled Trials , number IS RCT N32677491 . FINDINGS 374 men were allocated to the intervention group and 374 to the comparison group . 333 ( 89 % ) of the intervention group and 355 ( 95 % ) of the comparison group completed 12 month assessment s. At 12 months the mean difference in weight loss between groups , adjusted for baseline weight and club , was 4·94 kg ( 95 % CI 3·95 - 5·94 ) and percentage weight loss , similarly adjusted , was 4·36 % ( 3·64 - 5·08 ) , both in favour of the intervention ( p<0·0001 ) . Eight serious adverse events were reported , five in the intervention group ( lost consciousness due to drugs for pre-existing angina , gallbladder removal , hospital admission with suspected heart attack , ruptured gut , and ruptured Achilles tendon ) and three in the comparison group ( transient ischaemic attack , and two deaths ) . Of these , two adverse events were reported as related to participation in the programme ( gallbladder removal and ruptured Achilles tendon ) . INTERPRETATION The FFIT programme can help a large proportion of men to lose a clinical ly important amount of weight ; it offers one effective strategy to challenge male obesity . FUNDING Scottish Government and The UK Football Pools funded delivery of the programme through a grant to the Scottish Premier League Trust . The National Institute for Health Research Public Health Research Programme funded the assessment ( 09/3010/06 ) Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss . Design Eight arm r and omised controlled trial . Setting Primary care trust in Birmingham , Engl and . Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records . Interventions Weight loss programmes of 12 weeks ’ duration : Weight Watchers ; Slimming World ; Rosemary Conley ; group based , dietetics led programme ; general practice one to one counselling ; pharmacy led one to one counselling ; choice of any of the six programmes . The comparator group was provided with 12 vouchers enabling free entrance to a local leisure ( fitness ) centre . Main outcome measures The primary outcome was weight loss at programme end ( 12 weeks ) . Secondary outcomes were weight loss at one year , self reported physical activity , and percentage weight loss at programme end and one year . Results Follow-up data were available for 658 ( 88.9 % ) participants at programme end and 522 ( 70.5 % ) at one year . All programmes achieved significant weight loss from baseline to programme end ( range 1.37 kg ( general practice ) to 4.43 kg ( Weight Watchers ) ) , and all except general practice and pharmacy provision result ed in significant weight loss at one year . At one year , only the Weight Watchers group had significantly greater weight loss than did the comparator group ( 2.5 ( 95 % confidence interval 0.8 to 4.2 ) kg greater loss , ) . The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end ( mean difference 2.3 ( 1.3 to 3.4 ) kg ) . The primary care programmes were the most costly to provide . Participants allocated to the choice arm did not have better outcomes than those r and omly allocated to a programme . Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff , which are ineffective . Trial registration Current Controlled Trials IS RCT N25072883 Obesity and physical inactivity are associated with both elevated cardiovascular risk and blood pressure ( BP ) , but the interrelation of exercise , weight loss and BP is poorly understood . This study examines the independent effects of exercise and weight loss on both st and ard clinic and automated , ambulatory BP in 115 overweight , sedentary , normotensive men ( aged 30 to 59 years ) who were r and omly assigned to control status or to lose weight over 1 year by moderate caloric restriction ( dieting ) or by increased caloric expenditure ( exercise ) . Median daytime and evening BP were determined from measurements made every 20 minutes while the subjects were awake . After 1 year , the control group gained ( mean + /- st and ard deviation ) 0.5 + /- 3.8 kg while the diet group lost 6.9 + /- 4.4 kg and the exercise group lost 4.6 + /- 3.5 kg . Clinic BP decreased similarly in all 3 groups , but daytime and evening ambulatory BP decreased in both intervention groups and increased in the control group . Relative to the 1-year change in control subjects , net change in daytime ambulatory BP averaged -2 to -3 mm Hg in both dieters and exercisers , while net change in evening ambulatory BP averaged -3 to -4 mm Hg . These changes were all statistically significant ( p less than 0.05 ) when compared with control subjects except for daytime systolic BP in both intervention groups and evening diastolic BP in dieters . Weight loss achieved through caloric restriction or expenditure may cause important decreases in BP in normotensive men ; exercise appears to confer no unique benefit . If confirmed , these results have important public health implication s for the prevention of cardiovascular disease Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK ) Objective : To investigate the relationship of body weight and its changes over time with physical activity ( PA ) . Design : Population -based prospect i ve cohort study ( Norfolk cohort of the European Prospect i ve Investigation into Cancer and Nutrition , EPIC-Norfolk , United Kingdom).Subjects : A total of 25 639 men and women aged 39–79 years at baseline . PA was self-reported . Weight and height were measured by st and ard clinical procedures at baseline and self-reported at 18-month and 10-year follow-ups ( calibrated against clinical measures ) . Main outcome measure was PA at the 10-year follow-up . Results : Body weight and PA were inversely associated in cross-sectional analyses . In longitudinal analyses , an increase in weight was associated with higher risk of being inactive 10 years later , after adjusting for baseline activity , 18-month activity , sex , baseline age , prevalent diseases , socioeconomic status , education , smoking , total daily energy intake and alcohol intake . Compared with stable weight , a gain in weight of > 2 kg per year in the short- , medium- and long-term was consistently and significantly associated with greater likelihood of physical inactivity after 10 years , with the most pronounced effect for long-term weight gain , OR=1.89 ( 95 % CI : 1.30–2.70 ) in fully adjusted analysis . Weight gain of 0.5–2 kg per year over long-term was substantially associated with physical inactivity after full adjustment , OR=1.26 ( 95 % CI : 1.11–1.41 ) . Conclusion : Weight gain ( during short- , medium- and long-term ) is a significant determinant of future physical inactivity independent of baseline weight and activity . Compared with maintaining weight , moderate ( 0.5–2 kg per year ) and large weight gain ( > 2 kg per year ) significantly predict future inactivity ; a potentially vicious cycle including further weight gain , obesity and complications associated with a sedentary lifestyle . On the basis of current predictions of obesity trends , we estimate that the prevalence of inactivity in Engl and would exceed 60 % in the year 2020 Objective : To investigate the effect of dietary restraint with or without exercise during weight maintenance after energy restriction . Subjects and methods : In total , 40 obese male subjects ( mean BMI 32.3 kg/m2 ; mean age 39 y ) were recruited and r and omly divided into a diet ( D ; n=20 ) and a diet plus exercise ( DE ; n=20 ) group . Both groups participated in an energy restriction programme ( ER ) , which was followed by a weight maintenance phase ( WM ) . Subjects in the DE also participated in an exercise programme . Body mass ( BM ) and the scores on the three factor eating question naire ( TFEQ ) were measured before and after the ER and after WM . Results : No significant differences between both groups were found . All data taken together showed that BM loss during ER was explained by initial BM ( r 2=0.3 , P<0.0005 ) and inversely by initial cognitive restraint ( F1 ) ( r 2=0.4 , P<0.0005 ) in a stepwise regression . BM regain during WM was explained by BM loss ( r 2=0.5 , P<0.001 ) and by increase in F1 during ER ( r 2=0.6 , P<0.001 ) , while the exercise intervention did not contribute further to the explained variation . Subjects with a relatively high diet frequency prior to the study had relatively significant higher initial F1 scores ( P<0.05 ) . During ER , increase in F1 was associated with decrease in general hunger ( F3 ) . Conclusion : Successful BM loss was associated with higher initial BM and lower initial F1 . Successful WM was explained by BM loss and increase in F1 during ER , irrespective of possible exercise training effects . Successful WM was reduced when F1 scores reach their limit , due to diet-frequency The effect of a minimal intervention strategy on maintenance of weight lost through either energy restriction alone or exercise alone during the previous year was studied in a sample of middle-aged men . At the end of the initial year of weight loss , dieters ( n = 44 ) and exercisers ( n = 46 ) were r and omly assigned to either an intervention condition , comprising monthly mailed informational packets and monthly to quarterly telephone contacts , or an assessment -only condition . The intervention had a significantly greater impact on weight maintenance in exercisers than it did in dieters . In addition , dieters showed a more variable pattern of weight gain and weight loss during the maintenance year than did exercisers . Based on 7-day food records and a 7-day physical activity recall question naire , exercisers reported a greater energy intake and a greater amount of time spent in vigorous activity relative to dieters at both the beginning and the end of the maintenance year . We conclude that exercise is easier to maintain in men using minimal contact strategies than dietary approaches to weight control focusing on modification of energy intake , with subsequent benefits in terms of both overall maintenance and stability of weight BACKGROUND Few published data link overweight and obesity with measures of quality of life ( QoL ) including sexual health in men . OBJECTIVE To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men . DESIGN AND SETTING Cross-sectional , multicentre survey of 3369 community-dwelling men aged 40 - 79 ( mean±s.d . , 60±11 ) years r and omly selected from eight European centres . OUTCOMES Adiposity was assessed by body mass index ( BMI ) and waist circumference ( WC ) , QoL and functional impairments by physical and psychological function domains of the Short Form-36 question naire , Beck 's Depression Inventory and the European Male Ageing Study sexual function question naire . RESULTS Complete data on sexual activities and erectile function were available in 2734 ( 92 % ) and 3193 ( 95 % ) of the participants respectively . From the population studied , 814 men were obese ( BMI ≥30 kg/m(2 ) ) and 1171 had WC ≥102 cm , 25 % of all men were unable to do vigorous activity and 2 - 13 % reported depressive symptoms . Symptoms of sexual dysfunction ranged between 22 % ( low sexual desire ) and 40 % ( infrequent morning erections ) of the participants . Among obese men with both BMI ≥30 kg/m(2 ) and WC ≥102 cm , at least one symptom of impaired physical , psychological and sexual function was reported by 41 , 43 and 73 % of the participants respectively . Compared with the reference group of non-obese men ( BMI < 30 kg/m(2 ) and WC < 102 cm ) , men with BMI ≥30 kg/m(2 ) and WC ≥102 cm more frequently reported at least one symptom of impaired physical function ( odds ratio (OR)=2.67 ; confidence interval ( CI ) : 2.07 - 3.45 , P<0.001 ) , impaired psychological function ( OR=1.48 ; CI : 1.14 - 1.90 , P<0.01 ) and impaired sexual function ( OR=1.45 ; CI : 1.14 - 1.85 , P<0.01 ) . These functional impairments were also more prevalent in men who had WC ≥102 cm even with BMI < 30 kg/m(2 ) , but those with BMI ≥30 kg/m(2 ) and WC < 102 cm generally did not suffer from increased impaired physical or sexual health . Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC . CONCLUSIONS Men with high WC , including those who are ' non-obese ' with BMI < 30 kg/m(2 ) , have poor QoL with symptoms of impaired physical , psychological and sexual functions . Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation Objective : To investigate whether walking or resistance training improves weight maintenance after weight loss when added to dietary counselling . Design : Two months ' weight reduction with very-low-energy-diet ( VLED ) followed by r and omization into three groups ( control , walking , resistance training ) for 6 months ' weight maintenance ( WM ) program and 23 months ' unsupervised follow-up . During VLED and WM all groups received similar dietary counselling . Subjects : The main inclusion criteria were BMI > 30 kg/m2 , waist>100 cm and physical inactivity ( exercise ≤ once a week ) . Ninety healthy , obese ( mean BMI 32.9 kg/m2 and waist 112.5 cm ) , 35–50 y-old men started the study and 68 were measured at the end of the study . Measurements : Weight and body composition assessed by underwater weighing . Exercise diaries and dietary records to assess energy balance . Results : During VLED the mean body weight decreased from 106.0 ( s.d . 9.9 ) kg to 91.7 ( 9.4 ) kg . Weight was regained mostly during follow-up and in the end of the study the mean weight in groups was 99.9–102.0 kg . Exercise training did not improve short or long-term weight maintenance when compared to the control group . However , resistance training attenuated the regain of body fat mass during WM ( P=0.0l ) , but not during follow-up . In the combined groups the estimated total energy expenditure ( EE ) of reported physical activity was associated with less weight regain during WM . EE of 10.1 MJ/week was associated with maintaining weight after weight loss . EE of physical activity tended to decrease after WM in exercise groups due to poor long-term adherence to prescribed exercise . Energy intake seemed to increase during follow-up . Conclusion : Exercise training of moderate dose did not seem to improve long-term weight maintenance because of poor adherence to prescribed exercise The importance of diet in DNA damage prevention is well established ; however , the comparison of weight loss diets with different micronutrient and macronutrient profiles on genome stability in peripheral blood lymphocytes ( PBLs ) has not been studied . This study tested the hypothesis that genome stability in PBLs of overweight men who consume a high protein-high red meat ( HP ) weight loss diet is different from that of overweight men who consume a high carbohydrate ( HC ) weight loss diet . Thirty-three male subjects were r and omly assigned to an HP or HC isocaloric energy-restricted dietary intervention for 12 weeks intensive weight loss and weight maintenance up to 52 weeks . Blood sample s were collected at 0 , 12 and 52 weeks . DNA damage in PBLs was assessed using the cytokinesis-block micronucleus cytome ( CBMN-Cyt ) assay . Average weight loss after 12 weeks was 9.3 + /- 0.7 kg for both diets , with no further change at 52 weeks . Two-way analysis of variance showed no time or diet effect on micronucleus frequency ( chromosome loss/breaks ) . There was a significant trend with time ( P = 0.03 ) but not diet , for reduction of nuclear buds ( gene amplification ) . There was a positive trend with time for increased nucleoplasmic bridges ( chromosome rearrangement ) ( P = 0.051 ) . Necrosis and apoptosis both significantly decreased with time ( P = 0.037 and P = 0.007 , respectively ) with no diet effect . There was no significant effect of time or diet for nuclear division index , a biomarker of immune response . The results suggest that the effect of the HP weight loss diet on DNA damage measured using the CBMN-Cyt assay in PBLs was not different from that observed for the HC weight loss diet Reported is a 2-year follow-up of a behavioral weight reduction program for men using monetary contracts of varying size and group versus individual contingencies . Although initial weight losses were large , in the absence of an effective maintenance program weight losses at two years were modest , similar to those obtained with less effective initial weight loss procedures . Group contracts were significantly more effective in producing long term loss than individual contracts . Reported behaviors associated with weight loss at 2 years are presented In a r and omized controlled trial 145 sexually active overweight/obese men received either a male only SHED-IT ( Self Help Exercise and Diet Using IT ) weight loss program or a wait-list control . Erectile function ( IIEF-5 ) was compared between men in the active intervention versus controls . IIEF-5 was assessed at baseline , 3 months ( post-intervention ) and 6 months ( 3-month follow-up ) . Intention-to-treat analysis revealed a significant intervention effect for erectile function ( p = 0.018 ) at 6 months ( + 1.4 ; 95 % CI 0.3,2.4 ; d = 0.32 ) . A minimal contact , gender-tailored weight loss program significantly improved men 's erectile function . Further studies evaluating change in erectile function with weight loss are warranted |
13,034 | 28,876,390 | From the drugs assessed , paracetamol was unanimous for not interfering within orthodontic movement when compared to the control group .
However , drugs such as aspirin , ibuprofen , sodium diclofenac , and selective cyclooxygenase-2 inhibitors caused a reduction in tooth movement when compared to the control group .
paracetamol could be considered the drug of choice for pain relief because it interferes less within tooth movement | The present study aim ed to perform a systematic literature review to determine if there is a non-steroidal anti-inflammatory drug ( NSAID ) that interferes less within tooth movement . | BACKGROUND ProSorb diclofenac potassium ( K ) is a novel , liquid-filled rapid-dispersion formulation of the nonsteroidal anti-inflammatory drug diclofenac , placed into soft gelatin capsules . Its time to maximal plasma drug concentration has been shown to be approximately half , and its maximal plasma drug concentration nearly twice , that of immediate-release diclofenac K tablets . OBJECTIVE This study compared the analgesic dose-response relationship and tolerability of 3 doses of ProSorb diclofenac K and placebo in the treatment of pain after dental impaction surgery . METHODS This r and omized , double-blind , double-dummy , placebo-controlled parallel-group study was conducted at 6 centers across the United States . Patients aged 18 to 65 years with moderate or severe pain after the removal of > or = 1 impacted m and ibular third molar were r and omly assigned to receive a single dose of ProSorb diclofenac K 25 , 50 , or 100 mg or placebo . Pain intensity and relief were assessed up to 6 hours after dosing . Rescue treatment was allowed after 1 hour . Efficacy end points included the summed pain intensity difference over 3 and 6 hours ( SPID3 and 6 ) ; total pain relief at 3 and 6 hours ( TOTPAR3 and 6 ) ; median times to onset of perceptible and meaningful relief ( analgesic onset ) and rescue medication use ( analgesic duration ) ; and cumulative percentage of patients using rescue medication . Tolerability was assessed using vital sign measurements and spontaneous reporting of adverse events . RESULTS A total of 265 patients ( 154 women , 111 men ; mean age , 23.3 years ) were enrolled . All 3 ProSorb diclofenac K groups showed higher SPID6 and TOTPAR6 scores and longer median times to rescue medication use than the placebo group ( all , P < 0.001 ) . For these end points , a dose-response relationship was evident between the 100-mg dose and the 25- and 50-mg doses ( P < or = 0.05 ) ; the 25- and 50-mg doses were similar . In the diclofenac groups , median onset times for first perceptible ( < or = 22.5 min ) and meaningful ( < or = 53.0 min ) relief were significantly more rapid than placebo ( P < or = 0.01 ) . Proportions of patients requiring rescue analgesic were < or = 50.8 % with diclofenac compared with 79.4 % with placebo . Proportions of patients assigning a global evaluation of good or better was > or = 68 % with diclofenac compared with 21 % for placebo . Tolerability was similar across all treatment groups . CONCLUSION In this study of patients treated for pain following dental impaction surgery , single doses of ProSorb diclofenac K 25 , 50 , and 100 mg were more efficacious than placebo with respect to reduction of pain . All 3 doses provided a rapid analgesic onset and were well tolerated patients undergoing any form of dental treatment , to the extent that 77 % of a patient population reported some degree of pain from a visit to the dentist.1 Pain following orthodontic adjustments appears to be equally prevalent.2 - 10 Jones and Chan showed that compliance with orthodontic treatment may be predicated on the amount of initial pain and discomfort experienced.5 Other studies indicate that plaque control may suffer as a result of the pain associated with orthodontics.7,11 Although analgesics have been found to reduce such discomfort , in most cases they do not totally eliminate it.12 - 15 Moreover , some patients may be allergic to these agents , and one report suggested that nonsteroidal anti-inflammatory drugs may adversely affect the rate of tooth movement.14 Patients who do not respond to or elect not to use pharmacological therapy have had few practical alternatives . Some orthodontists recommend chewing on gum or a plastic wafer immediately after adjustments.16 Proffit suggested that lower force levels could reduce pain,17 but Lim and colleagues showed that pain or discomfort was still experienced by most patients even when “ physiologic and light forces ” were used.18 Recently , there have been major developments in the underst and ing of pain mechanisms and of new approaches to the management of pain.19 Low-level laser therapy has been shown to produce analgesic effects in many clinical applications , including orthodontics.18 Transcutaneous electrical nerve stimulation ( TENS ) is another non-pharmacological , non-invasive method of reducing post-orthodontic adjustment pain.20,21 Vibratory stimulation , a classic noninvasive and non-medicinal method of reducing pain , could also be effective in orthodontic patients .21 - 26 The orthodontic application of this method was first investigated by Dr. Powers on a patient with a history of painful post-adjustment episodes during closure of a wide maxillary midline diastema with elastic chain . After placing a new elastic chain , Dr. Powers observed that gentle vibration of the maxillary central incisors produced two effects : the blanching of the tissue between and above the incisors was quickly reversed , and the previous level of pain did not occur Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement . The two archwires used were a superelastic nickel-titanium alloy , 0.014 inch Sentalloy , Light ( GAC International Inc. Central Islip , NY , USA ) and a 0.014 inch Nitinol ( unitek , Monrovia , CA , USA ) , a conventional nickel-titanium aligning archwire . One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practice s for routine placement of a fixed appliance were r and omly assigned one of these 2 initial archwires . Assessment s of pain/discomfort were made daily by means of a 100 mm visual analog scale ( VAS ) over the first 7-day period after bonding . On the first day , recordings were made every hour for the first 11 hours . The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires , with a peak in the first night , remaining high on the second day and decreasing thereafter to baseline level after 7 days . During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire , although a significant difference could be found at 4 hours only . No significant gender-specific differences were found in either archwire group . A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire , with the lower arch having the higher pain experience . ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen , die häufig für die initiale Nivellierung verwendet werden , wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht . Das eine Bogen material war eine superelastische NiTi-legierung , 0,014 inch Sentalloy , Light ( GAC International Inc. , Central Islip , N. Y. ) , das and ere ein herkömmlicher 0,014 inch Nitinol-Bogen ( Unitek , Monrovia , Kalifornien).128 fortlaufend beh and elte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen , bei denen routinemäßig eine Multib and apparatur eingesetzt werden sollte , wurden r and omisiert für den einen oder den and eren Bogen vorgesehen . Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge ( visual analogue scale , VAS ) vorgenommen . Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet . Die Ergebnisse zeigten , daß die Beschwerden für den ersten Bogen , sowohl für den Sentalloy-als auch für den Nitinol-Bogen , kontinuierlich jede Stunde nach dem Einsetzen anstiegen . Der Höhepunkt wurde in der ersten Nacht erreicht , blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau . Während der ersten zehn Stunden war es offensichtlich , daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen ; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant . Keine signifikanten Unterschiede der Beschwerden zwischen den Bogen material ien f and en sich hinsichtlich des Geschlechts der Patienten . Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet ; i m Unterkiefer traten deutlich stärkere Beschwerden auf BACKGROUND Each year , clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs ( NSAIDs ) . We assessed whether rofecoxib , a selective inhibitor of cyclooxygenase-2 , would be associated with a lower incidence of clinical ly important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis . METHODS We r and omly assigned 8076 patients who were at least 50 years of age ( or at least 40 years of age and receiving long-term glucocorticoid therapy ) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily . The primary end point was confirmed clinical upper gastrointestinal events ( gastroduodenal perforation or obstruction , upper gastrointestinal bleeding , and symptomatic gastroduodenal ulcers ) . RESULTS Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis . During a median follow-up of 9.0 months , 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib , as compared with 4.5 per 100 patient-years with naproxen ( relative risk , 0.5 ; 95 percent confidence interval , 0.3 to 0.6 ; P<0.001 ) . The respective rates of complicated confirmed events ( perforation , obstruction , and severe upper gastrointestinal bleeding ) were 0.6 per 100 patient-years and 1.4 per 100 patient-years ( relative risk , 0.4 ; 95 percent confidence interval , 0.2 to 0.8 ; P=0.005 ) . The incidence of myocardial infa rct ion was lower among patients in the naproxen group than among those in the rofecoxib group ( 0.1 percent vs. 0.4 percent ; relative risk , 0.2 ; 95 percent confidence interval , 0.1 to 0.7 ) ; the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups . CONCLUSIONS In patients with rheumatoid arthritis , treatment with rofecoxib , a selective inhibitor of cyclooxygenase-2 , is associated with significantly fewer clinical ly important upper gastrointestinal events than treatment with naproxen , a nonselective inhibitor Background Pain is among the most cited negative effects of orthodontic treatment . Non-steroidal anti-inflammatory drugs seem to be an effective option for minimizing this but can have adverse effects on tooth movement owing to their ability to block prostagl and in synthesis . Acetaminophen has been suggested as the analgesic of choice during orthodontic treatment as it showed no effect on orthodontic tooth movement in previous animal studies . The purpose of this study was to compare the effects of ibuprofen and acetaminophen on the prostagl and in E2 ( PGE2 ) levels of the gingival crevicular fluid ( GCF ) during orthodontic tooth movement in human subjects . Methods A total of 42 patients ( mean age 18 ± 4.5 years ) were r and omly divided into three equal groups : ibuprofen , acetaminophen , and control groups . Maxillary canines were distalized with 150 g of force delivered by NiTi coil springs . GCF sample s were obtained before ( baseline ) and after spring activation at 24 , 48 , and 168 h. The PGE2 content of the GCF was determined using enzyme-linked immunosorbent assay . Results PGE2 levels in all groups increased significantly by 24 and 48 h of force application and decreased to baseline levels by 168 h. No significant difference was found between the acetaminophen and control groups at any time point . There was a significant decrease in PGE2 levels in the ibuprofen group at 24 and 48 h when compared to the other two groups . Conclusions Acetaminophen showed no significant effect on prostagl and in synthesis and may be the safe choice compared to ibuprofen for relieving pain associated with orthodontic tooth movement OBJECTIVE To test the hypothesis that the administration of aspirin , acetaminophen , meloxicam , celecoxib , and prednisolone have no effect on root resorption and tooth movement . MATERIAL S AND METHODS A mesial force of 50 g was applied to the left maxillary first molars of sixty 10-week-old male Wistar rats using nickel titanium closed coil springs attached to the cervical area of the incisors . The rats were r and omly divided into 12 groups of 5 each . High and low doses of aspirin , acetaminophen , meloxicam , celecoxib , and prednisolone were administered via drinking water for 2 weeks . The experimental control group had tooth movement but received no drug . The negative control group received neither tooth movement nor drugs . The amount of tooth movement was measured on digitized lateral cephalometric radiographs . Rats were sacrificed after 2 weeks . Mesial and distal roots ( distobuccal and distopalatal ) were examined using scanning electron and three-dimensional ( 3D ) scanning laser microscopes . The surface area , depth , volume , and roughness of the root resorption craters were measured . RESULTS When compared with experimental control rats , only prednisolone- and high-dose celecoxib-treated groups showed significantly less root resorption and less tooth movement . Although low dose celecoxib-treated group significantly decreased the tooth movement , root resorption was similar to the control group . Furthermore , resorption craters showed a smoother surface in the prednisolone-treated rats . CONCLUSIONS The hypothesis was rejected . Administration of prednisolone and high-dose celecoxib reduces root resorption and interferes with tooth movement in rats . Both drugs may interfere in the arachidonic acid cascade depending on dose thresholds OBJECTIVES To test the hypothesis that mechanical forces combined with low-level laser therapy stimulate the rate of orthodontic tooth movement . STUDY DESIGN This study was a double blind , r and omized placebo/control matched pairs clinical trial to test the efficacy of GaAlAs low-level laser therapy ( LLLT ) on 12 young adult patients who required retraction of maxillary canines into first premolar extraction spaces using tension coil springs with fixed edgewise appliance . LLLT was applied on the mucosa buccally , distally and palatally to the canine on the test side and using a pseudo-application on the placebo side . Dental impressions and casts were made at the commencement of the trial and at the end of the first , second and third months after starting the trial . Measurement of tooth movements was made on each stage model using a stereo microscope . RESULTS There was no significant difference of means of the canine distal movement between the LLLT side and the placebo side for any time periods ( p-value = 0.77 ) . CONCLUSION The energy density of LLLT ( GaAlAs ) at the surface level in this study ( 25 J/cm(2 ) ) was probably too low to express either stimulatory effect or inhibitory effect on the rate of orthodontic tooth movement Possible modifications in orthodontic tooth movement ( OTM ) and root resorption as a result of local injections of prostagl and in E2 ( PGE2 ) alone and with calcium gluconate ( Ca ) formed the aim of the present study . Twenty-four 8-week-old male Wistar rats were selected and r and omly divided into three groups of eight . Both quadrants of the upper jaws of the first group of animals were used ; therefore this group comprised two groups : control and normal . The upper left first molars of these eight animals were not placed under orthodontic force and received no injection , to serve as the normal group , considered for root resorption comparison only . The control group had localized submucosal injections of normal saline on the buccal side of the upper right first molar . In the third group , 0.1 ml of 1 mg/ml PGE2 was injected at the same site and the fourth group received an intraperitoneal injection of 200 mg/kg Ca ( 10 % ) in addition to the PGE2 . All the injections were performed on days 0 and 7 . The orthodontic appliance consisted of a closed coil spring ligated to the upper right first molar and incisor , exerting a force of 60 g during the 21-day experimental period , after which the animals were sacrificed . Palatal halves were removed for histological examination and for calculation of the amount of root resorption . Statistical analysis of data showed a significant ( P < 0.05 ) acceleration in OTM after PGE2 injection compared with the control group . The addition of Ca reduced OTM but a significant increase ( P < 0.05 ) was still recorded . A significant difference ( P < 0.05 ) in root resorption was only observed between the PGE2 and normal groups . The findings show the importance of calcium ions working in association with PGE2 in stabilizing root resorption while significantly increasing OTM The purpose of this study was to examine the effects of 2 different anti-inflammatory drugs on gingival crevicular fluid ( GCF ) volume and on prostagl and in E(2 ) ( PGE(2 ) ) levels of the GCF during orthodontic tooth movement . A total of 36 extraction patients , aged 17.6 + /- 2.5 years ( mean + /- st and ard deviation ) , were divided into 3 groups . Acetylsalicylic acid ( aspirin ) and rofecoxib ( Vioxx , Merck , Whitehouse Station , NJ ) were used for pain control in the first and second groups ; the third group was used as a control . Gingival crevicular fluid was sample d at the beginning of tooth movement and at 24 , 48 , and 168 hours . An automated enzyme immunoassay was used to measure PGE(2 ) in GCF . The intragroup differences were evaluated with the Wilcoxon test , and the differences between the groups were determined with the Mann-Whitney U test . Gingival crevicular fluid volumes of the groups did not change significantly during the experimental period . Depending on the variations of fibroblast activation , PGE(2 ) levels of all the groups increased at 24 and 48 hours and decreased at 168 hours . When the drugs were compared , it was found that the inhibition effect of aspirin on PGE(2 ) was more than that of rofecoxib . The results suggest that rofecoxib can be used during orthodontic treatment , but further study is recommended |
13,035 | 29,284,458 | Conclusions The strength and consistency of the associations in these studies support that the removal of menthol from cigarettes is likely to reduce youth smoking initiation , improve smoking cessation outcomes in adult smokers , and in turn , benefit public health | Background Although menthol was not banned under the Tobacco Control Act , the law made it clear that this did not prevent the Food and Drug Administration from issuing a product st and ard to ban menthol to protect public health .
The purpose of this review was to up date the evidence synthesis regarding the role of menthol in initiation , dependence and cessation . | BACKGROUND This is the first study to examine predictors of successful cessation in African American ( AA ) light smokers treated within a placebo-controlled trial of bupropion . METHODS We analyzed data from a r and omized , double-blind , placebo-controlled trial of bupropion and health education for 540 African American light smokers . African American light smokers ( ≤10 cigarettes per day , cpd ) were r and omly assigned to receive 150 mg bid bupropion SR ( n=270 ) or placebo ( n=270 ) for 7weeks . All participants received health education counseling at weeks 0 , 1 , 3 , 5 and 7 . Using chi-square tests , two sample t-tests , and multiple logistic regression analyses , we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment ( Week 7 ) and at the end of follow-up ( Week 26 ) . RESULTS Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo ( OR=2.72 , 95 % CI=1.60 - 4.62 , P=0.0002 ) . Greater study session attendance ( OR=2.47 , 95 % CI=1.76 - 3.46 , P=0.0001 ) , and smoking non-menthol cigarettes increased the likelihood of quitting ( OR=1.84 , 95 % CI=1.01 - 3.36 , P=0.05 ) ; while longer years of smoking ( OR=0.98 , 95 % CI=0.96 - 1.00 , P=0.05 ) and higher baseline cotinine ( OR=0.97 , 95 % CI=0.95 - 0.99 , P=0.002 ) significantly reduced the odds of quitting at Week 7 . Conversely , at the end of follow-up ( Week 26 ) , treatment with bupropion vs. placebo ( OR=1.14 , 95 % CI=0.65 - 2.02 , P=0.64 ) was not significantly associated with quitting and type of cigarette smoked ( menthol vs. non-menthol ) did not appear in the final logistic regression model . Greater study session attendance ( OR=1.96 , 95 % CI=1.44 - 2.66 , P=0.0001 ) ; BMI ( OR=1.03 , 95 % CI=1.00 - 1.07 , P=0.04 ) ; and weight efficacy ( OR=1.03 , 95 % CI=1.01 - 1.05 , P=0.01 ) increased the likelihood of quitting at Week 26 . Similar to our findings at Week 7 , longer years of smoking ( OR=0.96 , 95 % CI=0.94 - 0.99 , P=0.01 ) and higher baseline cotinine ( OR=0.97 , 95 % CI=0.95 - 0.99 , P=0.02 ) significantly reduced the odds of quitting at Week 26 . CONCLUSIONS Baseline cotinine levels , number of years smoked and study session attendance are associated with both short- and long-term smoking cessation , while bupropion and the type of cigarette smoked were associated with quitting on short term only Menthol may make cigarettes more addictive and rates of menthol cigarette smoking are disproportionately higher among Black . However , few studies have examined the association between menthol cigarette smoking and cessation , and the studies to date have produced conflicting findings . The present study examines the effect of menthol cigarette smoking on cessation among a multi-ethnic sample of smokers making a pharmacotherapy-aided quit attempt . We hypothesized that menthol cigarette smoking would be associated with lower smoking abstinence rates and conducted a secondary analysis of data from a multi-site r and omized controlled trial of an intervention design ed to facilitate repeat tobacco cessation treatment ( N = 1,343 ) . The intervention consisted of a patient phone call and a computerized provider prompt . The primary outcome for this analysis was 7-day point prevalence smoking abstinence . The average age of the sample was 56 years old . Overall , 25 % of the sample smoked menthol cigarettes : 19 % of Whites , 62 % of Blacks , and 25 % of other ethnicity ( p<.001 ) . We observed no significant effects for menthol cigarette smoking or ethnicity on smoking abstinence rates . In conclusion , combined with findings from previous research , this study suggests that smoking menthol cigarettes does not decrease smoking cessation among older smokers during a quit attempt aided with pharmacotherapy AIMS To assess the relations of menthol cigarette use with measures of cessation success in a large comparative effectiveness trial ( CET ) . DESIGN Participants were r and omized to one of six medication treatment conditions in a r and omized double-blind , placebo-controlled clinical trial . All participants received six individual counseling sessions . SETTING Community-based smokers in two communities in Wisconsin , USA . PARTICIPANTS A total of 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking . The analysis sample comprised 1439 participants : 814 white non-menthol smokers , 439 white menthol smokers and 186 African American ( AA ) menthol smokers . There were too few AA non-menthol smokers ( n = 16 ) to be included in the analyses . INTERVENTIONS Nicotine lozenge , nicotine patch , bupropion sustained release , nicotine patch + nicotine lozenge , bupropion + nicotine lozenge and placebo . MEASUREMENTS Biochemically confirmed 7-day point-prevalence abstinence assessed at 4 , 8 and 26 weeks post-quit . FINDINGS In longitudinal abstinence analyses ( generalized estimating equations ) controlling for cessation treatment , menthol smoking was associated with reduced likelihood of smoking cessation success relative to non-menthol smoking [ model-based estimates of abstinence = 31 versus 38 % , respectively ; odds ratio ( OR ) = 0.71 , 95 % confidence interval ( CI ) = 0.59 , 0.86 ] . In addition , among menthol smokers , AA women were at especially high risk of cessation failure relative to white women ( estimated abstinence = 17 versus 35 % , respectively ; OR = 2.63 , 95 % CI = 1.75 , 3.96 ; estimated abstinence rates for AA males and white males were both 30 % , OR = 1.06 , 95 % CI = 0.60 , 1.66 ) . CONCLUSION In the United States , smoking menthol cigarettes appears to be associated with reduced cessation success compared with non-menthol smoking , especially in African American females Objectives : As part of efforts to develop a smoking control strategy for Japanese adolescents , the results of two nationwide surveys on adolescent smoking behaviour were compared . Design : Descriptive study on smoking behaviour among high school students was conducted . Self-reporting anonymous question naires were administered to 115 814 students in 1996 and 106 297 in 2000 through r and omly sample d junior and senior high schools throughout Japan . Main outcome measures : Smoking prevalence , proportion of smokers by usual sources of cigarettes , national estimated cigarettes consumed by minors , share of cigarette br and s smoked by high school students . Results : The experiment rate among junior high school boys decreased in 2000 compared with that in 1996 , whereas current and daily smoking rates did not . Although prevalence among Japanese girls was much lower than that among boys , prevalence among girls increased in 2000 . The main source of cigarettes among high school smokers was vending machines . The proportion of smokers who usually purchased cigarettes from vending machines increased in 2000 , in spite of the 1998 introduction of restrictions on night-time operations . Japanese adolescents were more likely than adults to smoke American cigarette br and s , and the adolescent market share of American br and s has increased rapidly , especially for menthol br and s. Conclusions : This survey revealed the seriousness of the problem of smoking behaviour among Japanese high school students , and suggested that this behaviour may be influenced by social environmental factors , including the marketing strategies of the tobacco industry . Action should be taken to reduce the prevalence and impact of pro-tobacco marketing messages and to abolish cigarette vending machines BACKGROUND Menthol cigarettes account for 25 % of the market in the U.S. The Food and Drug Administration currently is considering regulatory action on tobacco products , including a ban on menthol cigarettes . With 39 % of menthol smokers reporting that they would quit smoking if menthol cigarettes were banned , there is a need to better underst and whether existing cessation programs , such as quitlines , are serving menthol smokers . PURPOSE This study compared baseline characteristics and cessation outcomes of menthol and nonmenthol smokers who were seeking treatment through a quitline . METHODS Data were collected between September 2009 and July 2011 on 6257 participants . A r and om sample of eligible participants who registered for services between March 2010 and February 2011 was contacted for a follow-up survey 7 months post- registration ( n=1147 ) . Data were analyzed in 2011 . RESULTS Among participants , 18.7 % of smokers reported using menthol cigarettes . Menthol smokers were more likely to be female , younger , African-American , and have less than a high school education . Menthol smokers who called the quitline were slightly less likely to enroll in services than nonmenthol smokers ( 92.2 % vs 94.8 % , p<0.001 ) . However , for those that did enroll , there were no significant differences in self-reported intent-to-treat 30-day point prevalence abstinence rates between menthol and nonmenthol smokers ( 17.3 % vs 13.8 % , p=0.191 ) . CONCLUSIONS Quitlines appear to be adequately serving menthol smokers who call for help . Cessation outcomes for menthol smokers are comparable to nonmenthol smokers . However , if a menthol ban motivates many menthol smokers to quit , quitlines may have to increase their capacity to meet the increase in dem and BACKGROUND African American smokers are more likely to experience tobacco-related morbidity and mortality than European American smokers , and higher rates of menthol cigarette smoking may contribute to these disparities . METHODS We prospect ively measured cumulative exposure to menthol and nonmenthol cigarettes and smoking cessation behavior ( 1985 - 2000 ) , coronary calcification ( 2000 ) , and 10-year change in pulmonary function ( 1985 - 1995 ) in African American and European American smokers recruited in 1985 for the Coronary Artery Risk Development in Young Adults Study . RESULTS We identified 1535 smokers in 1985 ( 972 menthol and 563 nonmenthol ) ; 89 % of African Americans preferred menthol vs 29 % of European Americans ( P<.001 ) . After adjustment for ethnicity , demographics , and social factors , we found nonsignificant trends in menthol smokers toward lower cessation ( odds ratio [ OR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.49 - 1.02 ; P = .06 ) and recent quit attempt ( OR , 0.77 ; 95 % CI , 0.56 - 1.06 ; P = .11 ) rates and a significant increase in the risk of relapse ( OR , 1.89 ; 95 % CI , 1.17 - 3.05 ; P = .009 ) . Per pack-year of exposure , however , we found no differences from menthol in tobacco-related coronary calcification ( adjusted OR , 1.27 ; 95 % CI , 1.01 - 1.60 for menthol cigarettes and 1.33 ; 95 % CI , 1.06 - 1.68 for nonmenthol cigarettes per 10-pack-year increase ; P = .75 for comparison ) or 10-year pulmonary function decline ( adjusted excess decline in forced expiratory volume in 1 second , 84 mL ; 95 % CI , 32 - 137 for menthol cigarettes and 80 mL ; 95 % CI , 30 - 129 for nonmenthol cigarettes , per 10-pack-year increase ; P = .88 for comparison ) . CONCLUSION Menthol and nonmenthol cigarettes seem to be equally harmful per cigarette smoked in terms of atherosclerosis and pulmonary function decline , but menthol cigarettes may be harder to quit smoking BACKGROUND Menthol cigarettes , preferred by African American smokers , have been conjectured to be harder to quit and to contribute to the excess lung cancer burden among black men in the Unites States . However , data showing an association between smoking menthol cigarettes and increased lung cancer risk compared with smoking nonmenthol cigarettes are limited . The Food and Drug Administration is currently considering whether to ban the sale of menthol cigarettes in the United States . METHODS We conducted a prospect i ve study among 85,806 racially diverse adults enrolled in the Southern Community Cohort Study during March 2002 to September 2009 according to cigarette smoking status , with smokers classified by preference for menthol vs nonmenthol cigarettes . Among 12,373 smokers who responded to a follow-up question naire , we compared rates of quitting between menthol and nonmenthol smokers . In a nested case-control analysis of 440 incident lung cancer case patients and 2213 matched control subjects , using logistic regression modeling we computed odds ratios ( ORs ) and accompanying 95 % confidence intervals ( CIs ) of lung cancer incidence , and applied Cox proportional hazards modeling to estimate hazard ratios ( HRs ) of lung cancer mortality , according to menthol preference . RESULTS Among both blacks and whites , menthol smokers reported smoking fewer cigarettes per day ; an average of 1.6 ( 95 % CI = 1.3 to 2.0 ) fewer for blacks and 1.8 ( 95 % CI = 1.3 to 2.3 ) fewer for whites , compared with nonmenthol smokers . During an average of 4.3 years of follow-up , 21 % of participants smoking at baseline had quit , with menthol and nonmenthol smokers having equal odds of quitting ( OR = 1.02 , 95 % CI = 0.89 to 1.16 ) . A lower lung cancer incidence was noted in menthol vs nonmenthol smokers ( for smokers of < 10 , 10 - 19 , and ≥ 20 cigarettes per day , compared with never smokers , OR = 5.0 vs 10.3 , 8.7 vs 12.9 , and 12.2 vs 21.1 , respectively ) . These trends were mirrored for lung cancer mortality . In multivariable analyses adjusted for pack-years of smoking , menthol cigarettes were associated with a lower lung cancer incidence ( OR = 0.65 , 95 % CI = 0.47 to 0.90 ) and mortality ( hazard ratio of mortality = 0.69 , 95 % CI = 0.49 to 0.95 ) than nonmenthol cigarettes . CONCLUSIONS The findings suggest that menthol cigarettes are no more , and perhaps less , harmful than nonmenthol cigarettes BACKGROUND African Americans have higher tobacco-related morbidity and mortality and are more likely to smoke menthol cigarettes than their white counterparts . This study examined differences between African American menthol and non-menthol smokers in smoking characteristics and cessation . METHODS The study sample consisted of 600 African American smokers enrolled in a clinical trial that assessed the efficacy of sustained-release bupropion for smoking cessation . Menthol ( n = 471 ) and non-menthol ( n = 129 ) smokers were compared on smoking-related characteristics and abstinence rates at 6 weeks and 6 months . RESULTS Menthol smokers were younger ( 41.2 versus 52.9 years ) , more likely to be female ( 73.7 % versus 56.6 % ) and more likely to smoke their first cigarette within 30 minutes of waking up ( 81.7 % versus 69.8 % ) compared to non-menthol smokers ( all P < 0.01 ) . Cigarette taste ( 50 % versus 40 % , P = 0.054 ) was rated non-significantly higher by menthol smokers . Seven-day point-prevalence abstinence from smoking at 6 weeks were 28 % and 42 % ( P = 0.006 ) and at 6 months were 21 % and 27 % ( P = 0.21 ) for menthol and non-menthol smokers , respectively . At 6 weeks follow-up , stepwise logistic regression revealed that among those younger than 50 years , non-menthol smokers were more likely to quit smoking ( odds ratio = 2.0 ; 95 % CI = 1.03 - 3.95 ) as were those who received bupropion ( odds ratio = 2.12 ; 95 % CI = 1.32 - 3.39 ) . CONCLUSION African American menthol smokers had lower smoking cessation rates after 6 weeks of treatment with bupropion-SR , thereby putting menthol smokers at greater risk from the health effects of smoking . Lower overall cessation rates among African Americans menthol smokers may partially explain ethnic differences in smoking-related disease risks Background African Americans are disproportionately exposed to cigarette advertisements , particularly for menthol br and s. Tobacco industry documents outline strategic efforts to promote menthol cigarettes to African Americans at the point of sale , and studies have observed more outdoor and retail menthol advertisements in neighborhoods with more African-American residents . Little research has been conducted to examine the effect of this target marketing on adolescents ’ recognition of cigarette br and advertising and on smoking uptake . To our knowledge , this is the first study to examine racial differences in br and recognition and to assess the prospect i ve relationship between br and recognition and smoking uptake . Methods School-based surveys assessing tobacco use and environmental and social influences to smoke were administered to 6th through 9th grade rs ( ages 11 to 15 ) in an urban and racially diverse California school district . The primary outcome for the cross-sectional analysis ( n = 2,589 ) was br and recognition , measured by students ’ identification of masked tobacco advertisements from the point of sale . The primary outcome for the longitudinal analysis ( n = 1,179 ) was progression from never to ever smoking within 12 months . Results At baseline , 52 % of students recognized the Camel br and , 36 % Marlboro , and 32 % Newport . African-American students were three times more likely than others to recognize Newport ( OR = 3.03 , CI = 2.45 , 3.74 , p < 0.01 ) and less likely than others to recognize Marlboro ( OR = 0.60 , CI = 0.48 , 0.73 , p < 0.01 ) . At follow-up , 17 % of never smokers reported trying smoking . In this racially diverse sample , br and recognition of Camel and Marlboro did not predict smoking initiation . Regardless of race , students who recognized the Newport br and at baseline were more likely to initiate smoking at follow-up ( OR = 1.49 , CI = 1.04 , 2.15 , p < 0.05 ) after adjusting for shopping frequency and other risk factors . Conclusions The study findings illustrate that African-American youth are better able to recognize Newport cigarette advertisements , even after adjustment for exposure to smoking by parents and peers . In addition , recognition of Newport cigarette advertising predicted smoking initiation , regardless of race . This longitudinal study contributes to a growing body of evidence that supports a ban on menthol flavored cigarettes in the US as well as stronger regulation of tobacco advertising at the point of sale BACKGROUND Research suggests that mentholated cigarettes may play a role in cocaine dependence . The purpose of the present study was to exp and upon the research on mentholated cigarettes and cocaine dependence and to evaluate the role of mentholated cigarettes in methamphetamine dependence . METHODS Secondary analysis of a multisite , r and omized trial evaluating the impact of smoking-cessation treatment in stimulant-dependent out patients ( N=538 ) . Participants ' reasons for concurrent use of cigarettes and illicit stimulants were assessed via self-report . Stimulant-abstinence was measured by self-report and urine drug screens . Smoking cessation was assessed via self-report and carbon monoxide levels . RESULTS Of the 301 cocaine-dependent participants , 201 ( 67 % ) were menthol and 100 ( 33 % ) were non-menthol cigarette smokers . Cocaine-dependent participants who smoked menthol , compared to non-menthol , cigarettes were significantly more likely to report that cigarettes prolong their cocaine high ( X(2)(1)=16.3 , p<.0001 , OR=3.58 [ 95 % CI : 1.88 - 6.79 ] ) and were less likely to be stimulant abstinent during active treatment ( W=3.6 , p<0.001 , d=.39 [ 95 % CI : 0.16 - 0.62 ] ) , at 3-month follow-up ( X(2)(1)=14.4 , p<0.001 , OR=.32 [ 95 % CI : 0.17 - 0.58 ] ) , and at 6-month follow-up ( X(2)(1)=4.6 , p=0.03 , OR=.53 [ 95 % CI : 0.29 - 0.95 ] ) . No parallel differences were found between menthol and non-menthol methamphetamine-dependent smokers . The prevalence of Caucasian menthol smokers was significantly greater in the cocaine-dependent participants ( 37.2 % ) than in the methamphetamine-dependent participants ( 17.61 % ) , ( X(2)(1)=14.4 , p<.001 , OR=2.77 [ 95 % CI:1.62 - 4.73 ] ) . Smoking cessation was not significantly associated with cigarette type for either cocaine- or methamphetamine-dependent participants . CONCLUSIONS The present results suggest that mentholated cigarettes play a role in cocaine , but not methamphetamine , dependence CONTEXT It has not been determined if a youth 's reaction to the first smoking experience is predictive of future nicotine dependence , or whether the impact of the first cigarette can be altered by manipulating levels of tar , nicotine and menthol . OBJECTIVE To determine if the recalled response to the first cigarette is predictive of the development of symptoms of nicotine dependence and whether it is influenced by the type of cigarette smoked . DESIGN AND SETTING A retrospective/ prospect i ve longitudinal study of the natural history of nicotine dependence employing individual interviews conducted three times annually in two urban school systems over 3 years . Subjects were asked to recall their first smoking experience . PARTICIPANTS A cohort of 237 subjects who had inhaled on a cigarette . MAIN OUTCOME MEASURES Symptoms associated with smoking ; the Hooked on Nicotine Checklist of 10 symptoms of dependence . RESULTS Reactions to the initial smoking experience were unrelated to gender or cigarette br and , strength or mentholation . Relaxation in response to the first inhalation was the strongest predictor of symptoms of nicotine dependence . Dizziness and nausea were also independent predictors of dependence symptoms . CONCLUSIONS The data suggest that increased sensitivity to nicotine as manifested by relaxation , dizziness , or nausea in response to the first exposure to nicotine represents a risk factor for the development of nicotine dependence AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed Objective : To examine the association between the use of menthol cigarettes and smoking cessation , amount smoked , and time to first cigarette in the morning . Background : The majority of African American smokers smoke mentholated cigarettes . Some evidence suggests that African Americans may be more nicotine dependent than whites . One theory is that menthol in cigarettes is responsible for enhancing the dependence producing capacity of cigarettes ; however , few studies have prospect ively examined the association between menthol use and indicators of nicotine dependence . Methods : Baseline smokers from the Community Intervention Trial for Smoking Cessation ( COMMIT ) completed a telephone tobacco use survey in 1988 and were re-interviewed in 1993 . Use of mentholated cigarettes was assessed by self report at baseline . Indicators of dependence examined were six month cessation in 1993 , amount smoked among continuing smokers in 1993 , and time to first cigarette in the morning in 1988 . Multivariate regression techniques were used to assess the association of baseline menthol use with these outcomes while controlling for other factors related to dependence . Results : Overall , 24 % of the sample smoked a mentholated br and in 1988 . No consistent associations were observed for menthol use and indicators of dependence in both overall and race specific analyses . Factors significantly associated with increased menthol use were female sex , age 25–34 years , African American and Asian race/ethnicity , greater education , greater than 60 minutes to the first cigarette in the morning , two or more past quit attempts , and use of premium br and cigarettes . Canadian respondents and those who smoked 15–24 cigarettes per day had lower rates of menthol use . Use of mentholated cigarettes was not associated with quitting , amount smoked , or time to first cigarette in the morning . Conclusion : Future work is needed to clarify the physiological and sociocultural mechanisms involved in mentholated cigarette smoking BACKGROUND Studies have shown that individuals who smoke menthol cigarettes are less likely to quit smoking and more likely to relapse during a quit attempt . The current study investigated menthol cigarette use as a potential predictor of smoking cessation outcomes in a sample of treatment-seeking smokers . METHODS This is a secondary analysis of data from a r and omized controlled trial of low-dose naltrexone augmentation of nicotine replacement design ed to examine smoking cessation and postcessation weight gain in weight-concerned smokers . RESULTS Analyses revealed that menthol use predicted lower quit rates . Among menthol smokers ( N = 61 ) , 13 % were abstinent at week 26 , and among nonmenthol smokers ( N = 105 ) , 30 % were abstinent ( Wald = 4.15 , p = .04 ; odds ratio [ OR ] = 2.47 ; 95 % CI = 1.04 - 5.90 ) . Further , menthol smokers who quit smoking gained significantly more weight at week 26 ( M = 14.87 lbs , SD = 9.08 ; t(37 ) = -2.22 , p = .03 ) than nonmenthol smokers who quit ( M = 7.95 lbs , SD = 7.53 ) . CONCLUSIONS Menthol cigarette use has not typically been evaluated as a predictor of smoking cessation outcomes , but emerging evidence suggests that consumption of menthol may make cessation more difficult . This study adds to the literature supporting the cl aim that smoking menthol cigarettes can have adverse effects on smoking cessation efforts and on other cessation-related outcomes , such as postcessation weight gain INTRODUCTION Menthol cigarettes were historically marketed as " healthier " cigarettes , and menthol possesses cooling qualities that may reduce the perceived harshness of cigarette smoke . As such , it is possible that smokers may perceive menthol cigarettes to be safer when , in fact , some research suggests that menthols may be more addictive than regular cigarettes . Research shows that smokers have a faulty underst and ing of the risks of cigarettes in general , but little is known about smokers ' risk perceptions for these particular products . METHODS We examined data from the 2005 New Jersey Adult Tobacco Survey , a statewide r and om-digit-dial telephone survey monitoring tobacco-use behavior , knowledge , and attitudes and which asked participants to compare how risky ( somewhat less risky , about the same , or somewhat more risky ) menthol cigarettes were with nonmenthol cigarettes . RESULTS Few menthol smokers ( 2.4 % ) and survey respondents overall ( 4.0 % ) believed menthol cigarettes to be less risky than nonmenthol cigarettes . In contrast , 30.2 % of menthol smokers and 25.9 % of all respondents ( including nonsmokers ) believed menthols to be more risky than nonmenthol cigarettes . Compared with never-smokers , nonmenthol smokers were most likely to believe this ( AOR = 4.51 ) , followed by former smokers ( AOR = 1.77 ) and current menthol smokers ( AOR = 1.58 ) . Among current smokers , Blacks ( AOR = 2.17 ) were more likely than Whites to indicate menthols as being more risky and young adults ( 18- to 24-year-olds ) were the age group most likely to hold this belief ( AOR = 3.30 ) . CONCLUSIONS Future research should explore whether these perceptions exist in broader population groups as well as their development and association with smoking-related behaviors BACKGROUND Despite smoking fewer cigarettes per day , African Americans have lower cessation rates and experience disproportionately higher rates of smoking-related health consequences . Because of their high preference for menthol cigarettes , it has been suggested that smoking menthol cigarettes may contribute to the excess smoking-related morbidity experienced by African Americans . Smoking menthol cigarettes could increase health risks from smoking if smokers of menthol cigarettes have lower cessation rates and thereby have longer duration of smoking compared to smokers of nonmentholated cigarettes . Few studies have examined associations between smoking of mentholated cigarettes and smoking cessation among African Americans . This study examined the smoking patterns of menthol cigarette smokers and their smoking cessation experiences . METHODS A cross-sectional survey of 480 African-American smokers at an inner-city health center . Survey examined sociodemographics , smoking characteristics , and smoking cessation experiences of participants . Menthol smokers ( n = 407 ) were compared to nonmenthol smokers ( n = 73 ) in these characteristics . RESULTS Menthol smokers were younger and more likely to smoke cigarettes with longer rod length , with filters , and those high in nicotine and tar . Although both groups did not differ by number of past quit attempts , time since most recent quit attempt was shorter for menthol smokers . The duration s of most recent and longest-ever quit attempts were nonsignificantly shorter for menthol , compared to nonmenthol smokers . CONCLUSIONS These data suggest that African-American menthol smokers are less successful with smoking cessation . Prospect i ve studies are needed to confirm these findings and examine mechanisms underlying such differences |
13,036 | 22,915,970 | Although some studies show promise regarding the benefits of patient-focused care , these methods require additional study on feasibility and strategies for implementation in real world setting s. Further , it is imperative that future studies must be , themselves , patient-centered ( eg , pragmatic comparative effectiveness studies ) and applicable to a variety of patient population s and setting s. Despite the need for further research , enough evidence exists that supports incorporating a patient-centered approach to asthma management , in order to achieve improved outcomes and patient health | Patient-centered care may be pivotal in improving health outcomes for patients with asthma .
In addition to increased attention in both research and clinical forums , recent legislation also highlights the importance of patient-centered outcomes research in the Patient Protection and Affordable Care Act .
However , whether patient-centered care has been shown to improve outcomes for this population is unclear .
To answer this question , we performed a systematic review of the literature that aim ed to define current patient-focused management issues , characterize important patient-defined outcomes in asthma control , and identify current and emerging treatments related to patient outcomes and perspectives . | RATIONALE Although inadequate health literacy has been associated with lower asthma medication knowledge and worse metered-dose inhaler ( MDI ) technique , the relationship between health literacy and the capacity to learn asthma self-management skills is unknown . OBJECTIVES In this prospect i ve cohort study of adults hospitalized for severe asthma exacerbations at two inner-city hospitals , we examined the relationship between inadequate health literacy and difficulties learning and retaining instructions about discharge medications and appropriate MDI technique . METHODS At hospital discharge , participants received one-on-one , 30-min , guideline -based , written and oral instruction about their asthma discharge regimen as well as appropriate MDI technique . MEASUREMENTS AND MAIN RESULTS Seventy-three patients were enrolled . Inadequate health literacy was identified in 16 ( 22 % ) participants . Before instruction , inadequate health literacy was associated with lower asthma medication knowledge ( 5.2/10 vs. 7.2/10 , p < 0.001 ) and worse MDI technique ( 3.2/6 vs. 3.9/6 , p = 0.03 ) . However , inadequate health literacy was not associated with difficulty learning ( p = 0.33 ) or retaining ( p = 0.35 ) instructions about the discharge regimen . Similarly , inadequate health literacy was not associated with difficulty learning ( p = 0.26 ) or retaining ( p = 0.97 ) appropriate MDI technique . Results were similar in multivariable models adjusted for demographic characteristics and asthma severity indicators . CONCLUSIONS These findings suggest that inadequate health literacy is a surmountable barrier to learning and remembering key asthma self-management skills Patients with chronic conditions are increasingly using complementary therapies . Asthma is the most common chronic disease in the UK . Qualitative research has suggested reasons why asthma patients use complementary therapies . However , there is little reliable quantitative evidence regarding the prevalence of complementary therapy use among asthma patients and predictors of use . A postal survey of complementary therapy use among asthma patients was therefore conducted via 27 general practice s across seven Primary Care Trusts within the South West Strategic Health Authority ( Engl and ) , during August 2005 to May 2006 . A total of 14,833 asthma patients were identified . A 1-in-4 r and om sample generated 3693 potential respondents , of whom 1320 ( 36 % ) returned question naires . Taking full account of the survey design , 14.5 % ( 190/1308 ; 95 % confidence interval 12.5 % to 16.6 % ) had used complementary therapies for asthma ; 54 % of these patients had not disclosed their complementary therapy use to a health professional . The three therapies most commonly used were homeopathy , herbal medicine and relaxation . Just over half of those using complementary therapies for asthma reported that they usually or always helped ; the most common reported benefits were symptom reduction , calming breathing and reducing panic . Multivariable analyses indicated an inverted U-shaped relationship between complementary therapy use for asthma and age , and increased likelihood of use among women , those with educational qualifications , those not usually helped by asthma medication , and those who have difficulty sleeping because of asthma symptoms . Dissatisfaction with conventional care was not associated with complementary therapy use for asthma . Asthma patients may use complementary therapies with or without the knowledge of their healthcare providers . Open communication between professionals and patients about complementary therapies may be valuable to give patients enhanced opportunities to discuss the impact of asthma on their quality of life and the effectiveness of their conventional treatment High re-attendance rates are common after asthma emergency department ( ED ) care . Inadequate patient education has been cited as a potential cause of re-attendance and the optimal format of education is uncertain . The present study aim ed to compare the effectiveness of patient-centred education ( PCE ) and st and ard asthma patient education on ED re-attendance . A r and omised controlled trial was conducted at two inner-city Australian teaching hospitals ’ EDs , where patients received either st and ard patient education ( SPE ) or PCE . Both groups received a six-topic curriculum . However , PCE patients reordered the topics according to their own priority and thus controlled the order of education . In total , 146 adult patients presenting to EDs with acute asthma were enrolled . After 4 months , ED re-attendance decreased from 22 to 12 % in the PCE group and remained unchanged in the SPE group ( between group odds ratio 0.4 , 95 % confidence interval ( 0.2–1.1 ) ) . In 78 patients discharged after ED care , the PCE group had fewer re-attendances after 4 and 12 months ( 0.3 ( 0.1–0.9 ) and 0.3 ( 0.1–0.8 ) , respectively ) . PCE patients with no general practitioner care in the preceding 7 days had fewer re-attendances after 4 and 12 months ( 0.1 ( 0.0–0.7 ) and 0.2 ( 0.0–0.6 ) , respectively ) . A trend of better asthma control was evident , with a reduction in activity limitation . In conclusion , patient-centred education offers promise as a brief education process in the emergency department . However , a large multicentre trial of patient-centred education is required BACKGROUND Psychosocial factors play an important role in outcomes of asthma . Perceived control , a measure of patients ' beliefs about their ability to control their disease , has not been studied in association with asthma health outcomes METHODS We used data from a prospect i ve cohort study of patients who were hospitalized for asthma ( n = 865 ) . After hospital discharge , we conducted structured telephone interviews to obtain demographic characteristics , asthma history , and psychological variables . Interviews included administration of the Perceived Control of Asthma Question naire ( PCAQ ) . We then prospect ively measured emergency department ( ED ) visits and hospitalizations for asthma over time , with a median follow-up time of 1.9 years RESULTS Greater perceived control was associated with better physical health status ( mean score increment per 2-point change in PCAQ score , 1.13 ; 95 % confidence interval [ CI ] , 0.79 to 1.47 ) , better asthma-related quality of life ( mean score increment , -2.24 ; 95 % CI , -2.6 to -1.83 ) , fewer days of restricted activity due to asthma ( mean increment , -1.23 ; 95 % CI , -1.62 to -0.83 ) , and lower asthma severity scores ( mean score increment , -0.40 ; 95 % CI , -0.53 to -0.27 ) . In a multivariate model , greater perceived control was associated with a significantly decreased prospect i ve risk of ED visits ( hazard ratio [ HR ] , 0.92 ; 95 % CI , 0.86 to 0.98 ; p = 0.008 ) and hospitalizations for asthma ( HR , 0.84 ; 95 % CI , 0.78 to 0.90 ; p < 0.0001 ) . There was no association found between perceived control and most aspects of preventive care or self-management CONCLUSIONS Greater perceived control is associated with improved asthma-related health status as well as with a decreased prospect i ve risk of severe asthma attacks result ing in emergency health-care utilization . This difference does not appear to be mediated by changes in preventive care or asthma self-management practice The purpose of the research was to develop , implement , and evaluate a new adult asthma self-management program with a multidisciplinary perspective . Small groups of adults met for 2 hr for 7 consecutive weekly meetings . Participants were asked to practice asthma specific behaviors ( including peak expiratory flow monitoring , avoidance/removal of asthma triggers , and controller medication adherence ) and general lifestyle behaviors ( including drinking water , practicing relaxation , washing h and s , and exercising ) . Learner-centered teaching techniques such as interactive communication and social support were utilized to help participants practice self-management behaviors including problem-solving and goal - setting . Paired sample t-tests included statistically significant improvements in asthma knowledge , asthma specific quality of life ( QOL ) , asthma specific behaviors such as peak flow monitoring and general life style behaviors such as frequency of daily exercise . These results provide evidence that this new adult asthma self-management program can lead to both knowledge acquisition and behavioral changes Background . Some asthma patients remain poorly controlled despite receiving care consistent with treatment guidelines . Objective . This study compared the ability to sleep , work , and participate in leisure activities among subjects with immunoglobulin E – mediated ( allergic ) asthma initiating omalizumab ( omalizumab start group ) with subjects receiving moderate-to-high doses of salmeterol/fluticasone combination therapy , who continued on salmeterol/fluticasone combination therapy for at least a year without adding omalizumab ( salmeterol/fluticasone combination continuation group ) . Methods . Subjects completed an Internet-based screener and , if eligible , an Internet-based question naire . A propensity score model was utilized in the analysis . Group differences were assessed through logistic and linear regression models . Analyses were adjusted for propensity score quintile , how subjects heard about the study , and responses to retrospective single-item questions . Results . The analysis population included 86 omalizumab start group subjects and 436 salmeterol/fluticasone combination continuation subjects , recruited from June to November 2006 . In the adjusted analyses , the omalizumab start group was more than twice as likely to have controlled asthma as measured by the Asthma Control Test ( odds ratio , 2.62 ; p = 0.005 ) . The omalizumab start group had significantly fewer sleep disturbances as measured by the Jenkins Sleep Evaluation Question naire ( least-square means difference , −1.65;p = 0.004 ) , less activity impairment as measured by the Work Productivity Activity Impairment-Asthma Scale ( least-square means difference , −13.36;p < 0.001 ) , and less difficulty in activities as measured by the Valued Life Activities Question naire ( least-square means difference , −0.24 ; p < 0.001 ) . Conclusion . Asthma subjects who started taking omalizumab reported more improvement in asthma control , fewer sleep problems , less activity impairment , and less difficulty with activities than a similar cohort of subjects who continued taking salmeterol/fluticasone combination therapy Background Internet-based self-management has shown to improve asthma control and asthma related quality of life , but the improvements were only marginally clinical ly relevant for the group as a whole . We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma . Methods In a 1-year r and omised controlled trial involving 200 adults ( 18 - 50 years ) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Question naire ( ACQ ) . Participants were assigned either to the Internet group ( n = 101 ) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group ( UC ) ( n = 99 ) . We analysed 3 subgroups : patients with well controlled ( ACQ ≤ 0.75 ) , partly controlled ( 0.75>ACQ ≤ 1.5 ) or uncontrolled ( ACQ>1.5 ) asthma at baseline . Results Overall monitoring adherence was 67 % ( 95 % CI , 60 % to 74 % ) . Improvements in ACQ score after 12 months were -0.14 ( p = 0.23 ) , -0.52 ( p < 0.001 ) and -0.82 ( p < 0.001 ) in the Internet group compared to usual care for patients with well , partly and uncontrolled asthma at baseline , respectively . Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma ( + 278 μg , p = 0.001 ) , but not in patients with well or partly controlled asthma . After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care . Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients ' needs . Trial registration Current Controlled Trials IS RCT Background : In clinical trials of asthma , the outcomes are often good , but when the same treatment regimens are implemented in primary care , equally good results are not obtained . Objective : To investigate if addition of structured patient information and monitoring by an asthma diary in primary care improves asthma control . Methods : 141 patients from 19 primary care centres were studied . The centres were r and omised to a st and ard care group or to an intervention group . The intervention group received structured written and oral information about asthma and asthma medication , and were instructed to keep an asthma diary . The primary outcome was asthma control as assessed by the Asthma Control Question naire . Secondary outcomes were costs of asthma medication , the Mini Asthma Quality of Life Question naire score and lung function . Results : Asthma Control Question naire score changes differed between the study groups ( p < 0.05 ) . In the intervention group , these changes ( M = –0.45 ) in asthma control were close to clinical significance ( minimal important difference ≈0.5 ) . Both groups improved in disease-specific quality of life scores . For the intervention group , which changed the most ( p < 0.05 ) , the change exceeded the threshold for the minimal important difference ( 0.5 ) . The costs of medications increased significantly in the intervention group , where adjustments of medication were made more often than in controls . Conclusion : Disease-specific quality of life of asthma patients could be improved by adding structured information and monitoring by diary to st and ard care Background : The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain . Methods : A prospect i ve , parallel group , single-blind , r and omised controlled trial comparing breathing training with asthma education ( to control for non-specific effects of clinician attention ) was performed . Subjects with asthma with impaired health status managed in primary care were r and omised to receive three sessions of either physiotherapist-supervised breathing training ( n = 94 ) or asthma nurse-delivered asthma education ( n = 89 ) . The main outcome was Asthma Quality of Life Question naire ( AQLQ ) score , with secondary outcomes including spirometry , bronchial hyper-responsiveness , exhaled nitric oxide , induced sputum eosinophil count and Asthma Control Question naire ( ACQ ) , Hospital Anxiety and Depression ( HAD ) and hyperventilation ( Nijmegen ) question naire scores . Results : One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training ( 0.38 units , 95 % CI 0.08 to 0.68 ) . At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety ( 1.1 , 95 % CI 0.2 to 1.9 ) , HAD depression ( 0.8 , 95 % CI 0.1 to 1.4 ) and Nijmegen ( 3.2 , 95 % CI 1.0 to 5.4 ) scores , with trends to improved ACQ ( 0.2 , 95 % CI 0.0 to 0.4 ) . No significant between-group differences were seen at 1 month . Breathing training was not associated with significant changes in airways physiology , inflammation or hyper-responsiveness . Conclusion : Breathing training result ed in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology . Such exercises may help patients whose quality of life is impaired by asthma , but they are unlikely to reduce the need for anti-inflammatory medication BACKGROUND Attendance for routine asthma review s is poor . A recent r and omised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates ; however , concerns have been expressed about the generalisability and implementation of the trial 's findings . AIM To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service . DESIGN OF STUDY Phase IV controlled before- and -after implementation study . SETTING A large UK general practice . METHOD Using existing administrative groups , all patients with active asthma ( n = 1809 ) received one of three asthma review services : structured recall with a telephone-option for review s versus structured recall with face-to-face-only review s , or usual-care ( to assess secular trends ) . Main outcome measures were : proportion of patients with active asthma review ed within the previous 15 months ( Quality and Outcomes Framework target ) , mode of review , enablement , morbidity , and costs to the practice . RESULTS A routine asthma review was provided for 397/598 ( 66.4 % ) patients in the telephone-option group compared with 352/654 ( 53.8 % ) in the face-to-face-only review group : risk difference 12.6 % ( 95 % confidence interval [ CI ] = 7.2 to 17.9 , P<0.001 ) . The usual-care group achieved a review rate of 282/557 ( 50.6 % ) . Morbidity was equivalent in the three groups ; however , enablement ( P = 0.03 ) and confidence ( P = 0.007 ) in asthma management were greater in the telephone-option versus face-to-face-only group . The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service ( 10.03 pounds versus 12.74 pounds , mean difference 2.71 pounds ; 95 % CI = 1.92 to 3.50 , P<0.001 ) ; usual-care costs were 11.85 pounds per review achieved . CONCLUSION Routinely offering telephone review s cost-effectively increased asthma review rates , enhancing patient enablement and confidence with management , with no detriment to asthma morbidity . Practice s should consider a telephone option for their asthma review service Background . Feeling a maintenance therapy work right away may provide positive reinforcement and may offer one way to improve adherence in patients with asthma . Precise measurement is required to accurately compare the presence of this effect across clinical trial treatment groups . Methods . Two r and omized , controlled studies tested whether timing of assessment ( daily vs weekly , study 1 ; and predose vs postdose , study 2 ) influenced patients ' reports of whether they can feel a medication working right away ( perception ) , and their satisfaction with this perception ( satisfaction ) . These 2-week US-based multicenter double-blind , parallel-group studies included patients ≥18 years of age with mild to moderate persistent asthma . In each , patients were r and omized to one of two drugs with different onset profiles : budesonide/formoterol pressurized metered-dose inhaler ( pMDI ) 80/4.5 μg × 2 inhalations ( 160/9 μg ) twice daily or budesonide pMDI 80 μg × 2 inhalations ( 160 μg ) twice daily . Patients were further r and omized to complete previously vali date d perception and satisfaction questions in a cross-over fashion , either daily and weekly ( N = 123 ) or predose and postdose ( N = 134 ) . Patient surveys also assessed perceptions of the onset of effect of medication and their value of these perceptions . Results . No significant differences were observed in patients ' reports of perception , either daily versus weekly or predose versus postdose . A statistically significant difference in satisfaction was found in study 1 only , favoring weekly recall ( p < 0.05 ) , with sensitivity analysis showing no difference by treatment group ( p = 0.162 ) . Across both studies , most patients ( 87 % ) who perceived their inhaler working right away ( 136 of 157 patients ) identified positive airway sensations . Most patients reported that feeling their medication work right away is reassuring and would help them manage their asthma . Conclusion . Assessment timing has no effect on patient response to the perception of feeling a medication working right away . Differences found in satisfaction levels reported with weekly versus daily recall were consistent across treatment groups , indicating that no bias was introduced in favor of either treatment group . Patients characterized the perception of feeling a maintenance therapy working right away as easier breathing and reported this perception as beneficial to patient self-care OBJECTIVE To report the results of a 2-year pilot program of asthma education based on National Heart , Lung , and Blood Institute treatment guidelines . PATIENTS AND METHODS Asthmatic members ( n = 6698 ) of a managed care organization received education about their condition directly or through their primary care physician . Medical and pharmacy administrative cl aims data were review ed to measure acute asthma events and prescribed therapies in the first ( the baseline ) and second years of the study . The cl aims data were augmented by member surveys from a stratified r and om sample of 2734 asthmatic patients who were members ( 6 years of age or older ) in the baseline year . RESULTS Compared with the first year , asthmatic members received fewer inpatient services and the proportion of asthmatic members prescribed oral inhaled corticosteroids increased 30 % in the second year . Health-related quality of life , measured with vali date d general and disease-specific instruments ; satisfaction with the quality of care ; exposure to patient education ; knowledge of the disease ; and member 's confidence in their ability to manage their disease showed statistically significant improvements during the follow-up year of the program for both adult and child asthmatic members . CONCLUSION For asthmatic members of this health plan , a comprehensive asthma health management program improved processes of care and outcomes Health-related quality of life and satisfaction with treatment are important and complementary measures of the patient 's health care experience . Whereas health-related quality of life provides information on the implication s and consequences of the disease or its treatment for the patient 's functional ability and well-being , satisfaction with received medical care has an important influence on compliance with therapy . Studies in patients with asthma have shown that health-related quality of life is correlated with symptom control and is a predictor of physician visits . Although few studies of treatment satisfaction using vali date d question naires have been performed , there is evidence that ease of use is an important determinant of patient satisfaction with inhalational devices . Prospect i ve , long-term , naturalistic assessment s of patient satisfaction with such devices , performed alongside studies of their efficacy , could help to improve the overall management of patients with asthma Objective - To examine the influence of inhalation device ( Autohaler versus metered dose inhaler ) and patients ' subjective opinion towards the different devices , as well as daily frequency and duration of treatment on medication compliance . Design - Prospect i ve study measuring compliance in the same patients of the Autohaler twice daily with the metered dose inhaler twice daily , as well the Autohaler twice daily with the Autohaler four times daily . Setting - Primary health care . Subjects - 34 subjects with asthma . Main outcome measures - Patients preference and compliance . Results - Patients preferred the Autohaler . The percentage of patients with a negative opinion towards the metered dose inhaler was 38 % compared with 12 % towards the Autohaler . The median values of the compliance rate of the Autohaler with twice and four times daily frequency were 90.8 % ( 25 - 75th percentile 61.6 - 98.0 % ) and 78.5 % ( 25 - 75th percentile 49.0%-91.2 % ) , respectively ( p < 0.001 ) . The duration of treatment period had a significant negative influence on compliance when four times daily dosage frequency was prescribed ( p = 0.05 ) . Conclusion - In conclusion , the devices ( metered dose inhaler and Autohaler ) and the patients ' opinion about the devices did not significantly contribute to the compliance rates . Compliance towards the medication treatment , however , is negatively influenced by a high daily frequency Background : A study was undertaken to determine the effectiveness of asthma self-management in general practice . Methods : Nineteen general practice s were r and omly allocated to usual care ( UC ) or self-management ( SM ) . Asthma patients were included after confirmation of the GP diagnosis . Follow up was 2 years . Patients kept diary cards and visited the lung function laboratory every 6 months . Outcomes were number of successfully treated weeks , limited activity days , asthma specific quality of life , forced expiratory volume in 1 second ( FEV1 ) , FEV1 reversibility , concentration of histamine provoking a fall in FEV1 of 20 % or more ( PC20 histamine ) , and amount of inhaled steroids . Results : A total of 214 patients were included in the study ( 104 UC/110 SM ; one third of the total asthma population in general practice ) ; 62 % were female . The mean percentage of successfully treated weeks per patient in the UC group was 72 % ( 74/103 weeks ) compared with 78 % ( 81/105 weeks ) in the SM group ( p=0.003 ) . The mean number of limited activity days was 1.2 ( 95 % CI 0.5 to 1.9 ) in the SM group and 3.9 ( 95 % CI 2.5 to 5.4 ) in the UC group . The estimated increase in asthma quality of life score was 0.10 points per visit in the UC group and 0.21 points per visit in the SM group ( p=0.055 ) . FEV1 , FEV1 reversibility , and PC20 histamine did not change . There was a saving of 217 puffs of inhaled steroid per patient in favour of the SM group ( p<0.05 ) . Conclusion : Self-management lowers the burden of illness as perceived by patients with asthma and is at least as effective as the treatment usually provided in Dutch primary care . Self-management is a safe basis for intermittent treatment with inhaled corticosteroids Education on optimal medication use is an essential strategy to improve asthma control . The current authors investigated whether pharmacist interventions , focused on appropriate use of asthma medication and tailor-made to the patient 's current asthma control , would improve asthma control in adult patients . A 6-month r and omised , controlled , parallel-group trial was conducted in 66 community pharmacies in Belgium . Patients were r and omly assigned to receive usual pharmacist care ( n = 94 ) or a pre-defined pharmacist intervention ( n = 107 ) . This intervention mainly focused on improving inhalation technique and medication adherence . Primary outcome was the level of asthma control , as assessed by the Asthma Control Test ® ( ACT ) . Mean ACT scores did not change from baseline for both study groups . However , a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care . The intervention also reduced , for the complete study group , reliever medication use and the frequency of night-time awakenings due to asthma . Inhalation technique and adherence to controller medication were significantly better in the intervention group . In conclusion , pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients BACKGROUND Daily inhaled corticosteroid ( ICS ) use is the cornerstone of asthma management , although it is often suboptimal , especially in inner-city population s. OBJECTIVE To assess the impact of potentially modifiable medication beliefs on adherence with ICS therapy across time . METHODS Asthma history , medication beliefs , and ICS therapy adherence were determined in a prospect i ve , observational cohort . Medication beliefs were based on self-regulation and self-efficacy theory . Self-reported adherence with ICS therapy was assessed using the Medication Adherence Reporting Scale , a vali date d 10-item instrument , at baseline and at 1 and 3 months . Repeated- measures multivariable regression identified beliefs independently associated with adherence across time after adjusting for age , sex , race , and asthma severity . RESULTS The 261 patients were low-income minorities with high rates of asthma hospitalization , emergency department visits , intubation , and oral corticosteroid use . Adherence with ICS therapy was stable across time , with 70 % of patients saying that they used ICS all or most of the time when asymptomatic . Most patients ( 82 % ) thought it was important to use ICS when asymptomatic , although 49 % worried about side effects and 37 % worried about becoming addicted . Although 82 % felt confident in using ICS , 7 % felt that their regimen was hard to follow . In multivariable analyses , the odds of adherence increased for those who felt that using ICS when asymptomatic was important ( odds ratio [ OR ] , 4.15 ) and for those who were confident in using ICS ( OR , 2.23 ) and decreased by worries about side effects ( OR , 0.52 ) or feeling the regimen was hard to follow ( OR , 0.48 ) . CONCLUSIONS Several positive and negative beliefs about ICS were associated with adherence . Eliciting and addressing these potentially modifiable beliefs may help improve adherence and outcomes Abstract Objective Asthma self-management programs are effective but often time-consuming . We evaluated the effects of a shortened asthma self-management program on asthma knowledge , morbidity and asthma-related behaviour in a group of moderate to severe adult asthmatics . Methods The effects of the program were evaluated with a one year prospect i ve trial in a group of 55 asthmatics ( mean age 45 yrs , 42 % males , N=26 in intervention group , N=29 in control group ) by administering question naires and diary exercises at baseline , immediately , 3 and 12 months after the end of the program . Results Asthma-related knowledge and hyperventilation symptoms improved more in the intervention than in the control group and this effect was maintained until 3 months after participation . General asthma symptoms improved significantly , but substantial symptom improvements were also found in the control group . The original effects in the intervention group persisted partly but not significantly 1 year after participation . No significant effects were found on pulmonary function . Conclusions Based on our preliminary results , we conclude that our shortened asthma self-management program had an impact on knowledge and asthma symptoms , especially hyperventilation symptoms , until 3 months after the end of the program . Continuous reinforcement and specifying the program content are essential aspects to obtain more robust and long-lasting effects when administering shortened asthma self-management programs OBJECTIVE --To determine the frequency of poor perception of severity of asthma in general practice . DESIGN --Asthmatic patients recorded their perceived severity of asthma , with a visual analogue score , and a coded measurement of their peak expiratory flow up to four times daily for 14 consecutive days . SETTING S--11 general practice s in and around Bristol . SUBJECTS--255 asthmatic patients ( 139 men and 116 women ) aged 17 - 76 who were recruited by r and om selection from the general practice s ' disease registers or when they requested prescriptions for inhaled bronchodilators . MAIN OUTCOME MEASURES --Correlation between visual analogue scores and peak expiratory flow ( as a percentage of predicted peak flow ) . RESULTS --152 ( 60 % ) of the patients showed no significant correlation between visual analogue asthma scores and simultaneous peak flow measurements ( p > 0.05 ) and were termed poor discriminators . The distribution of good and poor discriminators within each general practice was similar ( chi 2 = 6.11 , df = 10 ) . The two groups were not characterised by differences in the maximum , minimum , or st and ard deviation of peak expiratory flow or visual analogue score ; in age ; or in the proportion of men and women in each group . CONCLUSIONS --In general practice a high proportion of asthmatic patients do not reliably detect changes in their lung function . This reinforces the need for careful objective assessment of lung function in the management of asthma OBJECTIVE To identify any association between asthma and depression and quality of life . DESIGN AND SETTING A face-to-face Health Omnibus Survey of a r and om and representative sample of the South Australian population in August 1998 . PARTICIPANTS 3010 r and omly selected participants aged 15 years and over . MAIN OUTCOME MEASURES Prevalence of doctor-diagnosed asthma , and scores for depression ( measured by PRIME-MD instrument ) and quality of life ( measured by SF-36 ) in affected participants . RESULTS The prevalence of asthma was 9.9 % . The prevalence of major depression was significantly higher for those who experienced dyspnoea , wakening at night with asthma , and morning symptoms of asthma . Quality -of-life scores were also lower for the same groups . CONCLUSIONS Depression is a serious but potentially remediable comorbidity with asthma that may affect appropriate diagnosis and outcome BACKGROUND Asthma guidelines urge teaching patients the knowledge and skills required for self-management , based on the assumption that education will lead to improved skills and better asthma control . METHODS In a prospect i ve , r and omized controlled trial of 65 adults with mild-to-moderate asthma , we examined whether an educational self-management intervention would improve adherence to inhaled corticosteroid therapy , decrease markers of airway inflammation , and improve clinical control . Peak flow , symptoms , and adherence were monitored for 7 weeks . After a 1-week run-in , subjects were assigned r and omly to either the educational intervention or control group . The 30-minute intervention was delivered and reinforced at biweekly intervals . RESULTS Compared with the control group , the intervention group had improvements in adherence to inhaled corticosteroid therapy ( by 30 % vs. -5 % , P = 0.01 ) , self-reported control of asthma ( by 14 % vs. 5 % , P = 0.04 ) , and perhaps quality of life ( by 37 % vs. 21 % , P = 0.06 ) . The direction of change for all other clinical outcomes was more favorable in the intervention group , but not significantly so . Markers of inflammation in sputum decreased more in the intervention group , with sputum eosinophils declining significantly ( P = 0.02 ) . CONCLUSION In asthmatic patients treated with inhaled corticosteroids , education and training in self-management improves adherence with inhaled therapy , perceived control of asthma , and sputum eosinophilia This r and omized clinical trial evaluated the long-term impact of an interactive seminar for physicians based on principles of self-regulation on clinician behaviour , children 's use of health services for asthma , and parent 's views of physician performance . Seventy-four general practice paediatricians , and 637 of their asthma patients aged 1 - 12 yrs , were r and omized to treatment or control . Children and parents were blind to physicians ' participation . Data were collected at baseline and follow-up through self-administered surveys ( paediatricians ) , telephone interviews ( parents ) and medical records . The seminar focused on development of communication and teaching skills and use of therapeutic medical regimens for asthma as outlined in the National Asthma Education and Prevention Program guidelines . Approximately 2 yrs postintervention , treatment group physicians were more likely than control physicians to : use protocol s for delivering asthma education ( odds ratio ( OR ) 4.9 , p=0.2 ) , write down for patients how to adjust medicines when symptoms change ( OR 5.7 , p=0.05 ) , and provide more guidelines for modifying therapy ( OR 3.8 , p=0.06 ) . Parents scored treatment group physicians higher than control physicians on five specific positive communication behaviours . Children seen by treatment group physicians had fewer hospitalizations ( p=0.03 ) and those with higher levels of emergency department ( ED ) use at baseline had fewer subsequent ED visits ( p=0.03 ) . No differences regarding the number of office visits were noted . There were no significant differences found between treatment and control group physicians in the amount of time spent with patients during office visits ( 26 versus 29 min ) or in the number of patients treated with anti-inflammatory medicine . It is concluded that interactive asthma seminars for paediatricians had significant long-term benefits for their asthma care This paper reports on an application of discrete choice modelling to the measurement of patient preferences over asthma symptoms . A sample of patients with moderate to severe asthma was asked to choose between a series of pairs of scenarios characterised by different combinations of asthma symptoms . Their responses were analysed using a r and om effects ordered probit model . The results implied that patients weighted some symptoms more highly than others . Discrete choice modelling proved to be a useful approach for developing preference based outcome measures , although the results show how , in context s where preferences over health care outcomes based on symptoms or some measure of health status are involved , a conventional linear additive model may not always be suitable To assess the efficacy of self-management programs it is important to know what behavioural changes take place . This paper assesses whether including self-treatment guidelines ( action plans ) in a self-management program for adult asthmatics , leads to greater behavioural changes than a program without these guidelines . Patients were r and omised into a self-treatment group ( n=123 ) or an active control group ( n=122 ) . All subjects received self-management training . Discussed topics included the pathophysiology of asthma , medication and side-effects , triggers , symptoms , smoking , physical exercise , and compliance . The only difference was that the self-treatment group received instructions about self-treatment of exacerbations and the control group did not . At 1 year of follow-up asthma-specific self-efficacy expectancies , outcome expectancies , and asthma-specific knowledge improved significantly in all patients . Only self-treatment group patients demonstrated favourable changes in generalised self-efficacy , social support , and self-treatment and self-management behaviour , in case of a hypothetical scenario of a slow-onset exacerbation . We conclude that our self-management program is effective in changing the behavioural variables , and including self-treatment guidelines ( action plans ) has added benefit BACKGROUND Optimal asthma management requires accurate assessment of asthma severity . OBJECTIVE To compare patients ' perceptions of their asthma severity with that obtained by using the guidelines published by the National Asthma Education and Prevention Program 's Expert Panel and with functional impairment measured by spirometry and numeric criteria of the American Thoracic Society . METHODS We enrolled 323 patients age 18 to 50 years who were members of the Kaiser Foundation Health Plan for > or = 1 year in a r and omized control trial of an asthma education program . Each had a confirmed diagnosis of bronchial asthma and had been receiving antiasthma medication for > or = 1 year . Patients rated the severity of their asthma . Office spirometry was performed , and , using the Mini-Wright peak flow meter , patients kept 2-week diaries of at-home recordings of morning and evening peak expiratory flow rates . RESULTS A statistically significant association was noted between patients ' perceptions of asthma severity and both medication severity rating ( P < .001 ) and diurnal variation rating ( P = .003 ) and evening peak expiratory flow rate percentage ( P = .019 ) . In comparison with a severity composite based on criteria of the National Asthma Education Program , 54 % of patients accurately estimated asthma severity , 27 % overestimated , and 20 % underestimated severity . CONCLUSION A clinical ly significant proportion of asthmatic patients substantially underestimate disease severity and thereby may be at risk of increased mortality or morbidity Objective . This trial aim ed to evaluate the feasibility of estimating the effectiveness of acupuncture on asthmatic patients under conventional medical management . Participations and Methods . A prospect i ve r and omized , patient/assessor-blinded , sham acupuncture– , and waiting list – controlled pilot trial was conducted . Forty-five eligible asthmatic participants underwent a 1-week run-in period and were then r and omized into one of three groups : an active acupuncture group , a sham acupuncture group , and a waiting list group . They were instructed to maintain the use of antiasthmatic medications . Needling was administered three times per week for 4 weeks with a 2-week follow-up in the active and sham acupuncture groups . The primary outcome was daily morning peak expiratory flow ( PEF ) and the secondary outcomes included forced expiratory volume one second ( FEV1 ) , quality of life question naire for adult Korean asthmatics ( QLQAKA ) , transition dyspnea index ( TDI ) , serum eosinophil count , and total serum immunoglobulin E ( IgE ) . Results . No significant differences in the between- or within-group values of weekly average PEF ( recorded daily in the morning ) and FEV1 were found . For QLQAKA and TDI , the active acupuncture group showed a significant improvement over the waiting list group at 2 , 4 , and 6 weeks after r and omization . Discussion . Acupuncture as an adjunct therapy to conventional medical care does not seem to affect pulmonary function in asthmatic patients . However , 12 sessions of acupuncture treatment during 4 weeks showed a favorable effect on the quality of life in adult asthmatic patients . Further large trials assessing the effectiveness of acupuncture on the quality of life and symptoms in asthmatic patients are needed Device satisfaction and preference are important patient-reported outcomes to consider when choosing inhaled therapy . A subset of adults ( n = 153 ) with moderate or severe asthma participating in a r and omized parallel-group , double-dummy trial that compared the efficacy and safety of 12 weeks ’ treatment with budesonide delivered via Respimat ® Soft Mist ™ Inhaler ( SMI ) ( 200 or 400 μg bd ) or Turbuhaler ® dry powder inhaler ( 400 μg bd ) , completed a question naire on patient device preference and satisfaction ( PASAPQ ) as part of a psychometric validation . As the study used a double-dummy design to maintain blinding , patients used and assessed both devices , rating their satisfaction with , preference for , and willingness to continue using each device . The mean age of patients was 41 years , 69 % were female and the mean duration of disease was 16 years . Total PASAPQ satisfaction scores were 85.5 and 76.9 for Respimat ® SMI and Turbuhaler ® respectively ( p < 0.0001 ) ; 112 patients ( 74 % ) preferred Respimat ® SMI and 26 ( 17 % ) preferred Turbuhaler ® . Fourteen subjects ( 9 % ) indicated no preference for either inhaler . Willingness to continue using Respimat ® SMI was higher than that for Turbuhaler ® ( mean scores : 80/100 and 62/100 , respectively ) . Respimat ® SMI was preferred to Turbuhaler ® by adult asthma patients who used both devices in a clinical trial setting Background Improving patients ' health-related quality of life ( HRQoL ) is recognized as a fundamental part of asthma management . The aims of this study were to evaluate the long-term efficacy ( including symptom-free days and exacerbations ) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate ( SAL/FP ) and an adjustable maintenance dosing ( AMD ) regimen of formoterol/budesonide ( FOR/BUD ) where treatment is adjusted based on symptoms [ SAM40056 ] . Methods A total of 688 out patients with asthma receiving regular low-dose inhaled corticosteroids ( ICS ) plus a long-acting β2-agonist , or medium dose ICS alone participated in this r and omized , double-blind , double-dummy , parallel-group , 1-year trial , which was conducted in 91 centers in 15 countries . Patients were r and omized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4 . For Weeks 5–52 , patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP . Results The percentage of symptom-free days was significantly greater ( 58.8 % vs 52.1 % ; p = 0.034 ) and the annual exacerbation rate was significantly lower ( 47 % ; p = 0.008 ) with stable-dose SAL/FP compared with FOR/BUD AMD . A total of 568 patients completed the Asthma Quality of Life Question naire ( AQLQ ) at least once during the study . The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52 , but did not reach statistical significance ( p = 0.121 at Week 52 ) . However , in a post hoc logistic regression analyses for any AQLQ improvement , significant benefits with SAL/FP were seen at both time points ( p = 0.038 and p = 0.009 , respectively ) . The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 ( 68 % vs 60 % ; p = 0.049 ) ; a trend for this difference remained at Week 52 ( 71 % vs 65 % ) ( p = 0.205 ) . Conclusion In this population of patients with persistent asthma , stable-dose SAL/FP result ed in significantly greater increases in symptom-free days , a reduction in exacerbation rates , and provided greater HRQoL benefits compared with FOR/BUD AMD.Trial registration Clinical Trials registration number OBJECTIVES As part of the European Community Respiratory Health Survey ( ECRHS ) in 1992 - 1993 we assessed management practice s and treatment perceptions among young asthmatic adults in Melbourne , Australia . METHODOLOGY We conducted a postal question naire survey of 4500 r and omly selected adults ( aged 20 - 44 years ) , drawn from three electoral districts , of whom 3200 ( 71 % ) subjects responded . A r and omly selected sample of 1642 respondents , ' enriched ' by a further 433 symptomatic subjects , was invited to complete a second phase respiratory question naire . RESULTS The question naire was completed by 757 subjects who underwent laboratory testing . A further 119 subjects who were unable to attend the laboratory completed an identical question naire by telephone interview ( 42 % response rate ) . In the second phase , 16 % of subjects reported ' current asthma ' ( group I ) as defined by physician confirmation and a recent attack ( within 1 year ) , 10 % had confirmed asthma but reported no recent attack ( group II ) and 74 % did not have asthma ( group III ) . Inhaled corticosteroid use was significantly higher in group I than in group II subjects ( 45 % vs 24 % , P<0.01 ) , but only 11 % of asthmatic subjects overall reported daily prophylactic use . Regular treatment in any form was considered to be ' bad ' by 65 % of asthmatic subjects and only 43 % took medication as prescribed all of the time . CONCLUSION Despite national education campaigns , the majority of young asthmatic adults in Melbourne did not adhere to prescribed treatment , but continued to rely upon beta2-agonists alone with neglect of regular inhaled corticosteroid which has probably contributed to Australia 's continued high asthma morbidity and mortality rates Background : Anti‐IgE , omalizumab , inhibits the allergen response in patients with asthma . This has not been directly related to changes in inflammatory conditions . We hypothesized that anti‐IgE exerts its effects by reducing airway inflammation . To that end , the effect of anti‐IgE on allergen‐induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a r and omized , double‐blind , placebo‐controlled study BACKGROUND Internet and short message service are emerging tools for chronic disease management in adolescents , but few data exist on the barriers to and benefits of internet-based asthma self-management . Our objective was to reveal the barriers and benefits perceived by adolescents with well-controlled and poorly controlled asthma to current and internet-based asthma management . METHODS Ninety-seven adolescents with mild-to-moderate persistent asthma monitored their asthma control on a design ated Web site . After 4 weeks , 35 adolescents participated in eight focus groups . Participants were stratified in terms of age , gender , and asthma control level . We used qualitative and quantitative methods to analyze the written focus group transcripts . RESULTS Limited self-efficacy to control asthma was a significant barrier to current asthma management in adolescents with poor asthma control ( 65 % ) compared to adolescents with good asthma control ( 17 % ; p < 0.01 ) . The former group revealed the following several benefits from internet-based asthma self-management : feasible electronic monitoring ; easily accessible information ; e-mail communication ; and use of an electronic action plan . Personal benefits included the ability to react to change and to optimize asthma control . Patients with poor asthma control were able and ready to incorporate internet-based asthma self-management for a long period of time ( 65 % ) , whereas patients with good control were not ( 11 % ; p < 0.01 ) . CONCLUSIONS Our findings reveal a need for the support of self-management in adolescents with poorly controlled asthma that can be met by the application of novel information and communication technologies . Internet-based self-management should therefore target adolescents with poor asthma control BACKGROUND The ratio of controller medication to total asthma medications has been related to asthma utilization outcomes , but its relationship to patient-centered outcomes has not been explored . METHODS Surveys that included vali date d asthma quality -of-life , control , and symptom severity tools were completed by a r and om sample of 2,250 health maintenance organization members aged 18 to 56 years who had persistent asthma . Linked computerized pharmacy data provided dispensing information on beta-agonist canisters and asthma controller medication . The ratio was calculated as the number of controller medications dispensed during the year of the survey divided by the total number medications ( ie , inhaled beta-agonist plus controller medications ) dispensed . The relationships of the optimal ratio cutoff to patient-centered outcomes and to subsequent acute asthma exacerbations were determined . RESULTS Mean asthma quality -of-life , asthma control , and symptom severity scale scores were significantly ( p < 0.0001 ) more favorable in patients with ratios of > or = 0.5 . After adjusting for demographic characteristics , patients with ratios of > or = 0.5 were significantly less likely to have adverse results regarding asthma quality of life ( odds ratio [ OR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.52 to 0.80 ) , asthma control ( OR , 0.62 ; 95 % CI , 0.50 to 0.77 ) , and symptom severity ( OR , 0.53 ; 95 % CI , 0.43 to 0.65 ) , and were also less likely to experience subsequent asthma hospitalizations or emergency department visits ( OR , 0.44 ; 95 % CI , 0.26 to 0.74 ) than patients with lower ratios . CONCLUSION A higher controller medication/total asthma medication ratio is associated with better patient-centered asthma outcomes as well as with reduced emergency hospital utilization . This adds further support to the use of the medication ratio as an asthma quality -of-care measure Currently , patients have to keep track of doses to determine when to replace their metered-dose inhalers ( MDIs ) . This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter . In an open-label study at 38 outpatient centres , patients > or = 12 years old with asthma or chronic obstructive pulmonary disease ( COPD ) received two actuations of fluticasone propionate/salmeterol 125/25 microg ( 115/21 microg ex-actuator ) hydrofluoroalkane ( ADVAIR ) HFA ) via MDI with counter twice a day until all 120 actuations were completed . Concordance between counter and diary recordings in patients who reported use of > or = 90 % of labelled actuations ( completer population , n = 228 ) was high ( discrepancy rate of 0.94 % ) and the incidence of device firing without changes in counter readings was low ( 0.13 % ) . Mean expected actuations based on canister weights ( 114 ) were slightly lower than mean counter ( 121 ) and diary reported actuations ( 120 ) . Upon study completion , 95 % of patients were satisfied with the dose counter and 92 % agreed it would help prevent them from running out of medication . Safety assessment s ( intent-to-treat population , n = 237 ) indicated that the drug was well tolerated . This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply ABSTRACT Objective : To determine the effects of budesonide and formoterol administered via one pressurized metered-dose inhaler ( budesonide/formoterol pMDI ) on patient-reported outcomes ( PROs ) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma . Research design and methods : A 12-week , r and omized , double-blind , double-dummy , placebo-controlled , multicenter study was conducted in 480 patients aged ≥ 12 years with mild-to-moderate persistent asthma . After a 2-week run-in period during which current asthma therapy was discontinued , patients were r and omized to receive two inhalations twice daily of budesonide/formoterol pMDI 80/4.5 μg ( 160/9 μg ) , budesonide pMDI 80 μg ( 160 μg ) , formoterol via dry powder inhaler ( DPI ) 4.5 μg ( 9 μg ) , or placebo . Main outcome measures : Analyses included a sub population of 405 patients aged ≥ 18 years . PROs included the st and ardized Asthma Quality of Life Question naire ( AQLQ(S ) ) , the Medical Outcomes Study ( MOS ) Sleep Scale , the Patient Satisfaction with Asthma Medication ( PSAM ) question naire , and asthma control variables ( recorded via electronic diaries ) , such as asthma symptoms , rescue medication use , and nighttime awakenings due to asthma . Patient and physician global assessment s were collected at the end of the study . Results : Patients aged ≥ 18 years receiving budesonide/formoterol pMDI reported significantly greater improvements from baseline in AQLQ overall and domain scores , MOS Sleep Scale domain scores , and asthma control variables than patients receiving placebo ( p ≤ 0.033 ) . Improvements from baseline in AQLQ(S ) overall and domain scores , daily asthma symptoms scores , percentage of symptom-free days , percentage of rescue medication-free days , and percentage of asthma control days were significantly greater in patients receiving budesonide/formoterol pMDI versus formoterol DPI ( p ≤ 0.042 ) . Patients receiving budesonide/formoterol pMDI reported significantly greater PSAM scores than did patients in all other treatment arms ( p ≤ 0.004 ) . Study limitations may include the fact that the formoterol-alone arm used a different device and formulation than the other active arms as well as the absence of a treatment arm with budesonide and formoterol administered concomitantly in separate inhalers . In addition , these results may not be generalized to all patients with asthma , as this analysis included only patients aged ≥ 18 years . Conclusions : Patients receiving treatment with budesonide/formoterol pMDI experienced significantly greater improvements from baseline in asthma-related quality of life , quality of sleep , and asthma control and greater satisfaction with treatment than patients receiving placebo . The combination of budesonide and formoterol in one pMDI is beneficial in improving how a patient feels and functions as a result of treatment BACKGROUND AND OBJECTIVE Previous work has suggested that people with poor health-related quality of life ( HR-QOL ) as a result of asthma are willing to pay the most for successful therapy . There is also evidence that preferences are an important influence on adherence to therapy . We report a patient preference study using a discrete-choice experiment ( DCE ) to elicit willingness to pay ( WTP ) of patients with asthma in Spain , the Netherl and s , and the UK . METHODS The DCE survey included different attributes of asthma therapy ( days with symptoms , days needing reliever medication , asthma attacks [ none , attack that does not require doctor/emergency room { ER } visit , attack that requires doctor/ER visit ] , risk of adverse effects , number of preventer inhalers , and monthly out-of-pocket costs ) . Participants indicated which attribute combinations they preferred . The question naire survey included the mini Asthma Quality of Life Question naire ( mAQLQ ) . The validity of the choice experiment has been supported by two pilot studies conducted in the UK . Preferences and WTP were estimated using a r and om effects probit model . Symptom days and asthma attack attributes were segmented by mAQLQ score . RESULTS Demographic and clinical data were compared between the three country sample s ( UK , n = 124 ; Spain , n = 86 ; the Netherl and s , n = 269 ) . All study attributes were independently significant predictors of choice . People were willing to pay € 35 per month to avoid a day with symptoms , and € 109 per month ( year 2005 values ) to avoid experiencing asthma attacks that required emergency visits to their doctor or hospital . People with the worst HR-QOL were willing to pay the least to avoid days with symptoms and asthma attacks that required visits to their doctor/ER . This was not an income-related effect . CONCLUSION Patients who reported higher HR-QOL were willing to pay more to avoid days with symptoms and asthma attacks that required visits to their doctor/ER . Hypotheses were explored to explain this effect . It is possible that people with the least impairment of HR-QOL place the greatest value on avoiding the effects of asthma and so are most willing to alter their behavior . People with the worst HR-QOL may be exhibiting a response shift type of effect whereby their internal values are shifted down by the burden of their disease . These findings may help to illuminate why there are differences in asthma treatment adherence Background .Certain psychosocial variables are relatively unexplored as possible predictors of asthma outcomes . Objective . To determine if asthma self-efficacy , depressive symptoms , and unrealistic expectations predict urgent care use and change in health-related quality of life measured by the Asthma Quality of Life Question naire and the SF-36 during 2 years . Research Design . Prospect i ve cohort study in a primary care internal medicine practice at a tertiary care center in New York City . Patients . Adults with moderate asthma who were fluent in either English or Spanish . Measurements . At enrollment patients were interviewed in-person and completed a series of question naires including the Asthma Quality of Life Question naire ( AQLQ ) , the SF-36 , the Asthma Self-efficacy Scale , the Geriatric Depression Scale , and open-ended questions regarding their expectations of treatment . Patients also completed the AQLQ and SF-36 at various time intervals throughout the study and were interviewed by telephone every 3 months to record recent hospitalizations , emergency department visits and nonroutine office visits for asthma . Results . A total of 224 patients were followed for a mean of 23.8 months . In hierarchical analysis , independent predictors of lower AQLQ scores were less self-efficacy , more depressive symptoms , expecting to be cured of asthma , requiring methylxanthines , being Hispanic or black , and having difficult or very difficult access to asthma care ( all at P < 0.05 ) . Similar predictors were found for lower SF-36 scores . Another outcome , use of urgent care , was required by 60 % of patients during the study period . Predictors of using urgent care were having more depressive symptoms , expecting a cure , being female , requiring oral & bgr;-agonists , and having a history of prior hospitalizations for asthma ( all at P < 0.05 ) . Conclusions . Less asthma self-efficacy , more depressive symptoms , and unrealistic expectations predict worse asthma outcomes . These relatively unexplored patient-centered variables in asthma are potentially modifiable and may offer new ways to intervene to improve asthma outcomes Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids . This study investigates the relationship between the clinical effect seen in response to additional treatment and the effect on airway inflammatory indices . Seventy-five adult asthmatic patients , incompletely controlled on 800 mcg budesonide/day , were r and omised following a 4 week run-in period , to a double-blind , multi-centre controlled clinical trial of doubling inhaled corticosteroid ( budesonide 1600 mcg/day ) or adding 10 mg montelukast for 12 weeks . Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages , leukotrienes C4 , D4 and E4 , IL-8 , Eosinophil Cationic Protein ( ECP ) and histamine . Sputum evidence of inflammation ( 2.0 % eosinophils ) was seen in only 29 % of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group . There were significant improvements in am PEF ( montelukast : 31.7 L/min , budesonide : 32.3 L/min ) and quality of life with both treatments . We conclude that while both treatments showed similar improvements in lung function and quality of life , there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome Objective : This study was conducted to test the effectiveness of a theory-based interactive voice response ( IVR ) intervention to improve adherence to controller medications among adults with asthma . Methods : Fifty participants aged 18 to 65 years who had a physician diagnosis of asthma and a prescription for a daily inhaled corticosteroid , attended a baseline visit and a final visit 10 weeks later . Participants r and omized to the intervention group received 2 automated IVR telephone calls separated by one month , with one additional call if they reported recent symptoms of poorly controlled disease or failure to fill a prescription . Calls were completed in less than 5 minutes and included content design ed to inquire about asthma symptoms , deliver core educational messages , encourage refilling of inhaled corticosteroid prescriptions , and increase communication with providers . Adherence was tracked during 10 weeks , with objective measures that included either electronic monitors or calculation of canister weight . Participants completed the Asthma Quality of Life Question naire , the Asthma Control Test , and the Beliefs in Medications Question naire ( BMQ ) during both visits . Results : Adherence was 32 % higher among patients in the IVR group than those in the control group ( P = .003 ) . A more favorable shift in perception of inhaled corticosteroids was seen on BMQ scores of patients in the IVR group ( P = .003 ) , which in turn correlated with degree of adherence change ( r = 0.342 ; P = .0152 ) . No differences emerged for the Asthma Quality of Life Question naire or Asthma Control Test . Conclusions : The IVR intervention result ed in a significant increase in adherence to inhaled corticosteroid treatment and improved BMQ scores during the study interval . The association of increased adherence with increased BMQ scores suggests that the intervention succeeded in helping participants adopt a more favorable perception of their controller medication , leading in turn to improved adherence STUDY OBJECTIVES To evaluate whether direct feedback discussion on inhaled steroid use might influence subsequent adherence with this therapy . DESIGN AND SETTING A 10-week , single-blind , r and omized trial in asthma patients . Inclusion criteria included forced expiratory volume in 1 second < 80 % , one or more markers for low socioeconomic status , and the use of inhaled steroids . Inhaled steroid and beta-agonist use were electronically monitored . All patients received st and ard asthma care . The treatment group received direct clinician-to-patient feedback discussion on their inhaled steroid and beta-agonist use on all subsequent visits , whereas this information was withheld during the study period in the control group . MEASURES 1 ) Mean weekly inhaled steroid adherence [ ( number of actuations/prescribed number of actuations ) x 100 ] ; 2 ) number of days with overuse of inhaled steroids ; 3 ) 24-hour and nighttime albuterol use ; 4 ) included forced expiratory volume in 1 second ; and 5 ) Asthma Quality of Life Question naire total score . RESULTS Ten treatment and nine control patients completed the study . Mean weekly inhaled steroid adherence over the first week was not significantly different in the treatment and control groups : 61 + /- 9 % versus 51 + /- 5 % , respectively . However , by the second week , adherence increased to 81 + /- 7 % in the treatment group , whereas it decreased to 47 + /- 7 % in the control group ( P = 0.003 ) . Adherence remained above 70 % in the treatment group for the entire trial , but continued to decrease in the control group . Overuse of inhaled steroids was low in both groups . There were no group differences in any of the asthma outcomes . CONCLUSIONS Direct clinician-to-patient feedback discussion on inhaled steroid use using electronic printouts did improve adherence in the short-term in asthma patients at high-risk for poor adherence Many patients with asthma also have gastroesophageal reflux disease ( GERD ) , and GERD can cause symptoms that mimic those of poorly controlled asthma . Patients with poorly controlled asthma are often treated empirically for GERD , whether or not they have symptomatic reflux . However , a r and omized , placebo-controlled trial funded by the American Lung Association and the National Institutes of Health found that treating silent GERD does not improve asthma control . These results warrant a reevaluation of current guidelines and clinical practice . A recent multicenter trial indicated that empirically prescribing a proton pump inhibitor does not help control asthma symptoms and that current guidelines need to be reevaluated OBJECTIVE To assess the effectiveness of a non-pharmacological intervention in patients with asthma on conventional therapy including inhaled corticosteroid . DESIGN A r and omised controlled trial of the Buteyko technique in a group of adults with asthma . The control group was trained by a physiotherapist in breathing and relaxation techniques . SETTING A single centre associated with a University-based asthma programme . MAIN OUTCOME MEASURE Asthma control , defined by a composite score based on the Canadian asthma consensus report 6 months after completion of the intervention . RESULTS Both groups showed substantial and similar improvement and a high proportion with asthma control 6 months after completion of the intervention . In the Buteyko group the proportion with asthma control increased from 40 % to 79 % and in the control group from 44 % to 72 % . In addition the Buteyko group had significantly reduced their inhaled corticosteroid therapy compared with the control group ( p=0.02 ) . None of the other differences between the groups at 6 months were significant . CONCLUSIONS Six months after completion of the interventions , a large majority of subjects in each group displayed control of their asthma with the additional benefit of reduction in inhaled corticosteroid use in the Buteyko group . The Buteyko technique , an established and widely recognised intervention , or an intensive programme delivered by a chest physiotherapist appear to provide additional benefit for adult patients with asthma who are being treated with inhaled corticosteroid AIMS To determine the magnitude of morbidity from asthma within the New Zeal and population , the degree of satisfaction of patients with their asthma control , and the level of asthma control achieved in relation to treatment . METHODS Participants were r and omly selected from 29 r and omly chosen general practice s throughout New Zeal and . Information was collected from demographic and clinical question naires and from lung function tests . Criteria based on GINA guidelines were developed to define the level of asthma control for each participant , their opinion of their level of control , and to define which participants were under-treated . RESULTS A total of 445 patients ( 327 adults , age 16 - 68 ; 118 children , age 7 - 15 ) took part in the study . Ninety three per cent of adults had asthma that was sub-optimally controlled , 71 % had asthma that was not well controlled , and 19 % had asthma that was markedly out of control . For children , these figures were 90 % , 42 % and 4 % respectively . These results were consistent regardless of asthma severity . In adults and children whose asthma was not well controlled , 49 % and 71 % respectively were under-treated . For those whose asthma was markedly out of control , 89 % and 75 % of adults and children respectively were under-treated . CONCLUSIONS A significant proportion of patients have asthma that is not well controlled or that is markedly out of control , and the majority are under-treated RATIONALE Urban African-American youth , aged 15 - 19 years , have asthma fatality rates that are higher than in whites and younger children , yet few programs target this population . Traditionally , urban youth are believed to be difficult to engage in health-related programs , both in terms of connecting and convincing . OBJECTIVES Develop and evaluate a multimedia , web-based asthma management program to specifically target urban high school students . The program uses " tailoring , " in conjunction with theory-based models , to alter behavior through individualized health messages based on the user 's beliefs , attitudes , and personal barriers to change . METHODS High school students reporting asthma symptoms were r and omized to receive the tailored program ( treatment ) or to access generic asthma websites ( control ) . The program was made available on school computers . MEASUREMENTS AND MAIN RESULTS Functional status and medical care use were measured at study initiation and 12 months postbaseline , as were selected management behaviors . The intervention period was 180 days ( calculated from baseline ) . A total of 314 students were r and omized ( 98 % African American , 49 % Medicaid enrollees ; mean age , 15.2 yr ) . At 12 months , treatment students reported fewer symptom-days , symptom-nights , school days missed , restricted-activity days , and hospitalizations for asthma when compared with control students ; adjusted relative risk and 95 % confidence intervals were as follows : 0.5 ( 0.4 - 0.8 ) , p = 0.003 ; 0.4 ( 0.2 - 0.8 ) , p = 0.009 ; 0.3 ( 0.1 - 0.7 ) , p = 0.006 ; 0.5 ( 0.3 - 0.8 ) , p = 0.02 ; and 0.2 ( 0.2 - 0.9 ) , p = 0.01 , respectively . Positive behaviors were more frequently noted among treatment students compared with control students . Cost estimates for program delivery were $ 6.66 per participating treatment group student . CONCLUSIONS A web-based , tailored approach to changing negative asthma management behaviors is economical , feasible , and effective in improving asthma outcomes in a traditionally hard-to-reach population OBJECTIVE Asthma morbidity and mortality is highest among inner-city population s. Suboptimal beliefs about the chronicity of asthma may perpetuate poor asthma control among inner-city asthmatics . This study sought to characterize beliefs about the chronicity of disease and its correlates in a cohort of inner-city adults with persistent asthma . DESIGN Prospect i ve , longitudinal , observational cohort study . PATIENTS One hundred ninety-eight adults hospitalized with asthma over a 12-month period at an inner-city teaching hospital . MEASUREMENTS Sociodemographics , clinical history , disease beliefs , and self-management behaviors were collected by interview . Information on self-reported use of inhaled corticosteroids ( ICS ) , peak flowmeters , and regular asthma visits was collected during hospitalization , and 1 month and 6 months after discharge . RESULTS This cohort was predominantly low income and nonwhite , with high rates of prior intubation , oral steroid use , and emergency department visits and hospitalizations . Overall , 53 % of patients believed they only had asthma when they were having symptoms , what we call the no symptoms , no asthma belief . Men patients , those > or = 65 years old , and those with no usual place of care had greater odds of having the no symptoms , no asthma belief , and those receiving oral steroids all or most of the time or with symptoms most days had half the odds of having this belief ( p < 0.05 for all ) . The no symptoms , no asthma belief was negatively associated with beliefs about always having asthma , having lung inflammation , or the importance of using ICS , and was positively associated with expecting to be cured . The acute disease belief was associated with one-third lower odds of adherence to ICS when asymptomatic at all three time periods ( p < 0.02 for all ) . CONCLUSION The single question , " Do you think you have asthma all of the time , or only when you are having symptoms ? " can efficiently identify patients who do not think about or manage their asthma as a chronic disease AIM This paper is a report of a trial to examine the effectiveness of individualized self-care education programmes in older adults with moderate-to-severe asthma . BACKGROUND Asthma is a common chronic disease in adults and a major cause of frequent work absences , emergency room visits , and hospitalization . The results of studies of self-care education programmes have been largely supportive and suggest that they have positive outcomes for people with asthma . However , for older people with asthma , the effectiveness of computer-aided , self-learning video programmes has been controversial . METHODS Older adult patients with asthma ( N = 148 ) were r and omly assigned to one of three groups : usual care , individualized education , or individualized education with peak flow monitoring , and followed for 6 months . Data were collected from January to December 2006 . The variables studied included demographic data , asthma self-care competence , asthma self-efficacy , and asthma self-care behaviour . FINDINGS . Patients in both individualized education groups reported higher asthma self-care competence scores ( F = 334.06 and 481.37 , P < 0.001 ) and asthma self-care and self-efficacy scores ( F = 104.08 and 68.42 , P < 0.001 ) than patients in the usual care group . In addition , patients who received individualized education with peak flow monitoring had statistically significantly higher asthma self-care behaviour and self-efficacy scores ( P < 0.001 ) and asthma control indicators ( P = 0.025 ) than the education alone group . No differences were found among the three groups in unscheduled health service usage . CONCLUSION Our results suggest that individualized education helps older people with asthma to enhance their self-care behaviours , manage their disease , and increase their quality of life BACKGROUND Pressurized metered-dose inhalers ( pMDIs ) are the cornerstone of asthma treatment . The pMDI is an economic and portable medication delivery system , but the device does not indicate how much medicine remains in the canister once a patient starts using it . OBJECTIVE To determine how patients evaluate the contents of their pMDI and whether they are either discarding inhalers when medication remains or using inhalers beyond the indicated number of doses . METHODS This study was conducted in April 2003 via a 6.5-minute telephone interview with a r and om sample of 500 families with asthma from across the United States . RESULTS Of the 500 respondents participating in the telephone interview , nearly one third ( 31.6 % ) named an inhaled corticosteroid or bronchodilator and inhaled corticosteroid combination as the inhaler used when wheezing , coughing , or short of breath . Respondents using a bronchodilator ( n = 342 ) varied in the frequency with which they use their pMDIs : 31.9 % daily , 18.7 % weekly , 23.4 % monthly , and 23.1 % less than once per month . More than half ( 53.8 % ) of bronchodilator users refill their prescriptions more frequently than recommended by national guidelines . Only 36 % of bronchodilator users reported ever having been told to keep track of pMDI doses used . Of those , 79 % had been advised to do so by a physician , 6 % by a pharmacist , and 3 % by a nurse . Eighty-seven ( 25 % ) of the 342 respondents who named a bronchodilator reported having found their pMDI empty during an asthma exacerbation . Seven of those patients had to call 911 . Of these 87 patients , 71 ( 82 % ) considered their pMDI empty when absolutely nothing came out . CONCLUSIONS Patients do not have a reliable means of monitoring the contents of their metered-dose inhalers , which is causing serious problems that need to be addressed . Given the necessity of a reliable dose counting method , it is clear that manufacturers should include dose counters as a st and ard feature of every metered-dose inhaler UNLABELLED The use of communication technologies may overcome some of the difficulties of conventional , paper-based , self-management of chronic diseases . This paper aims to describe and evaluate the use of P'ASMA - a web based asthma self-management support tool regarding the opinion of patients and their adherence to monitoring in comparison to st and ard paper-based tools . SYSTEM DESCRIPTION P'ASMA allows the collection of asthma monitoring data and provides , to both patient and doctor , immediate feedback about patient 's condition . For each patient a set of forms and scheduling options can be chosen . EVALUATION METHODS Twenty-one adults with previous medical diagnosis of asthma were included in an exploratory r and omized crossover study . Patients used P'ASMA or a paper asthma diary and action-plan each during 4 weeks in a r and om sequence . RESULTS The number of patients who wrote negative remarks regarding P'ASMA was 2 and regarding paper-tools was 11 ; positive comments were 6 and 1 respectively for P'ASMA and Paper-based . Twelve patients were very interested to continue to monitor their asthma using P'ASMA whereas only 2 with Paper-based ( p=0.002 ) . Of the 19 problems reported with P'ASMA , 9 were related to the Internet connection , 5 to the user interface , 3 to internal system errors and 2 to the questions interpretation . The completeness of paper diary records was better ; however , 10 patients reported filling it several days at once which was not allowed in P'ASMA . CONCLUSIONS The intervention was feasible , safe and the problems detected in the web-application can be corrected . With P'ASMA data quality improved as the integrity features increase the reliability of the data . Moreover , patients preferred the web-based application to monitor their asthma Background : Low-income African-American adolescents suffer a disproportionate burden of asthma morbidity . Purpose : To evaluate the ability of our intervention , the Adolescents ’ Disease Empowerment and Persistency Technology ( ADEPT ) for asthma , to increase asthma knowledge in our target population . Methods : This was a 14-week ( 2-week run-in and 12-week treatment ) r and omized , double-blind , placebo-controlled pilot study in which 28 inner-city African-American adolescents with asthma , between 10 and 18 years of age , were r and omized to receive ( 1 ) celebrity asthma messages ( experimental group ) , or ( 2 ) general health messages ( control group ) between music tracks on an MP3 player . The asthma messages were recorded by famous athletes , musicians , and other celebrities popular among this group of teenagers . Asthma knowledge , assessed by the ZAP Asthma Knowledge instrament , was collected pre- and post-intervention . Results : Mean improvement in ZAP score was significantly higher in the experimental group ( 8.1 % , SD 7.2 % ) than the control group ( 0.4 % , SD 7.2 % ) ( p = 0.05 ) . Conclusion : These findings suggest that this may be an innovative and promising new approach to improving asthma outcomes in this difficult-to-reach population RATIONALE Poor adherence to asthma controller medications results in poor treatment outcomes . OBJECTIVES To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma r and omized to one of two different treatment decision-making models or to usual care . METHODS In shared decision making ( SDM ) , nonphysician clinicians and patients negotiated a treatment regimen that accommo date d patient goals and preferences . In clinician decision making , treatment was prescribed without specifically eliciting patient goals /preferences . The otherwise identical intervention protocol s both provided asthma education and involved two in-person and three brief phone encounters . MEASUREMENTS AND MAIN RESULTS Refill adherence was measured using continuous medication acquisition ( CMA ) indices-the total days ' supply acquired per year divided by 365 days . Cumulative controller medication dose was measured in beclomethasone canister equivalents . In follow-up Year 1 , compared with usual care , SDM result ed in : significantly better controller adherence ( CMA , 0.67 vs. 0.46 ; P < 0.0001 ) and long-acting beta-agonist adherence ( CMA , 0.51 vs. 0.40 ; P = 0.0225 ) ; higher cumulative controller medication dose ( canister equivalent , 10.9 vs. 5.2 ; P < 0.0001 ) ; significantly better clinical outcomes ( asthma-related quality of life , health care use , rescue medication use , asthma control , and lung function ) . In Year 2 , compared with usual care , SDM result ed in significantly lower rescue medication use , the sole clinical outcome available for that year . Compared with clinician decision making , SDM result ed in : significantly better controller adherence ( CMA , 0.67 vs. 0.59 ; P = 0.03 ) and long-acting beta-agonist adherence ( CMA , 0.51 vs. 0.41 ; P = 0.0143 ) ; higher cumulative controller dose ( CMA , 10.9 vs. 9.1 ; P = 0.005 ) ; and quantitatively , but not significantly , better outcomes on all clinical measures . CONCLUSIONS Negotiating patients ' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes . Clinical trials registered with www . clinical trials.gov ( NCT00217945 and NCT00149526 ) Objective . Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment . This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler with fixed-dose fluticasone propionate/salmeterol dry powder inhaler regimens on patient-reported outcomes in patients aged ≥18 years with moderate to severe asthma . Methods . In this phase III , r and omized , open-label study , 1225 patients were r and omized 2:1 to fixed-dose budesonide/formoterol 160/4.5 μg × 2 inhalations ( 320/9 μg ) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 μg twice daily for 1 month . In the subsequent 6 months , patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy , whereas those receiving fixed-dose budesonide/formoterol were r and omized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol ( adjustable from 320/9 μg twice daily to 320/9 μg once daily or 640/18 μg twice daily ) . Results . Mean improvements from baseline to end of treatment in the Asthma Quality of Life Question naire ( st and ardized ) overall and individual domain scores and the Asthma Control Question naire score were clinical ly important ( ≥0.5 points ) for all treatments . Patients in both budesonide/formoterol groups reported greater treatment satisfaction on the Asthma Treatment Satisfaction Measure question naire than patients in the fluticasone propionate/salmeterol dry powder inhaler group for the attributes of timely relief of symptoms ( p ≤ .037 ) and feel medication working ( p ≤ .020 ) . Onset of Effect Question naire scores showed a greater percentage of patients perceiving onset of effect with budesonide/formoterol regimens versus fixed-dose fluticasone propionate/salmeterol ( p ≤ .002 ) . Conclusions . Treatment regimens did not differ regarding improvements in asthma-specific quality of life and asthma control . Questions related to perceived rate of onset and feeling medication working in the Asthma Treatment Satisfaction Measure and Onset of Effect Question naire generally elicited somewhat more favorable responses with budesonide/formoterol pressurized metered-dose inhaler regimens versus fixed-dose fluticasone propionate/salmeterol dry powder inhaler The aim of this study was to examine the potential differences between beliefs relating to symptomatic and preventive inhaler treatment and to analyze the relationship between these beliefs and the use of inhalers by adult patients with asthma in general practice . Unstructured interviews with a stratified sample of 8 patients , taking a combination of salbutamol and beclomethasone inhalers , were used to develop themes for a structured interview , where questions relating to 8 main areas of interest were measured on a 5-point Likert scale . Forty patients prescribed the same combination of inhalers were r and omly selected for the structured interview . All agreed to participate ( 100 % response ) . Correlations between the responses to the 8 themes and measures of inhaler use were analyzed . High use of salbutamol for the relief of symptoms and low use of beclomethasone for the prevention of asthma were common . Perceived benefits of the inhalers , a positive attitude to using the inhalers , and concern about side effects had strong influences on the use of both inhalers . Uncertainty about the inhalers , a negative attitude to using the inhalers , and the involvement of others in asthma management had less influence on inhaler use . Satisfaction with the doctor and the ease of obtaining an inhaler were more important issues for beclomethasone use than for salbutamol use . There are important differences in the beliefs that patients hold in relation to symptomatic and preventive use of inhaler treatment . These findings suggest that focusing on very specific attitudes to treatment may be of benefit in the health education of adults with asthma . Further work is planned to refine the themes so that doctors will be able to explore patients ' views about their inhaler treatment by asking a few direct questions The national health care debate reflects the fervent and sometimes disparate views that patients and physicians have on what is important in health care . Research has found that patient satisfaction is clearly composed of many elements . Such diverse issues as technical skill , communication , accessibility , physical qualities of the facility , and coordination of care all seem to play a role in satisfying patients [ 1 - 4 ] . However , few research ers have attempted to determine the priorities that patients assign to attributes of care . In the early 1980s , Fletcher and colleagues [ 5 ] studied the priorities of 225 patients attending an academic medical clinic and found that continuity of care was the highest priority for these patients and that issues of cost and convenience were lowest . Robbins and colleagues [ 6 ] studied 100 patient visits to an academic primary care practice and found that overall satisfaction with the visit appeared to be related to aspects of the physical examination , time spent on health education , and discussion of the effects of treatment . We know of no published attempts to establish patient priorities in nonacademic setting s , and no empirical comparisons of patients ' and physicians ' opinions on the importance of various elements of health care are readily available . Thus , we surveyed patients and physicians for their opinions on the importance of various specific attributes of care to the overall quality of outpatient care . Methods Study Sample s Physicians Governors of the American College of Physicians from Arizona , Michigan , Oklahoma , Tennessee , Georgia , Maine , and Connecticut helped recruit a total of 74 members of the College from their respective states . These states were selected because they represented a wide geographic area . Only physicians who spent at least 60 % of their time practicing general internal medicine were eligible to participate . Full-time academicians , full-time specialists , full-time research ers , and trainees were excluded . The seven College governors each provided the names of 10 to 15 physicians from their own states who met these eligibility criteria and were thought to be exemplary clinicians . Research personnel sent these physicians ( n = 81 ) a letter explaining that the College governor had recommended them for participation in this project . Telephone follow-up was used to describe the project in detail . Of the 81 physicians recruited , 74 ( 91 % ) agreed to participate ; these 74 physicians make up our physician sample . Patients After participating physicians notified the patients they saw during a specified 2-week period that the patients might be contacted to participate in a voluntary , confidential study of quality of care , the physicians gave study personnel copies of their appointment logs for this period . Research staff r and omly selected 11 patients listed in each office 's log to participate in the study ( n = 814 ) according to the following procedure , which was devised by the firm that administered the surveys . Research staff divided the total number of patients listed on the log by 11 ( the target sample size for each practice ) to obtain a number , A. They rounded A up to the next highest integer and went to the Ath number on the r and om-number table . That r and om number was divided by 10 to obtain a number , B. The number B was rounded to the next highest integer , and the Bth patient on the log became the first patient in the sample . The second patient was selected by adding A and B to get a number , C. The Cth number on the r and om-number table was then divided by 10 and rounded to the next highest integer to obtain a number , D. The Dth patient listed on the physician 's log became the second patient in the sample . The third patient was selected by adding A and D and repeating the same process . The physicians and their staffs had no role in selecting patients from the logs and were not aware of subsequent patient participation . Question naire Using the literature on patient perceptions of care and separate focus groups with patients and physicians , we identified a comprehensive list of elements of medical office practice thought to be associated with quality of care in that setting . The 125 elements thought to be important in the delivery of high- quality office-based care covered the following nine domains , which were defined a priori : physician clinical skill , physician interpersonal skill , office support staff , office environment , provision of health-related information , patient involvement in care , nonfinancial access , finances , and coordination of care . The domains are defined in Table 3 . In this report , we refer to the 125 elements of care as elements , attributes , or items . Table 3 . Appendix : Definition of Domains We then constructed a question naire that asked both physician and patient respondents to rate , from their own perspectives , the importance of each of the 125 elements to the quality of care delivered in a physician 's office ( Table 4 ) . Respondents rated each item using a 4-point scale : 1 signified that the respondent considered the item not important ; 2 indicated that the item was of medium importance ; 3 meant that the item was of high importance ; and 4 indicated that the item was essential . Patients and physicians were asked to rate the importance of each item to office-based care in general , not to the performance of the patient 's individual physician or to the physician 's own practice . Table 4 . Appendix : Summary of Question naire : Instructions , Domains , and Sample Items Data Collection and Analysis An independent survey firm mailed the question naire to participants within 1 month of the index visit . Data collection remained open for 5 weeks , and reminders were sent 1 week after the initial mailing . We used group consensus to cluster items into the domains on the basis of qualitative assessment . When agreement about which domain an item belonged to was not unanimous , we discussed the item as a group until we reached a consensus . During a separate phase of our research that examined patients ' reports on the performance of their physicians , we also did a factor analysis that loosely guided the assignment of items to domains . The factor analysis identified two factors . The first was related to the specific skills and style of the physician and thus encompassed the domains of physician clinical skill , physician interpersonal skill , provision of health-related information , and patient involvement in care . The second factor was less directly related to physician skill or style and was thought to encompass the domains of office support staff , office environment , nonfinancial access , coordination of care , and finances . The assignment of items to the nine domains was guided by whether the item belonged to a domain related to the first factor or to the second factor . We examined the median importance ratings and interquartile ranges of physicians ' and patients ' ratings for each element of care and then analyzed items aggregated into the nine domains . For each respondent , we determined a domain-specific importance rating by calculating the average rating that the respondent assigned to items in each of the nine domains that the question naire addressed . For example , if a respondent assigned importance ratings of 2 , 3 , 3 , 3 , 4 , and 4 to the six items in the domain of office environment , that person 's rating of the importance of the office environment domain would be 3.17 ( [ 2 + 3 + 3 + 3 + 4 + 4]/6 ) . We then determined the median importance ratings assigned to each domain by the patients and by the physicians and used the Mann-Whitney U test to compare the two groups . We also ranked the perceived importance of the domains for patients and physicians by ordering the domains from those with the highest importance score to those with the lowest . We then compared the rank orders of physicians ' and patients ' ratings of the nine domains using the Spearman rank-order correlation coefficient . All reported P values are two sided . Results Physician and Patient Characteristics All 74 physicians who supplied appointment logs were in solo or small-group practice . The mean age was 44 years , 14.9 % were women , and 8 % belonged to an ethnic minority group . Nine physicians were from Arizona , 9 were from Michigan , 15 were from Oklahoma , 11 were from Tennessee , 12 were from Georgia , 9 were from Maine , and 9 were from Connecticut . Of the 74 physicians , 69 ( 93 % ) completed the study question naire . Of these 69 physicians , the mean age was 45.5 years , 16 ( 22 % ) were women , 5 ( 7 % ) belonged to an ethnic minority group , and all were in solo or small-group practice . The patient response rate was 60 % ( 485 of 815 patients ) . The characteristics of these patients are shown in Table 1 . Table 1 . Patient Characteristics Patients ' and Physicians ' Ratings of the Importance of Individual Elements Physicians and patients differed substantially in an element-by-element comparison of ratings . Disagreement about the level of importance was statistically significant for 58 % of the elements ( 72 of 125 ) . Table 2 shows data for the 15 elements on which patients ' and physicians ' ratings greatly differed . Of note , 9 of the 15 largest differences concerned the provision of information to the patient . Table 2 . Elements of Care for Which Patients ' and Physicians ' Importance Ratings Differed Most Patients ' and Physicians ' Ratings of the Importance of the Domains Patients and physicians agreed strongly about the rank order of the nine domains ( Spearman r , 0.80 ) . For example , both groups ranked clinical skills highest and office environment lowest . Provision of information was the only domain for which the rank order substantially differed between groups . Physicians ranked office support staff , physician interpersonal skill , patient involvement , and coordination of care higher than patients did , but these differences were not statistically significant . Although agreement on rank order ( that is , relative importance ) was BACKGROUND Adherence to inhaled anti-inflammatory therapy and self-management skills are essential parts of the asthma treatment plan to improve asthma control and prevent exacerbations . Whether self-management education improves long-term medication adherence is less clear . OBJECTIVE A 24-week prospect i ve , r and omized controlled trial was performed to study the effect of self-management education on long-term adherence to inhaled corticosteroid ( ICS ) therapy and markers of asthma control . METHODS After stabilization on ICS medication during a run-in phase , 95 adults with moderate-to-severe asthma were recruited from a large metropolitan community , and 84 were r and omized to individualized self-management education , including self-monitoring of symptoms and peak flow or usual care with self-monitoring alone . The key components of the 30-minute intervention were asthma information , assessment , and correction of inhaler technique ; an individualized action plan based on self-monitoring data ; and environmental control strategies for relevant allergen and irritant exposures . The intervention was personalized based on pulmonary function , allergen skin test reactivity , and inhaler technique and reinforced at 2-week intervals . RESULTS Participants r and omized to the self-management intervention maintained consistently higher ICS adherence levels and showed a 9-fold greater odds of more than 60 % adherence to the prescribed dose compared with control subjects at the end of the intervention ( P = .02 ) and maintained a 3-fold greater odds of higher than 60 % adherence at the end of the study . Perceived control of asthma improved ( P = .006 ) , nighttime awakenings decreased ( P = .03 ) , and inhaled beta-agonist use decreased ( P = .01 ) in intervention participants compared with control subjects . CONCLUSION Our results show that individualized asthma self-management education attenuates the usual decrease in medication adherence and improves clinical markers of asthma control BACKGROUND Patient-reported outcomes ( PROs ) are important for evaluating asthma therapy . OBJECTIVE To evaluate PROs in adults with moderate to severe persistent asthma receiving budesonide and formoterol administered via 1 pressurized metered-dose inhaler ( pMDI ) . METHODS This 12-week , double-blind , double-dummy , placebo-controlled , multicenter study r and omized 596 patients 12 years or older to budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations ( 320/9 microg ) ; budesonide pMDI 160 microg x 2 inhalations ( 320 microg ) + formoterol dry powder inhaler ( DPI ) 4.5 microg x 2 inhalations ( 9 microg ) ; budesonide pMDI 160 microg x 2 inhalations ( 320 microg ) ; formoterol DPI 4.5 microg x 2 inhalations ( 9 microg ) ; or placebo , each twice daily , after 2 weeks of budesonide pMDI 80 microg x 2 inhalations ( 160 microg ) twice daily . PROs were assessed in 553 patients 18 years or older using the st and ardized Asthma Quality of Life Question naire ( AQLQ[S ] ) , Medical Outcomes Survey ( MOS ) Sleep Scale , Patient Satisfaction With Asthma Medication ( PSAM ) question naire , diary data , and global assessment s. RESULTS Patients receiving budesonide/formoterol reported significantly greater improvements from baseline on the AQLQ(S ) and asthma control variables ( based on symptoms and rescue medication use ; all P < .001 ) vs placebo . Clinical ly important improvements ( increase of > or = 0.5 points ) from baseline to end of treatment in AQLQ(S ) overall scores were achieved by 43.6 % of patients receiving budesonide/formoterol vs 22.6 % of patients receiving placebo ( P = .001 ) . The MOS Sleep Scale scores generally showed no differences among treatment groups . Patients receiving budesonide/formoterol had significantly greater PSAM question naire scores and better outcomes on physician-patient global assessment s at end of treatment vs placebo ( all P < or = .001 ) . CONCLUSION Significantly greater improvements in health-related quality of life and asthma control and greater treatment satisfaction were observed with budesonide/formoterol pMDI vs placebo The aim of this study was to evaluate the effect of house dust mite impermeable covers on asthma-specific health-related quality of life in adult asthmatic patients that were trained in guided self-management . In a 2-year r and omized placebo-controlled clinical trial , information on the quality of life was collected . The improvement of Mini Asthma Quality of Life Question naire ( AQLQ ) score in the allergens-avoidance group ( 0.26 ) was comparable to the improvement in the placebo group ( 0.30 ) and not significant . HDM-impermeable covers for pillows , duvets , and mattresses did not result in improved health-related quality of life This study investigated the effectiveness of different educational programs in obtaining better asthma control and asthma-related quality of life ( QoL ) . In 60 adult patients with moderate persistent asthma we tested the benefit of individual verbal instructions ( IVI ) , written information ( " asthma booklet " , B ) , and integrated asthma classes ( " asthma school " , AS ) . At the enrollment and at the end of the study , all participants completed the question naires regarding their asthma-related knowledge ( ArK ) and QoL. During the 12-week period all patients recorded their asthma symptoms , morning and evening peek expiratory flow rates ( PEFR ) , and the use of rescue medication . AS and IVI groups showed a significantly greater improvement in QoL than the B group . AS group obtained the highest ArK but no difference in the level of improvement among the groups has been documented . The improved average asthma symptom score and decreased utilization of the rescue medication were documented in all groups without significant differences among them . We also found significant improvements in both morning and evening PEFR in IVI group as well as in the morning PEFR in AS group . We conclude that among tested educational interventions the AS caused the best improvement in QoL while IVI produced the best overall response in both parameters of the asthma control and Objective : We investigated if a higher proportion of adults with previously uncontrolled asthma can achieve total control when given salmeterol/fluticasone propionate ( 50/250 µg ) bid and compliance enhancement training ( CET ) compared to those given medication alone INTRODUCTION Depression and panic disorder are widely acknowledged as complicating factors in asthma patients . However , their impact on health outcomes in primary care patients is less well examined . This study prospect ively evaluated the impact of depression and panic disorder on outcomes of primary care patients with asthma over 1 year . METHODS At baseline , 256 asthma patients from 43 primary care practice s completed self-report question naires including the Patient Health Question naire ( PHQ ) , the Asthma Quality of Life Question naire ( AQLQ ) , and a structured question naire evaluating asthma severity , hospitalisation and emergency visits . One year later , 185 ( 72.3 % ) patients completed the same question naire . RESULTS At baseline , 3.9 % of patients suffered from major depressive disorder , 22.7 % from minor depressive disorder , and 7.8 % from panic disorder . In the year under evaluation , 17 patients ( 9.2 % ) received emergency home visits and 10 patients ( 5.4 % ) were admitted to a hospital . Depression at baseline predicted hospitalisation within the subsequent year ( OR 6.1 ; 95 % CI 1.5 - 24.6 ) and panic disorder predicted unscheduled emergency home visits ( OR 4.8 ; 95 % CI 1.3 - 17.7 ) . Depression but not panic disorder predicted the AQLQ scales activity ( p=0.001 ) , symptoms ( p=0.001 ) , emotions ( p=0.001 ) and environment ( p=0.001 ) at follow-up . CONCLUSIONS Although rates of hospitalisation and emergency visits in primary care are low , the impact of psychiatric comorbidity on health outcomes for patients with asthma is substantial . It might be helpful to identify patients with psychiatric comorbidity by analysing reasons for hospitalisation and emergency visits . For these patients , intensifying care with psychiatric interventions might help to reduce inappropriate healthcare utilisation and avoid adverse outcomes Context Patient self-management is an essential component of asthma care , and the Internet is a medium to potentially support patients in self-management . Contribution This r and omized trial compared Internet-based asthma self-management with usual care and found modest improvements in asthma control and lung function with the Internet intervention , but found no reduction in exacerbations and changes in asthma-related quality of life that were less than clinical ly significant at 12 months . Implication Although Internet-based self management can improve some asthma outcomes , the improvements were small and the program did not reduce the number of exacerbations . The Editors Asthma is a chronic disorder of the airways that is characterized by recurring respiratory symptoms , variable airflow obstruction , airway hyperresponsiveness , and underlying inflammation ( 1 , 2 ) . Recent clinical guidelines for the management of asthma distinguish 4 essential components of asthma care : assessment and monitoring , patient education , control of environmental and comorbid factors that affect asthma , and drug treatment . With appropriate medical care , well-informed and empowered patients can control their asthma and live full , active lives ( 1 , 2 ) . However , despite the availability of monitoring tools and effective therapy , asthma control is suboptimal in many patients worldwide , and long-term management falls far short of the goals set in the guidelines ( 3 ) . Self-monitoring , education , and specific medical care are important aspects in improving the lives of patients with asthma ( 1 , 2 ) . However , many patients with mild or moderate persistent asthma do not attend checkups regularly or visit their physician with symptoms of the disease ( 4 ) . In addition , in practice , both patients and their health care providers are reluctant to use written self-management plans ( 5 ) . Internet technology is increasingly seen as an appealing tool to support self-management for patients with chronic disease in remote and underserved population s ( 68 ) . However , to date , studies on Internet-based asthma self-management show only short-term improvements in asthma control , lung function , and quality of life ( 911 ) . Long-term studies on the effect of Internet-based self-management , including all its essential features , are not available . Therefore , we developed a guided self-management tool for adult patients with asthma that included Internet-based home monitoring and treatment advice ( action plan ) , online education , and remote Web communication with a specialized asthma nurse . The goal of our study was to assess the long-term clinical effectiveness of Internet-based self-management education compared with usual physician-provided care alone . Methods Design Overview We conducted a 12-month , multicenter , nonblinded , r and omized , controlled trial . We r and omly assigned patients to Internet-based self-management ( Internet group ) as an adjunct to usual care or to usual physician-provided care alone ( usual care group ) . The Internet-based self-management program included weekly asthma control monitoring and treatment advice , online and group education , and remote Web communications with a specialized asthma nurse . The intervention continued for 12 months after enrollment . The Medical Ethics Committee of the Leiden University Medical Center , Leiden , the Netherl and s , approved the study . Setting and Participants We recruited patients from 37 general practice s ( 69 general practitioners ) in the Leiden and The Hague area and the Outpatient Clinic of the Department of Pulmonology at the Leiden University Medical Center from September 2005 to September 2006 . Inclusion criteria were physician-diagnosed asthma coded according to the International Classification of Primary Care in the electronic medical record ( 12 ) , age 18 to 50 years , prescription of inhaled corticosteroids for at least 3 months in the previous year , no serious comorbid conditions that interfered with asthma treatment , access to the Internet at home , and mastery of the Dutch language . We excluded patients who were receiving maintenance oral glucocorticosteroid treatment . On the basis of diagnosis , age , prescribed asthma medication , and comorbid conditions , we sent eligible patients an invitation letter followed by 1 reminder letter after 2 to 4 weeks if they did not respond to the first . We continued this process until a total of 200 patients had entered the study ( September 2006 ) . All participants gave written consent . R and omization and Intervention In a 2-week baseline period before r and omization , we collected data on patient demographic characteristics , asthma-related quality of life , symptom control , lung function , and medication level . We provided basic education about core information on asthma , action of medications , and inhaler technique instructions to all patients . We trained all participants to measure FEV1 daily with a h and -held electronic spirometer ( PiKo-1 , Ferraris Respiratory , Hertford , United Kingdom ) and to report the highest value of 3 measurements in the morning before taking medication ( 2 , 13 ) . They were shown how to report these values on a personal page on a secure Web application by using a login password ( or how to report by mobile telephone text message ) . Patients were also asked to report their nighttime and daytime asthma symptom scores on this Internet page or by text message . We asked all participants to complete the Asthma Control Question naire on their personal Internet page each week ( 14 ) . We did not give any patients feedback about lung function or asthma control . After the 2-week baseline period , we r and omly assigned participants to either the Internet group or the usual care group . We stratified according to care provider ( primary vs. subspecialty care ) and asthma control at baseline ( 15 ) . We r and omly assigned patients to the 2 groups ( 1:1 ratio ) by using a computer-generated , permuted-block scheme . Allocation took place by computer after collection of the baseline data , ensuring concealment of allocation . The Internet-based self-management program consisted of the 4 principal components of asthma self-management and was accessed through the specially design ed Web site , which allowed monitoring through the Web site ( or text message on a mobile telephone ) , use of an Internet-based treatment plan , online education , and Web communications with a specialized asthma nurse ( 16 ) . Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Question naire on the Web site and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan ( Table 1 and Appendix Figures 1 , 2 , 3 , 4 , and 5 ) . Depending on the scores su bmi tted , patients received 4 types of self-treatment advice . When 4 consecutive Asthma Control Question naire scores were 0.5 or less , patients were advised to decrease treatment according to treatment plan . When 2 consecutive scores were greater than 0.5 but less than 1.0 , patients were advised to increase treatment according to treatment plan . When 1 score was 1.0 or more but less than 1.5 , patients were advised to immediately increase treatment according to treatment plan . Finally , when 1 score was 1.5 or more , patients were advised to immediately increase treatment and contact the asthma nurse . Table 1 . Treatment Plan Appendix Figure 1 . Algorithm based on consecutive ACQ scores to adjust medical treatment . * ACQ = Asthma Control Question naire . At entry of the algorithm , the evaluation period is bypassed . The evaluation period starts after treatment was stepped up . The optimal control period starts after 1 ACQ score 0.5 and ends after 1 ACQ score > 0.5 . Appendix Figure 2 . Screen shot of daily lung function and symptom monitoring . Appendix Figure 3 . Screen shot of feedback on daily lung function and symptom monitoring . Appendix Figure 4 . Screen shot of weekly Asthma Control Question naire monitoring . Appendix Figure 5 . Screen shot of feedback on Asthma Control Question naire , treatment advice according to personalized treatment plan , and results of past 6 months . We advised no medication changes during the 4 weeks after treatment was stepped up ( evaluation period ) . In addition to weekly assessment s , patients could optionally report daily symptoms and lung function and were able to contact our asthma nurse though the Web or by telephone . Thus , any acute deterioration warranting a visit to the general practitioner or hospital could be detected ( Appendix Figures 2 and 3 ) . We aim ed to empower patients to use the Internet-based self-management tool and to develop a patientprovider partnership in asthma care ( 2 ) . Self-management education consisted of both Web-based and face-to-face , group-based education . Web-based education included asthma information , news , frequently asked questions , and interactive communication with a respiratory nurse specialist . We scheduled 2 group-based education sessions , which lasted 45 to 60 minutes , for patients in the Internet-based self-management group within 6 weeks after entering the trial . Both sessions included exploration of a patient 's interests and previous knowledge ( negotiating an agenda and patient-centered education ) , personalized feedback , and empowerment of self-management ( self-efficacy and implementing a plan for change ) ( 2 , 17 ) . The first educational session also included pathophysiology of asthma , information on the Web-based action plan , and information and review of inhalation technique . The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance . Patients in the usual care group received asthma care according to the Dutch general practice guidelines on asthma management in adults , which recommend a medical review and treatment adjustment every 2 to 4 weeks in unstable asthma and medical review once or twice BACKGROUND Although , among adults , asthma predominates in women , the role of sex and gender in asthma has only recently been studied . Moreover , only one study has focused on the management of asthma by women , reporting that 1 year subsequent to an intervention addressing sex and gender role factors , women 's asthma status was improved . OBJECTIVE Data from a 2-year postintervention follow-up were assessed to determine whether there were longer-term effects on the asthma status and quality of life ( QoL ) of the participants . METHODS A r and omized controlled design was used in which female patients with asthma , who were receiving services at the University of Michigan Health System , Ann Arbor , Michigan ( 2002 - 2006 ) , were assigned to either a control group or a female-oriented intervention group that focused on management challenges related to sex and gender role factors . Data were collected at baseline and 2 years ' postintervention ( 2008 ) by telephone interview and review of medical records . Measures included asthma-related QoL , health care and medication use for asthma , level of self-regulation , self-confidence in managing the condition , sex and gender role-related asthma problems , and days of missed work or school because of asthma . Data were analyzed using both generalized estimating equations logistic regression and log-linear regression . RESULTS The mean ( SD ) age of the 808 women participating in the study was 48.2 ( 13.1 ) years in the intervention group and 48.7 ( 14.3 ) years in the control group , and the percentage of minority participants was 15.8 % and 16.3 % , respectively . Despite r and omization , women in the intervention group had more persistent asthma at baseline . At 2 years ' postr and omization , the only significant difference in health care use was associated with scheduled office visits ; no other significant health care use differences were evident . However , the women in the intervention group had a significantly greater decrease of asthma symptoms with sexual activity ( P = 0.01 ) and greater reduction in days of work/school missed for asthma in winter months ( P = 0.03 ) , were better able to self-regulate ( P = 0.01 ) , were more confident in managing their asthma ( P = 0.01 ) , and had higher levels of asthma-related QoL ( P = 0.02 ) . They also had a greater reduction in the use of short-acting bronchodilators ( ie , rescue medications ) than did women in the control group ( P < or = 0.05 ) . CONCLUSION An intervention that focuses on female-specific aspects of asthma management may result in improved QoL and health status for women with asthma , as was evident 2 years ' postintervention in this study Background and purpose . Asthma management programs ( AMP ) may reduce costs and improve outcomes in patients with moderate to severe asthma . However , it is not known which personnel are best able to deliver such interventions and what setting s are most effective . The purpose of this study was to compare the effects of an in-home AMP provided by respiratory therapists ( RTs ) to an AMP provided by nurses ( RNs ) and to usual care ( UC ) provided in physician offices or clinics . Methods . Subjects ( age 18–64 ) who had been admitted to the emergency department ( ED ) or hospital for acute asthma exacerbation were r and omized to three groups : AMP-RT , AMP-RN or UC . The AMP groups received five ( 5 ) weekly home visits to provide assessment and instruction ; the UC group was instructed to return to their physician for routine follow-up . Outcomes assessed at 6 months included hospitalizations , in patient days , hospitalization cost , ED visits and cost , clinic visits , pulmonary function , symptoms , health related quality of life ( HRQOL ) , asthma episode self-management score ( AESM ) , environmental assessment , and patient satisfaction ( PS ) . Variables were compared using ANOVA with a Neuman-Keuls follow-up for multiple comparisons using an intent-to-treat approach . Results . Upon enrollment , ( n = 159 ) there were no differences ( p > . 05 ) between groups for age , gender , pulmonary function or HRQOL ( SF-36 and St. Georges Respiratory Question naire – SGRQ ) . At 6 months , both AMP groups ( AMP-RN n = 54 ; AMP-RT n = 46 ) had significantly fewer ( p < 0.05 ) hospitalizations and in-patient days , lower hospitalization costs , and greater HRQOL physical component summary change scores ( PCS ) and PS than UC ( n = 59 ) . AMP-RT also had greater PEFR , SGRQ Total and SGRQ Symptoms change scores when compared to UC and significantly better AESM and PS scores as compared to AMP-RN and UC . Conclusions . An in-home asthma management program can be effectively delivered by respiratory therapists and may reduce hospitalizations , in-patient days , cost and improve measures of HRQOL and PS in a population prone to asthma exacerbation Abstract Background : There is ample evidence to support the efficacy of sublingual immunotherapy ( SLIT ) on allergic rhinitis , while there is less solid data regarding asthma . We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study . Methods : This double-blind , placebo-controlled , r and omised , single centre trial on SLIT with birch pollen allergen extract ( Stallergenes , Antony , France ) included 24 patients presenting severe rhinitis and slight to moderate asthma , 14 actively and 10 placebo treated . SLIT was performed by a pre-coseasonal protocol , and was repeated for 2 years . The study plan included a selection visit , a visit at the start of the first and the second treatment cycle , a follow-up visit after 1–3 months from the start of each cycle , and a final visit at the end of each yearly cycle . Results : A significant decrease ( p < 0.05 ) in rhinorrhoea and nasal obstruction occurred in actively treated patients . The median number of days with asthma at visit 3 was 10 ( 0–27 ) in the active ( SLIT ) group and 13 ( 0–29 ) in the placebo group . The median number of days with asthma at visit 6 was 2 ( 0–6 ) in the SLIT group and 7 ( 0–15 ) in the placebo group ( p < 0.05 between groups ) . A stepdown of asthma occurred in 77 % of actively treated vs. none of placebo treated patients ( p = 0.05 ) . No severe adverse events were observed . Conclusions : This pilot study suggests that SLIT with high dose birch extract may be able to step down seasonal pollen-induced asthma after prolonged treatment |
13,037 | 25,494,712 | There is little evidence from this review to indicate that men and women should adopt different weight loss strategies .
Current evidence supports moderate energy restriction in combination with exercise for weight loss in both men and women | Effective strategies are required to reduce the prevalence of overweight and obesity ; however , the effectiveness of current weight loss programmes is variable .
One contributing factor may be the difference in weight loss success between men and women .
A systematic review was conducted to determine whether the effectiveness of weight loss interventions differs between men and women . | Obesity has been linked with low levels of ω-3 fatty acids . Generally , intervention studies have failed to establish benefits of supplementation with ω-3PUFA in reducing body weight or fat mass in humans . The aim of this study was to investigate whether supplementation with LCω-3PUFA alone , then consumed concomitantly with a very low energy diet ( VLED ) , facilitated weight loss , improvements in blood lipids and positive changes to inflammatory mediators . This was a double blind r and omised controlled trial with two parallel groups . For 4 weeks of prior supplementation , one group consumed 6 × 1 g capsules per day monounsaturated oil ( placebo ) , the other group consumed 6 × 1 g capsules per day LCω-3PUFA ( fish oil ) each comprising 70 mg EPA and 270 mg DHA , while consuming their usual diet . Each group continued with their supplements for another 4 weeks while both groups followed a VLED regimen ( n = 19 placebo , n = 20 fish oil ) . Fasting blood sample s , anthropometric measurements and 3-day food diaries were collected at baseline , at 4 weeks and at 8 weeks . At 4 weeks levels of EPA and DHA increased two-fold in the fish oil group ( P < 0.001 ) , with no significant changes to anthropometric measurements for either group . At 8 weeks a significant 3-way interaction between time , group and gender was observed for percentage reduction in weight , F(1,35 ) = 5.55 , P = 0.024 , and BMI , F(1,35 ) = 5.3 , P = 0.027 with a greater percentage decrease for females in FO compared to PB for weight ( -7.21 % vs.-5.82 % ) and BMI ( -7.43 % vs.-5.91 % ) respectively ( P < 0.05 for both ) . It would appear that supplementation with LCω-3PUFA had a time dependent effect on weight loss in females Limited data on sex differences in body composition changes in response to higher protein diets ( PRO ) compared to higher carbohydrate diets ( CARB ) suggest that a PRO diet helps preserve lean mass ( LM ) in women more so than in men . Objective To compare male and female body composition responses to weight loss diets differing in macronutrient content . Design Twelve month r and omized clinical trial with 4mo of weight loss and 8mo weight maintenance . SubjectsOverweight ( N = 130 ; 58 male ( M ) , 72 female ( F ) ; BMI = 32.5 ± 0.5 kg/m2 ) middle-aged subjects were r and omized to energy-restricted ( deficit ~500 kcal/d ) diets providing protein at 1.6 g.kg-1.d-1 ( PRO ) or 0.8 g.kg-1.d-1 ( CARB ) . LM and fat mass ( FM ) were measured using dual X-ray absorptiometry . Body composition outcomes were tested in a repeated measures ANOVA controlling for sex , diet , time and their two- and three-way interactions at 0 , 4 , 8 and 12mo . Results When expressed as percent change from baseline , males and females lost similar amounts of weight at 12mo ( M:-11.2 ± 7.1 % , F:-9.9 ± 6.0 % ) , as did diet groups ( PRO:-10.7 ± 6.8 % , CARB:-10.1 ± 6.2 % ) , with no interaction of gender and diet . A similar pattern emerged for fat mass and lean mass , however percent body fat was significantly influenced by both gender ( M:-18.0 ± 12.8 % , F:-7.3 ± 8.1 % , p < 0.05 ) and diet ( PRO:-14.3 ± 11.8 % , CARB:-9.3 ± 11.1 % , p < 0.05 ) , with no gender-diet interaction . Compared to women , men carried an extra 7.0 ± 0.9 % of their total body fat in the trunk ( P < 0.01 ) at baseline , and reduced trunk fat during weight loss more than women ( M:-3.0 ± 0.5 % , F:-1.8 ± 0.3 % , p < 0.05 ) . Conversely , women carried 7.2 ± 0.9 % more total body fat in the legs , but loss of total body fat in legs was similar in men and women . Conclusion PRO was more effective in reducing percent body fat vs. CARB over 12mo weight loss and maintenance . Men lost percent total body fat and trunk fat more effectively than women . No interactive effects of protein intake and gender are evident Background Numerous gene loci are related to single measures of body weight and shape . We investigated if 55 SNPs previously associated with BMI or waist measures , modify the effects of fat intake on weight loss and waist reduction under energy restriction . Methods and Findings R and omized controlled trial of 771 obese adults . ( Registration : IS RCT N25867281 . ) One SNP was selected for replication in another weight loss intervention study of 934 obese adults . The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat ( fat% ) in range of 20–25 or 40–45 . The replication study used an 8-weeks diet of 880 kcal/d and 20 fat% ; change in fat% intake was used for estimation of interaction effects . The main outcomes were intervention weight loss and waist reduction . In the trial , mean change in fat% intake was −12/+4 in the low/high-fat groups . In the replication study , it was −23/−12 among those reducing fat% more/less than the median . TFAP2B-rs987237 genotype AA was associated with 1.0 kg ( 95 % CI , 0.4 ; 1.6 ) greater weight loss on the low-fat , and GG genotype with 2.6 kg ( 1.1 ; 4.1 ) greater weight loss on the high-fat ( interaction p-value ; p = 0.00007 ) . The replication study showed a similar ( non-significant ) interaction pattern . Waist reduction results generally were similar . Study -strengths include ( i ) the discovery study r and omised trial design combined with the replication opportunity ( ii ) the strict dietary intake control in both studies ( iii ) the large sample sizes of both studies . Limitations are ( i ) the low minor allele frequency of the TFAP2B polymorphism , making it hard to investigate non-additive genetic effects ( ii ) the different interventions preventing identical replication-discovery study design s ( iii ) some missing data for non-completers and dietary intake . No adverse effects/ outcomes or side-effects were observed . Conclusions Under energy restriction , TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction Objective To compare the effects of isocaloric , energy-restricted very low-carbohydrate ketogenic ( VLCK ) and low-fat ( LF ) diets on weight loss , body composition , trunk fat mass , and resting energy expenditure ( REE ) in overweight/obese men and women . Design R and omized , balanced , two diet period clinical intervention study . Subjects were prescribed two energy-restricted ( -500 kcal/day ) diets : a VLCK diet with a goal to decrease carbohydrate levels below 10 % of energy and induce ketosis and a LF diet with a goal similar to national recommendations ( % carbohydrate : fat : protein = ~60:25:15%).Subjects15 healthy , overweight/obese men ( mean ± s.e.m . : age 33.2 ± 2.9 y , body mass 109.1 ± 4.6 kg , body mass index 34.1 ± 1.1 kg/m2 ) and 13 premenopausal women ( age 34.0 ± 2.4 y , body mass 76.3 ± 3.6 kg , body mass index 29.6 ± 1.1 kg/m2 ) . Measurements Weight loss , body composition , trunk fat ( by dual-energy X-ray absorptiometry ) , and resting energy expenditure ( REE ) were determined at baseline and after each diet intervention . Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person . Results Actual nutrient intakes from food records during the VLCK ( % carbohydrate : fat : protein = ~9:63:28 % ) and the LF ( ~58:22:20 % ) were significantly different . Dietary energy was restricted , but was slightly higher during the VLCK ( 1855 kcal/day ) compared to the LF ( 1562 kcal/day ) diet for men . Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss , total fat loss , and trunk fat loss for men ( despite significantly greater energy intake ) . The majority of women also responded more favorably to the VLCK diet , especially in terms of trunk fat loss . The greater reduction in trunk fat was not merely due to the greater total fat loss , because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women . Absolute REE ( kcal/day ) was decreased with both diets as expected , but REE expressed relative to body mass ( kcal/kg ) , was better maintained on the VLCK diet for men only . Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet . Conclusion This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss , especially in men . A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinical ly significant but requires further validation . These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution Two studies were conducted to compare characteristics of consumers and non-consumers of vitamin and /or dietary supplements ( study 1 ) and to assess the effect of a multivitamin and mineral supplementation during a weight-reducing programme ( study 2 ) . Body weight and composition , energy expenditure , and Three-Factor Eating Question naire scores were compared between consumers and non-consumers of micronutrients and /or dietary supplements in the Québec Family Study ( study 1 ) . In study 2 , these variables and appetite ratings ( visual analogue scales ) were measured in forty-five obese non-consumers of supplements r and omly assigned to a double-blind 15-week energy restriction ( - 2930 kJ/d ) combined with a placebo or with a multivitamin and mineral supplement . Compared with non-consumers , male consumers of vitamin and /or dietary supplements had a lower body weight ( P < 0.01 ) , fat mass ( P < 0.05 ) , BMI ( P < 0.05 ) , and a tendency for greater resting energy expenditure ( P = 0.06 ) . In women , the same differences were observed but not to a statistically significant extent . In addition , female supplements consumers had lower disinhibition and hunger scores ( P < 0.05 ) . In study 2 , body weight was significantly decreased after the weight-loss intervention ( P < 0.001 ) with no difference between treatment groups . However , fasting and postpr and ial appetite ratings were significantly reduced in multivitamin and mineral-supplemented women ( P < 0.05 ) . Usual vitamin and /or dietary supplements consumption and multivitamin and mineral supplementation during a weight-reducing programme seems to have an appetite-related effect in women . However , lower body weight and fat were more detectable in male than in female vitamin and /or dietary supplements consumers To examine the effect of treatment-induced weight loss on Health-Related Quality of Life ( HRQL ) , 38 mildly-to-moderately overweight persons recruited to participate in a study to examine the efficacy of a lifestyle modification treatment program completed a sociodemographic question naire , the Beck Depression Inventory ( BDI ) , the Medical Outcomes Study Short-Form Health Survey ( SF-36 , as an assessment of HRQL ) , and underwent a series of clinical evaluations prior to treatment . After baseline evaluations , participants were r and omly assigned to either a program of lifestyle physical activity or a program of traditional aerobic activity . Participants again completed the SF-36 and BDI after the 13-week treatment program had ended . Weight loss averaged 8.6 ± 2.8 kg over the 13-week study . We found that weight loss was associated with significantly higher scores ( enhanced HRQL ) , relative to baseline , on the physical functioning , role-physical , general health , vitality and mental health domains of the SF-36 . The largest improvements were with respect to the vitality , general health perception and role-physical domains . There were no significant differences between the lifestyle and aerobic activity groups on any of the study measures . These data indicate that , at least in the short-term , weight loss appears to profoundly enhance HRQL Folklore has suggested that consuming grapefruit may promote weight control . Sparse data exist to support this hypothesis , although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids . The aim of this r and omized controlled trial was to prospect ively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults ( N = 74 ) . Following a 3-week washout diet low in bioactive-rich fruits and vegetables , participants were r and omized to either the control diet ( n = 32 ) or daily grapefruit ( n = 42 ) in the amount of one half of a fresh Rio-Red grapefruit with each meal ( 3 × daily ) for 6 weeks . No differences between group in weight , blood pressure , or lipids were demonstrated . Grapefruit consumption was associated with modest weight loss ( -0.61 ± 2.23 kg , P = .097 ) , a significant reduction in waist circumference ( -2.45 ± 0.60 cm , P = .0002 ) , and a significant reduction in systolic blood pressure ( -3.21 ± 10.13 mm Hg , P = .03 ) compared with baseline values . Improvements were observed in circulating lipids of those consuming grapefruit , with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL ( P = .002 ) and -18.7 mg/dL ( P < .001 ) , respectively , compared with baseline values . This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight , lipids , or blood pressure as compared with the control condition . However , the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention Background Although e-coach support increases the effectiveness of Internet weight loss interventions , no studies have assessed influence of type of e-coach support . Purpose The effects of nondirective ( collaborative , flexible ) and directive ( prescriptive , protocol driven ) e-coach support on weight loss , dietary behavior , physical activity , and engagement were assessed in a 12-week weight loss e-coaching program . Procedures Overweight adults ( N = 104 ) were r and omly assigned to nondirective , directive , or minimal support . All received weekly lessons and feedback graphs via e-mail . Participants in the nondirective and directive support conditions received individualized nondirective or directive weight loss support . Results For females , weight loss ( η2 = 0.10 ) and changes in waist circumference ( η2 = 0.07 ) were greater in the directive than in the nondirective and minimal support conditions . Conclusions Differences in type of e-coach support are salient to participants . Directive support is beneficial to females in a 12-week e-coach weight loss program BACKGROUND High levels of exercise may be necessary for long-term maintenance of weight loss . OBJECTIVE We aim ed to determine in a r and omized prospect i ve design whether encouraging 2500 kcal physical activity/wk produced greater 30-mo weight losses than did the st and ard 1000 kcal physical activity/wk prescription . DESIGN Overweight adults ( n = 202 ) were r and omly assigned to either 18 mo of st and ard behavioral treatment ( SBT ) with an exercise goal of 1000 kcal/wk or a high physical activity ( HPA ) treatment with a goal of 2500 kcal/wk . The HPA treatment included all procedures in the SBT plus encouragement to recruit 1 - 3 exercise partners and small-group counseling with an exercise coach . Participants were followed for 30 mo . RESULTS The HPA group achieved significantly greater exercise levels and weight losses than did the SBT group at 12 and 18 mo ( P < 0.01 ) . Weight losses did not differ significantly at 30 mo : 0.90 + /- 8.9 and 2.86 + /- 8.6 kg for the SBT and HPA groups , respectively ( P = 0.16 ) . At 30 mo , average exercise levels no longer differed significantly between groups ( 1390 and 1696 kcal/wk , respectively ; P > 0.10 ) . Participants sustaining high exercise levels ( > 2500 kcal/wk ) for 30 mo had significantly ( P < 0.001 ) greater 30-mo weight loss than did those exercising less ( 12 + /- 8.8 and 0.8 + /- 8.1 kg , respectively ) . CONCLUSIONS Although participants in the HPA group sustained the 2500-kcal activity goal during the 18-mo treatment , activity declined once treatment ended , which result ed in no between-group differences in activity or weight loss at 2.5 y. Participants who reported continuing to engage in high levels of exercise maintained a significantly larger weight loss BACKGROUND When substituted for carbohydrate in an energy-reduced diet , dietary protein enhances fat loss in women . It is unknown whether the effect is due to increased protein or reduced carbohydrate . OBJECTIVE We compared the effects of 2 isocaloric diets that differed in protein and fat content on weight loss , lipids , appetite regulation , and energy expenditure after test meals . DESIGN This was a parallel , r and omized study in which subjects received either a low-fat , high-protein ( LF-HP ) diet ( 29 + /- 1 % fat , 34 + /- 0.8 % protein ) or a high-fat , st and ard-protein ( HF-SP ) diet ( 45 + /- 0.6 % fat , 18 + /- 0.3 % protein ) during 12 wk of energy restriction ( 6 + /- 0.1 MJ/d ) and 4 wk of energy balance ( 7.4 + /- 0.3 MJ/d ) . Fifty-seven overweight and obese [ mean body mass index ( in kg/m(2 ) ) : 33.8 + /- 0.9 ] volunteers with insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( LF-HP group , 9.7 + /- 1.1 kg ; HF-SP group , 10.2 + /- 1.4 kg ; P = 0.78 ) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the LF-HP meal ( P = 0.02 ) . The decrease in resting energy expenditure was not significantly different between diet groups ( LF-HP , -342 + /- 185 kJ/d ; HF-SP , -349 + /- 220 kJ/d ) . The decrease in the thermic effect of feeding with weight loss was smaller in the LF-HP group than in the HF-SP group ( -0.3 + /- 1.0 % compared with -3.6 + /- 0.7 % ; P = 0.014 ) . Glucose and insulin responses to test meals improved after weight loss ( P < 0.001 ) with no significant diet effect . Bone turnover , inflammation , and calcium excretion did not change significantly . CONCLUSION The magnitude of weight loss and the improvements in insulin resistance and cardiovascular disease risk factors did not differ significantly between the 2 diets , and neither diet had any detrimental effects on bone turnover or renal function BACKGROUND It is not clear whether varying the protein-to-carbohydrate ratio of weight-loss diets benefits body composition or metabolism . OBJECTIVE The objective was to compare the effects of 2 weight-loss diets differing in protein-to-carbohydrate ratio on body composition , glucose and lipid metabolism , and markers of bone turnover . DESIGN A parallel design included either a high-protein diet of meat , poultry , and dairy foods ( HP diet : 27 % of energy as protein , 44 % as carbohydrate , and 29 % as fat ) or a st and ard-protein diet low in those foods ( SP diet : 16 % of energy as protein , 57 % as carbohydrate , and 27 % as fat ) during 12 wk of energy restriction ( 6 - 6.3 MJ/d ) and 4 wk of energy balance ( approximately 8.2 MJ/d ) . Fifty-seven overweight volunteers with fasting insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( 7.9 + /- 0.5 kg ) and total fat loss ( 6.9 + /- 0.4 kg ) did not differ between diet groups . In women , total lean mass was significantly ( P = 0.02 ) better preserved with the HP diet ( -0.1 + /- 0.3 kg ) than with the SP diet ( -1.5 + /- 0.3 kg ) . Those fed the HP diet had significantly ( P < 0.03 ) less glycemic response at weeks 0 and 16 than did those fed the SP diet . After weight loss , the glycemic response decreased significantly ( P < 0.05 ) more in the HP diet group . The reduction in serum triacylglycerol concentrations was significantly ( P < 0.05 ) greater in the HP diet group ( 23 % ) than in the SP diet group ( 10 % ) . Markers of bone turnover , calcium excretion , and systolic blood pressure were unchanged . CONCLUSION Replacing carbohydrate with protein from meat , poultry , and dairy foods has beneficial metabolic effects and no adverse effects on markers of bone turnover or calcium excretion BACKGROUND Despite the reported benefits , weight loss is not always advised for older adults because some observational studies have associated weight loss with increased mortality . However , the distinction between intentional and unintentional weight loss is difficult to make in an observational context , so the effect of intentional weight loss on mortality may be clarified in the setting of a r and omized controlled trial . OBJECTIVE The objective was to determine the effect of intentional weight loss on all-cause mortality by using follow-up data from a r and omized trial completed in 1995 that included a weight-loss arm . DESIGN The Trial of Nonpharmacologic Intervention in the Elderly ( TONE ) used a 2 × 2 factorial design to determine the effect of dietary weight loss , sodium restriction , or both on blood pressure control in 585 overweight or obese older adults being treated for hypertension ( mean ± SD age : 66 ± 4 y ; 53 % female ) . All-cause mortality was ascertained by using the Social Security Index and National Death Index through 2006 . RESULTS The mortality rate of those who were r and omly assigned to the weight-loss intervention ( n = 291 ; mean weight loss : 4.4 kg ) did not differ significantly from that of those who were not r and omly assigned to this group ( n = 294 ; mean weight loss : 0.8 kg ) . The adjusted HR was 0.82 ( 95 % CI : 0.55 , 1.22 ) . CONCLUSIONS Intentional dietary weight loss was not significantly associated with increased all-cause mortality over 12 y of follow-up in older overweight or obese adults . Additional studies are needed to confirm and extend our findings to older age groups . This trial is registered at clinical trials.gov as NCT00000535 OBJECTIVE : To describe methods , recruitment success , and 1-y results of a study evaluating the effectiveness of phone- and mail-based weight-loss interventions in a managed care setting . DESIGN : R and omized clinical trial with three groups , that is , usual care , mail intervention , and phone intervention . SUBJECTS : In total , 1801 overweight members of a managed-care organization ( MCO ) . MEASUREMENTS : Height , weight , medical status , and weight-loss history were measured at baseline . Participation in intervention activities was monitored for 12 months in the two active treatment groups . Self-reported weight was obtained at 6 and 12 months . RESULTS : More individuals assigned to mail treatment started it ( 88 % ) than did those assigned to phone treatment ( 69 % ) . However , program completion rates were higher in the phone ( 36 % ) than mail ( 7 % ) intervention . The mean weight losses were 1.93 , 2.38 , and 1.47 kg at 6 months in the mail , phone , and usual care groups , respectively . The differences between the phone and usual care groups were statistically significant . The mean weight losses at 12 months did not differ by treatment group ( 2.28 kg mail , 2.29 kg phone , and 1.92 kg usual care ) . Greater weight loss was seen in men , older participants , and those with no prior experience in a weight-loss program . Heavier participants and those who reported current treatment for depression lost less weight . CONCLUSION : Although mail- and phone-based weight-loss programs can be delivered to large numbers of people in an MCO setting , additional work is needed to enhance their clinical efficacy as well as to assess their costs Weight loss reduces energy expenditure , but it is unclear whether dietary macronutrient composition affects this reduction . We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet . The POUNDS LOST study , a prospect i ve , r and omized controlled trial in 811 overweight/obese people who were r and omized in a 2 × 2 design to diets containing 20en% or 40en% fat and 15en% or 25en% ( diets with 65 % , 55 % , 45 % and 35 % carbohydrate ) provided the data to test this hypothesis . Resting energy expenditure ( REE ) was measured at baseline , 6 and 24 months using a ventilated hood . REE declined at 6 months by 99.5±8.0 kcal/d in men and 55.2±10.6 kcal/d in women during the first 6 months . This decline was related to the weight loss , and there was no difference between the diets . REE had returned to baseline by 24 months , but body weight was still 60 % below baseline . Measured REE at 6 months was significantly lower than the predicted ( −18.2±6.7 kcal/d ) and was the result of significant reductions from baseline in the low fat diets ( 65 % or 55 % carbohydrate ) , but not in the high fat diet groups . By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted ( 21.8±10.1 kcal/d ) . In conclusion , we found that REE fell significantly after weight loss but was not related to diet composition . Adaptive thermogenesis was evident at 6 months , but not at 24 months OBJECTIVE : To determine the effect of replacing some dietary carbohydrate with protein , during energy restriction , on weight loss , total energy expenditure ( TEE ) , resting energy expenditure ( REE ) , respiratory quotient ( RQ ) , and the thermic effect of feeding ( TEF ) in subjects with hyperinsulinemia . DESIGN : Parallel , clinical intervention study of 12 weeks energy restriction ( 6.5 MJ/day ) and 4 weeks energy balance ( 8.2 MJ/day ) in two groups of subjects r and omly assigned to either a high-protein ( HP ) diet ( 27 % of energy ( % E ) as protein , 45%E as carbohydrate ) or a lower-protein ( LP ) diet ( 16%E as protein , 57%E as carbohydrate).SUBJECTS : A total of 36 obese nondiabetic volunteers with hyperinsulinemia ( 10 males/26 females , aged 34–65 y , BMI 28–43 kg/m2 , fasting insulin 12–45 mU/l ) . MEASUREMENTS : Body weight and composition , TEE , REE , and RQ were measured at baseline and at week 16 . In addition , the TEF to an HP or LP meal was determined for 3 h , at baseline and at week 16 . RESULTS : After 16 weeks , weight loss was similar in response to each diet ; the overall decrease was 7.9±0.6 kg ( P<0.001 ) , of which 6.8±0.5 kg was fat ( P<0.001 ) . REE fell similarly with each diet ; the overall decrease was 719±106 kJ/day ( P<0.001 ) . The TEF was 2 % greater after the HP than after the LP meal at baseline ( P<0.01 ) and 0.8 % greater at week 16 ( P=0.35 ) . After 16 weeks , the TEF was not reduced in either dietary group . There was no change in TEE after 16 weeks . CONCLUSION : In subjects with hyperinsulinemia an energy-restrictive diet containing an increased protein-to-carbohydrate ratio does not enhance weight loss or significantly affect energy expenditure . Caloric restriction , rather than the macronutrient composition of the diet , is the most important determinant of weight loss The purpose of the present study was to compare aerobic , anaerobic and strength performance changes induced by two short-term ( 3-week ) body mass reduction programs based on the same low-calory diet ( 1200–1500 kcal/day ) , nutritional education and psychological counseling , but entailing different exercise training protocol s. An individualized , low-volume and moderate-intensity exercise training ( IET ) was contrasted with a non-specific , high-volume , low-intensity exercise training ( NET ) . Thirty obese in- patients ( 12 males , 18 females ; mean age±SD : 33.9±9.4 yr , range : 19–51yr ; mean BMI : 40.5±3.8 kg/m2 , range : 35.3–51.4 kg/m2 ) were r and omly divided in two gender-matched groups of 15 subjects each undergoing a different exercise training protocol . Maximum oxygen uptake ( VİO2max ) determined with a submaximal indirect test on a bicycle ergometer , lower limb maximum power output ( Ẇmax ) determined with the jumping method , global motor capabilities determined by analysis of locomotor pattern during a short ( 8 m ) running , maximum strength ( 1-RM ) of upper and lower limb muscle groups determined with isotonic machines were tested before and after the program . Adherence to an individual exercise activity and maintenance of body weight ( bw ) loss were evaluated with a telephonic interview 6 months after the completion of the program . In both groups a significant ( p<0.001 ) and comparable weight loss was observed ( IET : −4.27 % ; NET : −4.17 % ) . In both groups VİO2max and Ẇmax increased significantly ( p<0.05–0.001 ) when expressed relatively to body mass , while in absolute terms they were significantly ( p<0.001 ) improved only in IET group . 1-RM in all tested muscle groups was significantly increased in both IET and NET subjects ( p<0.001–0.01 ) , but improvements were significantly greater in IET as compared with NET ( p<0.05–0.001 ) . The analysis of locomotor pattern during the short running indicated that IET subjects significantly improved their global motor capabilities ( p<0.05–0.001 ) , while no change was observed in NET group . After 6 months , IET subjects reported a level of spontaneously chosen physical activity significantly higher ( p<0.05 ) than NET subjects , displaying a trend of further decrease in bw . It was concluded that , although no difference in bw loss was appreciated between the two studied groups and significant improvements were found also in subjects performing NET protocol , the IET protocol offers better overall results in terms of muscle performance and physical fitness , with a possibly stronger motivation to subsequent exercise activity BACKGROUND Weight loss typically reduces bone mineral density ( BMD ) . Exercise may preserve or increase BMD even while reducing fatness . We examined the relationships among exercise-induced changes in fitness and fatness with BMD . DESIGN R and omized controlled trial conducted between July 1999 and November 2003 . PARTICIPANTS Men and women ( n = 115 ) aged 55 to 75 years . INTERVENTION Six months of exercise training . MAIN OUTCOME MEASURES Fitness measured as peak oxygen uptake and muscle strength , body composition by anthropometry , dual-energy x-ray absorptiometry , and magnetic resonance imaging . RESULTS A total of 51 men and 53 women completed the trial . Exercise increased aerobic and strength fitness and lean body mass , and reduced general and abdominal obesity . BMD did not change among men in either group . Among women exercisers , there were reductions in total skeleton BMD ( p = 0.02 ) and greater trochanter BMD ( p = 0.02 ) . By bivariate correlation , among women , increased femoral neck BMD was associated with increased aerobic fitness ( p = 0.01 ) and with reduced body weight ( p = 0.02 ) and BMI ( p = 0.02 ) . In the final regression model , 13 % of the change in femoral neck BMD was explained by the change in aerobic fitness ( p < 0.01 ) . Among the men , increased total hip BMD and femoral shaft BMD were associated with increased lean mass and lower-body strength . In the final regression models , the change in lean mass explained 9 % of the variance in total hip BMD ( p = 0.04 ) . The change in lean mass explained 20 % of the change in femoral shaft BMD ( p < 0.01 ) , and the change in lower-body strength explained an additional 6 % ( p < 0.04 ) . CONCLUSIONS When examined by group assignment , 6 months of exercise had no effect on BMD among men , and reduced BMD among women . When examined by change in fitness and fatness , women who had the greatest increases in aerobic capacity and men who had the greatest increases in strength and lean mass were more likely to increase their BMD . Exercise-induced reductions in fatness did not lead to bone loss CONTEXT The scarcity of data addressing the health effects of popular diets is an important public health concern , especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention . OBJECTIVE To assess adherence rates and the effectiveness of 4 popular diets ( Atkins , Zone , Weight Watchers , and Ornish ) for weight loss and cardiac risk factor reduction . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized trial at an academic medical center in Boston , Mass , of overweight or obese ( body mass index : mean , 35 ; range , 27 - 42 ) adults aged 22 to 72 years with known hypertension , dyslipidemia , or fasting hyperglycemia . Participants were enrolled starting July 18 , 2000 , and r and omized to 4 popular diet groups until January 24 , 2002 . INTERVENTION A total of 160 participants were r and omly assigned to either Atkins ( carbohydrate restriction , n=40 ) , Zone ( macronutrient balance , n=40 ) , Weight Watchers ( calorie restriction , n=40 ) , or Ornish ( fat restriction , n=40 ) diet groups . After 2 months of maximum effort , participants selected their own levels of dietary adherence . MAIN OUTCOME MEASURES One-year changes in baseline weight and cardiac risk factors , and self-selected dietary adherence rates per self-report . RESULTS Assuming no change from baseline for participants who discontinued the study , mean ( SD ) weight loss at 1 year was 2.1 ( 4.8 ) kg for Atkins ( 21 [ 53 % ] of 40 participants completed , P = .009 ) , 3.2 ( 6.0 ) kg for Zone ( 26 [ 65 % ] of 40 completed , P = .002 ) , 3.0 ( 4.9 ) kg for Weight Watchers ( 26 [ 65 % ] of 40 completed , P < .001 ) , and 3.3 ( 7.3 ) kg for Ornish ( 20 [ 50 % ] of 40 completed , P = .007 ) . Greater effects were observed in study completers . Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein ( HDL ) cholesterol ratio by approximately 10 % ( all P<.05 ) , with no significant effects on blood pressure or glucose at 1 year . Amount of weight loss was associated with self-reported dietary adherence level ( r = 0.60 ; P<.001 ) but not with diet type ( r = 0.07 ; P = .40 ) . For each diet , decreasing levels of total/HDL cholesterol , C-reactive protein , and insulin were significantly associated with weight loss ( mean r = 0.36 , 0.37 , and 0.39 , respectively ) with no significant difference between diets ( P = .48 , P = .57 , P = .31 , respectively ) . CONCLUSIONS Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year . Overall dietary adherence rates were low , although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group Long-term supplementation with conjugated linoleic acid ( CLA ) reduces body fat mass ( BFM ) and increases or maintains lean body mass ( LBM ) . However , the regional effect of CLA was not studied . The study aim ed to evaluate the effect of CLA per region and safety in healthy , overweight and obese adults . A total of 118 subjects ( BMI : 28 - 32 kg/m2 ) were included in a double blind , placebo-controlled trial . Subjects were r and omised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months . CLA significantly decreased BFM at month 3 ( Delta=- 0 x 9 % , P=0 x 016 ) and at month 6 ( Delta=- 3 x 4 % , P=0 x 043 ) compared with placebo . The reduction in fat mass was located mostly in the legs ( Delta=- 0 x 8 kg , P<0 x 001 ) , and in women ( Delta=-1 x 3 kg , P=0 x 046 ) with BMI > 30 kg/m2 ( Delta=-1 x 9 kg , P=0 x 011 ) , compared with placebo . The waist-hip ratio decreased significantly ( P=0 x 043 ) compared with placebo . LBM increased ( Delta=+0 x 5 kg , P=0 x 049 ) within the CLA group . Bone mineral content was not affected ( P=0 x 70 ) . All changes were independent of diet and physical exercise . Safety parameters including blood lipids , inflammatory and diabetogenic markers remained within the normal range . Adverse events did not differ between the groups . It is concluded that supplementation with CLA in healthy , overweight and obese adults decreases BFM in specific regions and is well tolerated Exercise is recommended by public health agencies for weight management ; however , the role of exercise is generally considered secondary to energy restriction . Few studies exist that have verified completion of exercise , measured the energy expenditure of exercise , and prescribed exercise with equivalent energy expenditure across individuals and genders . Objective The objective of this study was to evaluate aerobic exercise , without energy restriction , on weight loss in sedentary overweight and obese men and women . Design and Methods This investigation was a r and omized , controlled , efficacy trial in 141 overweight and obese participants ( body mass index , 31.0 ± 4.6 kg/m2 ; age 22.6 ± 3.9 years ) . Participants were r and omized ( 2:2:1 ratio ) to exercise at either 400 kcal/session or 600 kcal/session or to a non-exercise control . Exercise was supervised , 5 days/week , for 10 months . All participants were instructed to maintain usual ad libitum diets . Due to the efficacy design , completion of ≥ 90 % of exercise sessions was an a priori definition of per protocol , and these participants were included in the analysis . Results Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg ( 4.3 % ) and 5.2 ± 5.6 kg ( 5.7 % ) , respectively compared to weight gain for controls of 0.5 ± 3.5 kg ( 0.5 % ) ( p<0.05 ) . Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant . Conclusions Supervised exercise , with equivalent energy expenditure , results in clinical ly significant weight loss with no significant difference between men and women Based on previous cross-sectional findings , we hypothesized that weight loss could improve several hemostatic factors associated with cardiovascular disease . In a r and omized controlled trial , moderately overweight men and women were assigned to one of four weight loss treatment groups or to a control group . Measurements of plasminogen activator inhibitor-1 ( PAI-1 ) antigen , tissue-type plasminogen activator ( t-PA ) antigen , D-dimer antigen , factor VII activity , fibrinogen , and protein C antigens were made at baseline and after 6 months in 90 men and 88 women . Net treatment weight loss was 9.4 kg in men and 7.4 kg in women . There was no net change ( p > 0.05 ) in D-dimer , fibrinogen , or protein C with weight loss . Significant ( p < 0.05 ) decreases were observed in the combined treatment groups compared with the control group for mean PAI-1 ( 31 % decline ) , t-PA antigen ( 24 % decline ) , and factor VII ( 11 % decline ) . Decreases in these hemostatic variables were correlated with the amount of weight lost and the degree that plasma triglycerides declined ; these correlations were stronger in men than women . These findings suggest that weight loss can improve abnormalities in hemostatic factors associated with obesity Objective : Regular nut consumption is associated with lower rates of heart attack . However , as nuts are fatty foods , they may in theory lead to weight gain , although preliminary evidence has suggested otherwise . We tested the hypothesis that a free daily supplement ( averaging 76 kJ ) of almonds for six months , with no dietary advice , would not change body weight . Methods : Eighty-one male and female subjects completed the r and omized cross-over study . During two sequential six-month periods , diet , body weight and habitual exercise were evaluated repeatedly in each subject . Almonds were provided only during the second period . The design was balanced for seasonal and other calendar trends . Results : During the almond feeding period , average body weight increased only 0.40 ( kg ) ( p ∼ 0.09 ) . The weight change depended on baseline BMI ( p = 0.05 ) , and only those initially in the lower BMI tertiles experienced small and mainly unimportant weight gains with the almonds . We estimated that 54 % ( recalls ) or 78 % ( diaries ) of the extra energy from almonds was displaced by reductions in other foods . The ratio unsaturated/saturated dietary fat increased by 40 % to 50 % when almonds were included in the diet . Conclusion : Incorporating a modest quantity ( 76 kJ ) of almonds in the diet each day for six months did not lead on average to statistically or biologically significant changes in body weight and did increase the consumption of unsaturated fats . Further studies are necessary to evaluate longer term effects , especially in men Moderate intensity physical activity achieved through changes in lifestyle may promote weight management . However , little is known about changes in physiologic and metabolic variables when patients lose weight using moderate intensity lifestyle activity instead of traditional structured vigorous aerobic exercise . To compare changes in resting metabolic energy expenditure ( REE ) , fat mass ( FM ) , and fat-free mass ( FFM ) associated with a 12-week weight loss program combined with either : ( 1 ) aerobic exercise ( AER ) ; or ( 2 ) lifestyle activity ( LIFE ) , we r and omized 39 overweight adults ( mean body mass index [ BMI ] = 30.9 + /- 2.8 kg/m(2 ) ) to either diet plus AER ( N = 18 ) or diet plus LIFE ( N = 21 ) . Both groups consumed a self-selected diet of 1,200 to 1,800 kcal/d ( 5,021 to 7,531 kJ/d ) . The AER group performed vigorous aerobic exercise for up to 45 minutes 3 to 4 d/wk . The LIFE group accumulated 30 minutes of moderate intensity physical activity on most days of the week . Compliance with the respective protocol s was monitored on a weekly basis . REE was measured before and after treatment via open-circuit spirometry . The AER group decreased body weight by 8.4 % (P<.001)while the LIFE had a reduction of 6.7 % ( P < .001 ) after treatment . Over the course of the interventions , the AER and LIFE groups experienced 10.9 % ( P < .001 ) and 10.2 % ( P < .001 ) reductions in REE , respectively . Aerobic exercise did not prevent reductions in REE to a greater extent than did lifestyle activity in patients consuming a reduced calorie diet . Change in REE was not related to changes in FFM or FM for either group , and there were no differences between groups in reductions of REE , weight , FM , or FFM . A program of diet plus lifestyle physical activity may be a suitable alternative for dieting adults who have difficulty adhering to a program of vigorous activity OBJECTIVE To evaluate a weight loss and exercise program design ed to improve diabetes management in older African-Americans . RESEARCH DESIGN AND METHODS Overweight African-Americans ( n = 64 ) ages 55–79 years with NIDDM were r and omized to either an intervention ( 12 weekly group sessions , 1 individual session , and 6 biweekly group sessions ) or usual care ( 1 class and 2 informational mailings ) . Clinical and behavioral variables were assessed at 0 , 3 , and 6 months of treatment . RESULTS Significant net differences in the intervention versus usual care were observed for weight ( −2.0 kg , P = 0.006 ) , physical activity , and dietary intake of fat , saturated fat , cholesterol , and nutrition knowledge at 3 months ( all P < 0.05 ) and for weight at 6 months ( −2.4 kg ; P = 0.006 ) and mean HbA1c values at 3 and 6 months ( respectively , −1.6 and −2.4 % , both P < 0.01 ) . After the adjustment for changes in weight and activity , the intervention participants were ∼ twice as likely to have a one unit decrease in HbA1c value as those in usual care . Blood pressure increase sin usual care participants result ed in net differences ( intervention minus control ) at 3 and 6 months of −3.3 ( P = 0.09 ) and −4.0 ( P = 0.05 ) mmHg diastolic , respectively , and −8.4 ( P = 0.06 ) and −5.9 ( P > 0.10 ) mmHg systolic , respectively . Blood lipid profiles improved more in intervention than usual care participants , but not significantly . CONCLUSIONS The intervention program was effective in improving glycemic and blood pressure control . The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake , weight , and activity and may reflect indirect program effects on other aspects of self-care Participants in weight loss programs typically set unrealistically high weight loss goals that some believe are detrimental to success . This study examined outcomes associated with goal and ideal body mass index ( BMI ) . Participants ( N=1801 ) were enrolled in a weight loss trial comprised of low-intensity mail or telephone interventions vs usual care . Goal and ideal weight losses were assessed by asking participants how many pounds they expect to lose in the program ( goal ) and how much they would like to weigh ( ideal ) . Goal and ideal weight losses were unrealistically high ( men : −16 and −19 % , women : −21 and −27 % ) . For women , less realistic goals were associated with greater weight loss at 24 months . Goals were not associated with participation or weight loss for men . Results are more supportive of the idea that higher goals motivate women to lose weight than of the hypothesis that high goals undermine effort This study evaluated whether using a web-linked accelerometer , plus m and atory physical training , is associated with various weight- and fitness-related outcomes in overweight/obese active duty soldiers . Soldiers who failed the height/weight st and ards of the Army Physical Fitness Test ( APFT ) were r and omized to use a Polar FA20 accelerometer device ( polar accelerometer group [ PA ] , n = 15 ) or usual care ( UC , n = 13 ) for 6 months . Both groups received 1.5 hours of lifestyle instruction . We collected data at baseline , 2 , 4 , and 6 months , and evaluated group differences in temporal changes in study outcomes . At 6 months , 1/28 subjects ( UC ) passed the APFT height/weight st and ards . There were no group differences in changes in weight ( PA : -0.1 kg vs. UC : + 0.3 kg ; p = 0.9 ) , body fat ( PA : -0.9 % vs. UC : -1.1 % ; p = 0.9 ) , systolic blood pressure ( PA : + 1.3 mm Hg vs. UC : -2.1 mm Hg ; p = 0.2 ) , diastolic blood pressure ( PA : + 3.8 mm Hg vs. UC : -2.4 mm Hg ; p = 0.3 ) , or resting heart rate in beats per minute ( bpm ) ( PA : + 7.8 bpm vs. UC : + 0.1 bpm ; p = 0.2 ) . These results suggest that using an accelerometer with web-based feedback capabilities plus m and atory physical training does not assist in significant weight loss or ability to pass the APFT height/weight st and ards among overweight/obese soldiers The aim of the study was to compare group and individual weight reduction programmes in the treatment of severe obesity . The study population included 40 women and 20 men , mean age 41 years . The mean body mass index was 43.5 kg/m2 in women and 42.2 kg/m2 in men . The subjects were r and omly divided into two groups , one with group counselling ( GC group ) and the other with individual counselling ( IC group ) . The treatment programme of the GC group consisted of a two-week weight reduction period in a rehabilitation centre followed by group sessions for two years . The programme of the IC group consisted of individual counselling and follow-up by a physician . The adherence rate of the follow-up examinations was 97 % at two years and 88 % at five years . In the GC group the mean weight reduction in women at three months and at one , two and five years was 15.6 , 15.7 , 5.4 and 2.1 kg and in men 14.9 , 13.1 , 1.8 and 3.0 kg , respectively . In the IC group the corresponding values for women were 8.4 , 11.9 , 10.4 and 3.4 kg and for men 17.0 , 26.2 , 15.6 and 12.9 kg . Self-reported and measured weights at the five-year follow-up were closely correlated ( r = 0.99 ) . Weight loss during the first three months predicted a good result at two and five years . The results showed that group counselling starting with an in-patient period led to rapid weight reduction , but a better and more sustained effect was achieved by individual counselling , especially in men BACKGROUND In the literature , it is not yet clear whether sex may affect the outcomes of exercise training in obese adults . AIM The aim of this study was to investigate gender difference in the effects of combined aerobic resistance exercise ( ARE ) versus aerobic exercise ( AE ) alone on body composition in overweight and obese adults . DESIGN R and omized clinical trial . SETTING University-based outpatient clinic . POPULATION Sixty-five healthy , untrained overweight and obese men and women METHODS They were r and omized into one of two intervention groups ; AE group ( N.=33 ) performed leg cycle exercises with increasing duration and frequency ; ARE group ( N.=32 ) performed additionally progressive weight-resistance exercises for the upper and lower parts of body . Both groups were asked not to change their diet . Body composition including percentage of fat ( PF ) , fat mass ( FM ) and fat free mass ( FFM ) in regional and whole body was determined by dual-energy X-ray absorptiometry ( DXA ) at baseline and week 12 . RESULTS ARE leads to more gains on regional and whole body FFM than AE . ARE was more effective in increasing the FFM of arms , trunk and whole body and decreasing PF of trunk in men and superior on reducing FM of legs in women when comparing with AE . CONCLUSION In order to reduce the trunk fat in men and leg fat in women , resistance exercise can be added into an aerobic training program . CLINICAL REHABILITATION IMPACT Dissimilar results of exercises on sex obtained in our study serves as a guide for prescribing exercises in overweight and obese men and women Eight subjects , aged 26 to 50 years , who had long histories of carbohydrate ( CHO ) craving and were more than 45 kg above desirable body weight participated in a r and omized , double-blind , crossover pilot study on the effects of L-tryptophan on weight loss and mood state . One g of tryptophan with 10 g of CHO was administered three times a day , 30 min before meals , as an adjunct to a weight-loss protocol that included nutritional consultation teaching low fat , high fiber diets ranging from 1200 - 1600 kcals/day , behavior modification , and supportive therapy . During the pretreatment period , body weight and plasma tryptophan levels were measured and the Beck Depression Inventory , SCL 90 rating , and Profile-of-Mood State ( POMS ) were used to assess mood . During the treatment periods , subjects kept daily records of food intake and the timing of medication . All patients were seen at least biweekly . After six weeks on medication , baseline measurements were repeated and the crossover between tryptophan and placebo was implemented . After an additional six weeks on placebo or tryptophan , the same measurements were repeated . For the eight patients who completed the three-month protocol , the mean weight loss for six weeks on placebo was 1.14 kg and for six weeks on tryptophan was 2.3 kg . Mean Beck scores were 8.8 during the control period , 8.3 on placebo , and 10.9 on tryptophan . Mean SCL 90 ratings were 69.2 during the control , 54.6 on placebo , and 64.2 on tryptophan . Mean scores for total mood disturbance on the POMS were 48 during the control period , 43 on placebo , and 52 on tryptophan . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The objective of this study was to evaluate the effect of a 32-week personalized Polar weight management program ( PWMP ) compared with st and ard care ( SC ) on body weight , body composition , waist circumference , and cardiorespiratory fitness in overweight or obese adults . RESEARCH METHODS AND PROCEDURES Overweight or obese ( 29 + /- 2 kg/m(2 ) ) men and women ( n = 74 ) 38 + /- 5 years of age were r and omly assigned into either PWMP ( men = 20 , women = 21 ) or SC ( men = 15 , women = 18 ) . Both groups managed their own diet and exercise program after receiving the same st and ardized nutrition and physical activity advice . PWMP also received a weight management system with literature to enable the design of a personalized diet and exercise weight loss program . Body weight and body composition , waist circumference , and cardiorespiratory fitness were measured at weeks 0 , 16 , and 32 . RESULTS Eighty percent of participants completed the 32-week intervention , with a greater proportion of the dropouts being women ( PWMP : 2 men vs. 7 women ; SC : 2 men vs. 4 women ) . At 32 weeks , PWMP completers had significantly ( p < 0.001 ) greater losses in body weight [ 6.2 + /- 3.4 vs. 2.6 + /- 3.6 ( st and ard deviation ) kg ] , fat mass ( 5.9 + /- 3.4 vs. 2.2 + /- 3.6 kg ) , and waist circumference ( 4.4 + /- 4.5 vs. 1.0 + /- 3.6 cm ) . Weight loss and fat loss were explained by the exercise energy expenditure completed and not by weekly exercise duration . DISCUSSION More effective weight loss was achieved after treatment with the PWMP compared with SC . The results suggest that the PWMP enables effective weight loss through tools that support self-monitoring without the requirement of more costly approaches to program supervision Objective : To investigate the effect of including seafood and fish oils , as part of an energy-restricted diet , on weight loss in young overweight adults . Design : R and omized controlled trial of energy-restricted diet varying in fish and fish oil content was followed for 8 weeks . Subjects were r and omized to one of four groups : ( 1 ) control ( sunflower oil capsules , no seafood ) ; ( 2 ) lean fish ( 3 × 150 g portions of cod/week ) ; ( 3 ) fatty fish ( 3 × 150 g portions of salmon/week ) ; ( 4 ) fish oil ( DHA/EPA capsules , no seafood ) . The macronutrient composition of the diets was similar between the groups and the capsule groups , were single-blinded . Subjects : A total of 324 men and women aged 20–40 years , BMI 27.5–32.5 kg/m2 from Icel and , Spain and Irel and . Measurements : Anthropometric data were collected at baseline , midpoint and endpoint . Confounding factors were accounted for , with linear models , for repeated measures with two-way interactions . The most important interactions for weight loss were ( diet × energy intake ) , ( gender × diet ) and ( gender × initial-weight ) . Results : An average man in the study ( 95 kg at baseline receiving 1600 kcal/day ) was estimated to lose 3.55 kg ( 95 % CI , 3.14–3.97 ) ( 1 ) ; 4.35 kg ( 95 % CI , 3.94–4.75 ) ( 2 ) ; 4.50 kg ( 95 % CI , 4.13–4.87 ) ( 3 ) and 4.96 kg ( 95 % CI , 4.53–5.40 ) on diet ( 4 ) in 4 weeks , from baseline to midpoint . The weight-loss from midpoint to endpoint was 0.45 ( 0.41–0.49 ) times the observed weight loss from baseline to midpoint . The diets did not differ in their effect on weight loss in women . Changes in measures of body composition were in line with changes in body weight . Conclusion : In young , overweight men , the inclusion of either lean or fatty fish , or fish oil as part of an energy-restricted diet result ed in ∼1 kg more weight loss after 4 weeks , than did a similar diet without seafood or supplement of marine origin . The addition of seafood to a nutritionally balanced energy-restricted diet may boost weight loss Objective To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals . Design R and omized controlled trial . Setting Research studies unit . Participants Overweight hypertensive patients , receiving one or two antihypertensive drugs , were recruited by advertising , and allocated r and omly to a usual care group ( controls ; n = 118 ) or a lifestyle modification group ( programme group ; n = 123 ) . Intervention A 4-month programme of weight loss , a low-sodium ‘ Dietary Approaches to Stop Hypertension’-type diet with added fish , physical activity and moderation of alcohol intake . After 4 months , if mean 24-h ambulatory blood pressure ( ABP ) was less than 135/85 mmHg , antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun . Main outcome measures Antihypertensive drug requirements , ABP , weight , waist girth at 4 months and 1-year follow-up . Results Ninety control group and 102 programme group participants completed the study . Mean 24-h ABP changed after 4 months by −1.0/−0.3 ± 0.5/0.4 mmHg in controls and −4.1/−2.1 ± 0.7/0.5 mmHg with the lifestyle programme ( P < 0.01 ) . At follow-up , changes in the two groups were not significantly different ( 4.1/1.3 ± 1.1/1.0 mmHg in controls ; 2.5/−0.1 ± 1.1/0.8 mmHg in the programme group ; P = 0.73 ) . At 4 months , drug withdrawal differed significantly between the groups ( P = 0.038 ) in men ( control 44 % ; programme 66 % ) but not in women ( 65 and 64 % , respectively ; P = 0.964 ) . At follow-up , sex-related differences were not significant , and 41 % in the control group and 43 % in the programme group maintained drug-withdrawal status . With the programme , net weight loss was 3.3 kg ( P < 0.001 ) at 4 months and 3.0 kg ( P < 0.001 ) at follow-up ; respective net decreases in waist girth were 3.3 cm ( P < 0.001 ) and 3.5 cm ( P < 0.001 ) . Conclusions A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term . Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk OBJECTIVE : To examine the influence of sex on whole body and regional subcutaneous , visceral , total adipose tissue ( AT ) , skeletal muscle ( SM ) , and lean tissue in response to weight loss induced by diet alone ( DO ) or the combination of diet and aerobic ( DA ) or resistance exercise ( DR ) . DESIGN : Sixty upper‐body obese men and women were r and omly assigned to one of three treatments : DO , DA , or DR . All tissues were measured using a whole body , magnetic resonance imaging protocol . RESULTS : Within each group reductions were observed for body weight ( ~11 kg ) , subcutaneous and visceral AT ( P<0.01 ) . After controlling for pretreatment differences in tissue size , reductions in total adiposity , total and regional subcutaneous and visceral adipose tissue were not different between sexes ( P>0.1 ) . Independent of sex , the reduction in visceral AT was greater than subcutaneous AT ( P<0.05 ) in response to DO and DA . With the exception of DA women , the reduction in abdominal subcutaneous AT was greater ( P<0.05 ) than lower‐body subcutaneous AT in response to diet and exercise , but not diet alone , in both sexes ( P>0.05 ) . Independent of sex , skeletal muscle mass was preserved within the exercise groups ( P>0.05 ) but not diet alone ( P<0.05 ) . Peak VO2 ( l/min ) improved in the DA groups as did muscular strength in the DR groups ( P<0.01 ) . CONCLUSIONS : These findings indicate that in response to diet or diet and exercise‐induced weight loss , reductions in total adiposity , subcutaneous and visceral adipose tissue distribution are not different in obese men and women . Independent of sex , the combination of diet and exercise results in a preservation of skeletal muscle mass , a preferential reduction of abdominal subcutaneous AT , and improved functional capacity by comparison to diet alone BACKGROUND The National Cholesterol Education Program ( NCEP ) recommends a low-saturated-fat , low-cholesterol diet , with weight loss if indicated , to correct elevated plasma cholesterol levels . Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein ( HDL ) cholesterol . Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people . METHODS We tested the hypothesis that exercise ( walking or jogging ) will increase HDL cholesterol levels in moderately overweight , sedentary people who adopt a hypocaloric NCEP diet . We r and omly assigned 132 men and 132 women 25 to 49 years old to one of three groups : control , hypocaloric NCEP diet , or hypocaloric NCEP diet with exercise . One hundred nineteen of the men and 112 of the women returned for testing after one year . RESULTS After one year , the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly ( range of reduction in mean fat weight , 4.0 to 7.8 kg ) . Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group . Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted ( mean [ + /- SE ] change , + 13 + /- 3 percent ) than in the men who only dieted ( + 2 + /- 3 percent , P less than 0.01 ) or the men who acted as controls ( -4 + /- 2 percent , P less than 0.001 ) . HDL cholesterol levels remained about the same in the women who exercised and dieted ( + 1 + /- 2 percent ) ; they were higher than in the women who only dieted ( -10 + /- 3 percent , P less than 0.01 ) , but not higher than in the controls ( -3 + /- 3 percent ) . CONCLUSIONS Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat , low-cholesterol diet PURPOSE To evaluate a year-long behavioral weight control program , used with and without an intermittent very-low-calorie diet ( VLCD ) in the treatment of type II diabetes mellitus . PATIENTS AND METHODS Subjects ( n = 93 ) were r and omly assigned to 50-week treatment programs that used either a balanced low-calorie diet ( LCD ) of 1,000 to 1,000 kilocalories ( kcal ) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD . Weight , glycemic control , blood pressure , and lipids were assessed at baseline , at the end of the year-long treatment , and at 2-year follow-up . RESULTS Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program ( 14.2 kg versus 10.5 kg ; P = 0.057 ) and remained off diabetes medication longer ( P < 0.05 ) . These benefits of the VLCD were due primarily to the first 12 weeks of the diet ; the second diet maintained , but did not increase , these effects . Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program , but attendance declined in the latter weeks of treatment and weight was regained . There was also marked recidivism in both groups in the year following treatment . CONCLUSIONS The intermittent VLCD improved weight loss and glycemic control , but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD . Moreover , lengthening treatment to a full year did not prevent relapse . Thus , further research is needed to develop a successful approach to long-term weight control OBJECTIVE Conjugated linoleic acid ( CLA ) has several benefits , including body fat reduction , as proved in animals . However , the results of CLA-induced body composition alterations in humans are inconsistent , and no related data are available for Chinese population s. This study aim ed to determine whether CLA affects body weight ( BW ) loss and body composition of overweight and obese Chinese subjects . METHODS In this r and omized , double-blind , placebo-controlled trial , subjects with a body mass index ( BMI ) of 24 to 35 kg/m(2 ) r and omly received 1.7 g of cis-9,trans-11 and trans-10,cis-12 CLA ( n = 30 ) or placebo ( salad oil ; n = 33 ) in 200 mL of sterilized milk twice daily for 12 wk . Changes in body composition were determined by bioimpedance measurements . RESULTS Sixty-three subjects completed the study ( CLA , n = 30 ) . After 12 wk , compared with the baseline , the BW , BMI , total fat mass , fat percentage , subcutaneous fat mass , and waist-to-hip ratio decreased in the CLA group ( P < 0.05 ) . The CLA group was stratified by BMI and gender . The BW , BMI , subcutaneous fat mass , and waist-to-hip ratio decreased in 27 subjects with a BMI ≥ 27 , and these indices , except subcutaneous fat mass , were lower in female subjects . The levels of total cholesterol , triacylglycerol , low-density lipoprotein , and plasma fasting glucose increased , whereas those of high-density lipoprotein decreased after 3 mo of CLA treatment . The changes were not significantly different from the baseline values . CONCLUSION The supplementation of CLA for 12 wk in overweight and grade I obese Chinese subjects yielded lower obesity indices , with no obvious adverse effects OBJECTIVE Weight loss with preferential effect on the visceral adipose tissue ( VAT ) depot could have important clinical benefits . In this study , we investigated the independent and combined effect of regular exercise and diet induced weight loss on body fat distribution . DESIGN ; R and omized control design of i ) exercise-only ( EXO ; 12 weeks of exercise without diet-restriction ) , ii ) hypocaloric-diet ( DIO ; 8 weeks of very low energy diet ( VLED 600 kcal/day ) followed by 4-weeks weight maintenance diet ) and iii ) hypocaloric-diet and exercise ( DEX ; 8 weeks VLED 800 kcal/day+a 4-week weight maintenance diet combined with exercise throughout the 12 weeks ) . SUBJECTS Seventy-nine obese males and females were included . MEASUREMENTS Body fat distribution was quantified by magnetic resonance imaging (MRI)-technology . RESULTS In the EXO group , the weight loss ( 3.5 kg ) and the relative reduction in VAT ( 18 % ) was significantly lower compared with the weight losses in the DIO and DEX groups ( 12.3 kg ; P<0.01 ) and to the reduction in VAT ( 30 - 37 % ; P<0.01 ) . In all the three groups , the relative reduction of VAT was higher as compared with the reduction in fat mass ( FM ; combining all fat depots determined by MRI ; P<0.01 for all comparisons ) . The changes in VAT were associated with changes in FM and related to the initial VAT/FM ratio ( r(2)=0.72 ; P<0.01 ) . CONCLUSION Exercise has no additional effects in reduction of the VAT depot , compared with the major effects of hypocaloric diet alone . In addition , the effects of exercise per se on VAT are relatively limited . The effects on the VAT depot are closely associated with changes in total FM PURPOSE The study investigated the efficacy and cost-effectiveness of a cognitive-behavioral weight management program , complemented by an interactive Web site and brief telephone/e-mail coaching . METHODS In 2006 - 2007 , 1755 overweight , non-active-duty TRICARE beneficiaries were r and omized to one of three conditions with increasing intervention intensity : written material s and basic Web access ( RCT 1 ) , plus an interactive Web site ( RCT 2 ) , plus brief telephone/e-mail coaching support ( RCT 3 ) . The study assessed changes in weight , blood pressure , and physical activity from baseline to 6 , 12 , and 15 - 18 months . ( Study retention was 31 % at 12 months . ) Average and incremental cost-effectiveness and cost-offset analyses were conducted . RESULTS Participants experienced significant weight loss ( -4.0 % , -4.0 % , and -5.3 % , respectively , in each RCT group after 12 months and -3.5 % , -3.8 % , and -5.1 % , respectively , after 15 to 18 months ) , increased physical activity , and decreased blood pressure . Cost-effectiveness ratios were $ 900 to $ 1100/ quality -adjusted life year ( QALY ) for RCT 1 and RCT 2 and $ 1900/QALY for RCT 3 . The cost recovery period to the government was 3 years for RCTs 1 and 2 and 6 years for RCT 3 . CONCLUSION A relatively inexpensive cognitive-behavioral weight management intervention improved patient outcomes . Extrapolation of savings for the entire TRICARE population would significantly reduce direct medical costs OBJECTIVE To determine whether an intermittent very-low-calorie diet ( VLCD ) improves weight loss and glycemic control more than moderate caloric restriction alone . RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes ( n = 54 ) who were ≥ 20 % over ideal body weight participated in a 20-week behavioral weight control program . Subjects were r and omized to either a st and ard behavioral therapy ( SBT ) group or to one of two VLCD groups . SBT subjects received a 1,500−1,800 kcal/day diet throughout . Both VLCD groups followed a VLCD for 5 consecutive days during week 2 , followed by either intermittent VLCD therapy for 1 day/week for 15 weeks ( 1-day ) or for 5 consecutive days every 5 weeks ( 5-day ) , with a 1,500−1,800 kcal/day diet at other times . RESULTS Both VLCD groups lost more weight than the SBT group over the 20 weeks ( P = 0.04 ) . Although the groups did not differ in fasting plasma glucose ( FPG ) changes at 20 weeks , more subjects in the 5-day group attained a normal HbA1c when compared with the SBT group ( P = 0.04 ) . This benefit was independent of the effects of weight loss . The best predictor of overall change in FPG and HbA1c was the FPG response during the first 3 weeks of the program . CONCLUSIONS Periodic VLCDs improved weight loss in diabetic subjects . A regimen with intermittent 5-day VLCD therapy seemed particularly promising , because more subjects in this group attained a normal HbA1c . Moreover , the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks , and it was a better predictor of the 20-week response than initial or overall weight loss This study evaluated effects of a behavioral approach which placed emphasis on tailored behavior counseling , diet , weight loss and weight maintenance . A one-year r and omized controlled trial was conducted among 235 overweight/obese adults in Japan . The intervention group ( n=119 ) received individual-based counseling using a behavioral approach and the changes made in the diet and physical activity were dependent on each participant as much as possible . One year later , the intervention group lost significantly more weight than the control group ( -5.0 kg vs. 0.1 kg for men and -3.9 kg vs. -0.2 kg for women ) . Compared to the control group , the male intervention group reduced overall energy , cereals and dairy products consumption significantly , while increasing green and yellow vegetable intake , and the female intervention group significantly reduced intake of dairy products . Regarding behaviors , both male and female intervention groups increased the number of walking steps and women improved their irregular eating habits compared to those in the control groups . Behavior changes were related to weight loss ; participants who maintained the action/maintenance stage or moved to later stages lost significantly more weight than participants who remained in the pre-contemplation/contemplation/preparation stages or regressed to earlier stages . After one-year follow-up , the intervention group maintained significantly lower weights , lower energy intakes and improvements in irregular eating habits . Our behavioral approach led to diet and behavior modification , weight loss and maintenance . Because modified variables differed between men and women , gender-specific approaches may be necessary BACKGROUND AND AIMS In a cross-European study it was recently shown that consumption of cod increases weight loss in men and also has other positive health effects . The aim of this study was to investigate whether cod consumption increases weight loss and improves cardiovascular risk factors in a dose dependent manner during an 8-week energy restriction diet in young overweight and obese healthy adults . METHODS AND RESULTS In this dietary intervention 126 subjects ( 20 - 40 years , BMI 27.5 - 32.5 kg/m(2 ) ) comprised the group given energy-restricted diets ( -30 % ) ; they were prescribed an identical macronutrient composition but different amounts of cod : the control group were given no seafood ; group 1 were given 150 g cod 3 times a week ; and group 2 were given 150 g cod 5 times a week . Anthropometric measurements and cardiovascular risk factors were assessed at baseline and endpoint . Body weight decreased after 8-weeks ( 5.0+/-2.9 kg , P<0.001 ) , also waist circumference ( 5.0+/-3.2 cm , P<0.001 ) , BMI ( 1.65+/-0.95 kg , P<0.001 ) , systolic ( 3.4+/-8.9 mmHg , P=0.001 ) and diastolic blood pressure ( 2.4+/-6.9 mmHg , P<0.001 ) , triglycerides ( 1.26+/-0.567 mmol/L , P=0.030 ) and insulin ( 1.21+/-5.31 mU/L , P=0.025 ) . The prevalence of the metabolic syndrome dropped from 29 to 21 % . According to linear models weight loss was 1.7 kg greater among subjects consuming 150 g 5x/week compared to the control group ( P<0.015 ) . The trend analysis supported a dose-response relationship between cod consumption and weight loss ( P<0.001 ) , but changes of other measured cardiovascular risk factors were similar between the groups . CONCLUSION A dose-response relationship between cod consumption and weight loss during an 8-week energy restriction diet is found and 5 x 150 g cod/week results in 1.7 kg greater weight loss in young overweight or obese adults than a isocaloric diet without seafood Restricting dietary fat intake while consuming carbohydrates ad libitum has recently been promoted as a weight loss regimen . Sixty subjects ( 52 females and eight males ) were r and omized to low fat ad libitum carbohydrate ( low-fat ) or low fat with caloric restriction ( low-calorie ) behaviour modification treatments . Forty-nine subjects completed the 16 - 20 week programme . Subjects in both groups reported averaging over five exercise sessions per week during treatment . The low-calorie group lost significantly more weight ( males 11.8 kg , s.d . 6.4 ; females 8.2 kg , s.d . 4.2 ) than the low-fat group ( males 8.0 kg , s.d . 1.3 ; females 3.9 kg , s.d . 3.7 ) . Both groups of subjects lost similar amounts of lean body mass . There was significantly greater loss of body fat in the low-calorie group . A slight reduction in RMR , adjusted for changes in lean body mass , was observed in both groups . Fat intake was reduced from 90 to 30 g per day . Subjects in both groups reduced their total energy intake with the low-calorie group consuming fewer calories per day than the low-fat group . Both groups showed significant and equivalent improvements in eating habits based on micro analysis of eating diaries . Eating in social situations and emotional eating , however , continued to cause adherence problems during treatment for both groups . Follow-up data collected 9 - 12 months after completion of treatment on 65 % of the subjects completing the study showed no significant difference between the two groups in weight losses from baseline ( low-fat group 2.6 kg ; low-calorie group 5.5 kg ) OBJECTIVE Behavioral weight-loss programs ( BWL ) provide limited instruction on how to change the environmental context of weight-regulating behaviors , perhaps contributing to regain . Drawing on social ecological models , this trial evaluated a comprehensive weight-loss program that targeted both an individual 's behavior and his or her physical and social home environment . METHOD Overweight and obese adults ( N = 201 ; 48.9 ± 10.5 years ; 78.1 % women ) were r and omized to BWL or to BWL plus home-environment changes ( BWL + H ) . Groups met weekly for 6 months and bimonthly for 12 months . BWL + H participants were given items to facilitate healthy choices in their homes ( e.g. , exercise equipment , portion plates ) and attended treatment with a household partner . Weight loss at 6 and 18 months was the primary outcome . RESULTS BWL + H changed many aspects of the home environment and produced better 6-month weight losses than BWL ( p = .017 ) . At 18 months , no weight-loss differences were observed ( p = .19 ) and rates of regain were equivalent ( p = .30 ) . Treatment response was moderated by gender ( 6 months , p = .011 ; 18 months , p = .006 ) . Women lost more weight in BWL + H than BWL at 6 and 18 months , whereas men in BWL lost more weight than those in BWL + H at 18 months . Partners , regardless of gender , lost more weight in BWL + H than BWL at both time points ( ps < .0001 ) . CONCLUSION The home food and exercise environment is malleable and targeting this microenvironment appears to improve initial weight loss , and in women , 18-month outcomes . Research is needed to underst and this gender difference and to develop home-focused strategies with more powerful and sustained weight-loss effects 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 < .001 ) vs control group 1 and 21.5 ( 95 % CI , 5.4 - 85.6 ; P < .001 ) vs control group 2 . The 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 < .001 ) . The numbers of participants with 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 The goal of this study was to evaluate a correspondence weight control program , and to assess the impact of three program elements ( weekly homework , interim weigh-ins , and participation deposits ) individually and in combination . All treated participants received 15 weekly st and ard lessons by mail . Three program features were varied factorially : a ) homework assignments , b ) interim weigh-ins and c ) a deposit refunded contingent on returning homework and /or attending interim weigh-ins . Participants were assigned r and omly to active treatment conditions or a delayed treatment control group . Among treated males ( N = 14 ) , initial average weight loss and BMI reduction were 9.6 kg and 3.1 respectively ; average net weight loss and BMI reduction at one year follow-up were 5.8 kg and 1.9 respectively . Among treated females ( N = 128 ) , initial average weight loss and BMI reduction were 3.1 kg and 1.2 respectively ; average net weight loss and BMI reduction at one year were 2.3 kg and .88 respectively . Women in all treated groups , except lessons only , showed a greater BMI reduction than untreated controls at the end of treatment . Women in conditions including both homework and interim weigh-ins had greater initial BMI reductions ( M = 1.6 ) than those who received lessons only ( M = .76 ) . At one year , net BMI reductions were comparable across all treated groups . Of the 42 women initially registered in conditions that included both homework and weigh-ins , 12 who denied joining other programs lost at least 4.5 kg ( M = 7.1 ) during treatment , and 7 had a net loss of at least 4.5 kg ( M = 8.0 ) at one year without apparent involvement in any other program BACKGROUND In light of the current obesity epidemic , treatment models are needed that can prevent weight gain or provide weight loss . We examined the long-term effects of a supervised program of moderate-intensity exercise on body weight and composition in previously sedentary , overweight and moderately obese men and women . We hypothesized that a 16-month program of verified exercise would prevent weight gain or provide weight loss in the exercise group compared with controls . METHODS This was a r and omized controlled efficacy trial . Participants were recruited from 2 midwestern universities and their surrounding communities . One hundred thirty-one participants were r and omized to exercise or control groups , and 74 completed the intervention and all laboratory testing . Exercise was supervised , and the level of energy expenditure of exercise was measured . Controls remained sedentary . All participants maintained ad libitum diets . RESULTS Exercise prevented weight gain in women and produced weight loss in men . Men in the exercise group had significant mean + /- SD decreases in weight ( 5.2 + /- 4.7 kg ) , body mass index ( calculated as weight in kilograms divided by the square of height in meters ) ( 1.6 + /- 1.4 ) , and fat mass ( 4.9 + /- 4.4 kg ) compared with controls . Women in the exercise group maintained baseline weight , body mass index , and fat mass , and controls showed significant mean + /- SD increases in body mass index ( 1.1 + /- 2.0 ) , weight ( 2.9 + /- 5.5 kg ) , and fat mass ( 2.1 + /- 4.8 kg ) at 16 months . No significant changes occurred in fat-free mass in either men or women ; however , both had significantly reduced visceral fat . CONCLUSIONS Moderate-intensity exercise sustained for 16 months is effective for weight management in young adults CONTEXT Increasing dietary protein relative to carbohydrate and fat enhances weight loss , at least in part by increasing satiety . The mechanism for this is unclear . OBJECTIVE The objective of this study was to compare the effects of isocaloric test meals with differing protein to fat ratios on fasting and postpr and ial ghrelin , insulin , glucose , appetite , and energy expenditure before and after weight loss on the respective dietary patterns . DESIGN The study design was a r and omized parallel design of 12 wk of weight loss ( 6 MJ/d ) and 4 wk of weight maintenance ( 7.3 MJ/d ) with meals administered at wk 0 and 16 . SETTING The study was performed at an out-patient research clinic . PATIENTS AND OTHER PARTICIPANTS Fifty-seven overweight ( body mass index , 33.8 + /- 3.5 kg/m2 ) hyperinsulinemic men ( n = 25 ) and women ( n = 32 ) were studied . INTERVENTIONS High-protein/low-fat ( 34 % protein/29 % fat ) or st and ard protein/high-fat ( 18 % protein/45 % fat ) diets/meals were given . MAIN OUTCOME MEASURES The main outcome measures were weight loss and fasting and postpr and ial ghrelin , insulin , glucose , appetite , and energy expenditure before and after weight loss . RESULTS Weight loss ( 9.2 + /- 0.7 kg ) and improvements in fasting and postpr and ial insulin and glucose occurred independently of diet composition . At wk 0 and 16 , subjects wanted less to eat after the high-protein/low-fat than the st and ard protein/high-fat meal ( P = 0.02 ) . Fasting ghrelin increased ( 157.5 + /- 3.4 pg/ml or 46.6 + /- 1.0 pmol/liter ; P < 0.001 ) , and the postpr and ial ghrelin response improved with weight loss ( P = 0.043 ) independently of diet composition . Postpr and ial hunger decreased with weight loss ( P = 0.018 ) and was predicted by changes in fasting and postpr and ial ghrelin ( r2 = 0.246 ; P = 0.004 ) . Lean mass was the best predictor of fasting ( r2 = 0.182 ; P = 0.003 ) and postpr and ial ghrelin ( r2 = 0.096 ; P = 0.039 ) levels . CONCLUSIONS Exchanging protein for fat produced similar weight loss and improvements in metabolic parameters and ghrelin homeostasis . The reduced appetite observed with increased dietary protein appears not to be mediated by ghrelin homeostasis The aim of this work was to determine whether the effects of weight loss on coronary heart disease ( CHD ) risk factors are comparable in men and women and whether the long term impact of modest weight loss is as great as the initial response . Changes in CHD risk factors were examined at 6 month intervals in 159 moderately overweight subjects who were participating in an 18 month behavioral weight loss program . Men experienced greater decreases in blood pressure , triglycerides , and waist-to-hip ratio ( WHR ) and greater increases in HDL-cholesterol with weight loss than women . Most of these gender differences were removed by adjusting for baseline values and changes in BMI . After these adjustments , improvements in WHR at 18 months were shown to be greater in women than in men . Participants ( n = 39 ) who lost 4.5 kg or more from baseline to 6 months ( mean weight loss of 11.8 kg or 13 % of initial body weight ) and maintained this weight loss within + /- 2.3 kg had significant long term improvements ( through 18 months ) in triglycerides , HDL and LDL-cholesterol , WHR , systolic and diastolic blood pressure , and fasting and 2 h insulin . Changes in HDL-cholesterol , the HDL : Total cholesterol ratio , and WHR actually increased between 6 and 18 months and improvements in all other parameters were maintained over time . Men have greater improvements in CHD risk factors with weight loss than women , but this gender difference appears to derive from differences in CHD risk factors at baseline and differences in weight loss . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Phase 1 of the Trials of Hypertension Prevention was a collaborative , r and omized controlled clinical trial design ed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure . METHODS Participants aged 30 to 54 years who had a high-normal diastolic blood pressure ( 80 to 89 mm Hg ) , and were between 115 % and 165 % of their desirable body weight , were r and omly assigned to either an 18-month weight loss intervention ( n = 308 ) or a usual-care control condition ( N = 256 ) . Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions . Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aim ed at achieving a moderate reduction in energy intake and an increase in physical activity . RESULTS The average weight losses in the intervention group at 6 , 12 , and 18 months of follow-up were 6.5 , 5.6 , and 4.7 kg for men and 3.7 , 2.7 , and 1.6 kg for women . The mean ( + /- SE ) change in diastolic blood pressure for intervention participants compared with controls at termination was -2.8 + /- 0.6 mm Hg for men and -1.1 + /- 0.9 mm Hg for women . For systolic blood pressure , the corresponding change was -3.1 + /- 0.7 mm Hg for men and -2.0 + /- 1.3 mm Hg for women . Blood pressure reductions were greater for those who lost larger amounts of weight . Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women , and sex differences in weight loss could be accounted for by differences in baseline body weight . CONCLUSIONS During an 18-month follow-up period , this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure R and omised controlled trials are the best way to compare the effectiveness of different interventions . Only r and omised trials allow valid inferences of cause and effect . Only r and omised trials have the potential directly to affect patient care — occasionally as single trials but more often as the body of evidence from several trials , whether or not combined formally by meta- analysis . It is thus entirely reasonable to require higher st and ards for papers reporting r and omised trials than those describing other types of study . Like all studies , r and omised trials are open to bias if done badly.1 It is thus essential that r and omised trials are done well and reported adequately . Readers should not have to infer what was probably done , they should be told explicitly . Proper methodology should be used and be seen to have been used . Yet review s of published trials have consistently found major deficiencies in reporting,2 3 4 making the task This study explores whether the addition of aspartame-sweetened foods and beverages to a low fat , hypocaloric diet enhances compliance and result ing weight loss . Fifty-nine obese ( 130 - 225 % of ideal body weight ) , free living men and women were r and omly assigned to either a Balanced Deficit Diet ( BDD ) or a BDD supplemented with aspartame . Over a 12-week weight loss period , volunteers attended weekly support group meetings including behavior modification training and exercise instruction . Males achieved a clinical ly significant weight loss ( greater than 23 lb ) in both study groups , while females lost an average of 12.8 lb in the control group vs. 16.5 lb in the experimental group . In both treatment groups , sleep , general energy level , level of physical activity , and feeling of well-being showed clinical ly meaningful improvement . This study suggests possible advantages to supplementing a BDD with aspartame-sweetened foods as part of a multidisciplinary weight loss program . The small sample size prohibits definitive conclusions but does provide the protocol for a larger , outpatient clinical trial INTRODUCTION Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes , hypertension , dyslipidemia and gallbladder disease . OBJECTIVE To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia , treated over a period of 6 months . METHODOLOGY In a 6-month , multicenter ( 10 centers in Portugal ) , double-blind , parallel , placebo-controlled study , 166 patients , aged 18 - 65 years , body mass index ( BMI ) > or = 27 kg/m2 , LDL cholesterol > 155 mg/dl , were r and omized to a reduced calorie diet ( 600 kcal/day deficit ) plus orlistat three times a day or placebo . Exclusion criteria included triglycerides > 400 mg/dl , severe cardiovascular disease , uncontrolled hypertension , type 1 or 2 diabetes under pharmacological treatment , and gastrointestinal or pancreatic disease . RESULTS The mean difference in weight from baseline was 5.9 % ( 5.6 kg ) in the orlistat group vs. 2.3 % ( 2.2 kg ) in the placebo group . In the orlistat group 49 % of patients achieved 5 - 10 % weight loss and 8.8 % achieved > 10 % . The orlistat group showed a significant reduction in total and LDL cholesterol , with similar changes for HDL in both treatment groups . The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group , leading to discontinuation in 7 patients . CONCLUSION Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight , BMI and lipid parameters This report provides a further analysis of the year 4 weight losses in the Look AHEAD ( Action for Health in Diabetes ) study and identifies factors associated with long-term success . A total of 5,145 overweight/obese men and women with type 2 diabetes were r and omly assigned to an intensive lifestyle intervention ( ILI ) or a usual care group , referred to as Diabetes Support and Education ( DSE ) . ILI participants were provided approximately weekly group or individual treatment in year 1 ; continued but less frequent contact was provided in years 2 - 4 . DSE participants received three group educational sessions in all years . As reported previously , at year 4 , ILI participants lost an average of 4.7 % of initial weight , compared with 1.1 % for DSE ( P < 0.0001 ) . More ILI than DSE participants lost ≥ 5 % ( 46 % vs. 25 % , P < 0.0001 ) and ≥ 10 % ( 23 % vs. 10 % , P < 0.0001 ) of initial weight . Within the ILI , achievement of both the 5 % and 10 % categorical weight losses at year 4 was strongly related to meeting these goals at year 1 . A total of 887 participants in ILI lost ≥ 10 % at year 1 , of whom 374 ( 42.2 % ) achieved this loss at year 4 . Participants who maintained the loss , compared with those who did not , attended more treatment sessions and reported more favorable physical activity and food intake at year 4 . These results provide critical evidence that a comprehensive lifestyle intervention can induce clinical ly significant weight loss ( i.e. , ≥ 5 % ) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45 % of patients at 4 years |
13,038 | 25,580,086 | Conclusion TAP block and LAI provide comparable short-term postoperative analgesia , but TAP block has better long-lasting effect | Background Postoperative pain management is of great importance in perioperative anesthetic care .
Transversus abdominis plane ( TAP ) block has been described as an effective technique to reduce postoperative pain and morphine consumption after open lower abdominal operations .
Meanwhile , local anesthetic infiltration ( LAI ) is also commonly used as a traditional method .
However , the effectiveness of these two methods has not been compared before .
Methods A meta- analysis of all relevant r and omized controlled trials ( RCTs ) was conducted to compare the efficacy of single shot TAP block with that of single shot LAI for postoperative analgesia in adults . | Background : Transversus abdominis plane block is a safe , simple and effective technique of providing analgesia for lower abdominal surgeries with easily identifiable l and marks . Aims : To compare the analgesic efficacy of transversus abdominis plane block with that of direct infiltration of local anesthetic into surgical incision in lower abdominal procedures . Setting s and Design : Prospect i ve r and omized controlled trial in lower abdominal surgeries done under general anesthesia . Material s and Methods : 52 ASA I-II patients undergoing lower abdominal gynecological procedures under general anesthesia were divided r and omly into two groups each after written informed consent . A bilateral TAP block was performed on Group T with 0.25 % bupivacaine 0.6 ml/kg with half the volume on either side intra-operatively after skin closure before extubation using a short bevelled needle , whereas Group I received local infiltration intra-operatively after skin closure with the same amount of drug . The time taken for the first rescue analgesic and visual analog score ( VAS ) was noted , following which , the patient was administered intravenous morphine 0.1 mg/kg and connected to an intravenous patient controlled analgesia system with morphine for 24 hrs from the time of block administration . 24 h morphine requirement was noted . VAS and sedation scores were noted at 2 , 4 , 6 and 24 h postoperatively . Statistical Analysis Used : The results were analyzed with SPSS 16 . A P value < 0.05 was considered significant . Duration of analgesia and 24 h morphine requirement was analysed by Student 's t-test . VAS scores , with paired comparisons at each time interval , were performed using the t-test or Mann-Whitney U-test , as appropriate . Categorical data were analyzed using Chi square or Fisher 's exact test . Results : In Group T , the time to rescue analgesic was significantly more and the VAS scores were lower ( P = 0.001 and 0.003 respectively ) . The 24 hr morphine requirement and VAS at 2 , 4 , 6 and 24 h were less in the Group T ( P = 0.001 ) . Incidence of PONV was significant in Group I ( P = 0.043 ) , whereas Group T were less se date d at 2 and 4 h ( P = 0.001 and 0.014 ) . Conclusions : Transversus abdominis plane block proved to be an effective means of analgesia for lower abdominal surgeries with minimal side-effects A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Purpose In this prospect i ve , r and omized , double-blind study , our aim was to compare the analgesic efficacy of the semi-blind approach of transversus abdominis plane ( TAP ) block with a placebo block in patients undergoing unilateral inguinal hernia repair . Methods After receiving hospital ethical committee approval and informed patient consents , American Society of Anesthesiologists ( ASA ) I – III patients aged 18–80 were enrolled in the study . St and ard anesthesia monitoring was applied to all patients . After premedication , spinal anesthesia was administered to all patients with 3.5 mL heavy bupivacaine at the L3-L4 subarachnoid space . Patients were r and omly allocated into 2 groups . Group I ( n = 32 ) received a placebo block with 20 mL saline , Group II ( n = 32 ) received semi-blind TAP block with 0.25 % bupivacaine in 20 mL with a blunt regional anesthesia needle into the neurofascial plane via the lumbar triangle of Petit near the midaxillary line before fascial closure . At the end of the operation , intravenous ( IV ) dexketoprofen was given to all patients . The verbal analog scale ( VAS ) was recorded at 2 , 4 , 6 , 12 , and 24 hours postoperatively . Paracetamol IV was given to patients if their VAS score > 3 . A rescue analgesic of 0.05 mg/kg morphine IV was applied if VA S > 3 . Total analgesic consumption and morphine requirement in 24 hours were recorded . Results TAP block reduced VAS scores at all postoperative time points ( P < 0.001 ) . Postoperative analgesic and morphine requirement in 24 hours was significantly lower in group II ( P < 0.01 ) . Conclusion Semi-blind TAP block provided effective analgesia , reducing total 24-hour postoperative analgesic consumption and morphine requirement in patients undergoing elective unilateral inguinal hernia repair CONTEXT The transversus abdominis plane ( TAP ) block is a new regional anaesthesia technique applicable to infants and children . OBJECTIVE ( S ) The present study was design ed to evaluate the analgesic efficacy of ultrasound-guided TAP block with high volume local anaesthetic ( 0.5 ml kg−1 ) during the first 24 h after surgery in children undergoing inguinal hernia repair . DESIGN R and omised comparative study . SETTING Gaziantep University Hospital between December 2010 and May 2011 . PATIENTS OR OTHER PARTICIPANTS Fifty-seven children between 2 and 8 years of age undergoing unilateral inguinal hernia repair were r and omised to TAP block ( group T , n = 29 ) or to wound infiltration ( group C , n = 28 ) . INTERVENTION(S ) A TAP block using ultrasound guidance with 0.25 % levobupivacaine 0.5 ml kg−1 or wound infiltration with 0.2 ml kg−1 0.25 % levobupivacaine , was performed on the same side as the hernia under general anaesthesia . MAIN OUTCOME MEASURES Time to first analgesic , cumulative number of doses of analgesic , pain scores and adverse effects were assessed over the course of 24 h. RESULTS The time to first analgesic ( mean ± SD ) was significantly longer in group T than in group C ( 17 ± 6.8 vs. 4.7 ± 1.6 h , respectively ; P < 0.001 ) . Thirteen ( 45 % ) patients in group T did not require any analgesic within the first 24 h. The cumulative number of doses of analgesic was significantly lower in group T than in group C ( 1.3 ± 1.2 vs. 3.6 ± 0.7 , respectively , P < 0.001 ) . Pain scores were significantly different between the groups at all time points except at 1 , 20 and 24 h ( P < 0.001 ) . CONCLUSION Ultrasound-guided TAP block with high volume ( 0.5 ml kg−1 ) 0.25 % levobupivacaine provides prolonged postoperative analgesia and reduced analgesic use without any clinical side-effects after unilateral hernia repair in children . TRIAL REGISTRATION ACTRN12611000585921 ( 7/06/2011 ) from Australian New Zeal and Clinical Trials Registry BACKGROUND After renal transplantation , postoperative pain is usually mild to moderate . Postoperative pain is a concern and administration of systemic analgesic may be difficult because of underlying co-morbidities and variable responses of the graft . The transversus abdominis plane ( TAP ) block is one of the different approaches for postoperative pain relief following abdominal surgeries . We evaluated analgesic efficacy of TAP block on early postoperative pain by numeric rating scale ( NRS ) and morphine consumption during the first 24 hours after kidney transplantation . METHODS Forty-four patients , scheduled as kidney recipients were r and omized into two equal groups and were anesthetized with the same technique . After the induction of anesthesia , 15 mL of 0.25 % Bupivacaine plus 5 μ/ml epinephrine or saline was deposited into the transversus abdominis neuro-fascial plane on the side of surgery by ultrasound guide . Each patient was assessed by a blinded investigator using NRS at 1st , 4th , 8th , 12th , and 24th hour postoperatively . RESULTS Demographic data were not significantly different between the study groups . There was significant difference in median of NRS score measured at all time points in the study groups ( P < 0.001 ) . The 24-hour morphine consumption ( mean ± SD ) was 10.8 ± 9.5 mg in bupivacaine group compared with 41.2 ± 3.8 mg in the saline group ( P = 0.001 ) . There was statistically significant reduction in intraoperative fentanyl consumption in the TAP group 120 ± 20 μg compared to the control group 358 ± 24 μg ( P = 0.001 ) . In study group 4 patients and in control group 90 patients received morphine titration for pain relief ( P = 0.03 ) . There was no complication in the study groups related to nerve block . Only two patients in saline group had nausea ( P = 0.07 ) . None of our patients received any other oral or IV rescue medication . CONCLUSION Ultrasound TAP block can reduce postrenal transplantation pain and the amount of opioids consumption intraoperatively and during the first 24 hours after surgery in kidney recipients BACKGROUND : Laparoscopic cholecystectomy is associated with postoperative pain of moderate intensity in the early postoperative period . Recent r and omized trials have demonstrated the efficacy of transversus abdominis plane ( TAP ) block in providing postoperative analgesia after abdominal surgery . We hypothesized that a TAP block may reduce pain while coughing and at rest for the first 24 postoperative hours , opioid consumption , and opioid side effects in patients undergoing laparoscopic cholecystectomy in day-case surgery . METHODS : In this r and omized , double-blind study , 80 patients undergoing laparoscopic cholecystectomy in our day-case surgery unit were allocated to receive either bilateral ultrasound-guided posterior TAP blocks ( 20 mL 0.5 % ropivacaine ) or placebo blocks . Postoperative pain treatment consisted of oral acetaminophen 1000 mg × 4 , oral ibuprofen 400 mg × 3 , IV morphine ( 0–2 hours postoperatively ) , and oral ketobemidone ( 2–24 hours postoperatively ) . The primary outcome was postoperative pain scores while coughing calculated as area under the curve for the first 24 postoperative hours ( AUC/24 h ) . Secondary outcomes were pain scores at rest ( AUC/24 h ) , opioid consumption , and side effects . Patients were assessed 0 , 2 , 4 , 6 , 8 , and 24 hours postoperatively . Group-wise comparisons of visual analog scale ( VAS ) pain ( AUC/24 h ) were performed with the 2- sample t test . Morphine and ketobemidone consumption were compared with the Mann-Whitney test for unpaired data . Categorical data were analyzed using the & khgr;2 test . RESULTS : The primary outcome variable , VAS pain scores while coughing ( AUC/24 h ) , was significantly reduced in the TAP versus the placebo group ( P = 0.04 ) ; group TAP : 26 mm ( SD 13 ) ( weighted average level ) versus group placebo : 34 ( 18 ) ( 95 % confidence interval ) : 0.5–15 mm ) . VAS pain scores at rest ( AUC/24 h ) showed no significant difference between groups . Median morphine consumption ( 0–2 hours postoperatively ) was 7.5 mg ( interquartile range : 5–10 mg ) in the placebo group compared with 5 mg ( interquartile range : 0–5 mg ) in the TAP group ( P < 0.001 ) . The odds ratio of a r and om patient in group TAP having less morphine consumption than a r and om patient in group placebo was P ( group TAP < group placebo ) = 0.26 ( confidence interval : 0.15 , 0.37 ) where 0.5 represents no difference between groups . There were no between-group differences in total ketobemidone consumption , levels of nausea and sedation , number of patients vomiting , or consumption of ondansetron . CONCLUSIONS : TAP block after laparoscopic cholecystectomy may have some beneficial effect in reducing pain while coughing and on opioid requirements , but this effect is probably rather small Background : The transversus abdominis plane block is a promising approach to the provision of postoperative analgesia following abdominal incision . This effective method blocks the sensory nerve supply to the anterior abdominal wall . The authors evaluated its analgesic efficacy over the first 12 postoperative hours after abdominoplasty with liposculpture in a r and omized , controlled , double-blind clinical trial . Methods : Twenty-eight women undergoing abdominoplasty by means of a lower abdominal incision were r and omized to undergo transversus abdominis plane block ( n = 14 ) in addition to st and ard care therapy ( n = 14 ) . The investigators , who were blinded to the conditions of the study , assessed the patients in the postanesthesia care unit at 4 , 6 , and 12 hours postoperatively . Results : The transversus abdominis plane block group reported reduced pain scores ( F = 12.73 , p < 0.001 ) . Morphine requirement was also reduced in the first 12 postoperative hours ( & khgr;2 = 19.27 ; p < 0.005 ) . Transversus abdominis plane block group patients also exhibited early ambulation compared with the control group ( F = 65.15 , p < 0.001 ) . All of the patients in the transversus abdominis plane block group reported lower levels of pain with their postoperative analgesic regimen , which was demonstrated by their rates of recovery . The Mann-Whitney test was performed on the data , which illustrated that mean ranks consistently corresponded to the trend the authors predicted . Conclusions : The transversus abdominis plane block seems to hold considerable promise for patients undergoing abdominoplasty by providing effective postoperative analgesia in the first 12 postoperative hours after major abdominoplasty . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , II . Figure . No caption available BACKGROUND Transversus abdominis plane ( TAP ) block has been reported to provide effective analgesia after lower abdominal surgery , but there are few data comparing ilioinguinal/iliohypogastric nerve ( IHN ) block with ultrasound-guided TAP block in patients undergoing inguinal hernia repair . METHODS Two hundred and seventy-three patients undergoing day-case open inguinal hernia repair with a mesh were r and omly allocated to receive either ultrasound-guided TAP block or blind IHN block with levobupivacaine 0.5 % , before surgery . Patients were monitored for visual analogue scale ( VAS ) scores at rest ( in the post-anaesthesia care unit , and at 4 and 12 h ) and at rest and during movement ( at 24 , 48 h , 3 and 6 months ) . Pain at 6 months was also assessed using the DN4 question naire for neuropathic pain . RESULTS Median VAS pain scores at rest were lower in the ultrasound-guided TAP group at 4 h ( 11 vs 15 , P=0.04 ) , at 12 h ( 20 vs 30 , P=0.0014 ) , and at 24 h ( 29 vs 33 , P=0.013 ) . Pain after the first 24 h , at 3 and 6 months after surgery , and DN4 scores were similar in both groups ( P = NS ) . The proportion of patients with VAS > 40 mm on movement at 6 months was comparable { 18.2 % [ 95 % CI ( 12.2 - 26.1 % ) ] vs 22.4 % ( 15.8 - 30.6 % ) in the TAP and IHN groups , respectively , P=0.8}. Postoperative morphine requirements were lower during the first 24 h in the TAP block group ( P=0.03 ) . CONCLUSIONS Ultrasound-guided TAP block provided better pain control than ' blind ' IHN block after inguinal hernia repair but did not prevent the occurrence of chronic pain BACKGROUND The l and mark-guided transversus abdominis plane ( TAP ) block is an effective method of providing postoperative analgesia in patients undergoing lower abdominal surgery . We evaluated the analgesic efficacy of the ultrasound (US)-guided TAP block in patients undergoing Caesarean delivery . METHODS A r and omized , double-blind , placebo-controlled trial was performed at a tertiary maternity hospital . Fifty women undergoing Caesarean delivery received bilateral US-guided TAP blocks with either ropivacaine 0.5 % or saline . All participants received a spinal anaesthetic with bupivacaine and fentanyl , followed by postoperative acetaminophen , non-steroidal anti-inflammatory drugs , and patient-controlled i.v . morphine without long-acting intrathecal opioids . Each patient was assessed 24 h after delivery for morphine usage , average pain score , nausea , vomiting , pruritus , drowsiness , and satisfaction with pain relief . RESULTS Forty-seven participants completed the trial , 23 in the active group and 24 in the placebo group . Total morphine use in 24 h was reduced in the active group ( median 18.0 mg ) compared with the placebo group ( median 31.5 mg , P<0.05 ) . The active group reported improved satisfaction with their pain relief measured by visual analogue scale compared with the placebo group ( median 96 vs 77 mm , P=0.008 ) . Fewer patients required antiemetics in the active group ( P=0.03 ) . There were no local complications attributable to the TAP block , but one participant had an anaphylactoid reaction after ropivacaine injection . CONCLUSIONS The US-guided TAP block reduces morphine requirements after Caesarean delivery when used as a component of a multimodal analgesic regimen . Registered with the Australia New Zeal and Clinical Trials Registry ACTRN12608000540314 . URL : http://www.anzctr.org.au/trial_view.aspx?ID=83176 Background Although opioids are the main choice for acute postoperative pain control , many side effects have been reported for them . NSAIDs and paracetamol have been used extensively as alternatives , and it seems that they are more effective for minor to moderate pain control postoperatively when have been used alone or in combination with opioids . As laparoscopic cholecystectomy poses moderate pain postoperatively , this study was planned to assess whether paracetamol is able to provide effective analgesia as a sole analgesic at least in the first few hours post operatively . Objectives We evaluated the effect of intravenous Paracetamol on postoperative pain in patients undergoing laparoscopic cholecystectomy . Patients and Methods This is a r and omized double- blind clinical trial study . 30 patients ASA class I , aged 18 to 50 years , c and i date for laparoscopic cholecystectomy were recruited , and r and omly divided into two equal groups . Group A ( paracetamol group ) received 1 gr paracetamol and group B received placebo ten minutes after the induction of anesthesia . 0.1 mg/Kg Morphine was administered intravenously based on patients compliant and pain score > 3 . Pain score and the opioids consumption were recorded in the first six hours postoperative . Patient 's pain was measured by the VAS ( Visual Analog Scale ) . Results The pain score was lower in group A ( P= 0.01 ) , but the morphine consumption showed no significant difference between the groups ( P= 0.24 ) during the first 6 hours postoperatively . Conclusions Although paracetamol ( 1gr ) has caused a better pain relief quality but it is not a suitable analgesic for moderate pain control in acute phase after surgery alone AIM Control of postoperative pain is one of the most important concerns for both the patients and the surgical team . In this regard the efficacy of wound infiltration with local analgesia and the most proper drugs to be used are not settled . We conducted our study trying to investigate this point in a prospect i ve r and omized double blinded manner . METHODS With inclusion criteria of : age ( 18 - 65 y ) , volume < 90 mL , first time , no lymph node enlargement and exclusion criteria of : duration > 90 min , incision length > 10 cm , neck dissection decided during surgery and a postoperative complication within the first 24 hours . Sixty patients planned for total thyroidectomy under general anesthesia were enrolled in the study in three groups with twenty patients assigned r and omly to each one : group ( A ) a control group in which no wound infiltration was done , group ( B ) in which preoperative wound infiltration with 10 mL bupivacaine 0.5 % was done , and group ( C ) in which preoperative wound infiltration with 10 mL ropivacaine 0.75 % was done . Postoperative pain was evaluated by Visual Analogue Score ( VAS ) with a scale of ( 0 - 10 ) at 1 hour , 4 hours , 8 hours and 16 hours . RESULTS The postoperative pain experienced by all the patients reached a maximum point at 1 hour postoperatively then started to decrease to be minimal at 8 hours and almost negligible at 16 hours . Ropivacaine group showed a statistically significant decrease in pain perception at 1 hour postoperatively ( P=0.028 ) , bupivacaine group showed also a decrease in pain perception at 1 hour but it was not statistically significant . At 4 hours of operation and after ; neither ropivacaine nor bupivacaine showed an effect on pain perception . CONCLUSION The benefit of local wound infiltration with local analgesia in decreasing postoperative pain is limited to a short period after surgery in which the use of ropivacaine 0.75 % is recommended over pubivaccaine 0.5 % Background and Objectives Transversus abdominis plane ( TAP ) block has been shown to reduce pain and analgesic requirements after abdominal surgery . Our hypothesis was that bilateral TAP blocks decrease pain after laparoscopic cholecystectomy when compared with local anesthetic infiltration of trocar insertion sites . Methods Eighty patients undergoing laparoscopic cholecystectomy were r and omized to receive either bilateral TAP blocks or local anesthetic infiltration of trocar insertion sites with ropivacaine 0.5 % . Postoperative pain scores and analgesic use for the first 24 hrs were recorded . Results Eighty patients were enrolled in the study . After exclusions , data were analyzed on 39 patients in group T ( bilateral TAP block ) and 35 patients in group I ( infiltration ) . There was no statistically significant difference in pain scores on the numeric analog scale ( 0–10 ) between the groups at 4 hrs after surgery ( P = 0.18 ) or during the 24 hrs after surgery ( P = 0.23 ) . The time interval from anesthesia start to surgery start was greater in group T than group I ( 48 vs 35 mins , P < 0.001 ) . There was no significant difference found in analgesic use during the first 24 hrs after surgery . Conclusions Bilateral ultrasound-guided TAP block is equivalent to local anesthetic infiltration of trocar insertion sites for overall postoperative pain in a heterogeneous group of patients undergoing laparoscopic cholecystectomy Background Despite the laparoscopic approach , patients can suffer moderate to severe pain following bariatric surgery . This r and omized controlled double-blinded trial investigated the analgesic efficacy of ultrasound-guided transversus abdominis plane ( TAP ) blocks for laparoscopic gastric-bypass surgery . Methods Seventy patients undergoing laparoscopic gastric-bypass surgery were r and omized to receive either bilateral ultrasound-guided subcostal TAP block injections after induction of general anesthesia or none . All patients received trocar insertion site local anesthetic infiltration and systemic analgesia . The primary outcome was cumulative opioid consumption ( IV morphine equivalent ) during the first 24 h postoperatively . Interval opioid consumption , pain severity scores , rates of nausea or vomiting , and rates of pruritus were measured during phase I recovery , and at 24 and 48 h postoperatively . Results There was no difference in cumulative opioid consumption during the first 24 h postoperatively between the TAP ( 32.2 mg [ 95 % CI , 27.6–36.7 ] ) and control ( 35.6 mg [ 95 % CI , 28.6–42.5 ] ; P = 0.41 ) groups . Postoperative opioid consumptions during phase I recovery and the 24–48-h interval were similar between groups , as were pain scores at rest and with movement during all measured intervals . The rates of nausea or vomiting and pruritus were equivalent . Conclusions Bilateral TAP blocks do not provide additional analgesic benefit when added to trocar insertion site local anesthetic infiltration and systemic analgesia for laparoscopic gastric-bypass surgery The visual analogue scale ( VAS ) is a st and ard measurement tool in pain research and clinical practice , and has been shown to have linear scale properties for mild to moderate pain . Our aim was to evaluate the scaling properties of the VAS in subjects with severe acute pain . After Ethics Committee approval we studied 22 patients and asked them to rate the severity of their pain on a 100 mm VAS at the initial assessment ( VAS1 ) , and again after administration of analgesic medication . The subject was asked to nominate when they considered their pain intensity had halved , and at this time they were asked to rate this on a second VAS ( VAS0.5 ) . When the subject had received satisfactory relief of their pain , they were asked to describe how much their pain had been relieved and were then asked to rate their final pain state using a third VAS ( VASfinal ) . The mean ( SD ) scores were VAS1 84 ( 14 ) ( range 56–100 ) , VAS0.5 42 ( 13 ) and VASfinal 21 ( 16 ) . The mean ( 95 % CI ) for VASratio was 0.51 ( 0.45–0.57 ) . The mean ( SD ) patients ’ estimate of pain relief was 77 (21)% from that of baseline , with a mean ( SD ) VASfinal 0.26 ( 0.20 ) , 95 % CI 0.17–0.38 . The correlation of the patients ’ estimate of pain relief with the VASfinal was r=0.89 , rho=0.87 , both P<0.001 . The VAS is a linear scale in subjects with severe acute pain . Changes in the VAS score represent a relative change in the magnitude of pain sensation CONTEXT The analgesic effect of transversus abdominis plane ( TAP ) block after inguinal hernia repair is unclear . OBJECTIVE The aim of this r and omised and double-blind study was to evaluate the analgesic effect of a TAP block in patients scheduled for primary inguinal hernia repair . The TAP block was evaluated versus placebo and versus an active comparator ( ilioinguinal block and wound infiltration ) . DESIGN R and omised controlled trial . SETTING Single centre trial . Study period from June 2010 to November 2011 . PATIENTS Adults ( 18 to 75 years ) with American Society of Anesthesiologists ’ status 1–3 scheduled for primary inguinal hernia repair as day case surgery were included in the study . INTERVENTIONS Ninety patients were allocated to one of three groups : group TAP , group infiltration ( ilioinguinal nerve block and wound infiltration ) and group placebo . MAIN OUTCOME MEASURES The primary outcome measure was pain scores while coughing between group TAP and group placebo calculated as area under the curve for the first 24 h ( AUC24 h ) . Secondary outcomes were pain scores while coughing and at rest , opioid consumption and side effects in groups TAP , infiltration and placebo . RESULTS Visual analogue pain scores while coughing and at rest demonstrated no difference between groups . Pain scores in groups infiltration , TAP and placebo were 19 versus 22 versus 15 mm at rest ( P = 1.00 ) and 37 versus 41 versus 37 mm while coughing ( P = 1.00 ) . Pain scores at 6 h ( AUC6 h ) were significantly lower in group infiltration than in group TAP ( 10 versus 25 mm at rest , P < 0.001 ; 17 versus 40 mm while coughing , P < 0.001 ) , and than in group placebo ( 10 versus 20 mm at rest , P = 0.003 ; 17 versus 38 mm while coughing , P < 0.001 ) . Median morphine consumption was lower in group infiltration than in group placebo ( 0 versus 5 mg , P < 0.003 ) . No differences among groups were demonstrated for ketobemidone consumption or side effects . CONCLUSION Ultrasound-guided TAP block did not reduce postoperative pain after inguinal hernia repair . TRIAL REGISTRATION Clinical trials.gov identifier : NCT01052285 . EudraCT number 2010–018403 - 29 A prospect i ve study of blocking T10-L1 with local anaesthetic , bilaterally in 30 patients undergoing caesarean section under general anaesthesia has been shown to provide effective postoperative analgesia thus requiring significantly less narcotics ( mean 66.6 mg of pethidine ) compared to the 30 patients in the control group ( mean 163 mg of pethidine ) . A cocktail of 0.5 % of bupivacaine with adrenaline and xylocaine 1 % produced analgesia for the duration ranging from 8 to 12 hours ( mean 8.4 hours ) . Patients with abdominal field block were awake , alert and comfortable during the immediate postoperative period . They were pain-free sufficiently to put the babies to the breast early and frequently BACKGROUND The transversus abdominis plane ( TAP ) block is usually performed by l and mark-based methods . This prospect i ve , r and omized , and double-blinded study was design ed to describe a method of ultrasound-guided TAP block and to evaluate the intra- and postoperative analgesic efficacy in patients undergoing laparoscopic cholecystectomy under general anaesthesia with or without TAP block . METHODS Forty-two patients undergoing laparoscopic cholecystectomy were r and omized to receive st and ard general anaesthetic either with ( Group A , n=21 ) or without TAP block ( Group B , n=21 ) . Ultrasound-guided bilateral TAP block was performed with a high frequent linear ultrasound probe and an in-plane needle guidance technique with 15 ml bupivacaine 5 mg ml(-1 ) on each side . Intraoperative use of sufentanil and postoperative dem and of morphine using a patient-controlled analgesia device were recorded . RESULTS Ultrasonographic visualization of the relevant anatomy , detection of the shaft and tip of the needle , and the spread of local anaesthetic were possible in all cases where a TAP block was performed . Patients in Group A received significantly less [ corrected ] intraoperative sufentanil and postoperative morphine compared with those in Group B [ mean ( SD ) 8.6 ( 3.5 ) vs 23.0 ( 4.8 ) microg , P<0.01 , and 10.5 ( 7.7 ) vs 22.8 ( 4.3 ) mg , P<0.05 ] . CONCLUSIONS Ultrasonographic guidance enables exact placement of the local anaesthetic for TAP blocks . In patients undergoing laparoscopic cholecystectomy under st and ard general anaesthetic , ultrasound-guided TAP block substantially reduced the perioperative opioid consumption OBJECTIVE : To investigate whether local infiltration of bupivacaine reduces postoperative pain at trocar sites during gynecologic laparoscopy . METHODS : This was a r and omized , placebo-controlled , double-blind clinical trial , using patients as their own controls . For each patient , 2 opposite trocar sites were infiltrated . One site was r and omly chosen to receive 0.5 % bupivacaine , and the other received 0.9 % saline . In addition , patients were r and omized into 2 cohorts to receive either preincision or postsurgical infiltration . Surgeons , patients , and interviewers were blinded toward the exposure . Postoperative pain was evaluated at 1 hour , 4 hours , and 24 hours after surgery using a 100-mm visual analog scale . Patients rated their pain at each of the infiltrated trocar sites . A 20-mm difference between pain scores was considered clinical ly significant . A paired t test was used for analysis . RESULTS : Infiltration of bupivacaine at completion of surgery result ed in significantly decreased pain at 1 hour postoperatively ( mean pain score 25.8 versus 48.6 , P = .02 ) . Mean pain scores at 4 hours and 24 hours were decreased , but not statistically different . Patients receiving bupivacaine before surgery did not have a statistically significant decrease in pain scores . CONCLUSION : Infiltration of bupivacaine at completion of gynecologic laparoscopic surgery decreases pain at trocar sites in the immediate postoperative period . LEVEL OF EVIDENCE : The study objective of this prospect i ve , double-blind r and omised controlled study was to evaluate the efficacy of ultrasound guided transversus abdominis plane ( TAP ) block and bupivacaine infiltration of the skin and subcutaneous tissue of the wound in patients undergoing hysterectomy . Patients were r and omly allocated to three groups : a control group ( n=18 ) and TAP block group ( n=18 ) received bilateral TAP blocks with saline and bupivacaine respectively , and an infiltration group ( n=19 ) received skin and subcutaneous wound tissue infiltration with bupivacaine at the end of surgery . After surgery patients received patient-controlled intravenous tramadol and were assessed for pain and tramadol consumption at 1 , 2 , 4 , 6 and 24 hours . Both the TAP and infiltration groups had lower movement and rest pain scores than the control group , with lower scores in the TAP group than the infiltration group at 6 and 24 hours . Total tramadol consumption was significantly lower in the TAP group than in the other groups at all time points . We concluded that ultrasound-guided TAP block reduced rest and movement pain after total abdominal hysterectomy and was more effective than superficial wound infiltration for postoperative pain management |
13,039 | 24,830,290 | Greatest efficacy was associated with use of tenofovir-emtricitabine ( vs. other nucleoside analogue backbones ) and integrase str and transfer inhibitors ( vs. other third drug classes ) .
CONCLUSION Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy , but are more effective when commenced at plasma viral loads < 100,000 copies/mL. Rising viral load should be considered an indication for starting treatment .
Integrase inhibitors offer a treatment advantage ( vs. other third drug classes ) | BACKGROUND A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines . | BACKGROUND A hypersensitivity reaction to abacavir has been known to occur in approximately 4 % of patients treated with the drug . OBJECTIVE The goal of this study was to determine risk factors associated with the development of hypersensitivity reactions to abacavir . METHODS We constructed an analysis population from all protocol s conducted by GlaxoSmithKline that involved at least 24 weeks of abacavir exposure with a quality -assured or vali date d clinical data base by June 30 , 2000 . Demographic , clinical , and laboratory characteristics of patients who developed a hypersensitivity reaction to abacavir were compared with those of patients who did not . Univariate and multivariate logistic regression models were fit to underst and the predictive ability of each potential risk factor . Odds ratios ( ORs ) and 95 % Wald CIs were computed . RESULTS A total of 5332 patients exposed to abacavir were included in this analysis ; 197 cases of hypersensitivity reaction were reported ( 3.7 % ) . In univariate models , several associations were noted , but most subgroups produced rates within the expected range of 3 % to 6 % . The multivariate model using all demographic data available ( Model 1 ) indicated that the risk of hypersensitivity reaction among black patients ( 3 % hypersensitivity reaction ) was lower ( OR = 0.59 ; 95 % CI , 0.38 - 0.91 ) compared with other ethnic groups . In addition , a lower rate of hypersensitivity reaction was observed in patients who received previous therapy for HIV-1 infection with other antiretroviral agents ( 3 % hypersensitivity reaction ) compared with those receiving therapy for the first time ( OR = 0.58 ; 95 % CI , 0.44 - 0.78 ) . CONCLUSIONS The only characteristics identified as prognostic factors for hypersensitivity reaction to abacavir were antiretroviral treatment status ( ie , treatment experience ) and black race , each result ing in a lower rate compared with the expected incidence Thomas Campbell and colleagues report findings of a r and omized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing BACKGROUND The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors ( NRTIs ) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which NRTI combination has greater efficacy and safety is not known . METHODS In a r and omized , blinded equivalence study involving 1858 eligible patients , we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection : abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir . The primary efficacy end point was the time from r and omization to virologic failure ( defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks , or > or = 200 copies per milliliter at or after 24 weeks ) . RESULTS A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy , according to the NRTI combination , among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more . At a median follow-up of 60 weeks , among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group ( hazard ratio , 2.33 ; 95 % confidence interval , 1.46 to 3.72 ; P<0.001 ) , with 57 virologic failures ( 14 % ) in the abacavir-lamivudine group versus 26 ( 7 % ) in the tenofovir DF-emtricitabine group . The time to the first adverse event was also shorter in the abacavir-lamivudine group ( P<0.001 ) . There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48 . CONCLUSIONS In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the times to virologic failure and the first adverse event were both significantly shorter in patients r and omly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine . ( Clinical Trials.gov number , NCT00118898 . Abstract : Raltegravir as initial HIV therapy was examined in a double-blind study ; 160 patients were r and omized to raltegravir ( 400 mg bid after dose-ranging ) , 38 to efavirenz , both with tenofovir/lamivudine . At week 240 , HIV-RNA remained < 50 copies per milliliter in 68.8 % ( raltegravir ) versus 63.2 % ( efavirenz ) , and CD4 increases were 302 versus 276 cells per microliter , respectively . Early HIV-RNA decline predicted later CD4 increases in both groups . Raltegravir resistance was observed in 3 of 10 raltegravir recipients with virologic failure . Few drug-related adverse events were reported after week 48 . Raltegravir had minimal effect on laboratory values , including lipids . Raltegravir with tenofovir/lamivudine showed durable efficacy and good tolerability over 5 years Objective : To evaluate the efficacy and safety/tolerability of dolutegravir ( DTG , S/GSK1349572 ) , a potent inhibitor of HIV integrase , through the full 96 weeks of the SPRING-1 study . Design : ING112276 ( SPRING-1 ) was a 96-week , r and omized , partially blinded , phase IIb dose-ranging study . Methods : Treatment-naive adults with HIV received DTG 10 , 25 , or 50 mg once daily or efavirenz ( EFV ) 600 mg once daily ( control arm ) combined with investigator-selected dual nucleos(t)ide reverse transcriptase inhibitor backbone regimen ( tenofovir/emtricitabine or abacavir/lamivudine ) . The primary endpoint of the study was the proportion of participants with plasma HIV-1 RNA less than 50 copies/ml , based on time to loss of virologic response at 16 weeks ( conducted for the purpose of phase III dose selection ) , with a planned analysis at 96 weeks . Safety and tolerability were also assessed . Results : Of 208 participants r and omized to treatment , 205 received study drug . At week 96 , the proportion of participants achieving plasma HIV-1 RNA less than 50 copies/ml was 79 , 78 , and 88 % for DTG 10 , 25 , and 50 mg , respectively , compared with 72 % for EFV . The median increase from baseline in CD4 + cells was 338 cells/&mgr;l with DTG ( all treatment groups combined ) compared with 301 cells/&mgr;l with EFV ( P = 0.155 ) . No clinical ly significant dose-related trends in adverse events were observed , and fewer participants who received DTG withdrew because of adverse events ( 3 % ) compared with EFV ( 10 % ) . Conclusion : Throughout the 96 weeks of the SPRING-1 study , DTG demonstrated sustained efficacy and favorable safety/tolerability in treatment-naive individuals with HIV-1 Background : Atazanavir , an azapeptide protease inhibitor ( PI ) , has pharmacokinetics that allow once-daily dosing , and it is not associated with significant PI-associated dyslipidemia . Methods : A r and omized , double-blind , double-dummy , active-controlled , 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily . The 810 treatment-naive patients were stratified by HIV RNA level . The primary efficacy end point was the proportion of treated patients with HIV RNA levels < 400 copies/mL through week 48 . Results : At week 48 , HIV RNA levels were < 400 copies/mL in 70 % of patients receiving atazanavir and 64 % of patients receiving efavirenz ( intent-to-treat , difference ; 95 % confidence interval : 5.2 % ; −1.2 % , 11.7 % ) . Median CD4 + cell counts increased at comparable magnitudes and rates in the 2 treatment arms ( mean change at week 48 : 176 cells/mm3 with atazanavir , 160 cells/mm3 with efavirenz ) . Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol , fasting low-density lipoprotein cholesterol , or fasting triglycerides over 48 weeks of therapy . Atazanavir-linked bilirubin elevations infrequently result ed in treatment discontinuation ( < 1 % ) . Atazanavir treatment did not increase fasting glucose or insulin levels . Conclusions : For initial HIV treatment , a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine ABSTRACT Once-daily administration of 300 mg of lamivudine in combination with other antiretroviral agents has been proposed as a possible way to optimize anti-human immunodeficiency virus ( HIV ) treatment and to facilitate adherence . A single-center , r and omized , two-way , crossover study was conducted in 60 healthy subjects to compare the steady-state pharmacokinetics of lamivudine in plasma and its putative active anabolite , lamivudine 5′-triphosphate ( lamivudine-TP ) , in peripheral blood mononuclear cells ( P BMC s ) following 7 days of treatment with lamivudine at 300 mg once daily and 7 days of the st and ard regimen of 150 mg twice daily . Serial blood sample s were collected over 24 h for determination of plasma lamivudine concentrations by liquid chromatography-mass spectrometry and intracellular lamivudine-TP concentrations in peripheral blood mononuclear cells by high-performance liquid chromatography/radioimmunoassay methods . Pharmacokinetic parameters were calculated based on lamivudine and lamivudine-TP concentration-time data . Regimens were considered bioequivalent if 90 % confidence intervals ( CI ) for the ratio ( once daily/twice daily ) of geometric least-squares ( GLS ) means for lamivudine and lamivudine-TP pharmacokinetic values fell within the acceptance range of 0.8 to 1.25 . Steady-state plasma lamivudine pharmacokinetics following the once- and twice-daily regimens were bioequivalent with respect to the area under the drug concentration-time curve from 0 to 24 h at steady state ( AUC24,ss ) ( GLS mean ratio , 0.94 ; 90 % CI , 0.92 , 0.97 ) and average plasma lamivudine concentration over the dosing interval ( Cave , ss ) ( GLS mean ratio , 0.94 ; 90 % CI , 0.92 , 0.97 ) . Steady-state intracellular lamivudine-TP pharmacokinetics after the once- and twice-daily regimens were bioequivalent with respect to AUC24,ss ( GLS mean ratio , 0.99 ; 90 % CI , 0.88 , 1.11 ) , Cave , ss ( GLS mean ratio , 0.99 ; 90 % CI , 0.88 , 1.11 ) , and maximum lamivudine concentration ( Cmax , ss ) ( GLS mean ratio , 0.93 ; 90 % CI , 0.81 , 1.07 ) . Lamivudine-TP trough concentrations were modestly lower ( by 18 to 24 % ) during the once-daily regimen ; the clinical importance of this is unclear , given the large intersubject variability in values that was observed ( coefficient of variation , 48 to 124 % ) . Once-daily lamivudine was as well tolerated as the twice-daily regimen . Overall , the results of this study suggest that for key AUC-related parameters , lamivudine at 300 mg once daily is pharmacokinetically equivalent to lamivudine at 150 mg twice daily Emtricitabine ( FTC ) is a potent deoxycytidine nucleoside analogue that was recently approved for the treatment of HIV infection . Emtricitabine is activated by intracellular phosphorylation to its 5'-triphosphate ( FTC5'-TP ) , a competitive inhibitor of the HIV reverse transcriptase ( RT ) . Early clinical studies incorporating pharmacokinetic-pharmacodynamic ( PK-PD ) analyses provided a sound rationale for developing FTC as a once daily drug . A short-term open-label monotherapy trial in therapy naive HIV-infected subjects evaluated various dosage regimens of FTC , i.e. , 25 , 100 , and 200 mg qd and /or bid , with serial measurements of plasma HIV RNA , plasma FTC , and intracellular ( P BMC ) FTC-5'-TP levels over the 14 days of treatment . PK data were augmented by other steady-state studies , one in healthy volunteers and the other in HIV-infected patients receiving 200 mg FTC qd , with measurements of plasma FTC and /or intracellular FTC-5'-TP levels . Correlation between anti-HIV activity and FTC-5'-TP levels was examined with dose- and concentration-response relationships determined . The once daily dosing schedule is supported by the relatively long half-lives of plasma FTC ( 8 - 10 hr ) and P BMC FTC-TP ( 39 hr ) and the high plasma FTC and P BMC FTC-5'-TP concentrations . HIV RNA suppression ( PD ) correlates well with P BMC FTC-5'-TP levels ( PK ) , both reaching a plateau at doses > or = 200 mg/day . The PK and PD characteristics of FTC demonstrate that it is a once daily nucleoside RT inhibitor Background : Pooled analysis of phase 3 , double-blind , double-dummy ECHO and THRIVE trials comparing rilpivirine ( TMC278 ) and efavirenz . Methods : Treatment-naive HIV-1–infected adults were r and omized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily , with background tenofovir disoproxil fumarate/emtricitabine ( TDF/FTC ) ( ECHO ) or TDF/FTC , zidovudine/lamivudine , or abacavir/lamivudine ( THRIVE ) . The primary endpoint was confirmed response [ viral load < 50 copies per milliliter ; intent-to-treat time-to-loss-of-virologic-response ( ITT-TLOVR ) algorithm ] at week 48 . The pooled data set enabled analyses of subgroups and predictors of response/virologic failure . Results : Confirmed responses were 84 % ( rilpivirine ) and 82 % ( efavirenz ) . The difference in response rates ( 95 % confidence interval ) was 2.0 % ( –2.0 % to 6.0 % ) . The incidence of virologic failure was 9 % ( rilpivirine ) versus 5 % ( efavirenz ) . Responses in ITT-TLOVR and ITT-snapshot analyses were consistent . Responses were similar for rilpivirine and efavirenz by background regimen , gender , race and clade . Suboptimal adherence and higher baseline viral load result ed in lower responses , higher virologic failure , and development of resistance in both groups ; the effects on virologic failure were more apparent with rilpivirine . CD4 + cell count increased over time in both groups . Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation ( 3 % vs. 8 % , respectively ) , treatment-related grade 2–4 adverse events ( 16 % vs. 31 % ) , rash ( 3 % vs. 14 % ) , dizziness ( 8 % vs. 26 % ) , abnormal dreams/nightmares ( 8 % vs. 13 % ) , and grade 2−4 lipid abnormalities . Conclusions : At week 48 , rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates . Rilpivirine had more virologic failures and improved tolerability versus efavirenz Background : Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies , yet few studies have comprehensively compared their safety profiles . Methods : Forty-eight-week data are presented from this multicenter , r and omized , open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine , both administered with efavirenz , in HLA-B*5701-negative HIV-1-infected adults . Results : Three hundred eighty-five subjects were enrolled in the study . The overall rate of withdrawal was high ( 28 % ) . Changes in estimated glomerular filtration rate from baseline were similar between arms [ difference 0.953 mL·min−1·1.73 m−2 ( 95 % confidence interval : −1.445 to 3.351 ) , P = 0.435 ] . Urinary excretion of retinol-binding protein and β-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm ( + 50 % ; + 24 % ) compared with the abacavir/lamivudine arm ( no change ; −47 % ) ( P < 0.0001 ) . A lower proportion achieved viral load < 50 copies per milliliter in the abacavir/lamivudine arm ( 114 of 192 , 59 % ) compared with the tenofovir/emtricitabine arm ( 137 of 193 , 71 % ) [ difference 11.6 % ( 95 % confidence interval : 2.2 to 21.1 ) ] . The overall virological failure rate was low . The adverse event rate was similar between arms ( except drug hypersensitivity , reported more in the abacavir/lamivudine arm ) . Conclusions : The study showed no difference in estimated glomerular filtration rate between the arms , however , increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm , the long-term consequence of which is unclear . A significant difference in efficacy favoring tenofovir/emtricitabine was observed Background : STARTMRK , a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients , remained blinded until its conclusion at 5 years . We now report the final study results . Methods : Previously untreated patients without baseline resistance to efavirenz , tenofovir , or emtricitabine were eligible for a r and omized study of tenofovir/emtricitabine plus either raltegravir or efavirenz . Yearly analyses were planned , with primary and secondary end points stipulated at weeks 48 and 96 , respectively . The primary efficacy outcome was the percentage of patients with viral RNA ( vRNA ) levels < 50 copies per milliliter counting noncompleters as failures ( NC = F ) . Changes from baseline CD4 count were computed using an observed-failure approach to missing data . No formal hypotheses were formulated for testing at week 240 . Results : Overall , 71 of 281 raltegravir recipients ( 25 % ) and 98 of 282 efavirenz recipients ( 35 % ) discontinued the study ; discontinuations due to adverse events occurred in 14 ( 5 % ) and 28 ( 10 % ) patients in the respective groups . In the primary NC = F efficacy analysis at week 240 , 198 of 279 ( 71.0 % ) raltegravir recipients and 171 of 279 ( 61.3 % ) efavirenz recipients had vRNA levels < 50 copies per milliliter , yielding a treatment difference { [ INCREMENT ] [ 95 % confidence interval ( CI ) ] = 9.5 ( 1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol -stipulated sensitivity analyses and the prespecified subgroup analyses . The mean ( 95 % CI ) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups , respectively [ [ INCREMENT ] ( 95 % CI ) = 62 ( 22 to 102 ) ] . Overall , significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects ( 39.1 % vs 64.2 % , P < 0.001 ) or drug-related clinical adverse events ( 52.0 % vs 80.1 % , P < 0.001 ) . Conclusions : In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240 , vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients . Over the entire study , fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group . Based on better virologic and immunologic outcomes after 240 weeks , raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine |
13,040 | 29,718,793 | Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer | Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists ( GnRHa ) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial .
This systematic review and meta- analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer . | PURPOSE Observational studies suggested that luteinizing hormone-releasing hormone agonists ( LHRHa ) might prevent premature ovarian failure result ing from adjuvant chemotherapy in premenopausal patients . We aim ed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer . PATIENTS AND METHODS In a prospect i ve , r and omized , open-label , controlled multicenter study , 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide ( with or without taxane ) -based neoadjuvant chemotherapy with or without goserelin . The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle , continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle . The primary objective was the reappearance of normal ovarian function , defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy . RESULTS Fifty-three patients ( 88.3 % ) experienced temporary amenorrhea ( 93.3 % with v 83.3 % without goserelin ) . No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy ( 70.0 % with v 56.7 % without goserelin ; difference of 13.3 % ; 95 % CI , -10.85 to 37.45 ; P = .284 ) . All but one evaluable patient reported regular menses at 2 years after chemotherapy . Time to restoration of menstruation was 6.8 months ( 95 % CI , 5.2 to 8.4 ) with goserelin and 6.1 months ( 95 % CI , 5.3 to 6.8 ) without goserelin ( P = .304 ) . Chemotherapy result ed in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up , supporting the other findings . CONCLUSION Premenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone Background Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression ( OFS ) as part of adjuvant endocrine therapy . If chemotherapy is also given , it is uncertain whether to select concurrent or sequential OFS initiation . Design and methods We analyzed 1872 patients enrolled in the r and omized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive , HER2-negative breast cancer and upon r and omization to an OFS-containing adjuvant endocrine therapy , initiated gonadotropin-releasing-hormone-agonist triptorelin . Breast cancer-free interval ( BCFI ) was compared between patients who received OFS concurrently with chemotherapy in TEXT ( n = 1242 ) versus sequentially post-chemotherapy in SOFT ( n = 630 ) . Because timing of trial enrollment relative to adjuvant chemotherapy differed , we implemented l and mark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy ( median , 15.5 and 8.1 months from enrollment to l and mark in TEXT and SOFT , respectively ) . As a non-r and omized treatment comparison , we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling . Results Distributions of several clinico-pathologic characteristics differed between groups . Patients who were premenopausal post-chemotherapy in SOFT were younger on average . The median duration of adjuvant chemotherapy was 18 weeks in both groups . There were 231 ( 12 % ) BC events after post-l and mark median follow-up of about 5 years . Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-l and mark BCFI compared with sequential triptorelin post-chemotherapy , either in the overall population ( HR = 1.11 , 95 % CI 0.72 - 1.72 ; P = 0.72 ; 4-year BCFI 89 % in both groups ) , or in the subgroup of 692 women < 40 years at diagnosis ( HR = 1.13 , 95 % CI 0.69 - 1.84 ) who are less likely to develop chemotherapy-induced amenorrhea . Conclusion Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up , with limited statistical power especially for the subgroup < 40 years , neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected . Clinical trials.gov NCT00066690 and NCT00066703 Background Chemotherapy-induced premature ovarian insufficiency ( POI ) impacts fertility and other aspects of women 's health . The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI . Patients and methods This was a prospect i ve , r and omized , parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease . The primary outcome was amenorrhoea between 12 and 24 months after r and omization , supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI . Results A total of 227 patients were r and omized and the primary analysis was conducted on 202 patients . Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22 % versus 38 % in the control group ( P = 0.015 ) and the prevalence of POI to 18.5 % versus 34.8 % in the control group ( P = 0.048 ) . Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months ( P = 0.027 , P = 0.001 , respectively ) . The effect of goserelin was not statistically significant in women > 40 years . Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5 % of pretreatment levels in the control group and 7 % in the goserelin group , which were not significantly different between groups . Conclusion This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer , with particular efficacy in women aged ≤40 years old . The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined IMPORTANCE Whether the administration of luteinizing hormone-releasing hormone analogues ( LHRHa ) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy . OBJECTIVE To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy . DESIGN , SETTING , AND PARTICIPANTS Parallel , r and omized , open-label , phase 3 superiority trial conducted at 16 Italian sites . Between October 2003 and January 2008 , 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled . Last annual follow-up was June 3 , 2014 . INTERVENTIONS Patients were r and omized to receive adjuvant or neoadjuvant chemotherapy alone ( control group ) or chemotherapy plus triptorelin ( LHRHa group ) . MAIN OUTCOMES AND MEASURES The primary planned end point was incidence of chemotherapy-induced early menopause . Post hoc end points were long-term ovarian function ( evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle ) , pregnancies , and disease-free survival ( DFS ) . RESULTS A total of 281 women ( median age , 39 [ range , 24 - 45 ] years ) were r and omized . Median follow-up was 7.3 years ( interquartile range , 6.3 - 8.2 years ) . The 5-year cumulative incidence estimate of menstrual resumption was 72.6 % ( 95 % CI , 65.7%-80.3 % ) among the 148 patients in the LHRHa group and 64.0 % ( 95 % CI , 56.2%-72.8 % ) among the 133 patients in the control group ( hazard ratio [ HR ] , 1.28 [ 95 % CI , 0.98 - 1.68 ] ; P = .07 ; age-adjusted HR , 1.48 [ 95 % CI , 1.12 - 1.95 ] ; P = .006 ) . Eight pregnancies ( 5-year cumulative incidence estimate of pregnancy , 2.1 % [ 95 % CI , 0.7%-6.3 % ] ) occurred in the LHRHa group and 3 ( 5-year cumulative incidence estimate of pregnancy , 1.6 % [ 95 % CI , 0.4%-6.2 % ] ) in the control group ( HR , 2.56 [ 95 % CI , 0.68 - 9.60 ] ; P = .14 ; age-adjusted HR , 2.40 [ 95 % CI , 0.62 - 9.22 ] ; P = .20 ) . Five-year DFS was 80.5 % ( 95 % CI , 73.1%-86.1 % ) in the LHRHa group and 83.7 % ( 95 % CI , 76.1%-89.1 % ) in the control group ( LHRHa vs control : HR , 1.17 [ 95 % CI , 0.72 - 1.92 ] ; P = .52 ) . CONCLUSIONS AND RELEVANCE Among premenopausal women with either hormone receptor-positive or hormone receptor-negative breast cancer , concurrent administration of triptorelin and chemotherapy , compared with chemotherapy alone , was associated with higher long-term probability of ovarian function recovery , without a statistically significant difference in pregnancy rate . There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone , although study power was limited . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00311636 OBJECTIVE To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not . DESIGN Prospect i ve r and omized controlled study . SETTING Department of Obstetrics and Gynecology , Mansura University Hospital , Mansura , Egypt . PATIENT(S ) Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study . Patients were assigned r and omly to receive combined GnRHa and chemotherapy or chemotherapy alone . One woman in each group dropped out . MAIN OUTCOME MEASURE(S ) Return of spontaneous menstruation and ovulation . Hormonal changes ( FSH , LH , E(2 ) , P ) during and after the course of treatment . RESULT ( S ) In the study group , 89.6 % resumed menses and 69.2 % resumed spontaneous ovulation within 3 - 8 months of termination of the GnRHa/chemotherapy cotreatment ; 11.4 % experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment . In the control group ( chemotherapy without GnRHa ) , 33.3 % resumed menses and 25.6 % resumed normal ovarian activity . The median FSH and LH concentrations , 6 months after completion of the GnRHa/chemotherapy cotreatment group , were significantly less than the control group . During the GnRHa/chemotherapy cotreatment the concentrations of FSH , LH , and P decreased to almost prepubertal levels . However , within 1 - 3 months after the last GnRHa injection , an increase in LH and FSH concentrations was detected , followed several weeks later in by an increase in P concentrations to within normal levels . CONCLUSION ( S ) GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women < 40 years . Long-term studies are required PURPOSE Most research regarding fertility in young women with breast cancer has focused on long-term survivors . Little is known about how fertility concerns affect treatment decisions or fertility preservation strategies at the time of initial cancer diagnosis . PATIENTS AND METHODS As part of an ongoing prospect i ve multicenter cohort study , we surveyed women with newly diagnosed early-stage breast cancer at age ≤ 40 years . The baseline survey included sociodemographic , medical , and treatment data as well as a modified Fertility Issues Survey , including fertility concern and preservation items . Univariable and multivariable modeling were used to investigate predictors of greater fertility concern . RESULTS Among the first 620 eligible respondents included in this analysis , median age was 37 years ( range , 17 to 40 years ) ; 425 women ( 68 % ) discussed fertility issues with their physicians before starting therapy , and 319 ( 51 % ) were concerned about becoming infertile after treatment . Because of concerns about fertility , four women ( 1 % ) chose not to receive chemotherapy , 12 ( 2 % ) chose one chemotherapy regimen over another , six ( 1 % ) considered not receiving endocrine therapy , 19 ( 3 % ) decided not to receive endocrine therapy , and 71 ( 11 % ) considered receiving endocrine therapy for < 5 years ; 65 ( 10 % ) used fertility preservation strategies . Greater concern about fertility was associated with younger age , nonwhite race , not having children , and receipt of chemotherapy . CONCLUSION Many young women with newly diagnosed breast cancer have concerns about fertility , and for some , these substantially affect their treatment decisions . Only a minority of women currently pursue available fertility preservation strategies in this setting The purpose of this r and omized study was to examine if goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer , protects the ovaries from premature failure . A total of 285 premenopausal breast cancer patients , in a r and omized adjuvant trial ( Zoladex in premenopausal patients ( ZIPP ) ) , were assigned to a study on ovarian function . Node positive patients were assigned to CMF-(cyclophosphamide , methotrexate and 5-fluorouracil ) chemotherapy in addition to endocrine therapy . All patients were r and omly assigned to receive 2 years of goserelin , goserelin plus tamoxifen , tamoxifen alone or no endocrine treatment . We studied , if menses were affected in the treatment groups , up to 36 months after r and omization . One year after completed CMF- and endocrine therapy , 36 % of the women in the goserelin group reported menses , compared to 7 % in the goserelin plus tamoxifen group , 13 % in the tamoxifen group and 10 % of the controls . Among women treated with goserelin , there was a statistically significant increase in the proportion of menstruating women , 1 year after completed treatment compared to at 24 months of treatment ( P = 0.006 ) , in contrast to all other treatment groups , who were unchanged or more often amenorrheic . In our study , there is some evidence of protective effect of goserelin on ovarian function in CMF treated women . This effect was not observed in the combined tamoxifen and goserelin treatment UNLABELLED Twenty-five percent of breast cancer cases are detected during premenopausal period and the number of young women suffering from breast cancer is increasing in the world , especially in Iran . Preservation of fertility and ovarian function leads to improved quality of life of these patients . The aim of this study was to evaluate the effect of gonadotropin releasing hormone ( GnRH ) agonist on menstrual reverse in breast cancer cases treated with cyclophosphamide regimen . MATERIAL S AND METHODS This r and omized clinical trial ( RCT ) was conducted on 42 adenocarcinoma cases . Mean age of patients was 37 + /- 5 years ( range 25 to 45 ) . Primary stages to Stage II ( T2N1M0 ) whose histology reports were negative ER/PR were enrolled in this study . All the enrolled patients were c and i date s for cyclophosphamide ( 600 mg/m2 ) , adriamycin ( 60 mg/m2 ) , and taxoter ( 75 mg/m2 ) chemotherapy regimens . RESULTS Spontaneous menstrual reverse occurred in 90.5 % of patients receiving diphereline at three to six months after treatment which occurred in 33.3 % of control cases . In control group , 14.3 % ( three cases ) had oligomenorrhea and hypomenorrhea during chemotherapy and 19%(four cases ) had spontaneous menstrual reverse at three to six months . It should be noted that there was a significant difference between controls and cases ( p < 0.001 ) . This difference was insignificant in cases younger than 35 years ( p < 0.594 ) . In 100 % of patients older than 35 years who received diphereline , spontaneous menstrual reverse occurred during six months after chemotherapy , but this occurred in only 20 % of controls ( p < 0.001 ) . Mean serum level of follicle stimulating hormone ( FSH ) and luteinizing hormone ( LH ) during and at three months after therapy was significantly lower in cases in comparison with controls , but serum level of estradiol was significantly more in cases three months after chemotherapy ( p < 0.001 ) . CONCLUSION GnRH agonists significantly improve ovarian function and fertility . They also lead to spontaneous menstrual reverse in negative ER/PR breast cancer cases Previous studies provided inconclusive evidence for the effectiveness of gonadotropin-releasing hormone analogue on ovarian function protection against chemotherapy-induced genotoxicity in premenopausal patients . This study was design ed to examine the efficacy of leuprolide acetate on ovarian function preservation in patients with breast cancer . A total of 220 patients were recruited in this prospect i ve clinical trial and were assigned r and omly to receive cyclophosphamide – doxorubicin-based chemotherapy only or chemotherapy plus leuprolide acetate . Resumption of menses or premenopausal levels of both follicle-stimulating hormone ( FSH ) and estradiol ( E2 ) within 12 months after the end of chemotherapy were considered as effective ovarian preservation . A total of 183 patients were considered evaluable ( 94 in chemotherapy-only group and 89 in chemotherapy plus leuprolide acetate group ) . At the end of follow-up , 27 patients in chemotherapy group and 15 in chemotherapy plus leuprolide acetate group resumed menses ; seven patients in chemotherapy group and 14 in chemotherapy plus leuprolide acetate group restored premenopausal levels of FSH and E2 . The median time to resume menses was 9.2 months for patients in chemotherapy plus leuprolide acetate group and was not reached in chemotherapy-only group . In addition , our results demonstrated that age and chemotherapy doses made no significant difference in the occurrence of premature menopause . The leuprolide acetate treatment simultaneously with cyclophosphamide – doxorubicin-based chemotherapy reduced the risk of developing premature menopause in premenopausal patients with breast cancer OBJECTIVE : To estimate the effectiveness of gonadotropin-releasing hormone ( GnRH ) analogues cotreatment in preventing chemotherapy-induced amenorrhea in young breast cancer patients undergoing cyclophosphamide-based chemotherapy . METHODS : One hundred hormone-insensitive breast cancer participants ( aged 18 - 40 years ) were recruited from two university-affiliated oncology centers in Egypt . Opting for type of cotreatment was based on available timeframe until start of chemotherapy . Fifty women ready for early chemotherapy were r and omized to receive either chemotherapy alone ( arm I ) or chemotherapy after downregulation ( estradiol less than 50 pg/mL ) by GnRH antagonist and agonist ( arm II ) . Then , GnRH antagonist was discontinued and agonist was continued until the end of chemotherapy . When chemotherapy was to start later than 10 days after study inclusion , 50 women were r and omized to receive either chemotherapy alone ( arm III ) or chemotherapy after downregulation with GnRH agonist ( arm IV ) . Resumption of menstruation at 12 months after end of chemotherapy was the primary outcome . Postchemotherapy hormonal and ultrasound changes were secondary outcomes . RESULTS : Twelve months after termination of chemotherapy , there were no differences in menstruation resumption rates between GnRH-treated patients and control group individuals in either early ( 80 % in arms I and II , risk ratio 1 , 95 % confidence interval 0.7-.32 ; P=1.00 ) or delayed chemotherapy groups ( 80 % and 84 % in arms III and IV , risk ratio 0.95 , 95 % confidence interval 0.73 - 1.235 ; P=.71 ) . There were no differences in hormonal and ultrasound markers between GnRH analogue users and control group individuals . The use of GnRH analogue cotreatment did not predict independently the odds of menstruating at 12 months . CONCLUSION : GnRH analogue cotreatment does not offer a significant protective effect on ovarian function in patients treated by cyclophosphamide-based chemotherapy . CLINICAL TRIAL REGISTRATION : Australian New Zeal and Clinical Trials Registry . www.anzctr.org.au , ACTRN12609001059257 . LEVEL OF EVIDENCE : PURPOSE Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy . This prospect i ve r and omized trial evaluated the use of gonadotropin-releasing hormone ( GnRH ) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer . PATIENTS AND METHODS Premenopausal women age 44 years or younger were r and omly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age ( < 35 , 35 to 39 , > 39 years ) , estrogen receptor status , and chemotherapy regimen . Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone ( FSH ) and inhibin A and B levels . RESULTS Targeted for 124 patients with a planned 5-year follow-up , the trial was stopped for futility after 49 patients were enrolled ( median age , 39 years ; range , 21 to 43 years ) ; 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil , epirubicin , and cyclophosphamide . Menstruation resumed in 19 ( 90 % ) of 21 patients in the control group and in 23 ( 88 % ) of 26 in the triptorelin group ( P= .36 ) . Menses returned after a median of 5.8 months ( range , 1 to 19 months ) after completion of chemotherapy in the triptorelin versus 5.0 months ( range , 0 to 28 months ) in the control arm ( P= .58 ) . Two patients ( age 26 and 35 years at r and om assignment ) in the control group had spontaneous pregnancies with term deliveries . FSH and inhibin B levels correlated with menstrual status . CONCLUSION When stratified for age , estrogen receptor status , and treatment regimen , amenorrhea rates on triptorelin were comparable to those seen in the control group PURPOSE The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression ( OFS ) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy . We present the patient-reported outcomes . PATIENTS AND METHODS The quality -of-life ( QoL ) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor-positive breast cancer r and omly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone . Chemotherapy use before enrollment was optional . Patients completed a QoL form consisting of global and symptom indicators at baseline , every 6 months for 24 months , and annually during years 3 to 6 . Differences in the change of QoL from baseline between the two treatments were tested at 6 , 24 , and 60 months with mixed models for repeated measures with and without chemotherapy and overall . RESULTS Patients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months , by loss of sexual interest and sleep disturbance at 6 months , and by vaginal dryness up to 60 months . Without prior chemotherapy , patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS . Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy . Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period . CONCLUSION Overall , OFS added to tamoxifen result ed in worse endocrine symptoms and sexual functioning during the first 2 years of treatment , with variable magnitudes of treatment differences . Short-term differences in symptom-specific QoL , treatment burden , and coping effort between treatment groups were less pronounced for patients with prior chemotherapy , the cohort that benefited most from OFS in terms of disease control |
13,041 | 25,701,429 | A large benefit with the hysteroscopic removal of submucous fibroids for improving the chance of clinical pregnancy in women with otherwise unexplained subfertility can not be excluded .
The hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may increase the clinical pregnancy rate . | BACKGROUND Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps , submucous fibroids , uterine septum or intrauterine adhesions , which are detectable in 10 % to 15 % of women seeking treatment for subfertility .
OBJECTIVES To assess the effects of the hysteroscopic removal of endometrial polyps , submucous fibroids , uterine septum or intrauterine adhesions suspected on ultrasound , hysterosalpingography , diagnostic hysteroscopy or any combination of these methods in women with otherwise unexplained subfertility or prior to intrauterine insemination ( IUI ) , in vitro fertilisation ( IVF ) or intracytoplasmic sperm injection ( ICSI ) . | OBJECTIVE To determine if sectioning of the cervical septum in hysteroscopic metroplasty of the complete uterine septum is associated with intraoperative bleeding , cervical incompetence , and secondary infertility . DESIGN Multicenter , r and omized , controlled clinical trial . SETTING University hospitals . PATIENT(S ) Twenty-eight women with a diagnosis of complete uterine septum who had a history of pregnancy wastage or infertility . They were r and omized into two groups : group A underwent metroplasty including section of the cervical septum ; group B underwent the same procedure with preservation of the cervical septum . INTERVENTION(S ) Hysteroscopic metroplasty was performed for all patients in the two groups . MAIN OUTCOME MEASURE(S ) Operating time , distending media deficit , total distending media used , intraoperative bleeding , complications , and reproductive outcome . RESULT ( S ) Operating times were 36.40 + /- 10.67 minutes and 73 + /- 14.40 minutes in group A and group B , respectively . Distending media deficit was 456.66 + /- 165.68 mL in group A , while in group B it was 673.84 + /- 220.36 . Two cases of pulmonary edema and three cases of significant bleeding ( > 150 mL ) were seen in group B. The cesarean section rate was significantly higher in group B. There were no significant differences in the reproductive outcome in the two groups . CONCLUSION ( S ) Resection of the cervical septum during hysteroscopic metroplasty of complete uterine septum makes the procedure safer , easier , and less complicated than the procedure with preservation of the cervical septum . This procedure is recommended for all cases of complete uterine septum Background The success rate of IVF treatment is low . A recent systematic review and meta- analysis found that the outcome of IVF treatment could be improved in patients who have experienced recurrent implantation failure if an outpatient hysteroscopy ( OH ) is performed before starting the new treatment cycle . However , the trials were of variable quality , leading to a call for a large and high- quality r and omised trial . This protocol describes a multi-centre r and omised controlled trial to test the hypothesis that performing an OH prior to starting an IVF cycle improves the live birth rate of the subsequent IVF cycle in women who have experienced two to four failed IVF cycles . Methods and design Eligible and consenting women will be r and omised to either OH or no OH using an internet based trial management programme that ensures allocation concealment and employs minimisation for important stratification variables including age , body mass index , basal follicle stimulating hormone level and number of previous failed IVF cycles . The primary outcome is live birth rate per IVF cycle started . Other outcomes include implantation , clinical pregnancy and miscarriage rates . The sample size for this study has been estimated as 758 participants with 379 participants in each arm . Interim analysis will be conducted by an independent Data Monitoring Committee ( DMC ) , and final analysis will be by intention to treat . A favourable ethical opinion has been obtained ( REC reference : 09/H0804/32).Trail Registration The trial has been assigned the following IS RCT N number : IS RCT OBJECTIVE To highlight the efficiency of intrauterine device ( IUD ) guidance during hysteroscopic adhesiolysis for severe intrauterine adhesions . DESIGN A prospect i ve , r and omized trial . SETTING Private tertiary and referral infertility clinic . PATIENT(S ) Seventy-one subfertile patients who underwent hysteroscopic treatment of intrauterine synechiae or adhesions . INTERVENTION(S ) Thirty-six women in group 1 were initially examined by laparoscopy-hysteroscopy at first look , and an IUD was inserted during hysteroscopic adhesiolysis . The adhesions were further lysed by the guidance of IUD during the second-look office hysteroscopy , 1 week later . Patients were prescribed 2 months of estrogen as well as P therapy , and the IUD was removed by the end of this period . The uterine cavity was evaluated , and adhesions were further lysed by a third-look office hysteroscopy , 1 week after the removal of IUD . Thirty-five women in group 2 were similarly examined by first-look office hysteroscopy , and an IUD was inserted during hysteroscopic adhesiolysis . These patients did not undergo early intervention of office hysteroscopy , 1 week after the first procedure . They also used 2 months of estrogen and P therapy . The IUD was removed by the end of this period , and the uterine cavity was evaluated and adhesions were further lysed during a second-look office hysteroscopy . MAIN OUTCOME MEASURE(S ) Pregnancy rate and live birth rate . RESULT ( S ) Spontaneous pregnancy rates after treatment were 17/36 ( 47.2 % ) and 11/35 ( 30 % ) , and live birth rates were 10/36 ( 28 % ) and 7/35 ( 20 % ) in groups 1 and 2 , respectively . These differences between the two groups were not statistically significant . CONCLUSION ( S ) The method described especially for early intervention may prevent complications during the treatment of severe intrauterine adhesions and may present a secure and effective alternative for constructive clinical outcomes OBJECTIVE To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid ( HA ) gel for preventing intrauterine adhesion ( IUA ) after hysteroscopic adhesiolysis . METHODS A prospect i ve , r and omized , double blinded and controlled clinical trial ( level I ) was performed . According to American Fertility Society ( AFS ) scoring system , 120 patients ( treatment group : 60 cases , control group : 60 cases ) with moderate to severe IUA were enrolled . Upon completion of adhesiolysis , a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group ; patients in the control group , however , only received Foley balloon catheter . Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA . Primary endpoint was the reduction rate of IUA at 3 months after surgery . The secondary endpoints include total AFS score , score of each individual AFS category . RESULTS At 3 months after surgery , auto-crosslinked HA gel result ed in significantly higher effective rate for reduction of adhesion , the effective rate were 76 % ( 42/55 ) and 48 % ( 27/56 ) respectively ( P = 0.000 9 ) ; the total AFS score of treatment group was 2.1 ± 1.1 , and significantly lower than that of control group ( 3.7 ± 2.5 , P = 0.000 8) . Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern ( P = 0.037 8 , P = 0.000 4 ) . The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [ 13 % ( 7/55 ) versus 38 % ( 21/56 ) , P = 0.000 6 ] . No adverse events and complications were observed . CONCLUSIONS Auto-crosslinked HA gel coule be able to reduce IUA , decrease adhesion severity , and improve menopause postoperatively . This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures OBJECTIVE To evaluate prospect ively the effect of hysteroscopic septoplasty as therapy for unexplained primary infertility in women with uterine septum as a sole cause for reproductive failure and to define the factors influencing reproductive success . STUDY DESIGN In a prospect i ve comparative study , we enrolled 103 infertile women with uterine septum as a sole cause for reproductive failure . They had had unexplained primary infertility > 2 years and a follow-up > 12 months . Uterine anomalies were diagnosed by means of hysterosalpingography ( HSG ) and 2D-transvaginal sonography ( TVS ) with intrauterine saline infusion . Hysteroscopic septoplasty was performed in the early follicular phase . Pregnancy rates ( PR ) according to patient and septum characteristics ( septum size ) were the main outcome measures . RESULTS Follow-up was complete for 88 patients . The mean ( ±SD ) age of the patients was 36.1±2.1 years . Forty-two patients became pregnant ( 40.7 % ) . The mean ( ±SD ) delay in conception was 7.5±2.6 months . Nearly 80 % of the pregnant women conceived spontaneously . Of 44 pregnancies in 42 women , 36 live newborns were delivered . The PR was significantly higher in women < 35 years of age or with <3 years of unexplained primary infertility . Moreover , in women with a septum size larger than one-half of their uterine length the PR was significantly higher than those with septum size < 1/2 of their uterus ( P=.12 ) . CONCLUSION Fertility and pregnancy after hysteroscopic septoplasty in women with unexplained primary infertility and uterine septum as a sole cause for reproductive failure seems to depend on patient age , duration of infertility before septoplasty , and septum size . Women with a septum size larger than one-half of their uterine length have a higher chance of successful pregnancy after hysteroscopic septoplasty STUDY QUESTION Does the use of diagnostic criteria in the hysteroscopic diagnosis of a septate uterus improve inter-observer agreement ? SUMMARY ANSWER Pre-set diagnostic criteria slightly improve the inter-observer reproducibility of hysteroscopy in diagnosing a uterine septum , although agreement remains moderate . WHAT IS KNOWN ALREADY The inter-observer agreement on the hysteroscopic diagnosis of the septate uterus has been reported to be poor . STUDY DESIGN , SIZE , DURATION From April 2013 until May 2014 , a r and omized controlled comparative inter-observer study was performed . A total of 191 gynecologists from 43 countries took part . PARTICIPANTS / MATERIAL S , SETTING S , METHODS Each gynecologist was asked to assess 10 video recordings of hysteroscopy procedures with a specific focus on the internal uterine shape . The hysteroscopies had been performed in subfertile women and women with recurrent miscarriage . The recordings contained images of uterine cavities primarily diagnosed as septate , arcuate or normal . Participating gynecologists were r and omized into two groups : one group received diagnostic criteria for a septate uterus before assessment of the videos ( DC group ) , whereas the other group assessed the recordings without instruction ( no DC group ) . The inter-observer agreement , expressed as the intra-class correlation coefficient ( ICC ) , was compared between groups . Main outcomes were the inter-observer agreement on the uterine shape and the necessity of surgical correction . MAIN RESULTS AND THE ROLE OF CHANCE Eighty-six observers were r and omized to the DC group and 105 to the no DC group . The ICCs in the diagnosis of a septum were 0.59 versus 0.52 , in the DC group and the non-DC group , respectively ( P-value : 0.002 ) . The overall agreement on the need for surgical correction was found to be moderate ( DC ICC 0.43 versus no DC 0.39 , P-value : 0.70 ) . Most importantly , once a septate uterus had been diagnosed , the agreement on the need for surgery was poor in both groups ( DC ICC 0.05 versus no DC ICC 0.02 , P-value : 0.78 ) . LIMITATIONS , REASONS FOR CAUTION We used video recordings rather than study ing real-time hysteroscopic procedures , which may have influenced the accuracy of the assessment s. WIDER IMPLICATION S OF THE FINDINGS The reproducibility of hysteroscopy for the diagnosis of a septate uterus is moderate , even with the use of st and ardized criteria . The fact that the agreement among physicians on both the diagnosis of a uterine septum , as well as the decision to resect such septum after hysteroscopy is moderate , may imply that hysteroscopy is insufficient as single tool to diagnose and decide on treatment of a septate uterus . STUDY FUNDING /COMPETING INTERESTS No study funding was received and no competing interests are present BACKGROUND Hysteroscopy is often done in infertile women starting in-vitro fertilisation ( IVF ) to improve their chance of having a baby . However , no data are available from r and omised controlled trials to support this practice . We aim ed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths . METHODS We did a pragmatic , multicentre , r and omised controlled trial in seven university hospitals and 15 large general hospitals in the Netherl and s. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were r and omly assigned ( 1:1 ) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF ( hysteroscopy group ) or immediate start of the IVF treatment ( immediate IVF group ) . R and omisation was done with web-based concealed allocation and was stratified by centre with variable block sizes . Participants , doctors , and outcome assessors were not masked to the assigned group . The primary outcome was ongoing pregnancy ( detection of a fetal heartbeat at > 12 weeks of gestation ) within 18 months of r and omisation and result ing in livebirth . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01242852 . FINDINGS Between May 25 , 2011 , and Aug 27 , 2013 , we r and omly assigned 750 women to receive either hysteroscopy ( n=373 ) or immediate IVF ( n=377 ) . 209 ( 57 % ) of 369 women eligible for assessment in the hysteroscopy group and 200 ( 54 % ) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period ( relative risk 1·06 , 95 % CI 0·93 - 1·20 ; p=0·41 ) . One ( < 1 % ) woman in the hysteroscopy group developed endometritis after hysteroscopy . INTERPRETATION Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment . Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy . FUNDING The Dutch Organisation for Health Research and Development ( ZonMW ) OBJECTIVE The aim of this study was to compare traditional hysteroscopy with mini-hysteroscopy in terms of compliance , side effects and diagnostic efficacy . STUDY DESIGN We prospect ively considered 950 female c and i date s for an IVF programme . All women underwent outpatient hysteroscopy ; in 602 cases ( Group A ) a mini-hysteroscope was employed ; in 348 women ( Group B ) a 5-mm hysteroscope was adopted . RESULTS Cavity findings were similar in both groups . Endometrial polyps and uterine septum seem to be more frequent in our infertile patients than in the general population . No significant differences in terms of side effects were found between the groups . Mean visual analogue pain scale score was significantly lower in the patients of Group A than in those of Group B ( p<0.001 ) . CONCLUSIONS Office mini-hysteroscopy is a very effective diagnostic tool in an infertility work-up and is more widely accepted than traditional hysteroscopy . Routine use of the technique should be considered BACKGROUND Diagnostic hysteroscopy is not widely performed in the office setting , one of the reasons being the discomfort produced by the procedure . This r and omized controlled trial was performed to evaluate the effects of instrument diameter , patient parity and surgeon experience on the pain suffered and success rate of the procedure . METHODS Patients were r and omly assigned to undergo office diagnostic hysteroscopy either with 5.0 mm conventional instruments ( n=240 ) or with 3.5 mm mini-instruments ( n=240 ) . Procedures were stratified according to patient parity and surgeon 's previous experience . The pain experienced during the procedure ( 0 - 10 ) , the quality of visualization of the uterine cavity ( 0 - 3 ) and the complications were recorded . The examination was considered successful when the pain score was < 4 , visualization score was > 1 and no complication occurred . RESULTS Less pain , better visualization and higher success rates were observed with mini-hysteroscopy ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) , in patients with vaginal deliveries ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) and in procedures performed by experienced surgeons ( P=0.02 , P = NS and P = NS , respectively ) . The effects of patient parity and surgeon experience were no longer important when mini-hysteroscopy was used . CONCLUSIONS Our data demonstrate the advantages of mini-hysteroscopy and the importance of patient parity and surgeon experience , suggesting that mini-hysteroscopy should always be used , especially for inexperienced surgeons and when difficult access to the uterine cavity is anticipated . They indicate that mini-hysteroscopy can be offered as a first line office diagnostic procedure Background In in vitro fertilization ( IVF ) and intracytoplasmatic sperm injection ( ICSI ) treatment a large drop is present between embryo transfer and occurrence of pregnancy . The implantation rate per embryo transferred is only 30 % . Studies have shown that minor intrauterine abnormalities can be found in 11–45 % of infertile women with a normal transvaginal sonography or hysterosalpingography . Two r and omised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9–13 % increase in pregnancy rate . Therefore , screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated . In absence of a scientific basis for such a policy , this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy , with or without saline infusion sonography ( SIS ) , prior to a first IVF/ICSI cycle . Methods / design Multicenter r and omised controlled trial in asymptomatic subfertile women , indicated for a first IVF/ICSI treatment cycle , with normal findings at transvaginal sonography . Women with recurrent miscarriages , prior hysteroscopy treatment and intermenstrual blood loss will not be included . Participants will be r and omised for a routine fertility work-up with additional ( SIS and ) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests . The primary study outcome is the cumulative ongoing pregnancy rate result ing in live birth achieved within 18 months of IVF/ICSI treatment after r and omisation . Secondary study outcome parameters are the cumulative implantation rate ; cumulative miscarriage rate ; patient preference and patient tolerance of a SIS and hysteroscopy procedure . All data will be analysed according to the intention-to-treat principle , using univariate and multivariate logistic regression and cox regression . Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure . In total 700 patients will be included in this study . Discussion The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment . Trial registration Objective To compare saline with and without added lignocaine and carbon dioxide distension for out patient hysteroscopy with regards to patient discomfort and hysteroscopic view This study assessed the cost-effectiveness of office hysteroscopy screening prior to IVF . Therefore , the cost-effectiveness of two distinct strategies - hysteroscopy after two failed IVF cycles ( Failedhyst ) and routine hysteroscopy prior to IVF ( Routinehyst ) - was compared with the reference strategy of no hysteroscopy ( Nohyst ) . When present , intrauterine pathology was treated during hysteroscopy . Two models were constructed and evaluated in a decision analysis . In model I , all patients had an increase in pregnancy rate after screening hysteroscopy prior to IVF ; in model II , only patients with intrauterine pathology would benefit . For each strategy , the total costs and live birth rates after a total of three IVF cycles were assessed . For model I ( all patients benefit from hysteroscopy ) , Routinehyst was always cost-effective compared with Nohyst or Failedhyst . For the Routinehyst strategy , a monetary profit would be obtained in the case where hysteroscopy would increase the live birth rate after IVF by ≥ 2.8 % . In model II ( only patients with pathology benefit from hysteroscopy ) , Routinehyst also dominated Failedhyst . However , hysteroscopy performance result ed in considerable costs . In conclusion , the application of a routine hysteroscopy prior to IVF could be cost-effective . However , r and omized trials confirming the effectiveness of hysteroscopy are needed Objective To assess whether outpatient hysteroscopy using the ‘ no‐touch ’ technique confers any advantages in terms of patient discomfort over the traditional technique OBJECTIVE To determine if resectoscopic sectioning of complete uterocervicovaginal septum is as effective as cold knife excision of the vaginal part followed by resectoscopic cutting of the cervicouterine part in symptomatic patients . DESIGN R and omized controlled clinical trial . SETTING University hospital . PATIENT(S ) Thirty-two women with a diagnosis of complete uterocervicovaginal septum who had a history of pregnancy wastage or infertility . They were r and omized into two groups : Group A underwent resectoscopic excision of the complete septum starting from the vaginal interoitus ; group B underwent cold knife excision of the vaginal part followed by resectoscopic excision of the cervical and uterine parts . INTERVENTION(S ) Hysteroscopic metroplasty alone or preceded by cold knife excision of the vaginal part . MAIN OUTCOME MEASURE(S ) Operating time , perioperative bleeding , complications , reproductive outcome , and patient and husb and satisfaction . RESULT ( S ) Patients in group A showed significantly less operative time and scar-related dyspareunia . There were no significant differences in the reproductive outcome in the two groups . CONCLUSION ( S ) Resection of the vaginal part of symptomatizing complete vaginocervicouterine septum using resectoscopic metroplasty makes the procedure faster with less possibility of scar-related dyspareunia than cold knife excision STUDY OBJECTIVE To evaluate the safety and effectiveness of Oxiplex/AP gel ( Intercoat ) in reducing intrauterine adhesion formation after hysteroscopic treatment because of retained products of conception ( RPOC ) . DESIGN Prospect i ve double-blind , r and omized , controlled pilot study ( Canadian Task Force classification I ) . SETTING Tertiary medical center . PATIENTS All women who underwent hysteroscopic treatment because of RPOC at our institution between September 2009 and June 2012 were invited to participate . After operative hysteroscopy , participants were r and omized to either have their uterine cavity filled with Oxiplex/AP gel ( study group , n = 26 ) or not ( control group , n = 26 ) . INTERVENTIONS Diagnostic office hysteroscopy to assess for adhesion formation was performed after 6 to 8 weeks . Findings were grade d according to the American Fertility Society classification . Rates of subsequent pregnancy in the 2 groups were assessed . MEASUREMENTS AND MAIN RESULTS Intraoperative complication rates were similar between the 2 groups . There were no postoperative complications after Oxiplex/AP gel application . Moderate to severe adhesions developed in 1 woman ( 4 % ) in the study group and 3 ( 14 % ) in the control group ( p = .80 ) . During follow-up of 20 months ( range , 2 - 33 months ) , 7 women ( 27 % ) in the treatment group conceived , compared with 3 ( 14 % ) in the control group ( p = .50 ) . CONCLUSION Intrauterine application of Oxiplex/AP gel after hysteroscopic removal of RPOC is safe . In this small sample , the difference in the rate of intrauterine adhesions was not statistically significant . A larger study would enable further establishment of the safety and efficacy of use of this gel Objective To examine the cost implication s of outpatient versus daycase hysteroscopy to the National Health Service , the patient and their employer STUDY OBJECTIVES To compare hysteroscopic morcellation with bipolar resectoscopy for removal of endometrial polyps , in terms of procedure time , peri- and postoperative adverse events , tissue availability , and short-term effectiveness . DESIGN Multicenter , open label , r and omized controlled trial ( Canadian Task Force classification I ) . SETTING Day surgery setting of a teaching and a university hospital . PATIENTS Women with larger ( ≥1 cm ) endometrial polyps . INTERVENTIONS Hysteroscopic morcellation with the TRUCLEAR 8.0 Tissue Removal System or bipolar resectoscopy with a rigid 8.5-mm bipolar resectoscope . MEASUREMENTS AND MAIN RESULTS Eighty-four women were included in the intention-to-treat analysis . Median operating time was 4.0 min ( range : 2.5 - 7.1 ) and 6.0 min ( range : 3.8 - 11.7 ) in the hysteroscopic morcellation and resectoscopy groups , respectively . Operating time was reduced by 38 % ( 95 % confidence interval : 5%-60 % ; p = .028 ) in the hysteroscopic morcellation group . Procedure time , which was defined as the sum of the installation and operating time , tended to be less for the hysteroscopic morcellation group ( median 9.5 min [ range : 7.6 - 12.2 ] vs 12.2 min [ range : 8.8 - 16.0 ] ; p = .072 ) . Perforation occurred at dilation or hysteroscope ( re ) introduction in 3 patients of the resectoscopy group , result ing in procedure discontinuation or prolongation of hospital stay . Perforation occurred at dilation in 1 patient in the hysteroscopic morcellation group ; however , the procedure was successfully completed . Postoperatively , 2 patients of the hysteroscopic morcellation group were diagnosed with a urinary tract infection . Tissue was available for pathology analysis in all patients , except for 2 patients in the resectoscopy group in whom the procedure was discontinued due to perforation . CONCLUSION Hysteroscopic morcellation is a fast , effective , and safe alternative to bipolar resectoscopy for removal of endometrial polyps OBJECTIVE : To compare a “ no touch ” approach to diagnostic hysteroscopy without anesthesia with traditional diagnostic hysteroscopy after intracervical injection of mepivacaine hydrochloride 3 % . METHODS : A total of 130 women undergoing diagnostic hysteroscopy were included in the study and were r and omized , using a computer-generated r and omization list to one of two treatment groups in a ratio of 2:1 . Eighty-three women underwent hysteroscopy without speculum , tenaculum , or anesthesia . Forty-seven women received intracervical anesthesia with 10 mL of 3 % mepivacaine hydrochloride solution injected at two sites ( 3:00 and 9:00 positions ) and underwent traditional hysteroscopy . Hysteroscopy was performed using a rigid 3.7-mm hysteroscope and a medium of 0.9 % saline , and the image was transmitted to a screen visible to the patient . A visual analog scale ( VAS ) consisting of a 10-cm line was used to assess the intensity of pain experienced during and after the procedure . Overall patient satisfaction was assessed during , immediately after , 15 minutes later , and 3 days after hysteroscopy . RESULTS : The mean pain score was significantly lower in the group without the use of speculum , tenaculum , or anesthesia ( VAS1 : 3.8±2.7 versus 5.34±3.23 , P=.01 ; VAS2 : 3.02±2.50 versus 4.57±3.30 , P=.008 ) . Patient satisfaction rate was similar in both groups . CONCLUSION : Patients reported significantly less pain with the altered approach to diagnostic hysteroscopy compared with patients undergoing the traditional procedure with anesthesia . This new approach can therefore be considered as a useful hysteroscopic technique . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00319410 LEVEL OF EVIDENCE : BACKGROUND A r and omized , controlled study was performed to compare vaginoscopic versus traditional ( speculum with or without tenaculum ) hysteroscopy in terms of pain score and procedure time . METHODS Three hundred patients were r and omized in two groups : Group A , diagnostic hysteroscopy with vaginoscopic approach ( 150 patients ) and Group B , diagnostic hysteroscopy with traditional approach ( 150 patients ) . All procedures were performed using a semi-rigid 3.5-mm minihysteroscope with a 0 degrees grade optic . Patients of each group were divided into three subgroups according to their reproductive status : fertile nulliparous ( FN ) , fertile multiparous ( FM ) and post-menopausal ( MEN ) women . Women were asked to rate their degree of pain during four phases of the procedure : introduction of hysteroscope ( Group A ) or speculum ( Group B ) into the vagina ( Phase I ) and progression through cervical canal up to internal uterine orifice ( IUO ) ( Phase II ) , inspection of uterine cavity ( Phase III ) and performing of endometrial biopsy ( Phase IV ) . A total pain score was calculated for each group . For each patient , the duration of hysteroscopy was recorded from the introduction to the extraction of the scope ( Group A ) or of the speculum ( Group B ) . RESULTS Although the median total pain scores were 2 in each group , the 95 % confidence interval for vaginoscopic hysteroscopy ( 1.86 - 2.01 ) was significantly ( P < 0.05 ) lower than that for traditional hysteroscopy ( 2.10 - 2.26 ) . Comparison between the corresponding phases of the procedure showed the only significant difference during Phase I of the procedure [ Group A : 1 ( 95 % CI 1.0 - 1.18 ) versus Group B : 2 ( 95 % CI 2.3 - 2.8 ) ; P < 0.05 ] . No significant differences in terms of duration of the procedure were observed between the two approaches . CONCLUSIONS When surgeons using vaginoscopic hysteroscopy with a semi-rigid minihysteroscope were compared with those using traditional approach and the same instrumentation , the operating times and the patients ' pain scores were similar STUDY OBJECTIVE To compare 2 procedures for metroplasty : resectoscopy with monopolar knife versus small-diameter hysteroscopy fitted with a Versapoint device . DESIGN Prospect i ve r and omized study ( Canadian Task Force classification I ) . SETTING Endoscopic gynecology units at tertiary care university hospitals . PATIENTS One hundred-sixty patients with septate uterus and a history of recurrent abortion or primary infertility undergoing hysteroscopic metroplasty from 2001 to 2005 . INTERVENTIONS Hysteroscopic resection of the uterine septum performed with either a 26F resectoscope with unipolar knife ( 80 women , group A ) or a 5-mm diameter hysteroscope with Versapoint device ( 80 women , group B ) . All patients were managed expectantly , with follow-up lasting 1 year . MEASUREMENTS AND MAIN RESULTS Operative parameters ( operative time , fluid absorption , complications , need for second intervention ) and reproductive outcome parameters ( pregnancy , abortion , term and preterm delivery , modality of delivery , cervical cerclage ) were measured . Operative time and fluid absorption were significantly greater in group A than in group B ( 23.4 + /- 5.7 vs 16.9 + /- 4.7 minutes and 486.4 + /- 170.0 vs 222.1 + /- 104.9 mL , respectively ) . The cumulative complication rate was significantly lower in group B than in group A. No difference in any of the reproductive parameters was observed between the 2 groups : pregnancy and delivery rates were 70 % and 81.6 % in group A vs 76.9 % and 84 % in group B. Nine women ( 18.4 % ) from group B and 8 women ( 16 % ) from group B experienced spontaneous abortions . Most patients ( 54/82 ) delivered by cesarean section without differences according to the hysteroscopic technique used for metroplasty ( 65 % in group A vs 67.7 % in group B ) or to the gestational age ( 65.1 % of term and 68.7 % of preterm deliveries ) . CONCLUSIONS Small-diameter hysteroscopy with bipolar electrode for the incision of uterine septum is as effective as resectoscopy with unipolar electrode regarding reproductive outcome and is associated with shorter operating time and lower complication rate STUDY OBJECTIVE To examine efficacy of hysteroscopic removal of polyps and myomas on health-related quality of life and symptom severity at 1-year postprocedure . DESIGN R and omized , prospect i ve , comparative setting clinical trial ( Canadian Task Force classification II-2 ) . SETTING Nine outpatient obstetrics and gynecology practice s and hospitals in the United States . PATIENTS Women 18 to 55 years of age with polyps and /or type 0 or I myomas ≥1.5 and ≤3.0 cm . INTERVENTIONS Treatment of polyps and fibroids with the MyoSure device . MEASUREMENTS AND MAIN RESULTS A total of 118 lesions ( 76 polyps , 42 myomas ) were removed . Among the 118 pathologies removed , 53 were removed in an office setting ( 28 myomas , 25 polyps ) , and 55 were removed in an ambulatory surgical center ( ASC ) setting ( 14 myomas , 41 polyps ) . The mean percentage of pathology removed was 95.9 ± 6.8 % for fibroids and 99.9 ± 0.7 % for polyps . Symptom severity as measured by the Uterine Fibroid Symptom- Quality of Life ( UFS-QOL ) scale improved significantly ( p < .01 ) between baseline ( mean score of 67.5 ± 15.4 ) and 12 months postprocedure ( mean score of 22.3 ± 22.6 ) . The Health-Related Quality of Life ( HRQOL ) scale also improved significantly ( p < .01 ) between baseline ( mean score 38.7 ± 23.3 ) and 12 months postprocedure ( mean score of 83.9 ± 24.4 ) . Both the office and ASC groups demonstrated a statistically significant ( p < .01 ) improvement in UFS-QOL and HRQOL . CONCLUSION For women with intrauterine polyps and /or myomas who experienced abnormal uterine bleeding , hysteroscopic morcellation with the MyoSure device provided significant , durable health-related , quality -of-life improvements up to 12 months postprocedure . These findings were the same for patients treated in both an office-based setting and ASCs Objective : To evaluate the incidence of infectious complications and effect of prophylactic antibiotic administration during operative hysteroscopic procedures . Methods : A multicentric r and omized controlled trial was conducted between January 2012 and December 2013 . Women ( n = 180 ) affected by endometrial hyperplasia , myomas , or endometrial polyps undergoing operative hysteroscopy were r and omized to receive cefazolin 2 g intravenously 30 minutes prior to the procedure ( n = 91 ) and no treatment ( n = 89 ) . Results : No statistical difference in terms of postoperative fever ( 2.4 % vs 2.3 % , P = .99 ) , endometritis ( 0 % vs 0 % ) , pain ( 6.0 % vs 10.4 % , P = .40 ) , cervicitis – vaginitis ( 0 % vs 0 % ) , pelvic abscess ( 0 % vs 0 % ) , pelvic inflammatory disease ( 0 % vs 0 % ) , and bleeding ( 0 % vs 0 % ) was noticed . No statistical difference in terms of side effects attributable to antibiotic prophylaxis such as allergy ( 0 % vs 4.8 % , P = .12 ) , nausea ( 10.7 % vs 17.4 % , P = .27 ) , vomiting ( 3.6 % vs 4.6 % , P = .99 ) , diarrhea ( 4.8 % vs 5.4 % , P = .99 ) , cephalea ( 9.5 % vs 3.5 % , P = .13 ) , dizziness ( 4.8 % vs 2.3 % , P = .44 ) , and meteorism ( 5.4 % vs 3.4 % , P = .99 ) was noticed . Conclusion : The results of the current study support the recommendation not to prescribe routine antibiotic prophylaxis prior to operative hysteroscopy OBJECTIVE To assess fecundity of infertile women after surgical correction of uterine septum . DESIGN Prospect i ve controlled trial . SETTING Three academic infertility clinics . PATIENT(S ) Forty-four women affected by septate uterus and otherwise unexplained infertility represented the study group ( group A ) , and 132 women with unexplained infertility were enrolled as control subjects ( group B ) . INTERVENTION(S ) Hysteroscopic metroplasty was performed in group A , and group B was managed expectantly . All women were followed-up for 1 year without any other intervention . MAIN OUTCOME MEASURE(S ) Fecundity rate was calculated as the number of pregnancies per 100 person-months . RESULT ( S ) Pregnancy rate ( 38.6 % vs. 20.4 % ) and live birth rate ( 34.1 % and 18.9 % ) were significantly higher in group A than in group B. The survival analysis showed that the probability of a pregnancy in the twelve-months follow up was significantly higher in patients who had undergone metroplasty than in women with unexplained infertility . The corresponding fecundity ( 10-week pregnancy ) rates were 4.27 and 1.92 person-months in women who had undergone metroplasty and in women with unexplained infertility , respectively . CONCLUSION ( S ) Hysteroscopic resection of the septum improves fecundity of women with septate uterus and otherwise unexplained infertility . Patients with septate uterus and no other cause of sterility have a significantly higher probability of conceiving after removal of the septum than patients affected by idiopathic sterility STUDY OBJECTIVE To evaluate the amount of pain during office hysteroscopy and endometrial biopsy with and without intrauterine anesthesia . DESIGN Prospect i ve r and omized study ( Canadian Task Force classification I ) . SETTING Academic teaching center . PATIENTS A total of 82 women underwent outpatient hysteroscopy for evaluation of their uterine cavity . INTERVENTIONS R and omization to local cervical or combined cervical and intrauterine anesthesia . MEASUREMENTS AND MAIN RESULTS Amount of pain experienced during the procedure ; 10 , 30 , and 60 minutes after the procedure ; and during endometrial biopsy . We used a visual analog scale ranging from 0 to 10 ( 0 : no pain , 10 : excruciating pain ) . Of 82 patients , 4 patients were excluded , 36 patients underwent hysteroscopy using local cervical anesthesia , and 42 others with combined cervical and intrauterine anesthesia . The mean age of the patients in the local group was 37.4 + /- 0.8 years and in the combined group was 38.3 + /- 0.7 years . In both groups , patients experienced significantly more pain during and 10 minutes after the procedure than 30 and 60 minutes after . No significant differences occurred in the pain scores during the hysteroscopy , and 10 , 30 , and 60 minutes after between the 2 anesthesia groups . The pain score in the local group during endometrial biopsy was significantly higher than during ( p < .05 ) , 10 minutes after ( p < .001 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure , respectively . In the combined group , compared with the pain score during endometrial biopsy , the scores during the hysteroscopy ( p < .05 ) , 10 minutes after ( p < .01 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure were also less , respectively . CONCLUSION Intrauterine anesthesia with medicated saline as a distending medium is ineffective . Endometrial biopsy is associated with more pain than hysteroscopy Abstract Objective : To compare the resection of endometrial polyps with two different devices : the Versapoint biopolar electrode and the Diode Laser . Methods : One hundred and two patients diagnosed with endometrial polyps were r and omly assigned to undergo hysteroscopic polypectomy : one group ( n = 52 ) performed with Versapoint bipolar electrode through a 5Fr working channel and the other group with Biolitec Diode Laser ( n = 50 ) using a specific fiber for polyps in a 7Fr working channel . All cases were managed on an outpatient basis , without anesthesia and using a rigid 30o hysteroscope and saline solution as a distention medium . Main outcome measures : Complete resection rate , operative time , complications , intraoperative pain and relapse rate after three months . Results : Intraoperative pain and polyp resection time was similar in both groups . Upon second look hysteroscopy at 3–month , a higher percentage of women of the Versapoint group presented polyp relapse ( 32.6 versus 2.2 % , p = 0.001 ) . Elimination of the polyp after incomplete resection was higher in the Laser group . A significantly higher number of patients in the Laser group considered the procedure to be highly recommendable ( p = 0.02 ) . Conclusion : Polypectomy with Diode Laser result ed in fewer relapses and a higher procedure satisfaction rate as compared to Versapoint The study was conducted to evaluate if the diagnosis and treatment of intrauterine lesions with office hysteroscopy is of value in improving the pregnancy outcome in patients with recurrent in-vitro fertilization and embryo transfer failure . Four hundred and twenty-one patients who had undergone two or more failed IVF-embryo transfer cycles were prospect ively r and omized into two groups . Group I ( n = 211 ) did not have office hysteroscopic evaluation , Group II ( n = 210 ) had office hysteroscopy . The patients who had normal hysteroscopic findings were included in Group IIa ( n = 154 ) and patients who had abnormal hysteroscopic findings were included in Group IIb ( n = 56 ) . Intrauterine lesions diagnosed were operated during the office procedure . Fifty-six ( 26 % ) patients in Group II had intrauterine pathologies and the treatment was performed at the same time . No difference existed in the mean number of oocyte retrieved , fertilization rate , number of embryos transferred or first trimester abortion rates among the patients in groups . Clinical pregnancy rates in Group I , Group IIa and Group IIb were 21.6 % , 32.5 % and 30.4 % respectively . There was a significant difference in the clinical pregnancy rates between patients in Group I and Group IIa ( 21.6 % and 32.5 % , P = 0.044 , respectively ) and Group I and Group IIb ( 21.6 % and 30.4 % , P = 0.044 , respectively ) . There was no significant difference in the clinical pregnancy rate of patients in Groups IIa and IIb . Patients with normal hysterosalpingography but recurrent IVF-embryo transfer failure should be evaluated prior to commencing IVF-embryo transfer cycle to improve the clinical pregnancy rate This prospect i ve , controlled study was performed in order to evaluate whether the location of uterine fibroids may influence reproductive function in women and whether removal of the fibroid prior to conception may improve pregnancy rate and pregnancy maintenance . We examined 181 women affected by uterine fibroids who had been trying to conceive for at least 1 year without success . The main outcome measures were the pregnancy rate and the miscarriage rate . Among the patients who underwent myomectomy , the pregnancy rates obtained were 43.3 % in cases of submucosal , 56.5 % in cases of intramural , 40.0 % in cases of submucosal – intramural and 35.5 % in cases of intramural – subserosal uterine fibroids , respectively . Among the patients who did not undergo surgical treatment , the pregnancy rates obtained were 27.2 % in women with submucosal , 41.0 % in women with intramural , 15.0 % in women with submucosal – intramural and 21.43 % in women with intramural – subserosal uterine fibroids , respectively . Although the results were not statistically significant in the group of women with intramural and intramural – subserosal fibroids , this study confirms the important role of the position of the uterine fibroid in infertility as well as the importance of fibroids removal before the achievement of a pregnancy , to improve both the chances of fertilization and pregnancy maintenance Abstract Intrauterine adhesion ( IUA ) , also known as Asherman ’s syndrome , is a common disease for among women . The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity . This current study investigates the association of different doses of estrogen before transcervical resection of adhesions ( TCRA ) surgery and clinical outcome in serious IUA . About 120 newly diagnostic serious IUA patients who underwent TCRA were r and omly divided into three study groups : Estradiol valerate ( progynova ) 3 or 9 mg per diet before surgery and the control group . Follow-up hysteroscopy checkups were taken in 1- and 3-month post-operation . The effective power of 9 mg group was significantly higher than other groups . The 9 mg group achieved the best menstrual recovery rate in all study groups compared with the other two groups in 6 months post-operatively ( p < 0.05 ) . Our results confirmed estradiol valerateas an alternative effective drug for the prevention of IUAs before and after hysteroscopic surgery Uterine disorders like usual infertility factors ( male factor , ovarian and tubal problems of women ) may affect the outcome of infertility treatment in infertile patients . In our clinical trial , 110 couples diagnosed with infertility were c and i date for intra uterine insemination ( IUI ) . The patients were divided r and omly into two equal groups ( n = 55 ) : In group one ( control group ) , patients without hysteroscopy underwent ovulation induction by clomiphene citrate and hCG followed by intrauterine insemination . The second group ( experiment group ) , patients were undergoing hysteroscopy before intra uterine insemination on the day 21 of the cycle and due to abnormal findings , going under surgical treatment if they needed . The rates of pregnancy complications in patients were evaluated . The age , BMI , kind of infertility , duration of infertility , number of previous trial , duration of stimulation , the type of procedures used and semen analysis ( TMC , Motility and morphology of sperm ) were similar for both groups and no statistically significant differences emerged at all between them . In experimental group , hysteroscopy revealed pathology in the uterine cavity in 26 out of 55 cases . The overall rates of clinical pregnancy were higher in experimental group compared to the control group . The findings from this study showed that the use of hysteroscopy as a diagnostic or therapeutic procedure before IUI , can increase the rate of pregnancy and finally decrease the failure rate of infertility treatment and perinatal complications in infertile couples Background / Aims : To assess uterine cavity with office hysteroscopy in order to diagnose and treat pathologies in patients who have started their first intracytoplasmic sperm injection ( ICSI ) cycles and evaluate its impact on pregnancy rate . Methods : A number of 220 infertile women scheduled for ICSI participated in this prospect i ve r and omized study . They were r and omly divided into 2 equal groups . Group I ( intervention ) underwent office hysteroscopy before starting assisted reproductive techniques ( ART ) cycle . Group II ( control ) started ART cycles without office hysteroscopy . All women had normal transvaginal ultrasonography and hysterosalpingography . The detected intrauterine abnormalities were treated during hysteroscopy . Four weeks after embryo transfer , ultrasonography was done for detecting clinical pregnancy . Results : Abnormal findings were seen in hysteroscopy in 22.7 % of the intervention group . The pregnancy rate in the intervention group ( 48.20 % ) was significantly higher than that in the control group ( 38.60 % ; p = 0.004 ) . Conclusion : Routine office hysteroscopy before ICSI cycles provides direct evaluation of uterine cavity . Also , pregnancy rate improves after correction of endometrial cavity abnormalities BACKGROUND A prospect i ve , r and omized , controlled study was performed to assess the efficacy of auto-crosslinked hyaluronic acid ( ACP ) gel to prevent the development of de-novo intrauterine adhesions following hysteroscopic surgery . METHODS One hundred and thirty-two patients with a single surgically remediable intrauterine lesion ( myomas , polyps and uterine septa , subgroups I-III ) completed the study . Patients were r and omized to two different groups : group A underwent hysteroscopic surgery plus intrauterine application of ACP gel ( 10 ml ) while group B underwent hysteroscopic surgery alone ( control group ) . The rate of adhesion formation and the adhesion score was calculated for each group and subgroup 3 months after surgery . RESULTS Group A showed a significant reduction in the development of de-novo intrauterine adhesions at 3 months follow-up in comparison with the control group . Furthermore , the staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel . CONCLUSIONS ACP gel significantly reduces the incidence and severity of de-novo formation of intrauterine adhesions after hysteroscopic surgery BACKGROUND It was our intention to determine whether hysteroscopic polypectomy before intrauterine insemination ( IUI ) achieved better pregnancy outcomes than no intervention . METHODS A total of 215 infertile women from the infertility unit of a university tertiary hospital with ultrasonographically diagnosed endometrial polyps ( EP ) undergoing IUI were r and omly allocated to one of two pretreatment groups using an opaque envelope technique with assignment determined by a r and om number table . Hysteroscopic polypectomy was performed in the study group . Diagnostic hysteroscopy and polyp biopsy was performed in the control group . RESULTS Total pregnancy rates and time for success in both groups after four IUI cycles were compared by means of contingency tables and life-table analysis . A total of 93 pregnancies occurred , 64 in the study group and 29 in the control group . Women in the study group had a better possibility of becoming pregnant after polypectomy , with a relative risk of 2.1 ( 95 % confidence interval 1.5 - 2.9 ) . Pregnancies in the study group were obtained before the first IUI in 65 % of cases . CONCLUSIONS These data suggest that hysteroscopic polypectomy before IUI is an effective measure Objective : The aim of the study was to evaluate if the diagnosis and treatment of uterine cavity abnormalities by hysteroscopy in patients undergoing IVF programme is of any value in improving clinical pregnancy outcome . Methods : 520 patients participated in this prospect i ve r and omized study and were classified into two groups . Group I ( n = 265 ) without office hysteroscopy . Group II ( n = 255 ) had office hysteroscopy and was sub classified into Group II a and Group II b. Group II a ( n = 160 ) had normal hysteroscopic findings whereas Group II b ( n = 95 ) had abnormal office hysteroscopy findings , which were corrected at the same time . Result : There was no difference in the mean number of oocytes retrieved , fertilization rate , and number of embryos transferred among the patients in different groups . Statistically significant difference was observed in terms of clinical pregnancy rates between Group I and Group II a ( 26.2 and 44.44 % , P < 0.05 ) , and Group I and Group II b ( 26.2 and 39.55 % , P < 0.05 ) , respectively . Conclusion : Patients with recurrent IVF embryo transfer failures after normal hysterosalpingography findings should also be reevaluated using hysteroscopy prior to further commencing IVF-embryo transfer cycles in order to enhance the clinical pregnancy rates BACKGROUND Whether implantation occurs after in vitro fertilization ( IVF ) depends on the embryo , uterine receptivity or a combination of both . The prevalence of minor intrauterine abnormalities identified at hysteroscopy in cases with a normal transvaginal sonography ( TVS ) has been recorded to be as high as 20 - 40 % . Diagnosing and treating such pathology prior to initiating IVF/intra-cytoplasmic sperm injection ( ICSI ) , has been widely advocated without high- quality evidence of a beneficial effect . The objective of the current study was to assess , by screening office hysteroscopy , the prevalence of unsuspected intrauterine abnormalities in an asymptomatic population of IVF patients , in whom TVS had not revealed any pathology . METHODS The prevalence of unsuspected intrauterine abnormalities in patients allocated for a r and omized controlled trial was prospect ively assessed at two tertiary infertility care units : Academic Hospital at the Dutch-speaking Brussels Free University and University Medical Center Utrecht . A total of 678 unselected , asymptomatic , infertile women with a regular indication for a first IVF/ICSI treatment underwent office hysteroscopy . Only asymptomatic patients , aged < or = 42 years , with a normal TVS and no previous hysteroscopy were included . The presence of predefined intrauterine abnormalities was recorded and described in a st and ardized manner . RESULTS Endometrial polyps were identified in 41 ( 6 % ) women and submucous myomas in 6 women ( 1 % ) . Some women were also diagnosed with intrauterine adhesions ( 2 % ) or septa ( 2 % ) . The overall prevalence of any predefined intrauterine abnormality in this IVF/ICSI population was 11 % . CONCLUSIONS The observed prevalence of unsuspected intrauterine abnormalities in asymptomatic patients indicated for their first IVF/ICSI treatment appeared to be clearly lower than previously reported ( 11 versus 20 - 45 % ) . This may have implication s for the significance of these abnormalities regarding prospect s in IVF/ICSI treatment cycles STUDY OBJECTIVE To estimate the efficacy of fresh and dried amnion graft after hysteroscopic lysis of severe intrauterine adhesions in decreasing its recurrence and encouraging endometrial regeneration . DESIGN Pilot prospect i ve r and omized comparative study ( Canadian Task Force classification I ) . SETTING Ain Shams Medical School , Cairo , Egypt . PATIENTS Forty-five patients with severe intrauterine adhesions . Primary symptom was infertility with or without menstrual disorders such as amenorrhea or hypomenorrhea . INTERVENTIONS Patients were r and omized preoperatively using a computer-generated r and omization sheet into 3 groups of 15 patients each . Allocation to any group was concealed in an opaque envelope , which was opened at the time of operation . Hysteroscopic lysis of intrauterine adhesions was followed by insertion of an intrauterine balloon only ( group 1 ) or either fresh amnion graft ( group 2 ) or dried amnion graft ( group 3 ) for 2 weeks . Diagnostic hysteroscopy was performed at 2 to 4 months postoperatively . MEASUREMENTS AND MAIN RESULTS Adhesion grade , menstruation , uterine length , complications , and reproductive outcome were determined . There was significant improvement in adhesion grade with amnion graft vs intrauterine balloon alone ( p = .003 ) . Improvement was greater with fresh amnion than with dried amnion ( p = .01 ) . Normal menstruation occurred in 4 patients ( 28.6 % ) in group 1 , 5 ( 35.7 % ) in group 2 , and 7 ( 46.7 % ) in group 3 . Of 43 patients , 41 ( 95.3 % ) were treated in 2 endoscopic sessions ( 95.3 % ) , and 2 patients ( 4.7 % ) were treated in 3 endoscopic sessions . Uterine perforations occurred in 2 patients ( 4.7 % ) , and cervical tears in 3 ( 7.0 % ) . Ten patients ( 23.3 % ) achieved pregnancy , 8 ( 80 % ) after amnion graft and 2 ( 20 % ) without amnion . Six of the 10 patients ( 60 % ) miscarried , and 4 ( 40 % ) were either still pregnant or delivered at term without complications . CONCLUSION Hysteroscopic lysis of severe intrauterine adhesions with grafting of either fresh or dried amnion is a promising adjunctive procedure for decreasing recurrence of adhesions and encouraging endometrial regeneration BACKGROUND AND OBJECTIVES Although uterine stenting is performed routinely following hysteroscopic metroplasty , we were unable to find any evidence documenting its value with regards to septum reformation and /or obstetrical performance . To evaluate the benefits of intrauterine Foley catheter/balloon splinting after resectoscopic septum division on septum reformation , fertility , and pregnancy outcomes . DESIGN AND SETTING Prospect i ve , r and omized controlled pilot study ( Canadian Task Force Classification I ) conducted in university affiliated teaching hospital . PATIENTS AND METHODS Twenty-eight women with infertility and /or adverse pregnancy outcomes diagnosed with intrauterine septum were r and omized into having a No. 14 pediatric Foley catheter/balloon for 5 days ( n=13 ) vs. no balloon ( n=15 ) following resectoscopic septum division . None of the patients received preoperative endometrial thinning , antibiotic prophylaxis or adjuvant postoperative hormone therapy . All uterine septa were divided under general anaesthesia using a 26 F ( 9 mm ) resectoscope with a monopolar electrical knife using glycine irrigant solution ( 1.5 % ) and 120 watts of power of low voltage ( cut ) waveform . RESULTS The median age ( range ) was 29 years ( 23–38 ) and 32 years ( 22–40 ) , respectively ( P=.59 ) . The groups were comparable by age , past obstetrical performance and comorbidities including endometriosis stage I – IV in 3 and 4 women , in the catheter/balloon and balloon group , respectively , and one in each group of polycystic ovarian syndrome and Crohn disease and one case of tubal obstruction in the balloon group . There were no intra- or postoperative complications . At 3 months , a hysterosalpingogram was done in 10 ( 77 % ) and 13 ( 87 % ) women , respectively , the results of which were normal . At 12–18 months , 1 woman in the balloon and 3 in the control group were not trying to conceive and 1 in each group had not conceived . Of the remaining women , 11 ( 92 % ) in each group had conceived and pregnancy outcomes included spontaneous abortion 3 ( 25 % ) and 4 ( 33.3 % ) , ectopic pregnancy 0 and 1 , second trimester loss 1 ( 8.3 % ) and 0 and term pregnancy 8 ( 66.6 % ) in both groups . Conception through assisted reproductive technology occurred in 2 and 1 woman , respectively . CONCLUSIONS Following resectoscopic septum division with monopolar knife electrode , splinting the uterine cavity with Foley catheter provided no advantage in septum reformation , clinical pregnancy rate , and pregnancy outcomes BACKGROUND To compare the tolerability and feasibility of the transvaginal and st and ard approaches in outpatient diagnostic hysteroscopy . METHODS This r and omized prospect i ve trial was carried out in two centres to compare the transvaginal ( n = 200 ) and conventional ( n = 200 ) approaches during outpatient hysteroscopy . Patients were r and omized by a computer-generated list . The main outcome measure was pain during the examination , measured on a visual analogue scale ( VAS ) grade d from 0 to 10 ( 0 = lowest , 10 = highest ) . Secondary criteria were ease of instrument passage through the cervix , investigation quality and its duration . For data analysis , we used the chi-squared test or Fischer 's exact test for qualitative variables and the Mann-Whitney U-test for quantitative variables . RESULTS Median VAS was rated at 0.5 for the vaginoscopic and 2 for the st and ard ( P < 0.0001 ) approaches . The approaches did not differ significantly in investigation quality , procedure duration or ease of cervical passage ( although the latter was more often easy transvaginally ) . CONCLUSIONS The transvaginal approach is better tolerated than the conventional technique in outpatient diagnostic hysteroscopy OBJECTIVE To evaluate the role of endometrial injury in the cycle preceding ovarian stimulation for intrauterine insemination ( IUI ) cycle on the clinical pregnancy rate . STUDY DESIGN This was a prospect i ve r and omized controlled trial which included three hundred and thirty two infertile women with an indication for IUI . The subjects were r and omly divided into two groups . The intervention group ( group A ) ( n=166 ) subjects underwent office hysteroscopy with endometrial injury using grasping forceps with teeth , while the control group ( group B ) ( n=166 ) subjects underwent office hysteroscopy alone without endometrial injury . Primary outcome was clinical pregnancy rate . RESULTS There were no significant differences in baseline or clinical characteristics between the groups . There were no significant differences in clinical pregnancy rate [ 13.8 % ( 23/166 ) versus 12 % ( 20/166 ) ; RR 1.15 ( 95 % CI 0.66 - 2.01 ) , p=0.62 ] . The abortion rate [ 4.3 % ( 1/23 ) versus 15 % ( 3/20 ) ; RR 0.29 ( 95 % CI 0.03 - 2.57 ) , p=0.27 ] , the multiple pregnancy rate [ 13 % ( 3/23 ) versus 15 % ( 3/20 ) ; RR 0.87 ( 95 % CI 0.20 - 3.83 ) , p=0.85 ] and the live birth rate [ 13.6 % ( 22/166 ) versus 10.4 % ( 17/166 ) ; RR 1.28 ( 95 % CI 0.71 - 2.32 ) , p=0.42 ] . CONCLUSION There is no evidence of significant difference on the clinical pregnancy rate when endometrial scratching during hysteroscopy is compared to only hysteroscopy in women undergoing IUI AIM To compare the operation and reproductive outcome of hysteroscopic septal resection using unipolar resectoscope verses bipolar resectoscope . METHODS In this prospect i ve r and omized study , 70 women underwent hysteroscopic septal resection using either unipolar resectoscope or bipolar resectoscope . Intraoperative parameters ( operation time , fluid deficit and complications ) and pre- and postoperative serum sodium levels were compared between the two groups . A second-look hysteroscopy was performed after 6 weeks . All pregnancies occurring during the follow-up period were recorded . RESULTS There was no statistically significant difference between the two groups in terms of operation parameters and second-look hysteroscopy findings . Six patients in the unipolar group were found to have hyponatremia in the postoperative period compared to none in the bipolar group ( P = 0.025 ) . Regarding reproductive outcome , the difference between the two groups was not significant . CONCLUSION The use of bipolar resectoscope is associated with lesser risk of hyponatremia compared to unipolar resectoscope . Bipolar resectoscopy is a safe alternative to unipolar resectoscopy with similar reproductive outcome OBJECTIVE To determine whether hysteroscopic myomectomy for submucous fibroids in women with unexplained primary infertility achieved better pregnancy rates than no intervention . DESIGN Prospect i ve r and omized matched control trial . SETTING Tertiary university fertility care unit . PATIENT(S ) From January 1999 to February 2006 , a total of 215 women with unexplained primary infertility and with ultrasonographically diagnosed submucous myomas as the sole cause for fertility failure were recruited . INTERVENTION(S ) Women were r and omly allocated to one of two pretreatment groups matched by age . Hysteroscopic myomectomy was performed in the study group ( n = 101 ) . Diagnostic hysteroscopy and myoma biopsy was performed in the control group ( n = 103 ) . No fertility therapy was given for either group . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rates according to patient and myoma characteristics . RESULT ( S ) The baseline characteristics of both patients and submucous myomas were comparable . Among patients with complete follow-up , a total of 93 ( 45.6 % ) pregnancies occured-64 ( 63.4 % ) in the study group and 29 ( 28.2 % ) in the control group . Women in the study group had a better possibility of becoming pregnant after hysteroscopic myomectomy with a relative risk of 2.1 ( 95 % confidence interval , 1.5 - 2.9 ) . No difference in pregnancy rates was observed according to size , number , and location of myomas in both groups . However , fertility rates appeared to increase after hysteroscopic myomectomy of type 0 and type I myomas ( P < 0.05 ) . In contrast , for the subgroup of patients with type II myomas , no difference in fertility rates were noted . CONCLUSION ( S ) Hysteroscopic myomectomy for submucous fibroids in women with unexplained primary infertility is effective in achieving a better pregnancy rate . We think that a multicenter study should be conducted before evaluating the impact of submucous myoma characteristics on fertility outcome We did a double-blind , r and omized , placebo-controlled study to assess the incidence of infectious complications and the protective effect of antibiotic administration during operative hysteroscopic procedures in an office setting . A total of 1046 consecutively enrolled women with intrauterine lesions were r and omly allocated to the reference group ( 523 patients administered with 1 g of cefazolin intramuscularly ) and the study group ( 523 patients administered with 10 mL of isotonic sodium chloride solution ) , and treated in office setting by operative hysteroscopy for endometrial polypectomy , uterine septa , submucosal myomas , and intrauterine adhesions . The primary outcome measure was the computation of difference between groups in postsurgical infectious complications occurring in the 5 days after the procedures . The time spent in performing the various procedures did not differ significantly ( P > .05 ) between the groups . With respect to the overall rate of postsurgical infection , we found that 12 ( 1.15 % ) of 1046 patients referred with symptoms related to infective complications , 7 ( 1.3 % of 523 women ) in the study —untreated — group and 5 ( 1.0 % of 523 women ) in the reference group . Such incidences did not differ significantly between the groups ( P > .05 ) . Antibiotics were prescribed in all cases of postsurgical infection and the infective process resolved in few days . None of these patients developed serious infections with adnexal involvement , as confirmed by clinical and ultrasounds evaluation . The results of the current study would support the American College of Obstetricians and Gynecologists recommendation not to prescribe routine antibiotic administration in the case of hysteroscopic surgery The purpose of this r and omized controlled study was to compare conventional resectoscopy and hysteroscopic morcellation among residents in training ( Canadian Task Force classification I ) . Sixty women with an intrauterine polyp or myoma were r and omized to either hysteroscopic removal by conventional resectoscopy or hysteroscopic morcellation performed by 6 residents in training for obstetrics and gynecology ( 10 procedures per resident ) . The mean operating time for resectosocpy and morcellation was 17.0 ( 95 % confidence interval [ 95 % CI ] 14.1 - 17.9 , st and ard deviation [ SD ] 8.4 ) and 10.6 ( 95 % CI 7.3 - 14.0 , SD 9.5 ) min , respectively ( p = .008 ) . Multiple linear regression analysis showed that operating time increased significantly , for both resectoscopy and morcellator , when volume of intrauterine disorder increased . The use of the hysteroscopic morcellator reduced operating time more than 8 min in comparison to conventional resectoscopy ( p < .001 ) when correction for volume was applied . Subjective surgeon and trainer scores for convenience of technique on a visual analog scale were in favor of the morcellator . No learning curve was observed . In conclusion , the hysteroscopic morcellator for removal of intrauterine polyps and myomas offers a good alternative to conventional resectoscopy for residents in training STUDY OBJECTIVES To assess the efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel ( Intercoat ; Gynecare , division of Ethicon , Inc. , Somerville , NJ ) in preventing the development of de novo intrauterine adhesions ( IUAs ) after hysteroscopic surgery and to rate the patency of the internal uterine ostium at 1-month follow-up diagnostic hysteroscopy . DESIGN R and omized controlled study ( Canadian Task Force classification I ) . SETTING University hospital . PATIENTS One hundred ten patients diagnosed during office hysteroscopy as having single or multiple lesions suitable for surgical treatment or resistant dysfunctional uterine bleeding requiring endometrial ablation . INTERVENTIONS Patients were r and omized to 2 groups . Group 1 underwent hysteroscopic surgery plus intrauterine application of Intercoat gel , and group 2 underwent hysteroscopic surgery only ( control group ) . Follow-up office hysteroscopy was performed at 1 month after surgery to assess the rate and severity of IUA formation and to rate the patency of the internal uterine ostium after the surgical intervention . MEASUREMENTS AND MAIN RESULTS Compared with the group 2 , group 1 demonstrated a significant reduction in the incidence ( 6 % vs 22 % ; p < .05 ) of de-novo IUAs . Application of the gel seemed to reduce the severity of IUAs , with fewer moderate and severe IUAs at follow-up in group 1 in comparison with group 2 ( 33 % vs 92 % ) . Furthermore , group 1 demonstrated significant improvement in the degree of patency of the internal uterine ostium ( 41.9 % of cases ) in comparison with diagnostic office hysteroscopy performed at enrollment ( p < .05 ) . In contrast , in group 2 , worsening of patency of the internal uterine ostium was recorded in 18.2 % of cases ( p < .05 ) . CONCLUSIONS Intercoat gel seems to prevent de novo formation of IUAs and to improve the patency of the internal uterine ostium at follow-up hysteroscopy . However , larger studies are needed to confirm these findings STUDY OBJECTIVE To estimate the clinical effectiveness of transcervical resection of endometrial polyps . DESIGN R and omized controlled trial ( Canadian Task Force classification I ) . SETTING University teaching hospital . PATIENTS One hundred fifty premenopausal women with endometrial polyps . INTERVENTIONS Either transcervical resection of the polyp or observation for 6 months . MEASUREMENTS AND MAIN RESULTS There was no difference in periodic blood loss measured using the Pictorial Blood Assessment Chart between the study groups at 6-month follow-up . A significant difference between the groups was observed in favor of the intervention group for 2 secondary outcome measures : mean difference of periodic blood loss measured using a visual analog scale ( score , 0.7 ; 95 % confidence interval , 0.11 - 1.30 ; p = .02 ) and occurrence of gynecologic symptoms at follow-up ( 7 of 75 patients [ 9.3 % ] vs 28 of 75 [ 37.3 % ] ; p < .001 ) . Data were analyzed according to the principle of intention to treat . CONCLUSION Transcervical resection of endometrial polyps seems to have minimal effect on periodic blood loss ; however , the procedure seems to relieve symptoms such as intermenstrual bleeding in most premenopausal women BACKGROUND Uterine polyps cause abnormal bleeding in women and conventional practice is to remove them in hospital under general anaesthetic . Advances in technology make it possible to perform polypectomy in an outpatient setting , yet evidence of effectiveness is limited . OBJECTIVES To test the hypothesis that in women with abnormal uterine bleeding ( AUB ) associated with benign uterine polyp(s ) , outpatient polyp treatment achieved as good , or no more than 25 % worse , alleviation of bleeding symptoms at 6 months compared with st and ard inpatient treatment . The hypothesis that response to uterine polyp treatment differed according to the pattern of AUB , menopausal status and longer-term follow-up was tested . The cost-effectiveness and acceptability of outpatient polypectomy was examined . DESIGN A multicentre , non-inferiority , r and omised controlled trial , incorporating a cost-effectiveness analysis and supplemented by a parallel patient preference study . Patient acceptability was evaluated by interview in a qualitative study . SETTING Outpatient hysteroscopy clinics and inpatient gynaecology departments within UK NHS hospitals . PARTICIPANTS Women with AUB - defined as heavy menstrual bleeding ( formerly known as menorrhagia ) ( HMB ) , intermenstrual bleeding or postmenopausal bleeding - and hysteroscopically diagnosed uterine polyps . INTERVENTIONS We r and omly assigned 507 women , using a minimisation algorithm , to outpatient polypectomy compared with conventional inpatient polypectomy as a day case in hospital under general anaesthesia . MAIN OUTCOME MEASURES The primary outcome was successful treatment at 6 months , determined by the woman 's assessment of her bleeding . Secondary outcomes included quality of life , procedure feasibility , acceptability and cost per quality -adjusted life-year ( QALY ) gained . RESULTS At 6 months , 73 % ( 166/228 ) of women who underwent outpatient polypectomy were successfully treated compared with 80 % ( 168/211 ) following inpatient polypectomy [ relative risk ( RR ) 0.91 , 95 % confidence interval ( CI ) 0.82 to 1.02 ] . The lower end of the CIs showed that outpatient polypectomy was at most 18 % worse , in relative terms , than inpatient treatment , within the 25 % margin of non-inferiority set at the outset of the study . By 1 and 2 years the corresponding proportions were similar producing RRs close to unity . There was no evidence that the treatment effect differed according to any of the predefined subgroups when treatments by variable interaction parameters were examined . Failure to completely remove polyps was higher ( 19 % vs. 7 % ; RR 2.5 , 95 % CI 1.5 to 4.1 ) with outpatient polypectomy . Procedure acceptability was reduced with outpatient compared with inpatient polyp treatment ( 83 % vs. 92 % ; RR 0.90 , 95 % CI 0.84 to 0.97 ) . There were no significant differences in quality of life . The incremental cost-effectiveness ratios at 6 and 12 months for inpatient treatment were £ 1,099,167 and £ 668,800 per additional QALY , respectively . CONCLUSIONS When treating women with AUB associated with uterine polyps , outpatient polypectomy was non-inferior to inpatient polypectomy at 6 and 12 months , and relatively cost-effective . However , patients need to be aware that failure to remove a polyp is more likely with outpatient polypectomy and procedure acceptability lower . TRIAL REGISTRATION Current Controlled Trials IS RCT N 65868569 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 61 . See the NIHR Journals Library website for further project information AIM To determine if the incidence of small endometrial polyps detected hysteroscopically in an infertile eumenorrheic population differed from that in an apparently fertile eumenorrheic population . Evidence was sought to determine whether removal of such lesions would enhance reproductive performance . METHODS In a prospect i ve study , 266 consecutive infertile women had undergone complete fertility evaluation . None of the women had experienced any change in their menstrual cycle . They were divided into two groups ; 235 infertile patients ( group 1 ) and 31 requesting a reversal of a previous tubal sterilization ( group 2 ) . All patients were examined by simultaneous combined laparoscopy and hysteroscopy as part of their routine infertility evaluation . When endometrial polyps were noted they were removed by hysteroscopy and histopathologically examined . Patients in whom the only apparent finding was endometrial polyps were followed up to determine their reproductive outcomes subsequent to removal of the polyps . RESULTS Of the 224 uterine cavities successfully visualized in the infertile group , 134 were judged to be normal ( 60 % ) and 90 were abnormal ( 40 % ) . Endometrial polyps were noted in 35 patients of group 1 and in one patient of group 2 ( P < 0.01 ) . Most polyps were located in the region of the utero-tubal junction and proved to be functional . A 50 % pregnancy rate was achieved by hysteroscopic polypectomy . Fertility-related factors in women whose only apparent finding was endometrial polyps before and after hysteroscopy were comparable . CONCLUSION Diagnostic hysteroscopy should be used routinely in the work-up of infertile woman , even in the presence of eumenorrhea . Persistent functional endometrial polyps , even if small , are likely to impair fertility in this select patient group . Removal of such lesions may improve subsequent reproductive performance OBJECTIVE : To evaluate whether hysteroscopic morcellation or bipolar electrosurgical resection is more favorable for removing endometrial polyps in an office setting in terms of feasibility , speed , pain , and acceptability . METHODS : A multicenter , single-blind , r and omized , controlled trial of office hysteroscopic morcellation compared with electrosurgical resection was conducted . A total of 121 women were r and omly allocated to polyp removal by one of the two methods in an office setting . The outcomes assessed were time taken to complete the endometrial polypectomy , defined as the time from insertion to removal of vaginal instrumentation , completeness of polyp removal , acceptability , and pain measured on a 100-mm visual analog scale . RESULTS : The median time taken to complete the procedure was 5 minutes and 28 seconds for morcellation compared with 10 minutes and 12 seconds for electrosurgical resection ( P<.001 ) . The polyps were completely removed in 61 out of 62 ( 98 % ) women assigned to morcellation compared with 49 out of 59 ( 83 % ) women treated with electrosurgical resection ( odds ratio 12.5 ; 95 % confidence interval [ CI ] 1.5–100.6 ; P=.02 ) . The mean pain scores during the procedure favored morcellation by 16.1 points on average ( 35.9 compared with 52.0 ; 95 % CI for difference , −24.7 to −7.6 ; P<.001 ) . Overall , 99 % of women found office polypectomy to be acceptable , with only one woman in the electrosurgical resection group considering the procedure unacceptable . CONCLUSION : In comparison to electrosurgical resection during hysteroscopic polypectomy , morcellation was significantly quicker , less painful , more acceptable to women , and more likely to completely remove endometrial polyps compared with electrosurgical resection . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01509313 . LEVEL OF EVIDENCE : OBJECTIVE To evaluate operative resectoscopy versus hysteroscopic bipolar electrode excision for the treatment of endometrial polyps . DESIGN Prospect i ve , r and omized study . SETTING Tertiary-care university hospital . PATIENT(S ) One hundred consecutive patients with endometrial polyps . INTERVENTION(S ) Patients underwent diagnostic hysteroscopy , and after assignment on a r and om basis , they underwent polyp excision either by operative resectoscopy or by a bipolar electrode passed through the operating sheath of a small-caliber hysteroscope . MAIN OUTCOME MEASURE(S ) AND RESULT ( S ) : Operating times , difficulty of the operation , surgeon satisfaction with the procedure , intra- and postoperative complications , postoperative pain , and patient satisfaction were recorded . The two procedures did not differ in total surgery times . In subgroup analysis , the resectoscope was faster for large polyps ( > 2 cm ) and for polyps with a fundal implant . The bipolar electric probe was faster for small polyps ( < 2 cm ) and for polyps with a nonfundal implant . CONCLUSION ( S ) Operative resectoscopy appears to be the technique of choice for endometrial polyps > 2 cm or with a fundal implant . Bipolar electrode excision appears to be preferable for smaller , nonfundal polyps AIM The aim of this prospect i ve r and omized study was to evaluate the efficacy of estrogen in preventing intrauterine adhesions following hysteroscopic septal resection and to investigate its effect on reproductive outcome . MATERIAL S AND METHODS After hysteroscopic septal resection , 90 women received either estrogen or placebo ( n=45 per group ) for 30 days . A second-look hysteroscopy was performed after 2 months . All pregnancies occurring during the study period were recorded . RESULTS Adhesions developed in three of 43 ( 6.9 % ) patients in the control group compared to none in the estrogen group . This difference was not statistically significant ( P=0.24 ) . Regarding reproductive outcome , the differences between the two groups were also not significant . CONCLUSION Estrogen treatment was not found to prevent intrauterine adhesions or improve reproductive outcome after hysteroscopic septal resection During 1990 , we performed hysteroscopic incision of uterine septum in 23 women with repeated abortion . The patients were allocated r and omly to metroplasty with resectoscope ( 12 patients in group 1 ) or microscissors ( 11 patients in group 2 ) to compare surgical feasibility and anatomic results with these instruments . The uterine cavity was distended by instillation of sorbitol and mannitol solution under manometric control . Two patients in group 1 and three in group 2 had a complete septum . In group 1 , the mean operating time , plus or minus st and ard deviation ( S.D. ) , was 22 + /- 6 minutes compared with 17 + /- 5 minutes in group 2 ( p = 0.06 ) . The mean amount of distension medium used , plus or minus S.D. , was 890 + /- 153 milliliters in group 1 versus 671 + /- 170 milliliters in group 2 ( p = 0.003 ) . One woman in group 1 with complete uterine septum had a uterine perforation that was managed conservatively . Postoperative morbidity for the entire series was negligible . At follow-up ultrasonography and hysteroscopy performed two months postoperatively , a residual fundal notch > or = 1 centimeter deep was detected and corrected in four patients in group 1 and two in group 2 . Our findings indicate that , in terms of operating time and efficacy , the resectoscope and microscissors are equally valid instruments to correct a septate uterus , with a feasibility rate of 100 percent |
13,042 | 29,236,286 | Corticosteroid therapy reduced morbidity , but not mortality , for adults and children with non-severe CAP .
Corticosteroid therapy was associated with more adverse events , especially hyperglycaemia , but the harms did not seem to outweigh the benefits | BACKGROUND Pneumonia is a common and potentially serious illness .
Corticosteroids have been suggested for the treatment of different types of infection , however their role in the treatment of pneumonia remains unclear .
This is an up date of a review published in 2011 .
OBJECTIVES To assess the efficacy and safety of corticosteroids in the treatment of pneumonia . | Objective : To determine the efficacy of dexamethasone in the treatment of mechanically ventilated children with respiratory syncytial virus – severe lower respiratory tract infection . Design : International , multicenter , r and omized , double-blind , placebo-controlled trial . Setting : Twelve pediatric intensive care units . Subjects : Children ( < 2 yrs ) mechanically ventilated for respiratory syncytial virus lower respiratory tract infection . Children were prestratified for severity of oxygen abnormalities on admission . Intervention : Intravenous dexamethasone ( 0.6 mg/kg/day , 48 hrs ) or placebo . Measurements and Main Results : A superiority approach was used in the subgroup of patients with mild oxygen abnormalities ( arterial partial pressure of oxygen/fractional inspired oxygen concentration [ PaO2/Fio2 ] > 200 mm Hg and /or mean arterial pressure ≤10 cm H2O ) and a noninferiority approach in those with severe oxygen abnormalities ( PaO2/Fio2 ≤200 mm Hg and mean arterial pressure > 10 cm H2O ) . Primary outcome was the duration of mechanical ventilation . In the subgroup with mild oxygenation abnormalities , 45 of the 89 included patients received dexamethasone and 44 placebo ; in the subgroup with severe oxygenation abnormalities , 28 of the 56 included patients received dexamethasone and 28 placebo . Baseline characteristics in both treatment arms were similar for both subgroups . After the third interim analysis , the trial was stopped early for futility taking the slow enrollment into account . At that time , the median duration ( interquartile range ) of mechanical ventilation was 137 ( 91–195 ) hrs in the dexamethasone- and 139 ( 117–188 ) hrs in the placebo-treated patients in the subgroup with mild oxygenation abnormalities ( p = .6 ) . In the subgroup with severe oxygenation abnormalities , it was 171 ( 136–212 ) hrs in the dexamethasone- and 170 ( 125–201 ) hrs in the placebo-treated patients ( p = .6 ) . Conclusion : In this prematurely ended trial in children mechanically ventilated for severe respiratory syncytial virus – lower respiratory tract infection , we found no evidence of a beneficial effect of dexamethasone in children with mild oxygenation abnormalities . Neither was evidence found that dexamethasone may prolong mechanical ventilation in those with severe oxygenation abnormalities Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia ( CAP ) requiring hospital admission remains unclear . This study aim ed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP . Methods This was a prospect i ve , double-blind and r and omized study . All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone ( MPDN ) administered r and omly and blindly as an initial bolus , followed by a tapering regimen , or placebo . Results Of the 56 patients included in the study , 28 ( 50 % ) were treated with concomitant corticosteroids . Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever , as well as greater radiological improvement at seven days . The time to resolution of morbidity was also significantly shorter in this group . Six patients met the criteria for mechanical ventilation ( MV ) : five in the placebo group ( 22.7 % ) and one in the MPDN group ( 4.3 % ) . The duration of MV was 13 days ( interquartile range 7 to 26 days ) for the placebo group and three days for the only case in the MPDN group . The differences did not reach statistical significance . Interleukin (IL)-6 and C-reactive protein ( CRP ) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN . No differences in mortality were found among groups . Conclusions MPDN treatment , in combination with antibiotics , improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission . Trial Registration International St and ard R and omized Controlled Trials Register , IS RCT N22426306 Community-acquired pneumonia occurs 3 to 4 million times per year in the United States , accounting for about 500,000 hospitalizations annually . Empiric treatment is usually instituted because of a lack of early organism-specific diagnostic tests . This study compared empiric therapy with ofloxacin to st and ard antibiotic regimens ( usually a beta-lactam with or without a macrolide ) for patients hospitalized for community-acquired pneumonia . Therapy was administered to 298 patients ( 146 receiving ofloxacin and 152 receiving st and ard therapy ) ; 227 patients ( ofloxacin , 109 ; st and ard treatment , 118 ) were evaluable for treatment efficacy . The most common pyogenic respiratory pathogens were Haemophilus influenzae ( 30 isolates ) and Streptococcus pneumoniae ( 24 isolates ) . There was evidence of infection with either Mycoplasma pneumoniae ( 38 patients ) , Chlamydia pneumoniae ( 40 patients ) , or a Legionella sp. ( 8 patients ) in a total of 79 patients ( 35 % ) . The clinical success rates were similar in both groups among evaluable patients ( 92 % , ofloxacin ; 87 % , st and ard therapy ) and among patients with atypical respiratory pathogens ( 88 % , ofloxacin ; 81 % , st and ard therapy ) . The mean numbers ( + /- the st and ard deviations ) of intravenous doses of antibiotics were 7.5 + /- 8.0 in the ofloxacin group and 18.4 + /- 18.5 in the st and ard therapy group ( P < 0.001 ) ; the mean number of oral doses of ofloxacin per patient was 19.7 + /- 11.2 , compared with 30.2 + /- 16.0 oral antibiotic doses in the st and ard therapy group ( P < 0.001 ) . All treatments were well tolerated and associated with no significant clinical or laboratory abnormalities . The findings of this study indicate that ofloxacin is active against traditional bacterial pathogens as well as the major atypical respiratory pathogens . When given as monotherapy for the empiric treatment of community-acquired pneumonia , ofloxacin is as effective as st and ard antimicrobial therapy Objective : To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients . Participants : A multidisciplinary , multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine . In addition , international experts in endocrinology were invited to participate . Design / Methods : The task force members review ed published literature and provided expert opinion from which the consensus was derived . The consensus statements were developed using a modified Delphi methodology . The strength of each recommendation was quantified using the Modified GRADE system , which classifies recommendations as strong ( grade 1 ) or weak ( grade 2 ) and the quality of evidence as high ( grade A ) , moderate ( grade B ) , or low ( grade C ) based on factors that include the study design , the consistency of the results , and the directness of the evidence . Results : The task force coined the term critical illness – related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness . Critical illness – related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response . Critical illness – related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents , particularly in the setting of sepsis . At this time , the diagnosis of tissue corticosteroid resistance remains problematic . Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 & mgr;g/dL after adrenocorticotrophic hormone ( 250 & mgr;g ) administration or a r and om total cortisol of < 10 & mgr;g/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome ( Pao2/Fio2 of < 200 and within 14 days of onset ) . The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids . Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day ( 10 mg/hr ) for ≥7 days is recommended for septic shock . Methylprednisolone in a dose of 1 mg·kg−1·day−1 for ≥14 days is recommended in patients with severe early acute respiratory distress syndrome . Glucocorticoids should be weaned and not stopped abruptly . Reinstitution of treatment should be considered with recurrence of signs of sepsis , hypotension , or worsening oxygenation . Dexamethasone is not recommended to treat critical illness – related corticosteroid insufficiency . The role of glucocorticoids in the management of patients with community-acquired pneumonia , liver failure , pancreatitis , those undergoing cardiac surgery , and other groups of critically ill patients requires further investigation . Conclusion : Evidence -linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary , multispecialty task force BACKGROUND The reliability of chest physical examination and the degree of agreement among examiners in diagnosing pneumonia based on these findings are largely unknown . OBJECTIVES To determine the accuracy of various physical examination maneuvers in diagnosing pneumonia and to compare the interobserver reliability of the maneuvers among 3 examiners . METHODS Fifty-two male patients presenting to the emergency department of a university-affiliated Veterans Affairs medical center with symptoms of lower respiratory tract infection ( cough and change in sputum ) were prospect ively examined . A comprehensive lung physical examination was performed sequentially by 3 physicians who were blind to clinical history , laboratory findings , and x-ray results . Examination findings by lung site and whether the examiner diagnosed pneumonia were recorded on a st and ard form . Chest x-ray films were read by a radiologist . RESULTS Twenty-four patients had pneumonia confirmed by chest x-ray films . Twenty-eight patients did not have pneumonia . Abnormal lung sounds were common in both groups ; the most frequently detected were rales in the upright seated position and bronchial breath sounds . Relatively high agreement among examiners ( kappa approximately 0.5 ) occurred for rales in the lateral decubitus position and for wheezes . The 3 examiners ' clinical diagnosis of pneumonia had a sensitivity of 47 % to 69 % and specificity of 58 % to 75 % . CONCLUSIONS The degree of interobserver agreement was highly variable for different physical examination findings . The most valuable examination maneuvers in detecting pneumonia were unilateral rales and rales in the lateral decubitus position . The traditional chest physical examination is not sufficiently accurate on its own to confirm or exclude the diagnosis of pneumonia Background Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia . Objectives The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia ( CAP ) requiring hospitalization . Design and Setting An open label , prospect i ve , r and omized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan . Patients Thirty-one adult CAP patients who required hospitalization were enrolled . Measurements and Results Fifteen patients received 40 mg of prednisolone intravenously for 3 days ( steroid group ) . Sixteen patients did not receive prednisolone ( control group ) . Both groups were also evaluated for their adrenal function . The primary endpoint was length of hospital stay . Secondary endpoints were duration of intravenous ( IV ) antibiotics and time required to stabilize vital signs . Both groups demonstrated similar baseline characteristics and length of hospital stay , and yet a shorter duration of IV antibiotics was observed in the steroid group ( p < 0.05 ) . In addition , vital signs were stabilized earlier in the steroid group ( p < 0.05 ) . These differences were more prominent in the moderate – severe subgroup but not as significant in the mild – moderate subgroup . The prevalence of relative adrenal insufficiency ( RAI ) in both groups was high ( 43 % ) , yet there was no difference in baseline characteristics between patients , with or without RAI . In multiple regression models , RAI seemed to have no influence on clinical courses . Conclusions In moderate – severe CAP , administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy Context Bloodstream infections are traditionally classified as community-acquired or hospital-acquired ( nosocomial ) . Ideally , these classifications guide initial diagnostic and management decisions . As out-of-hospital care grows more complex , do we need finer classifications ? Contribution This prospect i ve study from three hospitals in North Carolina shows that about one third of patients with bloodstream infections have had recent contact with the health care system ( health c areas sociated infections ) through nursing homes , home health care programs , outpatient intravenous therapy , or recent hospitalizations . Staphylococcus aureus and intravascular devices were the most common pathogen and source , respectively , for both health c areas sociated and nosocomial infections . Implication s Health c areas sociated infections often resemble nosocomial infections , a fact to be considered in selecting empirical antibiotic therapy for these infections . The Editors A recent review ( 1 ) found that nearly equal proportions of bacteremias were community acquired ( 48 % ) and nosocomial ( 52 % ) . In the 1970s , by contrast , nearly two thirds of 500 bacteremic episodes were nosocomial ( 2 ) . At present , patients with complicated conditions , such as cancer or renal failure , are routinely cared for in outpatient setting s , yet such patients are still categorized as having community-acquired infections when they are admitted to the hospital with bloodstream infection . The Centers for Disease Control and Prevention ( CDC ) surveillance definitions include only nosocomial infection ( 3 ) ; infections that are not nosocomial are considered to be community acquired by default . The term nosohusial has been proposed to describe infections occurring in patients who are receiving care at home ( 4 ) . However , this term applies only to illnesses in patients who receive care at home ; it excludes patients in nursing homes and rehabilitation centers , patients receiving dialysis , and patients receiving chemotherapy in physicians ' offices . Although the authors of a recent study ( 5 ) proposed creating a more inclusive category , health c areas sociated infection , no consensus definition exists for this group of infections . We sought to devise a new classification scheme for bloodstream infections that distinguishes among and compares patients with community-acquired , health c areas sociated , and nosocomial infections . Methods This prospect i ve cohort study was done at Duke University Medical Center ( Durham , North Carolina ) , Durham Regional Hospital ( Durham , North Carolina ) , and Nash General Hospital ( Rocky Mount , North Carolina ) . Approval of the study protocol was obtained from the institutional review boards at each hospital , which waived the requirement for obtaining informed consent . Patient Selection Daily microbiology laboratory reports were review ed and case-report forms were completed by either a physician or an infection-control practitioner on consecutive adult patients who were admitted to the hospital with bloodstream infections or developed bloodstream infections during hospitalization . Patients younger than 17 years of age and patients who visited the emergency department but were not hospitalized were excluded . Data Collection We collected data on demographic characteristics , medication use , blood cultures , comorbid medical conditions , results of antimicrobial susceptibility testing , and date s of admission and discharge or death . Mortality data were retrieved from medical records and a Social Security death registry Web site ( 6 ) . The medical record was the gold st and ard for assessing mortality , and we search ed for deaths by Social Security number only if the medical record was not definitive . Follow-up continued for a maximum of 6 months after enrollment . A bloodstream-infection episode was defined by the first set of positive blood cultures in a series or by any new positive blood culture set occurring more than 48 hours after a previous positive result , unless it was clear to the investigator that the new positive culture was part of the previous episode [ 2 ] . To distinguish between true bloodstream infections and episodes of contamination , each positive blood culture was assessed critically by one investigator . All isolates were categorized as 1 ) true-positive , 2 ) contaminated , or 3 ) of unknown clinical significance . The determination was made after review of the patient 's clinical history , physical findings , temperature at the time of blood culture , leukocyte count , number of positive blood cultures , results of cultures of specimens from other sites , imaging results , histopathologic findings , clinical course , and response to therapy ( 1 ) . Nosocomial bloodstream infection was defined by a positive blood culture obtained from patients who had been hospitalized for 48 hours or longer ( 3 ) . If a patient was transferred from another hospital , the duration of inpatient stay was calculated from the date of the first hospital admission . Health c areas sociated bloodstream infection was defined by a positive blood culture obtained from a patient at the time of hospital admission or within 48 hours of admission if the patient fulfilled any of the following criteria : Received intravenous therapy at home ; received wound care or specialized nursing care through a health care agency , family , or friends ; or had self-administered intravenous medical therapy in the 30 days before the bloodstream infection . Patients whose only home therapy was oxygen use were excluded . Attended a hospital or hemodialysis clinic or received intravenous chemotherapy in the 30 days before the bloodstream infection . Was hospitalized in an acute care hospital for 2 or more days in the 90 days before the bloodstream infection . Resided in a nursing home or long-term care facility . Community-acquired bloodstream infection was defined by a positive blood culture obtained at the time of hospital admission or within the 48 hours after hospital admission for patients who did not fit the criteria for a health c areas sociated infection . Information about comorbid medical conditions , such as diabetes , chronic obstructive pulmonary disease , liver disease , active cancer , transplantation , or HIV infection , was obtained through medical record review . Active cancer was defined as a solid tumor or hematologic malignancy ( except squamous-cell or basal-cell skin cancer ) diagnosed or treated in the past 5 years . Vascular disease was defined by the clinical documentation of at least one of the following : coronary artery disease , cerebrovascular disease , peripheral vascular disease , or aortic aneurysm . Renal failure was defined as a serum creatinine concentration greater than 177 mol/L ( > 2.00 mg/dL ) . Factors predisposing to infection , such as chemotherapy , immunosuppressive therapy , and radiation therapy , were considered to be present if they had been administered within 30 days of the bloodstream infection . Neutropenia was defined as an absolute neutrophil count of less than 500 cells/mm3 within 30 days before the bloodstream infection . Immunosuppressive therapy included treatment with steroids , cyclophosphamide , azathioprine , methotrexate , mycophenolate mofetil , and calcineurin inhibitors . Sources of bloodstream infection were design ated as culture confirmed ( if the same organism was isolated from another site ) or suspected ( if clinical findings of infection were seen without microbiological proof ) . Primary bloodstream infections including intravascular deviceassociated infections were defined according to the National Nosocomial Infections Surveillance System ( 3 , 7 ) . Secondary bloodstream infection was declared to be present when an organism isolated from a blood culture was related to an infection at another site , as defined by both CDC and other published criteria ( 3 , 8) . Microbiology All isolates from patients were identified and speciated by using st and ard microbiologic techniques ( 2 ) . Antimicrobial susceptibility testing was done according to National Committee for Clinical Laboratory st and ards ( 9 ) . Statistical Analysis Statistical analysis was done by using SAS software , version 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . Distributions of baseline characteristics were analyzed by using the Wilcoxon rank-sum test for continuous variables . The chi-square test was used to assess associations among categorical variables , with 3 2 tables broken down into three 2 2 tables for pairwise comparisons . If any expected value for a cell in one of the 2 2 tables was less than 5 , the Fisher exact test was used and two-sided P values were reported . Associations between epidemiologic categories of infection and other variables were analyzed by using conditional fixed-effects logistic regression . Dummy variables ( 0/1 ) were used to represent two of the three hospitals ( the third hospital being the baseline ) as well as two of the three epidemiologic categories of infection , thereby adjusting for clustering of epidemiologic factors and outcomes by hospital site . This technique was vali date d by comparison with MantelHaenszel chi-square . A P value less than 0.05 was considered statistically significant . Role of the Funding Source The funding source had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results Between 16 October 2000 and 28 February 2001 , a total of 1175 positive blood cultures were detected at the three study hospitals . Of these 1175 cultures , 476 were the result of contamination , 655 represented true bloodstream infections , and 44 were of unknown clinical significance . Seven of the 1175 were excluded from analysis because the patients were not admitted to the hospital . Coagulase-negative staphylococci ( 66 % ) , gram-positive rods ( 16 % ) , and mixed skin flora ( 9 % ) constituted most of the contaminants . Either coagulase-negative staphylococci ( 64 % ) or yeast ( 11 % ) was present in three fourths of cases classified as bloodstream infection of We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock . Forty-six patients entered the study . At study entry , the hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 ) RATIONALE Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia ( CAP ) , possibly by diminishing local and systemic antiinflammatory host response . OBJECTIVES To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP . METHODS Hospitalized patients , clinical ly and radiologically diagnosed with CAP using st and ard clinical and radiological criteria , were r and omized to receive 40 mg prednisolone for 7 days or placebo , along with antibiotics . Primary outcome was clinical cure at Day 7 . Secondary outcomes were clinical cure at Day 30 , length of stay , time to clinical stability , defervescence , and C-reactive protein . Disease severity was scored using CURB-65 ( a severity index for community-acquired pneumonia evaluating Confusion , blood Urea nitrogen , Respiratory rate , Blood pressure , and age 65 or older ) and Pneumonia Severity Index . MEASUREMENTS AND MAIN RESULTS We enrolled 213 patients . Fifty-four ( 25.4 % ) patients had a CURB-65 score greater than 2 , and 93 ( 43.7 % ) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 ( 80.8 % ) and 69/104 ( 66.3 % ) in the prednisolone group and 93/109 ( 85.3 % ) and 84/109 ( 77.1 % ) in the placebo group ( P = 0.38 and P = 0.08 ) . Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo . Sub analysis of patients with severe pneumonia did not show differences in clinical outcome . Late failure ( > 72 h after admittance ) was more common in the prednisolone group ( 20 patients , 19.2 % ) than in the placebo group ( 10 patients , 6.4 % ; P = 0.04 ) . Adverse events were few and not different between the two groups . CONCLUSIONS Prednisolone ( at 40 mg ) once daily for a week does not improve outcome in hospitalized patients with CAP . A benefit in more severely ill patients can not be excluded . Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP BACKGROUND Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear . We aim ed to assess effect of addition of dexamethasone on length of stay in this group , which might result in earlier resolution of pneumonia through dampening of systemic inflammation . METHODS In our double-blind , placebo-controlled trial , we r and omly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherl and s to receive intravenous dexamethasone ( 5 mg once a day ) or placebo for 4 days from admission . Patients were ineligible if they were immunocompromised , needed immediate transfer to an intensive-care unit , or were already receiving corticosteroids or immunosuppressive drugs . We r and omly allocated patients on a one-to-one basis to treatment groups with a computerised r and omisation allocation sequence in blocks of 20 . The primary outcome was length of hospital stay in all enrolled patients . This study is registered with Clinical Trials.gov , number NCT00471640 . FINDINGS Between November , 2007 , and September , 2010 , we enrolled 304 patients and r and omly allocated 153 to the placebo group and 151 to the dexamethasone group . 143 ( 47 % ) of 304 enrolled patients had pneumonia of pneumonia severity index class 4 - 5 ( 79 [ 52 % ] patients in the dexamethasone group and 64 [ 42 % ] controls ) . Median length of stay was 6·5 days ( IQR 5·0 - 9·0 ) in the dexamethasone group compared with 7·5 days ( 5·3 - 11·5 ) in the placebo group ( 95 % CI of difference in medians 0 - 2 days ; p=0·0480 ) . In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups , although 67 ( 44 % ) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 ( 23 % ) of 153 controls ( p<0·0001 ) . INTERPRETATION Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia . FUNDING None The aim of this study was to assess the cytokine response after nasal exposure to organic dusts . In a double blinded , crossover study five garbage workers with occupational airway symptoms and five healthy garbage workers were intranasally exposed to endotoxin ( lipopolysaccharide LPS ) , beta-1,3-D-glucan ( GLU ) , Aspergillus sp. , compost or the saline dilute for 15 min . Nasal cavity volume and nasal lavage ( NAL ) were performed at baseline and 3 , 6 , 11 h postexposure . NAL was analysed with differential cell counts , cysteinyl-leukotrienes , tumour necrosis factor alpha , interleukin (IL)-1beta , IL-6 and IL-8 . A whole blood assay on cytokine-release was performed with LPS and GLU . NAL cytokines neutrophils , lymphocytes and albumin increased significantly at 6 h after LPS exposure . GLU induced an increase in albumin and a slight increase in IL-1beta 6 - 11 h post exposure . In the WBA a significant increase in all cytokines after exposure to LPS as well as GLU was found . Significantly more cells were seen in NAL of the control group 6 h post LPS exposure . In conclusion lipopolysaccharide is the most potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D-glucan only induce minor changes . This reaction to lipopolysaccharide is attenuated in workers with occupational airway symptoms . In whole blood assay , however , beta-1,3-D-glucan also induces cytokine release , indicating a different protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D-glucan Background : A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus ( RSV-LRTI ) . Methods : In a multicentre r and omised controlled trial patients were r and omised to receive either intravenous dexamethasone ( 0.15 mg/kg 6 hourly for 48 hours ) or placebo . End points were the duration of mechanical ventilation , length of stay ( LOS ) in the pediatric intensive care unit ( PICU ) and in hospital , and the duration of supplemental oxygen administration . Results : Thirty seven patients received dexamethasone and 45 received placebo . There was no significant difference in any of the end points between the two groups . In a post hoc analysis patients were stratified into those with mild gas exchange anomalies ( Pao2/Fio2 > 200 mm Hg and /or mean airway pressure ⩽ 10 cm H2O , bronchiolitis group ) and those with severe gas exchange anomalies ( Pao2/Fio2 ⩽200 mm Hg and mean airway pressure > 10 cm H2O , pneumonia group ) . In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group ( 4.9 v 9.2 days , 95 % CI −7.8 to −0.8 , p=0.02 ) and the duration of supplemental oxygen was 3.6 days shorter ( 7.7 v 11.3 days , 95 % CI −8.0 to −0.1 , p=0.048 ) . No differences in end points were found in the pneumonia group . Conclusions : Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis A controlled trial was carried out to investigate whether the rate of recovery from pneumonia treated with ampicillin is dose related . Sixty-three patients received 1 g ampicillin daily and 63 received 2 g ampicillin daily for seven or 14 days depending on the rate of response . Twenty patients in each of these groups received , in addition , 20 mg prednisolone daily for seven days . The treatment groups were comparable and the results of treatment were similar in the four groups . The only difference which was of statistical significance was that a larger proportion of patients receiving 1 g ampicillin daily became afebrile within one week . All the ampicillin rashes occurred in the patients receiving 2 g ampicillin daily with and without prednisolone . Ampicillin 1 g daily appears to be adequate dosage in the treatment of pneumonia , and the rate of recovery has not been shown to be accelerated by using 2 g. No deleterious effects were noted with additional prednisolone therapy and this appeared to increase the rate at which the patients became afebrile , although the figures were not statistically significant Despite advances in antimicrobial therapy and supportive measures , mortality for patients with severe community-acquired pneumonia admitted to the intensive care unit remains high , especially in case of development of sepsis with its complications . So , the early detection of the severity of pneumonia is crucial to achieve an optimal monitoring and treatment of the patients . Studies of serum and lung cytokines levels in patients with pneumonia show a compartimentalized response , that rarely appears in the serum . In case of severe community-acquired pneumonia inflammation spill over from the lungs , particularly there is a persistent increase of IL-6 and CRP in serum , and this is associated with a worst prognosis and possible development of sepsis-related complications . Hydrocortisone and other glucorticoid agents have a powerful modulating effect on inflammation and balance between pro- and anti-inflammatory factors . Recent r and omized controlled clinical trials on patients with severe community acquired pneumonia support the use of prolonged infusion of low doses of hydrocortisone to accelerate the resolution of the pneumonia and prevent the development of complications due to sepsis . Moreover , this therapeutic approach seems to be associated with a significant reduction in duration of mechanical ventilation , in length of hospital stay and mortality in hospital The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium ( INICC ) from January 2004 through December 2009 in 422 intensive care units ( ICUs ) of 36 countries in Latin America , Asia , Africa , and Europe are reported . During the 6-year study period , using Centers for Disease Control and Prevention ( CDC ) National Healthcare Safety Network ( NHSN ; formerly the National Nosocomial Infection Surveillance system [ NNIS ] ) definitions for device-associated health care-associated infections , we gathered prospect i ve data from 313,008 patients hospitalized in the consortium 's ICUs for an aggregate of 2,194,897 ICU bed-days . Despite the fact that the use of devices in the developing countries ' ICUs was remarkably similar to that reported in US ICUs in the CDC 's NHSN , rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals ; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs . The overall rate of ventilator-associated pneumonia also was far higher ( 15.8 vs 3.3 per 1,000 ventilator-days ) , as was the rate of catheter-associated urinary tract infection ( 6.3 vs. 3.3 per 1,000 catheter-days ) . Notably , the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem ( 47.2 % vs 23.0 % ) , Klebsiella pneumoniae isolates to ceftazidime ( 76.3 % vs 27.1 % ) , Escherichia coli isolates to ceftazidime ( 66.7 % vs 8.1 % ) , Staphylococcus aureus isolates to methicillin ( 84.4 % vs 56.8 % ) , were also higher in the consortium 's ICUs , and the crude unadjusted excess mortalities of device-related infections ranged from 7.3 % ( for catheter-associated urinary tract infection ) to 15.2 % ( for ventilator-associated pneumonia ) BACKGROUND Community-acquired pneumonia is a major cause of death in third world countries . Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia . We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha ( TNF-alpha ) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy . AIM To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia . DESIGN R and omized placebo-controlled study . SETTING Multidisciplinary ICU of a tertiary care teaching hospital . PATIENTS AND METHODS Patients with three or more British Thoracic Society criteria of severe pneumonia were studied . Patients were r and omized to receive either a single dose of hydrocortisone ( 10 mg/kg ) or placebo 30 min prior to commencing antibiotic therapy . Patients were treated with cefotaxime and other antibiotics as clinical ly indicated . Blood for TNF-alpha was taken at the time of hospital admission and repeated 2 , 6 , and 12 h after starting antibiotic therapy . RESULTS Thirty patients were studied : 16 received placebo and 14 received hydrocortisone . The patients who received placebo tended to be sicker than the patients who received hydrocortisone . The baseline TNF-alpha value was 989 + /- 374 pg/ml in the placebo group and 827 + /- 394 pg/ml in the hydrocortisone group . In both groups of patients , the TNF-alpha levels did not change significantly with time . There was no correlation between the TNF-alpha levels and the APACHE II score , lung injury score , or outcome . The only variable that predicted outcome was the APACHE II score . CONCLUSION Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia . Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia ABSTRACT The objective of the present trial was to compare the efficacy , safety , and tolerability of moxifloxacin ( 400 mg ) given intravenously ( i.v . ) once daily followed by oral moxifloxacin ( 400 mg ) for 7 to 14 days with the efficacy , safety , and tolerability of co-amoxiclav ( 1.2 g ) administered by i.v . infusion three times a day followed by oral co-amoxiclav ( 625 mg ) three times a day , with or without clarithromycin ( 500 mg ) twice daily ( i.v . or orally ) , for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy . A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication . Although the trial was design ed , on the basis of predefined outcomes , to demonstrate the equivalence of the two regimens , the results showed statistically significant higher clinical success rates ( for moxifloxacin , 93.4 % , and for comparator regimen , 85.4 % ; difference [ Δ ] , 8.05 % ; 95 % confidence interval [ CI ] , 2.91 to 13.19 % ; P = 0.004 ) and bacteriological success rates ( for moxifloxacin , 93.7 % , and for comparator regimen , 81.7 % ; Δ , 12.06 % ; 95 % CI , 1.21 to 22.91 % ) for patients treated with moxifloxacin . This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide . The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin ( median time , 2 versus 3 days ) , and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin . The treatment was converted to oral therapy immediately after the initial m and atory 3-day period of i.v . administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group ( 151 [ 50.2 % ] versus 57 [ 17.8 % ] patients ) . There were fewer deaths ( 9 [ 3.0 % ] versus 17 [ 5.3 % ] ) and fewer serious adverse events ( 38 [ 12.6 % ] versus 53 [ 16.5 % ] ) in the moxifloxacin group than in the comparator group . The rates of drug-related adverse events were comparable in both groups ( 38.9 % in each treatment group ) . The overall incidence of laboratory abnormalities was similar in both groups . Thus , it is concluded that monotherapy with moxifloxacin is superior to that with a st and ard combination regimen of a β-lactam and a β-lactamase inhibitor , co-amoxiclav , with or without a macrolide , clarithromycin , in the treatment of patients with community-acquired pneumonia admitted to a hospital Low-dose methylprednisolone and antibiotics were used to treat 30 patients with aspiration pneumonia , in a prospect i ve , r and omized , double-blind trial with placebo control . All patients received clindamycin phosphate 1200 mg per day . In addition , 15 patients received methylprednisolone 20 mg per day for three days and the other 15 patients received placebo according to the same schedule . In the methyl prednisolone group , CRP had decreased ( p < 0.05 ) from 12.7 + /- 9.8 to 6.4 + /- 5.4 mg/dl day 4 , neutrophil elastase had decreased ( p < 0.05 ) from 402 + /- 304 to 231 + /- 64 micrograms/dl by day 4 and to 184 + /- 59 micrograms/dl by day 7 , maximum body temperature had decreased ( p < 0.01 ) from 37.9 + /- 1.1 to 36.8 + /- 0.6 degrees C by day 7 , and the pneumonia score had improved ( p < 0.01 ) from 11.8 + /- 3.0 to 8.6 + /- 2.4 by day 4 . In the placebo group , there were no significant improvements by those days . We conclude that low-dose methylprednisolone therapy with antibiotics is effective against aspiration pneumonia The aim of the study was to assess the potential role of glucocorticoids ( GC ) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia . Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit ( RICU ) of a 1,000-bed teaching hospital were prospect ively studied . All patients had received prior antimicrobial treatment . Eleven patients received GC ( mean+/-SD dose of i.v . methylprednisolone 677+/-508 mg for 9+/-7 days ) , mainly for bronchial dilatation . Serum and bronchoalveolar lavage fluid ( BALF ) tumour necrosis factor (TNF)-alpha , interleukin (IL)-1beta , IL-6 and C-reactive protein levels were measured in all patients . The inflammatory response was attenuated in patients receiving GC , both systemically ( IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1 ) , p=0.03 ; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1 ) , p=0.04 ) and locally in BALF ( TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1 ) , p= 0.05 ; neutrophil count : 2.4+/-1.1 x 10(9 ) cells x L(-1 ) ( 93+/-3 % ) versus 1.9+/-1.8 x 10(9 ) cells x L(-1 ) ( 57+/-16 % ) , p=0.03 ) . Four of the 11 ( 36 % ) patients receiving GC died compared to six ( 67 % ) who were not receiving GC ( p=0.37 ) . The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment BACKGROUND Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy . There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia . DESIGN AND METHODS This was an uncontrolled retrospective and prospect i ve study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996 . Patient demographics , clinical and laboratory features , necessity for mechanical ventilation , and complications were review ed . The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids . Patients with comorbid disease and those already taking immunosuppressive agents were excluded . Key endpoints included length of ICU and hospital stay and mortality . MEASUREMENTS AND RESULTS Fifteen adult patients were evaluated , six of whom received corticosteroids in addition to antiviral and supportive therapy . These six patients demonstrated a clinical ly significant therapeutic response . They had significantly shorter hospital ( median difference , 10 days ; p<0.006 ) and ICU ( median difference , 8 days ; p=0.008 ) stays and there was no mortality , despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients ( n=9 ) who did not receive corticosteroid therapy ( 86.5 vs 129.5 ; p=0.045 ) . CONCLUSION When used in addition to appropriate supportive care and early institution of antiviral therapy , corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia . The observations presented in this study are important and should form the basis for a r and omized controlled trial , as no other relevant studies or guidelines are available A cooperative study at three children 's hospitals was devised to evaluate the efficacy of adrenocorticosteroid treatment in hydrocarbon pneumonitis of children . The drug used was methylprednisolone , and the study design was double-blind controlled . Seventy-one patients were completely studied . No differences were demonstrated between the groups when comparisons were made for the number of days with abnormal temperature , abnormal respiratory rate , abnormal pulse , and the number of days of hospitalization . Similarly , no differences were discernible when the subjective assessment of the patients morbidity rate and the radiographic changes were analyzed . Only three patients in the group were classified as having a severe pneumonitis ; there were no deaths . Although mostly mild and moderate cases of hydrocarbon pneumonitis were evaluated in the present investigation , the results do not support the use of adrenocorticosteroids in the treatment of this condition |
13,043 | 22,258,971 | AUTHORS ' CONCLUSIONS In summary , the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL .
No statistically significant differences in terms of OS , TRM and secondary cancers were detected .
Moreover , longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL.There is evidence that HDT + ASCT is advantageous in patients with relapsed FL | BACKGROUND Follicular lymphoma ( FL ) is the most common indolent and second most common Non-Hodgkin`s lymphoma ( NHL ) in the Western world .
St and ard treatment usually includes rituximab and chemotherapy .
High-dose therapy ( HDT ) followed by autologous stem cell transplantation ( ASCT ) is an option for patients in advanced stages or for second-line therapy , leading to improved progression-free survival ( PFS ) rates .
However , the impact of HDT and ASCT remains unclear , as there are hints of an increased risk of second cancers .
OBJECTIVES We performed a systematic review with meta- analysis of r and omised controlled trials ( RCTs ) comparing HDT plus ASCT with chemotherapy or immuno-chemotherapy in patients with FL with respect to overall survival ( OS ) , PFS , treatment-related mortality ( TRM ) , adverse events and secondary malignancies . | PURPOSE To assess myeloablative therapy with autologous bone marrow transplantation ( ABMT ) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival . PATIENTS AND METHODS Since June 1985 , 64 patients with follicular lymphoma have received cyclophosphamide ( CY ) 60 mg/kg x 2 and total-body irradiation ( TBI ) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission . The marrow mononuclear cell ( MNC ) fraction was treated in vitro with three cycles of the monoclonal antibody ( MAb ) anti-CD20 and baby rabbit complement before cryopreservation . At the time of treatment , 34 patients were in complete remission ( CR ) , and 30 had residual disease present . RESULTS The median time to engraftment was 28 days ( range , 15 to 46 ) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks , and three patients ( excluded from the range ) have had delayed recovery ( > 6 months ) of RBCs and platelets . Fifty two patients are alive ; three died as a consequence of the transplant procedure , two died in remission from other causes , and seven died of recurrent lymphoma . There was a significant correlation between survival and the total number of episodes of treatment required during the course of the illness ( < or = to three v > three , P = .01 ) . With a median follow-up duration of 3 1/2 years , 35 patients continue in remission between 1 and 8 years , and 24 have developed recurrent lymphoma , five with evidence of transformation to high- grade histology . Freedom from recurrence did not correlate with the time from diagnosis , the number of previous treatments , the presence or absence of residual disease at the time of treatment , or during which specific remission the treatment was given ( second v > second ) . However , comparison with an age-matched , remission-matched , historical control group shows a significant advantage in favor of treatment with CY plus TBI plus ABMT ( P = .001 ) ; currently , there is no difference in survival . CONCLUSION These results are encouraging , although preliminary ; it remains to be established whether this treatment prolongs survival Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma ( FL ) when it is added to chemotherapy . In the current study , 428 patients with untreated , advanced-stage FL were r and omly assigned for therapy with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) alone ( n = 205 ) or CHOP combined with rituximab ( R-CHOP ) ( n = 223 ) . R-CHOP reduced the relative risk for treatment failure by 60 % and significantly prolonged the time to treatment failure ( P < .001 ) . In addition , a significantly higher overall response rate ( 96 % vs 90 % ; P = .011 ) and a prolonged duration of remission ( P = .001 ) were achieved . In spite of a relatively short observation time , these beneficial effects even translated to superior overall survival ( P = .016 ) , with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years . The predominant treatment-related adverse effect was myelosuppression . Severe granulocytopenia was more frequently observed after R-CHOP ( 63 % vs 53 % ; P = .01 ) . However , severe infections were rare and of similar frequency after R-CHOP and CHOP ( 5 % and 7 % ) . Hence , adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been design ed to exploit the graft-versus-lymphoma immunity . The long-term effectiveness and toxicity of this strategy , however , is unknown . In this prospect i ve study , we analyzed our 8-year experience . Patients received a conditioning regimen of fludarabine ( 30 mg/m(2 ) daily for 3 days ) , cyclophosphamide ( 750 mg/m(2 ) daily for 3 days ) , and rituximab ( 375 mg/m(2 ) for 1 day plus 1000 mg/m(2 ) for 3 days ) . They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related ( n = 45 ) or unrelated donors ( n = 2 ) . Tacrolimus and methotrexate were used for graft-versus-host disease ( GVHD ) prophylaxis . Forty-seven patients were included . All patients experienced complete remission , with only 2 relapses . With a median follow-up time of 60 months ( range , 19 - 94 ) , the estimated survival and progression-free survival rates were 85 % and 83 % , respectively . All 18 patients who were tested and had evidence of JH/bcl-2 fusion transcripts in the bone marrow at study entry experienced continuous molecular remission . The incidence of grade 2-IV acute GVHD was 11 % . Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up . We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma BACKGROUND We compared a regimen of six chemotherapeutic agents administered sequentially at high doses , followed by myeloablative treatment and bone marrow transplantation , with a regimen of methotrexate , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ) as initial or salvage treatment for adults with diffuse large-cell lymphoma . METHODS Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were r and omly assigned to receive either MACOP-B ( 50 patients ) or high-dose sequential therapy ( 48 patients ) . The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group . RESULTS After a median follow-up of 55 months , the patients given high-dose sequential therapy , as compared with those treated with MACOP-B , had significantly higher rates of complete response ( 96 percent vs. 70 percent , P=0.001 ) , freedom from disease progression ( 84 percent vs. 49 percent , P<0.001 ) , freedom from relapse ( 88 percent vs. 70 percent , P=0.055 ) , and event-free survival ( 76 percent vs. 49 percent , P=0.004 ) . The difference in overall survival at seven years , which also favored the group assigned to high-dose sequential therapy , was marginally significant ( 81 percent vs. 55 percent , P=0.09 ) . CONCLUSIONS High-dose sequential therapy is superior to st and ard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type Myeloablative radio-chemotherapy with subsequent autologous stem cell transplantation ( ASCT ) significantly prolongs progression free and probably overall survival in follicular lymphoma ( FL ) in first remission . The current trial explored prospect ively the rate of successful stem cell mobilization in patients with advanced stage FL after initial therapy with either Mitoxantrone , Chlorambucil , Prednisone ( MCP ) or Cyclophosphamide , Doxorubicin , Vincristine , Prednisone ( CHOP ) as part of a prospect i ve r and omized comparison of both regimens . ASCT patients received Dexa-BEAM ( Dexamethasone , BCNU , Melphalan , Etoposide , Cytarabine ) for mobilization of stem cells . Stem cells were collected and a minimum of 2x2.0x106/kg bw CD34 + was required for ASCT . Of 79 evaluable patients , 58 ( 73 % ) had follicular lymphoma , 13 ( 16 % ) mantle cell lymphoma and 8 ( 10 % ) lymphoplasmacytic lymphoma . In the 45 patients assigned to CHOP , stem cell collection was successful in 42 cases ( 93 % , 95 % CI 82 % to 99 % ) . This high mobilization rate after CHOP could be confirmed in 61 subsequent patients ( 87 % ) . In contrast , after MCP therapy stem cell collection was successful in only 15 of 34 patients ( 44 % , 95 % CI 27 % to 62 % ; P=0.0003 ) . In conclusion , initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided for first line therapy of younger patients potentially qualifying for high dose consolidation and ASCT in first remission We evaluated the role of rituximab ( R ) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma ( FL ) . A total of 465 patients were r and omized to induction with 6 cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) ( every 3 weeks ) or R-CHOP ( R : 375 mg/m(2 ) intravenously , day 1 ) . Those in complete remission ( CR ) or partial remission ( PR ) were r and omized to maintenance with R ( 375 mg/m(2 ) intravenously once every 3 months for a maximum of 2 years ) or observation . R-CHOP induction yielded an increased overall response rate ( CHOP , 72.3 % ; R-CHOP , 85.1 % ; P < .001 ) and CR rate ( CHOP , 15.6 % ; R-CHOP , 29.5 % ; P < .001 ) . Median progression-free survival ( PFS ) from first r and omization was 20.2 months after CHOP versus 33.1 months after R-CHOP ( hazard ratio [ HR ] , 0.65 ; P < .001 ) . Rituximab maintenance yielded a median PFS from second r and omization of 51.5 months versus 14.9 months with observation ( HR , 0.40 ; P < .001 ) . Improved PFS was found both after induction with CHOP ( HR , 0.30 ; P < .001 ) and R-CHOP ( HR , 0.54 ; P = .004 ) . R maintenance also improved overall survival from second r and omization : 85 % at 3 years versus 77 % with observation ( HR , 0.52 ; P = .011 ) . This is the first trial showing that in relapsed/resistant FL rituximab maintenance considerably improves PFS not only after CHOP but also after R-CHOP induction In this r and omized multicenter study of 136 patients , 6 courses of CHOP ( cyclo-phosphamide/doxorubicin/vincristine/prednisone ) followed by rituximab ( CHOP-R ) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting ( R-HDS ) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma ( FL ) after the introduction of monoclonal antibodies . The analysis was intention to treat with event-free survival ( EFS ) as the primary endpoint . Complete remission ( CR ) was 62 % with CHOP-R and 85 % with R-HDS ( P < .001 ) . At a median follow-up ( MFU ) of 51 months , the 4-year EFS was 28 % and 61 % , respectively ( P < .001 ) , with no difference in overall survival ( OS ) . Molecular remission ( MR ) was achieved in 44 % of CHOP-R and 80 % of R-HDS patients ( P < .001 ) , and was the strongest independent outcome predictor . Patients relapsing after CHOP-R underwent salvage R-HDS in 71 % of cases . Salvage R-HDS had an 85 % CR rate and a 68 % 3-year EFS ( MFU , 30 months ) . We conclude that ( 1 ) achieving MR is critical for effective disease control , regardless of which treatment is used ; ( 2 ) R-HDS ensures superior disease control and molecular outcome than CHOP-R , but no OS improvement ; and ( 3 ) CHOP-R failures have a good outcome after salvage R-HDS , suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments . This trial was registered at www . clinical trials.gov as no. NCT00435955 Conventional chemotherapy has failed to substantially prolong survival for patients with advanced follicular lymphoma . To improve outcomes , the German Low- Grade Lymphoma Study Group ( GLSG ) initiated a r and omized trial to compare the effect of potentially curative myeloablative radiochemotherapy followed by autologous stem cell transplantation ( ASCT ) with interferon-alpha ( IFN-alpha ) maintenance therapy in first remission . Three hundred seven patients ( younger than 60 years ) with follicular lymphoma were recruited into the trial from 130 institutions . After 2 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone ( CHOP ) or mitoxantrone-chlorambucil-prednisone ( MCP ) induction chemotherapy , patients were r and omly assigned to either the ASCT or the IFN-alpha group . The respective therapy was started when patients achieved complete or partial remission after induction chemotherapy . Two hundred forty patients with follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha . In patients who underwent ASCT , the 5-year progression-free survival ( PFS ) rate was 64.7 % , and in the IFN-alpha arm it was 33.3 % ( P < .0001 ) . As expected , acute toxicity was higher in the ASCT group , but early mortality was below 2.5 % in both study arms . In this r and omized , multicenter trial , high-dose radiochemotherapy followed by ASCT significantly improved PFS compared with IFN-alpha in patients with follicular lymphoma when applied as consolidation in first remission . Longer follow-up is necessary to determine the effect of ASCT on overall survival BACKGROUND High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin 's lymphoma who have relapses . In this report we describe a prospect i ve r and omized study of such treatment . METHOD A total of 215 patients with relapses of non-Hodgkin 's lymphoma were treated between July 1987 and June 1994 . All patients received two courses of conventional chemotherapy . The 109 patients who had a response to chemotherapy were r and omly assigned to receive four courses of chemotherapy plus radiotherapy ( 54 patients ) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation ( 55 patients ) . RESULTS The overall rate of response to conventional chemotherapy was 58 percent ; among patients with relapses after chemotherapy , the response rate was 64 percent , and among those with relapses during chemotherapy , the response rate was 21 percent . There were three deaths from toxic effects among the patients in the transplantation group , and none among those in the group receiving chemotherapy without transplantation . The two groups did not differ in terms of prognostic factors . The median follow-up time was 63 months . The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation . At five years , the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation ( P = 0.001 ) , and the rate of overall survival was 53 and 32 percent , respectively ( P = 0.038 ) . CONCLUSIONS As compared with conventional chemotherapy , treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin 's lymphoma in relapse It is unclear whether new treatment modalities have improved the survival of follicular lymphoma patients . Some data show that there has been no improvement in survival in the last 3 decades of the 20th century , whereas the results of recent retrospective studies suggest that evolving therapy has improved the outcome for follicular lymphoma patients BACKGROUND Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low- grade non-Hodgkin lymphomas , even when combined with radiotherapy . Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use , in asymptomatic patients with advanced-stage , low- grade non-Hodgkin lymphoma . METHODS 309 patients with asymptomatic , advanced-stage , low- grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1 , 1981 , and July 31 , 1990 . 158 patients were r and omised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously . The remaining 151 were r and omised to an initial policy of observation , with systemic therapy delayed until disease progression . In both groups , local radiotherapy to symptomatic nodes was allowed . FINDINGS Median length of follow-up was 16 years . Overall survival or cause-specific survival did not differ between the two groups ( median overall survival for oral chlorambucil 5.9 [ range 0 - 17.8 ] years and for observation 6.7 [ 0.5 - 18.9 ] years , p=0.84 ; median cause-specific survival 9 [ 0 - 17.8 ] years and 9.1 [ 0.67 - 18.9 ] years , respectively p=0.44 ) . In a multivariate analysis , age younger than 60 years , erythrocyte sedimentation rate ( ESR ) 20 mm/h or less , and stage III disease , conferred significant advantages in both overall survival ( p<0.0001 , 0.03 , and 0.03 , respectively ) and cause-specific survival ( p=0.002 , 0.008 , and 0.001 , respectively ) . In the observation group , at 10 years ' follow-up , 19 patients were alive and had not received chemotherapy . The actuarial chance of not needing chemotherapy ( non-lymphoma deaths censored ) at 10 years was 19 % ( 40 % if older than 70 years ) . INTERPRETATION An initial policy of watchful waiting in patients with asymptomatic , advanced stage low- grade non-Hodgkin lymphoma is appropriate , especially in patients older than age 70 years Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma ( FCL ) at diagnosis , whereas data from prospect i ve multicenter trials are still lacking . This paper describes the results of a prospect i ve multicenter study of an intensified purging-free high-dose sequential ( i-HDS ) chemotherapy schedule with peripheral blood progenitor cell ( PBPC ) autografting . The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking , with no ex vivo manipulation of PBPCs . Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis . i-HDS proved feasible with limited toxicity ( 87 % patients completed the planned treatment schedule ) . i-HDS led to a complete remission rate of 88 % . The projected overall survival and disease-free survival ( DFS ) were , respectively , 84 % and 67 % at 4 years . Central ized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47 % of cases . Following autograft , 65 % of molecularly evaluable patients achieved clinical and molecular remission . The projected DFS at 4 years of this subgroup is 85 % . This result emphasizes the importance of achieving maximal tumor reduction in these patients . In conclusion , our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions , with no need for sophisticated and expensive cell manipulation procedures PURPOSE Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin 's lymphoma . In 1987 , we design ed a r and omized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide , carmustine , and etoposide ( CBV ) followed by autotransplantation over a consolidative sequential chemotherapy ( ifosfamide , etoposide , asparaginase , and cytarabine ) in patients in first complete remission with intermediate- and high- grade non-Hodgkin 's lymphoma . PATIENTS AND METHODS Patients were younger than 55 years and had at least one adverse prognostic factor . Induction treatment was that of the LNH84 protocol with an open r and omization on the anthracycline . Patients in complete remission were further r and omly assigned to receive either consolidation procedure . RESULTS After induction treatment , 464 patients were assessable for the consolidation phase . With a median follow-up duration of 28 months , the 3-year disease-free survival rate was 52 % ( 95 % confidence interval , 45 % to 59 % ) in the sequential chemotherapy arm and 59 % ( 95 % confidence interval , 52 % to 66 % ) in the autologous transplant arm ( P = .46 , relative risk = 0.90 ) . The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation , at 71 % ( 95 % confidence interval , 64 % to 78 % ) and 69 % ( 95 % confidence interval , 62 % to 76 % ) , respectively ( P = .60 , relative risk = 1.11 ) . CONCLUSION For such a subset of patients , consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy PURPOSE To determine whether a combination of high-dose therapy and autologous stem-cell transplantation ( ASCT ) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma . PATIENTS AND METHODS One hundred nineteen patients were entered onto this prospect i ve r and omized trial from 37 centers . Patients received st and ard remission induction therapy , and responding patients were r and omized either to continue with a conventional consolidation/maintenance protocol ( CC ) or to receive high-dose therapy and ASCT . In some centers , patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation ( BMT ) without r and omization . RESULTS Of the 119 patients entered , 111 were assessable for response to induction therapy . The overall response rate was 82 % ( 56 % complete response , 26 % partial response ) . Of the 98 patients eligible for r and omization , 65 were r and omized , 31 to ASCT and 34 to CC . Reasons for failure to r and omize included patient refusal ( 12 patients ) , early progression or death on induction therapy ( eight patients ) , excessive toxicity of induction regimen ( six patients ) , and elective allogeneic BMT ( 12 patients ) . With a median follow-up of 37 months , the actuarial 3-year relapse-free survival rate is 24 % for the CC arm and 55 % for the ASCT arm ( hazards ratio = 0.55 in favor of the ASCT arm ; 95 % confidence interval [ CI ] , 0.29 to 1.04 ; P = .065 ) . The corresponding figures for overall survival are 45 % and 56 % , respectively ( hazards ratio = 0.87 in favor of the ASCT arm ; 95 % CI , 0.42 to 1.81 ; P = .71 ) . CONCLUSION The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small r and omized trial BACKGROUND The long-term outcome for patients with aggressive non-Hodgkin 's lymphoma ( NHL ) is poor . Consequently , the European Organization for Research and Treatment of Cancer Lymphoma Group design ed a prospect i ve r and omized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation ( ABMT ) after st and ard combination chemotherapy improves long-term survival . METHODS Patients aged 15 - 65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy ( i.e. , a combination of cyclophosphamide , doxorubicin , teniposide , and prednisone , with bleomycin and vincristine added at mid-cycle ) . After these three cycles , patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were r and omly assigned to the ABMT arm ( a further three cycles of CHVmP/BV followed by BEAC [ i.e. , a combination of carmustine , etoposide , cytarabine , and cyclophosphamide ] chemotherapy and ABMT ) or to the control arm ( five more cycles of CHVmP/BV ) . All statistical tests are two-sided . RESULTS From December 1990 through October 1998 , 311 patients ( median age = 44 years ) were registered and received the first three cycles of CHVmP/BV , and 194 patients were r and omly assigned to the treatment arms . Approximately 70 % ( 140 patients ) of these patients were of low or low-intermediate International Prognostic Index ( IPI ) risk . After a median follow-up of 53 months , an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61 % ( 95 % confidence interval [ CI ] = 51 % to 72 % ) and 68 % ( 95 % CI = 57 % to 79 % ) , respectively , for the ABMT arm and 56 % ( 95 % CI = 45 % to 67 % ) and 77 % ( 95 % CI = 67 % to 86 % ) , respectively , for the control arm . Differences between arms were not statistically significant . A subset analysis on IPI risk groups , although too small for reliable statistical analysis , yielded similar results . CONCLUSIONS St and ard combination therapies remain the best choice for most patients with aggressive NHL . We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy BACKGROUND There is not univocal concordance for using high-dose sequential therapy ( HDS ) as first-line treatment for aggressive non-Hodgkin 's lymphoma ( NHL ) . We design ed this study to evaluate the usefulness of HDS followed by high-dose therapy ( HDT ) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL . PATIENTS AND METHODS Among 223 patients aged 15 - 60 years with aggressive , advanced stage NHL , 106 patients were r and omized to VACOP-B ( etoposide , doxorubicin , cyclophosphamide , vincristine , prednisone , bleomycin ) for 12 weeks ( plus HDS/HDT in case of persistent disease ) ( arm A ) , and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT ( arm B ) . RESULTS According to the intention-to-treat analysis , the complete response rate was 75 % for arm A and 72.6 % for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival ( 60 % and 57.8 % ; P = 0.5 ) , disease-free survival ( DFS ) ( 62 % and 71 % ; P = 0.2 ) and progression-free survival ( PFS ) ( 44.9 % and 40.9 % ; P = 0.7 ) between the two arms . Subgroup analyses confirmed that the best results in terms of survival , DFS and PFS were achieved by patients with large B-cell NHL without bone marrow ( BM ) involvement , independently of the treatment arm . Results were poorer in other categories of patients and poorest in patients with BM involvement . CONCLUSIONS Aggressive NHL patients do not benefit from upfront HDS/HDT With currently available combination chemotherapy regimens , the outcome of the patients newly diagnosed with aggressive non-Hodgkin 's lymphoma ( NHL ) identified as ‘ high ’ and ‘ high-intermediate ’ risk groups according to the international prognostic index ( IPI ) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients . The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisone ) and ESHAP ( etoposide , methylprednisolone , high-dose Ara-C , cisplatin ) vs CHOP-ESHAP and upfront high-dose therapy ( HDT ) and autologous stem cell transplantation ( ASCT ) vs st and ard CHOP in patients aged ≤65 years old newly diagnosed with ‘ high ’ and ‘ high-intermediate ’ risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute . Between May 1995 – July 2002 , 84 patients , aged 15 – 65 years old , with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled . The median age of the patients was 38 years ( range 15 – 65 ) . The baseline demographic features , in particular the major prognostic variables , were similar between the treatment groups . Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab ( 375 mg m−2 on day 1 of cycles 1 – 6 and days 21 and 28 of cycle 7 ) plus CHOP ( day 3 of cycles 1 , 3 and 5 ) and ESHAP ( day 3 of cycles 2 , 4 and 6 and day 1 of cycle 7 ) at 21-day intervals . Patients enrolled onto the CHOP-ESHAP-HDT arm ( n = 23 ) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT . Patients treated with CHOP alone ( n = 25 ) were treated with the st and ard eight cycles of CHOP . The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone ( 67 % compared with 44 % and 36 % , respectively ; p = 0.043 ) . With a median follow-up time of 53 months , the 5-year overall survival ( OS ) was improved by the addition of rituximab—61 % with rituximab-CHOP-ESHAP , compared with 43 % for CHOP-ESHAP-HDT and 24 % for CHOP alone ( p = 0.088 ) . Significant increases in failure-free survival ( FFS ) and disease-free survival ( DFS ) ( 61 % and 96 % ) , compared with CHOP-ESHAP-HDT ( 34 % and 90 % ) and CHOP ( 16 % and 44 % ; p = 0.002 and p < 0.001 , respectively ) were observed . Compared to CHOP , rituximab-CHOP-ESHAP yielded significantly superior OS ( p = 0.014 ) , FFS ( p < 0.001 ) and DFS ( p < 0.001 ) . The survivals , however , were not significantly different from patients treated with CHOP-ESHAP-HDT . It is concluded that rituximab-ESHAP-CHOP is superior over st and ard CHOP and fares comparably to upfront HDT/ASCT in previously untreated patients with aggressive lymphoma . A prospect i ve r and omized controlled trial is warranted to confirm these results PURPOSE The aim of this multicenter r and omized study was to compare conventional therapy with conventional plus high-dose therapy ( HDT ) and autologous bone marrow transplantation ( ABMT ) as front-line treatment for poor-prognosis non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Between October 1991 and June 1995 , 124 patients , aged 15 to 60 years , with diffuse intermediate- to high- grade NHL ( Working Formulation criteria ) , stages II bulky ( > or = 10 cm ) , III , or IV were enrolled . Sixty-one patients were r and omized to receive etoposide , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( VACOP-B ) for 12 weeks and cisplatin , cytarabine , and dexamethasone ( DHAP ) as a salvage regimen ( arm A ) , and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT ( Arm B ) . RESULTS There was no significant difference in terms of complete remissions ( CRS ) in the two groups : 75 % in arm A , and 73 % in arm B. The median follow-up observation time was 42 months . The 6-year survival probability was 65 % in both arms . There was no difference in disease-free survival ( DFS ) or progression-free survival ( PFS ) between the two groups . DFS was 60 % and 80 % ( P = .1 ) and PFS was 48 % and 60 % ( P = .4 ) for arms A and B , respectively . Procedure feasibility was the major problem . In arm B , 29 % of enrolled patients did not undergo HDT and ABMT . A statistical improvement in terms of DFS ( P = .008 ) and a favorable trend in terms of PFS ( P = .08 ) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed . CONCLUSION In this study , conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results . However , our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients This study provides an up date d report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified , purging-free , total body irradiation-free , high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft ( i-HDS ) in advanced-stage follicular lymphoma ( FL ) . Special interest has been devoted to late toxicities and outcome in terms of molecular status . Ninety-two untreated FL patients aged ⩽60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis . Main findings are as follows : ( 1 ) 5.5-years overall survival projection of 80 % ( median follow-up : 68 months ) , with no differences related to age-adjusted IPI score ; ( 2 ) 46 ( 50 % ) of 92 patients presently in continuous complete remission ; ( 3 ) projected long-term progression-free survival exceeding 80 % for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy ; ( 4 ) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7 % , with most of these events occurring in patients re-treated for recurrent lymphoma . These results demonstrate that i-HDS is feasible , effective and safe even in terms of long-term outcome . As the HDS schedule can be easily supplemented with Rituximab , it is one of the best options for r and om comparison with Rituximab-supplemented conventional chemotherapy The combination of cyclophosphamide , vincristine , and prednisone ( CVP ) is one of several st and ard treatment options for advanced follicular lymphoma . This , like similar chemotherapeutic regimens , induces response rates of 60 % to 80 % , with a median response duration of under 2 years . Rituximab , a chimeric monoclonal antibody against CD20 , is active in follicular lymphoma , both as monotherapy and in combination with chemotherapy . Previously untreated patients with stages III to IV follicular lymphoma were r and omly assigned to receive either 8 cycles of CVP plus rituximab ( R-CVP ; n = 162 ) or CVP ( n = 159 ) . Overall and complete response rates were 81 % and 41 % in the R-CVP arm versus 57 % and 10 % in the CVP arm , respectively ( P < .0001 ) . At a median follow-up of 30 months , patients treated with R-CVP had a very significantly prolonged time to progression ( median 32 months versus 15 months for CVP ; P < .0001 ) . Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm ( P < .0001 ) . Rituximab did not add significantly to the toxicity of CVP . The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma , without increased toxicity PURPOSE An increased risk of therapy-related myelodysplastic syndrome ( t-MDS ) and acute myeloid leukemia ( t-AML ) after high-dose therapy and autologous stem-cell transplantation ( ASCT ) for malignant lymphoma has been described by several studies , reporting a highly variable incidence ranging from 1 % to 12 % . To assess this risk more precisely , the German Low Grade Lymphoma Study Group investigated the incidence of t-MDS/t-AML after ASCT on the basis of a r and omized comparison of ASCT versus interferon alfa ( IFN-alpha ) maintenance in indolent lymphoma . PATIENTS AND METHODS Between 1996 and 2002 , 440 patients with indolent lymphoma were r and omly assigned after a cyclophosphamide , doxorubicin , vincristine , and prednisone-like induction therapy regimen to myeloablative radiochemotherapy followed by ASCT or IFN-alpha . The incidence of secondary hematologic malignancies was determined by st and ardized follow-up of all study patients . Bone marrow sample s from patients with proven or suspected t-MDS/t-AML were central ly review ed . RESULTS After a median follow-up of 44 months , 431 patients were assessable . Five of 195 patients developed a secondary hematologic malignancy after ASCT . Two of these patients developed a secondary AML . Accordingly , the estimated 5-year risk for secondary hematologic neoplasias after ASCT was 3.8 % . In contrast , in the IFN-alpha arm , the 5-year risk of hematologic neoplasias was 0.0 % ( P = .0248 ) . CONCLUSION The data of this r and omized trial demonstrate an increased risk of secondary hematologic malignancies after myeloablative radiochemotherapy and ASCT compared with conventional chemotherapy . However , as ASCT significantly improves progression-free survival , it is currently not evident to what extent the higher rate of t-MDS/t-AML will diminish the benefit of ASCT in indolent lymphoma PURPOSE The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy ( HDT ) with autologous stem-cell transplant then with rituximab . The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared . PATIENTS AND METHODS We analyzed two cohorts of patients treated in two successive r and omized studies with the same treatment , cyclophosphamide , doxorubicin , teniposide , and prednisolone plus interferon , to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse . RESULTS Of the 364 patients included in these two studies , 254 progressed or relapsed and constitute the population of this analysis . Among them , 98 had been treated with HDT , including 33 of them after rituximab-containing salvage regimen , and 69 with rituximab alone or combined with chemotherapy but without HDT . Patients ' characteristics at diagnosis were similar in all subgroups . If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires ( GELF ) -86 or GELF-94 studies , overall survival was longer in GELF-94 study . HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse ( SAR ) . Rituximab was associated with a greater benefit than HDT for these two end points . When both treatments were combined , patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90 % . CONCLUSION In follicular lymphoma , for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome The clinical activity of rituximab , a chimeric monoclonal antibody which binds to the CD20 antigen , was evaluated as a single first-line therapy for patients with follicular non-Hodgkin lymphoma ( NHL ) . Fifty patients with follicular CD20(+ ) NHL and a low tumor burden were analyzed for clinical and molecular responses . They received 4 weekly infusions of rituximab at a dose of 375 mg/m(2 ) . The response rate a month after treatment ( day 50 ) was 36 of 49 ( 73 % ) , with 10 patients in complete remission , 3 patients in complete remission/unconfirmed , and 23 patients in partial remission . Ten patients had stable disease , and the disease progressed in 3 patients . One of 13 ( 8 % ) patients in complete remission , 9 of 23 ( 39 % ) patients in partial remission , and 5 of 10 ( 50 % ) patients with stable disease exhibited disease progression during the first year . Within the study population , 32 patients were initially informative for polymerase chain reaction ( PCR ) data on bcl-2-J(H ) rearrangement . On day 50 , 17 of 30 patients ( 57 % ) were negative for bcl-2-J(H ) rearrangement in peripheral blood , and 9 of 29 ( 31 % ) were negative in bone marrow ; a significant association was observed between molecular and clinical responses ( P < .0001 ) . At month 12 , 16 of 26 patients ( 62 % ) were PCR negative in peripheral blood . These results indicate that early molecular responses can be sustained for up to 12 months and that this response is highly correlated with progression-free survival . Rituximab has a high clinical activity and a low toxicity and induces a high complete molecular response rate in patients with follicular lymphoma and a low tumor burden Doxorubicin-based immunochemotherapy , with interferon , has been shown to improve survival in patients with advanced follicular lymphoma . High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy . In a r and omized study using a purged autologous stem-cell support , we compared these 2 approaches in patients with advanced follicular lymphoma . Newly diagnosed advanced follicular lymphoma patients ( 172 patients ) were r and omly assigned either to an immunochemotherapy regimen ( cyclophosphamide , doxorubicin , teniposide , prednisone , and interferon ) or to a high-dose therapy followed by purged autologous stem-cell transplantation . Compared with the patients who received chemotherapy and interferon , patients treated with high-dose therapy had a higher response rate ( 69 % vs 81 % , P = .045 ) and a longer median event-free survival ( not reached vs 45 months ) . This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation . The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy . Autologous stem-cell transplantation can not be considered as the st and ard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden PURPOSE Rituximab has been shown to be active in follicular lymphoma ( FL ) , both as monotherapy and in combination with chemotherapy . We conducted a r and omized trial comparing mitoxantrone , chlorambucil , and prednisolone ( MCP ) chemotherapy plus rituximab with MCP alone . PATIENTS AND METHODS Previously untreated patients with stage III or IV CD20 + indolent or mantle cell lymphoma were r and omly assigned to either eight 28-day cycles of MCP plus rituximab ( R-MCP ; n = 181 ) or eight cycles of MCP alone ( n = 177 ) . All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse . Herein , we report the results from the primary analysis population of patients with FL , who constituted the majority of patients ( 56 % ) recruited to the trial ( n = 201 ; R-MCP , n = 105 ; MCP , n = 96 ) . RESULTS Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm ( overall response , 92 % v 75 % , respectively ; P = .0009 ; complete response , 50 % v 25 % , respectively ; P = .004 ) . With a median follow-up time of 47 months , median event-free survival ( EFS ) and progression-free survival ( PFS ) times were significantly prolonged with R-MCP compared with MCP ( EFS , not reached v 26 months , respectively ; P < .0001 ; PFS , not reached v 28.8 months , respectively ; P < .0001 ) , and overall survival ( OS ) was significantly improved with R-MCP compared with MCP ( 4-year OS rate , 87 % v 74 % , respectively ; P = .0096 ) . CONCLUSION The R-MCP regimen significantly improves complete and overall response rates , EFS , PFS , and OS in patients with previously untreated advanced FL , without a clinical ly significant increase in toxicity PURPOSE To up date the r and omized study that compared consolidative sequential treatment ( ifosfamide , etoposide , asporaginase , and cytarabine ) versus the high-dose regimen of cyclophosphamide , carmustine , and etoposide ( CBV ) followed by autotransplantation in patients with aggressive non-Hodgkin 's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index . PATIENTS AND METHODS Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open r and omization for the anthracycline . In a subsequent r and omization , 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy ( n = 273 ) or autotransplant ( n = 268 ) . Among the higher risk population ( two or three risk factors ) , 236 patients in complete remission were assessable for the consolidation phase , with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm . RESULTS Among 541 r and omized patients , disease-free survival and survival did not differ significantly between the two consolidative treatment arms . In the higher risk population , CBV was superior to sequential chemotherapy , with 5-year disease-free survival rates of 59 % ( 95 % confidence interval , 49 % to 69 % ) and 39 % ( 95 % confidence interval , 28 % to 50 % ) , respectively ( P = .01 , relative risk = 1.19 ) . The 5-year survival rate was superior in the CBV group at 65 % ( 95 % confidence interval , 56 % to 74 % ) compared with 52 % in the sequential chemotherapy group ( 95 % confidence interval , 42 % to 62 % ) ( P = .06 , relative risk = 1.49 ) . CONCLUSION This study shows a superior disease-free survival for higher risk patients in complete remission . Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment BACKGROUND The CUP trial was initiated to analyze the value of high-dose therapy and stem-cell transplantation and purging in patients with relapsed chemosensitive follicular NHL . PATIENTS AND METHODS After three cycles of chemotherapy responsive patients were r and omized to either three more cycles of the same chemotherapy ( C ) , high-dose therapy followed by autologous unpurged ( U ) or purged ( P ) stem-cell transplantation . Purging was performed using a cocktail of monoclonals . Pretransplant conditioning consisted of cyclophosphamide ( 60 mg/kg x 2 ) and total body irradiation . RESULTS Of the 140 patients registered from 26 centers in Europe , 89 fulfilled the criteria for r and omization ( C : 24 , U : 33 and P : 32 ) . Reasons for failure to r and omize were : no response ( 28 ) , persistent marrow infiltration ( 4 ) , patient refusal ( 7 ) , other ( 7 ) , no data ( 5 ) . With the current follow up ( median 26 months from r and omization ) 16 ( 66 % ) in C are known to have progressed or relapsed , in contrast to 13 ( 39 % ) of U and 12 ( 37 % ) of the P patients ( P-value 0.002 ) . Overall survival is premature with the current available data . CONCLUSIONS Patients in U and P arms had higher progression/relapse-free survival rate . There are some suggestions of some improvement in overall survival rate BACKGROUND Among the 566 patients with follicular lymphomas ( FL ) included in the GELF 86 prospect i ve trials from October 1986 to September 1995 , 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse . PATIENTS AND METHODS For progressive FL , patients received mono- ( 22 % ) or polychemotherapy ( 78 % ) followed by high-dose therapy ( HDT ) with ASCT for 83 patients ( 22 % ) . The median time to progression from initial treatment was 23 months ( range 3 - 102 months ) and 24 % of documented patients ( 52 of 217 ) had histological transformation ( HT ) . Salvage therapy produced an overall response in 64 % of patients and the five-year survival from progression was 42 % . RESULTS For patients who underwent HDT with ASCT compared to st and ard treatment , five-year freedom from second failure was at 42 % vs. 16 % ( P = 0.0001 ) and five-year survival was 58 % vs. 38 % ( P = 0.0005 ) , respectively . The benefit of HDT and ASCT remained if we consider only patients less than 65 years ( five-year survival at 60 % vs. 40 % ; P = 0.001 ) . Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression , age at relapse > 50 years , progression on-therapy were adversely significant on survival . CONCLUSIONS HDTwith ASCT compared to st and ard treatment prolonged remission and survival after first progression of FL patients PURPOSE To determine , in a r and omized clinical trial , whether high-dose therapy ( HDT ) followed by autologous stem-cell transplantation is more effective than st and ard treatment with regard to progression-free survival ( PFS ) and overall survival ( OS ) in patients with relapsed follicular non-Hodgkin 's lymphoma ; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS . PATIENTS AND METHODS Patients received three cycles of chemotherapy . Responding patients with limited bone marrow infiltration were eligible for r and om assignment to three further cycles of chemotherapy ( C ) , unpurged HDT ( U ) , or purged HDT ( P ) . RESULTS Between August 1993 and April 1997 , 140 patients were registered from 36 centers internationally , and 89 were r and omly assigned . Reasons for not r and omizing included patient refusal , early progression , or death on induction therapy . With a 69-month median follow-up , the log-rank P value for PFS and OS were.0037 and .079 , respectively . For PFS , the hazard ratios ( 95 % CIs ) for U versus C , P versus C , and P versus U were 0.33 ( 0.16 to 0.70 ) , 0.38 ( 0.19 to 0.79 ) , and 1.02 ( 0.51 to 2.05 ) , respectively . The hazard ratio ( 95 % CI ) for C versus U + P was 0.30 ( 0.15 to 0.61 ) . Hazard ratios ( 95 % CIs ) for OS were 0.43 ( 0.18 to 1.06 ) , 0.43 ( 0.18 to 1.02 ) , and 0.72 ( 0.32 to 1.63 ) . For C versus U + P , the hazard ratio ( 95 % CI ) was 0.40 ( 0.18 to 0.89 ) . Kaplan-Meier estimates ( 95 % CIs ) of 2-year PFS for C , U , and P were 26 % ( 8 % to 44 % ) , 58 % ( 37 % to 79 % ) , and 55 % ( 34 % to 75 % ) , respectively . OS at 4 years for C , U , and P are 46 % ( 25 % to 67 % ) , 71 % ( 52 % to 91 % ) , and 77 % ( 60 % to 95 % ) respectively . CONCLUSION HDT significantly improves PFS and OS . There is no clear evidence of benefit through purging Fifty patients with intermediate- or high- grade non-Hodgkin 's lymphoma who had relapsed following a complete remission ( CR ) induced by a doxorubicin-containing chemotherapy regimen participated in the PARMA pilot study . The patients ranged in age from 16 to 60 years ( median age , 42 ) . All patients received DHAP ( dexamethasone/high-dose cytarabine/cisplatin ) for two courses at 3- to 4-week intervals . Patients achieving a partial response ( PR ) or CR were scheduled to receive involved-field radiotherapy and high-dose BEAC ( carmustine/etoposide/cytarabine/cyclophosphamide ) followed by autologous bone marrow transplantation ( ABMT ) . Of 48 evaluable DHAP-treated patients ( one patient was lost to follow-up and one had no measurable disease ) , seven achieved CR , 21 PR , and 20 patients had no response or progressive disease . One responder died from treatment-related toxicity , and six others declined ABMT . The patient with no measurable disease did not progress on DHAP and received ABMT . In all , 22 patients underwent ABMT ( 20 with BEAC and two with cyclophosphamide plus total body irradiation ) ; two patients ( 9 % ) died from toxicity and ten ( 45 % ) relapsed . One patient in continuous CR committed suicide 28 months post-ABMT , and nine are alive and disease-free 24 to 32 months ( median , 30 ) post-ABMT . The actuarial 2-year event-free survival for patients undergoing transplantation is 40 % . This prospect i ve multicenter trial documented the ability of DHAP followed by ABMT to produce durable CR in a significant proportion of patients with relapsed aggressive non-Hodgkin 's lymphoma ( NHL ) . Forty-four percent of all study patients with relapsed lymphoma actually underwent ABMT , and 20 % of the total group are projected to be long-term disease-free survivors . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE This trial of the German High- Grade Non-Hodgkin 's Lymphoma Study Group compares the use of high-dose therapy ( HDT ) as part of primary treatment with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) plus etoposide followed by involved-field ( IF ) radiotherapy in a r and omized , multicenter , phase III study . PATIENTS AND METHODS Three hundred twelve patients with " aggressive " non-Hodgkin 's lymphoma aged < or= 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997 . Patients with at least a minor response after two cycles of CHOEP ( CHOP + etoposide 3 x 100 mg/m(2 ) ) were to receive three further cycles of CHOEP followed by IF radiotherapy ( arm A ) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy ( arm B ) . RESULTS Among 158 patients r and omized to arm B , 103 ( 65 % ) received HDT . The complete remission rate at the end of treatment was 62.9 % in arm A and 69.9 % in arm B. With a median observation time of 45.5 months , overall survival for all 312 patients was 63 % after 3 years ( 63 % for arm A , 62 % for arm B ; P = .68 ) . Event-free survival was 49 % for arm A versus 59 % for arm B ( P = .22 ) . Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A ( P < .05 ) . Relapse after HDT occurred early ( median interval , 3 months ) . Six patients developed secondary neoplasia , three in arm A and three in arm B. CONCLUSION Results of the r and omized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine , etoposide , cytarabine , and melphalan following shortened st and ard chemotherapy This prospect i ve multicenter r and omized trial compares conventional with early intensification with high-dose sequential chemotherapy ( HDS ) and autologous stem cell transplantation ( ASCT ) as frontline therapy in high-risk non-Hodgkin lymphomas ( NHL ) . Newly diagnosed patients with aggressive high-risk [ intermediate-high ( HI ) and high-risk ( HR ) ] NHL according to the international prognosis index ( IPI ) were r and omized to receive 12-week VACOP-B ( arm A , 27 patients ) or 6-week VACOP-B followed by HDS and ASCT ( arm B , 29 patients ) . Complete remission rate was52 % in arm A and 55 % in B. Nine patients ( 16 % ) died early due to progression . According to intention-to-treat , with a median follow-up of 23 months , the 5-year actuarial overall survival , progression-free survival and disease-free survival in arms A and B were 47 and 40 % ( p = nonsignificant ) , 47 and 30 % ( p = nonsignificant ) , and 97 and 47 % ( p = 0.02 ) , respectively . Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL Evaluating high-dose therapy ( HDT ) with autologous stem cell transplantation ( ASCT ) in term of both duration and quality of life ( QOL ) presents major interests for patients with non-Hodgkin lymphoma . The quality -adjusted time without symptom and toxicity ( Q-TWiST ) methodology was applied to the LNH87 - 2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission ( CR ) . Overall survival ( OS ) and disease-free survival ( DFS ) curves were used to estimate duration of 4 health states : acute short-term toxicity ( Tox1 ) , secondary toxicity ( Tox2 ) , time without symptom and toxicity ( TWiST ) , and relapse ( Rel ) . Areas under survival curves ( AUC ) were retrospectively weighted according to QOL coefficients . HDT increased , but not significantly , TWiST ( + 2 . 4 months in AUC , P = .17 ) and decreased Rel ( -3 months , P < .01 ) . Survival estimates did not differ between the 2 treatments ( AUC 47.7 months for OS , 39.7 months for DFS ) . High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS ( AUC 28.8 versus 24.9 months , P < .01 ) but not in OS ( AUC 37.3 versus 36 months , P = .27 ) . Sensitivity analysis , performed by varying QOL coefficients , demonstrated significant quality -adjusted survival gain in high-risk patients treated by HDT . In low-risk patients , a diagram provided an aid to clinical decision-making . This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR , even after adjusting for QOL using the Q-TWiST method . ( Blood . 2000;95:3687 - 3692 PURPOSE To compare st and ard and intensive treatment strategies for patients with high- grade non-Hodgkin 's lymphoma ( NHL ) of poor prognosis , defined by the international prognostic index . PATIENTS AND METHODS Thirty-four patients received st and ard chemotherapy with 11 weeks of doxorubicin , cyclophosphamide , vincristine , bleomycin , etoposide , prednisolone , and methotrexate ( VAPEC-B ) , and 33 received intensive treatment with 7 weeks of VAPEC-B , three cycles of ifosfamide/cytarabine , then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell ( BPC ) transplantation . RESULTS Twelve of 33 patients in the intensive group and 26 of 34 patients in the st and ard group have died . The median follow-up time for the surviving patients is 31 months and 68 months , respectively . At 2 years , the actuarial estimates of event-free survival ( EFS ) were 61 % versus 35 % ( P = .01 ) and of overall survival , 64 % versus 35 % ( P = .01 ) . A significant reduction in the event rate ( progression or death ) was maintained after adjustment for age and the number of risk factors . The estimated risk of experiencing an event was 0.37 ( 95 % confidence interval [ CI ] , 0.16 to 0.84 ) in the intensive group compared with the st and ard group . CONCLUSION Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS . The survival differences observed in this study justify a formal comparison in a r and omized study PURPOSE To evaluate , in a prospect i ve multicentric study , the efficacy of a conventional salvage chemotherapy ( dexamethasone , cisplatin , and cytarabine [ DHAP ] ) versus high-dose chemotherapy ( carmustine , etoposide , cytarabine , and cyclophosphamide [ BEAC ] ) followed by autologous bone marrow transplantation ( ABMT ) in patients with aggressive non-Hodgkin 's lymphoma ( NHL ) in clinical partial response ( PR ) after two thirds of a conventional front-line therapy . PATIENTS AND METHODS From August 1988 to August 1991 , 286 patients with aggressive NHL were r and omized in seven Italian institutions to receive fluorouracil , methotrexate , cytarabine , cyclophosphamide , doxorubicin , vincristine , and prednisone ( F-MACHOP ) or methotrexate with leucovorin , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ) as front-line therapy . Of the 286 patients enrolled onto the trial , 77 ( 27 % ) were considered in PR after two thirds of the front-line therapy , and 49 of 77 ( 64 % ) were r and omized : 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT . RESULTS The response after second-line treatment was as follows : in the DHAP group , four patients ( 15 % ) achieved a complete remission ( CR ) , 12 ( 44 % ) remained in stable PR , and 11 ( 41 % ) showed progressive disease ; in the ABMT group , three patients ( 14 % ) obtained a CR , 18 ( 82 % ) obtained a stable PR , and one ( 4 % ) progressed , with an overall response ( CR + stable PR ) of 59 % and 96 % ( P < .001 ) in the DHAP and ABMT groups , respectively . The overall survival was 59 % versus 73 % and the progression-free survival ( PFS ) was 52 % versus 73 % in the DHAP and ABMT groups , respectively ( P , not significant ) . The toxicity was mild , particularly in the ABMT group , and no treatment-related deaths occurred in either group . CONCLUSION Because of the small number of patients r and omized , we were unable to determine whether ABMT or a st and ard salvage regimen ( DHAP ) is superior for PR patients . However , we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients Thirty-six successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission . Eighteen patients in first CR ( median age 22 years , range 15 - 51 ) , underwent autologous bone marrow transplantation after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation . Of these 18 patients , 2 were in stage III and 16 in stage IV ; 15 showed mediastinal and 9 bone marrow involvement at diagnosis . The transplant procedure was well tolerated and no treatment-induced deaths occurred . At this time , 14 out of 18 patients are alive and well between 1 and 60 months post transplant ( median follow-up time 46 months ) with an actuarial disease-free survival of 74 % . This phase II study suggests that high-dose chemo-radiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma BACKGROUND A significant proportion of patients with aggressive non-Hodgkin 's lymphoma ( NHL ) become long-term survivors . A European Organisation for Research and Treatment of Cancer data base of patients with aggressive NHL , consistently treated with doxorubicin-based chemotherapy since 1980 , afforded the possibility to explore late complications in this patient group . PATIENTS AND METHODS Of 951 r and omized patients , complete data on late complications could be collected in 757 patients who were alive > or = 2 years after the start of therapy and were seen at yearly follow-ups ( median follow-up , 9.4 years ; range , 2.1 - 20.4 years ) . We computed cumulative incidences of late events in a competing risk model by Gray ( death being the competing event ) to avoid bias caused by the high percentage of NHL-related deaths . Risk factors were estimated in a Cox proportional-hazards model and also evaluated with the Gray test . RESULTS Late non-neoplastic events were found in 46 % of the 757 patients . At 15 years , the cumulative incidences of cardiac disease and infertility were 20 % and 29 % , respectively . Renal insufficiency ( 11 % ) , acquired hypertension ( 8 % ) , and disabling neuropathy ( 13 % ) were also frequent . Salvage treatment was a risk factor in most cases . Smoking , age > 50 years during treatment , and preexistent hypertension were the main risk factors for cardiovascular disease . In-field radiation therapy ( RT ) was related to hypothyroidism , lung fibrosis , hypertension , gastrointestinal toxicity , and renal insufficiency but not to cardiovascular events . Autologous stem cell transplantation and cisplatin- and MOPP (mechlorethamine/vincristine/procarbazine/prednisone)-containing therapies were associated with infertility and renal insufficiency . CONCLUSION Altogether , almost half the patients with aggressive NHL experienced events addressed as late non-neoplastic complications . Salvage therapy , smoking , age > 50 years , and in-field RT are important risk factors PURPOSE To evaluate the role of early intensification with high-dose therapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) as front-line chemotherapy for patients with high-risk , histologically aggressive non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS We planned a multicenter , r and omized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ; arm A ) with an abbreviated regimen of MACOP-B ( 8 weeks ) followed by HDT and ASCT ( arm B ) for intermediate-high-risk/high-risk patients ( according to the age-adjusted International Prognostic Index ) . From September 1994 to April 1998 , 150 patients with aggressive lymphoma were enrolled onto the trial . Seventy-five patients were r and omly assigned to arm A and 75 patients were r and omly assigned to arm B. In both arms , involved-field radiation therapy ( 36 Gy ) was delivered to the site of bulky disease . RESULTS The rate of complete response was 68 % in arm A and 76 % in arm B ( P = not significant [ NS ] ) . Three toxic deaths ( 4 % ) occurred in arm B and one ( 1 % ) occurred in arm A ( P = NS ) . In arm B , 30 patients ( 40 % ) did not undergo HDT and ASCT . According to the intention-to-treat analysis at a median follow-up of 24 months , 5-year overall survival probability in arms A and B was 65 % and 64 % ( P = .95 ) , 5-year progression-free survival was 49 % and 61 % ( P = .21 ) , and 5-year relapse-free survival was 65 % and 77 % ( P = .22 ) , respectively . CONCLUSION Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk , aggressive NHL . Additional r and omized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients Autologous stem cell transplantation ( ASCT ) as first-line therapy for follicular lymphoma ( FL ) remains controversial . The multicenter study r and omized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy ( HDT ) followed by purged ASCT . Conditioning was performed with total body irradiation ( TBI ) and cyclophosphamide . The 9-year overall survival ( OS ) was similar in the HDT and conventional chemotherapy groups ( 76 % and 80 % , respectively ) . The 9-year progression-free survival ( PFS ) was higher in the ASCT than the chemotherapy group ( 64 % vs 39 % ; P = .004 ) . A PFS plateau was observed in the HDT group after 7 years . On multivariate analysis , OS and PFS were independently affected by the per-formance status score , the number of nodal areas involved , and the treatment group . Secondary malignancies were more frequent in the HDT than in the chemotherapy group ( 6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia , P = .01 ) . The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT . However , the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL . This trial has been registered with Clinical Trials.gov under identifier NCT00696735 The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone ( CHOP ) chemotherapy with CHOP ( 3 courses ) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin ( ESHAP ) , high-dose therapy ( HDT ) , and autologous peripheral blood progenitor cell transplantation ( PBPCT ) as front-line treatment for poor-prognosis aggressive non-Hodgkin 's lymphoma ( NHL ) . Between May 1 , 1995 , and April 30 , 1998 , 58 patients , aged 15 - 55 years , newly diagnosed with poor-prognosis aggressive NHL ( category F-H by the Working Formulation ) were enrolled . According to the age-adjusted international prognostic index , 65 % of the patients were high-risk cases and 35 % made up the high-intermediate group . After 3 courses of CHOP , 25 of 48 patients were r and omized to continue with CHOP , and 23 were r and omized to receive 2 - 4 cycles of ESHAP followed by HDT and PBPCT . There was no significant difference in the rate of complete remission between the two groups ( 36 % , 95 % confidence interval [ CI ] : 18%-57 % in CHOP vs. 43 % , 95 % CI : 23%-65 % in ESHAP/HDT ) ( P = 0.77 ) . With a median follow-up duration of 39 months , the 4-year failure-free survival ( FFS ) was superior in the ESHAP/HDT group ( 38 % , 95 % CI : 18%-58 % vs. 15 % , 95 % CI : 4%-32 % ) ( P = 0.04 ) . The disease-free survival was marginally different in favor of the ESHAP/HDT arm ( 90 % , 95 % CI : 47%-98 % vs. 37 % , 95 % CI : 7%-69 % ) ( P = 0.06 ) . The 4-year overall survival between the two treatment arms was comparable ( 51 % , 95 % CI : 28%-70 % for ESHAP/HDT vs. 30 % , 95 % CI : 13%-48 % for CHOP ) ( P = 0.25 ) . Treatment-related mortalities were not significantly different between both groups ( 17 % , 95 % CI : 5%-39 % for ESHAP/HDT vs. 8 % , 95 % CI : 1%-26 % for CHOP ) ( P = 0.41 ) . However , only 61 % of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT . As compared with CHOP , the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed , poor-prognosis aggressive NHL |
13,044 | 31,828,771 | : Evidence to date does not support the use of shortened ATT regimens in adults with newly diagnosed drug-sensitive pulmonary tuberculosis .
Four-month ATT regimens that replace ethambutol with moxifloxacin or gatifloxacin , or isoniazid with moxifloxacin , increase relapse substantially compared to st and ard six-month ATT regimens , although treatment success and serious adverse events are little or no different . | BACKGROUND : Tuberculosis causes more deaths than any other infectious disease worldwide , with pulmonary tuberculosis being the most common form .
St and ard first-line treatment for drug-sensitive pulmonary tuberculosis for six months comprises isoniazid , rifampicin , pyrazinamide , and ethambutol ( HRZE ) for two months , followed by HRE ( in areas of high TB drug resistance ) or HR , given over a four-month continuation phase .
Many people do not complete this full course .
Shortened treatment regimens that are equally effective and safe could improve treatment success .
OBJECTIVES : To evaluate the efficacy and safety of shortened treatment regimens versus the st and ard six-month treatment regimen for individuals with drug-sensitive pulmonary tuberculosis . | BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) Summary Background Tuberculosis is the world 's leading infectious disease killer . We aim ed to identify shorter , safer drug regimens for the treatment of tuberculosis . Methods We did a r and omised controlled , open-label trial with a multi-arm , multi-stage design . The trial was done in seven sites in South Africa and Tanzania , including hospitals , health centres , and clinical trial centres . Patients with newly diagnosed , rifampicin-sensitive , previously untreated pulmonary tuberculosis were r and omly assigned in a 1:1:1:1:2 ratio to receive ( all orally ) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol , 20 mg/kg rifampicin per day with 400 mg moxifloxacin , 20 mg/kg rifampicin per day with 300 mg SQ109 , 10 mg/kg rifampicin per day with 300 mg SQ109 , or a daily st and ard control regimen ( 10 mg/kg rifampicin , 5 mg/kg isoniazid , 25 mg/kg pyrazinamide , and 15–20 mg/kg ethambutol ) . Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks , followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day . Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation . The primary endpoint was time to culture conversion in liquid media within 12 weeks . Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis ( modified intention to treat ) . Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables . The proportional hazard assumption was tested using Schoelfeld residuals , with threshold p<0·05 for non-proportionality . The trial is registered with Clinical Trials.gov ( NCT01785186 ) . Findings Between May 7 , 2013 , and March 25 , 2014 , we enrolled and r and omly assigned 365 patients to different treatment arms ( 63 to rifampicin 35 mg/kg , isoniazid , pyrazinamide , and ethambutol ; 59 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , SQ109 ; 57 to rifampicin 20 mg/kg , isoniazid , pyrazinamide , and SQ109 ; 63 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , and moxifloxacin ; and 123 to the control arm ) . Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis . Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group ( median 48 days vs 62 days , adjusted hazard ratio 1·78 ; 95 % CI 1·22–2·58 , p=0·003 ) , but not in other experimental arms . There was no difference in any of the groups in time to culture conversion on solid media . 11 patients had treatment failure or recurrent disease during post-treatment follow-up : one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm . 45 ( 12 % ) of 365 patients reported grade 3–5 adverse events , with similar proportions in each arm . Interpretation A dose of 35 mg/kg rifampicin was safe , reduced the time to culture conversion in liquid media , and could be a promising component of future , shorter regimens . Our adaptive trial design was successfully implemented in a multi-centre , high tuberculosis burden setting , and could speed regimen development at reduced cost . Funding The study was funded by the European and Developing Countries Clinical Trials partnership ( EDCTP ) , the German Ministry for Education and Research ( BmBF ) , and the Medical Research Council UK ( MRC ) Summary Background Tuberculosis is the world 's leading infectious disease killer . We aim ed to identify shorter , safer drug regimens for the treatment of tuberculosis . Methods We did a r and omised controlled , open-label trial with a multi-arm , multi-stage design . The trial was done in seven sites in South Africa and Tanzania , including hospitals , health centres , and clinical trial centres . Patients with newly diagnosed , rifampicin-sensitive , previously untreated pulmonary tuberculosis were r and omly assigned in a 1:1:1:1:2 ratio to receive ( all orally ) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol , 20 mg/kg rifampicin per day with 400 mg moxifloxacin , 20 mg/kg rifampicin per day with 300 mg SQ109 , 10 mg/kg rifampicin per day with 300 mg SQ109 , or a daily st and ard control regimen ( 10 mg/kg rifampicin , 5 mg/kg isoniazid , 25 mg/kg pyrazinamide , and 15–20 mg/kg ethambutol ) . Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks , followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day . Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation . The primary endpoint was time to culture conversion in liquid media within 12 weeks . Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis ( modified intention to treat ) . Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables . The proportional hazard assumption was tested using Schoelfeld residuals , with threshold p<0·05 for non-proportionality . The trial is registered with Clinical Trials.gov ( NCT01785186 ) . Findings Between May 7 , 2013 , and March 25 , 2014 , we enrolled and r and omly assigned 365 patients to different treatment arms ( 63 to rifampicin 35 mg/kg , isoniazid , pyrazinamide , and ethambutol ; 59 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , SQ109 ; 57 to rifampicin 20 mg/kg , isoniazid , pyrazinamide , and SQ109 ; 63 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , and moxifloxacin ; and 123 to the control arm ) . Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis . Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group ( median 48 days vs 62 days , adjusted hazard ratio 1·78 ; 95 % CI 1·22–2·58 , p=0·003 ) , but not in other experimental arms . There was no difference in any of the groups in time to culture conversion on solid media . 11 patients had treatment failure or recurrent disease during post-treatment follow-up : one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm . 45 ( 12 % ) of 365 patients reported grade 3–5 adverse events , with similar proportions in each arm . Interpretation A dose of 35 mg/kg rifampicin was safe , reduced the time to culture conversion in liquid media , and could be a promising component of future , shorter regimens . Our adaptive trial design was successfully implemented in a multi-centre , high tuberculosis burden setting , and could speed regimen development at reduced cost . Funding The study was funded by the European and Developing Countries Clinical Trials partnership ( EDCTP ) , the German Ministry for Education and Research ( BmBF ) , and the Medical Research Council UK ( MRC ) Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II – IV r and omized active-controlled clinical trials . Moxifloxacin 400 mg once-daily monotherapy was administered orally ( PO ) or sequentially ( intravenous/oral , IV/PO ) . Across 64 trials , 21,298 patients received PO therapy ( 10,613 moxifloxacin , 10,685 comparators ) while 6846 received sequential IV/PO therapy ( 3431 moxifloxacin , 3415 comparators ) . Treatment-emergent cardiac adverse event ( AE ) rates were similar for moxifloxacin and comparators in PO ( 6.6 % vs 5.8 % ) and IV/PO ( 11.0 % vs 12.0 % ) trials . Treatment-emergent cardiac adverse drug reactions were rare in PO ( moxifloxacin 3.2 % vs comparators 2.4 % ) and IV/PO ( moxifloxacin 1.4 % vs comparators 1.5 % ) patients . There were five ( < 0.02 % ) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients ; one PO patient died treated with comparators , one patient died treated with IV/PO moxifloxacin , and three patients died after treatment with IV/PO comparators . Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm . Incidence rates of cardiac AEs remained low in population s at elevated risk of cardiac events predisposed to QTc prolongation ( i.e. community-acquired pneumonia patients admitted to the intensive care unit and /or mechanical ventilation , patients with documented prolongation of baseline QTc interval , women , and patients ≥ 65 years old ) . There was no evidence of unexpected cardiac events . After moxifloxacin treatment , an expected small prolongation in QTcB and QTcF was found . This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin , when used appropriately and according to its label , versus other antibiotics Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II – IV r and omized active-controlled clinical trials . Moxifloxacin 400 mg once-daily monotherapy was administered orally ( PO ) or sequentially ( intravenous/oral , IV/PO ) . Across 64 trials , 21,298 patients received PO therapy ( 10,613 moxifloxacin , 10,685 comparators ) while 6846 received sequential IV/PO therapy ( 3431 moxifloxacin , 3415 comparators ) . Treatment-emergent cardiac adverse event ( AE ) rates were similar for moxifloxacin and comparators in PO ( 6.6 % vs 5.8 % ) and IV/PO ( 11.0 % vs 12.0 % ) trials . Treatment-emergent cardiac adverse drug reactions were rare in PO ( moxifloxacin 3.2 % vs comparators 2.4 % ) and IV/PO ( moxifloxacin 1.4 % vs comparators 1.5 % ) patients . There were five ( < 0.02 % ) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients ; one PO patient died treated with comparators , one patient died treated with IV/PO moxifloxacin , and three patients died after treatment with IV/PO comparators . Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm . Incidence rates of cardiac AEs remained low in population s at elevated risk of cardiac events predisposed to QTc prolongation ( i.e. community-acquired pneumonia patients admitted to the intensive care unit and /or mechanical ventilation , patients with documented prolongation of baseline QTc interval , women , and patients ≥ 65 years old ) . There was no evidence of unexpected cardiac events . After moxifloxacin treatment , an expected small prolongation in QTcB and QTcF was found . This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin , when used appropriately and according to its label , versus other antibiotics Rifapentine is a highly active antituberculosis antibiotic with treatment‐shortening potential ; however , exposure – response relations and the dose needed for maximal bactericidal activity have not been established . We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine ( n = 405 ) with rifampin ( n = 252 ) as part of intensive‐phase therapy . Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed‐effects modeling . Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy . Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus , black , male , or fasting when taking drug . Rifapentine exposure , large lung cavity size , and geographic region were independently associated with time to culture conversion in liquid media . Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily . Patients with large lung cavities appear less responsive to treatment , even at high rifapentine doses Rifapentine is a highly active antituberculosis antibiotic with treatment‐shortening potential ; however , exposure – response relations and the dose needed for maximal bactericidal activity have not been established . We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine ( n = 405 ) with rifampin ( n = 252 ) as part of intensive‐phase therapy . Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed‐effects modeling . Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy . Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus , black , male , or fasting when taking drug . Rifapentine exposure , large lung cavity size , and geographic region were independently associated with time to culture conversion in liquid media . Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily . Patients with large lung cavities appear less responsive to treatment , even at high rifapentine doses This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade , but no tuberculosis-specific drugs have been discovered in 40 years . We identified a diarylquinoline , R207910 , that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro ( minimum inhibitory concentration 0.06 μg/ml ) . In mice , R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit . Substitution of drugs included in the World Health Organization 's first-line tuberculosis treatment regimen ( rifampin , isoniazid , and pyrazinamide ) with R207910 accelerated bactericidal activity , leading to complete culture conversion after 2 months of treatment in some combinations . A single dose of R207910 inhibited mycobacterial growth for 1 week . Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers . Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate ( ATP ) synthase The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade , but no tuberculosis-specific drugs have been discovered in 40 years . We identified a diarylquinoline , R207910 , that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro ( minimum inhibitory concentration 0.06 μg/ml ) . In mice , R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit . Substitution of drugs included in the World Health Organization 's first-line tuberculosis treatment regimen ( rifampin , isoniazid , and pyrazinamide ) with R207910 accelerated bactericidal activity , leading to complete culture conversion after 2 months of treatment in some combinations . A single dose of R207910 inhibited mycobacterial growth for 1 week . Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers . Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate ( ATP ) synthase Tuberculosis kills more people than any other infectious disease . Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins ; however , approximately four-fifths of participants were cured . Through a pooled analysis of patient-level data with external validation , we identify population s eligible for 4-month treatment , define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes . In 3,405 participants included in analyses , baseline smear grade of 3 + relative to < 2 + , HIV seropositivity and adherence of ≤90 % were significant risk factors for unfavorable outcome . Four-month regimens were non-inferior in participants with minimal disease defined by < 2 + sputum smear grade or non-cavitary disease . A hard-to-treat phenotype , defined by high smear grade s and cavitation , may require duration s > 6 months to cure all . Regimen duration can be selected in order to improve outcomes , providing a stratified medicine approach as an alternative to the ‘ one-size-fits-all ’ treatment currently used worldwide . Analysis of tuberculosis drug trials identifies features to stratify patients for longer or shorter treatment duration than the st and ard of care , in order to improve therapeutic outcomes Tuberculosis kills more people than any other infectious disease . Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins ; however , approximately four-fifths of participants were cured . Through a pooled analysis of patient-level data with external validation , we identify population s eligible for 4-month treatment , define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes . In 3,405 participants included in analyses , baseline smear grade of 3 + relative to < 2 + , HIV seropositivity and adherence of ≤90 % were significant risk factors for unfavorable outcome . Four-month regimens were non-inferior in participants with minimal disease defined by < 2 + sputum smear grade or non-cavitary disease . A hard-to-treat phenotype , defined by high smear grade s and cavitation , may require duration s > 6 months to cure all . Regimen duration can be selected in order to improve outcomes , providing a stratified medicine approach as an alternative to the ‘ one-size-fits-all ’ treatment currently used worldwide . Analysis of tuberculosis drug trials identifies features to stratify patients for longer or shorter treatment duration than the st and ard of care , in order to improve therapeutic outcomes BACKGROUND Bedaquiline ( Sirturo , TMC207 ) , a diarylquinoline that inhibits mycobacterial ATP synthase , has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis , when added to a preferred background regimen for 8 weeks . METHODS In this phase 2b trial , we r and omly assigned 160 patients with newly diagnosed , smear-positive , multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks , followed by 200 mg three times a week for 22 weeks , or placebo , both in combination with a preferred background regimen . The primary efficacy end point was the time to sputum-culture conversion in liquid broth . Patients were followed for 120 weeks from baseline . RESULTS Bedaquiline reduced the median time to culture conversion , as compared with placebo , from 125 days to 83 days ( hazard ratio in the bedaquiline group , 2.44 ; 95 % confidence interval , 1.57 to 3.80 ; P<0.001 by Cox regression analysis ) and increased the rate of culture conversion at 24 weeks ( 79 % vs. 58 % , P=0.008 ) and at 120 weeks ( 62 % vs. 44 % , P=0.04 ) . On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis , cure rates at 120 weeks were 58 % in the bedaquiline group and 32 % in the placebo group ( P=0.003 ) . The overall incidence of adverse events was similar in the two groups . There were 10 deaths in the bedaquiline group and 2 in the placebo group , with no causal pattern evident . CONCLUSIONS The addition of bedaquiline to a preferred background regimen for 24 weeks result ed in faster culture conversion and significantly more culture conversions at 120 weeks , as compared with placebo . There were more deaths in the bedaquiline group than in the placebo group . ( Funded by Janssen Pharmaceuticals ; TMC207-C208 Clinical Trials.gov number , NCT00449644 . ) BACKGROUND Bedaquiline ( Sirturo , TMC207 ) , a diarylquinoline that inhibits mycobacterial ATP synthase , has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis , when added to a preferred background regimen for 8 weeks . METHODS In this phase 2b trial , we r and omly assigned 160 patients with newly diagnosed , smear-positive , multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks , followed by 200 mg three times a week for 22 weeks , or placebo , both in combination with a preferred background regimen . The primary efficacy end point was the time to sputum-culture conversion in liquid broth . Patients were followed for 120 weeks from baseline . RESULTS Bedaquiline reduced the median time to culture conversion , as compared with placebo , from 125 days to 83 days ( hazard ratio in the bedaquiline group , 2.44 ; 95 % confidence interval , 1.57 to 3.80 ; P<0.001 by Cox regression analysis ) and increased the rate of culture conversion at 24 weeks ( 79 % vs. 58 % , P=0.008 ) and at 120 weeks ( 62 % vs. 44 % , P=0.04 ) . On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis , cure rates at 120 weeks were 58 % in the bedaquiline group and 32 % in the placebo group ( P=0.003 ) . The overall incidence of adverse events was similar in the two groups . There were 10 deaths in the bedaquiline group and 2 in the placebo group , with no causal pattern evident . CONCLUSIONS The addition of bedaquiline to a preferred background regimen for 24 weeks result ed in faster culture conversion and significantly more culture conversions at 120 weeks , as compared with placebo . There were more deaths in the bedaquiline group than in the placebo group . ( Funded by Janssen Pharmaceuticals ; TMC207-C208 Clinical Trials.gov number , NCT00449644 . ) ABSTRACT The effects on ventricular repolarization — recorded on the electrocardiogram ( ECG ) as lengthening of the QT interval — of acute tuberculosis and those of st and ard and alternative antituberculosis regimens are underdocumented . A correction factor ( QTc ) is introduced to make the QT independent of the heart rate , translating into the slope of the regression line between QT and heart rate being close to zero . ECGs were performed predosing and 1 to 5 h postdosing ( month 1 , month 2 , and end of treatment ) around drugs ' peak concentration time in tuberculosis patients treated with either the st and ard 6-month treatment ( rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months ; “ control ” ) or a test regimen with gatifloxacin , rifampin , and isoniazid given for 4 months ( pyrazinamide for the first 2 months ) as part of the OFLOTUB study , a r and omized controlled trial conducted in five African countries . Drug levels were measured at steady state ( month 1 ) in a subset of patients . We compared treatment effects on the QTc and modeled the effect of individual drugs ' maximum concentrations of drug in serum ( Cmax ) on the Fridericia-corrected QT interval . A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline ( mean age , 30.7 years ; 27 % female ) . Median heart rate decreased from 96/min at baseline to 71/min at end of treatment , and body temperature decreased from 37.2 to 36.5 ° C . Pretreatment , the nonlinear model estimated the best correction factor at 0.4081 in between Bazett 's ( 0.5 ) and Fridericia 's ( 0.33 ) corrections . On treatment , Fridericia ( QTcF ) was the best correction factor . A total of 1,602 patients contributed to the analysis of QTcF by treatment arm . The peak QTcF value during follow-up was > 480 ms for 21 patients ( 7 and 14 in the test and control arms , respectively ) and > 500 ms for 9 patients ( 5 and 4 , respectively ) , corresponding to a risk difference of −0.9 % ( 95 % confidence interval [ CI ] , −2.0 % to 2.3 % ; P = 0.12 ) and 0.1 % ( 95 % CI , −0.6 % to 0.9 % ; P = 0.75 ) , respectively , between the test and control arms . One hundred six ( 6.6 % ) patients had a peak measurement change from baseline of > 60 ms ( adjusted between-arm difference , 0.8 % ; 95 % CI , −1.4 % to 3.1 % ; P = 0.47 ) . No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a st and ard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis . This is to date the largest data set study ing the effects of antituberculosis regimens on the QT , both for the st and ard regimen and for a fluoroquinolone-containing regimen . ( This study has been registered at Clinical Trials.gov under identifier NCT00216385 . ABSTRACT The effects on ventricular repolarization — recorded on the electrocardiogram ( ECG ) as lengthening of the QT interval — of acute tuberculosis and those of st and ard and alternative antituberculosis regimens are underdocumented . A correction factor ( QTc ) is introduced to make the QT independent of the heart rate , translating into the slope of the regression line between QT and heart rate being close to zero . ECGs were performed predosing and 1 to 5 h postdosing ( month 1 , month 2 , and end of treatment ) around drugs ' peak concentration time in tuberculosis patients treated with either the st and ard 6-month treatment ( rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months ; “ control ” ) or a test regimen with gatifloxacin , rifampin , and isoniazid given for 4 months ( pyrazinamide for the first 2 months ) as part of the OFLOTUB study , a r and omized controlled trial conducted in five African countries . Drug levels were measured at steady state ( month 1 ) in a subset of patients . We compared treatment effects on the QTc and modeled the effect of individual drugs ' maximum concentrations of drug in serum ( Cmax ) on the Fridericia-corrected QT interval . A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline ( mean age , 30.7 years ; 27 % female ) . Median heart rate decreased from 96/min at baseline to 71/min at end of treatment , and body temperature decreased from 37.2 to 36.5 ° C . Pretreatment , the nonlinear model estimated the best correction factor at 0.4081 in between Bazett 's ( 0.5 ) and Fridericia 's ( 0.33 ) corrections . On treatment , Fridericia ( QTcF ) was the best correction factor . A total of 1,602 patients contributed to the analysis of QTcF by treatment arm . The peak QTcF value during follow-up was > 480 ms for 21 patients ( 7 and 14 in the test and control arms , respectively ) and > 500 ms for 9 patients ( 5 and 4 , respectively ) , corresponding to a risk difference of −0.9 % ( 95 % confidence interval [ CI ] , −2.0 % to 2.3 % ; P = 0.12 ) and 0.1 % ( 95 % CI , −0.6 % to 0.9 % ; P = 0.75 ) , respectively , between the test and control arms . One hundred six ( 6.6 % ) patients had a peak measurement change from baseline of > 60 ms ( adjusted between-arm difference , 0.8 % ; 95 % CI , −1.4 % to 3.1 % ; P = 0.47 ) . No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a st and ard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis . This is to date the largest data set study ing the effects of antituberculosis regimens on the QT , both for the st and ard regimen and for a fluoroquinolone-containing regimen . ( This study has been registered at Clinical Trials.gov under identifier NCT00216385 . ABSTRACT The 2-year follow-up results for a r and omized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207 , recently renamed bedaquiline , or placebo , added to the first 8 weeks of a background regimen , are presented . Bedaquiline significantly reduced the time to culture conversion over 24 weeks ( hazard ratio , 2.253 ; 95 % confidence interval , 1.08 to 4.71 ; P = 0.031 ) . With the exception of nausea reported in 26 % of patients receiving bedaquiline and none receiving placebo , adverse events occurred at similar frequencies in both groups of patients : bilateral hearing impairment , extremity pain , acne , and noncardiac chest pain occurred in 13 and 21 % , 17 and 13 % , 9 and 17 % , and 4 and 17 % of patients , respectively , receiving bedaquiline or placebo . Excluding resistance to ethambutol and ethionamide , only one patient receiving bedaquiline acquired resistance to companion drugs , but five patients receiving placebo ( 4.8 % versus 21.7 % ; P = 0.18 ) acquired resistance to companion drugs , and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline ( 0 % versus 22 % ; 0 = 0.066 ) . In all , 23 patients ( 49 % ) , including 13 receiving placebo ( 54 % ) and 10 receiving bedaquiline ( 44 % ) , discontinued the study prior to its completion , 12 during the first 24 weeks of treatment . Eight subjects were withdrawn for noncompliance or default , and seven withdrew consent , citing the rigorous program of investigations for safety and pharmacokinetic monitoring . Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs ABSTRACT The 2-year follow-up results for a r and omized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207 , recently renamed bedaquiline , or placebo , added to the first 8 weeks of a background regimen , are presented . Bedaquiline significantly reduced the time to culture conversion over 24 weeks ( hazard ratio , 2.253 ; 95 % confidence interval , 1.08 to 4.71 ; P = 0.031 ) . With the exception of nausea reported in 26 % of patients receiving bedaquiline and none receiving placebo , adverse events occurred at similar frequencies in both groups of patients : bilateral hearing impairment , extremity pain , acne , and noncardiac chest pain occurred in 13 and 21 % , 17 and 13 % , 9 and 17 % , and 4 and 17 % of patients , respectively , receiving bedaquiline or placebo . Excluding resistance to ethambutol and ethionamide , only one patient receiving bedaquiline acquired resistance to companion drugs , but five patients receiving placebo ( 4.8 % versus 21.7 % ; P = 0.18 ) acquired resistance to companion drugs , and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline ( 0 % versus 22 % ; 0 = 0.066 ) . In all , 23 patients ( 49 % ) , including 13 receiving placebo ( 54 % ) and 10 receiving bedaquiline ( 44 % ) , discontinued the study prior to its completion , 12 during the first 24 weeks of treatment . Eight subjects were withdrawn for noncompliance or default , and seven withdrew consent , citing the rigorous program of investigations for safety and pharmacokinetic monitoring . Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs BACKGROUND The oxazolidinone PNU-100480 is superior to linezolid against experimental murine tuberculosis . Two metabolites contribute to but do not fully account for its superiority . This study examined the safety , tolerability , pharmacokinetics , and mycobactericidal activity of single ascending doses of PNU-100480 . METHODS Nineteen healthy volunteers received 2 escalating single oral doses ( 35 - 1500 mg ) of PNU-100480 or placebo . Eight subjects received 4 daily doses of 300 mg of linezolid . Drug concentrations and bactericidal activity against Mycobacterium tuberculosis in whole-blood bactericidal culture were measured . RESULTS All doses were safe and well tolerated . PNU-100480 doses to 1000 mg were well absorbed and showed approximately proportional increases in exposures of parent and metabolites . The geometric mean maximal concentrations of PNU-100480 , PNU-101603 , and PNU-101244 ( sulfoxide and sulfone metabolites ) at 1000 mg were 839 , 3558 , and 54 ng/mL , respectively . The maximal whole-blood bactericidal activity ( -0.37 + /- .06 log/day ) occurred at combined PNU levels > or = 2 times the minimum inhibitory concentration . The observed geometric mean maximal concentration for linezolid was 6425 ng/mL. Its maximal whole-blood bactericidal activity also occurred at > or = 2 times the minimum inhibitory concentration , but it was only -0.16 + /- .05 log/day ( P < .001 ) Neither drug showed enhanced activity at higher concentrations . CONCLUSIONS Single doses of PNU-100480 to 1000 mg were well tolerated and exhibited antimycobacterial activity superior to 300 mg of linezolid at steady state . Additional studies are warranted to define its role in drug-resistant tuberculosis BACKGROUND The oxazolidinone PNU-100480 is superior to linezolid against experimental murine tuberculosis . Two metabolites contribute to but do not fully account for its superiority . This study examined the safety , tolerability , pharmacokinetics , and mycobactericidal activity of single ascending doses of PNU-100480 . METHODS Nineteen healthy volunteers received 2 escalating single oral doses ( 35 - 1500 mg ) of PNU-100480 or placebo . Eight subjects received 4 daily doses of 300 mg of linezolid . Drug concentrations and bactericidal activity against Mycobacterium tuberculosis in whole-blood bactericidal culture were measured . RESULTS All doses were safe and well tolerated . PNU-100480 doses to 1000 mg were well absorbed and showed approximately proportional increases in exposures of parent and metabolites . The geometric mean maximal concentrations of PNU-100480 , PNU-101603 , and PNU-101244 ( sulfoxide and sulfone metabolites ) at 1000 mg were 839 , 3558 , and 54 ng/mL , respectively . The maximal whole-blood bactericidal activity ( -0.37 + /- .06 log/day ) occurred at combined PNU levels > or = 2 times the minimum inhibitory concentration . The observed geometric mean maximal concentration for linezolid was 6425 ng/mL. Its maximal whole-blood bactericidal activity also occurred at > or = 2 times the minimum inhibitory concentration , but it was only -0.16 + /- .05 log/day ( P < .001 ) Neither drug showed enhanced activity at higher concentrations . CONCLUSIONS Single doses of PNU-100480 to 1000 mg were well tolerated and exhibited antimycobacterial activity superior to 300 mg of linezolid at steady state . Additional studies are warranted to define its role in drug-resistant tuberculosis BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy . The objective of this phase 2 clinical trial was to determine the bactericidal activity , safety , and tolerability of a regimen comprised of rifapentine , moxifloxacin , isoniazid , and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment . Methods Adults with sputum smear-positive pulmonary tuberculosis were r and omized to receive either rifapentine ( approximately 7.5 mg/kg ) plus moxifloxacin ( investigational arm ) , or rifampin ( approximately 10 mg/kg ) plus ethambutol ( control ) daily for 8 weeks , along with isoniazid and pyrazinamide . The primary endpoint was sputum culture status at completion of 8 weeks of treatment . Results 121 participants ( 56 % of accrual target ) were enrolled . At completion of 8 weeks of treatment , negative cultures using Löwenstein-Jensen ( LJ ) medium occurred in 47/60 ( 78 % ) participants in the investigational arm vs. 43/51 ( 84 % , p = 0.47 ) in the control arm ; negative cultures using liquid medium occurred in 37/47 ( 79 % ) in the investigational arm vs. 27/41 ( 66 % , p = 0.23 ) in the control arm . Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium ( p = 0.03 ) , but there was no difference using LJ medium . Median rifapentine area under the concentration-time curve ( AUC0 - 24 ) was 313 mcg*h/mL , similar to recent studies of rifapentine dosed at 450–600 mg daily . Median moxifloxacin AUC0 - 24 was 28.0 mcg*h/mL , much lower than in trials where rifapentine was given only intermittently with moxifloxacin . The proportion of participants discontinuing assigned treatment for reasons other than microbiological in eligibility was higher in the investigational arm vs. the control arm ( 11/62 [ 18 % ] vs. 3/59 [ 5 % ] , p = 0.04 ) although the proportions of grade 3 or higher adverse events were similar ( 5/62 [ 8 % ] in the investigational arm vs. 6/59 [ 10 % , p = 0.76 ] in the control arm ) . Conclusion For intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide , a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus st and ard dose rifampin . Trial Registration www . Clinical Trials.gov Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy . The objective of this phase 2 clinical trial was to determine the bactericidal activity , safety , and tolerability of a regimen comprised of rifapentine , moxifloxacin , isoniazid , and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment . Methods Adults with sputum smear-positive pulmonary tuberculosis were r and omized to receive either rifapentine ( approximately 7.5 mg/kg ) plus moxifloxacin ( investigational arm ) , or rifampin ( approximately 10 mg/kg ) plus ethambutol ( control ) daily for 8 weeks , along with isoniazid and pyrazinamide . The primary endpoint was sputum culture status at completion of 8 weeks of treatment . Results 121 participants ( 56 % of accrual target ) were enrolled . At completion of 8 weeks of treatment , negative cultures using Löwenstein-Jensen ( LJ ) medium occurred in 47/60 ( 78 % ) participants in the investigational arm vs. 43/51 ( 84 % , p = 0.47 ) in the control arm ; negative cultures using liquid medium occurred in 37/47 ( 79 % ) in the investigational arm vs. 27/41 ( 66 % , p = 0.23 ) in the control arm . Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium ( p = 0.03 ) , but there was no difference using LJ medium . Median rifapentine area under the concentration-time curve ( AUC0 - 24 ) was 313 mcg*h/mL , similar to recent studies of rifapentine dosed at 450–600 mg daily . Median moxifloxacin AUC0 - 24 was 28.0 mcg*h/mL , much lower than in trials where rifapentine was given only intermittently with moxifloxacin . The proportion of participants discontinuing assigned treatment for reasons other than microbiological in eligibility was higher in the investigational arm vs. the control arm ( 11/62 [ 18 % ] vs. 3/59 [ 5 % ] , p = 0.04 ) although the proportions of grade 3 or higher adverse events were similar ( 5/62 [ 8 % ] in the investigational arm vs. 6/59 [ 10 % , p = 0.76 ] in the control arm ) . Conclusion For intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide , a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus st and ard dose rifampin . Trial Registration www . Clinical Trials.gov Background Tuberculosis ( TB ) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common . Evidence for tuberculosis treatment in children is largely extrapolated from adult studies . Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months . New paediatric , fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries , making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible . The safety and efficacy of these higher drug doses has not been systematic ally assessed in large studies in children , and the pharmacokinetics across children representing the range of weights and ages should be confirmed . Methods / design SHINE is a multicentre , open-label , parallel-group , non-inferiority , r and omised controlled , two-arm trial comparing a 4-month vs the st and ard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses . We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB , with or without HIV infection . The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post r and omisation and grade 3 or 4 adverse events . Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations , providing model-based predictions for optimal dosing , and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children . Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations . Discussion Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful , the question has never been addressed in children , who have mainly paucibacillary , non-severe smear-negative disease . SHINE should inform whether treatment-shortening of drug-susceptible TB in children , regardless of HIV status , is efficacious and safe . The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in setting s with a high burden of TB . A positive result from this trial could simplify and shorten treatment , improve adherence and be cost-saving for many children with TB.Recruitment to the SHINE trial begun in July 2016 ; results are expected in 2020.Trial registration International St and ard R and omised Controlled Trials Number : IS RCT N63579542 , 14 October 2014.Pan African Clinical Trials Registry Number : PACTR201505001141379 , 14 May 2015 . Clinical Trial Registry-India , registration number : CTRI/2017/07/009119 , 27 July 2017 Background Tuberculosis ( TB ) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common . Evidence for tuberculosis treatment in children is largely extrapolated from adult studies . Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months . New paediatric , fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries , making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible . The safety and efficacy of these higher drug doses has not been systematic ally assessed in large studies in children , and the pharmacokinetics across children representing the range of weights and ages should be confirmed . Methods / design SHINE is a multicentre , open-label , parallel-group , non-inferiority , r and omised controlled , two-arm trial comparing a 4-month vs the st and ard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses . We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB , with or without HIV infection . The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post r and omisation and grade 3 or 4 adverse events . Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations , providing model-based predictions for optimal dosing , and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children . Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations . Discussion Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful , the question has never been addressed in children , who have mainly paucibacillary , non-severe smear-negative disease . SHINE should inform whether treatment-shortening of drug-susceptible TB in children , regardless of HIV status , is efficacious and safe . The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in setting s with a high burden of TB . A positive result from this trial could simplify and shorten treatment , improve adherence and be cost-saving for many children with TB.Recruitment to the SHINE trial begun in July 2016 ; results are expected in 2020.Trial registration International St and ard R and omised Controlled Trials Number : IS RCT N63579542 , 14 October 2014.Pan African Clinical Trials Registry Number : PACTR201505001141379 , 14 May 2015 . Clinical Trial Registry-India , registration number : CTRI/2017/07/009119 , 27 July 2017 RATIONALE Cavitary disease and delayed culture conversion have been associated with relapse . Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients . OBJECTIVES To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months . METHODS This study was a r and omized , open-label equivalence trial . HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid , rifampin , pyrazinamide , and ethambutol for 2 months , followed by 2 months of isoniazid and rifampin . After 4 months , patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were r and omly assigned to continue treatment for 2 more months or to stop treatment . Patients were followed for relapse for 30 months after beginning treatment . MEASUREMENTS AND MAIN RESULTS Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm . A total of 370 patients were eligible for per protocol analysis . Thirteen patients in the 4-month arm relapsed , compared with three subjects in the 6-month arm ( 7.0 vs. 1.6 % ; risk difference , 0.054 ; 95 % confidence interval with Hauck- And erson correction , 0.01 - 0.10 ) . CONCLUSION Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs result ed in a greater relapse rate . The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse RATIONALE Cavitary disease and delayed culture conversion have been associated with relapse . Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients . OBJECTIVES To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months . METHODS This study was a r and omized , open-label equivalence trial . HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid , rifampin , pyrazinamide , and ethambutol for 2 months , followed by 2 months of isoniazid and rifampin . After 4 months , patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were r and omly assigned to continue treatment for 2 more months or to stop treatment . Patients were followed for relapse for 30 months after beginning treatment . MEASUREMENTS AND MAIN RESULTS Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm . A total of 370 patients were eligible for per protocol analysis . Thirteen patients in the 4-month arm relapsed , compared with three subjects in the 6-month arm ( 7.0 vs. 1.6 % ; risk difference , 0.054 ; 95 % confidence interval with Hauck- And erson correction , 0.01 - 0.10 ) . CONCLUSION Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs result ed in a greater relapse rate . The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse Background Shortening the st and ard 6-month treatment for drug-susceptible pulmonary tuberculosis ( DS-PTB ) would be a major improvement for TB case management and disease control . Methods We are conducting a r and omized , open-label , controlled , non-inferiority trial involving patients with smear-positive , newly diagnosed DS-PTB cases nationwide to assess the efficacy and safety of two 4.5- month regimens in comparison to the st and ard 6-month WHO recommended regimen . The regimen used in one experiment group is a 4.5-month fluoroquinolone-containing regimen , which consists of full course of levofloxacin , isoniazid ( H ) , rifampin ( R ) , parazinamid ( Z ) and ethambutol ( E ) . Regimen used in the second experiment group includes 4.5-month full course of H , R , Z , E with levofloxacin removed . Patients in the control group , receive H , R , Z and E for 2 months , followed by 4 months of H and R. The primary endpoint is treatment failure or relapse within 24 month after treatment completion . Discussion Results from this trial along with other studies will contribute to the science of constructing a shorter , effective and safe regiment for TB patients .Trial registration The protocol has been registered on Clinical Trials.gov on 2 September,2016 with identifier NCT02901288 Background Shortening the st and ard 6-month treatment for drug-susceptible pulmonary tuberculosis ( DS-PTB ) would be a major improvement for TB case management and disease control . Methods We are conducting a r and omized , open-label , controlled , non-inferiority trial involving patients with smear-positive , newly diagnosed DS-PTB cases nationwide to assess the efficacy and safety of two 4.5- month regimens in comparison to the st and ard 6-month WHO recommended regimen . The regimen used in one experiment group is a 4.5-month fluoroquinolone-containing regimen , which consists of full course of levofloxacin , isoniazid ( H ) , rifampin ( R ) , parazinamid ( Z ) and ethambutol ( E ) . Regimen used in the second experiment group includes 4.5-month full course of H , R , Z , E with levofloxacin removed . Patients in the control group , receive H , R , Z and E for 2 months , followed by 4 months of H and R. The primary endpoint is treatment failure or relapse within 24 month after treatment completion . Discussion Results from this trial along with other studies will contribute to the science of constructing a shorter , effective and safe regiment for TB patients .Trial registration The protocol has been registered on Clinical Trials.gov on 2 September,2016 with identifier NCT02901288 BACKGROUND New antituberculosis regimens are urgently needed to shorten tuberculosis treatment . Following on from favourable assessment in a 2 week study , we investigated a novel regimen for efficacy and safety in drug-susceptible and multidrug-resistant ( MDR ) tuberculosis during the first 8 weeks of treatment . METHODS We did this phase 2b study of bactericidal activity -- defined as the decrease in colony forming units ( CFUs ) of Mycobacterium tuberculosis in the sputum of patients with microscopy smear-positive pulmonary tuberculosis-at eight sites in South Africa and Tanzania . We enrolled treatment-naive patients with drug-susceptible , pulmonary tuberculosis , who were r and omly assigned by computer-generated sequences to receive either 8 weeks of moxifloxacin , 100 mg pretomanid ( formerly known as PA-824 ) , and pyrazinamide ( MPa100Z regimen ) ; moxifloxacin , 200 mg pretomanid , and pyrazinamide ( MPa200Z regimen ) ; or the current st and ard care for drug-susceptible pulmonary tuberculosis , isoniazid , rifampicin , PZA , and ethambutol ( HRZE regimen ) . A group of patients with MDR tuberculosis received MPa200Z ( DRMPa200Z group ) . The primary outcome was bactericidal activity measured by the mean daily rate of reduction in M tuberculosis CFUs per mL overnight sputum collected once a week , with joint Bayesian non-linear mixed-effects regression modelling . We also assessed safety and tolerability by monitoring adverse events . This study is registered with Clinical Trials.gov , number NCT01498419 . FINDINGS Between March 24 , 2012 , and July 26 , 2013 we enrolled 207 patients and r and omly assigned them to treatment groups ; we assigned 60 patients to the MPa100Z regimen , 62 to the MPa200Z regimen , and 59 to the HRZE regimen . We non-r and omly assigned 26 patients with drug-resistant tuberculosis to the DRMPa200Z regimen . In patients with drug-susceptible tuberculosis , the bactericidal activity of MPa200Z ( n=54 ) on days 0 - 56 ( 0·155 , 95 % Bayesian credibility interval 0·133 - 0·178 ) was significantly greater than for HRZE ( n=54 , 0·112 , 0·093 - 0·131 ) . DRMPa200Z ( n=9 ) had bactericidal activity of 0·117 ( 0·070 - 0·174 ) . The bactericidal activity on days 7 - 14 was strongly associated with bactericidal activity on days 7 - 56 . Frequencies of adverse events were similar to st and ard treatment in all groups . The most common adverse event was hyperuricaemia in 59 ( 29 % ) patients ( 17 [ 28 % ] patients in MPa100Z group , 17 [ 27 % ] patients in MPa200Z group , 17 [ 29 % ] patients . in HRZE group , and 8 [ 31 % ] patients in DRMPa200Z group ) . Other common adverse events were nausea in ( 14 [ 23 % ] patients in MPa100Z group , 8 [ 13 % ] patients in MPa200Z group , 7 [ 12 % ] patients in HRZE group , and 8 [ 31 % ] patients in DRMPa200Z group ) and vomiting ( 7 [ 12 % ] patients in MPa100Z group , 7 [ 11 % ] patients in MPa200Z group , 7 [ 12 % ] patients in HRZE group , and 4 [ 15 % ] patients in DRMPa200Z group ) . No on-treatment electrocardiogram occurrences of corrected QT interval more than 500 ms ( an indicator of potential of ventricular tachyarrhythmia ) were reported . No phenotypic resistance developed to any of the drugs in the regimen . INTERPRETATION The combination of moxifloxacin , pretomanid , and pyrazinamide , was safe , well tolerated , and showed superior bactericidal activity in drug-susceptible tuberculosis during 8 weeks of treatment . Results were consistent between drug-susceptible and MDR tuberculosis . This new regimen is ready to enter phase 3 trials in patients with drug-susceptible tuberculosis and MDR-tuberculosis , with the goal of shortening and simplifying treatment . FUNDING Global Alliance for TB Drug Development BACKGROUND New antituberculosis regimens are urgently needed to shorten tuberculosis treatment . Following on from favourable assessment in a 2 week study , we investigated a novel regimen for efficacy and safety in drug-susceptible and multidrug-resistant ( MDR ) tuberculosis during the first 8 weeks of treatment . METHODS We did this phase 2b study of bactericidal activity -- defined as the decrease in colony forming units ( CFUs ) of Mycobacterium tuberculosis in the sputum of patients with microscopy smear-positive pulmonary tuberculosis-at eight sites in South Africa and Tanzania . We enrolled treatment-naive patients with drug-susceptible , pulmonary tuberculosis , who were r and omly assigned by computer-generated sequences to receive either 8 weeks of moxifloxacin , 100 mg pretomanid ( formerly known as PA-824 ) , and pyrazinamide ( MPa100Z regimen ) ; moxifloxacin , 200 mg pretomanid , and pyrazinamide ( MPa200Z regimen ) ; or the current st and ard care for drug-susceptible pulmonary tuberculosis , isoniazid , rifampicin , PZA , and ethambutol ( HRZE regimen ) . A group of patients with MDR tuberculosis received MPa200Z ( DRMPa200Z group ) . The primary outcome was bactericidal activity measured by the mean daily rate of reduction in M tuberculosis CFUs per mL overnight sputum collected once a week , with joint Bayesian non-linear mixed-effects regression modelling . We also assessed safety and tolerability by monitoring adverse events . This study is registered with Clinical Trials.gov , number NCT01498419 . FINDINGS Between March 24 , 2012 , and July 26 , 2013 we enrolled 207 patients and r and omly assigned them to treatment groups ; we assigned 60 patients to the MPa100Z regimen , 62 to the MPa200Z regimen , and 59 to the HRZE regimen . We non-r and omly assigned 26 patients with drug-resistant tuberculosis to the DRMPa200Z regimen . In patients with drug-susceptible tuberculosis , the bactericidal activity of MPa200Z ( n=54 ) on days 0 - 56 ( 0·155 , 95 % Bayesian credibility interval 0·133 - 0·178 ) was significantly greater than for HRZE ( n=54 , 0·112 , 0·093 - 0·131 ) . DRMPa200Z ( n=9 ) had bactericidal activity of 0·117 ( 0·070 - 0·174 ) . The bactericidal activity on days 7 - 14 was strongly associated with bactericidal activity on days 7 - 56 . Frequencies of adverse events were similar to st and ard treatment in all groups . The most common adverse event was hyperuricaemia in 59 ( 29 % ) patients ( 17 [ 28 % ] patients in MPa100Z group , 17 [ 27 % ] patients in MPa200Z group , 17 [ 29 % ] patients . in HRZE group , and 8 [ 31 % ] patients in DRMPa200Z group ) . Other common adverse events were nausea in ( 14 [ 23 % ] patients in MPa100Z group , 8 [ 13 % ] patients in MPa200Z group , 7 [ 12 % ] patients in HRZE group , and 8 [ 31 % ] patients in DRMPa200Z group ) and vomiting ( 7 [ 12 % ] patients in MPa100Z group , 7 [ 11 % ] patients in MPa200Z group , 7 [ 12 % ] patients in HRZE group , and 4 [ 15 % ] patients in DRMPa200Z group ) . No on-treatment electrocardiogram occurrences of corrected QT interval more than 500 ms ( an indicator of potential of ventricular tachyarrhythmia ) were reported . No phenotypic resistance developed to any of the drugs in the regimen . INTERPRETATION The combination of moxifloxacin , pretomanid , and pyrazinamide , was safe , well tolerated , and showed superior bactericidal activity in drug-susceptible tuberculosis during 8 weeks of treatment . Results were consistent between drug-susceptible and MDR tuberculosis . This new regimen is ready to enter phase 3 trials in patients with drug-susceptible tuberculosis and MDR-tuberculosis , with the goal of shortening and simplifying treatment . FUNDING Global Alliance for TB Drug Development This study examined whether adding levofloxacin to a st and ard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis . Patients were r and omized to receive either four or five drugs , the fifth being levofloxacin . Patients who completed induction therapy were r and omized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin . In the r and omized induction phase , 97.3 % of patients in the four-drug group and 95.8 % in the five-drug group had sputum culture conversion at 8 weeks ( P = 1.00 ) . In the continuation phase , one patient ( 2 % ) assigned to 9 months and two patients ( 3.9 % ) assigned to 6 months of therapy had treatment failure/relapse ( P = 1.00 ) . In conclusion , this study showed that levofloxacin added no benefit to a highly effective , largely intermittent , four-drug induction regimen . Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates This study examined whether adding levofloxacin to a st and ard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis . Patients were r and omized to receive either four or five drugs , the fifth being levofloxacin . Patients who completed induction therapy were r and omized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin . In the r and omized induction phase , 97.3 % of patients in the four-drug group and 95.8 % in the five-drug group had sputum culture conversion at 8 weeks ( P = 1.00 ) . In the continuation phase , one patient ( 2 % ) assigned to 9 months and two patients ( 3.9 % ) assigned to 6 months of therapy had treatment failure/relapse ( P = 1.00 ) . In conclusion , this study showed that levofloxacin added no benefit to a highly effective , largely intermittent , four-drug induction regimen . Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates BACKGROUND Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control . This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis . METHODS We conducted a noninferiority , r and omized , open-label , controlled trial involving patients 18 to 65 years of age with smear-positive , rifampin-sensitive , newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries . A st and ard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin ( 400 mg per day ) was substituted for ethambutol during the intensive phase and was continued , along with rifampin and isoniazid , during the continuation phase . The primary efficacy end point was an unfavorable outcome ( treatment failure , recurrence , or death or study dropout during treatment ) measured 24 months after the end of treatment , with a noninferiority margin of 6 percentage points , adjusted for country . RESULTS A total of 1836 patients were assigned to the 4-month regimen ( experimental group ) or the st and ard regimen ( control group ) . Baseline characteristics were well balanced between the groups . At 24 months after the end of treatment , the adjusted difference in the risk of an unfavorable outcome ( experimental group [ 21.0 % ] minus control group [ 17.2 % ] ) in the modified intention-to-treat population ( 1356 patients ) was 3.5 percentage points ( 95 % confidence interval , -0.7 to 7.7 ) . There was heterogeneity across countries ( P=0.02 for interaction , with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal ) and in baseline cavitary status ( P=0.04 for interaction ) and body-mass index ( P=0.10 for interaction ) . The st and ard regimen , as compared with the 4-month regimen , was associated with a higher dropout rate during treatment ( 5.0 % vs. 2.7 % ) and more treatment failures ( 2.4 % vs. 1.7 % ) but fewer recurrences ( 7.1 % vs. 14.6 % ) . There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen . CONCLUSIONS Noninferiority of the 4-month regimen to the st and ard regimen with respect to the primary efficacy end point was not shown . ( Funded by the Special Program for Research and Training in Tropical Diseases and others ; Clinical Trials.gov number , NCT00216385 . ) BACKGROUND Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control . This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis . METHODS We conducted a noninferiority , r and omized , open-label , controlled trial involving patients 18 to 65 years of age with smear-positive , rifampin-sensitive , newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries . A st and ard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin ( 400 mg per day ) was substituted for ethambutol during the intensive phase and was continued , along with rifampin and isoniazid , during the continuation phase . The primary efficacy end point was an unfavorable outcome ( treatment failure , recurrence , or death or study dropout during treatment ) measured 24 months after the end of treatment , with a noninferiority margin of 6 percentage points , adjusted for country . RESULTS A total of 1836 patients were assigned to the 4-month regimen ( experimental group ) or the st and ard regimen ( control group ) . Baseline characteristics were well balanced between the groups . At 24 months after the end of treatment , the adjusted difference in the risk of an unfavorable outcome ( experimental group [ 21.0 % ] minus control group [ 17.2 % ] ) in the modified intention-to-treat population ( 1356 patients ) was 3.5 percentage points ( 95 % confidence interval , -0.7 to 7.7 ) . There was heterogeneity across countries ( P=0.02 for interaction , with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal ) and in baseline cavitary status ( P=0.04 for interaction ) and body-mass index ( P=0.10 for interaction ) . The st and ard regimen , as compared with the 4-month regimen , was associated with a higher dropout rate during treatment ( 5.0 % vs. 2.7 % ) and more treatment failures ( 2.4 % vs. 1.7 % ) but fewer recurrences ( 7.1 % vs. 14.6 % ) . There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen . CONCLUSIONS Noninferiority of the 4-month regimen to the st and ard regimen with respect to the primary efficacy end point was not shown . ( Funded by the Special Program for Research and Training in Tropical Diseases and others ; Clinical Trials.gov number , NCT00216385 . ) Background There have been no major advances in tuberculosis ( TB ) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago . Since then , the l and scape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection , the spread of resistant TB bacilli strains , recent advances in mycobacteriological capacity , and drug discovery . As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials . To highlight key issues discussed : Is a superiority , equivalence , or non-inferiority design most appropriate ? What should be the primary efficacy outcome ? How to consider re-infections in the definition of the outcome ? What is the optimal length of patient follow-up ? Is blinding appropriate when treatment duration in test arm is shorter ? What are the appropriate assumptions for sample size calculation ? Methods Various drugs are currently in the development pipeline . We are presenting in this paper the design of the most recently completed phase III TB trial , the OFLOTUB project , which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen . It is a r and omized , open-label , multicenter , controlled trial aim ing to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen ( trial registration : Clinical Trial.gov data base : NCT00216385 ) . Results In the light of the recent scientific and regulatory discussion s , we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices , in order to best answer the trial objectives , while at the same time satisfying regulatory authority requirements . Conclusion When shortening TB treatment , we are advocating for a non-inferiority , non-blinded design , with a composite unfavorable endpoint assessed 12 months post treatment completion , and added trial procedures specifically aim ing to : ( 1 ) minimize endpoint unavailability ; and ( 2 ) distinguish between relapse and re-infection Background There have been no major advances in tuberculosis ( TB ) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago . Since then , the l and scape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection , the spread of resistant TB bacilli strains , recent advances in mycobacteriological capacity , and drug discovery . As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials . To highlight key issues discussed : Is a superiority , equivalence , or non-inferiority design most appropriate ? What should be the primary efficacy outcome ? How to consider re-infections in the definition of the outcome ? What is the optimal length of patient follow-up ? Is blinding appropriate when treatment duration in test arm is shorter ? What are the appropriate assumptions for sample size calculation ? Methods Various drugs are currently in the development pipeline . We are presenting in this paper the design of the most recently completed phase III TB trial , the OFLOTUB project , which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen . It is a r and omized , open-label , multicenter , controlled trial aim ing to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen ( trial registration : Clinical Trial.gov data base : NCT00216385 ) . Results In the light of the recent scientific and regulatory discussion s , we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices , in order to best answer the trial objectives , while at the same time satisfying regulatory authority requirements . Conclusion When shortening TB treatment , we are advocating for a non-inferiority , non-blinded design , with a composite unfavorable endpoint assessed 12 months post treatment completion , and added trial procedures specifically aim ing to : ( 1 ) minimize endpoint unavailability ; and ( 2 ) distinguish between relapse and re-infection Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis ( TB ) control measures . The present study determines the prevalence of drug resistance among new sputum smear positive ( NSP ) and previously treated ( PT ) pulmonary TB patients , diagnosed at public sector design ated microscopy centers ( DMCs ) in the state of Tamil Nadu , India . In this single-stage cluster-sampling prevalence survey , 70 of 700 DMCs were r and omly selected using a probability-proportional to size method . A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC . Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid ( INH ) , rifampicin ( RMP ) , ofloxacin ( OFX ) and kanamycin ( KAN ) . Human Immunodeficiency Virus ( HIV ) status was collected from patient records . From June 2011 to August 2012 , 1524 NSP and 901 PT patients were enrolled . Any RMP resistance and any INH resistance were observed in 2.6 % and 15.1 % , and in 10.4 % and 30 % respectively in NSP and PT cases . Among PT patients , multi drug resistant TB ( MDR-TB ) was highest in the treatment failure ( 35 % ) group , followed by relapse ( 13 % ) and treatment after default ( 10 % ) groups . Extensively drug resistant TB ( XDRTB ) was seen in 4.3 % of MDR-TB cases . Any OFX resistance was seen in 10.4 % of NSP , 13.9 % of PT and 29 % of PT MDR-TB patients . The HIV status of the patient had no impact on drug resistance levels . RMP resistance was present in 2.6 % of new and 15.1 % of previously treated patients in Tamil Nadu . Rates of OFX resistance were high among NSP and PT patients , especially among those with MDR-TB , a matter of concern for development of new treatment regimens for TB Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis ( TB ) control measures . The present study determines the prevalence of drug resistance among new sputum smear positive ( NSP ) and previously treated ( PT ) pulmonary TB patients , diagnosed at public sector design ated microscopy centers ( DMCs ) in the state of Tamil Nadu , India . In this single-stage cluster-sampling prevalence survey , 70 of 700 DMCs were r and omly selected using a probability-proportional to size method . A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC . Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid ( INH ) , rifampicin ( RMP ) , ofloxacin ( OFX ) and kanamycin ( KAN ) . Human Immunodeficiency Virus ( HIV ) status was collected from patient records . From June 2011 to August 2012 , 1524 NSP and 901 PT patients were enrolled . Any RMP resistance and any INH resistance were observed in 2.6 % and 15.1 % , and in 10.4 % and 30 % respectively in NSP and PT cases . Among PT patients , multi drug resistant TB ( MDR-TB ) was highest in the treatment failure ( 35 % ) group , followed by relapse ( 13 % ) and treatment after default ( 10 % ) groups . Extensively drug resistant TB ( XDRTB ) was seen in 4.3 % of MDR-TB cases . Any OFX resistance was seen in 10.4 % of NSP , 13.9 % of PT and 29 % of PT MDR-TB patients . The HIV status of the patient had no impact on drug resistance levels . RMP resistance was present in 2.6 % of new and 15.1 % of previously treated patients in Tamil Nadu . Rates of OFX resistance were high among NSP and PT patients , especially among those with MDR-TB , a matter of concern for development of new treatment regimens for TB BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed . METHODS We r and omly assigned patients with newly diagnosed , smear-positive , drug-sensitive tuberculosis to one of three regimens : a control regimen that included 2 months of ethambutol , isoniazid , rifampicin , and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin ; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months ; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months . Sputum specimens were examined on microscopy and after culture at regular intervals . The primary end point was a composite treatment failure and relapse , with noninferiority based on a margin of 6 percentage points and 90 % confidence intervals . RESULTS We enrolled a total of 827 patients from South Africa , Zimbabwe , Botswana , and Zambia ; 28 % of patients were coinfected with the human immunodefiency virus . In the per- protocol analysis , the proportion of patients with an unfavorable response was 4.9 % in the control group , 3.2 % in the 6-month group ( adjusted difference from control , -1.8 percentage points ; 90 % confidence interval [ CI ] , -6.1 to 2.4 ) , and 18.2 % in the 4-month group ( adjusted difference from control , 13.6 percentage points ; 90 % CI , 8.1 to 19.1 ) . In the modified intention-to-treat analysis these proportions were 14.4 % in the control group , 13.7 % in the 6-month group ( adjusted difference from control , 0.4 percentage points ; 90 % CI , -4.7 to 5.6 ) , and 26.9 % in the 4-month group ( adjusted difference from control , 13.1 percentage points ; 90 % CI , 6.8 to 19.4 ) . CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen . The 4-month regimen was not noninferior to the control regimen . ( Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust ; RIFAQUIN Current Controlled Trials number , IS RCT N44153044 . ) BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed . METHODS We r and omly assigned patients with newly diagnosed , smear-positive , drug-sensitive tuberculosis to one of three regimens : a control regimen that included 2 months of ethambutol , isoniazid , rifampicin , and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin ; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months ; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months . Sputum specimens were examined on microscopy and after culture at regular intervals . The primary end point was a composite treatment failure and relapse , with noninferiority based on a margin of 6 percentage points and 90 % confidence intervals . RESULTS We enrolled a total of 827 patients from South Africa , Zimbabwe , Botswana , and Zambia ; 28 % of patients were coinfected with the human immunodefiency virus . In the per- protocol analysis , the proportion of patients with an unfavorable response was 4.9 % in the control group , 3.2 % in the 6-month group ( adjusted difference from control , -1.8 percentage points ; 90 % confidence interval [ CI ] , -6.1 to 2.4 ) , and 18.2 % in the 4-month group ( adjusted difference from control , 13.6 percentage points ; 90 % CI , 8.1 to 19.1 ) . In the modified intention-to-treat analysis these proportions were 14.4 % in the control group , 13.7 % in the 6-month group ( adjusted difference from control , 0.4 percentage points ; 90 % CI , -4.7 to 5.6 ) , and 26.9 % in the 4-month group ( adjusted difference from control , 13.1 percentage points ; 90 % CI , 6.8 to 19.4 ) . CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen . The 4-month regimen was not noninferior to the control regimen . ( Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust ; RIFAQUIN Current Controlled Trials number , IS RCT N44153044 . ) Summary Background Tuberculosis is the world 's leading infectious disease killer . We aim ed to identify shorter , safer drug regimens for the treatment of tuberculosis . Methods We did a r and omised controlled , open-label trial with a multi-arm , multi-stage design . The trial was done in seven sites in South Africa and Tanzania , including hospitals , health centres , and clinical trial centres . Patients with newly diagnosed , rifampicin-sensitive , previously untreated pulmonary tuberculosis were r and omly assigned in a 1:1:1:1:2 ratio to receive ( all orally ) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol , 20 mg/kg rifampicin per day with 400 mg moxifloxacin , 20 mg/kg rifampicin per day with 300 mg SQ109 , 10 mg/kg rifampicin per day with 300 mg SQ109 , or a daily st and ard control regimen ( 10 mg/kg rifampicin , 5 mg/kg isoniazid , 25 mg/kg pyrazinamide , and 15–20 mg/kg ethambutol ) . Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks , followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day . Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation . The primary endpoint was time to culture conversion in liquid media within 12 weeks . Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis ( modified intention to treat ) . Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables . The proportional hazard assumption was tested using Schoelfeld residuals , with threshold p<0·05 for non-proportionality . The trial is registered with Clinical Trials.gov ( NCT01785186 ) . Findings Between May 7 , 2013 , and March 25 , 2014 , we enrolled and r and omly assigned 365 patients to different treatment arms ( 63 to rifampicin 35 mg/kg , isoniazid , pyrazinamide , and ethambutol ; 59 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , SQ109 ; 57 to rifampicin 20 mg/kg , isoniazid , pyrazinamide , and SQ109 ; 63 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , and moxifloxacin ; and 123 to the control arm ) . Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis . Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group ( median 48 days vs 62 days , adjusted hazard ratio 1·78 ; 95 % CI 1·22–2·58 , p=0·003 ) , but not in other experimental arms . There was no difference in any of the groups in time to culture conversion on solid media . 11 patients had treatment failure or recurrent disease during post-treatment follow-up : one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm . 45 ( 12 % ) of 365 patients reported grade 3–5 adverse events , with similar proportions in each arm . Interpretation A dose of 35 mg/kg rifampicin was safe , reduced the time to culture conversion in liquid media , and could be a promising component of future , shorter regimens . Our adaptive trial design was successfully implemented in a multi-centre , high tuberculosis burden setting , and could speed regimen development at reduced cost . Funding The study was funded by the European and Developing Countries Clinical Trials partnership ( EDCTP ) , the German Ministry for Education and Research ( BmBF ) , and the Medical Research Council UK ( MRC ) Summary Background Tuberculosis is the world 's leading infectious disease killer . We aim ed to identify shorter , safer drug regimens for the treatment of tuberculosis . Methods We did a r and omised controlled , open-label trial with a multi-arm , multi-stage design . The trial was done in seven sites in South Africa and Tanzania , including hospitals , health centres , and clinical trial centres . Patients with newly diagnosed , rifampicin-sensitive , previously untreated pulmonary tuberculosis were r and omly assigned in a 1:1:1:1:2 ratio to receive ( all orally ) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol , 20 mg/kg rifampicin per day with 400 mg moxifloxacin , 20 mg/kg rifampicin per day with 300 mg SQ109 , 10 mg/kg rifampicin per day with 300 mg SQ109 , or a daily st and ard control regimen ( 10 mg/kg rifampicin , 5 mg/kg isoniazid , 25 mg/kg pyrazinamide , and 15–20 mg/kg ethambutol ) . Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks , followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day . Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation . The primary endpoint was time to culture conversion in liquid media within 12 weeks . Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis ( modified intention to treat ) . Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables . The proportional hazard assumption was tested using Schoelfeld residuals , with threshold p<0·05 for non-proportionality . The trial is registered with Clinical Trials.gov ( NCT01785186 ) . Findings Between May 7 , 2013 , and March 25 , 2014 , we enrolled and r and omly assigned 365 patients to different treatment arms ( 63 to rifampicin 35 mg/kg , isoniazid , pyrazinamide , and ethambutol ; 59 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , SQ109 ; 57 to rifampicin 20 mg/kg , isoniazid , pyrazinamide , and SQ109 ; 63 to rifampicin 10 mg/kg , isoniazid , pyrazinamide , and moxifloxacin ; and 123 to the control arm ) . Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis . Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group ( median 48 days vs 62 days , adjusted hazard ratio 1·78 ; 95 % CI 1·22–2·58 , p=0·003 ) , but not in other experimental arms . There was no difference in any of the groups in time to culture conversion on solid media . 11 patients had treatment failure or recurrent disease during post-treatment follow-up : one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm . 45 ( 12 % ) of 365 patients reported grade 3–5 adverse events , with similar proportions in each arm . Interpretation A dose of 35 mg/kg rifampicin was safe , reduced the time to culture conversion in liquid media , and could be a promising component of future , shorter regimens . Our adaptive trial design was successfully implemented in a multi-centre , high tuberculosis burden setting , and could speed regimen development at reduced cost . Funding The study was funded by the European and Developing Countries Clinical Trials partnership ( EDCTP ) , the German Ministry for Education and Research ( BmBF ) , and the Medical Research Council UK ( MRC ) Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II – IV r and omized active-controlled clinical trials . Moxifloxacin 400 mg once-daily monotherapy was administered orally ( PO ) or sequentially ( intravenous/oral , IV/PO ) . Across 64 trials , 21,298 patients received PO therapy ( 10,613 moxifloxacin , 10,685 comparators ) while 6846 received sequential IV/PO therapy ( 3431 moxifloxacin , 3415 comparators ) . Treatment-emergent cardiac adverse event ( AE ) rates were similar for moxifloxacin and comparators in PO ( 6.6 % vs 5.8 % ) and IV/PO ( 11.0 % vs 12.0 % ) trials . Treatment-emergent cardiac adverse drug reactions were rare in PO ( moxifloxacin 3.2 % vs comparators 2.4 % ) and IV/PO ( moxifloxacin 1.4 % vs comparators 1.5 % ) patients . There were five ( < 0.02 % ) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients ; one PO patient died treated with comparators , one patient died treated with IV/PO moxifloxacin , and three patients died after treatment with IV/PO comparators . Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm . Incidence rates of cardiac AEs remained low in population s at elevated risk of cardiac events predisposed to QTc prolongation ( i.e. community-acquired pneumonia patients admitted to the intensive care unit and /or mechanical ventilation , patients with documented prolongation of baseline QTc interval , women , and patients ≥ 65 years old ) . There was no evidence of unexpected cardiac events . After moxifloxacin treatment , an expected small prolongation in QTcB and QTcF was found . This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin , when used appropriately and according to its label , versus other antibiotics Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II – IV r and omized active-controlled clinical trials . Moxifloxacin 400 mg once-daily monotherapy was administered orally ( PO ) or sequentially ( intravenous/oral , IV/PO ) . Across 64 trials , 21,298 patients received PO therapy ( 10,613 moxifloxacin , 10,685 comparators ) while 6846 received sequential IV/PO therapy ( 3431 moxifloxacin , 3415 comparators ) . Treatment-emergent cardiac adverse event ( AE ) rates were similar for moxifloxacin and comparators in PO ( 6.6 % vs 5.8 % ) and IV/PO ( 11.0 % vs 12.0 % ) trials . Treatment-emergent cardiac adverse drug reactions were rare in PO ( moxifloxacin 3.2 % vs comparators 2.4 % ) and IV/PO ( moxifloxacin 1.4 % vs comparators 1.5 % ) patients . There were five ( < 0.02 % ) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients ; one PO patient died treated with comparators , one patient died treated with IV/PO moxifloxacin , and three patients died after treatment with IV/PO comparators . Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm . Incidence rates of cardiac AEs remained low in population s at elevated risk of cardiac events predisposed to QTc prolongation ( i.e. community-acquired pneumonia patients admitted to the intensive care unit and /or mechanical ventilation , patients with documented prolongation of baseline QTc interval , women , and patients ≥ 65 years old ) . There was no evidence of unexpected cardiac events . After moxifloxacin treatment , an expected small prolongation in QTcB and QTcF was found . This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin , when used appropriately and according to its label , versus other antibiotics BACKGROUND Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment . We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment . METHODS Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were r and omized to receive a 3- or 4-month moxifloxacin regimen ( moxifloxacin [ M ] , isoniazid [ H ] , rifampicin [ R ] , pyrazinamide [ Z ] , ethambutol [ E ] ) or the control regimen ( RHZE thrice weekly ) . Bacteriological assessment s were done at 15 , 30 , 45 , and 60 days of treatment . Because all patients in the moxifloxacin groups received 2 months of daily RHZEM , they were grouped together for analysis . Statistical methods included χ(2 ) test and logistic regression analysis . RESULTS Sputum culture conversion was analyzed in 780 ( 616 in the moxifloxacin group and 164 in the control group ) of 801 enrolled patients . Ninety-five percent of 590 patients in the moxifloxacin group and 81 % of 151 patients in the control group had negative sputum cultures at month 2 ( P < .001 ) . The control regimen , age ( ≥35 years ) , initial sputum culture grade ( 2 + or 3 + ) , and male sex were significantly associated with higher odds of positive sputum cultures at 2 months . CONCLUSIONS A 5-drug daily regimen with moxifloxacin results in significantly higher sputum culture conversion in the first 2 months compared with a thrice-weekly , 4-drug regimen in patients with newly diagnosed sputum-positive pulmonary tuberculosis BACKGROUND Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment . We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment . METHODS Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were r and omized to receive a 3- or 4-month moxifloxacin regimen ( moxifloxacin [ M ] , isoniazid [ H ] , rifampicin [ R ] , pyrazinamide [ Z ] , ethambutol [ E ] ) or the control regimen ( RHZE thrice weekly ) . Bacteriological assessment s were done at 15 , 30 , 45 , and 60 days of treatment . Because all patients in the moxifloxacin groups received 2 months of daily RHZEM , they were grouped together for analysis . Statistical methods included χ(2 ) test and logistic regression analysis . RESULTS Sputum culture conversion was analyzed in 780 ( 616 in the moxifloxacin group and 164 in the control group ) of 801 enrolled patients . Ninety-five percent of 590 patients in the moxifloxacin group and 81 % of 151 patients in the control group had negative sputum cultures at month 2 ( P < .001 ) . The control regimen , age ( ≥35 years ) , initial sputum culture grade ( 2 + or 3 + ) , and male sex were significantly associated with higher odds of positive sputum cultures at 2 months . CONCLUSIONS A 5-drug daily regimen with moxifloxacin results in significantly higher sputum culture conversion in the first 2 months compared with a thrice-weekly , 4-drug regimen in patients with newly diagnosed sputum-positive pulmonary tuberculosis Background Shortening tuberculosis ( TB ) treatment duration is a research priority . This paper presents data from a prematurely terminated r and omized clinical trial , of 4-month moxifloxacin or gatifloxacin regimens , in South India . Methods Newly diagnosed , sputum-positive HIV-negative pulmonary TB patients were r and omly allocated to receive gatifloxacin or moxifloxacin , along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months ( G or M ) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months ( C ) . All regimens were administered thrice-weekly . Clinical and bacteriological assessment s were done monthly during treatment and for 24 months post-treatment . The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens . Results Of 416 patients in intent-to-treat analysis , 6 ( 5 % ) of 124 , 2 ( 2 % ) of 110 and 2 ( 2 % ) of 137 patients with drug-susceptible TB in the G , M and C arms respectively had unfavorable response at the end of treatment ; during the next 24 months , 17 ( 15 % ) of 115 , 11 ( 11 % ) of 104 and 8 ( 6 % ) of 132 patients respectively , had TB recurrence . Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment ; and TB recurrence occurred in 2 of 7 and 2 of 23 patients , respectively . The differences in TB recurrence rates between the G and C arms was statistically significant ( p = 0.02 ) . Gastro-intestinal symptoms occurred in 23 % , 22 % and 9 % of patients in the G , M and C arms respectively , but most reactions were mild and manageable with symptomatic measures ; 1 % required regimen modification . Conclusions 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid , rifampicin and pyrazinamide , were inferior to st and ard 6-month treatment , in patients with newly diagnosed sputum positive pulmonary TB . Trial Registration Clinical Trials Registry of India Background Shortening tuberculosis ( TB ) treatment duration is a research priority . This paper presents data from a prematurely terminated r and omized clinical trial , of 4-month moxifloxacin or gatifloxacin regimens , in South India . Methods Newly diagnosed , sputum-positive HIV-negative pulmonary TB patients were r and omly allocated to receive gatifloxacin or moxifloxacin , along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months ( G or M ) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months ( C ) . All regimens were administered thrice-weekly . Clinical and bacteriological assessment s were done monthly during treatment and for 24 months post-treatment . The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens . Results Of 416 patients in intent-to-treat analysis , 6 ( 5 % ) of 124 , 2 ( 2 % ) of 110 and 2 ( 2 % ) of 137 patients with drug-susceptible TB in the G , M and C arms respectively had unfavorable response at the end of treatment ; during the next 24 months , 17 ( 15 % ) of 115 , 11 ( 11 % ) of 104 and 8 ( 6 % ) of 132 patients respectively , had TB recurrence . Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment ; and TB recurrence occurred in 2 of 7 and 2 of 23 patients , respectively . The differences in TB recurrence rates between the G and C arms was statistically significant ( p = 0.02 ) . Gastro-intestinal symptoms occurred in 23 % , 22 % and 9 % of patients in the G , M and C arms respectively , but most reactions were mild and manageable with symptomatic measures ; 1 % required regimen modification . Conclusions 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid , rifampicin and pyrazinamide , were inferior to st and ard 6-month treatment , in patients with newly diagnosed sputum positive pulmonary TB . Trial Registration Clinical Trials Registry of India RATIONALE Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis ( TB ) chemotherapy , but data regarding its activity in humans are limited . OBJECTIVES Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB . METHODS Adults with sputum smear-positive pulmonary TB were r and omly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo , or isoniazid 300 mg plus moxifloxacin placebo , administered 5 days/week for 8 weeks , in addition to rifampin , pyrazinamide , and ethambutol . All doses were directly observed . Sputum was collected for culture every 2 weeks . The primary outcome was negative sputum culture at completion of 8 weeks of treatment . MEASUREMENTS AND MAIN RESULTS Of 433 participants enrolled , 328 were eligible for the primary efficacy analysis . Of these , 35 ( 11 % ) were HIV positive , 248 ( 76 % ) had cavitation on baseline chest radiograph , and 213 ( 65 % ) were enrolled at African sites . Negative cultures at Week 8 were observed in 90/164 ( 54.9 % ) participants in the isoniazid arm , and 99/164 ( 60.4 % ) in the moxifloxacin arm ( P = 0.37 ) . In multivariate analysis , cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity . The proportion of participants who discontinued assigned treatment was 31/214 ( 14.5 % ) for the moxifloxacin group versus 22/205 ( 10.7 % ) for the isoniazid group ( RR , 1.35 ; 95 % CI , 0.81 , 2.25 ) . CONCLUSIONS Substitution of moxifloxacin for isoniazid result ed in a small but statistically nonsignificant increase in Week-8 culture negativity RATIONALE Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis ( TB ) chemotherapy , but data regarding its activity in humans are limited . OBJECTIVES Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB . METHODS Adults with sputum smear-positive pulmonary TB were r and omly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo , or isoniazid 300 mg plus moxifloxacin placebo , administered 5 days/week for 8 weeks , in addition to rifampin , pyrazinamide , and ethambutol . All doses were directly observed . Sputum was collected for culture every 2 weeks . The primary outcome was negative sputum culture at completion of 8 weeks of treatment . MEASUREMENTS AND MAIN RESULTS Of 433 participants enrolled , 328 were eligible for the primary efficacy analysis . Of these , 35 ( 11 % ) were HIV positive , 248 ( 76 % ) had cavitation on baseline chest radiograph , and 213 ( 65 % ) were enrolled at African sites . Negative cultures at Week 8 were observed in 90/164 ( 54.9 % ) participants in the isoniazid arm , and 99/164 ( 60.4 % ) in the moxifloxacin arm ( P = 0.37 ) . In multivariate analysis , cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity . The proportion of participants who discontinued assigned treatment was 31/214 ( 14.5 % ) for the moxifloxacin group versus 22/205 ( 10.7 % ) for the isoniazid group ( RR , 1.35 ; 95 % CI , 0.81 , 2.25 ) . CONCLUSIONS Substitution of moxifloxacin for isoniazid result ed in a small but statistically nonsignificant increase in Week-8 culture negativity Background Despite recent increased clinical trials activity , no regimen has proved able to replace the st and ard 6-month regimen for drug-sensitive tuberculosis . Underst and ing the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials . Methods Using data from the r and omized controlled phase III trial REMoxTB , we evaluated sputum-based markers of speed of clearance of bacilli : time to smear negative status ; time to culture negative status on LJ or in MGIT ; daily rate of change of log10(TTP ) to day 56 ; and smear or culture results at weeks 6 , 8 or 12 ; as individual- and trial-level surrogate endpoints for long-term clinical outcome . Results Time to culture negative status on LJ or in MGIT , time to smear negative status and daily rate of change in log10(TTP ) were each independent predictors of clinical outcome , adjusted for treatment ( p < 0.001 ) . However , discrimination between low and high risk patients , as measured by the c-statistic , was modest and not much higher than the reference model adjusted for BMI , history of smoking , HIV status , cavitation , gender and MGIT TTP . Conclusions Culture conversion during treatment for tuberculosis , however measured , has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients . REMoxTB Clinical Trials.gov number : NCT00864383 Background Despite recent increased clinical trials activity , no regimen has proved able to replace the st and ard 6-month regimen for drug-sensitive tuberculosis . Underst and ing the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials . Methods Using data from the r and omized controlled phase III trial REMoxTB , we evaluated sputum-based markers of speed of clearance of bacilli : time to smear negative status ; time to culture negative status on LJ or in MGIT ; daily rate of change of log10(TTP ) to day 56 ; and smear or culture results at weeks 6 , 8 or 12 ; as individual- and trial-level surrogate endpoints for long-term clinical outcome . Results Time to culture negative status on LJ or in MGIT , time to smear negative status and daily rate of change in log10(TTP ) were each independent predictors of clinical outcome , adjusted for treatment ( p < 0.001 ) . However , discrimination between low and high risk patients , as measured by the c-statistic , was modest and not much higher than the reference model adjusted for BMI , history of smoking , HIV status , cavitation , gender and MGIT TTP . Conclusions Culture conversion during treatment for tuberculosis , however measured , has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients . REMoxTB Clinical Trials.gov number : NCT00864383 Rifapentine is a highly active antituberculosis antibiotic with treatment‐shortening potential ; however , exposure – response relations and the dose needed for maximal bactericidal activity have not been established . We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine ( n = 405 ) with rifampin ( n = 252 ) as part of intensive‐phase therapy . Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed‐effects modeling . Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy . Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus , black , male , or fasting when taking drug . Rifapentine exposure , large lung cavity size , and geographic region were independently associated with time to culture conversion in liquid media . Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily . Patients with large lung cavities appear less responsive to treatment , even at high rifapentine doses Rifapentine is a highly active antituberculosis antibiotic with treatment‐shortening potential ; however , exposure – response relations and the dose needed for maximal bactericidal activity have not been established . We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine ( n = 405 ) with rifampin ( n = 252 ) as part of intensive‐phase therapy . Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed‐effects modeling . Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy . Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus , black , male , or fasting when taking drug . Rifapentine exposure , large lung cavity size , and geographic region were independently associated with time to culture conversion in liquid media . Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily . Patients with large lung cavities appear less responsive to treatment , even at high rifapentine doses BACKGROUND Delamanid ( OPC-67683 ) , a nitro-dihydro-imidazooxazole derivative , is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis . METHODS In this r and omized , placebo-controlled , multinational clinical trial , we assigned 481 patients ( nearly all of whom were negative for the human immunodeficiency virus ) with pulmonary multidrug-resistant tuberculosis to receive delamanid , at a dose of 100 mg twice daily ( 161 patients ) or 200 mg twice daily ( 160 patients ) , or placebo ( 160 patients ) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines . Sputum cultures were assessed weekly with the use of both liquid broth and solid medium ; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis . The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months . RESULTS Among patients who received a background drug regimen plus 100 mg of delamanid twice daily , 45.4 % had sputum-culture conversion in liquid broth at 2 months , as compared with 29.6 % of patients who received a background drug regimen plus placebo ( P=0.008 ) . Likewise , as compared with the placebo group , the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion ( 41.9 % , P=0.04 ) . The findings were similar with assessment of sputum-culture conversion in solid medium . Most adverse events were mild to moderate in severity and were evenly distributed across groups . Although no clinical events due to QT prolongation on electrocardiography were observed , QT prolongation was reported significantly more frequently in the groups that received delamanid . CONCLUSIONS Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis . This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis . ( Funded by Otsuka Pharmaceutical Development and Commercialization ; Clinical Trials.gov number , NCT00685360 . ) BACKGROUND Delamanid ( OPC-67683 ) , a nitro-dihydro-imidazooxazole derivative , is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis . METHODS In this r and omized , placebo-controlled , multinational clinical trial , we assigned 481 patients ( nearly all of whom were negative for the human immunodeficiency virus ) with pulmonary multidrug-resistant tuberculosis to receive delamanid , at a dose of 100 mg twice daily ( 161 patients ) or 200 mg twice daily ( 160 patients ) , or placebo ( 160 patients ) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines . Sputum cultures were assessed weekly with the use of both liquid broth and solid medium ; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis . The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months . RESULTS Among patients who received a background drug regimen plus 100 mg of delamanid twice daily , 45.4 % had sputum-culture conversion in liquid broth at 2 months , as compared with 29.6 % of patients who received a background drug regimen plus placebo ( P=0.008 ) . Likewise , as compared with the placebo group , the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion ( 41.9 % , P=0.04 ) . The findings were similar with assessment of sputum-culture conversion in solid medium . Most adverse events were mild to moderate in severity and were evenly distributed across groups . Although no clinical events due to QT prolongation on electrocardiography were observed , QT prolongation was reported significantly more frequently in the groups that received delamanid . CONCLUSIONS Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis . This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis . ( Funded by Otsuka Pharmaceutical Development and Commercialization ; Clinical Trials.gov number , NCT00685360 . ) RATIONALE Moxifloxacin has promising pre clinical activity against Mycobacterium tuberculosis , but has not been evaluated in multidrug treatment of tuberculosis in humans . OBJECTIVE To compare the impact of moxifloxacin versus ethambutol , both in combination with isoniazid , rifampin , and pyrazinamide , on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens . METHODS Adults with smear-positive pulmonary tuberculosis were r and omized in a factorial design to receive moxifloxacin ( 400 mg ) versus ethambutol given 5 d/wk versus 3 d/wk ( after 2 wk of daily therapy ) . All doses were directly observed . MEASUREMENTS The primary endpoint was sputum culture status at 2 mo of treatment . RESULTS Of 336 patients enrolled , 277 ( 82 % ) were eligible for the efficacy analysis , 186 ( 67 % ) were male , 175 ( 63 % ) were enrolled at African sites , 206 ( 74 % ) had cavitation on chest radiograph , and 60 ( 22 % ) had HIV infection . Two-month cultures were negative in 71 % of patients ( 99 of 139 ) treated with moxifloxacin versus 71 % ( 98 of 138 ) treated with ethambutol ( p = 0.97 ) . Patients receiving moxifloxacin , however , more often had negative cultures after 4 wk of treatment . Patients treated with moxifloxacin more often reported nausea ( 22 vs. 9 % , p = 0.002 ) , but similar proportions completed study treatment ( 88 vs. 89 % ) . Dosing frequency had little effect on 2-mo culture status or tolerability of therapy . CONCLUSIONS The addition of moxifloxacin to isoniazid , rifampin , and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points RATIONALE Moxifloxacin has promising pre clinical activity against Mycobacterium tuberculosis , but has not been evaluated in multidrug treatment of tuberculosis in humans . OBJECTIVE To compare the impact of moxifloxacin versus ethambutol , both in combination with isoniazid , rifampin , and pyrazinamide , on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens . METHODS Adults with smear-positive pulmonary tuberculosis were r and omized in a factorial design to receive moxifloxacin ( 400 mg ) versus ethambutol given 5 d/wk versus 3 d/wk ( after 2 wk of daily therapy ) . All doses were directly observed . MEASUREMENTS The primary endpoint was sputum culture status at 2 mo of treatment . RESULTS Of 336 patients enrolled , 277 ( 82 % ) were eligible for the efficacy analysis , 186 ( 67 % ) were male , 175 ( 63 % ) were enrolled at African sites , 206 ( 74 % ) had cavitation on chest radiograph , and 60 ( 22 % ) had HIV infection . Two-month cultures were negative in 71 % of patients ( 99 of 139 ) treated with moxifloxacin versus 71 % ( 98 of 138 ) treated with ethambutol ( p = 0.97 ) . Patients receiving moxifloxacin , however , more often had negative cultures after 4 wk of treatment . Patients treated with moxifloxacin more often reported nausea ( 22 vs. 9 % , p = 0.002 ) , but similar proportions completed study treatment ( 88 vs. 89 % ) . Dosing frequency had little effect on 2-mo culture status or tolerability of therapy . CONCLUSIONS The addition of moxifloxacin to isoniazid , rifampin , and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points SETTING Current treatment for pulmonary tuberculosis ( TB ) might be shortened by the incorporation of fluoroquinolones ( FQs ) . OBJECTIVES A Phase II study aim ed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin ( GFX ) . DESIGN A total of 217 newly diagnosed smear-positive patients were r and omly allocated to one of four regimens : isoniazid ( INH ) , pyrazinamide and rifampicin ( RMP ) with either ethambutol , GFX , moxifloxacin ( MFX ) or ofloxacin ( OFX ) for 2 months . At the end of the study , RMP and INH were given for 4 months . The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts ( SSCC ) during the first 8 weeks . RESULTS After adjustment for covariates , MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts , but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX ( P = 0.002 ) . Substitution of OFX had no effect . These findings were supported by estimates of time to conversion , using Cox regression , but there were no significant differences in proportions culture-negative at 8 weeks . CONCLUSIONS GFX and MFX improve the sterilising activity of regimens and might shorten treatment ; their progression into Phase III trials therefore seems warranted SETTING Current treatment for pulmonary tuberculosis ( TB ) might be shortened by the incorporation of fluoroquinolones ( FQs ) . OBJECTIVES A Phase II study aim ed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin ( GFX ) . DESIGN A total of 217 newly diagnosed smear-positive patients were r and omly allocated to one of four regimens : isoniazid ( INH ) , pyrazinamide and rifampicin ( RMP ) with either ethambutol , GFX , moxifloxacin ( MFX ) or ofloxacin ( OFX ) for 2 months . At the end of the study , RMP and INH were given for 4 months . The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts ( SSCC ) during the first 8 weeks . RESULTS After adjustment for covariates , MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts , but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX ( P = 0.002 ) . Substitution of OFX had no effect . These findings were supported by estimates of time to conversion , using Cox regression , but there were no significant differences in proportions culture-negative at 8 weeks . CONCLUSIONS GFX and MFX improve the sterilising activity of regimens and might shorten treatment ; their progression into Phase III trials therefore seems warranted This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence The efficacy of ofloxacin , rifampicin and isoniazid was prospect ively compared with the regimen of ethambutol , rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients . All drugs were given orally daily for nine months . Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group ; by six months all patients in both groups were culture-negative . Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment . No relapse in either group was observed during a two-year follow-up period after the cessation of chemotherapy . Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin The efficacy of ofloxacin , rifampicin and isoniazid was prospect ively compared with the regimen of ethambutol , rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients . All drugs were given orally daily for nine months . Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group ; by six months all patients in both groups were culture-negative . Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment . No relapse in either group was observed during a two-year follow-up period after the cessation of chemotherapy . Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade , but no tuberculosis-specific drugs have been discovered in 40 years . We identified a diarylquinoline , R207910 , that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro ( minimum inhibitory concentration 0.06 μg/ml ) . In mice , R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit . Substitution of drugs included in the World Health Organization 's first-line tuberculosis treatment regimen ( rifampin , isoniazid , and pyrazinamide ) with R207910 accelerated bactericidal activity , leading to complete culture conversion after 2 months of treatment in some combinations . A single dose of R207910 inhibited mycobacterial growth for 1 week . Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers . Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate ( ATP ) synthase The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade , but no tuberculosis-specific drugs have been discovered in 40 years . We identified a diarylquinoline , R207910 , that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro ( minimum inhibitory concentration 0.06 μg/ml ) . In mice , R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit . Substitution of drugs included in the World Health Organization 's first-line tuberculosis treatment regimen ( rifampin , isoniazid , and pyrazinamide ) with R207910 accelerated bactericidal activity , leading to complete culture conversion after 2 months of treatment in some combinations . A single dose of R207910 inhibited mycobacterial growth for 1 week . Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers . Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate ( ATP ) synthase BACKGROUND New treatments are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains . The fluoroquinolone moxifloxacin is a promising new agent that might have additive activity to existing antituberculosis agents . We assessed the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment . METHODS We undertook a phase II , double-blind , r and omised controlled trial of a regimen that included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital in Rio de Janeiro , Brazil . 170 participants received isoniazid , rifampicin , and pyrazinamide at st and ard doses and were assigned by permuted block r and omisation to receive either moxifloxacin ( 400 mg ) with an ethambutol placebo ( n=85 ) or ethambutol ( 15 - 20 mg/kg ) plus moxifloxacin placebo ( n=85 ) 5 days per week for 8 weeks . The primary endpoint was the proportion of patients whose sputum culture had converted to negative by week 8 . Analysis was by modified intention to treat ( ITT ) ; patients whose baseline cultures were negative , contaminated , or contained drug-resistant Mycobacterium tuberculosis were excluded from the analysis . Additionally , all missing 8-week results were deemed treatment failures . This study is registered with Clinical Trials.gov , number NCT00082173 . FINDINGS 74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were included in the modified ITT population . 125 patients had 8-week data ( moxifloxacin n=64 , ethambutol n=61 ) ; the main reason for absence of data was culture contamination . At 8 weeks , culture conversion to negative had occurred in 59 ( 80 % ) of 74 patients in the moxifloxacin group compared with 45 ( 63 % ) of 72 in the ethambutol group ( difference 17.2 % , 95 % CI 2.8 - 31.7 ; p=0.03 ) . There were 16 adverse events ( eight in each group ) in 12 patients . Only one event was judged related to study drug ( grade 3 cutaneous reaction in the ethambutol group ) . INTERPRETATION Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment . Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis treatment are justified BACKGROUND New treatments are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains . The fluoroquinolone moxifloxacin is a promising new agent that might have additive activity to existing antituberculosis agents . We assessed the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment . METHODS We undertook a phase II , double-blind , r and omised controlled trial of a regimen that included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital in Rio de Janeiro , Brazil . 170 participants received isoniazid , rifampicin , and pyrazinamide at st and ard doses and were assigned by permuted block r and omisation to receive either moxifloxacin ( 400 mg ) with an ethambutol placebo ( n=85 ) or ethambutol ( 15 - 20 mg/kg ) plus moxifloxacin placebo ( n=85 ) 5 days per week for 8 weeks . The primary endpoint was the proportion of patients whose sputum culture had converted to negative by week 8 . Analysis was by modified intention to treat ( ITT ) ; patients whose baseline cultures were negative , contaminated , or contained drug-resistant Mycobacterium tuberculosis were excluded from the analysis . Additionally , all missing 8-week results were deemed treatment failures . This study is registered with Clinical Trials.gov , number NCT00082173 . FINDINGS 74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were included in the modified ITT population . 125 patients had 8-week data ( moxifloxacin n=64 , ethambutol n=61 ) ; the main reason for absence of data was culture contamination . At 8 weeks , culture conversion to negative had occurred in 59 ( 80 % ) of 74 patients in the moxifloxacin group compared with 45 ( 63 % ) of 72 in the ethambutol group ( difference 17.2 % , 95 % CI 2.8 - 31.7 ; p=0.03 ) . There were 16 adverse events ( eight in each group ) in 12 patients . Only one event was judged related to study drug ( grade 3 cutaneous reaction in the ethambutol group ) . INTERPRETATION Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment . Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis treatment are justified Tuberculosis kills more people than any other infectious disease . Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins ; however , approximately four-fifths of participants were cured . Through a pooled analysis of patient-level data with external validation , we identify population s eligible for 4-month treatment , define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes . In 3,405 participants included in analyses , baseline smear grade of 3 + relative to < 2 + , HIV seropositivity and adherence of ≤90 % were significant risk factors for unfavorable outcome . Four-month regimens were non-inferior in participants with minimal disease defined by < 2 + sputum smear grade or non-cavitary disease . A hard-to-treat phenotype , defined by high smear grade s and cavitation , may require duration s > 6 months to cure all . Regimen duration can be selected in order to improve outcomes , providing a stratified medicine approach as an alternative to the ‘ one-size-fits-all ’ treatment currently used worldwide . Analysis of tuberculosis drug trials identifies features to stratify patients for longer or shorter treatment duration than the st and ard of care , in order to improve therapeutic outcomes Tuberculosis kills more people than any other infectious disease . Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins ; however , approximately four-fifths of participants were cured . Through a pooled analysis of patient-level data with external validation , we identify population s eligible for 4-month treatment , define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes . In 3,405 participants included in analyses , baseline smear grade of 3 + relative to < 2 + , HIV seropositivity and adherence of ≤90 % were significant risk factors for unfavorable outcome . Four-month regimens were non-inferior in participants with minimal disease defined by < 2 + sputum smear grade or non-cavitary disease . A hard-to-treat phenotype , defined by high smear grade s and cavitation , may require duration s > 6 months to cure all . Regimen duration can be selected in order to improve outcomes , providing a stratified medicine approach as an alternative to the ‘ one-size-fits-all ’ treatment currently used worldwide . Analysis of tuberculosis drug trials identifies features to stratify patients for longer or shorter treatment duration than the st and ard of care , in order to improve therapeutic outcomes BACKGROUND Bedaquiline ( Sirturo , TMC207 ) , a diarylquinoline that inhibits mycobacterial ATP synthase , has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis , when added to a preferred background regimen for 8 weeks . METHODS In this phase 2b trial , we r and omly assigned 160 patients with newly diagnosed , smear-positive , multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks , followed by 200 mg three times a week for 22 weeks , or placebo , both in combination with a preferred background regimen . The primary efficacy end point was the time to sputum-culture conversion in liquid broth . Patients were followed for 120 weeks from baseline . RESULTS Bedaquiline reduced the median time to culture conversion , as compared with placebo , from 125 days to 83 days ( hazard ratio in the bedaquiline group , 2.44 ; 95 % confidence interval , 1.57 to 3.80 ; P<0.001 by Cox regression analysis ) and increased the rate of culture conversion at 24 weeks ( 79 % vs. 58 % , P=0.008 ) and at 120 weeks ( 62 % vs. 44 % , P=0.04 ) . On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis , cure rates at 120 weeks were 58 % in the bedaquiline group and 32 % in the placebo group ( P=0.003 ) . The overall incidence of adverse events was similar in the two groups . There were 10 deaths in the bedaquiline group and 2 in the placebo group , with no causal pattern evident . CONCLUSIONS The addition of bedaquiline to a preferred background regimen for 24 weeks result ed in faster culture conversion and significantly more culture conversions at 120 weeks , as compared with placebo . There were more deaths in the bedaquiline group than in the placebo group . ( Funded by Janssen Pharmaceuticals ; TMC207-C208 Clinical Trials.gov number , NCT00449644 . ) BACKGROUND Bedaquiline ( Sirturo , TMC207 ) , a diarylquinoline that inhibits mycobacterial ATP synthase , has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis , when added to a preferred background regimen for 8 weeks . METHODS In this phase 2b trial , we r and omly assigned 160 patients with newly diagnosed , smear-positive , multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks , followed by 200 mg three times a week for 22 weeks , or placebo , both in combination with a preferred background regimen . The primary efficacy end point was the time to sputum-culture conversion in liquid broth . Patients were followed for 120 weeks from baseline . RESULTS Bedaquiline reduced the median time to culture conversion , as compared with placebo , from 125 days to 83 days ( hazard ratio in the bedaquiline group , 2.44 ; 95 % confidence interval , 1.57 to 3.80 ; P<0.001 by Cox regression analysis ) and increased the rate of culture conversion at 24 weeks ( 79 % vs. 58 % , P=0.008 ) and at 120 weeks ( 62 % vs. 44 % , P=0.04 ) . On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis , cure rates at 120 weeks were 58 % in the bedaquiline group and 32 % in the placebo group ( P=0.003 ) . The overall incidence of adverse events was similar in the two groups . There were 10 deaths in the bedaquiline group and 2 in the placebo group , with no causal pattern evident . CONCLUSIONS The addition of bedaquiline to a preferred background regimen for 24 weeks result ed in faster culture conversion and significantly more culture conversions at 120 weeks , as compared with placebo . There were more deaths in the bedaquiline group than in the placebo group . ( Funded by Janssen Pharmaceuticals ; TMC207-C208 Clinical Trials.gov number , NCT00449644 . ) |
13,045 | 31,107,902 | The limited evidence supports the use of HFS interventions to improve HFS knowledge and behaviour in children , families with children and adults | PURPOSE To assess the effectiveness of Home Fire Safety ( HFS ) interventions versus other interventions /no interventions /controls on HFS knowledge and behaviour at short- , intermediate- and long-term follow ups . | OBJECTIVE To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers ' behaviors and practice s related to home safety . METHODS We conducted a r and omized , clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home . After completing a structured home safety question naire via face-to-face interview , caregivers were r and omly assigned to receive either comprehensive home safety education and free safety devices or focused , injury-specific ED discharge instructions . Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety question naire . The pretest and posttest question naires were scored such that the accrual of points correlated with reporting of safer practice s. Scores were then normalized to a 100-point scale . The overall safety score reflected performance on the entire question naire , and the 8 category safety scores reflected performance in single areas of home injury prevention ( fire , burn , poison , near-drowning , aspiration , cuts/piercings , falls , and safety device use ) . The main outcome was degree of improvement in safety practice s as assessed by improvement in safety scores . RESULTS The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group ( 73.3 % + /- 8.4 % vs 66.8 % + /-11.1 ) and significant improvements in poison , cut/piercing , and burns category scores . Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices . CONCLUSIONS This educational and device disbursement intervention was effective in improving the home safety practice s of caregivers of young children . Moreover , the ED was used effectively to disseminate home injury prevention information In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : to evaluate the effectiveness of a school-based injury prevention program . Design : Cluster r and omised controlled trial . Setting : 20 primary schools in Nottingham , UK . Participants : 459 children aged 7 to 10 years . Intervention : The “ Risk Watch ” program delivered by teachers , aim ed at improving bike and pedestrian , falls , poisoning and fire and burns safety . Main outcome measures : Safety knowledge , observed safety skills and self-reported safety behaviour . Results : At follow-up , intervention group children correctly answered more fire and burn prevention knowledge questions than control group children ( difference between means 7.0 % ( 95 % CI 1.5 % to12.6 % ) ) . Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet ( difference between school means 35.3 % ( 95 % CI 22.7 % to 47.9 % ) and 6.3 % ( 95 % CI 1.4 % to 11.1 % ) respectively ) . They were also more likely to know the correct actions to take in a house fire and on finding tablets ( OR 2.80 ( 95 % CI 1.08 to 7.22 ) and OR 3.50 ( 95 % CI 1.18 to 10.38 ) respectively ) and correctly demonstrated more safety skills than control group children ( difference between means 11.9 % ( 95 % CI 1.4 % to 22.5 % ) ) . There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours . Conclusions : The Risk Watch program delivered by teachers in primary schools increased some aspects of children ’s safety knowledge and skills and primary schools should consider delivering this program . Longer term , larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Background Toddler-aged children are vulnerable to unintentional injuries , especially those in low-income families . Objective To examine the effectiveness of an intervention grounded in social cognitive theory ( SCT ) on the reduction of home safety problems among low-income families with toddlers . Methods 277 low-income mother – toddler dyads were r and omised into a safety promotion intervention ( n=91 ) or an attention-control group ( n=186 ) . Mothers in the safety promotion intervention group received an eight-session , group-delivered safety intervention targeting fire prevention , fall prevention , poison control and car seat use , through health education , goal - setting and social support . Data collectors observed participants ' homes and completed a nine-item checklist of home safety problems at study enrolment ( baseline ) , 6 and 12 months after baseline . A total score was summed , with high scores indicating more problems . Linear mixed models compared the changes over time in home safety problems between intervention and control groups . Results The intent-to-treat analysis indicated that the safety promotion intervention group significantly reduced safety problems to a greater degree than the attention-control group at the 12-month follow-up ( between-group difference in change over time β=−0.54 , 95 % CI −0.05 to −1.03 , p=0.035 ) , with no significant differences at the 6-month follow-up . Conclusions A safety promotion intervention built on principles of SCT has the potential to promote toddlers ' home safety environment . Future studies should examine additional strategies to determine whether better penetration/compliance can produce more clinical ly important improvement in home safety practice s. Trial registration number NCT02615158 ; post- results This study offers evidence that computer-based instruction is a feasible and effective alternative training method for long-term care staff . Participants were 289 nursing facility staff r and omly divided into two treatment groups . One group completed instructor-led ( IL ) fire safety training and the other completed computer-based ( CB ) training adapted from the IL version . Both the CB and IL groups significantly increased their scores from pre- to posttest . Differences between the two groups were not significant The objective of this study was to determine the impact of a community based fire prevention intervention directed only to parents on the fire safety knowledge and behavior in elementary school children . This was a prospect i ve , quasi-r and omized controlled study in which third and fourth grade students from two elementary schools in an urban , poor , minority community completed knowledge/behavior surveys at baseline and following completion of the intervention . The intervention group received an in-home visit from fire department personnel who installed free lithium smoke detectors and provided a fire escape plan . After accounting for a small difference in baseline summary scores of knowledge and behavior between the control and intervention groups , this study found a modest improvement in fire safety behavior among children whose families received a fire prevention intervention reflecting a change in household fire safety practice s. However , there was no significant change in fire safety knowledge Background Fires and burns are a leading cause of unintentional injury death in the USA . Although it has been anecdotally reported that vacant dwellings are at a higher risk for fire , the association between vacancy and fire risk at the individual household level has not been empirically measured . Methods In this cross-sectional study , geocoded residential vacant properties ( VP ) and fire events are analysed in Baltimore City at the census tract level and the individual household level . Results On average , a 10 % increase in the proportion of vacancies in a census tract was associated with a 9.9 % increase in fires ( 95 % CI : 5 % to 15 % ) . R and om-effects Poisson models , controlling for housing and neighbourhood conditions , found contagion effects . The risk of fire in an occupied dwelling increased by 8 % ( 95 % CI : 1 % to 10 % ) for every vacant structure within 10 m , and the risk of fire decreased by half ( 95 % CI : 45 % to 62 % ) for every km between an occupied dwelling and vacant building . Close proximity to VP was associated with trash fires within dwellings ( p=0.039 ) and structure fires ( p=0.012 ) . Conclusions We believe that this is the first study to demonstrate increased risk posed by nearby VP at the household level , confirming earlier ecological analyses of the role of VP as strong correlates of home fires . Measurement of this risk can motivate property owners , policy makers and insurers to invest in risk reduction measures that include building maintenance and trash removal OBJECTIVE Fire is a leading cause of unintentional injury and , although young children are at particularly increased risk , there are very few evidence -based re sources available to teach them fire safety knowledge and behaviors . Using a pre-post r and omized design , the current study evaluated the effectiveness of a computer game ( The Great Escape ) for teaching fire safety information to young children ( 3.5 - 6 years ) . METHOD Using behavioral enactment procedures , children 's knowledge and behaviors related to fire safety were compared to a control group of children before and after receiving the intervention . RESULTS The results indicated significant improvements in knowledge and fire safety behaviors in the intervention group but not the control . CONCLUSION Using computer games can be an effective way to promote young children 's underst and ing of safety and how to react in different hazardous situations Background Although proven measures for reducing injury due to motor vehicle collision and residential fires exist , the number of families properly and consistently using child passenger restraints and smoke alarms remains low . This paper describes the design of the Safety In Seconds ( SIS ) 2.0 study , which aims to evaluate the impact of a smartphone app on parents ' use of child restraints and smoke alarms . Methods SIS is a multisite r and omised controlled trial . Participants are parents of children aged 4–7 years who are visiting the Pediatric Emergency Department or Pediatric Trauma Service . Parents are r and omised to receive tailored education about child passenger safety or about fire safety via the SIS smartphone app . A baseline and two follow-up surveys at 3 months and 6 months are conducted . Primary outcomes are : ( 1 ) having the correct child restraint for the child 's age and size ; ( 2 ) restraining the child in the back seat of the car ; ( 3 ) buckling the child up for every ride ; ( 4 ) having the restraint inspected by a child passenger safety technician ; ( 5 ) having a working smoke alarm on every level of the home ; ( 6 ) having hard-wired or lithium battery smoke alarms ; ( 7 ) having and ( 8) practising a fire escape plan . Discussion Finding ways to communicate with parents about child passenger and fire safety continues to be a research priority . This study will contribute to the evidence about how to promote benefits of proper and consistent child restraint and smoke alarm use . Trial registration number NCT02345941 ; Pre- results |
13,046 | 27,466,743 | This meta- analysis demonstrates a cross-sectional link between depression and low serum LDL | BACKGROUND A cross-sectional association between depression and serum low-density lipoprotein ( LDL ) has been noted in the literature .
This study aims to employ meta-analytic techniques to clarify the relationship between depression and serum LDL . | Cholesterol is an essential constituent of eukaryotic membranes and plays a crucial role in membrane organization , dynamics , function , and sorting . It is often found distributed non-r and omly in domains or pools in biological and model membranes and is thought to contribute to a segregated distribution of membrane constituents . Signal transduction events mediated by seven transmembrane domain G-protein coupled receptors ( GPCRs ) are the primary means by which cells communicate with and respond to their external environment . We analyzed the role of cholesterol in the plasma membrane organization of the G-protein coupled serotonin(1A ) receptor by fluorescence recovery after photobleaching ( FRAP ) measurements with varying bleach spot sizes . Our results show that lateral diffusion parameters of serotonin(1A ) receptors in normal cells are consistent with models describing diffusion of molecules in a homogenous membrane . Interestingly , these characteristics are altered in cholesterol-depleted cells in a manner that is consistent with dynamic confinement of serotonin(1A ) receptors in the plasma membrane . Importantly , analysis of lig and binding and downstream signaling of the serotonin(1A ) receptor suggests that receptor function is affected in a significantly different manner when intact cells or isolated membranes are depleted of cholesterol . These results assume significance in the context of interpreting effects of cholesterol depletion on diffusion characteristics of membrane proteins in particular , and cholesterol-dependent cellular processes in general Serum lipids have been associated with depression in the adult population ; however , this association during pregnancy remains unclear . The aim of this study was to evaluate the association between serum lipids and depressive symptom scores during pregnancy . A prospect i ve cohort of 238 pregnant women was followed at the 5th-13th , 20th-26th and 30th-36th weeks of gestation . Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale ( EPDS ) . Serum concentrations ( mg/dL ) of triglycerides , total cholesterol , and low- and high-density lipoproteins ( LDL-c ; HDL-c ) were the main exposures . Marital status ( married/single ) , physical activity ( active or very active/low or very low active ) , unplanned pregnancy ( no/yes ) , pre-pregnancy BMI ( < 25/≥ 25 kg/m(2 ) ) , generalized anxiety disorder ( no/yes ) and current suicidal ideation ( no/yes ) were considered as potential confounders . Analyses were performed using linear mixed-effects models . The results showed that the EPDS mean score ( 95%CI ) decreased with time during pregnancy trimesters [ 1st : 8.89 ( 95%CI = 8.28 - 9.51 ) , 2nd : 7.32 ( 95%CI = 6.67 - 7.97 ) and 3rd : 7.08 ( 95%CI = 6.41 - 7.74 ) ] . Suicidal ideation frequency at baseline was 18 % . HDL-c concentrations were inversely associated with changes in EPDS score ( β = -0.080 , 95%CI = -0.157 to -0.002 ) , while low or very low active women ( β = 1.288 , 95%CI = 0.630 - 1.946 ) , with single marital status ( β = 1.348 , 95%CI = 0.163 - 2.534 ) , unplanned pregnancy ( β = 1.922 , 95%CI = 0.714 - 3.131 ) , generalized anxiety disorder ( β = 2.139 , 95%CI = 0.410 - 3.868 ) and current suicidal ideation ( β = 1.927 , 95%CI = 0.596 - 3.258 ) tended to have higher EPDS scores . No relationship was observed between other lipids and EPDS scores . HDL-c concentration was inversely associated with changes in depressive symptom scores during pregnancy after adjusting for socio-economic , demographic , behavioral , nutritional , biochemical and mental health disorders BACKGROUND Lipids appear to mediate depressive vulnerability in the elderly ; however , sex differences and genetic vulnerability have not been taken into account in previous prospect i ve studies . METHODS Depression was assessed in a population of 1040 women and 752 men aged 65 years and older at baseline and after 7-year follow-up . Clinical level of depression ( DEP ) was defined as having either a score of 16 or higher on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini-International Neuropsychiatric Interview . Lipid levels , apolipoprotein E , and serotonin transporter linked promoter region ( 5-serotonin transporter gene linked promoter region ) genotypes were evaluated at baseline . RESULTS Multivariate analyses adjusted by sociodemographic and behavioral variables , measures of physical health including ischemic pathologies , and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP , independent of the use of lipid-lowering agents or apolipoprotein E status . Men with low low-density lipoprotein cholesterol levels had twice the risk of prevalent and incident DEP , whereas in women low high-density lipoprotein cholesterol levels were found to be significantly associated with increased prevalent DEP ( odds ratio = 1.5 ) only . A significant interaction was observed between low low-density lipoprotein-cholesterol and 5-serotonin transporter gene linked promoter region genotype , men with s/s or s/l genotype being at increased risk of DEP ( odds ratio = 6.0 and 2.7 , respectively ) . No significant gene-environment interaction was observed for women . CONCLUSIONS DEP is associated with higher atherogenic risk in women ( low high-density lipoprotein cholesterol ) , whereas the reverse is observed in men ( low low-density lipoprotein cholesterol ) . Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men AIMS We investigated the longitudinal association of depression , with and without cognitive dysfunction , with hemoglobin A1c ( HbA1c ) , systolic blood pressure ( SBP ) , and low-density lipoprotein ( LDL ) in a predominantly minority cohort . METHODS There were 613 participants . Presence of depression was defined by a score ≥7 on the Short-CARE depression scale . We tested participants for executive dysfunction using the Color Trails Test ( CTT ) , part 2 , and for memory dysfunction using the total recall task of the Selective Reminding Test ( TR-SRT ) . We classified performance in these tests as abnormal based on st and ardized score cutoffs ( < 16th percentile and one st and ard deviation below the sample mean ) . R and om effects models were used to compare repeated measures of the diabetes control measures between those with depression versus those without depression and ever versus never cognitively impaired . RESULTS Baseline depression was present in 36 % of participants . Over a median follow-up of 2 years , depression was not related to worse HbA1c , SBP , or LDL . The presence of ( 1 ) abnormal performance on a test of executive function and depression ( n=57 ) or ( 2 ) abnormal performance on a test of verbal recall and depression ( n=43 ) was also not associated with clinical ly significant worse change in diabetes control . CONCLUSIONS Depression , with or without low performance in tests of executive function and memory , may not affect clinical ly significant measures of diabetes control in the elderly This study compared the serum lipid concentrations in 100 patients with major depressive disorder ( MDD ) with those from 100 matched healthy controls . It was found that the serum total cholesterol concentration in patients with MDD ( 5.27 + /- 1.18 mmol/L ) was significantly lower than the value ( 6.63 + /- 1.32 mmol/L ) in sex- , age- , and weight-matched healthy controls . This significant decrease in serum cholesterol in patients with MDD was noted in both sexes and in all age groups . Patients with MDD , however , had significantly higher HDL cholesterol than matched controls . There were no statistically significant differences in serum concentrations of triglycerides , apolipoprotein ( Apo ) A1 , Apo B , transferrin , and albumin between patients and controls . Clinical recovery of patients with MDD was accompanied by a significant increase in serum total cholesterol from 5.27 + /- 1.18 mmol/L to 6.12 + /- 1.2 mmol/L. These results suggest an association between low serum total cholesterol and depression in both sexes and at all age groups BACKGROUND Cohort and case-control studies found that lower serum total cholesterol is associated with depression . It is , however , unclear whether low cholesterol or its lipoprotein fractions are causally related to depression . Using a Mendelian r and omization design , the potential association between apolipoprotein E ( APOE ) genotype ( affecting lifetime cholesterol levels ) and depressive symptoms was studied . METHODS In the longitudinal Finl and , Italy , the Netherl and s Elderly ( FINE ) Study 1089 men were included in 1985 . The 435 men from Finl and , 418 men from The Netherl and s , and 236 men from Italy ( aged 65 - 84 years ) were free of myocardial infa rct ion , stroke , diabetes mellitus and cancer at all time points . They were prospect ively studied around 1985 ( n=658 ) , 1990 ( n=668 ) , 1995 ( n=327 ) , and 2000 ( n=82 ) . Associations between serum cholesterol , lipoprotein fractions and APOE genotype , with depressive symptoms ( by Zung self-rating depression scale [ SDS ] ) were analyzed using multilevel regression models . RESULTS Serum total cholesterol was inversely associated with the Zung SDS ( -0.61 points per 1 mmol/L increase in cholesterol ; 95 % confidence interval : -1.05 to -0.17 ; P=0.007 ) , after adjustment for country , age , body mass index , smoking , and alcohol intake . However , none of the cholesterol lipoprotein fractions were associated with the Zung SDS . The APOE genotypes epsilon4/4 , epsilon4/3 ; epsilon3/3 ; epsilon4/2 , and epsilon3/2 or epsilon2/2 were associated with decreasing levels of serum total and LDL cholesterol ( Ps<0.001 ) , but not with increasing depressive symptoms ( P=0.67 ) . LIMITATIONS APOE genotype was assessed through protein isoforms and not actual DNA-based typing . CONCLUSIONS There was a modest inverse relationship between depression scores and serum total cholesterol in elderly men , but no associations with lipoprotein fractions or with the APOE genotype |
13,047 | 28,552,612 | CONCLUSIONS Incretin-based treatment in patients with T1DM may improve glycemic control and reduce insulin dose and weight without increasing the risk of serious adverse event , such as severe hypoglycemia , ketosis or ketoacidosis . | AIMS In patients with type 2 diabetes , incretin-based therapies can improve glucose control without increased weight gain or hypoglycemia .
Incretin-based drugs added to insulin therapy in type 1 diabetes ( T1DM ) have also been tried in many studies .
However , the results were controversial .
We thus performed a meta- analysis to assess the efficacy and safety of incretin-based therapies in patients with T1DM . | OBJECTIVE To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes ( T1D ) results in significant reduction in glycemia , body weight , and insulin dose . RESEARCH DESIGN AND METHODS We r and omized 72 patients ( placebo = 18 , liraglutide = 54 ) with T1D to receive placebo and 0.6 , 1.2 , and 1.8 mg liraglutide daily for 12 weeks . RESULTS In the 1.2-mg and 1.8-mg groups , the mean weekly reduction in average blood glucose was −0.55 ± 0.11 mmol/L ( 10 ± 2 mg/dL ) and −0.55 ± 0.05 mmol/L ( 10 ± 1 mg/dL ) , respectively ( P < 0.0001 ) , while it remained unchanged in the 0.6-mg and placebo groups . In the 1.2-mg group , HbA1c fell significantly ( −0.78 ± 15 % , −8.5 ± 1.6 mmol/mol , P < 0.01 ) , while it did not in the 1.8-mg group ( −0.42 ± 0.15 % , −4.6 ± 1.6 mmol/mol , P = 0.39 ) and 0.6-mg group ( −0.26 ± 0.17 % , −2.8 ± 1.9 mmol/mol , P = 0.81 ) vs. the placebo group ( −0.3 ± 0.15 % , −3.3 ± 1.6 mmol/mol ) . Glycemic variability was reduced by 5 ± 1 % ( P < 0.01 ) in the 1.2-mg group only . Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups ( P < 0.05 ) . There was a 5 ± 1 kg weight loss in the two higher-dose groups ( P < 0.05 ) and by 2.7 ± 0.6 kg ( P < 0.01 ) in the 0.6-mg group vs. none in the placebo group . In the 1.2- and 1.8-mg groups , postpr and ial plasma glucagon concentration fell by 72 ± 12 % and 47 ± 12 % , respectively ( P < 0.05 ) . Liraglutide led to higher gastrointestinal adverse events ( P < 0.05 ) and ≤1 % increases ( not significant ) in percent time spent in hypoglycemia ( < 55 mg/dL , 3.05 mmol/L ) . CONCLUSIONS Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss , small insulin dose reductions , and frequent gastrointestinal side effects . These findings do not justify the use of liraglutide in all patients with T1D Summary Background Type 1 diabetes results from autoimmune destruction of pancreatic β cells . Findings from pre clinical studies suggest that dipeptidyl peptidase-4 inhibitors and proton-pump inhibitors might enhance β-cell survival and regeneration . We postulated that sitagliptin and lansoprazole would preserve β-cell function in patients with recent-onset type 1 diabetes . Methods We did a double-blind , placebo-controlled , phase 2 trial ( REPAIR-T1D ) . Participants aged 11–36 years , diagnosed with type 1 diabetes within the past 6 months were recruited from Sanford Health Systems ( Sioux Falls , SD , USA ; Fargo , ND , USA ) , Children 's Hospitals and Clinics of Minnesota ( St Paul , MN , USA ) , and Rady Children 's Hospital ( San Diego , CA , USA ) . Participants were r and omly assigned ( 2:1 ) to receive oral sitagliptin ( 100 mg for participants ≥18 years , 50 mg for those < 18 years ) and lansoprazole ( 60 mg for participants ≥18 years , 30 mg for those < 18 years ) or matched placebo for 12 months . R and omisation was done by a blocked r and omisation process ( blocks of three and six ) , with separate streams for younger ( < 18 years ) and older ( ≥18 years ) participants , and males and females . All participants and personnel remained masked until after the completion of the final 12 month visit , at which time data were unmasked to the analysis team . The primary endpoint was C-peptide response to a mixed meal challenge at 12 months measured as 2 h area under curve . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01155284 . Findings Between Sept 21 , 2010 , and May 29 , 2012 , 46 participants were r and omly assigned to the treatment group and 22 to the placebo group ; of whom 40 participants in the treatment group and 18 in the placebo group completed the 12-month treatment . At 12 months , the mean change in C-peptide area under curve was −229 pmol/L ( 95 % CI −316 to −142 ) for the treatment group and −253 pmol/L ( −383 to −123 ) for the placebo group ; this difference was not significant ( p=0·77 ) . No adverse or serious adverse events were probably or definitely related to the study treatment . Interpretation Although the expected change in the primary endpoint was not achieved , not all participants had increases in glucagon-like peptide-1 and gastrin concentrations that were expected with treatment . Although participants did not have adverse events related to study drugs , the study is not powered to address safety definitively . Further trials including these drugs might be warranted , but should be design ed to ensure appropriate selection of participants and increases in these intermediary hormones . Funding Sanford Research and JDRF Incretin based therapies are known to have pleotropic benefits in type 2 diabetes but have not been studied in new onset type 1 diabetes . In this r and omized , open label study , we investigated the effect of the addition of exenatide or sitagliptin to insulin in patients with new onset type 1 diabetes . Our data suggest that the addition of exenatide and sitagliptin decreases insulin requirements without increasing endogenous insulin production and hypoglycemic events BACKGROUND The combination of insulin and glucagon-like peptide-1 ( GLP-1 ) receptor agonist therapy improves glycaemic control , induces weight loss , and reduces insulin dose needed in type 2 diabetes . We assessed the efficacy and safety of the GLP-1 receptor agonist liraglutide as an add-on therapy to insulin for overweight adult patients with type 1 diabetes . METHODS We did a r and omised , double-blind , placebo-controlled trial at Steno Diabetes Center ( Gentofte , Denmark ) . Patients aged 18 years or older with type 1 diabetes , insufficient glycaemic control ( HbA1c > 8 % [ 64 mmol/mol ] ) , and overweight ( BMI > 25 kg/m(2 ) ) were r and omly assigned ( 1:1 ) to receive insulin treatment plus either liraglutide or placebo ( saline solution ) by subcutaneous injection once per day . R and omisation was done in blocks of four . Treatment assignment was masked to investigators and patients . Treatment lasted 24 weeks and liraglutide was started at a dose of 0·6 mg per day , escalated to 1·2 mg per day after 1 week , and then again to 1·8 mg per day after another week . Intervals between dose increments could be extended at the discretion of the investigator . The primary endpoint was change in HbA1c from baseline to week 24 . Secondary endpoints were changes in hypoglycaemic events , glycaemic variability , glycaemic excursions , insulin dose , bodyweight , postpr and ial plasma concentrations of glucagon and GLP-1 , gastric emptying , blood pressure , heart rate , patient-reported outcome measures , time spent in hypoglycaemia , near-normoglycaemia , and hyperglycaemia , plasma fasting glucose , mean glucose , and cholesterol . Efficacy analyses were calculated by use of a mixed model , whereby a patient 's data are used as long as the patient is in the study . The safety analyses were done in the intention-to-treat population , which consisted of all patients who received at least one dose of their r and omly assigned study drug . This study is registered with Clinical Trials.gov , number NCT01612468 . FINDINGS Between July 10 , 2012 , and May 30 , 2014 , we enrolled 100 patients with type 1 diabetes , with 50 patients allocated liraglutide and 50 to placebo . Four patients from the liraglutide group and six patients from the placebo group discontinued treatment before 24 weeks . At the end of treatment , change in HbA1c from baseline did not differ between groups ( -0·5 % , 95 % CI -0·8 to -0·4 [ -6·0 mmol/mol , 95 % CI -8·7 to -4·4 ] with liraglutide vs -0·3 % , -0·6 to -0·2 [ -4·0 mmol/mol , -6·6 to -2·3 ] with placebo ; between-group difference -0·2 % [ -0·5 to 0·1 ; 2·2 mmol/mol , -5·5 to 1·1 ] , p=0·1833 ) . The number of hypoglycaemic events was reduced with liraglutide , with an incident rate ratio of 0·82 ( 95 % CI 0·74 to 0·90 ) . However , we detected no changes in glycaemic variability ( continuous overall net glycaemic action per 60 min from 10·3 [ 95 % CI 9·8 to 10·8 ] to 9·9 [ 9·2 to 10·6 ] in the liraglutide treated patients vs 10·2 [ 9·7 to 10·7 ] to 9·7 [ 9·1 to 10·3 ] in the placebo treated patients ) . Both bolus insulin ( difference -5·8 IU , 95 % CI -10·7 to -0·8 , p=0·0227 ) and bodyweight ( difference -6·8 kg , 95 % CI -12·2 to -1·4 , p=0·0145 ) decreased with liraglutide treatment compared with placebo . Heart rate increased with liraglutide , with a difference between groups of 7·5 bpm ( 95 % CI 2·8 - 12·2 , p=0·0019 ) . Postpr and ial plasma glucagon and GLP-1 concentrations did not differ between groups ( difference between groups at end of treatment : -408 mmol/L per 240 min [ 95 % CI -941 to 125 , p=0·1309 ] for glucagon and -266 mmol/L per 240 min [ -1034 to 501 , p=0·4899 ] for GLP-1 ) . Gastric emptying was delayed after 3 weeks of treatment with liraglutide ( 19·9 min , 95 % CI 0·8 to 39·0 , p=0·0412 ) , but we detected no difference after 24 weeks of treatment ( -1·5 min , -20·5 to 17·6 , p=0·8793 ) . Patient-reported outcome measures differed between groups only with respect to perceived frequency of hypoglycaemia , which was higher with placebo , with a difference between groups of -0·6 ( 95 % CI -1·1 to -0·07 , p=0·0257 ) . Liraglutide was associated with more frequent nausea ( 29 [ 58 % ] patients with liraglutide vs five [ 10 % ] with placebo ) , dyspepsia ( 11 [ 22 % ] patients with liraglutide vs one [ 2 % ] with placebo ) , diarrhoea ( ten [ 20 % ] patients with liraglutide vs one [ 2 % ] with placebo ) , decreased appetite ( seven patients [ 14 % ] with liraglutide vs none with placebo ) , and vomiting ( seven [ 14 % ] patients with liraglutide vs one [ 2 % ] with placebo ) . INTERPRETATION In patients with type 1 diabetes , overweight , and insufficient glycaemic control , the reduction in HbA1c did not differ between insulin plus placebo and insulin plus liraglutide treatment . Liraglutide was associated with reductions in hypoglycaemic events , bolus and total insulin dose , and bodyweight , and increased heart rate . FUNDING Novo Nordisk OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual β-cell function . RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual β-cell function ( C-peptide positive ) and 19 without ( C-peptide negative ) were studied . All C-peptide – positive patients were treated with liraglutide plus insulin , whereas C-peptide – negative patients were r and omly assigned to liraglutide plus insulin or insulin monotherapy . Continuous glucose monitoring with identical food intake and physical activity was performed before ( week 0 ) and during ( week 4 ) treatment . Differences in insulin dose ; HbA1c ; time spent with blood glucose < 3.9 , > 10 , and 3.9–9.9 mmol/L ; and body weight were evaluated . RESULTS Insulin dose decreased from 0.50 ± 0.06 to 0.31 ± 0.08 units/kg per day ( P < 0.001 ) in C-peptide – positive patients and from 0.72 ± 0.08 to 0.59 ± 0.06 units/kg per day ( P < 0.01 ) in C-peptide – negative patients treated with liraglutide but did not change with insulin monotherapy . HbA1c decreased in both liraglutide-treated groups . The percent reduction in daily insulin dose was positively correlated with β-cell function at baseline , and two patients discontinued insulin treatment . In C-peptide – positive patients , time spent with blood glucose < 3.9 mmol/L decreased from 3.0 to 1.0 h ( P = 0.03 ) . A total of 18 of 19 patients treated with liraglutide lost weight during treatment ( mean [ range ] −2.3 ± 0.3 kg [ −0.5 to −5.1 ] ; P < 0.001 ) . Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide . CONCLUSIONS Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control We have recently described a novel phenotype in a group of subjects with type 1 diabetes that is manifested by glucose > 11.1 mmol/l 120 min after an oral glucose load , but with normal fasting glucose levels . We now describe the metabolic characteristics of these subjects by comparing parameters of islet hormone secretion and glucose disposal in these subjects to age-matched nondiabetic control subjects . The patients with type 1 diabetes had fasting glucose , insulin , and glucagon values similar to those of control subjects . Additionally , the insulin secretory response to intravenous arginine at euglycemia was similar in the control and diabetic groups ( 264 + /- 33.5 and 193 + /- 61.3 pmol/l ; P = 0.3 ) . However , marked differences in beta-cell function were found in response to hyperglycemia . Specifically , the first-phase insulin response was lower in diabetic subjects ( 329.1 + /- 39.6 vs. 91.3 + /- 34.1 pmol/l ; P < 0.001 ) , as was the slope of glucose potentiation of the insulin response to arginine ( 102 + /- 18.7 vs. 30.2 + /- 6.1 pmol/l per mmol/l ; P = 0.005 ) and the maximum insulin response to arginine ( 2,524 + /- 413 vs. 629 + /- 159 pmol/l ; P = 0.001 ) . Although plasma levels of glucagon-like peptide (GLP)-1 and gastric inhibitory peptide ( GIP ) did not differ between control and diabetic subjects , the incretin effect was lower in the diabetic patients ( 70.3 + /- 5.4 vs. 52.1 + /- 5.9 % ; P = 0.03 ) . Finally , there was a lack of suppression of glucagon in the patients after both oral and intravenous glucose administration , which may have contributed to their postpr and ial hyperglycemia . Glucose effectiveness did not differ between patients and control subjects , nor did insulin sensitivity , although there was a tendency for the patients to be insulin resistant ( 9.18 + /- 1.59 vs. 5.22 + /- 1.17 pmol.(-1).min(-1 ) ; P = 0.08 ) . These data characterize a novel group of subjects with type 1 diabetes manifested solely by hyperglycemia following an oral glucose load in whom islet function is normal at euglycemia , but who have marked defects in both alpha- and beta-cell secretion at hyperglycemia . This pattern of abnormalities may be characteristic of islet dysfunction early in the development of type 1 diabetes BACKGROUND To assess the efficacy and tolerability of saxagliptin and C-peptide secretion in patients with diagnosed type 2 diabetes classified as glutamic acid decarboxylase antibody (GADA)-positive or GADA-negative . METHODS Post hoc analysis of data pooled from five r and omized , placebo-controlled , 24-week phase 3 studies ( n = 2709 ) was conducted . We evaluated mean change from baseline at week 24 in HbA1c , fasting plasma glucose , postpr and ial plasma glucose , fasting and postpr and ial C-peptide , and HOMA2-%β and the proportion of patients achieving HbA1c < 7 % ( 53 mmol/mol ) at week 24 . RESULTS Saxagliptin produced greater adjusted mean reductions from baseline in HbA1c versus placebo for GADA-negative [ difference vs placebo ( 95 % CI ) , -0.62 % ( -0.71 % to -0.54 % ) ; -6.8 mmol/mol ( -7.8 , -5.9 ) ] and GADA-positive patients [ -0.64 % ( -1.01 % to -0.27 % ) ; -7.0 mmol/mol ( -11.0 , -3.0 ) ] . Consistently , saxagliptin produced a greater reduction from baseline in fasting plasma glucose and postpr and ial plasma glucose versus placebo in GADA-positive versus GADA-negative patients , and more patients achieved HbA1c < 7 % ( 53 mmol/mol ) with saxagliptin versus placebo in both GADA-negative and GADA-positive patients . Saxagliptin increased β-cell function as assessed by HOMA2-%β and postpr and ial C-peptide area under the curve from baseline in patients in both GADA-positive and GADA-negative patients . Adverse events and hypoglycaemic events were similar across treatment groups and GADA categories . CONCLUSION Saxagliptin was effective in lowering blood glucose levels and generally well tolerated in GADA-positive patients . Interestingly , saxagliptin appears to improve β-cell function in these patients , although a longer treatment duration may be needed to confirm this finding OBJECTIVE To investigate whether liraglutide added to treat-to-target insulin improves glycemic control and reduces insulin requirements and body weight in subjects with type 1 diabetes . RESEARCH DESIGN AND METHODS A 52-week , double-blind , treat-to-target trial involving 1,398 adults r and omized 3:1 to receive once-daily subcutaneous injections of liraglutide ( 1.8 , 1.2 , or 0.6 mg ) or placebo added to insulin . RESULTS HbA1c level was reduced 0.34–0.54 % ( 3.7–5.9 mmol/mol ) from a mean baseline of 8.2 % ( 66 mmol/mol ) , and significantly more for liraglutide 1.8 and 1.2 mg compared with placebo ( estimated treatment differences [ ETDs ] : 1.8 mg liraglutide −0.20 % [ 95 % CI −0.32 ; −0.07 ] ; 1.2 mg liraglutide −0.15 % [ 95 % CI −0.27 ; −0.03 ] ; 0.6 mg liraglutide −0.09 % [ 95 % CI −0.21 ; 0.03 ] ) . Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus placebo ( estimated treatment ratios : 1.8 mg liraglutide 0.92 [ 95 % CI 0.88 ; 0.96 ] ; 1.2 mg liraglutide 0.95 [ 95 % CI 0.91 ; 0.99 ] ; 0.6 mg liraglutide 1.00 [ 95 % CI 0.96 ; 1.04 ] ) . Mean body weight was significantly reduced in all liraglutide groups compared with placebo ETDs ( 1.8 mg liraglutide −4.9 kg [ 95 % CI −5.7 ; −4.2 ] ; 1.2 mg liraglutide −3.6 kg [ 95 % CI −4.3 ; −2.8 ] ; 0.6 mg liraglutide −2.2 kg [ 95 % CI −2.9 ; −1.5 ] ) . The rate of symptomatic hypoglycemia increased in all liraglutide groups ( estimated rate ratios : 1.8 mg liraglutide 1.31 [ 95 % CI 1.07 ; 1.59 ] ; 1.2 mg liraglutide 1.27 [ 95 % CI 1.03 ; 1.55 ] ; 0.6 mg liraglutide 1.17 [ 95 % CI 0.97 ; 1.43 ] ) , and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg only ( event rate ratio 2.22 [ 95 % CI 1.13 ; 4.34 ] ) . CONCLUSIONS Liraglutide added to insulin therapy reduced HbA1c levels , total insulin dose , and body weight in a population that was generally representative of subjects with type 1 diabetes , accompanied by increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis , thereby limiting clinical use in this group IMPORTANCE Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results . OBJECTIVE To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes . DESIGN , SETTING , AND PARTICIPANTS Multicenter ( 26 pediatric endocrinology clinics ) , double-blind , placebo-controlled r and omized clinical trial involving 140 adolescents aged 12.1 to 19.6 years ( mean [ SD ] 15.3 [ 1.7 ] years ) with mean type 1 diabetes duration 7.0 ( 3.3 ) years , mean body mass index ( BMI ) 94th ( 4 ) percentile , mean total daily insulin 1.1 ( 0.2 ) U/kg , and mean HbA1c 8.8 % ( 0.7 % ) . INTERVENTIONS R and omization to receive metformin ( n = 71 ) ( ≤2000 mg/d ) or placebo ( n = 69 ) . MAIN OUTCOMES AND MEASURES Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c . Secondary outcomes included change in blinded continuous glucose monitor indices , total daily insulin , BMI , waist circumference , body composition , blood pressure , and lipids . RESULTS Between October 2013 and February 2014 , 140 participants were enrolled . Baseline HbA1c was 8.8 % in each group . At 13-week follow-up , reduction in HbA1c was greater with metformin ( -0.2 % ) than placebo ( 0.1 % ; mean difference , -0.3 % [ 95 % CI , -0.6 % to 0.0 % ] ; P = .02 ) . However , this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2 % in each group ( mean difference , 0 % [ 95 % CI , -0.3 % to 0.3 % ] ; P = .92 ) . At 26-week follow-up , total daily insulin per kg of body weight was reduced by at least 25 % from baseline among 23 % ( 16 ) of participants in the metformin group vs 1 % ( 1 ) of participants in the placebo group ( mean difference , 21 % [ 95 % CI , 11 % to 32 % ] ; P = .003 ) , and 24 % ( 17 ) of participants in the metformin group and 7 % ( 5 ) of participants in the placebo group had a reduction in BMI z score of 10 % or greater from baseline to 26 weeks ( mean difference , 17 % [ 95 % CI , 5 % to 29 % ] ; P = .01 ) . Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group ( mean difference , 36 % [ 95 % CI , 19 % to 51 % ] ; P < .001 ) . CONCLUSIONS AND RELEVANCE Among overweight adolescents with type 1 diabetes , the addition of metformin to insulin did not improve glycemic control after 6 months . Of multiple secondary end points , findings favored metformin only for insulin dose and measures of adiposity ; conversely , use of metformin result ed in an increased risk for gastrointestinal adverse events . These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control . TRIAL REGISTRATION clinical trials.org Identifier : NCT01881828 OBJECTIVE This study investigated the efficacy and safety of once-daily liraglutide 1.2 mg versus placebo as add-on to insulin treatment in normal-weight patients with poorly controlled type 1 diabetes . RESEARCH DESIGN AND METHODS In a r and omized ( 1:1 ) , double-blind , placebo-controlled design , 40 patients with type 1 diabetes ( HbA1c ≥8 % [ 64 mmol/mol ] ) received once-daily liraglutide 1.2 mg or placebo for 12 weeks . Continuous glucose monitoring was performed before and at the end of treatment . The primary end point was change in HbA1c . Secondary end points included change in insulin dose , weight , glycemic excursions , heart rate , and blood pressure . RESULTS Baseline HbA1c was similar in the liraglutide and placebo group ( 8.8 ± 0.2 and 8.7 ± 0.1 % [ 72.5 ± 2.2 and 71.8 ± 1.5 mmol/mol ] ) . Change in HbA1c from baseline was −0.6 ± 0.2 % ( −6.22 ± 1.71 mmol/mol ) with liraglutide and −0.5 ± 0.2 % ( −5.56 ± 1.67 mmol/mol ) with placebo ( P = 0.62 ) . Variation in glycemic excursions did not change in either group . Change in body weight was −3.13 ± 0.58 and + 1.12 ± 0.42 kg ( P < 0.0001 ) with liraglutide and placebo , respectively . The bolus insulin dose decreased in liraglutide-treated patients and did not change with placebo treatment ( 4.0 ± 1.3 vs. 0.0 ± 1.0 IU , P = 0.02 ) . Heart rate increased within the liraglutide group ( P = 0.04 ) but not compared with placebo , whereas mean systolic blood pressure decreased compared with placebo ( between-group difference 3.21 mmHg [ 95 % CI −8.31 to 1.90 ] , P = 0.04 ) . Liraglutide was more frequently associated with gastrointestinal adverse effects . The incidence of hypoglycemia did not differ between groups . CONCLUSIONS Liraglutide significantly reduces body weight and insulin requirements but has no additional effect on HbA1c in normal-weight patients with type 1 diabetes inadequately controlled on insulin alone OBJECTIVE Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postpr and ial glucagon increase . This study evaluated the effects of sitagliptin ( dipeptidyl peptidase-IV [ DPP-IV ] inhibitor , approved for patients with type 2 diabetes ) , in adults with type 1 diabetes to improve glycemic control through decreasing postpr and ial glucagon . METHODS This investigator-initiated , double-blind , r and omized-parallel 20-week study enrolled 141 subjects . Subjects received sitagliptin 100 mg/day or placebo for 16 weeks . A subset of 85 patients wore blinded continuous glucose monitors ( CGM ) for 5 separate 7-day periods . The primary outcome was post-meal ( Boost ™ ) reduction in 4-hour glucagon area under the curve ( AUC ) . Secondary endpoints included changes in glycated hemoglobin ( A1c ) , CGM data , insulin dose , glucagon-like peptide-1 ( GLP-1 ) , glucose-dependent insulinotropic peptide ( GIP ) , and C-peptide levels . RESULTS There were no differences at screening between groups ; however , after a 4-week run-in phase , A1c was significantly lower in the sitagliptin vs. placebo group . Post-meal GLP-1 levels were higher ( P<.001 ) and GIP levels lower ( P = .03 ) , with glucagon suppression at 30 minutes ( LS means 23.2 ± 1.9 versus 16.0 ± 1.8 ; P = .006 ) in the sitagliptin group at 16 weeks . There were no differences between the groups in change in A1c , insulin dose , weight , or C-peptide after 16 weeks of treatment . However , C-peptide positive patients r and omized to sitagliplin had a non-significant trend toward decrease in A1c , mean glucose , and time spent in hyperglycemia . CONCLUSION Sitagliptin use in type 1 diabetes did not change glucagon AUC , A1c , insulin dose , or weight despite post-meal rise in GLP-1 levels . C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia , which needs further evaluation CONTEXT Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors have been widely used in type 2 diabetes . An important unanswered question concerns the effect of DPP-4 inhibition on β-cell function in patients with autoimmune diabetes . OBJECTIVE The objective of the study was to investigate the effects of the DPP-4 inhibitor on β-cell function in patients with recent-onset latent autoimmune diabetes in adults ( LADA ) . DESIGN AND SETTING This study was an open-label , r and omized-controlled study conducted in the Department of Endocrinology at the Second Xiangya Hospital . PATIENTS AND INTERVENTION Thirty recently diagnosed LADA patients were r and omized 1:1 to receive insulin therapy with 100 mg/d sitagliptin ( group A , n = 15 ) or without sitagliptin ( group B , n = 15 ) for 12 months . MAIN OUTCOME MEASURES Fasting and 2-hour postpr and ial blood sample s were obtained at baseline and after 3 , 6 , 9 , and 12 months of treatment to determine blood glucose , glycosylated hemoglobin , and C-peptide levels . RESULTS There were no differences in the clinical baseline data between the two groups . During the 12 months of follow-up , there were no significant differences in glucose and glycosylated hemoglobin levels between the two groups . At 12 months , fasting C-peptide ( FCP ) , 2-hour postpr and ial C-peptide ( CP ) , and ΔCP ( ΔCP = 2 h CP-FCP ) levels were not different in group A ( P > .05 ) compared with baseline , whereas in group B the levels of FCP , 2-hour CP and ΔCP were significantly decreased compared with baseline ( P < .05 ) . Levels of 2-hour CP were higher in group A than group B at 12 months ( P < .05 ) . CONCLUSIONS LADA patients treated with sitagliptin and insulin maintained β-cell function by comparison with insulin alone OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes . RESEARCH DESIGN AND METHODS A 26-week , placebo-controlled , double-blind , parallel-group trial enrolling 835 subjects r and omized 3:1 receiving once-daily subcutaneous liraglutide ( 1.8 , 1.2 , and 0.6 mg ) or placebo added to an individually capped total daily dose of insulin . RESULTS Mean baseline glycated hemoglobin ( HbA1c ) ( 8.1 % [ 65.0 mmol/mol ] ) was significantly decreased with liraglutide versus placebo at week 26 ( 1.8 mg : –0.33 % [ 3.6 mmol/mol ] ; 1.2 mg : –0.22 % [ 2.4 mmol/mol ] ; 0.6 mg : –0.23 % [ 2.5 mmol/mol ] ; placebo : 0.01 % [ 0.1 mmol/mol ] ) . Liraglutide significantly reduced mean body weight ( –5.1 , –4.0 , and –2.5 kg for 1.8 , 1.2 , and 0.6 mg , respectively ) versus placebo ( –0.2 kg ) . Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo . There were higher rates of symptomatic hypoglycemia ( 21.3 vs. 16.6 events/patient/year ; P = 0.03 ) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis > 1.5 mmol/L with liraglutide 1.8 mg vs. placebo ( 0.5 vs. 0.1 events/patient/year ; P = 0.01 ) . CONCLUSIONS In a broad population of subjects with long-st and ing type 1 diabetes , liraglutide added to capped insulin reduced HbA1c , body weight , and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg |
13,048 | 31,700,579 | MBL in all dental implants can be considered independent of the type of prosthetic rehabilitation and the moment of load ; this was emphasized .
The MBL is smaller in dental implants with rough surfaces , switch platforms and infracrestal localization , as they are of multifactorial origin . | Background The marginal bone of dental implants is subjected to slight load modifications over time , conditioning implant survival .
Objective : Perform a systematic review of the literature analyzing the factors that contribute to marginal bone loss ( MBL ) and the subsequent development of peri-implantitis . | OBJECTIVE To investigate the effect of a 1-week postoperative course of 600 mg of ibuprofen taken four times a day on marginal bone level around oral implants . MATERIAL S AND METHODS Twenty-eight patients were allocated to the ibuprofen group ( 14 patients ) or no-ibuprofen group ( 14 patients ) . Overall , 57 implants were inserted , 31 implants in the ibuprofen group and 26 in the no-ibuprofen group . The primary outcome measure was the change in marginal bone level around oral implants from baseline ( 2 weeks postplacement ) to the 3- and 6-month radiographic examinations . The paralleling technique and a film holder coupled to a beam- aim ing device were used to take the periapical radiographs . Measurement of changes in bone level was made using a viewing box and ×8 magnifier . RESULTS Three subjects were withdrawn from the therapy early as they did not complete the dose of ibuprofen ( e.g. because of self-reported stomach upset ) . The mean marginal mesial bone loss from the baseline was 0.37 mm at the 3-month and 0.27 mm at the 6-month follow up for the ibuprofen group , while the corresponding values for the no-ibuprofen group were 0.15 mm and 0.08 mm . The mean marginal distal bone loss from the baseline was 0.42 mm at the 3-month and 0.2 mm at the 6-month follow up for the ibuprofen group , while the corresponding values for the no-ibuprofen group were 0.08 mm and 0.15 mm . There were no significant differences between the ibuprofen and no-ibuprofen groups when comparing the bone changes . CONCLUSION Administration of a short course of systemic ibuprofen for postoperative pain management following implant insertion may not have a significant effect on the marginal bone loss around oral implants in the early healing phase The results of a r and omised trial with bisphosphonate-coated dental implants have been reported previously . Each patient received one coated and one uncoated implant in a double-blind split-mouth design study . After 6 months of osseointegration , resonance frequency analysis indicated better fixation of the coated implants . Reduced marginal bone resorption was also shown . However , it was not known whether the advantage of the bisphosphonate coating would persist over time . The radiographic results at 5 years after implant installation are reported herein . A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients ( two had died ) and compared these with the post-implantation images . Non-parametric statistics were used . All implants functioned well . The median marginal bone loss for control implants was found to be 0.70 mm , which is less than usually reported in the literature . The bisphosphonate-coated implants showed even less resorption ( median 0.20 mm ) . The median difference within each pair of implants after 5 years of use was 0.34 mm ( 95 % confidence interval 0.00 - 0.75 mm ; P=0.04 ) . The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone This study was design ed to radiographically evaluate the effect of surface macro- and microstructures within the coronal portion of the external hex implant at the marginal bone change after loading . The fifty-four patients included in the study were r and omly assigned to treatment groups with rough-surface implants ( TiUnite , n = 45 ) , a hybrid of smooth and rough surface implants ( Restore , n = 45 ) or rough-surface with microthreads implants ( Hexplant , n = 45 ) . Clinical and radiographic examinations were conducted at the time of implant loading ( baseline ) and at 1-year post-loading . A three-level mixed-effect ancova was used to test the significance of the mean marginal bone change of the three implant groups from baseline to 1-year follow-up . At 1-year , significant differences were noted in marginal bone loss recorded for the three groups ( P < 0.0001 ) . The rough surface with microthread implants had a mean crestal bone loss of 0.42 + /- 0.27 mm ; the rough surface implants , 0.81 + /- 0.27 mm ; and the hybrid surface implants , 0.89 + /- 0.41 mm . Within the limitations of this study , a rough surface with microthreads at the coronal part of implant maintained the marginal bone level against functional loading better than implants without these two features PURPOSE The purpose of this prospect i ve study was to assess the change of marginal bone level around three different types of external-hex implants after 5 years using radiography . MATERIAL S AND METHODS Included in this study were 54 patients r and omly put into three different groups ; rough-surface implants ( Brånemark ) , machined coronal aspect implants ( Restore ) , and microthreaded coronal aspect implants ( Hexplant ) . Clinical and radiographic assessment s were performed contemporaneously with implant loading ( baseline ) and at 1 , 3 , and 5 years post-functional loading . A mixed-model analysis was employed to examine mean marginal bone change significance in the three treatment groups . RESULTS In a total of 31 out of 54 patients , 81 of 135 implants remained to the end of the study . At 5 years , the microthreaded coronal aspect implants had 0.61 ± 0.32 mm mean crestal bone loss ; the rough-surface implants without microthread , 0.99 ± 0.38 mm ; and the machined coronal aspect implants , 1.06 ± 0.39 mm . The rough-surface implants and the machined coronal aspect implants did not exhibit statistically significantly different marginal bone loss , whereas the microthreaded coronal aspect implants exhibited significantly less marginal bone loss ( P = .0015 ) . CONCLUSION In this research , rough-surface implants with microthreads showed positive long-term effects in preserving peri-implant bone level against functional loads when compared with implants lacking these aspects at the coronal part . Most of the bone loss was shown within 1 year of loading , and all types of implants stabilized after 1 year OBJECTIVES This r and omised , controlled multicentre trial aim ed at comparing two versions of a variable-thread dental implant design to a st and ard tapered dental implant design in cases of immediate functional loading for 36 months after loading . MATERIAL S AND METHODS 177 patients ( 325 implants ) were included at 12 study centres and r and omly allocated into one of three treatment groups : NAI ( variable-thread design , NobelActive internal connection ) , NAE ( variable-thread design , NobelActive external connection ) and , as control , NR ( st and ard tapered design , NobelReplace tapered groovy ) . Inclusion criteria concerned healed bony implant sites and feasibility for immediate loading . Clinical and radiographic examinations were performed at implant placement and after 3 , 6 , 12 , 24 and 36 months . The outcome measures were marginal bone remodelling ( primary outcome ) , implant survival and success , papilla score , plaque accumulation , and bleeding on probing . RESULTS 127 patients ( NAI : 45 , NAE : 41 , NR : 41 ) were followed-up and evaluated after 36 months . No significant differences in cumulative survival rates were seen for the groups ( NAI : 95.7 % ; NAE : 96.3 % ; NR : 96.6 % ) . In all groups , bone remodelling occurred during the first 3 months , with stable or even increasing bone levels after the initial remodelling period . The bone remodelling from insertion to 36 months for the NAI group ( -0.89 ± 1.65 mm ) was comparable ( P = 0.98 ) to that of the NR group ( -0.85 ± 1.32 mm ) . The NAE group showed comparable bone remodelling during the first year , with an increase in following years result ing in significantly less overall bone loss ( -0.16 ± 1.06 mm ) ( P = 0.041 ) . Overall improvement in papilla size was observed in all treatment groups . CONCLUSIONS Over 36 months , the results show stable or improving bone levels for all treatment groups after the initial bone remodelling seen during the first 3 months after placement . The variable- thread implants showed results comparable to those of st and ard tapered implants in cases of immediate function , and therefore can be considered as a treatment option for immediate loading PURPOSE The purpose of this clinical trial was to evaluate whether the crestal bone height around dental implants could be influenced by the use of a platform-switching protocol . MATERIAL S AND METHODS All implants placed in the year 2006 in healed bone without any need for ridge augmentation were included in this study . The following groups were created : ( 1 ) wide-diameter implants were placed subcrestally and regular-diameter cover screws were connected ; ( 2 ) regular-diameter implants were placed at the crest and regular-diameter cover screws were connected . St and ardized radiographs were obtained after insertion of the definitive prosthesis and after 1 year . Calibrated measurements were conducted initiating from the mesial and distal bone peaks to the implant-abutment junction . The average value of the mean medial and mean distal values was calculated and analyzed with an unpaired two-tailed t test . P values < .05 were regarded as statistically significant . RESULTS In all , 89 dental implants in 36 patients were evaluated . The implants with a platform-switched configuration ( n = 75 ) exhibited statistically significantly less bone loss at time of insertion of the definitive prosthesis ( 0.30 + /- 0.07 mm versus 0.68 + /- 0.17 mm ; P < .05 ) and at 1 year ( 0.39 + /- 0.07 mm versus 1.00 + /- 0.22 mm , P < .01 ) when compared to the nonplatform-switched implants ( n = 14 ) . CONCLUSION Platform-switched implants seem to limit crestal bone remodeling OBJECTIVE To evaluate the 3-year clinical and radiographic data of fixed implant-supported dental prosthesis delivered to patients having taken alendronate 35 - 70 mg weekly for at least 3 years before implant placement . MATERIAL S AND METHODS Forty consecutive patients treated with oral bisphosphonates and requiring an implant-supported restoration were recruited in two private centers between January 2008 and December 2011 . Implants were inserted through minimally invasive approach under antibacterial and antibiotic treatment , 6 months after alendronate administration stopping . After 4 months of submerged healing , implants underwent prosthetic loading . Hygiene maintenance and clinical assessment s were scheduled every 4 months for 3 years . Outcome measures were the following : implant and prosthetic success , survival rates , any observed clinical complications , marginal bone remodeling , probing pocket depth and bleeding-on-probing . RESULTS At the end of the study , eight patients dropped out . The final sample size result ed in 32 consecutive partially or fully edentulous patients ( 32 females ; mean age 64.6 years ) with 98 submerged implants . In only one patient , maxillary implant failed during healing period . No prosthesis failed during the entire follow-up , and no major complications were recorded . Implant and prostheses success result ed in an overall survival rate of 98 , 98 % and 100 % , respectively . Three-year mean marginal bone loss was 1.35 ± 0.21 ( CI 95 % 1.24 - 1.38 ) . Successful soft tissue parameters were found around all implants . CONCLUSIONS Oral bisphosphonate therapy did not appear to significantly affect implant survival and success in case of accurate treatment time selection , minimally invasive surgical approach and constant follow-up . Further prospect i ve studies involving larger sample sizes and longer duration s of follow-up are required to confirm these results Abstract Objective Evaluation of differences in the clinical performance and crestal bone levels between implants restored with single crowns with platform‐matched or platform‐switched abutments after 3 years . Material and Methods The study enrolled adult patients missing two or more adjacent teeth in the posterior m and ible with natural teeth mesial to the implant site . R and omization followed open‐flap implant insertion and the corresponding matching or switching healing abutments placed at surgery . Conventional loading was made with cemented crowns . Clinical follow‐up took place annually after loading up to 3 years . Bone level changes were measured in st and ardized radiographs as the variation in crestal bone from one evaluation to the next . Results Sixty‐three patients with a total of 135 implants ( 66 platform matching , 69 platform switching ) were analysed . From surgery to 36 months , mean bone loss was 0.28 ± 0.56 mm for the platform‐switching group and 0.68 ± 0.64 mm for the platform‐matching group . A statistically significant difference was found between groups ( p = 0.002 ) with an estimate of 0.39 mm ( 0.15–0.64 , 95 % CI ) in favour of platform switching . Conclusions After 3 years , platform‐switching restorations showed a significant effect in the preservation of marginal bone levels compared to platform‐matching restorations BACKGROUND It has been reported in many articles that marginal bone resorptions are prevented by platform-switching design . However , what occurs when these implants are placed in the apical position is not completely known . PURPOSE This report describes a r and omized controlled clinical trial study that aims to test the hypothesis that less resorption will occur when platform-switching implants are placed 1 mm below bone level . MATERIAL S AND METHODS A total of 56 r and omly selected implants were inserted bilaterally , either 1 mm below bone level ( test group , 28 implants ) or at bone level ( control group , 28 implants ) of the patients ' posterior regions . Marginal bone resorptions were examined through periapical radiographies taken with the parallel technique at the time of crown cementation and the third , sixth , 12th , and 36th months after prosthetic loading . The modified plaque index , gingival index , bleeding on probing , and probing depths were used for follow-up periodontal care of the implants . RESULTS After 3 years , the mean radiographic vertical bone loss in the control group was significantly lower than in the test group ( 0.56 ± 0.35 mm and 1.21 ± 1.05 mm , respectively ) ( p < .01 ) . In terms of periodontal indexes , there were no statistically significant differences between the two groups ( p > .05 ) . No peri-implantitis or peri-implant mucositis was observed around the test or control implants . CONCLUSIONS More marginal bone resorptions occurred after the third year of loading in implants placed 1 mm below bone level . However , the resorptions did not reach the implants thread . In the control group , the first bone implant contact was placed under the level of the first threads . Therefore , the present r and omized clinical trial confirmed the hypothesis that placing platform-switching implants 1 mm below bone level reduced marginal bone loss . It can be noted that to reduce resorption , platform-switching implants should be placed below bone level Purpose : This study was design ed to compare radiographically the effect of microthread on the coronal portion of the fixture on marginal bone level ( MBL ) around immediately placed dental implants in human subjects . Material and Methods : Forty-one roughened surface screw type Dentium oral implants ( Dentium ) were inserted in fresh extraction sockets of the anterior segment of maxilla of 30 patients . The implants were selected r and omly using either microthread design on coronal portion of the fixture ( Implantium ) ( test group ) or without microthread thread design ( Superline ) ( control group ) . MBL was measured using digital subtraction radiography technique after 3 , 6 , and 12 months . Results : At month 3 , the microthread groups have been associated with more marginal bone loss than the control group ( P = 0.04 ) . At months 6 and 12 , both groups had comparable bone levels ( P = 0.21 ) . Conclusion : The microthread design of the implant collar could not have a positive effect in maintaining the MBL around implants placed in fresh extraction socket in anterior maxilla BACKGROUND The design of the implant neck might be significant for preservation of marginal bone . PURPOSE To compare the 5-year radiographic and clinical outcome of single anterior implants provided with a smooth neck , a rough neck or a scalloped rough neck . MATERIAL S AND METHODS 93 Patients with a missing anterior tooth in the maxilla were included . At r and om , patients received an implant with a 1.5 mm smooth neck ( " smooth group " ) , a rough neck with grooves ( " rough group " ) or a scalloped rough neck with grooves ( " scalloped group " ) . Implants were installed in healed sites . Follow-up visits were conducted after final crown delivery and 1 year and 5 years later . RESULTS Scalloped implants showed significantly more initial marginal bone resorption . The total amount of bone loss was 1.26 ± 0.90 mm in the smooth group , 1.20 ± 1.1 mm in the rough group and 2.28 ± 0.97 mm in the scalloped group ( P < .05 ) . Survival rates were 96.2 % for the smooth and scalloped group and 100 % for the rough group . Scalloped implants showed deeper pocket depths , more bleeding and more technical complications . There were no differences in esthetic outcome nor in patient satisfaction . CONCLUSIONS For anterior single tooth replacements , scalloped implants show less favorable radiographic and clinical outcome compared to regular implants with a smooth neck or rough neck PURPOSE To evaluate crestal bone changes around implants with platform-switched abutments placed 1 mm subcrestally in a prospect i ve clinical investigation . MATERIAL S AND METHODS Forty consecutive systemically healthy patients ( mean age ± st and ard deviation [ SD ] , 55.2 ± 8.7 years ) with one or more missing teeth were consecutively treated with 1-mm subcrestally positioned , platform-switched , tapered , full treated implants restored with coded abutments . A total of 58 implants were placed . Final restorations were delivered 4 to 8 months after implant insertion . Digital st and ardized periapical radiographs using customized film holders were obtained at the time of implant insertion , and at 12 and 24 months after final prosthesis placement . Marginal peri-implant bone levels were measured at the mesial and distal surfaces of each implant using digital image software . RESULTS All implants osseointegrated and were clinical ly stable at the 2-year follow-up . The cumulative survival rate was 100 % . From implant insertion to the 2-year follow-up , the mean bone loss was 0.32 ± 0.37 mm . No significant differences related to sex , implant site , and bone density were observed . The mean midbuccal and interproximal soft tissue margin positions were 1.13 ± 0.5 mm and 1.15 ± 0.6 mm coronal to the prosthetic finish line , respectively . CONCLUSION There is limited clinical information regarding the amount of marginal bone loss around two-piece platform-switched implants placed at subcrestal positions . Results of this study suggest that platform switching and subcrestal location of the implant-abutment interface may be effective in reducing bone loss and in preserving esthetics around dental implants BACKGROUND The mechanisms behind the impact of smoking on osseointegration are not fully understood . PURPOSE To investigate the initial clinical and molecular course of osseointegration of different implants in smokers and non-smokers in a r and omized controlled trial ( RCT ) . MATERIAL S AND METHODS Smoking ( n = 16 ) and non-smoking ( n = 16 ) patients received 3 implant types : machined , oxidized , and laser-modified surfaces . Baseline bone biopsies were retrieved from the implant sites . After 60 and 90 days , the pain score , implant stability quotient ( ISQ ) , and peri-implant crevicular fluid ( PICF ) gene expression were analyzed . Furthermore , radiological and clinical assessment s were made at 90 days . RESULTS At 90 days , no pain was reported , irrespective of smoking habit . A higher ISQ was found in smokers compared with non-smokers . Marginal bone loss ( MBL ) was greater in smokers than in non-smokers . The comparison of implant surfaces revealed greater MBL exclusively at the machined implants in smokers . At 90 days in smokers , the PICF around machined implants revealed a higher expression of the proinflammatory cytokine , interleukin-6 ( IL-6 ) , and a lower expression of the osteogenic gene , osteocalcin ( OC ) , compared with the PICF around modified implants . Furthermore , OC expression was lower at machined implants in smokers compared with machined implants in non-smokers . After adjustment for age and implant location ( maxilla/m and ible ) , multivariate regression revealed the following predictors of MBL : smoking , bleeding on probing at 90 days , hypoxia-inducible factor 1 alpha ( HIF-1α ) expression at baseline and IL-6 expression in PICF at 90 days . CONCLUSIONS During the early phase of osseointegration , non-smokers and smokers present a similar , high implant survival . In contrast , smokers present a greater MBL , particularly at machined implants . HIF-1α baseline expression in the recipient bone and IL-6 expression in PICF cells are important molecular determinants for MBL after 90 days . It is concluded that smoking has an early effect on osseointegration , which is dependent on the implant surface properties and the local host response BACKGROUND Osteoporosis has been called a potential risk factor for bone healing around implants . AIM The aim of this multicentre study was to verify the clinical performance of fluori date d implants in the maxilla of subjects with diagnosed systemic primary osteoporosis/osteopenia . MATERIAL AND METHODS Postmenopausal women in need of 2 - 8 splinted implants in maxilla underwent bone mineral density measurements in the hip and spine , using dual-energy X-ray absorptiometry scans . Based on their T-scores , they were divided into two study groups : Group O ( osteoporosis/osteopenia group ) subjects had a T-score ≤-2 , Group C ( control group ) had a T-score of ≥-1 , and subjects with a T-score < -1 but > -2 were excluded . Implants were placed with a two-stage procedure and loaded 4 - 8 weeks after abutment surgery . At 6 months and 1 year after functional loading , clinical parameters ( including peri-apical radiographs ) were assessed . RESULTS One hundred and forty-eight implants were placed in 48 subjects ( mean age : 67 years ( range [ 59 - 83 ] ) . Sixty-three implants were placed in 20 osteoporosis subjects ( Group O , mean age : 69 years ; range [ 59 - 83 ] ) , and 85 were placed in control subjects ( Group C , mean age : 65 years ; range [ 60 - 74 ] ) . The cumulative survival rate , on an implant level , was 99.3 % ( Group O : 98.4 % ; Group C : 100.0 % ) . The cumulative survival rate , on a subject level , was 97.9 % ( Group O : 94.7 % ; Group C : 100.0 % ) . Marginal bone level ( MBL ) alterations from functional loading to the 1-year follow-up visit were measured on an implant level and a subject level . The overall MBL alteration on an implant level was -0.01 ± 0.51 mm ( Group O : -0.11 ± 0.49 mm ; Group C : 0.05 ± 0.52 mm ) . The overall MBL alteration on a subject level was -0.04 ± 0.27 mm ( Group O : -0.17 ± 0.30 mm ; Group C : 0.04 ± 0.23 mm ) . CONCLUSION Within the limitations of this prospect i ve , non-r and omized , controlled , multicentre study , it can be concluded that oral implant therapy in patients suffering from osteoporosis/osteopenia is a reliable treatment option with comparable integration rates as in healthy patients . Long-term follow of the study groups is necessary to compare marginal bone alterations and treatment outcomes PURPOSE To evaluate advantages and disadvantages of identical implants with internal or external connections . MATERIAL S AND METHODS One hundred and twenty patients with any type of edentulism ( single tooth , partial and total edentulism ) , requiring one implant-supported prosthesis were r and omly allocated in two equal groups to receive either implants with an external connection ( EC ) or implants of the same type with an internal connection ( IC ) ( EZ Plus , MegaGen Implant , Gyeongbuk , South Korea ) , at four centres . Due to slight differences in implant design and components , IC implants were platformswitched while EC were not . Patients were followed for 5 years after initial loading . Outcome measures were prosthesis/implant failures , any complication , marginal bone level changes and clinician preference , assessed by blinded outcome assessors . RESULTS Sixty patients received 96 EC implants and 60 patients received 107 IC implants . Three patients dropped out with four EC implants and five patients with ten IC implants , but all remaining patients were followed up to 5-year post-loading . One prosthesis supported by EC implants and two by IC implants failed ( P = 0.615 , difference = -0.02 , 95 % CI : -0.08 to 0.04 ) . One EC implant failed versus three IC implants in two patients ( P = 0.615 , difference = -0.02 , 95 % CI : -0.08 to 0.04 ) . Ten complications occurred in 10 EC patients versus nine complications in 9 IC patients ( P = 1.000 , difference = 0.01 , 95 % CI : -0.13 to 0.15 ) . There were no statistically significant differences for prosthesis and implant failures and complications between the different connection types . Five years after loading , there were no statistically significant differences in marginal bone level estimates between the two groups ( difference = 0.14 mm , 95 % CI : -0.28 to 0.56 , P ( ancova ) = 0.505 ) and both groups lost bone from implant placement in a statistically significant way : 1.13 mm for the EC implants and 1.21 mm for the IC implants . Two operators had no preference and two preferred IC implants . CONCLUSIONS Within the limitations given by the difference in neck design and platform switching between EC and IC implants , 5-year post-loading data did not show any statistically significant differences between the two connection types , therefore clinicians could choose whichever they preferred PURPOSE The aim of this study is to assess the impact of insertion torque and implant neck design on peri-implant bone levels and gain insights into dynamic crestal tissue alterations by radiological , clinical , and biochemical examinations . MATERIAL AND METHODS In this prospect i ve trial , a total of 84 implants ( four implants in each patient ) in the interforaminal region of 21 edentulous m and ibles were r and omly alternated according to a split-mouth design . Implant placement was performed using different insertion torques ( ≤20 Ncm vs > 50 Ncm ) . In each group , one machined and one anodized implant neck design ( 1.5 mm length ) was used in the same jaw side . Evaluation of peri-implant tissues involved radiological , clinical examination and immunoassays for interleukin-1β . RESULTS No significant influence of insertion torque or implant neck design on peri-implant bone level was found . Protein levels of interleukin-1β in the peri-implant crevicular fluid revealed no difference between both insertion torque groups and different neck design s. CONCLUSION Interactive effects of insertion torque and neck surface modification may exist ; however , no clinical ly significant differences in marginal bone resorption after 1 year could be observed in the edentulous anterior m and ible PURPOSE The aim of this prospect i ve clinical trial was to compare the three-dimensional marginal bone level , implant stability , and peri-implant health of two types of submerged dental implants that were restored with matching or platform-switched abutments . MATERIAL S AND METHODS Twenty-five subjects were recruited ( test group : 43 implants with internal conical connection and back-tapered collar carrying a platform-switched abutment ; control group : 50 implants carrying a matched-platform abutment ) . Implant uncovering and conventional loading were performed after 3 months of healing , and the total observation time was 15 months . Marginal bone levels , resonance frequency analysis , insertion torque , and peri-implant health indices were recorded and analyzed statistically . RESULTS The cumulative implant survival rate was 100 % . At the second-stage surgery , bone levels were similar between groups . One year after loading , mean crestal bone loss was 0.35 ± 0.13 mm for test implants and 0.83 ± 0.16 mm for control implants , a significant difference . Primary stability was significantly higher in the test group than in the control group , but this difference disappeared after 3 months of healing prior to loading . Between-group differences for peri-implant health indices were negligible . CONCLUSIONS Both implant systems had the same survival rates . Implants with a built-in platform switch and conical connection with back-tapered collar design achieved higher primary stability at insertion and less bone resorption after 15 months |
13,049 | 25,415,364 | Results Maternal pre-pregnancy weight is a significant factor in the preconception period with underweight contributing to a 32 % higher risk of preterm birth , and obesity more than doubling the risk for preeclampsia , gestational diabetes .
Overweight women are more likely to undergo a Cesarean delivery , and their newborns have higher chances of being born with a neural tube or congenital heart defect .
Among nutrition-specific interventions , preconception folic acid supplementation has the strongest evidence of effect , preventing 69 % of recurrent neural tube defects .
Multiple micronutrient supplementation shows promise to reduce the rates of congenital anomalies and risk of preeclampsia . | Introduction There is increasingly a double burden of under-nutrition and obesity in women of reproductive age .
Preconception underweight or overweight , short stature and micronutrient deficiencies all contribute to excess maternal and fetal complications during pregnancy . | Objective : To investigate the association between ( self-reported ) maternal pre-pregnancy body mass index ( p BMI ) , and child ’s weight , height and BMI at age 14 months . Design : Prospect i ve multi-ethnic community-based cohort study . Setting : Amsterdam , The Netherl and s. Participants : 8266 pregnant women from the Amsterdam Born Children and their Development study , filled out a question naire covering socio-demographic data , obstetric history , lifestyle , dietary habits and psychosocial factors , 2 weeks after their first antenatal visit . 7730 gave birth to a viable term singleton infant with information on birth weight , gender and pregnancy duration . Growth data were available for 3171 of these children . Main outcome measures : Weight ( g ) , height ( cm ) and BMI ( kg/m2 ) of the child at age 14 months . Results : p BMI was linearly associated with weight and BMI of the child at age 14 months . One unit increase in p BMI result ed in an increment of 29 g ( 95 % CI 19 to 39 ) in weight and 0.041 kg/m2 ( 95 % CI 0.030 to 0.053 ) in BMI . The effect size decreased after adjustment for birth weight ( weight : β coefficient 19 g , 95 % CI 10 to 28 ; BMI : β coefficient 0.034 kg/m2 , 95 % CI 0.023 to 0.046 ) and hardly changed after adjustment for all other variables ( weight : β coefficient 21 g , 95 % CI 11 to 30 ; BMI : β coefficient 0.031 kg/m2 , 95 % CI 0.019 to 0.043 ) . p BMI was not related to height . Conclusions : p BMI is an independent determinant of weight and BMI of the child at age 14 months . At least one third of this effect is mediated through birth weight OBJECTIVE To evaluate whether morbidly obese women have an increased risk of pregnancy complications and adverse perinatal outcomes . METHODS In a prospect i ve population -based cohort study , 3,480 women with morbid obesity , defined as a body mass index ( BMI ) more than 40 , and 12,698 women with a BMI between 35.1 and 40 were compared with normal-weight women ( BMI 19.8 - 26 ) . The perinatal outcome of singletons born to women without insulin-dependent diabetes mellitus was evaluated after suitable adjustments . RESULTS In the group of morbidly obese mothers ( BMI greater than 40 ) as compared with the normal-weight mothers , there was an increased risk of the following outcomes ( adjusted odds ratio ; 95 % confidence interval ) : preeclampsia ( 4.82 ; 4.04 , 5.74 ) , antepartum stillbirth ( 2.79 ; 1.94 , 4.02 ) , cesarean delivery ( 2.69 ; 2.49 , 2.90 ) , instrumental delivery ( 1.34 ; 1.16 , 1.56 ) , shoulder dystocia ( 3.14 ; 1.86 , 5.31 ) , meconium aspiration ( 2.85 ; 1.60 , 5.07 ) , fetal distress ( 2.52 ; 2.12 , 2.99 ) , early neonatal death ( 3.41 ; 2.07 , 5.63 ) , and large-for-gestational age ( 3.82 ; 3.50 , 4.16 ) . The associations were similar for women with BMI s between 35.1 and 40 but to a lesser degree . CONCLUSION Maternal morbid obesity in early pregnancy is strongly associated with a number of pregnancy complications and perinatal conditions . LEVEL OF EVIDENCE Low maternal prepregnancy BMI is associated with adverse birth outcomes , but the BMI at which risk increases is not well defined . We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospect i ve study in Anhui , China . The women ( n = 575 ) were 20 - 34 y old , married , nulliparous and nonsmokers . All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22 - 23 kg/m2 . Infants born to the 27 % of women who were severely underweight before pregnancy ( BMI < or = 18.5 kg/m2 ) were at increased risk for fetal growth deficits associated with infant morbidity . Compared with a normal BMI , being severely underweight was associated with mean ( + /- SEM ) reductions of 219 + /- 40 g in infant birthweight and 6.7 + /- 1.3 % in the birthweight ratio and an 80 % increase in risk of intrauterine growth restriction [ odds ratio ( OR ) 1.8 ; 95 % CI : 1.0 , 3.3 ; P = 0.05 ] . Being severely underweight was also associated with smaller infant head circumference and lower ponderal index . Being moderately underweight ( 18.5 < BMI < 19.8 kg/m2 ) was not significantly associated with adverse pregnancy outcomes . Gestational age and risk of preterm birth were not associated with maternal BMI . More than half of the women in this study were underweight before pregnancy . Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes , being severely underweight was an important risk factor for reduced fetal growth One cost-effective strategy for controlling iron deficiency is the fortification of staple foods or condiments with iron . We evaluated the effectiveness of fortifying fish sauce with NaFeEDTA for improving iron status in women of childbearing age in Vietnam in a double-blind intervention with r and omization by village . All families in the selected villages were supplied with fish sauce that was either unfortified ( Group C , 10 villages ) or fortified with NaFeEDTA [ 9 mmol ( 500 mg ) Fe/L , Group F , 11 villages ] for 18 mo . The effect of fortification was assessed in the 576 women ( n = 288/group ) by measuring hemoglobin and serum ferritin ( SF ) at 6 , 12 , and 18 mo . Analysis of the group x time interaction using a repeated- measures test for each response demonstrated a significant effect of fortification on hemoglobin ( P = 0.039 ) and log SF ( P < 0.0001 ) in Group F with no significant changes in Group C. The prevalence of iron deficiency ( SF < 12 microg/L ) decreased from 22.3 to 4.0 % and the prevalence of anemia ( hemoglobin < 120 g/L ) from 24.7 to 8.5 % in Group F with no significant changes in Group C. NaFeEDTA fortification of fish sauce is an effective method for reducing the prevalence of iron deficiency in women in Vietnam BACKGROUND There is a growing interest in periconceptional iron supplementation in developing countries by research ers and policy makers ; however , there are no r and omized controlled trials that examine the effectiveness of this strategy in decreasing anemia during pregnancy . OBJECTIVE The aim was to determine whether periconceptional iron supplementation reduces anemia during pregnancy . DESIGN A r and omized , double-blind , controlled trial was conducted in rural Bangladesh . Married , nulliparous women were r and omly assigned to receive daily iron and folic acid ( IFA ; 60 mg ferrous fumarate and 400 microg folic acid ) ( n = 134 ) or folic acid ( FA ; 400 microg ) ( n = 138 ) in the form of a powdered supplement added to food . Women were followed until pregnancy or the end of 9 mo . Primary outcomes included hemoglobin , plasma ferritin , and plasma transferrin receptor concentrations . RESULTS Among 88 pregnant women , periconceptional IFA in comparison with FA did not affect anemia or iron status at 15 wk gestation . However , each 1 % increase in adherence was associated with a 10-g/L increase in change in hemoglobin from baseline ( P = 0.03 ) , and those who initiated supplementation at a mean ( + /-SD ) time of 72.9 + /- 57.8 d before conception showed a 7.3-g/L increase in change in hemoglobin from baseline compared with those who initiated supplementation at 26.3 + /- 12.3 d after conception ( P = 0.01 ) . Among 146 nonpregnant women , IFA decreased anemia ( odds ratio : 0.19 ; 95 % CI : 0.04 , 0.95 ) and improved iron stores ( P = 0.001 ) more than did FA . CONCLUSION Good adherence and initiation of supplementation before conception are needed to reduce anemia during early pregnancy . This trial was registered at www . clinical trials.gov as NCT00953134 CONTEXT The prevalence of overweight and obesity in the United States remains high . Commercial weight loss programs may contribute to efforts to reduce the prevalence of overweight and obesity , although few studies have examined their efficacy in controlled trials . OBJECTIVE To test whether a free prepared meal and incentivized structured weight loss program promotes greater weight loss and weight loss maintenance at 2 years compared with usual care . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial of weight loss and weight loss maintenance in 442 overweight or obese women ( body mass index , 25 - 40 ) aged 18 to 69 years ( mean age , 44 years ) conducted at US institutions over 2 years with follow-up between November 2007 and April 2010 . INTERVENTION The program , which involves in-person center-based or telephone-based one-to-one weight loss counseling , was available over a 2-year period . Behavioral goals were an energy-reduced , nutritionally adequate diet , facilitated by the inclusion of prepackaged food items in a planned menu during the initial weight loss phase , and increased physical activity . Participants assigned to usual care received 2 individualized weight loss counseling sessions with a dietetics professional and monthly contacts . MAIN OUTCOME MEASURES Weight loss and weight loss maintenance . RESULTS Weight data were available at 24 months for 407 women ( 92.1 % of the study sample ) . In an intent-to-treat analysis with baseline value substitution , mean weight loss was 7.4 kg ( 95 % confidence interval [ CI ] , 6.1 - 8.7 kg ) or 7.9 % ( 95 % CI , 6.5%-9.3 % ) of initial weight at 24 months for the center-based group , 6.2 kg ( 95 % CI , 4.9 - 7.6 kg ) or 6.8 % ( 95 % CI , 5.2%-8.4 % ) for the telephone-based group , and 2.0 kg ( 95 % CI , 0.6 - 3.3 kg ) or 2.1 % ( 95 % CI , 0.7%-3.5 % ) for the usual care control group after 24 months ( P < .001 for intervention effect ) . CONCLUSION Compared with usual care , this structured weight loss program result ed in greater weight loss over 2 years . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640900 OBJECTIVES To evaluate the efficacy of an Internet behavioral weight loss program ; and determine if adding periodic in-person sessions to an Internet intervention improves outcomes . METHODS 481 healthy overweight adults ( 28 % minority ) were r and omized to one of 3 delivery methods of a behavioral weight loss program with weekly meetings : Internet ( n=161 ) , InPerson ( n=158 ) , or Hybrid ( Internet+InPerson , n=162 ) . Outcome variables were weight at baseline and 6 months and percent of subjects achieving a 5 and 7 % weight loss . The study took place in two centers in Vermont and Arkansas from 2003 to 2008 . RESULTS Conditions differed significantly in mean weight loss [ 8.0 ( 6.1 ) kg vs. 5.5 ( 5.6 ) kg vs. 6.0 ( 5.5 ) kg ] , for InPerson , Internet , and Hybrid respectively , p<0.01 , n=462 ) . Weight loss for InPerson was significantly greater than the Internet and Hybrid conditions ( p<0.05 ) . Although the proportion reaching a 5 % weight loss did not differ , the proportion losing 7 % did differ significantly ( 56.3 % vs. 37.3 % vs. 44.4 % for InPerson , Internet , and Hybrid respectively , p<0.01 ) . CONCLUSIONS These results demonstrate that the Internet is a viable alternative to in-person treatment for the delivery and dissemination of a behavioral weight-control intervention . The addition of periodic in-person sessions did not improve outcomes OBJECTIVE Maternal folate deficiency is associated with neural tube defects ( NTDs ) , the most common congenital birth defect at Maternity Hospital , Kathm and u , Nepal . NTDs can be prevented with periconceptional folic acid supplementation ( FAS ) . This study was performed to assess the awareness of FAS among women of reproductive age in Kathm and u. METHODS A semi-structured question naire was administered to 400 r and omly selected patients aged 15 to 45 years visiting Kathm and u Model Hospital from May to July 2011 , seeking any awareness of FAS , knowledge of its impact on fetal development and knowledge of the appropriate time of supplementation . RESULTS Forty percent ( 95 % CI 35.1 - 45.0 ) of women had heard about FAS , 16.3 % ( 95 % CI 12.8 - 20.2 ) knew that folate affects fetal health and 5.0 % ( 95 % CI 3.1 - 7.6 ) knew that it should be taken pre-pregnancy . Level of education was strongly associated with awareness ( multivariate Odds Ratio for lowest vs. highest level of education : 0.29 , 95 % CI 0.15 - 0.56 ) . CONCLUSIONS Knowledge of FAS is very low among women of childbearing age in Kathm and u. Inclusion of FAS information in health awareness programs is recommended BACKGROUND Although gestational diabetes mellitus ( GDM ) has been associated with substantial adverse health outcomes for both mothers and offspring , few modifiable risk factors for GDM have been identified . METHODS We conducted a prospect i ve cohort study among women in the Nurses ' Health Study II to assess whether the amount , type , and intensity of pregravid physical activity and sedentary behaviors are associated with GDM risk . The analysis included 21,765 women who reported at least 1 singleton pregnancy between 1990 and 1998 . Physical activity and sedentary behaviors were assessed through vali date d question naire . RESULTS We documented 1428 incident GDM cases . After controlling for body mass index , dietary factors , and other covariates , there was a significant inverse association between vigorous activity and the risk of GDM . The multivariate relative risk ( RR ) comparing the highest with the lowest quintile of vigorous activity was 0.77 ( 95 % confidence interval [ CI ] , 0.69 - 0.94 ) ( P = .002 for trend ) . Among women who did not perform vigorous activity , brisk walking pace was associated with significantly lower GDM risk ( RR , 0.66 ; 95 % CI , 0.46 - 0.95 ) compared with an easy pace . Women who spent 20 h/wk or more watching television but did not perform vigorous activity had a significantly higher GDM risk than women who spent less than 2 h/wk watching television and were physically active ( multivariate RR , 2.30 ; 95 % CI , 1.06 - 4.97 ) . CONCLUSION Our prospect i ve study provides strong evidence that regular physical activity before pregnancy is associated with lower GDM risk Background Postpartum weight retention may contribute to the development of obesity . We studied whether individual counselling on diet and physical activity from 2 to 10 months postpartum has positive effects on diet and leisure time physical activity and increases the proportion of primiparas returning to their pre-pregnancy weight . Methods A controlled trial including ninety-two postpartum primiparas was conducted in three intervention and three control child health clinics in primary health care in Finl and . The intervention included individual counselling on diet and physical activity during five routine visits to a public health nurse ; the controls received the usual care . Results In total , 50 % of the intervention group and 30 % of the control group returned to their pre-pregnancy weight ( weight retention ≤ 0 kg ) by 10 months postpartum ( p = 0.06 ) . The confounder-adjusted odds ratio for returning to pre-pregnancy weight was 3.89 ( 95 % CI 1.16–13.04 , p = 0.028 ) for the intervention group compared with the controls . The mean proportion of high-fibre bread ( of total weekly amount of bread ) increased by 16.1 % ( 95 % CI 4.3–27.9 ) by 10 months postpartum in the intervention group compared with the controls when adjusted for confounders ( p = 0.008 ) . No significant differences were observed in changes in leisure time physical activity between the groups . Conclusion The intervention increased the proportion of primiparas returning to pre-pregnancy weight and the proportion of high-fibre bread in their diet . Larger r and omized controlled trials are needed to show whether counselling can improve dietary and leisure time physical activity habits in postpartum women and also to confirm the results concerning the effect on reducing postpartum weight retention . Trial registration Current Controlled Trials IS RCT To study the relation of maternal periconceptional vitamin use to the risk of a congenital urinary tract anomaly ( CUTA ) , we conducted a case-control study using the Washington State Birth Defect Registry . We identified CUTA cases with no known chromosomal abnormality in seven counties in western Washington State occurring between January 1 , 1990 , and December 31 , 1991 . We r and omly selected a sample , as controls , of all infants delivered in five large hospitals in King County who did not have a birth defect and who were born in the same year as the cases . About 55 % of all infants in King County and a smaller proportion of infants in the other six counties are delivered in these five hospitals . We interviewed mothers of 118 cases and 369 controls to obtain information about their vitamin use during the pregnancy and during the year before the conception . After adjustment for maternal race , family income , county of maternal residence , and birth year , we found that women who used multivitamins during the first trimester had only 15 % the risk of bearing a child with a CUTA compared with women who did not take vitamins [ odds ratio ( OR ) = 0.15 ; 95 % confidence interval ( CI ) = 0.05–0.43 ] . The reduction was smaller for use restricted to the second or third trimesters ( OR = 0.31 ; 95 % CI = 0.09–1.02 ) . Among women who used vitamins during the first trimester , vitamin use before conception was not associated with any further reduction in the risk , nor did there appear to be an association with the amount or br and of vitamin used . Restricting the analysis to residents of King County did not change the results . Our results indicate that prenatal multivitamin use , particularly during the first trimester , may reduce the risk of a CUTA . Because all of the preparations taken by study participants contained many vitamins as well as folic acid , it was not possible to identify which one ( or several ) chemical(s ) may have been responsible for the reduced risk of a CUTA Aim : The aim of the study was to develop and implement an obesity and weight gain prevention program targeted to a high-risk group . Method : Women , 18–28 years old , with at least one severely obese parent , were r and omized to the intervention or control group of the ‘ Health Hunters ’ program . During 1 year of follow-up , the intervention group received an individualized behavioral program focusing on food choice , physical activity and other lifestyle factors . Anthropometric measures , DXA-based body composition and fitness levels were measured at baseline and after 1 year . Self-reported changes in obesity-related behaviors were also assessed . Results : Baseline examinations were conducted in 40 women , of whom 30 completed follow-up examinations 1 year later . Pregnancy was the most common reason for failure to complete the study . Compared to the control group ( which gained weight ) , the intervention group displayed significant improvements in body weight , body mass index , waist circumference , waist-to-hip ratio and self-reported physical activity . Changes in body composition , although not significant , suggested that the intervention tended to be associated with improved body composition . Further analysis of changes in diet and fitness in relation to concurrent weight changes indicated that the strongest ‘ protective ’ associations were for energy percent protein , fiber density and fitness . Conclusion : Pilot data from the Health Hunters obesity prevention program indicates that it is effective in high-risk young women with familial predisposition for obesity OBJECTIVE This paper describes the design and findings of a pilot Mothers In Motion ( P-MIM ) program . DESIGN A r and omized controlled trial that collected data via telephone interviews and finger stick at 3 time points : baseline and 2 and 8 months post-intervention . SETTING Three Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) sites in southern Michigan . PARTICIPANTS One hundred and twenty nine overweight and obese African-American and white mothers , 18 - 34 years old . INTERVENTION The 10-week , theory-based , culturally sensitive intervention messages were delivered via a series of 5 chapters on a DVD and complemented by 5 peer support group teleconferences . MAIN OUTCOME MEASURES Dietary fat , fruit , and vegetable intake ; physical activity ; stress ; feelings ; body weight ; and blood glucose . ANALYSIS General linear mixed model was applied to assess treatment effects across 2 and 8 months post-intervention . RESULTS No significant effect sizes were found in primary and secondary outcome variables at 2 and 8 months post-intervention . However , changes in body weight and blood glucose showed apparent trends consistent with the study 's hypotheses . CONCLUSIONS AND IMPLICATION S The P-MIM showed promise for preventing weight gain in low-income overweight and obese women . However , a larger experimental trial is warranted to determine the effectiveness of this intervention OBJECTIVE To examine the association between gestational weight gain and maternal body mass index ( BMI ) among Vietnamese women and the risk of delivering an infant too small or too large for gestational age . METHODS A prospect i ve health-facility-based study of 2989 pregnant Vietnamese women was conducted in the city of Nha Trang in 2007 - 2008 . Cubic logistic regression was used to investigate the association of interest . Infants were classified into weight-for-gestational-age categories according to weight centiles for the Asian population . Gestational age was based on the date of last menstrual period and adjusted by the results of first-trimester ultrasound . FINDINGS BMI was low ( < 18.5 ) , normal ( 18.5 - 22.9 ) and high ( ≥ 23.0 ) in 26.1 % , 65.4 % and 8.5 % of the women , respectively . In each of these BMI categories , the percentage of women who delivered infants too small for gestational age was 18.1 , 10.0 and 9.4 , respectively , and the mean gestational weight gain was 12.5 kg ( st and ard deviation , SD : ± 3.6 ) , 12.2 kg ( SD : ± 3.8 ) and 11.5 kg ( SD : ± 4.7 ) , respectively . Among women with low BMI , the risk of delivering an infant too small for gestational age ranged from approximately 40 % if the gestational weight gain was < 5 kg to 20 % if it was 5 - 10 kg . CONCLUSION Having a low BMI , commonly found in Viet Nam , puts women at risk of delivering an infant too small for gestational age , especially when total maternal gestational weight gain is < 10 kg 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 Hookworm infections are significant public health issues in South-East Asia . In women of reproductive age , chronic hookworm infections cause iron deficiency anaemia , which , upon pregnancy , can lead to intrauterine growth restriction and low birth weight . Low birth weight is an important risk factor for neonatal and infant mortality and morbidity . Methodology We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam . The program was made available to all women of reproductive age ( estimated 51,623 ) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection . Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention , but had similar maternal and child health indicators and socio-economic background s. The primary outcome was low birth weight . Principal Findings The birth weights of 463 infants born in district hospitals in the intervention ( 168 ) and control districts ( 295 ) were recorded . Twenty-six months after the program was started , the prevalence of low birth weight was 3 % in intervention districts compared to 7.4 % in control districts ( adjusted odds ratio 0.29 , 95 % confidence interval 0.10 to 0.81 , p = 0.017 ) . The mean birth weight was 124 g ( CI 68 - 255 g , p<0.001 ) greater in the intervention districts compared to control districts . Conclusions / Significance The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam . The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive r and omised-controlled trial Background Nutritional status of women has been considered an important prognostic indicator of pregnancy outcomes . Few studies have evaluated patterns of weight gain and pre-pregnancy body mass index in developing regions where malnutrition and poor weight gain as well as maternal obesity have significant influences on the pregnancy outcome . This study aims to show effect of pregnancy body mass index and the corresponding gestational weight gain on the outcome of pregnancy . Methods On a prospect i ve cross sectional study , two hundred and seventy women from urban areas of Northwest Iran were recruited for participation during their first eight weeks of pregnancy . Body mass index ( BMI ) was categorized and gestational weight gain was divided into two groups of normal and abnormal based on recommendations of Institute of Medicine ( IOM ) published in 1990 . Chi square and one way ANOVA were used in the univariate analysis of the association between weight gain and corresponding adverse outcomes including cesarean , preterm labor and low neonatal birth weight . Adjusted odds ratios for adverse outcomes were determined by multiple logistic regression models , while controlling for the following factors : maternal age , parity , and education . Results Both pre-pregnancy BMI < 19 and abnormal weight gain during pregnancy were found to be associated with low neonatal birth weight defined as < 2500 g. Abnormal weight gain , during pregnancy was not related to an increased risk of preterm labor or cesarean delivery but it was highly associated with low birth weight (LBW)(P < 0.05 ) . Conclusion Low pre-pregnancy BMI is an established risk factor for LBW . Abnormal gestational weight gain may further complicate the pregnancy as an additional risk factor for neonatal LBW . All women , regardless of their pre-pregnancy BMI may be at risk for abnormal weight gain and hence low birth weight . Pre-pregnancy and gestation nutritional assessment s remain significant part of all prenatal visits Physical activity has been associated with a reduced risk of gestational diabetes mellitus , but inferences have been hampered by recall and selection bias . The authors examined the relation between recreational physical activity before and during pregnancy and risk of gestational diabetes mellitus in a prospect i ve cohort study . In 1996 - 2000 , 909 normotensive , nondiabetic women in Seattle and Tacoma , Washington , were question ed during early gestation about physical activity performed during the year before and 7 days prior to the interview during pregnancy . Compared with inactive women , women who participated in any physical activity during the year before experienced a 56 % risk reduction ( relative risk ( RR ) = 0.44 , 95 % confidence interval ( CI ) : 0.21 , 0.91 ) . Women spending > /=4.2 hours/week engaged in physical activity experienced a 76 % reduction in gestational diabetes mellitus risk ( RR = 0.24 , 95 % CI : 0.10 , 0.64 ) , and those expending > /=21.1 metabolic equivalent-hours/week experienced a 74 % reduction ( RR = 0.26 , 95 % CI : 0.10 , 0.65 ) compared with inactive women . Physical activity during pregnancy was also associated with reductions in gestational diabetes mellitus risk . Women who engaged in physical activity during both time periods experienced a 69 % reduced risk ( RR = 0.31 , 95 % CI : 0.12 , 0.79 ) . Findings suggest that efforts to increase maternal physical activity may contribute to substantial reductions in gestational diabetes mellitus risk Fe-deficiency anaemia is a worldwide health problem . We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women . A r and omised , double-blind , placebo-controlled study of 16 weeks of duration was performed . Subjects were r and omised into two groups : the P group ( n 58 ) or the F group ( n 64 ) , and consumed , as a supplement to their usual diet , 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice , respectively . The Fe-fortified fruit juice , containing microencapsulated iron pyrophosphate , provided 18 mg Fe/d ( 100 % of the RDA ) . At baseline and monthly , dietary intake , body weight and Fe parameters were determined : total erythrocytes , haematocrit , mean corpuscular volume ( MCV ) , red blood cell distribution width ( RDW ) , Hb , serum Fe , serum ferritin , serum transferrin , transferrin saturation , soluble transferrin receptor ( sTfR ) and zinc protoporphyrin ( ZnPP ) . The fruit juice consumption involved increased intake of carbohydrates and vitamin C , and increased BMI within normal limits . Ferritin was higher in the F group after week 4 ( P < 0·05 ) and became 80 % higher than in the P group after week 16 ( P < 0·001 ) , and transferrin decreased in the F group compared with the P group after week 4 ( P < 0·001 ) . RDW was higher at weeks 4 and 8 in the F group compared with the P group ( P < 0·05 ) . Transferrin saturation increased after week 8 , and haematocrit , MCV and Hb increased after week 12 , in the F group compared with the P group . Serum Fe did not change . sTfR and ZnPP decreased in the F group at week 16 ( P < 0·05 ) . Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia PURPOSE Prior studies of the association between physical activity and risk of hypertensive disorders of pregnancy have been conflicting , failed to assess total physical activity , and included few Hispanic women , the largest minority group in the United States with the highest birth rates . METHODS We examined this association among 1043 participants in the Latina Gestational Diabetes Mellitus Study , a prospect i ve cohort of predominantly Puerto Rican prenatal care patients conducted from 2000 to 2004 in western Massachusetts . Physical activity before and in early pregnancy was assessed by bilingual interviewers using a modified version of the Kaiser Physical Activity Survey . RESULTS Fifty women ( 4.8 % ) were diagnosed with hypertensive disorders of pregnancy and 30 ( 2.9 % ) with preeclampsia . In multivariable analyses , there was a statistically significant trend of decreasing risk of hypertensive disorders with increasing sports/exercise in early pregnancy ( P(trend ) = 0.04 ) . High levels of early pregnancy active living activity ( odds ratio ( OR ) = 0.4 , 95 % confidence interval ( CI ) = 0.1 - 1.1 , P(trend ) = 0.07 ) and household/care giving activity ( OR = 0.4 , 95 % CI = 0.1 - 1.3 , P(trend ) = 0.07 ) were associated with a 60 % reduction in risk of hypertensive disorders relative to low levels ; however , these associations were of marginal statistical significance . High levels of total physical activity ( OR = 0.3 , 95 % CI = 0.1 - 1.0 , P(trend ) = 0.06 ) in early pregnancy were associated with a 70 % reduction in the risk of hypertensive disorders relative to low levels ; however , this association was also of marginal statistical significance . Prepregnancy physical activity was not associated with hypertensive disorders . CONCLUSIONS These results in a Hispanic population , although based on small numbers of cases , corroborate previous studies suggesting that recreational activity in early pregnancy reduces the risk of hypertensive disorders of pregnancy OBJECTIVE In 1982 , Tolarova(4 ) found a reduction in the recurrence rate of isolated cleft lip ( CL ) with or without cleft palate ( CP ; CL + /- CP ) after periconceptional supplementation with a multivitamin including a very high dose ( 10 mg ) of folic acid . The Hungarian r and omized , double-blind , controlled trial of periconceptional supplementation with a multivitamin including a physiologic dose ( .8 mg ) of folic acid did not show any preventive effect on the first occurrence of isolated CL + /- CP and CP . However , the general evaluation of congenital abnormalities in the Hungarian Case-Control Surveillance of Congenital Abnormalities indicated , among others , a reduction of isolated CL + /- CP and CP after the use of high doses of folic acid in the critical period for the development of these congenital abnormalities in the 12-year data set between 1980 and 1991 . We hypothesized that the prevention of orofacial clefts by folic acid has a dose-dependent effect , and this hypothesis was tested in 2 recent Hungarian data sets . DESIGN In a prospect i ve cohort study , the occurrence of isolated CL + /- CP and CP was studied in the newborn infants born to mothers with or without periconceptional folic acid-containing ( .8 mg ) multivitamin supplementation . Supplemented women with confirmed pregnancy were recruited from the participants of the periconceptional service . Unsupplemented women were invited to take part in the study after the first visit between the 8th and 12th week of gestation in the antenatal care . Supplemented and unsupplemented women were matched based on age , socioeconomic status , and residence . In contrast , the occurrence of high-dose ( in general daily 6 mg ) folic acid supplementation was evaluated in the case-control pairs of CL + /- CP and CP , particularly during the critical period of these 2 types of orofacial clefts in the 17 years data set of the Case-Control Surveillance of Congenital Abnormalities , between 1980 and 1996 . Cases were selected from the population -based Hungarian Congenital Abnormality Registry , whereas population controls without congenital abnormality were ascertained from the national birth registry . Two population controls were matched to every case according to sex , week of birth , and district of parental residence . The drug uses , including pregnancy supplements as folic acid , were evaluated based on retrospective self-reported maternal question naire and prospect i ve medically documented data of antenatal care logbook . RESULTS In the prospect i ve cohort study , of 3019 informative offspring ( termination of pregnancies in the second and third trimesters because of fetal defect , stillborn fetuses , and liveborn infants ) in the supplemented group , 3 had CL + /- CP and 1 was affected with CP , whereas of 3432 informative offspring in the unsupplemented group , 2 had CL + /- CP and 1 had CP . The lack of preventive effect was in agreement with the result of the previous Hungarian r and omized double-blind controlled trial ; thus , these 2 data sets were combined . The preventive effect of a folic acid containing multivitamin used in the periconceptional period for the first occurrence of isolated CL + /- CP and CP was estimated by the Mantel-Haenszel test . Of 5488 supplemented women , 6 had CL + /- CP , and of 5821 unsupplemented women , 4 had CL + /- CP . Of 5489 supplemented women , 1 had CP , and of 5823 unsupplemented pregnant women , 3 had CP . The Hungarian Case-Control Surveillance of Congenital Abnormalities , 1980 - 1996 , included 38 151 population controls ( 1.8 % of the Hungarian births ) and 22 865 cases with congenital abnormalities . Within the latter group , 1368 had isolated CL + /- CP , and 596 had CP . A significantly more frequent use of high-dose folic acid ( in general daily 6 mg ) supplementation was found in controls than in cases of 1246 case-control pairs of CL + /- CP group and of 537 case-control pairs of CP group , respectively . ( ABSTRACT TRUNCATED St and ards of scientific reporting have evolved from the very beginning of scientific reporting . Virtually all journals now publish instructions for authors and most medical journals adhere to certain st and ards of publication . Such st and ards have been promoted by international groups such as the International Committee of Medical Journal Editors ( ICMJE ) and Committee on Publication Ethics ( COPE ) . The ICMJE has published general st and ards for crafting scientific articles : the “ Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals : Writing and Editing for Biomedical Publication ” [ 7 ] . These guidelines include suggestions not only for manuscript preparation , but also guidelines for ethical issues related to publishing . COPE , however , focuses on ethical issues [ 1 ] . CORR adheres to these guidelines ; authors may find links to these guidelines in our online Instructions for Authors . Such guidelines , as important as they are , lack sufficient detail to ensure all important information is included . Therefore , in addition to these general guidelines for preparing a manuscript , numerous international groups have published guidelines to ensure various sorts of studies contain all essential information . These include the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines for r and omized trials [ 2 , 3 , 8 ] , QUORUM ( Quality of Reporting of Meta-analyses ) [ 6 ] and MOOSE ( Meta- analysis Of Observational Studies in Epidemiology ) [ 13 ] for meta-analyses , and STROBE ( Strengthening the Reporting of Observational Studies in Epidemiology ) for various sorts of observational studies ( the majority of clinical studies in surgical disciplines ) [ 12 , 15 ] . In essence , these guidelines tell investigators and authors what information is required to ensure readers ( and review ers ) can properly evaluate the study . Despite these st and ards , most reports of clinical studies lack such critical information . I suspect this is less by intent than lack of awareness of what information is required . In addition , although many journals , including CORR require a Level of Evidence [ 5 , 10 , 16 ] for studies involving patients , most clinical articles published in surgical journals have a relatively low level ; prospect i ve , r and omized trials are uncommon ( and often impractical ) , and even sufficiently large retrospective cohort studies to control for confounding variables may be unachievable for many conditions or treatments in single institutions . In the absence of high levels of evidence , systematic review s [ 9 , 11 , 17 ] and meta-analyses [ 4 ] have become increasingly common . My search of PubMed for articles limited to meta- analysis yielded 276 articles from 1950–1989 , 2116 from 1990–1994 , 3736 from 1995–1999 , 7920 from 2000–2004 , and 9313 from 2005 to 2009 . Most of these analyses undoubtedly collected information from lower level studies , thereby incurring the limitations of the individual studies . Virtually all systematic and meta-analyses we have recently published noted missing and variably reported data . In contrast to medical disciplines , surgical disciplines do not have the advantage of being able to conduct tightly design ed prospect i ve , r and omized , blinded , controlled trials . ( A PubMed search limited to r and omized controlled trials suggested The Journal of Bone and Joint Surgery and CORR had together published 556 RCTs and although I did not individually check these for quality , they reflect a small fraction of the articles both journals publish . ) For the foreseeable future , most of our information will arise from observational studies rather than prospect i ve trials . In this setting , it is especially important that each article contain all relevant information for future systematic review s and meta-analyses . The STROBE guidelines [ 12 ] provide authors with lists of critical information for reporting three sorts of observational studies : cohort ( longitudinal studies typically reporting outcomes of treatment in one or more cohorts ) , case-control ( studies identifying factors in outcomes ) , and cross-sectional studies ( studies to identify prevalence of factors or characteristics in a population at a single time ) . CORR now requires authors to adhere to CONSORT guidelines for r and omized clinical trials , QUORUM guidelines for meta-analyses , and STROBE guidelines for observational clinical studies . Authors will be able to download from our Instructions to Authors convenient templates for the various sorts of articles we publish ; these templates contain the information required . In addition , we request authors read and follow the guidelines in the Cochrane H and book for Systematic Review s of Interventions 4.2.6 [ 14 ] . Adherence to these st and ards will enhance our ability to answer key clinical questions in more definitive ways than we have in the past , and to answer more questions STUDY OBJECTIVE To determine the relationship between adolescents ' pre-pregnancy body mass index ( BMI ) , and gestational weight gain and postpartum weight retention . DESIGN We review the medical records of adolescents participating in a prospect i ve cohort study on comprehensive health care and parenting education to determine pre-pregnancy BMI , gestational weight gain , and postpartum weight retention at one year . SETTING Urban academic hospital clinic . PARTICIPANTS 102 pregnant adolescents aged 15 - 21 years . MAIN OUTCOMES Gestational weight gain and weight retention at one year postpartum . RESULTS AND CONCLUSIONS Fifty-two ( 51 % ) adolescent women had normal pre-pregnancy BMI according to the Institute of Medicine classification . Adolescent women with normal ( 36.5 % ) and high pre-pregnancy BMI ( 66.5 % ) were more likely than women with low pre-pregnancy BMI ( 26.5 % ) to exceed recommended gestational weight gain . Adolescent women who exceeded recommended weight gain retained significantly more weight at 1 year postpartum than women with weight gain within or below the recommendation . In a linear regression model that controlled for age , smoking , pregnancy complication , and post partum contraceptive use , pre-pregnancy BMI and gestational weight gain were the strongest predictors of postpartum weight retention at 1 year . A normal to high pre-pregnancy BMI and excessive gestational weight gain are important predictors of postpartum weight retention in adolescents . These two predictors must be monitored systematic ally with the aim of preventing postpartum obesity and its associated diseases among this population A r and omised trial was initiated in Irel and in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects ( NTDs ) in women with a previously affected pregnancy from 5.0 % to 1.0 % or less . The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed . A total of 354 women were r and omised to receive one of three treatments : folic acid , multivitamins without folic acid , and folic acid plus multivitamins . At the end of the trial 257 women had had a first trial pregnancy outcome ( 261 infants/fetuses ) where the presence or absence of NTDs was ascertainable . There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups , a non-significant difference . Otherwise eligible women who were pregnant when first contacted constituted a non-r and omised control group ; there were three recurrences among the 103 infants in this group . The difference in the recurrence rate between the folic acid groups and the non-r and omised controls was statistically significant but we have reservations about the validity of this comparison . Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council ( MRC ) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial Summary .¶ Objectives : The periconceptional intake of 0.4 mg folic acid is recommended in many countries to prevent neural tube defects . This paper describes the poor implementation of corresponding guidelines in Germany , the effectiveness of an intervention-based on providing adequate information and the problems associated with the implementation.¶ Methods : Two cross sectional studies investigated knowledge , attitude , and behaviour of r and omly sample d gynaecologists ( n = 24/27 ) , pharmacists ( n = 21/21 ) , and women in childbed ( n = 131/118 ) before and after the information campaign.¶ Results : Before the intervention , 3.8 % of the women implemented folic-acid-prophylaxis compared with 9.3 % afterwards ( p = n.s . ) . The awareness of the prophylaxis before pregnancy correlated with socio-economic status and rose from 28 % ( before ) to 42 % after intervention ( p<0.05 ) . Before the intervention , 38 % of the gynaecologists and 38 % of the pharmacists recommended the prophylaxis compared with 74 % ( p<0.05 ) and 43 % ( p = n.s . ) afterwards.¶ Conclusions : The effect of the intervention was small . To improve the situation , fortification of specially selected and labelled food should be considered . An accompanying nation-wide information campaign should focus on women with lower socio-economic status Objectives : To determine the changes since 1996 in knowledge of folate for the prevention of neural tube defects ( NTDs ) among women of child‐bearing age and measure the residual effect of an earlier consumer‐directed information campaign Objectives Infant birth weight is influenced by modifiable maternal pre-pregnancy behaviors and characteristics . We evaluated the relationship among pre-pregnancy body mass index ( BMI ) , gestational weight gain , and infant birth weight , in a prospect i ve cohort study . Methods Women were enrolled at ≤20 weeks gestation , completed in-person interviews and had their medical records review ed after delivery . Infant birth weight was first analyzed as a continuous variable , and then grouped into Low birth weight ( LBW ) ( < 2,500 g ) , normal birth weight ( 2,500–3,999 g ) , and macrosomia ( ≥4,000 g ) in categorical analysis . Pre-pregnancy BMI and gestational weight gain were categorized based on Institute of Medicine BMI groups and gestational weight gain guidelines . Associations among infant birth weight and pre-pregnancy BMI , gestational weight gain , and other factors were evaluated using multivariate regression . Risk ratios were estimated using generalized linear modeling procedures . Results Pre-pregnancy BMI was independently and positively associated with infant birth weight ( β = 44.7 , P = 0.001 ) after adjusting for confounders , in a quadratic model . Gestational weight gain was positively associated with infant birth weight ( β = 19.5 , P < 0.001 ) . Lower infant birth weight was associated with preterm birth ( β = −965.4 , P < 0.001 ) , nulliparity ( β = −48.6 , P = 0.015 ) , and female babies ( β = −168.7 , P < 0.001 ) . Less than median gestational weight gain was associated with twice the risk of LBW ( RR = 2.04 , 95 % CI 1.34–3.11 ) . Risk of macrosomia increased with increasing pre-pregnancy BMI and gestational weight gain ( P for linear trend < 0.001 ) . Conclusions These findings support the need to balance pre-pregnancy weight and gestational weight gain against the risk of LBW and macrosomia among lean and obese women , respectively A pilot study was conducted to determine if a nutritional intervention aim ed at portion control leads to significant weight loss in a community of low-income Mexican American women . Nineteen low-income Mexican American women were r and omized to a st and ard care group or an intervention group in portion control . The trial was 20 weeks in length , and the intervention included four 2-hour classes . Both interventions were administered by a certified nurse-midwife ( CNM ) and a promotora de salud ( i.e. , lay health advisor ) . Women in the intervention group lost more weight than women in the st and ard care group , though this difference was not statistically significant . The mean weight loss in the intervention group was 6.57 pounds ( 2.9 kg ) compared to a mean weight loss of 2.8 pounds ( 1.3 kg ) in the st and ard care group ( P = .47 ) . Mean weight loss , regardless of group , was significantly greater when participants reported self-weighing ( P = .02 ) . This pilot study in portion control for low-income Mexican American women merits further study Background Universal fortification of staple foods with iron has been widely promoted as a cost-effective strategy to reduce iron deficiency in developing-country population s. Nonetheless , relatively few efficacy trials have been reported to date to demonstrate impact on iron status . The Ultra Rice technology provides a means of delivering fortificant iron via rice . Objective The objective of this study was to test the efficacy of rice fortified with microencapsulated , micronized iron pyrophosphate to improve the iron status of women in Mexico in a r and omized , controlled intervention trial . Methods Nonpregnant , nonlactating women 18 to 49 years of age were recruited from six factories . The women received a daily portion of cooked rice 5 days per week for a period of 6 months , before and after which iron status indicators were determined in venous blood sample s. Results The average intake of iron from the fortificant was 13 mg/day . Mean plasma ferritin concentration and estimated body iron stores were significantly higher , and transferrin receptors were lower , in the iron-fortified rice group following the intervention . Mean hemoglobin concentration also increased in the treatment group , but the increase was significant only when the analysis was restricted to those with baseline hemoglobin < 12.8 g/dL. The absolute reduction in anemia and iron deficiency was 10.3 and 15.1 percentage points , respectively . Total iron intake from fortificant was a significant covariate of change in body iron stores . The overall prevalence of anemia was reduced by 80 % . Conclusions Fortification of rice with iron using this technology is an efficacious strategy for preventing iron deficiency OBJECTIVE To study the human teratogenic risk of a folic acid – containing multivitamin . METHODS We evaluated the data set of two Hungarian intervention studies : a r and omized double-blind , controlled trial and a two-cohort , controlled study of the same folic acid – containing multivitamin in participants of the Hungarian periconceptional service . RESULTS Of 2471 supplemented and 2391 unsupplemented women , 18 and 21 , respectively , had multiple congenital abnormalities in the r and omized , controlled trial . Of 3056 supplemented and unsupplemented pairs in the two-cohort , controlled study , 33 and 32 , respectively , were affected with multiple congenital abnormalities . After the combination of two data sets , the number of cases with multiple congenital abnormalities was 51 in the supplemented group and 53 in the unsupplemented group ( odds ratio 0.89 ; 95 % confidence interval 0.45 , 1.68 ) . In addition , there was no difference in the occurrence of specified multiple congenital abnormality entities or of unidentified multimalformed informative offspring . CONCLUSION We found no evidence that periconceptional folic acid – containing multivitamin supplementation either prevents or induces multiple congenital abnormalities Adverse sensory changes prevent the addition of highly bioavailable ferrous sulfate ( FeSO4 ) to most wheat flours . Poorly absorbable reduced Fe powders are commonly used . Encapsulation of FeSO4 can overcome these sensory changes , but the particle size of commercial compounds is too large to be used by flour mills . The first objective of the study was to measure the efficacy in wheat flour of two newly developed Fe compounds , an H-reduced Fe powder ( NutraFine RS ; North America Höganäs High Alloys LLC , Johnstown , PA , USA ) and small particle-sized ( 40 microm ) encapsulated FeSO4 . As a second objective , the microcapsules were evaluated as a vehicle for iodine fortification . A r and omised , double-blind controlled intervention trial was conducted in Kuwaiti women ( n 279 ; aged 18 - 35 years ) with low body Fe stores ( serum ferritin ( SF ) < 25 microg/l ) r and omly assigned to one of three groups ( 20 mg Fe as NutraFine RS , 10 mg Fe as encapsulated FeSO4 and 150 microg iodine , or no fortification Fe ) who consumed wheat-based biscuits 5 d per week . At baseline and 22 weeks , Hb , SF , transferrin receptor , urinary iodine and body Fe stores were measured . Relative to control , mean SF in the encapsulated FeSO4 group increased by 88 % ( P < 0.001 ) and body Fe stores increased from - 0.96 to 2.24 mg/kg body weight ( P < 0.001 ) , while NutraFine RS did not significantly increase SF or body Fe stores . The median urinary iodine concentration increased from 140 to 213 microg/l ( P < 0.01 ) . NutraFine RS added at double the amount of Fe as FeSO4 was not efficacious in improving Fe status . The newly developed microcapsules were highly efficacious in improving both Fe stores and iodine status BACKGROUND The 1984 - 1991 Hungarian r and omized controlled trial ( RCT ) of periconceptional multivitamin supplementation containing folic acid ( 0.8 mg ) showed a significant reduction in the first occurrence of neural tube defects ( NTDs ) , and of urinary tract and cardiovascular abnormalities , but no reduction in orofacial clefts . A controlled cohort trial was design ed to confirm or deny these results . METHODS Supplemented women were recruited from the Hungarian Periconceptional Service using the same multivitamin as the Hungarian RCT . Unsupplemented pregnant women were recruited in the st and ard regional antenatal care clinics and were matched to each supplemented pregnant woman on the basis of age , socioeconomic status , place of residence , and year of pregnancy . RESULTS A total of 3056 informative offspring were evaluated in each cohort . The occurrence of congenital cardiovascular malformations ( 31 vs. 50 ) was reduced ( odds ratio [ OR ] , 0.60 ; 95 % confidence interval [ CI ] , 0.38 - 0.96 ) in the supplemented cohort , accounted for mainly by ventricular septal defects ( 5 vs. 19 ; OR , 0.26 ; 95 % CI , 0.09 - 0.72 ) . There was no significant difference ( 14 vs. 19 ) in the occurrence of urinary tract defects between the two cohorts , but stenosis/atresia of pelvic-ureteric junction ( 2 vs. 13 ) showed a significant reduction ( OR , 0.19 ; 95 % CI , 0.04 - 0.86 ) . The protective effect of the folic acid-containing multivitamin for NTDs ( one offspring in the supplemented vs. nine in the unsupplemented cohort ) was confirmed ( OR , 0.11 ; 95 % CI , 0.01 - 0.91 ) . There was , however , no protective effect on orofacial clefts or on multiple congenital abnormalities . CONCLUSIONS The results of this cohort-controlled trial support the findings of the previous Hungarian RCT . The primary prevention of some major structural birth defects by multivitamins containing folic acid or by folic acid has great public health importance Background : Preeclampsia has been shown to be associated with obesity , with other risk factors for cardiovascular disease , and with subsequent cardiovascular disease itself . However , the possible association with weight gain and weight cycling has not been evaluated . Methods : In this prospect i ve study of a cohort of 1644 pregnant women , we assessed adult weight change , intentional weight cycling , and prepregnancy obesity in relation to preeclampsia risk . Net weight change from age 18 years to the period 3 months before conception was determined for each participant . Weight cycling was defined as intentional weight loss and unintentional regain of at least 15 pounds during periods not related to pregnancy or lactation . We used multivariate regression procedures to calculate risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) . Results : Relative to women with stable weight ( gained or lost < 2.5 kg ) women who gained 5.0–9.9 kg experienced a 2.6-fold increased risk of preeclampsia ( 95 % CI = 1.0–6.7 ) . The corresponding risk ratio ( RR ) for women who gained ≥10 kg was 5.1 ( 2.2–12.2 ) . Intentional weight cycling , after controlling for weight at age 18 years , adult weight change , and other risk factors , was not associated with increased risk of preeclampsia ( RR = 1.1 ; CI = 0.6–1.8 ) . RRs increased monotonically with increasing prepregnancy body mass index greater than 19.8 kg/m2 . After adjusting for confounders , the RR for prepregnancy overweight women and obese women were 1.7 ( 0.6–4.9 ) and 3.4 ( 1.5–7.6 ) respectively . Conclusions : These results suggest that adult weight gain and prepregnancy overweight and obesity status are associated with an increased risk of preeclampsia BACKGROUND & OBJECTIVES A folic acid containing multivitamin preparation was evaluated for its efficacy in preventing recurrence of open neural tube defect ( NTD ) in a blind , placebo-controlled r and omized trial . The trial was carried out at the five centres in India , viz . , Bangalore , Mumbai , Lucknow , New Delhi and Pune . METHODS The preparation contained 4 mg of folic acid besides calcium , iron , zinc and vitamins A , B1 , B2 , B6 , C , D and nicotinamide . The placebo contained calcium and iron only . A total of 466 women with previous history of giving birth to a child with open NTD were included in the trial ( 231 in the vitamin group and 235 in the placebo group ) . The supplementation was given for at least one month prior to conception and up to three months after conception . All women were offered antenatal diagnosis with screening of maternal serum alpha foetoprotein ( AFP ) and ultrasound . RESULTS Pregnancy outcome with reference to recurrence of NTD was unknown in 137 women in the vitamin group and 142 in the placebo group . The recurrence of open NTD in the vitamin group was 2.92 per cent compared to 7.04 per cent in the placebo group , a reduction by about 60 per cent . The difference , however , was not statistically significant ( P = 0.06 ) . INTERPRETATION & CONCLUSIONS The study seems to support the role of periconceptional folic acid supplementation in prevention of recurrence of NTDs in the Indian population . The reason for high recurrence rate observed in the placebo group requires further investigation Although it has been well established that periconceptional use of multivitamins containing folic acid ( FA ) reduces the risk for neural tube defects , two recent U.S. studies have shown an increased risk for multiple congenital anomalies ( MCAs ) associated with periconceptional use of vitamins containing FA . This study assessed the association between the periconceptional use of vitamins containing FA and MCAs in a third U.S. population . Mothers of infants with MCAs and a r and om sample of live births ( control infants ) born in Iowa during 1993–1995 were eligible to participate in the Birth Defects Risk Factor Surveillance case‐control study . During a telephone interview , participants reported on exposure to FA through vitamins , cereal , and food supplements . There was no association between taking vitamins containing FA during the periconceptional period ( 3 months before conception through the first trimester ) and MCAs in the crude estimates or after adjusting for maternal race or ethnicity , education , gravidity , smoking , or alcohol use in the first trimester , or body mass index prior to pregnancy [ adjusted odds ratio ( aOR ) = 1.12 , 95 % confidence interval ( CI ) 0.75–1.69 ] . There was also no association between vitamin exposure beginning in the first trimester and MCAs outcome ( aOR = 1.05 , 95 % CI 0.59–1.87 ) . In contrast to the two recently published reports , there was no association between periconceptional vitamin exposure and MCAs in the Iowa population . Published 2007 Wiley‐Liss , Numerous studies have reported reduced risks for a variety of single congenital anomaly phenotypes associated with maternal periconceptional use of vitamin supplements containing folic acid . Here we investigated whether periconceptional use of vitamin supplements containing folic acid by women altered their risk for delivering infants with multiple congenital anomalies ( MCAs ) . Data were derived from a case-control study representing deliveries ( fetal deaths and infants ) from 2 California counties between January 1993 and July 1996 . MCAs were defined as 2 or more congenital anomalies affecting more than one organ system or a major anomaly in combination with 2 minor anomalies . Controls were r and omly selected from nonmalformed live-born infants . Telephone interviews were conducted with 112 ( 73.7 % of eligible ) case and 195 ( 78.0 % of eligible ) control mothers . Compared to women who did not use multivitamin supplements containing folic acid in the period 3 months before through 3 months after conception , women who used in this time period were observed to have an elevated risk to deliver fetuses or infants with MCAs , odds ratio = 2.6 ( 95 % confidence interval 1.1 - 6.2 ) . This elevated risk was not substantially altered ( adjusted odds ratio = 2.9 [ 0.8 - 10.3 ] ) by adjusting for maternal race/ethnicity , education , gravidity , body mass index , alcohol consumption , and cigarette smoking . No particular organ system seemed to be uniquely represented among the MCA fetuses and infants whose mothers used vitamin supplements . The observed elevated risk associated with maternal vitamin use is considered to be preliminary and needs to be replicated in other population The effect of periconceptional multivitamin/trace element supplementation on pregnancy outcomes was evaluated in a r and omised controlled trial . The final data -base included 5,502 females with confirmed pregnancy . A multivitamin including 0.8 mg folic acid or a trace element were supplemented for at least 28 days before conception and continuing for at least until the second missed menstrual period . Number of pregnancies , terminations of pregnancies , four types of fetal deaths , livebirths including low birth weight , preterm birth and sex ratio were analysed . Periconceptional multivitamin supplementation increased fertility ( higher rates of cumulative conceptions and multiple births ) , had no significant effect on the rate of different groups of fetal deaths , low birth weight and preterm birth in singletons . This primary preventive method can reduce the occurrence and recurrence of neural-tube defects and had no other significant effect on pregnancy outcomes except multiple births STUDY OBJECTIVE --The aim was to assess the association of neural tube defects with periconceptional vitamin supplementation . DESIGN --This was a matched , population based case-control study . SETTING --Western Australia , 1982 - 1984 . PARTICIPANTS --Mothers of 77 cases ( 93 % of those eligible ) with isolated neural tube defects , mothers of 77 matched control infants with defects other than neural tube defects ( control group I ) , and mothers of 154 liveborn , matched , control infants with no birth defects ( control group II ) participated in the study . MEASUREMENTS AND MAIN RESULTS --Information was collected by interview and self administered question naire . Crude and adjusted odds ratios ( and their 95 % confidence intervals ) showed a small but non-significant protective effect of folate supplementation in comparisons with both control groups . The adjusted ratios for the three months before pregnancy were 0.69 ( 0.06 , 8.53 ) with control group I , and 0.11 ( 0.01 , 1.33 ) with control group II . In the first six weeks of pregnancy , the adjusted odds ratios were 0.70 ( 0.32 , 1.52 ) with control group I and 0.74 ( 0.29 , 1.88 ) with control group II . The odds ratios for vitamin supplementation of any kind were all very close to or greater than one , and all confidence intervals embraced unity . CONCLUSIONS --These data do not provide evidence of an association between periconceptional vitamin supplementation and neural tube defects , although a protective effect of folate supplementation can not be excluded with confidence , due to the low power of the study . Of three other observational studies of vitamins and neural tube defects , two have shown an association . While further studies of this kind may be of value , evidence must now be sought from r and omised controlled trials The objective in the Hungarian r and omised double-blind controlled trial was to study the preventive effect of periconceptional multivitamin supplementation on neural tube-defects and other congenital abnormalities . There were 2,471 and 2,391 informative offspring ( prenatally diagnosed and terminated malformed fetuses , stillborn fetuses , and liveborn infants ) in the multivitamin and placebo-like trace element groups , respectively . A single tablet either of a multivitamin containing 0.8 mg of folic acid or trace element supplement was given daily for at least one month before conception and at least until the date of the second missed menstrual period . The total rate of major congenital abnormalities was 20.6/1,000 in the multivitamin and 40.6/1,000 in the trace element group . After the exclusion of six cases of neural-tube defects in the trace element group the difference was very highly significant [ P = 0.0003 ; relative risk of 0.54 ( 95 % CI 0.39 , 0.76 ) ] . Multivitamin supplementation appeared to result in a significant reduction in the rate of urinary tract abnormalities , mainly obstructive defects , and in the rate of sporadic cardiovascular malformations , mainly ventricular septal defects . This report is regarded as a hypothesis-generating study encouraging others to see if the result can be repeated OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention OBJECTIVE Prepregnancy body mass index ( BMI ) and gestational weight gain have been associated with hypertensive disorders of pregnancy , but previous studies have included few Latinas , a group at increased risk . STUDY DESIGN We examined these associations in the Latina Gestational Diabetes Mellitus Study , a prospect i ve cohort of 1231 women conducted from 2000 to 2004 . RESULTS In multivariable analysis , obese women ( BMI > 29.0 kg/m(2 ) ) had 2.5 times the risk of hypertensive pregnancy ( 95 % confidence interval [ CI ] , 1.3 - 4.8 ) and 2.7 times the risk of preeclampsia ( 95 % CI , 1.2 - 5.8 ) , compared with women whose BMI was 19.8 to 26.0 kg/m(2 ) . Women with excessive gestational weight gain had a 3-fold increased risk of a hypertensive disorder of pregnancy ( 95 % CI , 1.1 - 7.2 ) and a 4-fold risk of preeclampsia ( 95 % CI , 1.2 - 14.5 ) , compared with women achieving weight gain guidelines . CONCLUSION These findings suggest prepregnancy obesity and excessive weight gain are associated with hypertension in pregnancy in a Latina population and could be potentially modifiable risk factors OBJECTIVES : To determine the effect of a consumer-directed information campaign to increase knowledge of folate for the prevention of neural tube defects among women of child-bearing age , and to measure women 's recall of sources of information and knowledge about folate . DESIGN : A community r and omized trial . SETTING : Three matched pairs of geographically distinct Local Government Areas in the state of Victoria , Australia . INTERVENTION : Printed information recommending folate intake to decrease the risk of neural tube defects was disseminated to women of child-bearing age in three of the Local Government Areas selected r and omly . MAIN OUTCOME MEASURE : The proportion of women aware of the association between folate and spina bifida . RESULTS : Of 1197 women interviewed prior to the intervention , 12.4 % ( adjusted for the cluster and population sampling unit ) were aware of folate and neural tube defects . After the intervention , there was not only a significant background increase of 3.4 % ( P=0.02 ) in folate awareness since the pre-intervention survey ( n=603 ) , but also a significant additional increase of 4.0 % ( P=0.04 ) owing to the intervention itself ( n=603 ) . Only 70 % of women who were aware of folate knew the correct timing . CONCLUSIONS : The provision of printed educational material can increase folate awareness among women of child-bearing age . A comprehensive , long-term and ongoing health promotion campaign including such material , together with initiatives by relevant health service providers and the food industry , could best address the current low levels of folate awareness among women of child-bearing age PURPOSE : Recent studies suggest prepregnancy obesity is a risk factor for preeclampsia , although only a h and ful of studies have examined the effect of gestational weight gain . The authors analyzed the effect of prepregnancy body mass index ( BMI ) and weight gain during pregnancy on risk of preeclampsia and transient hypertension . METHODS : Subjects were participants in a prospect i ve cohort study of women who received prenatal care from thirteen obstetric practice s in southern Connecticut ( 4/88 - 12/91 ) . The women were interviewed in-person before 16 weeks gestation and in the immediate postpartum period . All subjects ' hospital delivery charts were abstract ed . BMI was categorized as : < 19.8 ( underweight ) , 19.8 - 26 ( normal : referent ) , 26 - 29 ( overweight ) , > 29 ( obese ) . A gestational weight gain index , created using multiple linear regression , compared observed weight gain to the weight gain expected after adjustment for significant covariables ( e.g. gestational aged at delivery ) . Logistic regression was used to estimate risk of preeclampsia ( N = 44 ) and transient hypertension ( N = 172 ) associated with prepregnancy BMI and gestational weight gain . RESULTS : Obese women had a mild increased risk of preeclampsia ( OR = 1.81 ; 0.73 - 4.52 ) ; women in the other BMI categories had risks similar to that of normal BMI subjects . In contrast , risk of transient hypertension was substantially decreased among underweight women ( OR = 0.35 ; 0.14 - 0.87 ) and substantially increased among obese women ( OR = 3.43 ; 2.27 - 5.21 ) . Higher than expected gestational weight gain did not increase the risk of preeclampsia . In contrast , risk of transient hypertension was increased over twofold among women in the highest quartile of the weight gain index ( OR = 2.55 ; 1.66 - 3.92 ) . CONCLUSIONS : Obesity appears to be a strong risk factor for transient hypertension and a milder risk factor for preeclampsia . High gestational weight gain was associated with increased risk of transient hypertension but not preeclampsia OBJECTIVE The preventive efficacy of the periconceptional use of multivitamins is well established for neural tube defects , much less so for other birth defects . We conducted a population -based , case-control study to assess the effects of multivitamin use on the risk for conotruncal defects , a group of severe heart defects that includes transposition of the great arteries , tetralogy of Fallot , and truncus arteriosus . METHODS From the population -based Atlanta Birth Defects Case-Control Study , we identified 158 case infants with conotruncal defects and 3026 unaffected , r and omly chosen control infants , born from 1968 through 1980 to mothers residing in metropolitan Atlanta . Periconceptional multivitamin use was defined as reported regular use from 3 months before conception through the third month of pregnancy . We present the results of the crude analysis , because the multivariate model yielded essentially identical results . RESULTS Mothers who reported periconceptional multivitamin use had a 43 % lower risk of having infants with conotruncal defects ( odds ratio [ OR ] , 0.57 ; 95 % confidence interval [ CI ] , 0.33 to 1.00 ) than did mothers who reported no use . The estimated relative risk was lowest for isolated conotruncal defects ( OR , 0.41 ; 95 % CI , 0.20 to 0.84 ) compared with those associated with noncardiac defects ( OR , 0.91 ; 95 % CI , 0.33 to 2.52 ) or a recognized syndrome ( OR , 1.82 ; 95 % CI , 0.31 to 10.67 ) . Among anatomic subgroups of defects , transposition of the great arteries showed the greatest reduction in risk ( OR , 0.36 ; 95 % CI , 0.15 to 0.89 ) . CONCLUSIONS Periconceptional multivitamin use is associated with a reduced risk for conotruncal defects . These findings could have major implication s for the prevention of these birth defects OBJECTIVE The study investigated the effectiveness of home-based exercise combined with a slight caloric restriction on weight change during 12 months in non-obese women . METHODS A r and omized clinical trial with a factorial design was conducted from 2003 to 2005 . Two hundred three middle-aged women ( Rio de Janeiro/Brazil ) , 25 - 45 years , were r and omly assigned to one of two groups : control ( CG ) and home-based exercise ( HB ) . The HB group received a booklet on aerobic exercise that could be practice d at home ( 3 times/week-40 min/session ) , in low-moderate intensity , during 12 months . Both groups received dietary counseling aim ed at a slight energy restriction of 100 - 300 calories per day . RESULTS The HB experienced a greater weight loss in the first 6 months ( -1.4 vs. -0.8 kg ; p=0.04 ) , but after 12 months there was no differences between groups ( -1.1 vs. -1.0 ; p=0.20 ) . Of the serum biochemical markers , HDL cholesterol showed major change , with an increase at month 12 of 18.3mg/dl in the HB compared to 9.5 in the CG ( p<0.01 ) . CONCLUSION Home-based exercise promoted greater weight reduction during the first 6 months after which no further benefits are observed . Continuous favorable changes in HDL cholesterol after 1 year suggest that home-based exercise promote health benefits There is accumulating evidence that periconceptional multivitamin use may prevent the occurrence of some birth defects other than neural tube defects . Using data from the population ‐based Atlanta Birth Defects Case‐Control Study , we investigated the possible association between periconceptional multivitamin use and the occurrence of limb deficiency . We examined the periconceptional use of multivitamins among mothers of 117 babies with nonsyndromic limb deficiency who were liveborn or stillborn to residents of metropolitan Atlanta from 1968 to 1980 and among mothers of 3,029 control babies born without birth defects who were r and omly selected through birth certificates . We found that children whose mothers were periconceptional multivitamin users had a lower risk of having a limb deficiency [ odds ratio ( OR ) = 0.47 ; 95 % confidence interval ( CI ) = 0.23–0.97 ] . This protective effect , however , was mostly seen for transverse limb deficiency ( OR = 0.30 ; 95 % CI = 0.07–1.32 ) and not for longitudinal deficiency ( including preaxial and postaxial deficiencies ; OR = 1.03 ; 95 % CI = 0.17–4.30 ) . Adjustment for potential confounding factors did not change these findings . We found a trend of decreasing risk for all transverse limb deficiencies with earlier vitamin use . These data indicate that mothers ' periconceptional multivitamin use may reduce the risk for some types of limb deficiency among their offspring . In addition , because we did not find the protective effect for all types of limb deficiency , the data may also indicate causal heterogeneity of limb deficiencies 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 Background : Physical activity has been associated with decreased risk of gestational diabetes mellitus . Exp and ing on 2 previously published analyses of absolute exertion measures ( time spent and energy expended ) , we assessed the relation between perceived exertion during usual prepregnancy recreational physical activity and gestational diabetes . Methods : We analyzed data from a Washington State 1998–2002 case – control study ( 216 cases , 472 controls ) and a 1996–2002 prospect i ve cohort study ( 897 participants ) separately . We used logistic regression models to derive odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . Results : Among case – control participants , risk of gestational diabetes was markedly lower for women who reported very strenuous to maximal exertion in usual activity during the year before pregnancy versus those who reported negligible or minimal exertion ( adjusted OR = 0.19 ; CI = 0.15–0.50 ) . There was a direct inverse relation between perceived exertion and risk of gestational diabetes . This relation was also evident among the subset of participants who did not meet physical activity guidelines in the year before pregnancy . Similarly , the OR among cohort participants reporting very strenuous to maximal exertion was 0.57 ( 0.24–1.37 ) versus those reporting negligible to moderate exertion . Conclusions : These results suggest that risk of gestational diabetes is inversely related to the exertion perceived during recreational physical activity in the year before pregnancy . Perceived exertion may be a valuable addition to behavior and fitness measures in assessing relations between physical activity and pregnancy-related health outcomes OBJECTIVE The effect of folic acid supplement on the prevalence of congenital anomalies was studied in a Danish population . MATERIAL AND METHODS From 1983 to 1986 all Danish women resident in the county of Funen were offered free folic acid when pregnant or planning a pregnancy . Folic acid dose was r and omised to 2.5 or 1.0 mg . A r and omised control group was not feasible for ethical reasons . Hospitals , midwives and most general practitioners cooperated to procure information on close to all pregnancies and congenital anomalies were recorded . RESULTS AND CONCLUSIONS In a total of 14,021 pregnancies result ing in child birth 8184 women ( 58.4 % ) had folic acid with r and omisation . Supplement was started in the r and omised group before the last menstrual period in 1359/8184 ( 16.6 % ) and in the first 19 weeks of pregnancy in 6825/8184 ( 83.4 % ) . The prevalence of congenital anomalies was 224 in 8293 children ( 27.0/1000 ) . No dose-dependent differences were found in either total anomalies or in those specific malformations which have been reported to occur with reduced prevalence with periconceptional folic acid . The result was probably influenced by a start of supplement too late to affect malformation development in many cases and by the high level of both folic acid doses given compared to usual recommendations . Pregnancies without folic acid supplement showed prevalences similar to the supplemented groups OBJECTIVES To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect . DESIGN AND SETTING The campaign , conducted in October 1994 - -August 1995 , targeted women of reproductive age and health professionals . Evaluation was by computer-assisted telephone interviews undertaken by r and om dialling throughout the State before and after the campaign , and by self-administered question naires to health professionals and women in the postnatal period . PARTICIPANTS Women of reproductive age and four groups of health professionals . MAIN OUTCOME MEASURES Knowledge about folate , folate-rich foods and the periconceptional period ; participation of health professionals in advising women about folate ; use of periconceptional folic acid supplements ; sales of folic acid tablets ; and prevalence of neural tube defects . RESULTS Significant increases in knowledge about folate followed the campaign . Health professionals and women in the postnatal period had higher initial levels of knowledge about folate , which also increased significantly . The proportions of women taking periconceptional folic acid supplements , and of health professionals advising women planning a pregnancy about folate , also increased significantly , and folic acid tablet sales doubled . Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births ( Poisson regression , P= 0.03 ; average decline of 1.0 % per year ) . CONCLUSIONS A short educational campaign with a limited budget ( $ 40,000 ) can promote folate successfully , but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women Background : Studies of the association of prepregnancy body mass index ( BMI ) and preterm birth have been inconclusive , and no studies have examined the effect of central adiposity on risk . There is also uncertainty about optimal gestational weight gain among Black women . Methods : Using self-reported prospect i ve data from the Black Women 's Health Study , we investigated the relation of preterm birth to prepregnancy BMI ( kg/m2 ) , waist circumference , and gestational weight gain among 7840 singletons born to black women , ages 21–44 , during 1995–2003 . We compared mothers of 1114 infants born 3 or more weeks early ( 597 spontaneous preterm births and 517 medically-indicated preterm births ) with mothers of 6726 term infants . We used generalized estimating equation models to derive multivariable odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . Results : Relative to normal weight women ( BMI : 18.5–24.9 ) , underweight women ( BMI : < 18.5 ) were at increased risk of both preterm birth subtypes ; obese women ( BMI ≥30.0 ) were at increased risk of medically-indicated preterm birth and very early spontaneous preterm birth ( < 32 weeks ' gestation ) . Waist circumference , a measure of central adiposity , was positively associated with medically-indicated preterm birth . Among obese women , average gestational weight gain in the second and third trimesters of < 0.4 or > 0.6 lbs/wk was associated with an increased risk of both preterm birth subtypes . Conclusions : Our data suggest that underweight increases risk of both preterm birth subtypes , while obesity increases risk of medically-indicated preterm birth and only a subgroup of spontaneous preterm births ( < 32 weeks ' gestation ) . Central adiposity was an independent risk factor for medically-indicated preterm birth only . Among obese women , gestational weight gain within the range recommended by the 2009 Institute of Medicine report ( 0.4–0.6 lbs/week in the second and third trimesters ) was associated with the lowest risk of preterm birth CONTEXT Weight gain in young adults is an important public health problem and few interventions have been successful . BACKGROUND This pilot study evaluated the preliminary efficacy of two self-regulation approaches to weight-gain prevention : Small Changes ( changes in energy balance of roughly 200 kcal/day ) and Large Changes ( initial weight loss of 5 - 10 lbs to buffer against future weight gains ) . INTERVENTION Participants were enrolled in 8-week programs teaching Small or Large Changes ( SC ; LC ) . Both approaches were presented in a self-regulation framework , emphasizing daily self-weighing . DESIGN R and omized controlled pilot study . SETTING / PARTICIPANTS Young adults ( N=52 ) aged 18 - 35 years ( 25.6+/-4.7 years , BMI of 26.7+/-2.4 kg/m(2 ) ) were recruited in Providence RI and Chapel Hill NC . MAIN OUTCOME MEASURES Adherence to intervention , weight change , and satisfaction/confidence in approach assessed at 0 , 8 , and 16 weeks . Data were collected in 2008 and analyzed in 2008 - 2009 . RESULTS Participants attended 84 % of sessions , and 86.5 % and 84.5 % of participants completed post-treatment and follow-up assessment s , respectively . Participants adhered to their prescriptions . Daily weighing increased markedly in both groups , whereas the eating and exercise changes observed in the SC and LC reflected the specific approach taught . Weight changes were significantly different between groups at 8 weeks ( SC= -0.68+/-1.5 kg , LC= -3.2+/-2.5 kg , p<0.001 ) and 16 weeks ( SC= -1.5+/-1.8 kg , LC= -3.5+/-3.1 kg , p=0.006 ) . Participants in both groups reported high levels of satisfaction and confidence in the efficacy of the approach they were taught . CONCLUSIONS Both Small and Large Change approaches hold promise for weight-gain prevention in young adults ; a fully powered trial comparing the long-term efficacy of these approaches is warranted OBJECTIVE To assess 1 ) knowledge of neural tube defect ( NTD ) prevention by folic acid , 2 ) frequency of intake of multivitamins and folate- and folic acid-fortified food , and 3 ) factors associated with knowledge and prevention practice s among sexually active minority adolescent and young adult women . METHODS Young minority women were enrolled in a folic acid program at 3 urban Houston , Texas , reproductive health clinics and assessed for NTD knowledge and preventive practice s. A 3-month supply of multivitamins was also dispensed at enrollment . A 3-month program follow-up survey of a r and omly selected sample at 2 sites was conducted . RESULTS Of 387 women ( mean age : 18 + /- 1.9 years ) , 72 % were black and 28 % were Hispanic . At enrollment , clinics were a major source of information of NTD prevention ( 44 % ) ; 52 % had heard of folic acid , 45 % had heard of NTDs , and 50 % had heard of birth defects prevention by multivitamins . Significantly more Hispanic than black young women had heard of NTDs ( 59 % vs 39 % ) . Pregnancy history , regular birth control use , and education level for age were independently associated with knowledge . In young women with low education level for age , regular birth control use was significantly associated with knowledge . At enrollment , daily multivitamin intake was very low ( 9 % ) and folate-rich foods were consumed in inadequate amounts . Adequate folate diet was not associated with knowledge . The program follow-up survey indicated that 88 % to 92 % had knowledge of NTDs and folic acid , and 67 % reported taking a daily multivitamin . CONCLUSIONS Publicly funded clinics may be the only source of information on NTD prevention for many minority young women . Preliminary evidence suggests that a promotion program improves knowledge , and dispensing of multivitamins increases multivitamin use . However , clinicians in such programs need to reinforce daily adherence to multivitamins in young women Background Weekly iron – folic acid supplementation in small-scale research trials and as administered in institutions has been demonstrated to be effective in reducing anemia in adolescent girls . Objective To assess the effectiveness of weekly iron – folic acid supplementation in a large-scale project in reducing the prevalence of anemia in adolescent girls . Methods The project provided weekly iron – folic acid tablets , family life education , and deworming tablets every 6 months to 150,700 adolescent school girls and non-schoolgirls of a total district population of 3,647,834 . Consumption of the iron – folic acid tablets was supervised for schoolgirls but not for non-schoolgirls . Hemoglobin levels were assessed in a r and om sample of non-schoolgirls at 6 and 12 months and schoolgirls at 6 months . The effect of supplementation on the prevalence of anemia and the compliance rate were assessed over a 4-year period . Results In 4 years , the overall prevalence of anemia was reduced from 73.3 % to 25.4 % . Hemoglobin levels and anemia prevalence were influenced significantly at 6 months . No difference in the impact on hemoglobin or anemia prevalence was observed between supervised and unsupervised girls . Counseling on the positive effects of regular weekly iron – folic acid intake contributed to a high compliance rate of over 85 % . The cost of implementation was US$ 0.36 per beneficiary per year . Conclusions Weekly iron – folic acid supplementation combined with monthly education sessions and deworming every 6 months is cost-effective in reducing the prevalence of anemia in adolescent girls . Appropriate counseling , irrespective of supervision , is critical for achieving positive outcomes A r and omized controlled double-blind trial was undertaken in south Wales to prevent the recurrence of neural-tube defects in women who had had one child with a neural-tube defect . Sixty women were allocated before conception to take 4 mg of folic acid a day before and during early pregnancy and 44 complied with these instructions . Fifty-one women were allocated to placebo treatment . There were no recurrences among the compliant mothers but two among the non-compliers and four among the women in the placebo group . Thus there were no recurrences among those who received supplementation and six among those who did not ; this difference is significant ( p = 0.04 ) . It is concluded that folic acid supplementation might be a cheap , safe , and effective method of primary prevention of neural-tube defects but that this must be confirmed in a large , multicentre trial We studied the association between multivitamin use during the periconceptional period and the occurrence of neural tube defects using data from the Atlanta Birth Defects Case-Control Study . There were 347 babies with neural tube defects who were live born or stillborn to residents of metropolitan Atlanta from 1968 through 1980 . The 2829 control-babies born without birth defects were r and omly selected through birth certificates . Periconceptional multivitamin use was defined as reported use for each of the three months before conception through the first three months of pregnancy . Mothers who reported not using multivitamins any time during the six-month period were defined as nonusers . Fourteen percent of mothers reported periconceptional multivitamin use and 40 % reported nonuse . Multivitamin users were different from nonusers in a number of demographic , health-related , and life-style characteristics . We found an overall apparent protective effect of periconceptional multivitamin use on the occurrence of neural tube defects , with a crude estimated relative risk of 0.40 ( 95 % confidence interval , 0.25 to 0.63 ) . At this time , it is not possible to determine whether this apparently lower risk is the direct result of multivitamin use or the result of other characteristics of women who use multivitamins PURPOSE Although literature suggests that physical activity may reduce preeclampsia risk , most prior studies have relied on retrospective exposure assessment . We aim ed to assess prospect ively the relation between recreational physical activity before and during pregnancy and risk of preeclampsia . METHODS We used data from a 1996 - 2003 cohort study of 2241 pregnant western Washington State residents . During structured interviews conducted at 15 wk of gestation , on average , women reported recreational activities during the year before pregnancy and during the previous 7 d. Preeclampsia diagnosis was established for 111 women using medical record data and st and ard guidelines . RESULTS Recreational activity in the year before pregnancy was nonstatistically significantly associated with reduced preeclampsia risk ( adjusted odds ratio [ OR ] for any vs none 0.55 , 95 % confidence interval [ CI ] 0.30 - 1.02 ) . Any activity during early pregnancy was not strongly associated with preeclampsia risk ( adjusted OR = 1.07 , 95 % CI = 0.67 - 1.69 ) . Compared with women who reported no recreational activity before or during early pregnancy , risk was nonsignificantly lower among those who were active only before pregnancy ( OR = 0.73 , 95 % CI = 0.30 - 1.77 ) and during both periods ( OR = 0.76 , 95 % CI = 0.34 - 1.73 ) . Those who were active only in early pregnancy had nonsignificantly increased preeclampsia risk ( OR = 2.03 , 95 % CI = 0.71 - 5.81 ) . CONCLUSION These results corroborate previous case-control studies suggesting that prepregnancy recreational activity reduces preeclampsia risk . The absence of an association with early-pregnancy recreational activity in this cohort may be due to misclassification of usual early-pregnancy activity |
13,050 | 17,715,447 | Electronic-only topics that have been published on the BestBets site ( www.bestbets.org ) and may be of interest to paediatricians include : N Is two thumb or two finger compression better in rescuscitating infants who have sustained a cardiac arrest ? | I n order to give the best care to patients and families , paediatricians need to integrate the highest quality scientific evidence with clinical expertise and the opinions of the family .
Archimedes seeks to assist practising clinicians by providing ‘ ‘ evidence based ’ ’ answers to common questions which are not at the forefront of research but are at the core of practice . | Objective : To evaluate carbamezapine ( CBZ ) for neuritic pain relief in Guillain‐Barré syndrome ( GBS ) patients in the intensive care unit ( ICU ) . Design : Prospect i ve , double‐blind , r and omly allocated crossover study days . Setting : ICU in a tertiary care university hospital . Participants : Twelve consecutive , conscious adult ( 22‐54 yrs ) patients with GBS during recovery from the muscular weakness and receiving pressure‐support ventilation in the ICU . All patients complained of severe backache and /or leg cramps and tenderness in muscles , and they required opioids for pain relief . Interventions : CBZ ( 100 mg every 8 hrs ) or equivalent placebo was given to nursing staff in coded powder form . Medication was given to patients through a nasogastric feeding tube . The same coded medicine was given for 3 days , and after a 1‐day omission , a second set of coded powder was given for the next 3 days in a r and omized , double‐blind , crossover fashion . Pethidine ( 1 mg·kg−1 ) was given intravenously in between , if the pain score was > 2 . Group 1 ( n = 6 ) patients were given a placebo on the first 3 days , followed by CBZ . Group 2 ( n = 6 ) patients were given CBZ on the first 3 days , followed by a placebo . Measurements and Main Results : In these two study periods of different medications , we observed and scored pain ( 1 , no pain ; 5 , severe pain ) , sedation ( 1 , alert ; 6 , asleep , does not respond to verbal comm and ) , and total pethidine requirement per day . In group 1 patients , a significant ( p < .001 ) improvement in the sedation score and a low requirement for pethidine was observed 3 days later , when CBZ was started . However , in group 2 patients , a gradual increase in the pethidine requirement and a high sedation score were noteworthy in the later days of placebo medication . Observations were also analyzed for CBZ days vs. placebo days . Overall , the pain score ( 1.7 ± 0.8 ) during the CBZ period of both regimens was significantly ( p < .001 ) lower than during the placebo days ( 3.1 ± 0.9 ) . Significantly higher doses of pethidine ( 3.7 ± 0.9 mg/kg/day ) were used on the placebo days than on the CBZ days ( 1.7 ± 1.0 mg/kg/day ) . Conclusion : The pain in GBS has a dual origin , and we recommend CBZ as an adjuvant to treat pain in GBS patients , during the recovery phase in the ICU , to reduce the narcotic requirement In a double-blind crossover study of 39 children with established migraine , there was no difference between treatment with propanolol and placebo as regards frequency , severity or average duration of migraine attacks . There was some evidence that propanolol increased the average length of headaches Pain syndromes of Guillain-Barré are neuropathic as well as nociceptive in origin . We aim ed to evaluate the therapeutic efficacy of gabapentin in relieving the bimodal nature of pain in Guillain-Barré syndrome in a r and omized , double-blinded , placebo-controlled , crossover study in 18 patients admitted to the intensive care unit for ventilatory support . Patients were assigned to receive either gabapentin ( 15 mg · kg−1 · d−1 in 3 divided doses ) or matching placebo as initial medication for 7 days . After a 2-day washout period , those who previously received gabapentin received placebo , and those previously receiving placebo received gabapentin as in the initial phase . Fentanyl 2 & mgr;g/kg was used as a rescue analgesic on patient dem and or when the pain score was > 5 on a numeric rating scale of 0–10 . The numeric rating score , sedation score , consumption of fentanyl , and adverse effects were noted , and these observed variables were compared . The numeric pain score decreased from 7.22 ± 0.83 to 2.33 ± 1.67 on the second day after initiation of gabapentin therapy and remained low during the period of gabapentin therapy ( 2.06 ± 0.63 ) ( P < 0.001 ) . There was a significant decrease in the need for fentanyl from Day 1 to Day 7 during the gabapentin therapy period ( 211.11 ± 21.39 to 65.53 ± 16.17 [ & mgr;g ] ) in comparison to the placebo therapy period ( 319.44 ± 25.08 to 316.67 ± 24.25 [ & mgr;g ] ) ( P < 0.001 ) In a prospect i ve study we compared propranolol , placebo , and self-hypnosis in the treatment of juvenile classic migraine . Children aged 6 to 12 years with classic migraine who had no previous specific treatment were r and omized into propranolol ( at 3 mg/kg/d ) or placebo groups for a 3-month period and then crossed over for 3 months . After this 6-month period , each child was taught self-hypnosis and used it for 3 months . Twenty-eight patients completed the entire study . The mean number of headaches per child for 3 months during the placebo period was 13.3 compared with 14.9 during the propranolol period and 5.8 during the self-hypnosis period . Statistical analysis showed a significant association between decrease in headache frequency and self-hypnosis training ( P = .045 ) . There was no significant change in subjective or objective measures of headache severity with either therapy OBJECTIVES This study sought to compare the safety , efficacy and clinical utility of the Amplatzer septal occluder ( ASO ) for closure of secundum atrial septal defect ( ASD ) with surgical closure . BACKGROUND The clinical utility of a device such as the ASO can only be judged against the results of contemporaneous surgery . METHODS A multicenter , nonr and omized concurrent study was performed in 29 pediatric cardiology centers from March 1998 to March 2000 . The patients were assigned to either the device or surgical closure group according to the patients ' option . Baseline physical exams and echocardiography were performed preprocedure and at follow-up ( 6 and 12 months for device group , 12 months for surgical group ) . RESULTS A total of 442 patients were in the group undergoing device closure , whereas 154 patients were in the surgical group . The median age was 9.8 years for the device group and 4.1 years for the surgical group ( p < 0.001 ) . In the device group , 395 ( 89.4 % ) patients had a single ASD ; in the surgical group , 124 ( 80.5 % ) ( p = 0.008 ) had a single ASD . The size of the primary ASD was 13.3 + /- 5.4 mm for the device group and 14.2 + /- 6.3 mm for the surgery group ( p = 0.099 ) . The procedural attempt success rate was 95.7 % for the device group and 100 % for the surgical group ( p = 0.006 ) . CONCLUSIONS The early , primary and secondary efficacy success rates were 94.8 % , 98.5 % and 91.6 % , respectively , for the device group , and 96.1 % , 100 % and 89.0 % for the surgical group ( all p > 0.05 ) . The complication rate was 7.2 % for the device group and 24.0 % for the surgical group ( p < 0.001 ) . The mean length of hospital stay was 1.0 + /- 0.3 day for the device group and 3.4 + /- 1.2 days for the surgical group ( p < 0.001 ) . Mortality was 0 % for both groups . The early , primary and secondary efficacy success rates for surgical versus . device closure of ASD were not statistically different ; however , the complication rate was lower and the length of hospital stay was shorter for device closure than for surgical repair . Appropriate patient selection is an important factor for successful device closure . Transcatheter closure of secundum ASD using the ASO is a safe and effective alternative to surgical repair About 4 per cent of schoolchildren suffer from migraine . In some cases the attacks can be frequent and severe . Often symptomatic and prophylactic treatments are either ineffective or cause pronounced side effects . There have been reports on studies in which a prophylactic effect on migraine by propranolol has been noted . This beta‐receptor blocking agent has been tested in a double‐blind single crossover study in 32 children aged 7–16 with migraine . Propranolol had an excellent prophylactic effect on migraine attacks . Since propranolol does not cause serious side effects provided certain patients are excluded , it seems justifiable to recommend this preparation where prophylactic therapy is indicated in cases of severe and frequent migraine . Forty-seven children with migraine have been included in a double-blind cross-over study with pizotifen and placebo . The children received either pizotifen for 3 months followed by placebo or vice versa . Thirty-nine children completed the trial and there was no significant difference between active and placebo treatment as regards reduction of number of attacks , total and mean duration of attacks and duration of longest attacks . Pizotifen was well tolerated by the children |
13,051 | 27,694,485 | The effectiveness of the BTS campaigns in publicising the benefits of the supine position is confirmed by this paper .
However , the decrease in the knowledge about non-prone positions suggests that the campaigns may not have focused enough on the dangers of the prone position | OBJECTIVES From the late 1980s ' Back-to-Sleep ' ( BTS ) campaigns were run in most developed countries to increase awareness of the supine position 's protective effect against sleep-related infant deaths .
Once the media awareness-raising action associated with these campaigns ended , healthcare professionals ' role became crucial .
The goal of this paper is to determine if healthcare professionals ' knowledge and parent advice consistent with evidence -based infant sleep recommendations have changed over the past 20 years .
RESULTS The correctness of healthcare professionals ' knowledge and parent advice about the supine sleeping position increased over the past 20 years .
More and more healthcare professionals know that it is the best position to reduce the risk of sleep-related deaths and they recommend it exclusively . | A controlled , prospect i ve comparison of the use of the infant seat versus prone , head-elevated positioning in a harness was undertaken in 15 infants with gastroesophageal reflux . pH monitoring of the distal esophagus demonstrated less reflux in the harness than in the seat ( P less than 0.001 ) during 19 pairs of two-hour postpr and ial trials . This difference was the result of both fewer episodes ( P less than 0.001 ) and briefer episodes ( P less than 0.05 ) . Prone-elevated positioning in the harness described is superior to positioning in an infant seat in the treatment of gastroesophageal reflux in infants younger than 6 months To assess the association between infant sleeping position and risk of sudden infant death syndrome ( SIDS ) in an ethnically diverse US population , the authors conducted a population -based case-control study in 11 counties in California from May 1997 through April 2000 . The authors conducted in-person interviews with the mothers of 185 SIDS cases and 312 r and omly selected race/ethnicity- and age-matched controls to collect information on sleeping positions . Infants who had last been put down to sleep in the prone or side position were at greater risk of SIDS than were infants who had last been put down on their backs ( adjusted odds ratio ( AOR ) = 2.6 ( 95 % confidence interval ( CI ) : 1.5 , 4.5 ) and AOR = 2.0 ( 95 % CI : 1.2 , 3.4 ) for the prone and side positions , respectively ) . The risk of SIDS was especially high for an unstable side position in which an infant was placed on its side and found prone ( AOR = 8.7 , 95 % CI : 3.3 , 22.7 ) . Infants who were usually placed on their backs to sleep but had last been put down in the prone or side position ( an unaccustomed position ) had a significantly high risk of SIDS ( AOR = 8.2 ( 95 % CI : 2.6 , 26.0 ) and AOR = 6.9 ( 95 % CI : 2.3 , 20.6 ) for the prone and side positions , respectively ) . Infants placed in an unaccustomed prone or side sleeping position had a higher risk of SIDS than infants who were always placed prone or on the side The AAP has alerted pediatricians to the importance of safe sleep environment for infants . The elements of a safe sleep environment include supine sleep position , safe crib , and avoidance of smoke exposure , soft bedding , and overheating . With the Back to Sleep campaign , prone sleeping among all U.S. infants has decreased to less than 20 % , and the incidence of SIDS has decreased 40 % . However , the decline in SIDS and prone sleeping has leveled off in recent years . Further declines may be possible with decreasing other modifiable risk factors , such as prenatal and postnatal exposure to cigarette smoking . Prior studies have demonstrated that health care professional advice is influential in determining infant care practice s. It is important that physicians caring for infants be aware of the importance of a safe sleep environment and underst and other modifiable risk factors for SIDS . We surveyed a r and om sample of 3,717 physicians in North Carolina and the metropolitan Washington , DC , area to determine knowledge , beliefs , and practice s regarding SIDS and SIDS risk reduction among physicians caring for pregnant women and infants . Twenty-three percent ( 835 ) responded . Most physicians are aware of prone sleeping and cigarette smoke exposure as risk factors for SIDS . Almost all physicians agree that there are measures that can be taken to reduce the risk of SIDS , and they consider it important to discuss SIDS and SIDS risk reduction strategies with parents of young infants . In spite of this belief , only 56 % of family/general practitioners , 18 % of obstetrician-gynecologists , and 79 % of pediatricians discuss SIDS routinely . Only 35 % of pediatricians , 15 % of family/general practitioners , and 16 % of obstetrician-gynecologists provide written information . In addition , only 38 % of physicians recommend supine , while 50 % recommend side or back , 6 % side , and 7 % prone . Only two thirds of pediatricians and one third of family/general practitioners are aware that the AAP recommends supine as the preferred sleep position for infants . Pediatricians are more likely to be aware of the AAP recommendation ( p < O.OOOJ ) and to discuss SIDS risk reduction strategies with parents ( p=0.03 ) . We conclude that many physicians who care for infants are unaware of the AAP 's most current recommendation for sleep position and are incorrectly recommending the side position . Physicians may also be unaware of other sleep environment hazards . Further educational efforts must continue for physicians who provide care to pregnant women and children to ensure a continued decline in the incidence of SIDS OBJECTIVES To identify the risk factors for sudden infant death syndrome ( SIDS ) following a national campaign to prevent SIDS . METHODS For 2 years ( October 1 , 1991 through September 30 , 1993 ) data were collected by community child health nurses on all infants born in New Zeal and at initial contact and at 2 months . RESULTS There were 232 SIDS cases in the postneonatal age group ( 2.0/1000 live births ) and these were compared with 1200 r and omly selected control subjects . Information was available for 127 cases ( 54.7 % ) and 922 ( 76.8 % ) of controls . The previously identified modifiable risk factors were examined . The prevalence of prone sleeping position of the infant was very low ( 0.7 % at initial contact and 3 . 0 % at 2 months ) , but was still associated with an increased risk of SIDS . In addition , the side sleeping position was also found to have an increased risk of SIDS compared with the supine sleeping position ( at 2 months : adjusted odds ratio ( OR ) = 6.57 ; 95 % confidence interval ( CI ) = 1.71 , 25.23 ) . Maternal smoking was found to be the major risk factor for SIDS . Bed sharing was also associated with an increased risk of SIDS . There was an interaction between maternal smoking and bed sharing on the risk of SIDS . Compared with infants not exposed to either bed sharing or maternal smoking , the adjusted OR for infants of mothers who smoked was 5.01 ( 95 % CI = 2.01 , 12.46 ) for bed sharing at the initial contact and 5.02 ( 95 % CI = 1.05 , 24 . 05 ) for bed sharing at 2 months . In this study breastfeeding was not associated with a statistically significant reduction in the risk of SIDS . The other risk factors for SIDS identified were : unmarried mother , leaving school at a younger age , young mother , greater number of previous pregnancies , late attendance for antenatal care , smoking in pregnancy , male infant , Maori ethnicity , low birth weight , and shorter gestation . CONCLUSIONS After adjustment for potential confounders , prone and side sleeping positions , maternal smoking , and the joint exposure to bed sharing and maternal smoking were associated with statistically significant increased risk of SIDS . A change from the side to the supine sleeping position could result in a substantial reduction in SIDS . Maternal smoking is common in New Zeal and and with the reduction in the prevalence of prone sleeping position is now the major risk factor in this country . However , smoking behavior has been difficult to change . Bed sharing is also a major factor but appears only to be a risk to infants of mothers who smoke . Addressing bed sharing among mothers who smoke could reduce SIDS by at least one third . Breastfeeding did not appear to offer a statistically significant reduction in SIDS risk after adjustment of potential confounders , but as breastfeeding rates are comparatively good in New Zeal and , this result should be interpreted with caution as the power of this study to detect a benefit is small Background : Although advice from healthcare professionals may influence parental infant placement choice to reduce sudden infant death syndrome risk , literature on nursery staff infant placement behaviors and the degree to which they influence maternal infant sleep positioning is limited . Objective : To assess newborn placement practice s of the mother and nursery staff and their interrelationship in the hospital setting . Methods : A cross-sectional survey-based study was conducted among hospital newborn nursery staff ( n = 96 ) and mothers of newborns ( n = 579 ) at eight perinatal hospitals in Orange County , California . Results : Although a majority of sample d nursery staff ( 72 % ) identified the supine position as the placement that most lowers sudden infant death syndrome risk , only 30 % reported most often placing infants to sleep in that position , with most staff ( 91 % ) citing fear of aspiration as the motivation for supine position avoidance . Only 34 % of staff reported advising exclusive supine infant positioning to mothers . Approximately 36 % of mothers reported using supine infant placement exclusively . Maternal infant placement choice varied by both the advice ( p < .01 ) and the placement modeling ( p < .01 ) provided by staff , with the highest proportion of usual supine infant placement found among mothers who reported receiving both . A mother ’s race/ethnicity also affected the reception of exclusive supine placement recommendations ( p < .01 ) . Conclusions : Exclusive supine infant placement appears to be underused by both nursery staff and mothers of newborn infants . Culturally grounded educational intervention with nursery staff regarding infant positioning and placement in the hospital setting is indicated & NA ; There is a direct relationship between nonsupine sleeping and sudden infant death syndrome ( SIDS ) . Premature infants are at greater risk for SIDS and are often cared for in nonsupine positions during the course of hospitalization . Healthy premature infants should be placed supine for sleep before discharge from the neonatal intensive care unit ( NICU ) , and parents receive specific instruction about infant sleep position and other risk factors for SIDS . Most published literature addressing nursing practice s for SIDS reduction reflects practice s with the healthy newborn population . PURPOSE : To examine and describe NICU nurses ' knowledge of SIDS risk-reduction measures , modeling of safe infant sleep interventions prior to discharge , and inclusion of SIDS risk reduction in parent education . SUBJECTS : Convenience sample of nurses practicing in level II and III NICUs located in 2 Middle Atlantic States . DESIGN AND METHODS : A prospect i ve survey design was used for the study . The 14-item question naire was developed by a team of neonatal clinical experts and distributed via site coordinators to nurses in 19 NICUs . PRINCIPAL RESULTS : A total of 1080 surveys were distributed and 430 ( 40 % ) NICU nurses completed the survey . The majority of nurses ( 85 % ) identified the American Academy of Pediatrics SIDS risk-reduction strategies for safe sleep . The investigators found that age , years of nursing and neonatal nursing experience , and educational preparation did not significantly contribute to the practice of “ supine-only ” position for sleep for infants in NICUs . The study revealed that nurses frequently position healthy preterm infants supine for sleep when weaned to an open crib ( 50 % ) . Others wait one to a few days before discharge ( 15 % ) and some never position supine for sleep ( 6 % ) . Stuffed toys are removed from cribs 90.5 % of the time . For term infants without major medical complications , 45.5 % of surveyed nurses continued to use positioning aids/rolls in infants ' cribs . The most common reasons nurses cited to position preterm infants side-lying or prone in a crib were fear of aspiration ( 29 % ) , infant comfort ( 28 % ) , and infant safety ( 20 % ) . NICU nurses educated parents about SIDS and reduction strategies , using various media . At discharge , 73 % of the nurses verbally communicated with parents , 53 % provided printed literature , and 14 % used audiovisual aids with parents . CONCLUSIONS : NICU nurses are in influential positions to educate parents and model SIDS risk-reduction strategies . This study supports other published research that points to inconsistencies in nursing practice regarding implementation of methods to reduce the risk of SIDS |
13,052 | 20,393,961 | There is some evidence to suggest that there is no difference between the speed of tooth alignment or pain experienced by patients when using one initial aligning arch wire over another . | BACKGROUND The initial arch wire is the first arch wire to be inserted into the fixed appliance at the beginning of orthodontic treatment and is used mainly for correcting crowding and rotations of teeth .
With a number of orthodontic arch wires available for initial tooth alignment , it is important to underst and which wire is most efficient , as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment .
OBJECTIVES To identify and assess the evidence for the effects of initial arch wires for alignment of teeth with fixed orthodontic braces in relation to alignment speed , root resorption and pain intensity . | INTRODUCTION The aim of this study was to investigate the duration of m and ibular-crowding alleviation with self-ligating brackets compared with conventional appliances and the accompanying dental effects . METHODS Fifty-four subjects were selected from a pool of patients satisfying the following inclusion criteria : non extraction treatment in the m and ibular or maxillary arches ; eruption of all m and ibular teeth ; no spaces in the m and ibular arch ; irregularity index greater than 2 in the m and ibular arch ; and no therapeutic intervention planned with any extraoral or intraoral appliance . The patients were r and omly assigned to 2 groups : 1 group received treatment with a self-ligating bracket ( Damon 2 , Ormco , Glendora , Calif ) and the other with a conventional edgewise appliance ( Microarch , GAC , Central Islip , NY ) , both with 0.022-in slots . The irregularity index of the m and ibular arch was normalized between the groups , and the time to alignment was estimated in days . Treatment duration was assessed by data modeling with the Cox proportional hazard regression . Lateral cephalometric radiographs were used to assess the alteration of m and ibular incisor position before and after alignment . Measurements of intercanine and intermolar widths were also made on dental casts to determine changes associated with correction . RESULTS AND CONCLUSIONS Overall , no difference in the time required to correct m and ibular crowding with Damon 2 and conventional brackets was observed . For moderate crowding ( irregularity index < 5 ) , however , the self-ligating group had 2.7 times faster correction . This difference was marginally insignificant for subjects with irregularity index scores greater than 5 . Greater crowding prolonged treatment by an additional 20 % for each irregularity index unit . Increases in intercanine and intermolar widths associated with crowding correction regardless of bracket group were noted . The self-ligating group showed a statistically greater intermolar width increase than the conventional group . Also , an alignment-induced increase in the proclination of the m and ibular incisors was observed for both bracket groups , but no difference was found between Damon 2 and conventional brackets for this parameter In a clinical trial involving 155 dental arches with irregularity > 5 mm , the rate of alignment was used to compare the alignment efficiency of 16 mil superelastic Ni-Ti versus 17.5 mil triple-str and ed steel archwires , and to determine whether ion implantation of the Ni-Ti wire improved its performance . Subjects were r and omly assigned to archwire types ; both 18 and 22 slot edgewise appliances were employed . Pre-treatment equivalence of the experimental groups was verified . Anterior irregularity was determined monthly ( using Little 's irregularity index ) until it decreased below 2 mm , and the elastomeric ligatures were replaced at each appointment . Effective tooth movement occurred with each of the archwire types . There were no significant differences among wires , but the rate of alignment was significantly faster in the lower arch for subjects with the 22 slot appliance Two arch wires commonly used for initial tooth alignment were compared with regard to their clinical effectiveness . The two arch wires tested were 0.0155-inch diameter multiple-str and ed stainless steel wire ( Dentaflex , Dentaurium , Optident , Yorkshire , Engl and ) and 0.014-inch diameter nickel-titanium alloy wire ( NiTi , ORMCO Co. , Monrovia , Calif. ) . Consecutive patients attending an orthodontic clinic for routine placement of a fixed appliance were r and omly assigned one of these two initial arch wires . Good quality alginate impressions of the appropriate dental arch were taken before arch wire placement and also at the subsequent appointment , which was , on average , 6 weeks later . Seventy-four arches were used in this study . The degree of tooth alignment achieved for each wire type was compared with a Reflex Microscope ( Reflex Measurement Ltd. , Butleigh , Engl and ) to make detailed measurements on the result ant casts . The degree of initial alignment achieved with the two wires was similar over this 6-week period . However , some differences were found for the lower labial segment where the interbracket span is usually reduced and where the superelastic nickel-titanium wire was found to give improved alignment . No threshold of crowding was found where one arch wire performed better than the other Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement . The two archwires used were a superelastic nickel-titanium alloy , 0.014 inch Sentalloy , Light ( GAC International Inc. Central Islip , NY , USA ) and a 0.014 inch Nitinol ( unitek , Monrovia , CA , USA ) , a conventional nickel-titanium aligning archwire . One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practice s for routine placement of a fixed appliance were r and omly assigned one of these 2 initial archwires . Assessment s of pain/discomfort were made daily by means of a 100 mm visual analog scale ( VAS ) over the first 7-day period after bonding . On the first day , recordings were made every hour for the first 11 hours . The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires , with a peak in the first night , remaining high on the second day and decreasing thereafter to baseline level after 7 days . During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire , although a significant difference could be found at 4 hours only . No significant gender-specific differences were found in either archwire group . A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire , with the lower arch having the higher pain experience . ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen , die häufig für die initiale Nivellierung verwendet werden , wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht . Das eine Bogen material war eine superelastische NiTi-legierung , 0,014 inch Sentalloy , Light ( GAC International Inc. , Central Islip , N. Y. ) , das and ere ein herkömmlicher 0,014 inch Nitinol-Bogen ( Unitek , Monrovia , Kalifornien).128 fortlaufend beh and elte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen , bei denen routinemäßig eine Multib and apparatur eingesetzt werden sollte , wurden r and omisiert für den einen oder den and eren Bogen vorgesehen . Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge ( visual analogue scale , VAS ) vorgenommen . Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet . Die Ergebnisse zeigten , daß die Beschwerden für den ersten Bogen , sowohl für den Sentalloy-als auch für den Nitinol-Bogen , kontinuierlich jede Stunde nach dem Einsetzen anstiegen . Der Höhepunkt wurde in der ersten Nacht erreicht , blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau . Während der ersten zehn Stunden war es offensichtlich , daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen ; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant . Keine signifikanten Unterschiede der Beschwerden zwischen den Bogen material ien f and en sich hinsichtlich des Geschlechts der Patienten . Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet ; i m Unterkiefer traten deutlich stärkere Beschwerden auf The aim of this study was to compare three orthodontic archwire sequences . One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and r and omly allocated to one of three groups : A = 0.016-inch nickel titanium ( NiTi ) , 0.018 x 0.025-inch NiTi , and 0.019 x 0.025-inch stainless steel ( SS ) ; B = 0.016-inch NiTi , 0.016-inch SS , 0.020-inch SS , and 0.019 x 0.025-inch SS ; and C = 0.016 x 0.022-inch copper ( Cu ) NiTi , 0.019 x 0.025-inch CuNiTi , and 0.019 x 0.025-inch SS . At each archwire change and for each arch , the patients completed discomfort scores on a seven-point Likert scale at 4 hours , 24 hours , 3 days , and 1 week . Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated . A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed . There were no statistically significant differences between archwire sequences A , B , or C for patient discomfort ( P > 0.05 ) or root resorption ( P = 0.58 ) . The number of visits required to reach the working archwire was greater for sequence B than for A ( P = 0.012 ) but this could not be explained by the increased number of archwires used in sequence The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain OBJECTIVES To examine whether the transition temperature of Cu-NiTi archwires has an effect on the tooth movement during the alignment phase of orthodontic treatment . DESIGN ' Split mouth ' design in r and omly selected patients . SETTING AND SAMPLE POPULATION The Department of Orthodontics , School of Dentistry , University of Aarhus . Fifteen r and omly selected patients with identical level of irregularity in the alignment phase of their treatment . Experiment Variable - Specially manufactured Cu-NiTi archwires for the upper arch were inserted . These consisted of two separate halves , each with its own transition temperature , respectively 27 degrees and 40 degrees C , and clamped together in the middle . OUTCOME MEASURE The tooth movement , expressed as two translations and a rotation , in the occlusal plane was measured from the patients ' intraoral photographs taken upon insertion of the archwires and again after 1 month . RESULTS Tooth movements tended to be larger on the 40 degrees C-side , however only in case of the total translation of the premolars was this difference significant . In general , patients had not noticed any difference between the two sides of the archwire , although one patient stated the 27 degrees C-side to be more comfortable as the 40 degrees C-side had bothered her when drinking hot beverages . CONCLUSION The transition temperature of Cu-NiTi archwires has indeed an effect on the amount of tooth movement during alignment . However , the differences are so small though that it is the question whether they can be noticed clinical ly . The study corroborates the trend towards the use of lower forces within orthodontics To comprehend the result of a r and omized controlled trial ( RCT ) , readers must underst and its design , conduct , analysis and interpretation . That goal can be achieved only through complete 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 using a checklist and flow diagram . The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticism of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Comment . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the 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 or participants through an RCT . The revised flow diagram depicts information from 4 stages of a trial ( enrollment , intervention allocation , follow-up and analysis ) . The diagram explicitly includes the number of participants , according to each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting or an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results A prospect i ve r and omized clinical study was design ed to evaluate the effects of full continuous arch wires , rectangular in cross section , on the axial inclination of lower incisors . The intention of rectangular arch wires is to counteract the labial crown moment usually produced during leveling the curve of Spee with full arch mechanics . Patients were r and omly assigned to 2 groups . Group 1 ( N = 12 ) received round arch wires throughout the leveling stage . Group 2 ( N = 16 ) started with flat 0.016 x 0.022 nickel titanium arch wires progressing to 0.016 x 0.022 stainless steel . The preadjusted 0.018 x 0.025 edgewise appliance was used in all cases . Lateral cephalometric radiographs and m and ibular study models were taken before treatment and when the curve of Spee was leveled ( or in some cases when the overbite was considered clinical ly acceptable ) . In group 1 , the lower incisor proclined a mean of 6.75 degrees + /- 4.85 degrees ( P < .01 ) and in group 2 it proclined a mean of 6.10 degrees + /- 3.95 degrees ( P < .01 ) . However , no significant difference in proclination was detected between the 2 groups . Statistically significant , but low , correlations were demonstrated between change in lower incisor axial inclination and relief of crowding r = 0.45 ) and change in m and ibular arch depth r = 0.54 ) , which was in turn inversely correlated with change in intercanine width r = -0.45 ) . In both groups , the lower incisors proclined with uncontrolled tipping that can probably be attributed to the intrusive force introduced by the arch wire being labial to the center of resistance of the lower incisors . The ability of the rectangular arch wires to control labial proclination following leveling of the curve of Spee , as used in this study , was not supported OBJECTIVES To clinical ly evaluate three commonly used orthodontic tooth aligning arch wires : 016 x 022 inch active martensitic medium force nickel titanium , 016 x 022 inch grade d force active martensitic nickel titanium , and 0.0155 inch multistr and stainless steel . DESIGN A prospect i ve r and omized clinical trial . DATA SOURCE Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients . Analysis based on completed records for 98 arch wires and 51 patients . METHOD A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were r and omly allocated two different arch wires from a possible three under trial . Good quality impressions were taken of the dental arches at the design ated serial stages of alignment ( start , T0 ; 4 weeks , T4 ; 8 weeks , T8 ) . The result ant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions ( horizontal plane only ) . RESULTS The measurement error was within acceptable limits ( range , 0.05 to 0.09 mm ) and showed no significant bias . ANOVA statistical models were fitted to the data to adjust for a number of variables . No significant difference in aligning capability ( p > 0.05 ) , in either two or three dimensions , was demonstrated between the three arch wires in the trial . CONCLUSION Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistr and stainless steel wires in this r and omized clinical trial . The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response . Alternatively , it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment The aims of this study were to investigate the initial time at which pain occurs after insertion of two initial wires of different sizes , the duration of the pain , the areas affected within the mouth , the level of self-medication , the effect of this pain on daily life , and whether gender is important in the perception of pain . The study group consisted of 109 patients ( 52 boys , 57 girls ) with a mean chronological age of 13.6 years for boys and 14.7 years for girls . Insertion of either a 0.014 or 0.016 inch wire was by r and om selection . Following insertion of the archwires , a question naire comprising a total of 49 questions was given to the patients . They described the time of initial pain in the first question , answered the next 24 questions as ' yes ' or ' no ' , and used a visual analogue scale for the final 24 questions . No significant differences were found in terms of gender , in the perception period of initial pain as regards the areas affected within the mouth or the effect of pain on daily living when the 0.014 and 0.016 inch wire groups were compared at 6 hours , 1 , 2 , 3 , 4 , 5 , 6 and 7 days . At 24 hours , which was found to be statistically significant , more pain relief was used in the 0.014 inch archwire group . The results show that in both groups , initial pain was perceived at 2 hours , peaked at 24 hours and had decreased by day 3 The physical properties of a super-elastic archwire alloy ( Titanol ) and Nitinol were investigated by the means of a bending test . It was found that the alloy possessed super-elastic properties . A clinical trial was then carried out to compare the properties of two types of aligning archwire . Two groups of 20 patients with crowded dentitions were r and omly allocated either Titanol or Nitinol , a conventional nickel-titanium alloy aligning archwire . High quality alginate impressions were taken after archwire placement in Edgewise fixed appliances and were repeated after a mean period of 35 days . The impressions were cast in dental stone and digitized using the Reflex Metrograph . The contact points of the teeth of the labial segments , together with four stable points in the rugae were recorded . This enabled the co-ordinates for the sequential study models to be superimposed upon one another , allowing tooth movement in three dimensions to be calculated . The measurement error expressed as error variance was 0.028 mm . The coefficient of reliability was 97 per cent . When tooth movement was analysed the mean movement per contact point for Titanol was 1.7 mm and for Nitinol 1.42 mm . This difference was not statistically significant ( P less than 0.05 , t-test ) . However , a clinical impression was that the super-elastic archwire proved superior to the Nitinol , because it was more readily engaged into grossly displaced teeth A r and omized controlled clinical trial was performed to compare the nature , prevalence , intensity , and duration of pain related to the use of a relatively recently developed superelastic arch wire and a more traditional multistr and ed steel arch wire . Other factors likely to influence the pain experience were also investigated . Forty-three subjects participated in the study , the pain response being assessed by each of the visual analogue scales , the question naires , and an analgesic consumption record . In 18 of the 43 subjects a st and ardized preliminary dental extraction procedure was used as a control . Subsequent to the r and om allocation of an initial arch wire in 43 patients , 22 of them underwent a second arch wire in the opposing arch , the wire again being determined by r and om allocation . It was found that the prevalence , intensity , and duration of pain after the insertion of the two types of wire was similar but much greater than in the post extraction control phase . The pain score peaked on the morning after the placement of the arch wire , lasting typically for 5 to 6 days . The pain and discomfort experienced after the insertion of the second arch wire was similar to that of the first , no conditioning response being evident . Overall a diurnal variation was found with a tendency to an increase in pain in the evenings and nights , although this did not greatly affect sleep . The pain response was found to be highly and consistently subjective , not related to the dental arch , crowding , sex , or social class ; however , a statistically significant association was found between the age and the pain experienced INTRODUCTION Our objective was to compare the effects of 2 preadjusted appliances on angular and linear changes of the m and ibular incisors , and transverse m and ibular arch dimensional changes over a minimum of 30 weeks . This was a prospect i ve , r and omized , controlled , clinical trial a the Royal London Hospital , School of Dentistry , in London and the Kent and Canterbury Hospital in Canterbury , United Kingdom . METHODS Sixty- six consecutive patients satisfying the inclusion criteria were enrolled and r and omly allocated to treatment with a self-ligating bracket system ( SmartClip , 3 M Unitek , Monrovia , Calif ) and conventional preadjusted edgewise brackets ( Victory , 3 M Unitek ) . Initial study models and cephalograms were obtained within a month of starting the trial . All subjects received treatment with the following archwire sequence : 0.016-in round , 0.017 x 0.025-in rectangular , 0.019 x 0.025-in rectangular martensitic active nickel-titanium archwires , and 0.019 x 0.025-in stainless steel archwires . Final records , including study models and a lateral cephalogram , were collected a minimum of 30 weeks after initial appliance placement . Lateral cephalograms were assessed for treatment-related changes in m and ibular incisor inclination and position . Transverse dimensional changes in intercanine , interpremolar , and intermolar dimensions , and the amount of crowding alleviated during the study period were assessed by comparison of pretreatment and posttreatment models . All measurements were made with a digital caliper ( 150 mm ISO 9001 electronic caliper , Tesa Technology , Renens , Switzerl and ) . RESULTS Sixty patients completed the study . After adjustment for pretreatment values , duration of treatment , and amount of crowding alleviated during the study period , bracket type had little effect on incisor inclination ( P = 0.437 ) and positional changes ( P = 0.35 ) , and intercanine ( P = 0.967 ) , inter-first premolar ( P = 0.495 ) , and inter-second premolar ( P = 0.905 ) dimensions . However , the self-ligating appliance produced slightly more expansion in the molar region , a difference that was statistically significant ( P = 0.009 ) . Pretreatment values for incisor inclination ( P = 0.044 ) and transverse dimensions ( P = 0.000 ) affected inclination and transverse changes , respectively , with proclination less likely when the labial segment was proclined at the outset and expansion unlikely during leveling and alignment in wider arches . Greater alleviation of crowding during the study period result ed in more incisor proclination ( P = 0.000 ) and advancement ( P = 0.000 ) . CONCLUSIONS There was little difference overall in the pattern of arch alignment and leveling related to the 2 preadjusted appliances . However , there was a statistically greater increase in intermolar width in the group treated with the self-ligating appliance , although the difference was only 0.91 mm OBJECTIVES To test the hypotheses that ( 1 ) there is no difference in the pain experience during the week following initial placement of two orthodontic appliances ( SmartClip and Victory ; 3 M Unitek , Monrovia , Calif ) ; and ( 2 ) there is no difference in the pain experience during removal and insertion of orthodontic archwires with these brackets . MATERIAL S AND METHODS Sixty-six consecutive patients were treated with a self-ligating bracket system ( SmartClip ) or a conventional appliance ( Victory ) on the basis of computer-generated r and om allocation . After appliance placement and engagement of a 0.016 ' ' nickel-titanium archwire , pain experience was recorded after 4 , 24 , and 72 hours and after 7 days with the use of a visual analog system ( VAS ) question naire . At a subsequent visit , participants documented pain experiences during removal and insertion of 0.019 x 0.025 ' ' archwires on an additional 100 mm VAS question naire . Independent t-tests and analyses of covariance were used to analyze normally distributed data ; the Mann-Whitney U-test was used for skewed distributions . RESULTS Forty-eight ( 72.2 % ) and fifty-one ( 77.3 % ) subjects completed the first and second parts of the study , respectively . Bracket type had no influence on pain experience at 4 hours ( P = .958 ) , 24 hours ( P = .289 ) , 72 hours ( P = .569 ) , and 7 days ( P = .756 ) following appliance placement . However , bracket type significantly influenced pain experience during archwire removal ( P = .001 ) and insertion ( P = .013 ) . CONCLUSIONS Hypothesis 1 can not be rejected . The bracket type had no effect on subjective pain experience during the first week after initial placement of two preadjusted orthodontic appliances . Hypothesis 2 was rejected . Significantly greater discomfort was experienced during archwire insertion and removal with the SmartClip appliance |
13,053 | 28,685,082 | DWI performed with ADC values was useful for predicting the chemotherapeutic response of osteosarcoma .
This method may have promising potential as a preoperative non-invasive modality | The histological examination of the tumor necrosis upon surgery remains the most reliable prognostic factor for osteosarcoma .
However , the detection of more early prognostic factors is desirable in order to increase the survival rates and decrease the risk rates for iatrogenic toxicity .
The purpose of the current systematic review and meta- analysis was to provide an up-to- date summary of the role of diffusion-weighted imaging ( DWI ) for the preoperative assessment of the chemotherapy response in osteosarcoma . | Background Preoperative diffusion-weighted MRI ( DW-MRI ) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients . A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy . Objective To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma , more specifically at mid-course of treatment . Material s and methods This study was carried out on a prospect i ve series of adolescents treated for long-bone osteosarcoma . MR examinations were performed at diagnosis ( MRI-1 ) , at mid-course of chemotherapy ( MRI-2 ) , and immediately before surgery ( MRI-3 ) . A DW sequence was performed using diffusion gradients of b0 and b900 . The apparent diffusion coefficients ( ADC1 , ADC2 , ADC3 , respectively ) , their differentials ( ADC2 − ADC1 and ADC3 − ADC1 ) , and their variation ( ADC2 − ADC1/ADC1 and ADC3 − ADC1/ADC1 ) were calculated for each of these three time points . Results Fifteen patients were included . Patients with no increase in ADC showed a poor response to chemotherapy on their histology results . At mid-course , the three calculated values were significantly different between good and poor responders . ADC2 − ADC1 enabled us to detect , with 100 % specificity , four out of seven of the poor responders . There was no significant difference in the values at MRI-3 between the two groups . Conclusion DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma . This method could be used as an early prognostic factor to monitor preoperative chemotherapy The objective of this study was to prospect ively evaluate dynamic contrast‐enhanced magnetic resonance imaging ( DCE‐MRI ) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event‐free survival ( EFS ) and overall survival in pediatric patients with newly diagnosed , nonmetastatic osteosarcoma who were treated on a single , multi‐institutional phase 2 trial BACKGROUND Previous r and omized controlled trials that used the two-drug chemotherapy regimen of cisplatin and doxorubicin as the conventional arm showed no evidence of benefit from an increase in the number of agents or the length of treatment . It was then proposed that survival could be improved by increasing the planned dose intensity of cisplatin and doxorubicin . METHODS Previously untreated patients with nonmetastatic , high- grade , central osteosarcoma of an extremity were r and omly assigned to Regimen-C ( conventional treatment with six 3-week cycles of cisplatin [ 100 mg/m2 by 24-hour infusion ] and doxorubicin [ 25 mg/m2/day by 4-hour infusion for 3 days ] ) or to Regimen-DI ( intensified treatment with identical total doses of cisplatin and doxorubicin , planned as six 2-week cycles supported by granulocyte colony stimulating factor ( G-CSF ) . Surgery was scheduled for week 6 in both arms . Primary and secondary outcome measures were overall and progression-free survival , respectively . Intention-to-treat analyses were performed using st and ard survival analysis methods . L and mark analyses were performed in patients with known surgical details and central ly review ed histologic response . All statistical tests were two-sided . RESULTS Between May 1993 and September 2002 , treatment was r and omly allocated to 497 eligible patients . Six cycles of chemotherapy were completed by 78 % of patients in Regimen-C and 80 % of patients in Regimen-DI . The delivered preoperative median dose intensity of cisplatin was 86 % in Regimen-C and 111 % in Regimen-DI ( as the percentage of that planned for the conventional regimen ) . Postoperative median dose intensity of cisplatin was 82 % in Regimen-C and 110 % in Regimen-DI ( the corresponding figures for doxorubicin dose intensity were similar ) . Regimen-DI was associated with lower risks of severe leucopenia and neutropenia and higher risks of thrombocytopenia and mucositis . Good histologic response ( > 90 % tumor necrosis ) was observed in 36 % of Regimen-C patients and 50 % of Regimen-DI patients ( P = .003 , chi2 test ) . There was no evidence of a difference in overall survival ( hazard ratio [ HR ] = 0.94 , 95 % CI = 0.71 to 1.24 ; P = .64 ) or progression-free survival ( HR = 0.98 , 95 % CI = 0.77 to 1.24 ; P = .83 ) . L and mark analyses showed similar results . CONCLUSIONS Planned intensification of chemotherapy with cisplatin and doxorubicin increased received dose intensity and result ed in a statistically significant increase in favorable histologic response rate , but not in increased progression-free or overall survival . Our results call into question the use of histologic response as a surrogate outcome measure in trials of this disease PURPOSE To prospect ively assess whether there is a relationship between the apparent diffusion coefficient ( ADC ) and the histopathologic cell count and whether the ADC can enable differentiation of benign and malignant extracranial mass lesions in children . MATERIAL S AND METHODS Institutional ethics approval and parent or guardian consent were obtained . Eleven malignant and eight benign lesions in 19 children ( 11 girls , eight boys ; median age , 3.9 years ; age range , 11 days to 15.5 years ) who underwent magnetic resonance ( MR ) imaging of extracranial mass lesions-including a diffusion-weighted sequence ( with b values 0 , 500 , and 1000 sec/mm(2))- and histopathologic analysis to prove findings were studied . The median ADC within each mass lesion was compared with the median cell count for 10 high-power microscopic fields in the specimen . The inverse regression between cell count and ADC was calculated . The difference in ADC between benign and malignant lesions was assessed by using the Mann-Whitney U test . RESULTS There was an inverse relationship between ADC and cell count , expressed as ADC ( in x10(-3 ) mm(2)/sec ) = 0.56 + ( 66.2/cell count ) , with a relatively good fit to the observed data ( analysis of variance R(2 ) = 0.541 , F = 20.0 , P < .001 ) . The ADCs of benign lesions ranged from ( 0.84 - 2.83 ) x 10(-3 ) mm(2)/sec ( median , 1.35 x 10(-3 ) mm(2)/sec ; st and ard deviation , 0.68 ) . The ADCs of malignant lesions ranged from ( 0.73 - 1.53 ) x 10(-3 ) mm(2)/sec ( median , 1.00 x 10(-3 ) mm(2)/sec ; st and ard deviation , 0.29 ) . There was no significant difference in ADC between benign and malignant lesions ( Mann-Whitney U = 22 , P = .069 ) . All highly cellular ( > 150 cells per high-power field ) lesions had an ADC lower than 1.5 x 10(-3 ) mm(2)/sec . CONCLUSION Although there is a significant relationship between cellularity and ADC , cell count probably is not the sole determinant of the ADC . Use of the ADC can not enable accurate differentiation of malignant and benign lesions We evaluated the potential of 18F-FDG PET/CT and diffusion-weighted imaging ( DWI ) to monitor the histologic response in patients with extremity osteosarcoma receiving neoadjuvant chemotherapy , using sequential PET/CT and MR imaging . Methods : We prospect ively registered 28 patients with high- grade osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy and surgery . All patients underwent sequential 18F-FDG PET/CT and MR imaging before ( PET/MR1 ) and after neoadjuvant chemotherapy ( PET/MR2 ) . Maximum st and ardized uptake value ( SUV ) , tumor volume based on MR imaging ( MRV ) , and the mean apparent diffusion coefficient ( ADC ) values were measured on PET/MR1 ( SUV1 , MRV1 , and ADC1 ) and PET/MR2 ( SUV2 , MRV2 , and ADC2 ) . The percentage changes in maximum SUV ( ΔSUV ) , MRV ( ΔMRV ) , and ADC ( ΔADC ) were calculated , and the correlations among these parameters were evaluated . After surgery , the effects of neoadjuvant chemotherapy were grade d histopathologically : grade s III and IV ( necrosis of ≥ 90 % ) indicated a good response , and grade s I and II ( necrosis of < 90 % ) indicated a poor response . The optimum cutoff values of ΔSUV , ΔMRV , ΔADC , and their combination for predicting histologic response were assessed by single- and multi-receiver-operating-characteristic curve analysis . Results : Twenty-seven patients were enrolled in the present study after 1 patient with inadequate acquisition of MR imaging was excluded . ΔSUV and ΔADC negatively correlated with each other ( ρ = −0.593 , P = 0.001 ) , and ΔMRV did not correlate with ΔSUV or ΔADC . The cutoff value , sensitivity , specificity , and accuracy for predicting good histologic response were ≤ −52 % , 67 % , 87 % , and 78 % , respectively , for ΔSUV and > 13 % , 83 % , 73 % , and 78 % , respectively , for ΔADC . However , ΔMRV did not predict histologic response . Sensitivity , specificity , and accuracy were 83 % , 87 % , and 85 % , respectively , using the combined criterion of ΔSUV ≤ −31 % and ΔADC > 13 % . Conclusion : In the current preliminary study , both PET/CT and DWI are useful for predicting histologic response after neoadjuvant chemotherapy in osteosarcoma . Combining PET/CT and DWI may be an effective method to predict the histologic response of patients to neoadjuvant chemotherapy From January 1993 to March 1995 , 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol . 133 patients had localised disease , while 29 had metastases at diagnosis . These last patients were simultaneously operated upon for their primary and metastatic lesions . Chemotherapy consisted preoperatively of two cycles of high dose methotrexate ( HDMTX ) and one cycle each of cisplatin (CDP)-doxorubicin ( ADM ) , CDP/ifosfamide ( IFO ) and IFO/ADM . After surgery , patients were treated with the aforementioned drugs used as single agents . The mean follow-up of all patients was 6.5 years ( 5.5 - 8 years ) . Surgery was a limb salvage in 94 % of cases , and the 5-year event-free survival ( EFS ) and overall survival ( OS ) rates were 56 and 71 % for patients with localised disease , and 17 and 24 % for patients with metastases at diagnosis . These results did not differ from those achieved in our previous study ( IOR/OS-3 ) in which IFO was used only postoperatively in poor responders PURPOSE It has been observed previously in osteosarcoma ( OS ) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival ( EFS ) . The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS . PATIENTS AND METHODS Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center ( MSKCC ) on the T12 protocol between 1986 and 1993 . Patients were r and omized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy . The more intensive preoperative regimen consisted of two courses of cisplatin ( CDDP ) and doxorubicin ( DOX ) in addition to the usual preoperative regimen of high-dose methotrexate ( HD MTX ) and bleomycin , cyclophosphamide , and dactinomycin ( BCD ) . RESULTS The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response ( 44 % with a grade III or IV histologic response v 37 % in the control arm , 33 % with grade IV histologic response v 13 % in the control arm ) . EFS continued to correlate with histologic response . The actuarial 5-year EFS in patients with localized disease was 78 % for the regimen with more intensive preoperative chemotherapy and 73 % for the control arm . CONCLUSION Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy , no improvement in EFS was observed Objective The objective of this study was to evaluate whether the average apparent diffusion coefficient ( ADC ) or the minimum ADC is more useful for evaluating the chemotherapeutic response of osteosarcoma . Material s and methods Twenty-two patients with osteosarcoma were examined in this study . Diffusion-weighted ( DW ) and magnetic resonance ( MR ) images were performed for all patients before and after chemotherapy . The pre- and post-chemotherapy values were obtained both in the average and minimum ADC . The pre-chemotherapy values of the average ADC and minimum ADC respectively were compared with the post-chemotherapy values . In addition , the ADC ratios ( [ ADCpost - ADCpre ] / ADCpre ) were calculated using the average ADC and the minimum ADC . Twenty-two patients with osteosarcomas were divided into two groups , those with a good response to chemotherapy ( ≥ 90 % tumor necrosis , n = 7 ) and those with a poor response ( < 90 % tumor necrosis , n = 15 ) . The average ADC ratio and the minimum ADC ratio of the two groups were compared . Results With both the average ADC and the minimum ADC , post-chemotherapy values were significantly higher than pre-chemotherapy values ( P < 0.05 ) . The patients with a good response had a significantly higher minimum ADC ratio than those with a poor response ( 1.01 ± 0.22 and 0.55 ± 0.29 respectively , P < 0.05 ) . However , with regard to the average ADC ratio , no significant difference was observed between the two groups ( 0.66 ± 0.18 and 0.46 ± 0.31 respectively , P = 0.19 ) . Conclusion The minimum ADC is useful for evaluating the chemotherapeutic response of osteosarcoma PURPOSE To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas , extending well beyond those of the typical young patient with seemingly localized extremity disease . PATIENTS AND METHODS A total of 1,702 consecutive newly diagnosed patients with high- grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic , tumor-related , and treatment-related variables , response , and survival . The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions . RESULTS Axial tumor site , male sex , and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis . Actuarial 10-year overall and event-free survival rates were 59.8 % and 48.9 % . Among the variables assessable at diagnosis , patient age ( actuarial 10-year survival > or = 40 , 41.6 % ; < 40 , 60.2 % ; P = .012 ) , tumor site ( axial , 29.2 % ; limb , 61.7 % ; P < .0001 ) , and primary metastases ( yes , 26.7 % ; no , 64.4 % ; P < .0001 ) , and for extremity osteosarcomas , also size ( > or = one third , 52.5 % ; < one third , 66.7 % ; P < .0001 ) and location within the limb ( proximal , 49.3 % ; other , 63.9 % ; P < .0001 ) , had significant influence on outcome . Two additional important prognostic factors were treatment related : response to chemotherapy ( poor , 47.2 % ; good , 73.4 % ; P < .0001 ) and the extent of surgery ( incomplete , 14.6 % ; macroscopically complete , 64.8 % ; P < .0001 ) . All factors except age maintained their significance in multivariate testing , with surgical remission and histologic response emerging as the key prognostic factors . CONCLUSION Tumor site and size , primary metastases , response to chemotherapy , and surgical remission are of independent prognostic value in osteosarcoma |
13,054 | 24,660,201 | IL presents similar implant survival rates as EL or CL for partially edentulous patients with extended edentulous sites in the posterior zone , as long as strict inclusion /exclusion criteria are followed .
There is a lack of evidence for IL of multiple implants in the anterior zone of partially edentulous patients .
Preliminary evidence suggests that IL may be equally successful in either the maxilla or m and ible . | PURPOSE The aim of this study was to systematic ally review the evidence for immediate implant loading in partially edentulous patients with extended edentulous sites and evaluate potential treatment modifiers . | PURPOSE To compare the efficacy of immediate functionally loaded implants placed with a flapless procedure ( test group ) versus implants placed after flap elevation and conventional load-free healing ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Forty patients were r and omized : 20 to the flapless immediately loaded group and 20 to the conventional group . To be immediately loaded , implants had to be inserted with a minimum torque > 45 Ncm . Implants in the immediately loaded group were provided with full acrylic resin temporary restorations the same day . Implants in the conventional group were submerged ( anterior region ) or left unsubmerged ( posterior region ) and were left load-free for 3 months ( m and ibles ) or 4 months ( maxillae ) . Provisional restorations were replaced with definitive single metal-ceramic crowns 1 month postloading . Outcome measures were prosthesis and implant failures , biological and prosthetic complications , postoperative edema , pain , and use of analgesics . Independent sample chi2 tests , Mann-Whitney tests , t tests , and paired t tests were used with a significance level of .05 . RESULTS Fifty-two implants were placed in the flapless group and 56 in the conventionally loaded group . In the flapless group , 1 flap had to be raised to control the direction of the bur and 1 implant did not reach the planned primary stability and was treated as belonging to the conventional group . After 3 years no dropouts or failures occurred . There was no statistically significant difference for complications ; however , patients in the conventional group had significantly more postoperative edema and pain and consumed more analgesics than those in the flapless group . Osstell values were significantly higher at baseline in the flapless group ( P = .033 ) . When comparing baseline data with years 1 , 2 , and 3 within each group , mean Osstell values of the flapless group did not increase , whereas there were statistically significant increases in the Periotest values . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately without compromising success rates ; the procedure decreases treatment time and patient discomfort OBJECTIVES The aim of this prospect i ve cohort study was to evaluate the success rate of titanium screw-type implants with the s and blasted and acid-etched ( SLA ) surface loaded early , after 6 weeks of healing . MATERIAL AND METHODS A total of 104 implants were inserted into posterior sites of 51 partially edentulous patients exhibiting bone densities of class I-III . After a healing period of 6 weeks , all implants were functionally loaded with cemented crowns or fixed partial dentures . The patients were recalled at 3 , 12 , 24 , 36 , 48 and 60 months for clinical and radiographic examination . RESULTS One implant failed to integrate during healing , and three implants were lost to follow-up and were considered drop-outs . The remaining 100 implants showed favorable clinical and radiographic findings at the 5-year examination . The peri-implant soft tissues were stable over time ; the mean probing depths and mean attachment levels did not change during the follow-up period . None of the radiographs exhibited signs of continuous peri-implant radiolucency , which confirmed ankylotic stability for all 100 implants . The measurement of the bone crest levels ( DIB values ) indicated stability as well . Based on strict success criteria , all 100 implants were considered successfully integrated , result ing in a 5-year success rate of 99 % . CONCLUSION This prospect i ve study using an early loading protocol with 6 weeks of healing demonstrated that titanium implants with the SLA surface can achieve and maintain successful tissue integration with high predictability for at least 5 years of follow-up in selected patients and sites PURPOSE The aim of this study was to report on the rehabilitation of partial edentulism with immediate function implants placed in predominantly soft bone with flap and flapless surgical techniques . MATERIAL S AND METHODS The prospect i ve clinical study comprises 72 implants ( 50 in the maxilla and 22 in the m and ible ) placed in 41 consecutively included patients rehabilitated from partial edentulism , followed for 1 year . An implant specially design ed for immediate function was used . The evaluation included clinical examinations and radiographic assessment of the marginal bone level at 6 months and 1 year . The outcome measure was the implant success , evaluated using the following implant success criteria : clinical stability ( fixed dental prostheses removed and implants individually checked ) ; fulfilled purported function without any discomfort to the patient ; no suppuration or infection present ; no radiolucent areas around the implants at time of evaluation ; and no aesthetic complaints from the patient . RESULTS No dropouts were registered during the follow-up of the study . The overall cumulative survival rate at 1 year was 98.6 % ( 1 implant lost ) , with 100 % for the implants placed with the flap surgical technique , and 96.9 % for the implants placed with the flapless surgical technique . The overall average marginal bone resorption was 1.6 mm ( SD=1.1 mm ) at 1-year follow-up , with 1.4 mm ( SD=0.8 mm ) and 2.0 mm ( SD = 1.4 mm ) for the flap and flapless surgical technique study groups , respectively . The complications registered were : peri-implant pathology ( 3 implants in 3 patients ) ; fracture of the provisional crown/prosthesis ( 2 patients ) ; crown loosening ( 1 patient ) and prosthetic screw loosening ( 1 patient ) . CONCLUSIONS The placement of the specially design ed implant for immediate function in predominantly soft bone is viable , as given by the overall 98.6 % cumulative survival rate , and the rehabilitation using flapless surgery is safe and predictable . However , the flapless technique revealed more marginal bone resorption compared with the flap technique . Extra care should be taken in the flapless approach with respect to the inclusion criteria and difficulty of the surgery PURPOSE The aim of the present study was to evaluate the concept of an immediate loading protocol in the posterior maxilla and m and ible through analysis of implant survival at 1 year . MATERIAL S AND METHODS One year follow-up data of a multicenter study are reported . Eighty-two ITI s and blasted , acid-etched ( SLA ) implants in 40 patients were loaded between 0 and 11 days after implant placement ( mean 4.3 + /- 2.8 days ) . The restorations consisted of either 2 splinted crowns or a 3-unit fixed prosthesis . All restorations were put into full functional occlusion . Periapical radiographs were evaluated for changes in crestal bone level from baseline to 1 year postloading . Primary stability of the implants was checked initially and before the fitting of the definitive prosthesis . The restorations were evaluated by the practitioners for retention , stability , and esthetics . RESULTS Three patients ' implants were not loaded because of lack of primary stability , and a fourth patient was excluded from the study because of a protocol violation ( more than 4 implants were used ) . All 4 patients were successfully treated outside the protocol . The overall survival rate of the remaining implants at 1 year was 98.8 % . The mean bone loss at 1 year was 0.52 + /- 0.98 mm , which is within the reported limits of less than 1 mm ( range 0.4 to 1.4 mm ) loss in the first year . DISCUSSION AND CONCLUSION The early results from this study indicate that early and immediate loading of 2 implants in the posterior maxilla and m and ible may be suitable in selected patients . On the basis of 1 year of observation , the results appear similar to those achieved with a delayed procedure OBJECTIVE The aim of this prospect i ve study was to evaluate the outcome of immediately provisionally restored implants in the posterior m and ible after a minimum of 60 months in function . MATERIAL AND METHODS Twenty-four patients were treated with 40 screw-type implants replacing m and ibular molars and premolars . Implants were provisionalized immediately after placement . Radiographic coronal bone levels , implant survival and success were evaluated 12 , 24 , 36 , 48 and 60 months after the final restoration . RESULTS Measurements of the mean marginal bone levels around immediately loaded implants after 12 months showed a significant bone loss ( P<0.001 ) within the first year after the final restoration . Measurements of coronal bone levels after 24 , 36 , 48 and 60 months , respectively , showed no further significant increase of bone resorption . Two implants were lost within the first year after the final restoration , result ing in an overall survival rate of 95 % ; a total of three implants were recorded as failures ( two implant losses and one excessive bone resorption above 50 % ) , result ing in an overall success rate of 92.5 after an implant observation period of up to 8 years . CONCLUSION The present data revealed results comparable to conventionally loaded implants . Careful patient selection in combination with high primary stability seem to be key factors for immediately loaded implants . Larger long-term r and omized clinical trials are needed to confirm the final evidence of this protocol as the st and ard treatment concept for the partially edentulous m and ible PURPOSE To compare peri-implant bone and soft-tissue levels of immediately non-occlusally loaded versus non-submerged early loaded implants in partially edentulous patients 5 years after implant placement . MATERIAL S AND METHODS Fifty-two patients were r and omised in five Italian private practice s : 25 in the immediately loaded group and 27 in the early loaded group . To be immediately loaded , single implants had to be inserted with a torque of > 30 Ncm , and splinted implants with a torque of > 20 Ncm . Immediately loaded implants were provided with non-occluding temporary restorations within 48 hours . After 2 months , the provisional restorations were put in full occlusion . Implants were early loaded after 2 months . Final restorations were provided 8 months after implant placement . Outcome measures were prosthesis and implant failures as well as biological and prosthetic complications recorded by non-blinded assessors . Blinded assessors evaluated peri-implant bone and soft-tissue levels . RESULTS Fifty-two implants were immediately loaded and 52 early loaded . One patient of the early loaded group dropped out after the 1-year recall . One single immediately loaded implant failed 2 months after placement . Only one complication ( iatrogenic peri-implantitis ) occurred in one patient of the early loading group . Both groups gradually lost peri-implant bone in a highly statistically significant way at 2 , 8 and 14 months and at 4 and 5 years . After 5 years , patients of both groups had lost an average of 1.2 mm of peri-implant marginal bone . There were no statistically significant differences in peri-implant bone and soft-tissue level changes between the 2 groups . At 5 years , there was a statistically significant recession ( 0.2 mm ) of the vestibular soft tissues from baseline ( delivery of the final restorations 8 months after implant placement ) only for immediately loaded implants . CONCLUSIONS In well maintained patients , complications are uncommon and healthy and stable periimplant tissues can be maintained for 5 years around immediately and early loaded implants PURPOSE To evaluate the predictability of early and immediate loading protocol s of implants in the posterior m and ible and to investigate whether there is a difference in success rates , survival rates , and peri-implant parameters , including marginal bone level changes , between loading protocol s. MATERIAL S AND METHODS A comprehensive systematic review of the literature was conducted . The selection of publications reporting on human clinical studies was based on predetermined inclusion criteria and was agreed upon by two review ers . RESULTS A total of 19 papers were selected : 8 on early loading , 9 addressing immediate loading , and 2 comparing immediate and early loading . Of the 19 studies , 5 were r and omized clinical trials and 14 were prospect i ve studies . CONCLUSIONS Existing literature supports the early loading of microroughened dental implants in the partially edentulous posterior m and ible at 6 to 8 weeks in the absence of modifying factors . Therefore , loading within this time frame can be considered routine for the majority of clinical situations in the posterior m and ible , either with single crowns or fixed dental prostheses . Immediate loading of microroughened dental implants in the partially edentulous posterior m and ible proved to be a viable treatment alternative . Caution is necessary when interpreting published outcomes for immediate loading , as the inclusion exclusion criteria are inconsistent and many subjective confounding factors are evident . Additional studies with longer follow-ups , specifically r and omized clinical trials , are needed to consoli date the data for immediate loading . Priority should be given to trials testing immediate loading PURPOSE To evaluate early and immediate loading of implants in the posterior maxilla and to investigate whether there is a difference in success rates , survival rates , and peri-implant parameters , including marginal bone level changes . MATERIAL S AND METHODS A comprehensive systematic review of the literature was conducted . The selection of publications reporting on human clinical studies was based on predetermined inclusion criteria and was agreed upon by two review ers . RESULTS Twelve papers were identified on early loading ( two r and omized controlled clinical trials [ RCTs ] and 10 prospect i ve case series studies ) . Six papers were found on immediate loading ( one RCT , four prospect i ve case series , and one retrospective study ) . CONCLUSIONS Under certain circumstances it is possible to successfully load dental implants in the posterior maxilla early or immediately after their placement in selected patients . The success rate appears to be technique sensitive , although no study has directly assessed this . A high degree of primary implant stability ( high value of insertion torque ) and implant surface characteristics play an important role . It is not possible to draw evidence -based conclusions concerning contraindications , threshold values for implant stability , bone quality and quantity needed , or impact of occlusal loading forces . As for the impact of the surgical technique on implant outcome in different bone densities , no studies prove significant superior results with one technique over another . Well- design ed RCTs with a large number of patients are necessary to make early/immediate loading protocol s in posterior maxilla evidence based , but ethical and practical considerations may limit the real possibility of such studies in the near future OBJECTIVE The aim of this study was to compare the survival rate , the bone loss and soft-tissue healing patterns of immediately loaded and immediately restored implants in cases of partial posterior m and ibular edentulism . MATERIAL AND METHODS Fifty patients with partial posterior m and ibular edentulism were r and omly selected for two treatments : 25 were included in the immediate loading group ( test ) and 25 in the immediate restoration group ( control ) . All implants were placed in healed sites with a torque of > 25 N cm . The temporary prosthesis of the immediate restoration group was placed so as to avoid occlusal contact in centric and lateral excursions . Both groups received fully occluding final restorations 6 months after surgery . Mean marginal bone loss was assessed at 6- , 12- , 24- and 36-month follow-up examinations by a blinded examiner . RESULTS A total of 100 implants were placed in the period between February 2004 and October 2006 , of which 42 ( 42 % ) were for men and 58 ( 58 % ) for women . Five and 7 weeks after surgery , mobility of one implant was assessed in one ( 4 % ) patient in the test group and one ( 4 % ) patient in the control group , respectively . At the 36-month follow-up , the accumulated mean marginal bone loss was 0.987 mm ( SD=0.375 ) for the immediate restoration group ( n=48 ) and 0.947 mm ( SD=0.323 ) for the immediate loading group ( n=48 ) . There was no statistically significant difference ( P>0.05 ) for the tested outcome measures between the two procedures . CONCLUSIONS This study was unable to detect any statistically significant difference in the survival rate , bone loss and soft tissue healing patterns between the immediately loaded and the immediately restored implants in cases of partial posterior m and ibular edentulism . The immediate temporary rehabilitation of the partially edentulous posterior m and ible is a predictable procedure using both procedures BACKGROUND Many longitudinal studies of different implant systems have been published but few controlled r and omized investigations have been reported . A 1-year report of a comparative study of ITI Dental Implant System implants ( Straumann AG , Waldenburg , Switzerl and ) and Brånemark System implants ( Nobel Biocare AB , Gothenburg , Sweden ) has been published by the present authors . This paper is a 3-year follow-up of that r and omized study . PURPOSE The aim of the study was to compare the outcome of fixed partial prostheses supported by ITI or Brånemark implants . The outcome was evaluated primarily in terms of survival rates and changes in marginal bone level . MATERIAL AND METHODS The study group comprised 28 patients with anterior residual dentition in the maxilla . The patients were provided with two to four implants on each side of the dentition and were r and omly allocated to Brånemark implants or ITI implants ; 77 ITI implants and 73 Brånemark implants were inserted . After 6 months abutment connections were made to both ITI and Brånemark implants . All patients were provided with fixed partial prostheses of gold-ceramic . The patients were followed up annually with clinical and radiographic examinations for 3 years RESULTS Two Brånemark implants and two ITI implants were lost . The Brånemark implants were lost before loading whereas the ITI implants were lost because of periimplantitis . The survival rate for both groups was 97.3 % . The mean marginal bone level of the Brånemark implants was situated 1.8 mm from the reference point at both the baseline and the 3-year examinations . The corresponding values for the ITI implants were 1.4 mm at baseline and 1.3 mm after 3 years . There was no significant difference between the implant systems with regard to bone level or bone level change . A steady state of the marginal bone level was calculated to have been reached after 3 years for 95.5 % of the Brånemark implants and 87.1 % of the ITI implants . Periimplantitis ( infection including pus and bone loss ) was observed with seven ITI implants but with none of the Brånemark implants . This difference was statistically significant . CONCLUSIONS No statistically significant differences were found between the implants studied , except for the frequency of periimplantitis , which was higher for the ITI implants . The survival rates were high , and the marginal bone loss was small for both systems A total of 114 ITI solid-screw implants was consecutively placed in 55 partially edentulous patients and restored with 68 fixed prostheses . The patients were followed for at least 5 years in a prospect i ve study that focused on implant success and longitudinal reactions of the peri-implant hard and soft tissues . During the study period , 5 implants failed and 15 implants were lost to follow-up , result ing in a cumulative survival rate of 95.3 % after 5 years of loading . The success analysis included additional strictly defined events ( " first occurrence of marginal bone loss > or = 4 mm , " " first occurrence of pocket depth > or = 4 mm , " and " first occurrence of crevicular fluid volume > or = 2.5 mm " ) and result ed in a cumulative 5-year success rate of 89.0 % . Median loss of marginal bone , as observed on radiographs , was 0.7 mm between implant placement and prosthetic treatment and 0.5 mm between prosthesis placement and the 5-year evaluation . Compared to the previous year 's value , the annual increase in marginal bone loss did not reach a level of statistical significance between 1 and 5 years of function , so that a steady state prevailed . The incidence of lingual-palatal surfaces affected with remarkable plaque deposits increased from 13 % after prosthesis placement to 23 % after 5 years . Sulcus Bleeding index , probing depth , attachment level , and crevicular fluid volume were used to describe the health of the peri-implant soft tissues . The research parameters remained almost unchanged and indicated a soft tissue response within physiologic levels . Most mechanical complications were experienced during the first year of loading and were related to loosening of occlusal screws , which occurred in 8 ( 12 % ) of 68 restorations OBJECTIVE Immediate and early loading of implants can simplify treatment and increase patient satisfaction . This 3-year r and omized-controlled trial will therefore evaluate survival rates and bone-level changes with immediately and early loaded Straumann implants with the SLActive surface . MATERIAL AND METHODS Partially edentulous patients > or=18 years of age were enrolled . Patients received a temporary restoration ( single crown or two to four unit fixed partial denture ) out of occlusal contact either immediately ( immediate loading ) or 28 - 34 days later ( early loading group ) , with permanent restorations placed 20 - 23 weeks after surgery . The primary endpoint was change in crestal bone level from baseline ( implant placement ) to 12 months ; the secondary variables were implant survival and success rates . RESULTS A total of 383 implants ( 197 immediate and 186 early ) were placed in 266 patients ; 41.8 % were placed in type III and IV bone . The mean patient age was 46.3+/-12.8 years . Four implants failed in the immediate loading group and six in the early loading group , giving implant survival rates of 98 % and 97 % , respectively ( P = NS ) . There were no implant failures in type IV bone . The overall mean bone level change from baseline to 12 months was 0.77+/-0.93 mm ( 0.90+/-0.90 and 0.63+/-0.95 mm in the immediate and early groups , respectively ; P<0.001 ) . However , a significant difference in implantation depth between the two groups ( P<0.0001 ) was found . After adjusting for this slight difference in initial surgical placement depth , time to loading no longer had a significant influence on bone-level change . Significant influence was found for : center ( P<0.0001 ) , implant length ( P<0.05 ) and implant position ( P<0.0001 ) . Bone gain was observed in approximately 16 % of implants . CONCLUSIONS The results demonstrated that Straumann implants with the SLActive surface are safe and predictable when used in immediate and early loading procedures . Even in poor- quality bone , survival rates were comparable with those from conventional or delayed loading . The mean bone-level change was not deemed to be clinical ly significant and compared well with the typical bone resorption observed in conventional implant loading PURPOSE A single-blind r and omized controlled split-mouth trial was performed to compare the 36-month outcomes of machined and titanium oxide-anodized ( ADZ ) dental implant surfaces immediately loaded with fixed partial dentures in the posterior m and ible . MATERIAL S AND METHODS Ten patients with bilateral partial edentulism in the posterior m and ible received 42 implants ; 20 were placed on the test side ( ADZ ) and 22 were placed on the control ( machined ) side . The implants were loaded within 24 hours after placement . Changes in the radiographic bone level ( RBL ) were measured on st and ardized periapical films at baseline , 12 months , and 36 months . The mean changes in RBL were compared using a paired t test , and the mean changes in RBL with regard to implant position and implant surface type were compared via two-way analysis of variance . RESULTS After 36 months of functional loading , the overall cumulative success rate for all implants was 95 % . The mean change in RBL at 36 months was 0.35 mm and 0.32 mm for ADZ and machined implants , respectively ( not statistically significantly different between groups ; P = .88 ) . A reduction in RBL was observed for both machined and ADZ implants between 12 and 36 months , but only the machined implants demonstrated a statistically significant decrease in RBL during the observation period . CONCLUSIONS No statistically significant differences in RBL change were found between machined and ADZ implant surfaces after 36 months in function , and both surfaces demonstrated minimal marginal bone remodeling . As such , immediate loading of ADZ and machined dental implants supporting fixed partial dentures may be a suitable long-term treatment option in the posterior m and ible PURPOSE The present study was undertaken to determine the feasibility of using primary stability as a predictor of implant success in patients whose implants were immediately loaded . MATERIAL S AND METHODS The study included 40 patients , in whom a total of 190 implants were placed , 102 in maxillary sites and 88 in m and ibular sites . All were loaded within 72 hours of placement . Sixteen patients were completely edentulous in the m and ible and /or the maxilla . The remaining 24 , who were partially edentulous , received fixed partial dentures or single-implant restorations . All of the definitive implant restorations were screw retained . The criterion for loading was clinical judgment of primary stability , verified by a " screw test . " Impressions were made after implant placement to facilitate the fabrication of a laboratory-made heat-processed provisional restoration from acrylic resin . Following a 4-month period for osseointegration and soft tissue healing , definitive fixed prostheses were fabricated . RESULTS There were no surgical complications . After 1 to 2 years , all 190 implants had survived and were considered 100 % successful , as determined by independent testing of mobility and radiographic evidence of osseointegration . In 4 patients , fracture of the provisional restoration occurred during the healing period . DISCUSSION Clinical research has shown that immediate loading is a viable treatment modality . The favorable success rate reported in this study for rough-surfaced implants suggests that adherence to a protocol , an important parameter of which is primary stability above 32 Ncm , can lead to osseointegration . CONCLUSION The results of this limited investigation suggest that patients who are partially or completely edentulous may be immediately restored with implants and fixed provisional restorations , provided that the dental implants are adequately stable immediately after their surgical placement . This alternative therapeutic approach did not appear to affect the up-to-2-year survival of the implants in this patient population BACKGROUND The aim of this study was to evaluate the survival of dental implants in periodontally susceptible patients using immediate loading/restoration ( ILR ) protocol s and the factors that modulate this response . METHODS Systemically healthy patients who were treated previously for chronic periodontitis and who required implant therapy were recruited . Following data collection , " surgical templates " and provisional fixed restorations were fabricated . Transgingival implants were inserted , and surgical measurements were performed . After abutment connection , the crown/bridge was relined and cemented . Patients were monitored for 12 months , at which time final measurements were performed . RESULTS Twenty patients ( 49 implants ) completed this study ; five implants failed and were removed ( 90 % survival rate ) . All implants were removed during the first 6 months . At 12 months , the mean implants ' probing depth was 2.87 + /- 0.9 mm . The mean electronic mobility testing device value ( -1.3 + /- 0.7 ) was slightly higher than at baseline ( -3.53 + /- 10.7 ) . Radiographic bone loss ranged between -1.24 and 2.77 mm ( mean + /- SD : 0.91 + /- 0.2 mm ) . All of the implants ( 16 ) that were inserted in the premolar region were successful , whereas three of nine implants in the molar region and two of 24 implants in the canine/incisor region failed ( P = 0.0278 ) . Survival in the immediately loaded group ( 83 % ) was slightly lower than in the immediately restored group ( 96 % ) ; however , these differences did not reach statistical significance . None of the other variables ( smoking , arch , stability , implant length and diameter , and bone width ) affected the outcome of this procedure . CONCLUSIONS ILR protocol s are predictable alternatives in periodontally susceptible patients . Results in the molar regions suggested that careful consideration should be given to implants placed in these sites . Long-term success in these patients has not been addressed PURPOSE To compare the efficacy of immediate nonocclusal loading ( test group ) versus early loading ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Fifty-two patients in 5 Italian private practice s were r and omized to 1 of the treatments : 25 to the immediately loaded group and 27 to the early loaded group . To be immediately loaded , single implants had to be inserted with a torque of > 30 Ncm , and splinted implants had to be inserted with a torque of > 20 Ncm . Implants in the immediately loaded group were provided with full acrylic resin nonoccluding temporary restorations within 48 hours after placement . After 2 months , full occluding provisional restorations were provided . Implants in the early loading group were not submerged and were loaded after 2 months . At 8 months , provisional restorations were replaced with definitive metal-ceramic prostheses . Outcome measures were prosthesis and implant failures as well as biologic and prosthetic complications recorded by nonblinded assessors . The Fisher exact test was used to compare the proportion of implant failures . RESULTS Fifty-two implants were placed in the immediately loaded group and 52 in the early loaded group . No dropouts or complications occurred up to 14 months postinsertion . One single implant failed in the immediately loaded group 2 months after placement . There was no statistically difference for the tested outcome measures between the 2 procedures ( P > .99 ) . CONCLUSIONS The results of this r and omized controlled clinical trial with 25 patients rehabilitated with immediately restored nonocclusally loaded implant-supported prostheses compared to 27 patients restored 2 months following placement suggest that there are no major clinical differences in implant survival between these 2 protocol s. No biologic or prosthetic complications occurred PURPOSE The aim of the present clinical trial was to evaluate the 12-month success rate of titanium dental implants placed in the posterior m and ible and immediately loaded with 3-unit fixed partial dentures . MATERIAL S AND METHODS Patients with missing m and ibular premolars and molars were enrolled in this study . To be included in the study , the implants had to show good primary stability . Implant stability was measured with resonance frequency analysis using the Osstell device ( Integration Diagnostics ) . Implants were included in the study when the stability quotient ( ISQ ) exceeded 62 . Clinical measurements , such as width of keratinized tissue , ISQ , and radiographic assessment of peri-implant bone crest levels , were performed at baseline and at the 12-month follow-up . The comparison between the baseline and the 12-month visits was performed with the Student t test for paired data ( statistically significant at a level of alpha = 0.05 ) . RESULTS Forty implants with a s and blasted , large grit , acid-etched ( SLA ) surface ( Straumann ) were placed in 20 patients . At 12 months , only 1 implant had been lost because of an acute infection . The remaining 39 implants were successful , result ing in a 1-year success rate of 97.5 % . Neither peri-implant bone levels , measured radiographically , nor implant stability changed significantly from baseline to the 12-month follow-up ( P > .05 ) . DISCUSSION The immediate functional loading of implants placed in this case series study result ed in a satisfactory success rate . CONCLUSION The findings from this clinical study showed that the placement of SLA transmucosal implants in the m and ibular area and their immediate loading with 3-unit fixed partial dentures may be a safe and successful procedure PURPOSE The aim of this study was to evaluate the success rate of ITI implants with the SLA surface that were loaded after 6 weeks of healing . MATERIAL S AND METHODS In this prospect i ve cohort study , a total of 104 implants were placed in posterior sites of 51 partially edentulous patients exhibiting bone densities of Class 1 , 2 , or 3 . After a healing period of 6 weeks , all implants were functionally loaded with cemented crowns or fixed partial dentures . The patients were recalled at 3 , 12 , 24 , and 36 months for clinical and radiographic examination . RESULTS One implant failed to integrate during healing , and 1 implant was lost to follow-up and considered a dropout . The remaining 102 implants showed favorable clinical and radiographic findings and were considered successfully integrated at the 3-year examination . This result ed in a 3-year success rate of 99.03 % . DISCUSSION The peri-implant soft tissues were stable over time , as evidence d by no changes in the mean probing depths and the mean attachment levels during the follow-up period . None of the radiographs exhibited signs of continuous peri-implant radiolucency , which confirmed ankylotic stability of all 102 implants . The radiographic evaluation of the bone level at the implant indicated stability of the bone crest levels . CONCLUSION The results of this prospect i ve study demonstrated that early loading of ITI implants with the SLA surface after an unloaded healing period of 6 weeks provided successful tissue integration with high predictability , and that successful tissue integration was well maintained up to 3 years of follow-up in this study population CONFLICT OF INTEREST All material s used in this study were purchased by the author and it is therefore free of any commercial or institutional interest . PURPOSE To evaluate the success rate 1 year after loading of early loaded implants placed in vertically augmented bone using deproteinised bovine bone ( Bio-Oss ) and a titanium-reinforced membrane ( Gore-Tex ) . MATERIAL S AND METHODS Twenty patients provided 25 sites that were treated with vertical guided tissue regeneration ( GBR ) using Bio-Oss and exp and ed polytetrafluoroethylene titanium-reinforced membranes . After 1 year of healing , the membranes were removed and 64 implants were placed ( baseline ) and loaded 30 days later . St and ardised periapical radiographs were obtained at baseline and 1 year thereafter . One independent assessor clinical ly evaluated the amount of tissue regenerated and peri-implant bone level based on the radiographs . Outcome measures were prosthesis success , implant success , complications , amount of vertically regenerated bone , peri-implant marginal bone levels and histology . RESULTS No patient dropped out . A total of 23 out of 25 sites healed uneventfully . Two sites showed early membrane exposure . In these sites , the surgery was repeated with success 2 months later . Clinical evaluation showed a mean vertical bone defect of 5.6 mm ( SD 1.7 ) . Mean vertical bone gain after GBR was 5.2 mm ( SD 1.5 ) . The histology of five sample s retrieved from four patients showed a total percentage of xenograft and new bone of 52.6 % , with dispersed graft particles surrounded by layers of bone . All implants were stable after 1 year of function , yielding a survival rate of 100 % . Statistically significant peri-implant bone loss ( 0.95 mm ; SD 0.21 ; 95 % confidence interval 0.85 to 1.05 ; P < 0.001 ) was observed radiographically from baseline to the 1-year follow-up . CONCLUSIONS This prospect i ve cohort study shows that by using deproteinised bovine bone and a non-resorbable titanium-reinforced membrane , vertical bone gain can be obtained and implants can be loaded after 30 days . The vertical regenerated tissue exhibited good stability over 1 year of implant function OBJECTIVE To evaluate bone-level alterations that occurred at implants of the Astra Tech(R ) System that were placed in the load carrying , posterior parts of the dentition using either a submerged ( two-stage ) or a non-submerged ( one-stage ) installation protocol . MATERIAL AND METHODS Eighty-four patients that required 115 fixed partial dentures ( FPDs or cases ) entered the prospect i ve study . All subjects were assigned one patient and > or = one case numbers . For the r and omization of cases , a custom-made program based on balanced r and om permuted blocks was utilized . The cases were assigned to two treatment groups , namely one-stage installation procedure , non-submerged technique ( group A ) and two-stage installation procedure , submerged technique ( group B ) . Several subjects contributed with cases to both groups A and B. Periodontal , endodontal and open caries lesions were treated prior to implant installation . All patients received careful oral hygiene instruction and training in self-performed plaque control measures . The surgical technique used for fixture installation followed the outline described in the manual for the Astra Tech System . The FPDs were placed 3 months ( m and ible ) and 6 months ( maxilla ) following implant installation . Immediately following FPD placement , a baseline examination was performed that included assessment of plaque , soft-tissue inflammation and bone level . Clinicians who were otherwise not involved in the study performed the radiographic measurements . Clinical and radiographical examinations were repeated once a year after the baseline examination . DATA ANALYSIS The primary outcome variable was the change in the bone level at the implants from the time of placement of the bridge ( FPD ) to the 1- and 2-year reexaminations . Fisher 's permutation test was used to test if differences existed between groups A and B , and between patients ( men/women , smokers/non-smokers , age ) , sites ( maxilla/m and ible ) and implants ( length , diameter ) . Pitman 's test was used to study correlations between bone shape and quality data and different radiographic bone-level data . RESULTS It was demonstrated that tissue healing following implant installation appeared to be independent of the surgical protocol , i.e. whether the marginal portions of the implants during surgery were fully or only partly submerged under the ridge mucosa . Thus , ( i ) in both treatment groups the number of implants that failed to osseointegrate ( early failures ) was small ( < 2 % ) ; ( ii ) at the end of the recommended periods of bone healing prior to loading , - in both groups , maxilla=6 months and m and ible=3 months - the level of the marginal bone was close to the coronal rim of the fixture ; group A : 1.54+/-0.92 mm , group B : 1.31+/-0.77 mm . The current study also demonstrated that irrespective of surgical protocol ( two-stage , one-stage ) , implants supporting the FPDs exhibited only small amount of radiographic bone loss during the first year of function ( group A : 0.02+/-038 mm , group B : 0.17+/-0.64 mm ) . Moreover , during the second year of function , the amount of additional bone loss that occurred in the two treatment groups was close to zero . CONCLUSION Periimplant bone-level change during function seemed to be unrelated to whether initial soft- and hard-tissue healing following implant installation had occurred under submerged or non-submerged conditions BACKGROUND Immediate or early loading of implants placed in maxillas and posterior m and ibles has been a concern as bone density is often low in these areas , making it difficult to establish good initial implant stability . By adapting implant design and insertion protocol s , however , high initial implant stability may be achieved in these regions . Further , a modified implant surface texture has been proved to help in maintaining stability during the initial healing period . PURPOSE The aim of the present study was to investigate the clinical performance of oxidized titanium implants ( TiUnite , Nobel Biocare AB , Gothenburg , Sweden ) when used for early function in the maxilla and in the posterior m and ible , locations where the bone density often is low . A further aim was to evaluate the marginal bone level at oxidized implants and compare it with that of machined-surface implants used in a previous study . MATERIAL S AND METHODS Thirty-one patients were consecutively included in the study , and 37 edentulous areas in maxillas and posterior m and ibles were treated . Bruxism and uncontrolled periodontal disease were exclusion criteria . Temporary prostheses were generally placed within 9 days but not after 16 days from implant placement . A previous study applying the same study design and clinical protocol but using machined-surface implants was used for comparisons . RESULTS Of the 111 implants installed , 1 failed , giving an overall survival rate of 99.1 % after 18 months . The prosthesis survival was 100 % . The marginal bone resorption was 0.8 mm ( st and ard deviation [ SD ] , 1.0 ) , as opposed to 1.6 mm ( SD , 1.3 ) in the previous study with machined-surface implants , but was not statistically significantly different ( p = .10 ) . CONCLUSION The present clinical protocol ( aim ing at high primary stability ) and the use of oxidized titanium implants for early functional loading in the maxilla and the posterior m and ible result ed in a high implant survival rate and a favorable marginal bone level during a follow-up of 18 months . The difference in marginal bone resorption between the oxidized implants in the present study and the machined implants from a previous investigation with the same study design was not statistically significant BACKGROUND The advantages of placing implants in fresh extraction sockets and putting them in immediate/early function are many . A predicable protocol opens the possibility of performing a single surgical procedure , giving the patient a temporary prosthesis immediately , and minimizing the shrinkage of hard tissue and soft tissue recession . PURPOSE The aim of the present study was to develop a strict protocol for and to evaluate the feasibility of immediate/ early function on implants placed in fresh extraction sockets located in maxillae and posterior m and ibles , including defects around the implants treated according to a regenerative procedure . MATERIAL S AND METHODS Nineteen patients were treated after tooth extraction according to an immediate function protocol and were observed for 18 months . Fifty Mk IV TiUnite ( Nobel Biocare AB , Göteborg , Sweden ) implants were installed in partially edentulous areas in maxillae ( n = 17 ) and posterior m and ibles ( n = 5 ) . Implants were installed directly into the alveoli , and the temporary prostheses were connected immediately after surgery ( n = 11 ) or within 7 days , that is , an " early function " procedure ( n = 11 ) . Thirteen implants did not require any type of regenerative procedure , whereas the remaining 37 implants had filling with autogenous bone , 4 of which also had a resorbable membrane . St and ardized intraoral radiographs were taken for evaluation of marginal bone level , and 38 of the implants were systematic ally checked by resonance frequency analysis . RESULTS All patients were followed for 18 months , and none of the 50 implants failed . However , one implant showed signs of failure after 6 weeks , but once the occlusal load was removed , the implant regained its stability completely , no longer demonstrated symptoms , and could be used successfully for prosthetic rehabilitation . The mean value of the implant stability quotient was 60 at baseline ( range 45 - 75 ) and 63 after 6 months ( range 46 - 75 ) . The marginal bone resorption was 0.9 mm ( SD 1.1 mm ; n = 48 ) 18 months after implant insertion ( 1 year after final prosthesis ) . CONCLUSION The immediate placement of implants into fresh extraction sockets combined with immediate/early function procedures seems to be a safe and reliable procedure when using a strict protocol PURPOSE The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients . MATERIAL S AND METHODS Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants ( Centerpulse Dental , Carlsbad , CA ) . Test implants were placed into immediate full occlusal loading , and control implants were restored using a conventional delayed loading procedure . Otherwise , both groups of patients received similar therapy from the same treatment team . Radiographs , periodontal indices , and Periotest values were recorded every 6 months during routine clinical follow-up appointments . The mean loading time for all prostheses was 24 months at the time of this report . RESULTS No implants failed in the test group , and 1 implant failed before loading in the control group . Cumulative implant success was 98.9 % for all implants placed ( test group = 100 % ; control group = 92.9 % ) . Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol . DISCUSSION Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results , with no adverse periodontal effects after 24 months of function . Additional follow-up will provide invaluable information on the long-term effects of this technique . CONCLUSION Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene The aim of this investigation was to evaluate the clinical success of immediately loaded implants versus implants loaded in a delayed fashion in the posterior m and ible . Three implants were placed distal to the canines bilaterally in the edentulous distal m and ibular ridges of 12 patients . One side was r and omly selected for placement of three implants ( delayed loading ; control sites ) with a progressive thread design for submerged healing , and after 3 months the implants were exposed and loaded with provisional splinted crowns , which were replaced 6 weeks later by the definitive restorations . Three additional implants ( immediately loaded ; test sites ) , of the same size were placed in the contralateral side of the m and ible . The test implants had abutments placed and were loaded immediately using the same protocol as the control implants . After a mean loading period of 25.3 months , the patients showed normal mean clinical values without significant differences ( P < 0.05 ) for test and control implants , respectively , as follows : Plaque Index : 0.4 versus 0.8 ; Sulcus Bleeding Index : 0.5 versus 0.3 ; probing pocket depth : 1.9 mm versus 2.1 mm ; width of keratinized mucosa : 2.5 mm versus 3.3 mm ; Periotest value : -3.7 versus -3.2 . Twenty-nine of the examined sites showed no bone loss . After 2 years of loading in the posterior m and ible , test and control implants had the same prognosis BACKGROUND An increasing number of studies show that immediate/early function of dental implants can be as successful as two-stage procedures . However , the results may not be universal for all implant types and it is important that new implants are tested for this treatment modality . PURPOSE The aim was to evaluate an immediate/early function protocol in the maxilla and in the posterior m and ible using Neoss implants ( Neoss Ltd. , Harrogate , UK ) . MATERIAL S AND METHODS A total of 21 patients were provided with 69 Neoss implants ( 4 mm in diameter and 9 - 15 mm in length ) and a provisional bridge within 7 days ( mean 4.6 days ) . Sixteen implants were placed in immediate extraction sites where seven were treated with autologous bone grafts ( n = 6 ) or bone grafts + resorbable membrane ( n = 1 ) . A final fixed prosthesis was made 3 to 6 months later . The patients were followed-up with clinical examinations for 18 months . In addition , the implants were monitored with resonance frequency analysis ( RFA ) measurements at surgery and after 1 , 2 , and 6 months . Intraoral radiographs were taken after surgery and after 1 , 6 , and 18 months . RESULTS One implant in an extraction site in the maxilla failed after 1 month , giving a survival rate of 98.5 % after 18 months . The mean marginal bone loss was 0.7 mm ( SD 0.7 ) after 18 months . RFA showed a mean implant stability quotient ( ISQ ) value of 68.1 ( SD 8.8 ) at surgery , which increased to 73.7 ( SD 5.7 ) after 6 months . The primary stability for maxillary and m and ibular implants was similar , although m and ibular implants showed slightly higher values with time . Implants in extraction sockets showed a lower initial stability than in healed sites , ISQ 65.8 ( SD 7.5 ) , which increased to ISQ 67.5 ( SD 6.9 ) after 6 months . The failed implant showed an ISQ of 74 at placement , which decreased to 42 1 month after surgery . CONCLUSION Within the limitations of the present study , it is concluded that immediate/early function with Neoss implants is a reliable method with an implant survival rate comparable to that of the traditional two-stage protocol |
13,055 | 24,057,808 | Most of the selected studies showed the effectiveness of HMB in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases . | Beta-hydroxy-beta-methylbutyrate ( HMB ) , a metabolite of the branched-chain amino acid leucine , is extensively used by athletes and bodybuilders in order to increase strength , muscle mass and exercise performance .
We performed a systematic review of the clinical literature on the effectiveness of HMB supplementation in healthy and pathological conditions ( i.e. training programs , aging , acute and chronic diseases , and after bariatric surgery ) . | Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy . In this study , the anticatabolic agent beta-hydroxy-beta-methylbutyrate ( HMB ) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aim ing to determine if tumor burden could be reduced . Male Wistar rats were r and omly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented ( 76 mg/kg body weight ) . Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo , totally prevented glycemia reduction , as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats . Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100 % . In contrast , nuclear factor-kappaB p65 subunit content was suppressed by 17 % with HMB supplementation . In conclusion , HMB supplementation , at a similar dose used in humans to increase muscle mass , caused antitumor and anticachectic effects , with tumor-cell nuclear factor-kappaB pathway participation , which might be a potential nutritional strategy in cancer therapy Studies in young adults have demonstrated that beta-hydroxy-beta-methylbutyrate ( HMB ) can increase gains in strength and fat-free mass during a progressive resistance-training program . The purpose of this study was to determine whether HMB would similarly benefit 70-y-old adults undergoing a 5 d/wk exercise program . Thirty-one men ( n = 15 ) and women ( n = 16 ) ( 70 + /- 1 y ) were r and omly assigned in a double-blind study to receive either capsules containing a placebo or Ca-HMB ( 3 g/d ) for the 8-wk study . Skin fold estimations of body composition as well as computerized tomography ( CT ) and dual X-ray absorptiometry ( DXA ) scans were measured before the study and immediately after the 8-wk training program . HMB supplementation tended to increase fat-free mass gain ( HMB , 0.8 + /- 0.4 kg ; placebo , -0.2 + /- 0.3 kg ; treatment x time , P = 0.08 ) . Furthermore , HMB supplementation increased the percentage of body fat loss ( skin fold : HMB , -0.66 + /- 0.23 % ; placebo , -0.03 + /- 0.21 % ; P = 0.05 ) compared with the placebo group . CT scans also indicated a greater decrease in the percentage of body fat with HMB supplementation ( P < 0.05 ) . In conclusion , changes in body composition can be accomplished in 70-y-old adults participating in a strength training program , as previously demonstrated in young adults , when HMB is supplemented daily BACKGROUND & AIMS Rheumatoid arthritis ( RA ) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting ( cachexia ) . The aim of this r and omised controlled trial was to investigate the efficacy of a mixture of beta-hydroxy-beta-methylbutyrate , glutamine and arginine ( HMB/GLN/ARG ) as nutritional treatment for rheumatoid cachexia . METHODS Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen ( 7.19 g/day ) and calorie ( 180 kcal/day ) balanced mixture of alanine , glutamic acid , glycine , and serine ( placebo ) for 12 weeks . Body composition and other outcomes were assessed at baseline and follow-up , and analysed by mixed ANOVA . RESULTS Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia ( groupxtime interactions P>0.05 for all outcomes ) . Both amino acid mixtures significantly increased ( main effect of time ) fat-free mass ( 727+/-1186 g , P<0.01 ) , total body protein ( 719+/-1703 g , P=0.02 ) , arms ( 112+/-183 g , P<0.01 ) and legs ( 283+/-534 g , P<0.01 ) lean mass , and some measures of physical function . No significant adverse event occurred during the study , but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo . CONCLUSIONS Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo . Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population This study assesses the effects of daily beta-hydroxy beta-methylbutyrate ( HMB ) supplementation on muscular strength ( bench press , squats , and power cleans ) and body composition ( body weight and body fat ) among collegiate football players undergoing a strenuous exercise program . Subjects were collegiate football players ( n = 35 ) training under the supervision of certified strength coaches averaging 20 hours of weekly exercise . In the first supplementation period , 16 of the 35 subjects were supplemented with 3 g of HMB per day for 4 weeks ; the other 19 received a placebo followed by a 1-week washout period and then a second supplementation period in a r and omized double-blind crossover , placebo design . There were no significant changes ( p > 0.05 ) in muscular strength , including bench press , squats , and power cleans , among the subjects . There were also no significant changes ( p > 0.05 ) in body composition , including body fat and body weight . Very little clinical evidence exists for supplementing HMB in athletic population β-hydroxy-β-methylbutyrate ( HMB ) , a leucine metabolite , improves muscle mass and function . This study aim ed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia ( CC ) . Wistar rats were r and omized to receive st and ard or 4 % HMB-enriched chow . Rats from both groups were r and omized to receive an i.p . inoculum of AH-130 cells ( TB ) . All rats were weighed and sacrificed at day 24 . Liver , heart and muscles were dissected and weighed . The protein levels of p-p70S6k , p-eIf2α , p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle ( GSN ) . As expected , the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss . HMB treatment significantly increased GSN and heart weight in controls ( p=0.002 and p<0.001 , respectively ) . In HMB-treated TB , body weight was not lost but significantly ( p=0.003 ) increased , and GSN loss was significantly ( p=0.04 ) attenuated with respect to TB . Phosphorylated eIF2α markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet result ed in decreased p-eIF2α levels in control animals , while no changes could be observed in the TB group . Phosphorylated p70S6 K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB . Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment . Administration of HMB attenuates body weight and muscle loss in experimental CC . Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle Objective To examine the effect of arginine , & bgr;-hydroxy-&bgr;-methylbutyrate ( HMB ) , and glutamine supplementation on wound collagen accumulation in a double-blind , r and omized study . Summary Background Data Control of wound collagen synthesis has been an elusive goal for clinicians and scientists alike . In many clinical instances , it is desired to increase collagen deposition as a means of enhancing wound strength and integrity . Arginine , a semiessential amino acid , has been shown to increase wound collagen accumulation in rodents and humans . HMB , a metabolite of leucine , regulates muscle proteolysis in animals and humans and increases collagen deposition in rodents . Methods Thirty-five healthy , nonsmoking human volunteers 70 years or older were enrolled and underwent subcutaneous implantation of two small , sterile polytetrafluoroethylene ( PTFE ) tubes into the deltoid region under strict aseptic techniques . The tubes were 1 mm in diameter and 6 cm in length with pore size of 90 to 120 & mgr;m to allow optimal ingrowth of fibroblasts and the deposition of matrix . Eighteen volunteers ( mean age 75.4 years ; 2 men , 16 women ) were r and omized to receive daily supplementation of 14 g arginine , 3 g HMB , and 14 g glutamine ( total nitrogen 3.59 g ) in two divided doses . The control group ( n = 17 ; mean age 75.3 years ; 6 men , 11 women ) received an isonitrogenous , isocaloric supplementation of nonessential amino acids . Catheters were removed at 7 and 14 days postimplantation and analyzed for hydroxyproline ( OHP , nmol/cm catheter , an index of collagen accumulation ) and & agr;-amino nitrogen ( & agr;-AN , mmol/cm , an index of total protein deposition ) . Results Supplements were well tolerated , without any reported side effects . Supplementation with the specialized amino acid mixture led to a significant rise in plasma arginine and ornithine levels . The specialized amino acid supplement led to a significant increase in collagen deposition ( as reflected by OHP content ) in the PTFE tubes without an effect on total protein accumulation . Conclusions Collagen synthesis is significantly enhanced in healthy elderly volunteers by the oral administration of a mixture of arginine , HMB , and glutamine . This provides a safe nutritional means for increasing wound repair in patients This study examined the effects of supplemental beta-hydroxy-beta-methylbutyrate ( HMB ) on muscle damage as a result of intense endurance exercise . Subjects ( n = 13 ) were paired according to their 2-mile run times and past running experience . Each pair was r and omly assigned a treatment of either HMB ( 3 g/day ) or a placebo . After 6 wk of daily training and supplementation , all subjects participated in a prolonged run ( 20-km course ) . Creatine phosphokinase and lactate dehydrogenase ( LDH ) activities were measured before and after a prolonged run to assess muscle damage . The placebo-supplemented group exhibited a significantly greater ( treatment main effect , P = 0.05 ) increase in creatine phosphokinase activity after a prolonged run than did the HMB-supplemented group . In addition , LDH activity was significantly lower ( treatment main effect , P = 0.003 ) with HMB supplementation compared with the placebo-supplemented group . In conclusion , supplementation with 3.0 g of HMB results in a decreased creatine phosphokinase and LDH response after a prolonged run . These findings support the hypothesis that HMB supplementation helps prevent exercise-induced muscle damage The use of ergogenic nutritional supplements is becoming inseparable from competitive sports . β-Hydroxy-β-Methylbutyric acid ( HMB ) has recently been suggested to promote fat-free mass ( FFM ) and strength gains during resistance training in adults . In this prospect i ve r and omized , double-blind , placebo-controlled study , we studied the effect of HMB ( 3 g/day ) supplementation on body composition , muscle strength , anaerobic and aerobic capacity , anabolic/catabolic hormones and inflammatory mediators in elite , national team level adolescent volleyball players ( 13.5–18 years , 14 males , 14 females , Tanner stage 4–5 ) during the first 7 weeks of the training season . HMB led to a significant greater increase in FFM by skinfold thickness ( 56.4 ± 10.2 to 56.3 ± 8.6 vs. 59.3 ± 11.3 to 61.6 ± 11.3 kg in the control and HMB group , respectively , p < 0.001 ) . HMB led to a significant greater increase in both dominant and non-dominant knee flexion isokinetic force/FFM , measured at fast ( 180 ° /sec ) and slow ( 60 ° /sec ) angle speeds , but had no significant effect on knee extension and elbow flexion and extension . HMB led to a significant greater increase in peak and mean anaerobic power determined by the Wingate anaerobic test ( peak power : 15.5 ± 1.6 to 16.2 ± 1.2 vs. 15.4 ± 1.6 to 17.2 ± 1.2 watts/FFM , mean power : 10.6 ± 0.9 to 10.8 ± 1.1 vs. 10.7 ± 0.8 to 11.8 ± 1.0 watts/FFM in control and HMB group , respectively , p < 0.01 ) , with no effect on fatigue index . HMB had no significant effect on aerobic fitness or on anabolic ( growth hormone , IGF-I , testosterone ) , catabolic ( cortisol ) and inflammatory mediators ( IL-6 and IL-1 receptor antagonist ) . HMB supplementation was associated with greater increases in muscle mass , muscle strength and anaerobic properties with no effect on aerobic capacity suggesting some advantage for its use in elite adolescent volleyball players during the initial phases of the training season . These effects were not accompanied by hormonal and inflammatory mediator changes Background While chronic β-Hydroxy β-Methylbutyrate ( HMB ) supplementation ( ≥ 2 wk ) lowers exercise induced muscle damage , its acute or timing effects have not been examined . The purpose of this study was to investigate the acute and timing effects of oral HMB supplementation on serum creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) , muscle soreness , and maximal voluntary contraction ( MVC ) . Methods Sixteen non-resistance trained men ( 22 ± 2 yrs ) were assigned to HMB-Pre or HMB-Post groups . In a crossover design , all subjects performed 55 maximal eccentric knee extension/flexion contractions on 2 occasions on either the right or left leg . HMB-Pre ( N = 8) r and omly received 3 grams of either a placebo or HMB before and a placebo after exercise . HMB-Post ( N = 8) received a placebo before and either 3 grams of HMB or a placebo after exercise . Muscle damage tests were recorded before , at 8 , 24 , 48 , and 72 hrs post exercise . Results There was a reduction in MVC and an increase in soreness in the quadriceps and hamstrings following exercise ( p < 0.001 ) . Although HMB-Pre approached significance in attenuating soreness for the quadriceps ( p = 0.07 ) , there was no time × group effect . Serum indices of damage increased , peaking at 48 hrs for CK ( 773 % ) ( p < 0.001 ) and 72 hrs for LDH ( 180 % ) ( p < 0.001 ) . While there were no time × group effects of HMB on CK and LDH , post hoc analysis revealed that only HMB-Pre showed no significant increase in LDH levels following exercise . Conclusion Our findings suggest no clear acute or timing effects of HMB supplementation . However , consuming HMB before exercise appeared to prevent increases in LDH BACKGROUND Protein supplements are routinely used after a laparoscopic gastric bypass ( LGB ) . The aim of this study was to evaluate the impact of an amino acid supplement on glucose homeostasis and hormonal and inflammatory markers after LGB . STUDY DESIGN Thirty patients undergoing LGB were r and omized to receive or not 24 g of an oral supplement containing a leucine metabolite , glutamine , and arginine twice daily . Changes in weight , glucose , insulin , C-peptide , insulin sensitivity , interleukin ( IL ) 6 , C-reactive protein ( CRP ) , leptin , insulin-like growth factor ( IGF ) 1 , ghrelin , and incretins were assessed preoperatively and 2 weeks and 8 weeks postoperatively . RESULTS Thirty patients ( 96.7 % female , age 46.9 ± 8.4 years , body mass index 43.3 ± 4.1 kg/m(2 ) ) were r and omized . The experimental ( n = 14 ) and control ( n = 16 ) groups were not significantly different at baseline . Weight loss was similar for the 2 groups . Fasting glucose decreased significantly at 2 and 8 weeks compared with base line ( p < 0.0001 ) with no difference between the experimental and control groups ( p = 0.8 ) , but insulin and calculated insulin sensitivity , which were similar at baseline , became significantly worse in the experimental group 8 weeks after surgery ( p = 0.02 for insulin ; p = 0.04 for the homeostasis model assessment of insulin resistance ) . CRP and IL-6 , which were similar at baseline , were found to be significantly higher at 8 weeks in the experimental group ( p = 0.018 and p = 0.05 , respectively ) . Leptin and IGF-1 levels decreased significantly from baseline at 2 and 8 weeks ( p < 0.0001 ) , but there was no difference between the 2 groups . No significant changes in GLP-1 , ghrelin , or gastric inhibitory polypeptide were noticed after 8 weeks . CONCLUSIONS An amino acid supplement had no effect on the early postoperative incretins after LGB . It may have a negative influence on glucose kinetics and degree of inflammation . Future studies are needed to clarify these effects This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation on training responses in resistance-trained male athletes who were r and omly administered HMB in st and ard encapsulation ( SH ) , HMB in time release capsule ( TRH ) , or placebo ( P ) in a double-blind fashion . Subjects ingested 3 g x day(-1 ) of HMB or placebo for 6 weeks . Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation . The testing battery assessed body mass , body composition ( using dual energy x-ray absorptiometry ) , and 3-repetition maximum isoinertial strength , plus biochemical parameters , including markers of muscle damage and muscle protein turnover . While the training and dietary intervention of the investigation result ed in significant strength gains ( p < .001 ) and an increase in total lean mass ( p = .01 ) , HMB administration had no influence on these variables . Likewise , biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation . The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes BACKGROUND Cancer-related cachexia is caused by a diverse combination of accelerated protein breakdown and slowed protein synthesis . The hypothesis proposed in this study is that supplementation of specific nutrients known to positively support protein synthesis and reduce protein breakdown will reverse the cachexia process in advanced cancer patients . METHODS Patients with solid tumors who had demonstrated a weight loss of at least 5 % were considered for the study . Patients were r and omly assigned in a double-blind fashion to either an isonitrogenous control mixture of nonessential amino acids or an experimental treatment containing beta-hydroxy-beta-methylbutyrate ( 3 g/d ) , L-arginine ( 14 g/d ) , and L-glutamine ( 14 g/d [ HMB/Arg/Gln ] ) . The primary outcomes measured were the change in body mass and fat-free mass ( FFM ) , which were assessed at 0 , 4 , 8 , 12 , 16 , 20 , and 24 weeks . RESULTS Thirty-two patients ( 14 control , 18 HMB/Arg/Gln ) were evaluated at the 4-week visit . The patients supplemented with HMB/Arg/Gln gained 0.95 + /- 0.66 kg of body mass in 4 weeks , whereas control subjects lost 0.26 + /- 0.78 kg during the same time period . This gain was the result of a significant increase in FFM in the HMB/Arg/Gln-supplemented group ( 1.12 + /- 0.68 kg ) , whereas the subjects supplemented with the control lost 1.34 + /- 0.78 kg of FFM ( P = 0.02 ) . The response to 24-weeks of supplementation was evaluated by an intent-to-treat statistical analysis . The effect of HMB/Arg/Gln on FFM increase was maintained over the 24 weeks ( 1.60 + /- 0.98 kg ; quadratic contrast over time , P < 0.05 ) . There was no negative effect of treatment on the incidence of adverse effects or quality of life measures . CONCLUSIONS The mixture of HMB/Arg/Gln was effective in increasing FFM of advanced ( stage IV ) cancer . The exact reasons for this improvement will require further investigation , but could be attributed to the observed effects of HMB on slowing rates of protein breakdown , with improvements in protein synthesis observed with arginine and glutamine The purpose of this study was to determine the effect of beta-hydroxy beta-methylbutyrate ( HMB ) supplementation on maximal oxygen consumption ( .V(O)(2)peak ) and the onset of blood lactate accumulation ( OBLA ) in endurance-trained cyclists . Eight cyclists r and omly ( double blind ) completed 3 2-week supplementation periods ( HMB , 3g.day(-1 ) ; leucine [ LEU ] , 3g.day(-1 ) ; placebo [ CON ] , 3g.day(-1 ) ) followed by a 2-week washout period . Testing consisted of a grade d cycle ergometry test to measure .V(O)(2)peak and OBLA , the .V(O)(2 ) at 2 mM blood lactate . .V(O)(2)peak was unaffected by HMB ( 4.0 + /- 1.4 % ) , LEU ( -1.9 + /- 1.3 % ) , and CON ( -2.6 + /- 2.6 % ) . HMB result ed in a greater time to reach .V(O)(2)peak , whereas LEU and CON did not affect this time ( HMB , 3.6 + /- 1.5 min , LEU , -1.2 + /- 1.5 min ; CON , -3.6 + /- 3.5 min ) . Lactate accumulation peak was unaffected by supplementation ( HMB , 8.1 + /- 1.1 mM ; LEU , 6.2 + /- 0.8 mM ; CON , 7.5 + /- 1.3 mM ) . OBLA increased with HMB ( 9.1 + /- 2.4 % ) and LEU ( 2.1 + /- 1.5 % ) , but not in the CON trial ( 0.75 + /- 2.1 % ) . Blood glucose was significantly greater during the HMB trial compared with the LEU trial . It is concluded that HMB supplementation may have positive affects on performance by increasing the onset of blood lactate accumulation ; however , the mechanism is unknown The leucine metabolite , β-hydroxy-β-methylbutyrate ( HMB ) , is a nutritional supplement that increases lean muscle and strength with exercise and in disease states . HMB is presently available as the Ca salt ( CaHMB ) . The present study was design ed to examine whether HMB in free acid gel form will improve HMB availability to tissues . Two studies were conducted and in each study four males and four females were given three treatments in a r and omised , cross-over design . Treatments were CaHMB ( gelatin capsule , 1 g ) , equivalent HMB free acid gel swallowed ( FASW ) and free acid gel held sublingual for 15 s then swallowed ( FASL ) . Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2 . In both the studies , the times to peak plasma HMB were 128 ( sem 11 ) , 38 ( sem 4 ) and 38 ( sem 1 ) min ( P < 0·0001 ) for CaHMB , FASW and FASL , respectively . The peak concentrations were 131 ( sem 6 ) , 249 ( sem 14 ) and 239 ( sem 14 ) μmol/l ( P < 0·0001 ) for CaHMB , FASW and FASL , respectively . The areas under the curve were almost double for FASW and FASL ( P < 0·0001 ) . Daily urinary HMB excretion was not significantly increased result ing in more HMB retained ( P < 0·003 ) with FASW and FASL . Half-lives were 3·17 ( sem 0·22 ) , 2·50 ( sem 0·13 ) and 2·51 ( sem 0·14 ) h for CaHMB , FASW and FASL , respectively ( P < 0·004 ) . Free acid gel result ed in quicker and greater plasma concentrations ( + 185 % ) and improved clearance ( + 25 % ) of HMB from plasma . In conclusion , HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease PURPOSE The purpose of this investigation was to examine the effects of differing amounts of beta-hydroxy-beta-methylbutyrate ( HMB ) , 0 , 36 , and 76 mg x kg(-1 ) x d(-1 ) , on hematology , hepatic and renal function during 8 wk of resistance training . METHODS Thirty-seven , untrained collegiate males and were r and omly assigned to one of the three groups , 0 , 38 , or 76 mg x kg(-1 ) x d(-1 ) . Resistance training consisted of 10 exercises , performed 3 d x wk(-1 ) for 8 wk at 80 % of their 1-repetition maximum . Blood and urine was obtained before training , 48 h after the initial session , 1 wk , 2 wk , 4 wk , and at 8 wk of resistance training . Blood was analyzed for glucose , blood urea nitrogen , hemoglobin , hepatic enzymes , lipid profile , total leukocytes , and individual leukocytes . Urine was analyzed for pH , glucose , and protein excretion . RESULTS The 38 mg x kg(-1 ) x d(-1 ) group had a greater increase in basophils compared with 0 or 76 mg x kg(-1 ) x d(-1 ) groups ( P < 0.05 ) . No difference occurred in any other blood and urine measurements . CONCLUSION These data indicate that 8 wk of HMB supplementation ( < or = 76 mg x kg(-1 ) x d(-1 ) ) during resistance training had no adverse affects on hepatic enzyme function , lipid profile , renal function , or the immune system Thomson , JS , Watson , PE , and Rowl and s , DS . Effects of nine weeks of β-hydroxy-β-methylbutyrate supplementation on strength and body composition in resistance trained men . J Strength Cond Res 23(3 ) : 827 - 835 , 2009-The dietary supplement β-hydroxy-β-methylbutyrate ( HMB ) is cl aim ed to increase strength , lean body mass , and decrease fat mass when used in conjunction with resistance training . Although there is some support for these cl aims , the evidence is not conclusive , and it is even less so for resistance trained individuals . Therefore , we aim ed to further eluci date the effects of HMB supplementation in trained men . A r and omized , double-blind , controlled study design was used to investigate the effects of supplementing 22 resistance trained men with 3 g·d-1 of HMB or corn starch placebo for 9 weeks with resistance training . The effect of HMB on strength was determined using the 1-repetition maximum ( 1RM ) method for the lower body ( leg extension ) and upper body ( bench press , bicep preacher curl ) at baseline and after the supplementation period . Body composition was assessed by skinfolds and bioelectrical impedance analysis ( BIA ) . Overall , 9 weeks ' HMB supplementation result ed in a clear-cut , trivial increase in combined averaged strength measures of 1.6 % ( 90 % confidence limits : ±4.3 % ) . When considered in isolation , however , leg extension 1RM increased by a substantial 9.1 % ( 90 % confidence limits : ±7.5 % ) , but the effect on upper-body strength was inconclusive ( bench press : −1.9 ± 9.3 % ; bicep curl : −1.7 ± 4.7 % ) . Based on BIA estimates , HMB had a decreasing ( although inconclusive ) influence on fat mass of −9 ± 14 % , but it had a clear , trivial effect on fat-free mass of 0.2 ± 2.2 % . The magnitude of change in body mass was trivial , but the probability of substantial reductions in skinfold thicknesses ranged from negligible to likely . In previously trained men , supplementation of HMB in conjunction with resistance training provides a substantial benefit to lower-body strength , but it has negligible effects on body composition Calcium beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation has been reported to reduce muscle catabolism and promote gains in fat-free mass and strength in subjects initiating training . However , whether HMB supplementation promotes these adaptations in trained athletes is less clear . This study examined the effects of HMB ( as the calcium salt ) supplementation during resistance training ( 6.9+/-0.7 hr x wk(-1 ) ) on markers of catabolism , body composition and strength in experienced resistance-trained males . In a double-blind and r and omized manner , 40 experienced resistance-trained athletes were matched and assigned to supplement their diet for 28 d with a fortified carbohydrate/protein powder containing either 0 , 3 or 6 g x d(-1 ) of calcium HMB . Fasting venous blood and urine sample s , dual energy X-ray absorptiometer-determined body composition , and isotonic bench press and leg press one repetition maximums ( 1 RM ) were determined prior to and following 28 d of supplementation . HMB supplementation result ed in significant increases in serum and urinary HMB concentrations . However , no statistically significant differences were observed in general markers of whole body anabolic/catabolic status , muscle and liver enzyme efflux , fat/bone-free mass , fat mass , percent body fat , or 1 RM strength . Results indicate that 28 d of HMB supplementation ( 3 to 6 g x d(-1 ) ) during resistance-training does not reduce catabolism or affect training-induced changes in body composition and strength in experienced resistance-trained males PURPOSE The purpose of this investigation was 1 ) to determine whether HMB supplementation results in an increase in strength and FFM during 8 wk of resistance training and 2 ) determine whether a higher dose of HMB provides additional benefits . METHODS Thirty-seven , untrained , college-aged men were assigned to one of three groups : 0 , 38 , or 76 mg x kg(-1 ) x d(-1 ) of HMB ( approximately equal to 3 and 6 g x d(-1 ) , respectively ) . Resistance training consisted of 10 different exercises performed 3 d x wk(-1 ) for 8 wk at 80 % of 1-repetition maximum ( 1RM ) . The 1RM was reevaluated every 2 wk with workloads adjusted accordingly . RESULTS No differences were observed in 1RM strength among the groups at any time . However , the 38 mg x kg ( -1 ) x d(-1 ) group showed a greater increase in peak isometric torque than the 0 or 76 mg.kg(-1 ) x d(-1 ) groups ( P < 0.05 ) . The 76 mg x kg(-1 ) x d(-1 ) group had a greater increase in peak isokinetic torque than the 0 or 38 mg x kg(-1 ) x d(-1 ) groups at 2.1 , -3.15 , and -4.2 rad x s(-1 ) ( P < 0.05 ) . Plasma creatine phosphokinase ( CPK ) activity was greater for the 0 mg x kg(-1 ) x d(-1 ) versus the 38 or 76 mg x kg(-1 ) x d(-1 ) groups at 48 h after the initial training bout ( P < 0.05 ) . In addition , no differences were observed in body fat between the three groups . However , the 38 mg x kg(-1 ) x d(-1 ) group exhibited a greater increase in FFM ( P < 0.05 ) . CONCLUSIONS Although the IRM strength gains were not significantly different , HMB supplementation appears to increase peak isometric and various isokinetic torque values , and increase FFM and decrease plasma CPK activity . Lastly , it appears that higher doses of HMB ( i.e. , > 38 mg x kg(-1 ) x d(-1 ) ) do not promote strength or FFM gains The dietary supplement , beta-hydroxy-beta-methylbutyrate ( HMB ) , has been shown to decrease muscle proteolysis during the stress of exercise and disease . The aim of this investigation was to determine the time course kinetics of HMB and to determine whether oral glucose ingestion alters the kinetics . In Study 1 , eight males ( 32 + /- 10 yrs ) participated in two r and omize trials : 1 ) oral ingestion of 1 g of HMB with water in capsule form ( HMB ) , and 2 ) placebo . Blood sample s were obtained prior to ingestion of treatment and at 30 , 60 , 90 , 120 , 150 , and 180 min for the measurement of plasma HMB . Additional blood sample s were obtained at 6 , 9 , and 12 hr . Urine was collected prior to ingestion and at 3 , 6 , 9 , and 12 h for the measurement of urinary HMB . In Study 2 , eight males ( 25 + /- 6 yrs ) followed the same study design and testing procedure as for Study 1 . Treatments were 1 ) modified glucose tolerance test ( 75 g glucose ) ( GLU ) , 2 ) oral ingestion of 3 g of HMB with water ( HMB ) , and 3 ) ingestion of 3 g of HMB with 75 g of glucose ( HMB+GLU ) . Blood sample s were analyzed for insulin , glucose , and HMB . Additional blood sample s were obtained at 24h and 36h for the measurement of HMB . Additional urine sample s were collected at 24h and 36h . In Study 1 , plasma HMB peaked at 120 nmol/ml at 2.0 + /- 0.4 hr in HMB trial . Half-life was 2.37 + /- 0.1 hr . Following the consumption of 1 g of HMB , approximately 14 % of the HMB consumed accumulated in the urine . In Study 2 , plasma glucose and insulin levels were significantly greater in GLU and HMB+GLU treated subjects compared to HMB treated subject at minutes 30 , 60 and 90 . Plasma HMB peaked at 487.9 + /- 19.0 nmol/ml at 1.0 + /- 0.1 hr in the HMB treated subjects and at 352.1 + /- 15.3 nmol/ml at 1.94 + /- 0.2 hr when subjects consumed HMB+GLU . The time to reach peak was different ( P < 0.001 ) between HMB and HMB+GLU . The plasma HMB half-life was less ( P = 0.08 ) 2.38 + /- 0.1 hr in HMB trial compared to 2.69 + /- 0.2 hr in HMB+GLU trial . Area under the plasma HMB curve during the first 3 hr was less ( P = 0.002 ) in the HMB+GLU trial compared to the HMB trial . From 3 h through 36 h the area under the HMB curve tended to be less ( P = 0.106 ) for the HMB+GLU compared to the HMB alone . HMB accumulation in the urine as well as the area under the curve were similar with both HMB ( 94875.8 + /- 15159.5 nmol/36 hrs ) and HMB+GLU ( 80678.2 + /- 3863.1 nmol/36 hrs ) . The percentage of the HMB dose that accumulates in the urine was 27 % for HMB+GLU and 29 % for HMB alone . In conclusion , HMB plasma levels peak within 60 to 120 min depending on the amount of HMB consumed and whether glucose is consumed with HMB . The plasma half-life is approximately 2.5 hr . Plasma HMB reaches baseline levels at approximately 9 hr following ingestion . However , 70 to 85 % of the ingested oral HMB is retained in the body for further metabolism Purpose Cancer cachexia is a common problem among advanced cancer patients . A mixture of β-hydroxyl β-methyl butyrate , glutamine , and arginine ( HMB/Arg/Gln ) previously showed activity for increasing lean body mass ( LBM ) among patients with cancer cachexia . Therefore a phase III trial was implemented to confirm this activity . Material s and methods Four hundred seventy-two advanced cancer patients with between 2 % and 10 % weight loss were r and omized to a mixture of β-hydroxyl β-methyl butyrate , glutamine , and arginine or an isonitrogenous , isocaloric control mixture taken twice a day for 8 weeks . Lean body mass was estimated by bioimpedance and skin-fold measurements . Body plethysmography was used when available . Weight , the Schwartz Fatigue Scale , and the Spitzer Quality of Life Scale were also measured . Results Only 37 % of the patients completed protocol treatment . The majority of the patient loss was because of patient preference ( 45 % of enrolled patients ) . However , loss of power was not an issue because of the planned large target sample size . Based on an intention to treat analysis , there was no statistically significant difference in the 8-week lean body mass between the two arms . The secondary endpoints were also not significantly different between the arms . Based on the results of the area under the curve ( AUC ) analysis , patients receiving HMB/Arg/Gln had a strong trend higher LBM throughout the study as measured by both bioimpedance ( p = 0.08 ) and skin-fold measurements ( p = 0.08 ) . Among the subset of patients receiving concurrent chemotherapy , there were again no significant differences in the endpoints . The secondary endpoints were also not significantly different between the arms . Conclusion This trial was unable to adequately test the ability of β-hydroxy β-methylbutyrate , glutamine , and arginine to reverse or prevent lean body mass wasting among cancer patients . Possible contributing factors beyond the efficacy of the intervention were the inability of patients to complete an 8-week course of treatment and return in a timely fashion for follow-up assessment , and because the patients may have only had weight loss possible not related to cachexia , but other causes of weight loss , such as decreased appetite . However , there was a strong trend towards an increased body mass among patients taking the Juven ® compound using the secondary endpoint of AUC We investigated whether creatine ( CR ) and beta-hydroxy-beta-methylbutyrate ( HMB ) act by similar or different mechanisms to increase lean body mass ( LBM ) and strength in humans undergoing progressive resistance-exercise training . In this double-blind , 3-wk study , subjects ( n = 40 ) were r and omized to placebo ( PL ; n = 10 ) , CR ( 20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d ; n = 11 ) , HMB ( 3.0 g of HMB/d ; n = 9 ) , or CR- and -HMB ( CR/HMB ; n = 10 ) treatment groups . Over 3 wk , all subjects gained LBM , which was assessed by bioelectrical impedance analysis . The CR , HMB and CR/HMB groups gained 0.92 , 0.39 , and 1.54 kg of LBM , respectively , over the placebo group , with a significant effect with CR supplementation ( main effect P = 0.05 ) and a trend with HMB supplementation ( main effect P = 0.08 ) . These effects were additive because there was no interaction between CR and HMB ( CR x HMB main effect P = 0.73 ) . Across all exercises , HMB , CR , and CR/HMB supplementation caused accumulative strength increases of 37.5 , 39.1 , and 51.9 kg , respectively , above the placebo group . The exercise-induced rise in serum creatine phosphokinase was markedly suppressed with HMB supplementation ( main effect P = 0.01 ) . However , CR supplementation antagonized the HMB effects on serum creatine phosphokinase ( CR x HMB interactive effect P = 0.04 ) . Urine urea nitrogen and plasma urea were not affected by CR supplementation , but both decreased with HMB supplementation ( HMB effect P < 0.05 ) , suggesting a nitrogen-sparing effect . In summary , CR and HMB can increase LBM and strength , and the effects are additive . Although not definitive , these results suggest that CR and HMB act by different mechanisms Twenty-six members of a collegiate football team were r and omly assigned to either a supplement ( S ) ( 3 g of beta-hydroxy beta-methylbutyrate [ HMB ] per day ) or placebo ( P ) group . Testing occurred before ( PRE ) and at the end of 10 days of preseason football training camp ( POST ) . During each testing session , subjects performed an anaerobic power test , and blood sample s were obtained for testosterone , cortisol , creatine kinase , and myoglobin analysis . No differences in anaerobic power were seen between PRE and POST in either group . Cortisol concentrations were significantly decreased from PRE ( 333 + /- 81 nmol . L(-1 ) ) to POST ( 246 + /- 79 nmol . L(-1 ) ) , and a sixfold increase was seen in creatine kinase concentrations at POST . However , no significant differences between the groups were seen . No significant time or group effects were observed in testosterone or myoglobin concentrations . Results suggest that short duration HMB supplementation does not provide any ergogenic benefit in collegiate football players during preseason training camp BACKGROUND Older adults supplemented for 1 year with β-hydroxy-β-methylbutyrate , arginine , and lysine ( HMB/ARG/LYS ) were previously shown to have significant gains in fat-free mass ( FFM ) but not muscular strength . OBJECTIVE Recently , increasing levels of serum vitamin D have been associated with an increase in muscle function , particularly in the elderly . To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS , the authors performed post hoc analysis of strength based on the participants ' vitamin D status . METHODS Elderly ( age 76.0 ± 1.6 years ) adults were recruited for a double-blinded , controlled study and were r and omly assigned to either an isonitrogenous control ( n = 37 ) or HMB/ARG/LYS ( n = 40 ) for the yearlong study . Participants were further segregated based on their vitamin D status of either < 30 or ≥30 ng 25OH-vitD(3)/mL serum , and an analysis was performed on the 4 cohorts . RESULTS Regardless of vitamin D status , HMB/ARG/LYS result ed in significantly increased FFM ( P < .02 ) , but only in those with vitamin D status ≥30 ng 25OH-vitD(3)/mL was there a significant increase in strength with HMB/ARG/LYS ( P < .01 ) . Control-supplemented participants , regardless of vitamin D status , and the HMB/ARG/LYS-supplemented participants with vitamin D status < 30 ng 25OH-vitD(3 ) failed to show improvements in strength . CONCLUSIONS The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status , but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and vitamin PURPOSE We examined the effects of short-term beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation on symptoms of muscle damage following an acute bout of eccentric exercise . METHODS Non-resistance trained subjects were r and omly assigned to a HMB supplement group ( HMB , 40mg/kg bodyweight/day , n = 8) or placebo group ( CON , n = 9 ) . Supplementation commenced 6 days prior to a bout of 24 maximal isokinetic eccentric contractions of the elbow flexors and continued throughout post-testing . Muscle soreness , upper arm girth , and torque measures were assessed pre-exercise , 15 min post-exercise , and 1 , 2 , 3 , 4 , 7 , and 10 days post-exercise . RESULTS No pre-test differences between HMB and CON groups were identified , and both performed a similar amount of eccentric work during the main eccentric exercise bout ( p > .05 ) . HMB supplementation had no effect on swelling , muscle soreness , or torque following the damaging eccentric exercise bout ( p > .05 ) . CONCLUSION Compared to a placebo condition , short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage . If HMB can produce an ergogenic response , a longer preexercise supplementation period may be necessary AIM The aim of this study was to investigate the effects of 6 wks oral supplementation of beta-hydroxy-beta-methylbutyrate ( HMB ) and a mixture of HMB and creatine monohydrate ( HMBCr ) on aerobic and anaerobic capacity in highly trained athletes . It was hypothesised that HMB and HMBCr would have positive effects on aerobic and anaerobic power . METHODS A prospect i ve study involving a repeated measures design was utilised where subjects underwent testing prior to , and immediately after , a 6 wks supplementation period . Elite , male rugby league players ( n=27 ) were divided into 3 groups , a control group ( n=6 ) , a HMB group ( 3 g/d ; n=10 ) and a HMBCr group ( 3 g/d HMB + 3 g/d Cr ; n=11 ) . Testing involved a multistage fitness test to determine aerobic power and a 60 sec maximal cycle test to determine anaerobic capacity . Peak power , total work and peak lactate levels were measured in the anaerobic cycle test . RESULTS Two-way repeated measures ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters in comparison to the control group . CONCLUSION Aerobic and anaerobic ability of highly trained male athletes is unaffected by 6 wks oral supplementation with HMB or a combination of HMB and creatine monohydrate Elevated inflammatory markers and muscle wasting were common in chronic obstructive pulmonary disease ( COPD ) patients . The purpose of this study was to investigate the effect of 7-day beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation on inflammation , protein metabolism , and pulmonary function in COPD patients in an intensive care unit . Thirty-four COPD patients who required mechanical ventilators were r and omly assigned to HMB ( n=18 ) or control ( n=16 ) groups . The HMB group received HMB 3 g/d for 7 days . White blood cell count , C-reactive protein , and creatinine were significantly lower , while cholesterol and total protein were significantly higher after HMB supplementation . The body weight remained unchanged in both groups . Ten subjects ( 55.6 % ) in the HMB group and 4 subjects ( 25.0 % ) in the control group had improved pulmonary function , indicated by their ventilator modes . This short-term study suggests that HMB supplementation may have anti-inflammatory and anticatabolic effect and improve pulmonary function in COPD patients in an intensive care unit setting BACKGROUND Negative nitrogen balance and skeletal muscle loss are common in critically injured patients and may contribute to morbidity , mortality and re source utilization . Juven , an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate ( HMB ) , arginine ( ARG ) , and glutamine ( GLN ) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome ( AIDS ) and cancer patients . More recently HMB has been shown to attenuate cancer-induced muscle loss by decreasing muscle proteolysis . The purpose of this study was to analyze whether HMB alone or in combination with ARG and GLN would have a similar effect on critically injured trauma patients . We hypothesized that nitrogen balance would be improved and muscle proteolysis decreased with HMB and HMB/ARG/GLN supplementation . METHODS There were 100 adult trauma patients with Injury Severity Score ( ISS ) > 18 were enrolled in this prospect i ve , r and omized , blinded study . All patients received st and ard tube feeds and one of three iso-nitrogenous supplements ; HMB , HMB/ARG/ GLN , or placebo ( PLAC ) for 28 days . Urine , serum , and clinical data were collected for 72 patients receiving at least 7 days of supplementation during the first 14 days of treatment . Urinary 3-methylhistidine ( 3-MH ) was used as a proxy for muscle proteolysis . RESULTS The three groups were similar in age , gender , mechanism , and severity of injury , with the average ISS being 31.9 . Utilizing covariant ( ISS ) repeated measure ( days 1 - 14 ) mixed model ( SAS ) analysis , there was a significant treatment effect ( p = 0.05 ) on nitrogen balance ( g/d ) . Change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group . 3-MH to creatinine ratios were not different in the PLAC group as compared with the HMB/ARG/GLN and HMB groups ( Treatment Effect , p = 0.80 ) . CONCLUSIONS These data suggest that supplementation with HMB alone may improve nitrogen balance in critically injured adult patients and that this effect is not a result of lowered muscle protein turnover as originally hypothesized BACKGROUND The current study was design ed to examine whether a combination of three nutrients , consisting of beta-hydroxy-beta-methylbutyrate ( HMB ) , a metabolite of leucine , L-glutamine ( Gln ) and L-arginine ( Arg ) , each of which has been previously shown to slow muscle proteolysis , could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome ( AIDS ) . METHODS Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5 % in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center . The subjects were r and omly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture ( HMB/Arg/Gln ) containing 3 g HMB , 14 g L-glutamine , and 14 g L-arginine given in two divided doses daily for 8 weeks . Body weights ( BW ) were recorded weekly and lean body mass ( LBM ) and fat mass ( FM ) were measured by air displacement plethysmography and by a single computerized tomography ( CT ) slice through the thigh at 0 , 4 , and 8 weeks . RESULTS Forty-three subjects completed the 8-week protocol , ( placebo , n = 21 ; HMB/Arg/Gln , n = 22 ) . At 8 weeks , the subjects consuming the HMB/Arg/Gln mixture gained 3.0 + /- 0.5 kg of BW while those supplemented with the placebo gained 0.37 + /- 0.84 kg ( p = .009 ) . The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM ( 2.55 + /- 0.75 kg ) compared with the placebo-supplemented subjects who lost lean mass ( -0.70 + /- 0.69 kg , p = .003 ) . No significant change in FM gain was observed ( 0.43 + /- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 + /- 0.64 kg for the group receiving the placebo , p > .20 ) . Similar percentage changes in muscle mass and fat mass were observed with CT scans . Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation . CONCLUSIONS The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting The aim of this study was to determine the effects of oral beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation ( 3 g/d ) on selected components of aerobic performance and body composition of active college students . Subjects were r and omly assigned to either an HMB ( n=8 ) or a placebo ( PLA ) group ( n=8 ) for a 5-wk supplementation period during which they underwent interval training 3 times a week on a treadmill . Aerobic-performance components were measured using a respiratory-gas analyzer . Body composition was determined using dual-energy X-ray absorptiometry . After the intervention , there were significant differences ( P<0.05 ) between the 2 groups in gains in maximal oxygen consumption ( + 8.4 % for PLA and + 13.4 % for HMB ) . Regarding body composition , there were no significant differences . The authors concluded that HMB supplementation positively affects selected components of aerobic performance in active college students INTRODUCTION Previous research has demonstrated that ingestion of essential amino acids and their metabolites induce anabolic effects with the potential to augment gains in lean body mass and strength after resistance exercise training . PURPOSE The purpose of the present study was to examine the effects of an essential amino acid-based formula ( Muscle Armor ( MA ) ; Abbott Laboratories , Abbott Park , IL ) containing beta-hydroxy-beta-methylbutyrate ( HMB ) on hormonal and muscle damage markers in response to 12 wk of resistance exercise . METHODS Seventeen healthy men ( mean body mass : 77.9 + /- 7.2 kg ; mean height : 174.3 + /- 12.4 cm ; mean age : 22.9 + /- 3.8 yr ) were matched and r and omized into two groups and performed 12 wk of periodized heavy resistance training while supplementing with either MA or an isocaloric , isonitrogenous placebo ( CON ) . Every 2 wk during the 12-wk intervention , resting blood draws were obtained , and muscle strength and power were measured . In addition , blood draws were obtained before , during , and after a st and ardized resistance exercise challenge performed pre- , mid- , and posttraining . RESULTS Lean body mass , muscle strength , and muscle power significantly ( P < or= 0.05 ) increased in both groups after training ; however , MA supplementation augmented these responses to a significantly greater extent when compared with the CON group . MA supplementation promoted increases in resting and exercise-induced testosterone and resting growth hormone concentrations . In addition , MA reduced preexercise cortisol concentrations . Throughout the training protocol , MA attenuated circulating creatine kinase and malondealdehyde compared with the CON group , suggesting that MA might have influenced a reduction in muscle damage . CONCLUSION MA supplementation beneficially affected training-induced changes in lean body mass , muscle strength , and power , as well as hormonal responses and markers of muscle damage in response to 12 wk of resistance exercise training when compared with an isonitrogenous control |
13,056 | 17,943,747 | AUTHORS ' CONCLUSIONS The continuous suturing techniques for perineal closure , compared to interrupted methods , are associated with less short-term pain .
Moreover , if the continuous technique is used for all layers ( vagina , perineal muscles and skin ) compared to perineal skin only , the reduction in pain is even greater | BACKGROUND Millions of women worldwide undergo perineal suturing after childbirth and the type of repair may have an impact on pain and healing .
For more than 70 years , research ers have been suggesting that continuous non-locking suture techniques for repair of the vagina , perineal muscles and skin are associated with less perineal pain than traditional interrupted methods .
OBJECTIVES To assess the effects of continuous versus interrupted absorbable sutures for repair of episiotomy and second degree perineal tears following childbirth . | BACKGROUND Trauma to the perineum is a serious and frequent problem after childbirth , with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery , and many millions more worldwide . We compared the continuous technique of perineal repair with the interrupted method , and the more rapidly absorbed polyglactin 910 suture material with the st and ard polyglactin 910 material . METHODS 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous ( n=771 ) or interrupted ( 771 ) suturing method , and to either the more rapidly absorbed polyglactin 910 suture material ( 772 ) or st and ard polyglactin 910 material ( 770 ) . Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum . Analysis was by intention to treat . FINDINGS At day 10 , three women had dropped out of the study . Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method ( 204/770 [ 26.5 % ] vs 338/769 [ 44.0 % ] , odds ratio 0.47 , 95 % CI 0.38 - 0.58 , p<0.0001 ) . Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or st and ard material ( 256/769 [ 33.3 % ] vs 286/770 [ 37.1 % ] , 0.84 , 0.68 - 1.04 , p=0.10 ) . Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method ( 98/581 [ 16.9 % ] vs 102/593 [ 17.2 % ] , 0.98 , 0.72 - 1.33 , p=0.88 ) or the more rapidly absorbed versus st and ard material ( 105/586 [ 17.9 % ] vs 95/588 [ 16.2 % ] , 1.13 , 0.84 - 1.54 , p=0.42 ) . Suture removal was done less with the more rapidly absorbed material than with st and ard suture material ( 22/769 [ 3 % ] vs 98/770 [ 13 % ] , p<0.0001 ) , and with the continuous versus interrupted method ( 24/770 [ 3 % ] vs 96/769 [ 12 % ] , p<0.0001 ) . INTERPRETATION A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days . Also , the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications typic abnormalities in early onset severe growth retardation ( Fisk et al. 1989 ; Nicolaides et al. 1989 ; Sipes et al. 1991 ) . However , since there is an overlap in mean corpuscular volume between triploid and chromosomally normal growth-retarded fetuses ( Nicolaides et al. 1989 ) it is necessary that the diagnosis is confirmed by cytogenetic analysis which usually takes 7 - 10 days . Using flow cytometry and st and ard DNA quantification techniques , which are now widely used in the clinical management of haematological and other neoplasias , it is possible to diagnose fetal triploidy from fetal blood , within l h of sampling One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity Commonly used suture material s and techniques for perineal repair following vaginal delivery were compared in a r and omized controlled trial involving 1574 women . Three comparisons were made using a modified factorial design . In the comparison of teflon‐coated polyglycolic acid ( Dexon plus ) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short‐term analgesia being required in association with polyglycolic acid . Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk , although silk repair required more packets of material and was associated with delay in resuming sexual intercourse ; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing . There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin STUDY OBJECTIVE To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth DESIGN A r and omized controlled trial . DESIGN CLASSIFICATION Canadian Task Force Classification I. SETTING This study was undertaken in a university hospital with more than 2200 deliveries per year . The static population of this district includes a wide range of socioeconomic classes and is predominately white . PATIENTS From May 1 to November 19 , 2003 , 214 primiparous women with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous knotless technique ( CKT ; n=107 ) or the interrupted technique ( IT ; n=107 ) suturing method . INTERVENTIONS The interrupted technique ( IT ) involves placing 3 layers of sutures whereas the continuous knotless technique ( CKT ) involves reapproximating vaginal trauma , perineal muscles , and skin with a loose , continuous , nonlocking technique . MEASUREMENTS AND MAIN RESULTS The primary outcomes of the study were perineal pain ( evaluated by visual analogue scale ) at 48 hours and day 10 and dyspareunia 3 months after delivery . Secondary outcomes included suture removal , wound dehiscence , analgesia use up to 48 hours , and satisfaction with repair established at 3 and 12 months after childbirth . At day 10 , 19 women had dropped out of the study . Significantly fewer women reported pain at 10 days with the CKT than with the IT ( 32.3 % vs 60.4 % ; p<.001 ) . Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group ( 33.6 % vs 54.2 % ; p<.05 ) . No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group . CONCLUSION The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures |
13,057 | 29,979,797 | Conclusions Adding copeptin to cTn improved the sensitivity and negative predictive value for the diagnosis of NSTEMI compared to cTn alone .
Thus , adding copeptin to cTn might help to screen NSTEMI early upon admission to the ED | Introduction This study aim ed to determine the diagnostic accuracy of adding copeptin to cardiac troponin ( cTn ) on admission to the emergency department ( ED ) for non-ST elevation myocardial infa rct ion ( NSTEMI ) compared to cTn alone . | BACKGROUND The rapid and reliable diagnosis of acute myocardial infa rct ion is a major unmet clinical need . METHODS We conducted a multicenter study to examine the diagnostic accuracy of new , sensitive cardiac troponin assays performed on blood sample s obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infa rct ion . Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays ( Abbott-Architect Troponin I , Roche High-Sensitive Troponin T , Roche Troponin I , and Siemens Troponin I Ultra ) and a st and ard assay ( Roche Troponin T ) . The final diagnosis was adjudicated by two independent cardiologists . RESULTS Acute myocardial infa rct ion was the adjudicated final diagnosis in 123 patients ( 17 % ) . The diagnostic accuracy of measurements obtained at presentation , as quantified by the area under the receiver-operating-characteristic curve ( AUC ) , was significantly higher with the four sensitive cardiac troponin assays than with the st and ard assay ( AUC for Abbott-Architect Troponin I , 0.96 ; 95 % confidence interval [ CI ] , 0.94 to 0.98 ; for Roche High-Sensitive Troponin T , 0.96 ; 95 % CI , 0.94 to 0.98 ; for Roche Troponin I , 0.95 ; 95 % CI , 0.92 to 0.97 ; and for Siemens Troponin I Ultra , 0.96 ; 95 % CI , 0.94 to 0.98 ; vs. AUC for the st and ard assay , 0.90 ; 95 % CI , 0.86 to 0.94 ) . Among patients who presented within 3 hours after the onset of chest pain , the AUCs were 0.93 ( 95 % CI , 0.88 to 0.99 ) , 0.92 ( 95 % CI , 0.87 to 0.97 ) , 0.92 ( 95 % CI , 0.86 to 0.99 ) , and 0.94 ( 95 % CI , 0.90 to 0.98 ) for the sensitive assays , respectively , and 0.76 ( 95 % CI , 0.64 to 0.88 ) for the st and ard assay . We did not assess the effect of the sensitive troponin assays on clinical management . CONCLUSIONS The diagnostic performance of sensitive cardiac troponin assays is excellent , and these assays can substantially improve the early diagnosis of acute myocardial infa rct ion , particularly in patients with a recent onset of chest pain . ( Clinical Trials.gov number , NCT00470587 . BACKGROUND High-sensitivity troponin ( HS-TnT ) combined with copeptin have been proposed to expedite the diagnostic exclusion of acute myocardial infa rct ion . The Global Registry of Acute Coronary Events ( GRACE ) has been vali date d and recommended by the European Society of Cardiology as a prognostic score in the management of acute coronary syndrome ( ACS ) without ST-segment elevation ( non-ST+ ) on the electrocardiogram . Our study examined whether a low GRACE score ( < 108 ) combined with negative HS-TnT ( < 14 ng/L ) and copeptin ( < 14 pmol/L ) reliably exclude the diagnosis of non-ST+ ACS , including non-ST-segment elevation myocardial infa rct ion and unstable angina . METHODS This observational , prospect i ve study included patients presenting with chest pain lasting < 6 hours , consistent with non-ST+ ACS . Blood was collected early for measurements of copeptin and HS-TnT. The negative predictive value of combined copeptin , HS-TnT , and GRACE score was calculated in the diagnosis of non-ST+ ACS . The thresholds of positivity were 14 ng/L for HS-TnT , 14 pmol/L for copeptin and 108 for the GRACE score . RESULTS Among 247 patients retained in the analysis , the diagnosis of ACS was made in 50 ( 20.4 % ) , including 39 non-ST-segment elevation myocardial infa rct ion and 11 unstable angina . The negative predictive value of combined HS-TnT , copeptin and GRACE score was 99 % . CONCLUSION A negative copeptin associated with a negative HS-TnT in a patient presenting with a low GRACE score expedited the diagnostic exclusion of non-ST+ ACS Background — The role of the vasopressin system after acute myocardial infa rct ion is unclear . Copeptin , the C-terminal part of the vasopressin prohormone , is secreted stoichiometrically with vasopressin . We compared the prognostic value of copeptin and an established marker , N-terminal pro-B-type natriuretic peptide ( NTproBNP ) , after acute myocardial infa rct ion . Methods and Results — In this prospect i ve single-hospital study , we recruited 980 consecutive post – acute myocardial infa rct ion patients ( 718 men , median [ range ] age 66 [ 24 to 95 ] years ) , with follow-up over 342 ( range 0 to 764 ) days . Plasma copeptin was highest on admission ( n=132 , P<0.001 , day 1 versus days 2 to 5 ) and reached a plateau at days 3 to 5 . In the 980 patients , copeptin ( measured at days 3 to 5 ) was elevated in patients who died ( n=101 ) or were readmitted with heart failure ( n=49 ) compared with survivors ( median [ range ] 18.5 [ 0.6 to 441.0 ] versus 6.5 [ 0.3 to 267.0 ] pmol/L , P<0.0005 ) . With logistic regression analysis , copeptin ( odds ratio , 4.14 , P<0.0005 ) and NTproBNP ( odds ratio , 2.26 , P<0.003 ) were significant independent predictors of death or heart failure at 60 days . The area under the receiver operating characteristic curves for copeptin ( 0.75 ) and NTproBNP ( 0.76 ) were similar . The logistic model with both markers yielded a larger area under the curve ( 0.84 ) than for NTproBNP ( P<0.013 ) or copeptin ( P<0.003 ) alone , respectively . Cox modeling predicted death or heart failure with both biomarkers ( log copeptin [ hazard ratio , 2.33 ] , log NTproBNP [ hazard ratio , 2.70 ] ) . In patients stratified by NTproBNP ( above the median of ≈900 pmol/L ) , copeptin above the median ( ≈7 pmol/L ) was associated with poorer outcome ( P<0.0005 ) . Findings were similar for death and heart failure as individual end points . Conclusions — The vasopressin system is activated after acute myocardial infa rct ion . Copeptin may predict adverse outcome , especially in those with an elevated NTproBNP ( more than ≈900 pmol/L ) Aims To test the utility of a single copeptin determination at presentation to the emergency department ( ED ) as a short-term prognosis marker in patients with non-ST-elevation acute coronary syndrome ( NSTEACS ) . To compare the results with those achieved with conventional troponin . Methods A multicentric , prospect i ve , observational , longitudinal , cohort study involving 15 Spanish EDs . Inclusion : consecutive patients with chest pain ( < 12 h ) finally diagnosed of NSTEACS . Measurements : copeptin and troponin at arrival . Cut-off point for copeptin : 25.9 pmol/l . Follow-up : within 2 months after ED attendance to identify 30-day adverse events . Discriminatory capacity of copeptin and troponin was compared by receiver operating characteristic ( ROC ) curves . Results We included 377 patients with NSTEACS . Adverse events : 11 ( 2.9 % ) patients died , 27 ( 7.2 % ) had an adverse coronary event , 14 ( 3.7 % ) had a stroke , and 48 ( 12.7 % ) a composite endpoint . The initial copeptine value was over 25.9 pmol/l in 114 patients , and they presented a higher mortality rate ( OR : 4.2 , ( 95 % CI 1.2 to 14.8 ) ; p=0.03 ) . This association disappeared after adjusting by clinical variables or troponin level . No significant differences were found for the remaining endpoints . The area under the curve of the ROC curve of 30-day mortality was 0.73 ( 95 % CI 0.58 to 0.87 ) for copeptin , and 0.80 ( 95 % CI 0.73 to 0.87 ) for troponin . Conclusions In patients with NSTEACS , determination of copeptin at presentation to the ED is associated with risk of death during the subsequent month . This association , however , disappears after adjusting by baseline features or troponin level , so copeptin does not add complementary prognostic information over that provided by troponin Abstract Background : Identifying older patients with non-ST- elevation myocardial infa rct ion ( NSTEMI ) within the very large proportion with elevated high-sensitive cardiac troponin T ( hs-cTnT ) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department ( ED ) . We prospect ively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive ( copeptin-us ) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients . Methods : We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED . In addition to clinical examination , copeptin-us and hs-cTnT were measured at admission . Two cardiologists independently adjudicated the final diagnosis of NSTEMI after review ing all available data . All patients were followed up for cardiovascular-related death within the following 12 months . Results : NSTEMI was diagnosed in 38 ( 12 % ) patients ( age 81±6 years ) . The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21 % vs. 19 % to rule in NSTEMI . The combination of copeptin-us < 14 pmol/L and hs-cTnT < 0.014 µg/L compared to hs-cTnT < 0.014 µg/L alone had a negative predictive value of 100 % vs. 99 % to rule out NSTEMI . Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome . When copeptin-us ≥14 pmol/L was added , the net reclassification improvement for outcome was not significant ( p=0.809 ) . Conclusions : In unselected older patients presenting to the ED , the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone Background The combination of the new high sensitivity troponin T ( hsTnT ) assays and copeptin , a biomarker of endogenous stress , has been suggested to have the potential of early rule-out of acute coronary syndrome ( ACS ) . The aim of this study was to examine the ability of this combination to rule out ACS in patients presenting with chest pain and to compare the diagnostic performance to hsTnT alone . Method In this prospect i ve observational study , patients with chest pain admitted for observation were consecutively included . Patients presenting with ST elevation were excluded . Copeptin and hsTnT were analyzed at admission and hsTnT was thereafter determined approximately every 3rd hour as long as clinical ly indicated . The follow-up period was 60 days . A combined primary endpoint of ACS , non-elective percutanous coronary intervention , non-elective coronary artery bypass surgery and death of all causes was used . Results 478 patients were included . 107 ( 22 % ) patients were diagnosed with ACS during hospital stay . 70 ( 14 % ) had non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) and 37 ( 8 % ) had unstable angina pectoris (UAP).The combination of hsTnT > 14 ng/L or copeptin ≥14 pmol/L at admission identified ACS with a higher sensitivity than hsTnT alone : 0.83 ( 95 % confidence interval ( CI ) : 0.74 - 0.89 ) versus 0.69 ( 95 % CI : 0.59 - 0.77 ) , p < 0.001 . Negative predictive values ( NPV ) 91 % ( 95 % CI : 86 - 94 ) versus 89 % ( 95 % CI : 84 - 92 ) . A repeated hsTnT analyzed 3 - 4 hours after admission result ed in a sensitivity of : 0.77 ( 95 % CI : 0.65 - 0.86 ) , p = 0.031 for comparison with the combination analyzed at admission . Conclusions In patients presenting with chest pain admitted for observation , the combination of hsTnT and copeptin analyzed at admission had a significantly higher sensitivity to diagnose ACS than hsTnT alone . We report a sensitivity of 83 % and a NPV of 91 % for the combination of hsTnT and copeptin and we conclude that biomarkers alone are not sufficient to rule out ACS . However , the combination of hsTnT and copeptin seems to have a significantly higher sensitivity to identify ACS than a repeated hsTnT test , and thus enables an earlier risk stratification of chest pain patients . This can be time-saving and beneficial for the individual patient by contributing to early decisions on treatment , need of further assessment and level of care Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific findings vary by particular subgroups , and may provide summary estimates with a stronger generalizability than estimates from a single study . Systematic review s may help identify the risk for bias that may be present in the original studies and can be used to address questions that were not directly considered in the primary studies , such as comparisons between tests . The Cochrane Collaboration is the largest international organization preparing , maintaining , and promoting systematic review s to help people make well-informed decisions about health care ( 2 ) . The Collaboration decided in 2003 to make preparations for including systematic review s of diagnostic test accuracy in their Cochrane Data base of Systematic Review s. To enable this , a working group ( Appendix ) . was formed to develop methodology , software , and a h and book The first diagnostic test accuracy review was published in the Cochrane Data base in October 2008 . In this paper , we review recent method ological developments concerning problem formulation , location of literature , quality assessment , and meta- analysis of diagnostic accuracy studies by using our experience from the work on the Cochrane H and book . The information presented here is based on the recent literature and up date s previously published guidelines by Irwig and colleagues ( 3 ) . Definition of the Objectives of the Review Diagnostic test accuracy refers to the ability of a test to distinguish between patients with disease ( or more generally , a specified target condition ) and those without . In a study of test accuracy , the results of the test under evaluation , the index test , are compared with those of the reference st and ard determined in the same patients . The reference st and ard is an agreed-on and accurate method for identifying patients who have the target condition . Test results are typically categorized as positive or negative for the target condition . By using such binary test outcomes , the accuracy is most often expressed as the test 's sensitivity ( the proportion of patients with positive results on the reference st and ard that are also positive on the index test ) and specificity ( the proportion of patients with negative results on the reference st and ard that are also negative on the index test ) . Other measures have been proposed and are in use ( 46 ) . It has long been recognized that test accuracy is not a fixed property of a test . It can vary between patient subgroups , with their spectrum of disease , with the clinical setting , or with the test interpreters and may depend on the results of previous testing . For this reason , inclusion of these elements in the study question is essential . In order to make a policy decision to promote use of a new index test , evidence is required that using the new test increases test accuracy over other testing options , including current practice , or that the new test has equivalent accuracy but offers other advantages ( 79 ) . As with the evaluation of interventions , systematic review s need to include comparative analyses between alternative testing strategies and should not focus solely on evaluating the performance of a test in isolation . In relation to the existing situation , 3 possible roles for a new test can be defined : replacement , triage , and add-on ( 7 ) . If a new test is to replace an existing test , then comparing the accuracy of both tests on the same population and with the same reference st and ard provides the most direct evidence . In triage , the new test is used before the existing test or testing pathway , and only patients with a particular result on the triage test continue the testing pathway . When a test is needed to rule out disease in patients who then need no further testing , a test that gives a minimal proportion of falsenegative results and thus a relatively high sensitivity should be used . Triage tests may be less accurate than existing ones , but they have other advantages , such as simplicity or low cost . A third possible role of a new test is add-on . The new test is then positioned after the existing testing pathway to identify false-positive or false-negative results after the existing pathway . The review should provide data to assess the incremental change in accuracy made by adding the new test . An example of a replacement question can be found in a systematic review of the diagnostic accuracy of urinary markers for primary bladder cancer ( 10 ) . Clinicians may use cytology to triage patients before they undergo invasive cystoscopy , the reference st and ard for bladder cancer . Because cytology combines high specificity with low sensitivity ( 11 ) , the goal of the review was to identify a tumor marker with sufficient accuracy to either replace cytology or be used in addition to cytology . For a marker to replace cytology , it has to achieve equally high specificity with improved sensitivity . New markers that are sensitive but not specific may have roles as adjuncts to conventional testing . The review included studies in which the test under evaluation ( several different tumor markers and cytology ) was evaluated against cystoscopy or histopathology . Included studies compared 1 or more of the markers , cytology only , or a combination of markers and cytology . Although information on accuracy can help clinicians make decisions about tests , good diagnostic accuracy is a desirable but not sufficient condition for the effectiveness of a test ( 8) . To demonstrate that using a new test does more good than harm to patients tested , r and omized trials of test- and -treatment strategies and review s of such trials may be necessary . However , with the possible exception of screening , in most cases , such r and omized trials are not available and systematic review s of test accuracy may provide the most useful evidence available to guide clinical and health policy decision making and use as input for decision and cost-effectiveness analysis ( 12 ) . Identification and Selection of Studies Identifying test accuracy studies is more difficult than search ing for r and omized trials ( 13 ) . There is not a clear , unequivocal keyword or indexing term for an accuracy study in literature data bases comparable with the term r and omized , controlled trial . The Medical Subject Heading sensitivity and specificity may look suitable but is inconsistently applied in most electronic bibliographic data bases . Furthermore , data on diagnostic test accuracy may be hidden in studies that did not have test accuracy estimation as their primary objective . This complicates the efficient identification of diagnostic test accuracy studies in electronic data bases , such as MEDLINE . Until indexing systems properly code studies of test accuracy , search ing for them will remain challenging and may require additional manual search es , such as screening reference lists . In the development of a comprehensive search strategy , review authors can use search strings that refer to the test(s ) under evaluation , the target condition , and the patient description or a subset of these . For tests with a clear name that are used for a single purpose , search ing for publications in which those tests are mentioned may suffice . For other review s , adding the patient description may be necessary , although this is also often poorly indexed . A search strategy in MEDLINE should contain both Medical Subject Headings and free text words . A search strategy for articles about tests for bladder cancer , for example , should include as many synonyms for bladder cancer as possible in the search strategy , including neoplasm , carcinoma , transitional cell , and hematuria . Several method ological electronic search filters for diagnostic test accuracy studies have been developed , each attempting to restrict the search to articles that are most likely to be test accuracy studies ( 1316 ) . These filters rely on indexing terms for research methodology and text words used in reporting results , but they often miss relevant studies and are unlikely to decrease the number of articles one needs to screen . Therefore , they are not recommended for systematic review s ( 17 , 18 ) . The incremental value of search ing in language s other than English and in the gray literature has not yet been fully investigated . In systematic review s of intervention studies , publication bias is an important and well-studied form of bias in which the decision to report and publish studies is linked to their findings . For clinical trials , the magnitude and determinants of publication bias have been identified by tracing the publication history of cohorts of trials review ed by ethics committees and research boards ( 19 ) . A consistent observation has been that studies with significant results are more likely to be published than studies with nonsignificant findings ( 19 ) . Investigating publication bias for diagnostic tests is problematic , because many studies are done without ethical review or study registration ; therefore , identification of cohorts of studies from registration to final publication status BACKGROUND High-sensitivity cardiac troponin assays have improved the detection of acute coronary syndrome . AIM To examine the possible incremental value of copeptin in the detection of acute coronary syndrome . METHODS We design ed a prospect i ve cohort study to compare the performance of high-sensitivity cardiac troponin T ( hs-cTnT ) measured at admission in combination with copeptin , and the performance of hs-cTnT alone , measured at admission , 3 hours and 6 hours , in patients with suspected acute coronary syndrome of < 6 hours ' duration after onset of symptoms ( exclusion of patients with ST-segment elevation myocardial infa rct ion ) . RESULTS Fifty-eight consecutive patients fulfilled our criteria and were included . After detailed investigations , the final adjudicated diagnosis was acute coronary syndrome in 30 patients ( including acute myocardial infa rct ion in 13 and unstable angina in 17 ) and non-acute coronary syndrome in 28 patients . Measured on admission , hs-cTnT concentration was > 14 ng/mL ( 99 th percentile ) in 22 patients with acute coronary syndrome ; repetition of the measurement at 3 hours and 6 hours identified three and four additional patients , respectively . The combination of copeptin with hs-cTnT determined on admission identified 26 patients with acute coronary syndrome , with a negative predicted value of 82.6 % . The area under the receiver operating characteristic curve was 0.90 for hs-cTnT measured on admission , and 0.94 if repeated at 3 hours and 6 hours or combined with copeptin measurement at admission ( non-significant difference ) . CONCLUSIONS This prospect i ve study demonstrated that a dual marker strategy that combines hs-cTnT with copeptin increased slightly the detection of acute coronary syndrome at admission OBJECTIVES The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infa rct ion ( AMI ) . BACKGROUND The rapid and reliable exclusion of AMI is a major unmet clinical need . Copeptin , the C-terminal part of the vasopressin prohormone , as a marker of acute endogenous stress may be useful in this setting . METHODS In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI , we measured levels of copeptin at presentation , using a novel s and wich immunoluminometric assay in a blinded fashion . The final diagnosis was adjudicated by 2 independent cardiologists using all available data . RESULTS The adjudicated final diagnosis was AMI in 81 patients ( 17 % ) . Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses ( median 20.8 pmol/l vs. 6.0 pmol/l , p < 0.001 ) . The combination of troponin T and copeptin at initial presentation result ed in an area under the receiver-operating characteristic curve of 0.97 ( 95 % confidence interval : 0.95 to 0.98 ) , which was significantly higher than the 0.86 ( 95 % confidence interval : 0.80 to 0.92 ) for troponin T alone ( p < 0.001 ) . A copeptin level < 14 pmol/l in combination with a troponin T < or = 0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8 % and a negative predictive value of 99.7 % . CONCLUSIONS The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients . ( Advantageous Predictors of Acute Coronary Syndromes Evaluation [ APACE ] ; NCT00470587 ) BACKGROUND Point of care testing ( POCT ) assays for cardiac troponin ( cTn ) are hampered by lower analytical sensitivity and thus suboptimal rule-out of myocardial infa rct ion ( MI ) . We investigated , whether additional measurement of copeptin using an ultrasensitive assay improves diagnostic performance of POCT for cTn T compared to a high sensitivity troponin T ( hsTnT ) assay . METHODS 131 patients with suspected acute coronary syndrome were prospect ively enrolled in our center 08/2010 to 11/2011 . In blood sample s obtained at presentation , ultrasensitive copeptin ( Kryptor , BRAHMS ) and two commercially available POCT assays , AQT90 Flex Radiometer ( Radiometer ) and Cobas h232 POC-System ( Cobas ) , were tested . HsTnT ( Cobas E411 , Roche ) at baseline and after 3 and 6h in the central laboratory served as reference . RESULTS Copeptin improved rule-out of non-STEMI combined with all tested troponin assays . Addition of copeptin increased sensitivity of Cobas from 67.9 % ( 95 % CI : 0.506 ; 0.852 ) to 89.3 % ( 95 % CI : 0.778 ; 1.007 ) and Radiometer from 71.4 % ( 95 % CI : 0.547 ; 0.882 ) to 85.7 % ( 95 % CI : 0.728 ; 0.987 ) , achieving the sensitivity of hsTnT alone at admission of 85.7 % ( 95 % CI : 0.728 ; 0.987 ) . The area under the curve ( AUC ) of Radiometer ( 0.822 ) was numerically but insignificantly ( p=0.17 ) higher than AUC of Cobas ( 0.725 ) . Addition of copeptin increased AUC of Radiometer to 0.826 ( p=0.96 ) and AUC of Cobas to 0.814 ( p=0.20 ) . CONCLUSIONS Additional use of ultrasensitive copeptin improves diagnostic performance of conventional sensitive POCT assays overcoming lower sensitivities at the cost of a drop of clinical specificity . When hsTn is temporarily unavailable , copeptin and POCT for cTn may allow initial evaluation at a comparable performance as hsTnT at admission Objective To investigate the relationship between circulating plasma copeptin values and infa rct size as well as myocardial function at baseline and 4 months after mechanical reperfusion for ST segment elevation myocardial infa rct ion ( STEMI ) . Design Prospect i ve observational cohort study . Setting University Hospital of Innsbruck . Patients 54 patients with acute STEMI . Main outcome measures Correlation of plasma copeptin with infa rct size as well as left ventricular ejection fraction ( LVEF ) and remodelling . Methods Participants underwent contrast enhanced cardiac MRI at baseline and 4 months thereafter . Blood sample s were drawn 2 days after the onset of symptoms . Copeptin values were determined by an immunofluorescent assay . Results Copeptin concentrations ( median 10.4 pmol/l , IQR 6.0–14.4 ) were associated with early and chronic infa rct size ( r=0.388 , p=0.004 at baseline ; r=0.385 , p=0.011 at follow-up ) and inversely related to LVEF at both times ( r=−0.484 , p<0.001 at baseline ; r=−0.461 , p<0.001 at follow-up ) . Patients with adverse remodelling showed higher baseline copeptin values compared to patients without remodelling ( p=0.02 ) . Receiver operating characteristic analysis indicated a cut-off value of 16.7 pmol/l for copeptin to best identify patients with future adverse remodelling . Conclusions Increased copeptin values 2 days after STEMI are associated with larger acute and chronic infa rct sizes . Moreover , elevated copeptin concentrations at baseline were associated with myocardial function and remodelling 4 months post-STEMI . These findings strengthen the role of copeptin as a biomarker of adverse outcome after STEMI OBJECTIVES To test the diagnostic accuracy for detecting an acute myocardial infa rct ion ( AMI ) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation , myocardial ischaemia and necrosis ; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers ; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement . DESIGN Sub study of the point-of-care arm of the RATPAC ( R and omised Assessment of Treatment using Panel Assay of Cardiac markers ) trial . SETTING The emergency departments of six hospitals . PARTICIPANTS Prospect i ve admissions with chest pain and a non-diagnostic electrocardiogram r and omised to point-of-care assessment or conventional management . INTERVENTIONS Blood sample s taken on admission and 90 minutes from admission for measurement of cardiac markers [ cardiac troponin I ( cTnI ) , myoglobin and creatine kinase MB isoenzyme ( CK-MB ) ] by point-of-care testing . An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI ( two methods ) and cardiac troponin T ( cTnT ) , myoglobin , heart-type fatty acid-binding protein ( H-FABP ) , copeptin and B-type natriuretic peptide ( NTproBNP ) . MAIN OUTCOME MEASURES 1 . Diagnostic accuracy compared with the universal definition of myocardial infa rct ion utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory . 2 . Ability of biomarker measurements to predict major adverse cardiac events ( death , non-fatal AMI , emergency revascularisation or hospitalisation for myocardial ischaemia ) at 3 months ' follow-up . 3 . Comparison of incremental cost per quality -adjusted life-year ( QALY ) of different biomarker measurement strategies for the diagnosis of myocardial infa rct ion . RESULTS Sample s were available from 850 out of 1132 patients enrolled in the study . Measurement of admission myoglobin [ area under the curve ( AUC ) 0.76 ] and CK-MB ( AUC 0.84 ) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI ( AUC 0.90 - 0.94 ) or cTnT ( AUC 0.92 ) measurement on admission . Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78 - 0.92 , but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission ( 0.78 - 0.95 ) . Copeptin ( AUC 0.62 ) and NTproBNP ( AUC 0.85 ) measured on admission were not useful as diagnostic markers . As a prognostic marker , troponin measured on admission using a high-sensitivity assay ( AUC 0.73 - 0.83 ) was equivalent to NTproBNP measurement ( AUC 0.77 ) on admission , but superior to copeptin measurement ( AUC 0.58 ) . From modelling , 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £ 30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available . CONCLUSIONS The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain . Additional measurements of myoglobin or CK-MB are not clinical ly effective or cost-effective . The optimal timing for measurement of cardiac troponin remains to be defined . Copeptin measurement is not recommended . H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain . TRIAL REGISTRATION IS RCT N37823923 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 15 . See the HTA programme website for further project information OBJECTIVE We sought to evaluate the added value of ultrasensitive copeptin ( us-copeptin ) for early rule out of acute myocardial infa rct ion in a prospect i ve cohort of emergency department ( ED ) patients with acute chest pain . METHODS This was a prospect i ve study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset . High-sensitivity cardiac troponin T ( hs-cTnT , Roche Diagnostics , Meylan , France ) and us-copeptin ( ThermoFisher Scientific , Clichy , France ) were blindly assayed from venous blood sample s obtained at admission . Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical st and ard . Diagnostic performances of us-copeptin combined with hs-cTnT were assessed using logistic regression . Analysis was conducted in all patients and in patients without ST-elevation myocardial infa rct ion . RESULTS A total of 194 patients were included ( age , 61 [ 48 - 75 ] years ; male sex , 63 % ) . Acute myocardial infa rct ion occurred in 52 ( 27 % ) patients , including non-ST-elevation myocardial infa rct ion ( NSTEMI ) in 25 ( 13 % ) . Patients with acute myocardial infa rct ion had higher levels of hs-cTnT ( 50 [ 95 % confidence interval , 19 - 173 ] ng/L ) and us-copeptin ( 30 [ 13 - 113 ] pmol/L ) at admission compared with those without ( P < .05 ) . Combination of markers significantly improved receiver operating characteristic area under the curve ( from 0.89 [ 0.85 - 0.92 ] for hs-cTnT alone to 0.93 [ 0.89 - 0.97 ] , P = .018 ) . Sensitivity and negative predictive value were increased , particularly for NSTEMI diagnosis ( sensitivity , 76 % [ 54.9 - 90.6 ] to 96 % [ 79.6 - 99.9 ] ; negative predictive value , 95 % [ 90.4 - 98.3 ] to 98.9 % [ 94.2 to 100 ] ) . CONCLUSION Assessment of us-copeptin combined with hs-cTnT on ED admission could allow safe and early rule out of NSTEMI for patients with negative results on both markers and help identify patients who may be suitable for discharge OBJECTIVES The goal of this study was to demonstrate that copeptin levels < 14 pmol/L allow ruling out acute myocardial infa rct ion ( AMI ) when used in combination with cardiac troponin I ( cTnI ) < 99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department ( ED ) . BACKGROUND Copeptin is secreted from the pituitary early in the course of AMI . METHODS This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset . Baseline demographic characteristics and clinical data were collected prospect ively . Copeptin levels and a contemporary sensitive cTnI ( 99 th percentile 40 ng/l ; 10 % coefficient of variation 0.03 μg/l ) were measured in a core laboratory . Patients were followed up for 180 days . The primary outcome was diagnosis of AMI . Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results . RESULTS AMI was the final diagnosis in 156 patients ( 7.9 % ) . A negative copeptin and cTnI at baseline ruled out AMI for 58 % of patients , with a negative predictive value of 99.2 % ( 95 % confidence interval : 98.5 to 99.6 ) . AMIs not detected by the initial cTnI alone were picked up with copeptin > 14 pmol/l in 23 ( 72 % ) of 32 patients . Non-ST-segment elevation myocardial infa rct ions undetected by cTnI at 0 h were detected with copeptin > 14 pmol/l in 10 ( 53 % ) of 19 patients . Projected average time-to-decision could be reduced by 43 % ( from 3.0 h to 1.8 h ) by the early rule out of 58 % of patients . Both abnormal copeptin and cTnI were predictors of death at 180 days ( p < 0.0001 for both ; c index 0.784 and 0.800 , respectively ) . Both were independent of age and each other and provided additional predictive value ( all p < 0.0001 ) . CONCLUSIONS Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value > 99 % in patients presenting with suspected acute coronary syndromes . This combination has the potential to rule out AMI in 58 % of patients without serial blood draws OBJECTIVES The aim of this study was to analyze the diagnostic accuracy and the clinical usefulness of the combination of troponin I ( cTnI ) and copeptin measured at presentation with an automated assay to rapidly rule out non-ST elevation myocardial infa rct ion ( NSTEMI ) in patients with suspected cardiac chest pain presenting to an emergency department ( ED ) . METHODS This study was an ancillary analysis of a prospect i ve observational study . Copeptin and cTnI levels were sample d at presentation in 641 consecutive patients admitted to the ED for chest pain with onset within the last 12 hours and without ST elevation on a 12-lead electrocardiogram ( ECG ) . Copeptin was measured with an automated assay and troponin with conventional assay . The performance of a combination of cTnI and copeptin for NSTEMI diagnosis was studied , the clinical utility was assessed by multivariate analysis , and an area under the curve ( AUC ) calculation was used to determine accuracy . RESULTS NSTEMI was diagnosed in 95 patients ( 15 % ) . The sensitivity and negative predictive value ( NPV ) of the combination of copeptin and cTnI measures were 90.4 % ( 95 % confidence interval [ CI ] = 88.2 % to 92.7 % ) and 97.6 % ( 95 % CI = 96.4 % to 98.7 % ) versus 55.3 % ( 95 % CI = 51.5 % to 59.2 % ) and 92.8 % ( 95 % CI = 90.8 % to 94.8 % ) with cTnI alone . The AUC of the combination of copeptin and cTnI was 0.89 ( 95 % CI = 0.85 % to 0.92 % ) and was significantly higher than the AUC of cTnI alone ( 0.77 , 95 % CI = 0.72 % to 0.82 % , p < 0.05 ) . The patient classification was slightly improved when copeptin was added to the usual diagnostic tools used for NSTEMI management . CONCLUSIONS In this study , determination of copeptin , in addition to cTnI , improves early diagnostic accuracy of NSTEMI . However , the sensitivity of this combination even using a conventional troponin assay remains insufficient to safely rule out NSTEMI at the time of presentation Objective The early diagnosis of acute myocardial infa rct ion ( AMI ) can be particularly challenging in patients with known coronary artery disease ( CAD ) due to pre-existing ECG changes and chronic increases in cardiac troponin ( cTn ) levels . Design Of 1170 consecutive patients presenting with symptoms suggestive of AMI , 433 ( 37 % ) with pre-existing CAD were analysed in a prospect i ve multicentre study and the diagnostic and prognostic impact of copeptin in combination with either fourth generation cardiac troponin T ( cTnT ) or high-sensitivity cTnT ( hs-cTnT ) was evaluated . Results AMI was the final diagnosis in 78 patients with pre-existing CAD ( 18 % ) . Copeptin was significantly higher in patients with AMI than in those without ( 26 pmol/l ( IQR 9–71 ) vs 7 pmol/l ( IQR 4–16 ) , p<0.001 ) . The diagnostic accuracy for AMI as quantified by the area under the receiver operating characteristic curve ( AUC ) was significantly higher for the combination of copeptin and cTnT than for cTnT alone ( 0.94 vs 0.86 , p<0.001 ) . The combination of copeptin and hs-cTnT ( 0.94 ) was trending to superiority compared with hs-cTnT alone ( 0.92 , p=0.11 ) . The combination of copeptin and the cTn assays was able to improve the negative predictive value up to 99.5 % to rule out AMI . Copeptin was a strong and independent predictor of 1-year mortality ( HR 4.18–4.63 ) . Irrespective of cTn levels , patients with low levels of copeptin had an excellent prognosis compared with patients with raised levels of both copeptin and cTn ( 360-day mortality 2.8–3.6 % vs 23.1–33.8 % , p<0.001 ) . Conclusion In patients with pre-existing CAD , copeptin significantly improves the diagnostic accuracy if used in addition to cTnT , but only trended to superiority compared with hs-cTnT alone . Copeptin provides independent prognostic information , largely by overcoming the challenging interpretation of mild increases in hs-cTnT. Clinical trial registration number Clinical Trials Gov number NCT00470587 |
13,058 | 30,516,874 | Patient reported experiences included trusted and supportive care providers , safe and trusted services , easily accessible care , and positive psychological and behavioural changes . | Several community-based models for treating hepatitis C virus ( HCV ) infection have been implemented to improve treatment accessibility and health outcomes .
However , there is a lack of knowledge regarding how well these models achieve the desired goals . | Background Direct-acting antiviral ( DAA ) therapy for hepatitis C virus ( HCV ) infection has result ed in high rates of disease cure ; however , not enough specialists currently are available to provide care . Objective To determine the efficacy of HCV treatment independently provided by nurse practitioners ( NPs ) , primary care physicians ( PCPs ) , or specialist physicians using DAA therapy . Design Nonr and omized , open-label clinical trial initiated in 2015 . ( Clinical Trials.gov : NCT02339038 ) . Setting 13 urban , federally qualified health centers ( FQHCs ) in the District of Columbia . Patients A referred sample of 600 patients , of whom 96 % were black , 69 % were male , 82 % were treatment naive , and 20 % had cirrhosis . Seventy-two percent of the patients had HCV genotype 1a infection . The baseline characteristics of patients seen by each provider type were similar . Intervention Patients were assigned in a nonr and omized but specified manner to receive treatment from 1 of 5 NPs , 5 PCPs , or 6 specialists . All providers underwent an identical 3-hour training session based on guidelines . Patients received treatment with ledipasvir-sofosbuvir , which was provided on site , according to U.S. Food and Drug Administration labeling requirements . Measurements Sustained virologic response ( SVR ) . Results 516 patients achieved SVR , a response rate of 86 % ( 95 % CI , 83.0 % to 88.7 % ) , with no major safety signals . Response rates were consistent across the 3 provider types : NPs , 89.3 % ( CI , 83.3 % to 93.8 % ) ; PCPs , 86.9 % ( CI , 80.6 % to 91.7 % ) ; and specialists , 83.8 % ( CI , 79.0 % to 87.8 % ) . Patient loss to follow-up was the major cause of non-SVR . Limitation Nonr and omized patient distribution ; possible referral bias . Conclusion In a real-world cohort of patients at urban FQHCs , HCV treatment administered by nonspecialist providers was as safe and effective as that provided by specialists . Nurse practitioners and PCPs with compact didactic training could substantially exp and the availability of community-based providers to escalate HCV therapy , bridging existing gaps in the continuum of care for patients with HCV infection . Primary Funding Source National Institutes of Health and Gilead Sciences AIMS To estimate adherence and response to therapy for chronic hepatitis C virus ( HCV ) infection among people with a history of injecting drug use . A secondary aim was to identify predictors of HCV treatment response . DESIGN Prospect i ve cohort recruited between 2009 and 2012 . Participants were treated with peg-interferon alfa-2a/ribavirin for 24 ( genotypes 2/3 , G2/3 ) or 48 weeks ( genotype 1 , G1 ) . SETTING Six opioid substitution treatment ( OST ) clinics , two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales , Australia . PARTICIPANTS Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse , 101 were assessed for treatment outcomes ( 21 % female ) . MEASUREMENTS Study outcomes were treatment adherence and sustained virological response ( SVR , undetectable HCV RNA > 24 weeks post-treatment ) . FINDINGS Among 101 treated , 37 % ( n = 37 ) had recently injected drugs ( past 6 months ) and 62 % ( n = 63 ) were receiving OST . Adherence ≥ 80 % was 86 % ( n = 87 ) . SVR was 74 % ( 75 of 101 ) , with no difference observed by sex ( males : 76 % , females : 67 % , P = 0.662 ) . In adjusted analysis , age < 35 ( versus ≥ 45 years ) [ adjusted odds ratio ( aOR ) = 5.06 , 95 % confidence interval ( CI ) = 1.47 , 17.40 ] and on-treatment adherence ≥ 80 % independently predicted SVR ( aOR = 19.41 , 95 % CI = 3.61 , 104.26 ] . Recent injecting drug use at baseline was not associated with SVR . CONCLUSIONS People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other population s , despite injecting drugs at baseline . Younger age and adherence are predictive of improved response to hepatitis C virus therapy BACKGROUND Among people who inject drugs ( PWID ) , the prevalence of hepatitis C virus ( HCV ) infection is high ; however HCV treatment uptake remains low . New models of care are needed to address the growing burden of HCV-related disease in PWID and to underst and the barriers to assessment and treatment of HCV . This study evaluated assessment and treatment for HCV infection among PWID attending an opioid substitution treatment ( OST ) clinic with an integrated peer support worker model . METHODS Clients with a history of IDU and chronic HCV infection , attending the Newcastle Pharmacotherapy Service , Newcastle Australia , were recruited as part of a multisite prospect i ve observational study ( the ETHOS Cohort ) . Additional chart review was conducted for clients not enrolled in the ETHOS Cohort . A peer support worker was introduced to complement and extend services offered by the clinical team . Client contacts and assessment s with a nurse and /or peer worker were evaluated , including those who commenced HCV treatment . RESULTS A total of 1447 clients attended the OST service during February 2009 and June 2014 . Of these , 378 ( 26 % ) were assessed by a nurse and 242 ( 17 % ) by a clinician . HCV treatment was commenced by 20 ( 5 % ) participants and 15 ( 75 % ) achieved a sustained virological response ( SVR ) . During May 2009 and July 2011 , 332 nurse contacts and 726 peer worker contacts were evaluated . The nurse-led contacts were related to HCV treatment ( 50 % ) and review of pathology tests ( 34 % ) , whereas peer worker contacts included discussion about HCV treatment ( 75 % ) , education , counselling and /or support ( 53 % ) and general discussion about HCV infection ( 59 % ) . CONCLUSION These data demonstrate that peer support workers facilitate broader discussion about HCV treatment , education and /or support , allowing nurses to focus on HCV-related assessment and treatment . HCV treatment uptake was very low in this cohort , but SVR was high . The integration of peer support workers in treatment programs within OST clinics may address barriers to HCV care , but further studies are needed to assess their impact on assessment and treatment outcomes Background : Hepatitis C virus ( HCV ) is a prevalent chronic blood-borne infection among opioid-dependent patients on methadone maintenance treatment ( MMT ) . Despite case reports and case – control studies , a r and omized controlled trial ( RCT ) examining HCV treatment adherence in methadone-maintained patients is lacking and was the impetus for this ongoing RCT examining modified directly administered therapy for HCV treatment integrated within a MMT . Methods : Subjects were r and omized 1:1 to receive HCV treatment as modified directly observed therapy ( mDOT ) into the MMT program or at a liver specialty clinic as self-administered therapy ( SAT ) . R and omization was stratified based on HIV status and HCV genotype . Results : Twenty-one subjects to date have enrolled in this pilot study . The mDOT subjects have had greater success in starting treatment and 10 of the 12 mDOT subjects achieved early virologic response ( EVR ) at week 12 and 6 of those 10 achieved sustained virologic response ( SVR ) . Of the nine SAT subjects , only three achieved EVR at week 12 and only one achieved SVR despite not completing the treatment . Conclusions : Hepatitis C treatment can be successfully integrated into a methadone maintenance clinic , and mDOT can be implemented with a methadone clinic ’s existing nursing and medical staff . Patients struggling with concurrent substance use and mental illness comorbidity may be successfully addressed in such setting s and facilitate access to and completion of treatment through the utilization of on-site clinical services for HCV treatment and adherence support with mDOT . The exact importance of site of services and adherence support remains a significant area for future investigation The aim of the present prospect i ve observational study was to assess uptake and success of hepatitis C virus ( HCV ) treatment among a group of former and current injection drug users with chronic HCV infection at the Street Health Centre in Kingston , Ontario . The Street Health Centre offers hepatitis C education , assessment and treatment within a multidisciplinary , integrated and collaborative treatment model of care delivered by primary care professionals . The study enrolled a convenience sample of 34 patients . Seventy per cent of study patients had no post secondary education , 85 % were unemployed and one-third were unstably housed . A majority of study patients self-reported mental health problems . Of the 14 patients who initiated antiviral treatment in the study period , eight ( 57 % ) achieved sustained virological response . Regardless of virological outcome , patients who initiated treatment showed positive trends toward increased social and psychiatric stability , and decreases in high-risk behaviours . These results suggest that not only is successful treatment of chronic HCV infection in current and former injection drug users with concurrent psychiatric disorders possible , but the benefits of such treatment delivered in a community-based , multidisciplinary , primary care model may extend beyond narrowly defined virological outcomes BACKGROUND Access to hepatitis C virus ( HCV ) treatment remains extremely limited among people who inject drugs ( PWID ) . HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection . METHODS Enhancing Treatment for Hepatitis C in Opioid Substitution Setting s ( ETHOS ) was a prospect i ve observational cohort . Recruitment was through 5 opioid substitution treatment ( OST ) clinics , 2 community health centers , and 1 Aboriginal community controlled health organization in New South Wales , Australia . RESULTS Among 387 enrolled participants , mean age was 41 years , 71 % were male , and 15 % were of Aboriginal ethnicity . Specialist assessment was undertaken in 191 ( 49 % ) participants , and 84 ( 22 % ) commenced interferon-based treatment . In adjusted analysis , HCV specialist assessment was associated with non-Aboriginal ethnicity ( adjusted odds ratio [ AOR ] , 4.02 ; 95 % confidence interval [ CI ] , 2.05 - 7.90 ) , no recent benzodiazepine use ( AOR , 2.06 ; 95 % CI , 1.31 - 3.24 ) , and non-1 HCV genotype ( AOR , 2.13 ; 95 % CI , 1.32 - 3.43 ) . In adjusted analysis , HCV treatment was associated with non-Aboriginal ethnicity ( AOR , 4.59 ; 95 % CI , 1.49 - 14.12 ) , living with the support of family and /or friends ( AOR , 2.15 ; 95 % CI , 1.25 - 3.71 ) , never receiving OST ( AOR , 4.40 ; 95 % CI , 2.27 - 8.54 ) , no recent methamphetamine use ( AOR , 2.26 ; 95 % CI , 1.12 - 4.57 ) , and non-1 HCV genotype ( AOR , 3.07 ; 95 % CI , 1.67 - 5.64 ) . CONCLUSIONS HCV treatment uptake was relatively high among this highly marginalized population of PWID . Potentially modifiable factors associated with treatment include drug use and social support BACKGROUND An estimated 250,000 Canadians are infected with the hepatitis C virus ( HCV ) . The present study describes a cohort of individuals with HCV referred to community-based , integrated prevention and care projects developed in British Columbia . Treatment outcomes are reported for a subset of individuals undergoing antiviral therapy at four project sites . METHODS Four demonstration projects based on a public health nurse and physician partnership were established in rural and small urban centres in British Columbia . Comprehensive medical assessment s determined whether individuals received treatment , or counselling and education . Outcomes of the treatment group were compared with published r and omized controlled trials . Client demographics were mapped using geographical information systems applications . RESULTS A total of 1795 individuals were referred to the clinics for medical assessment between September 2001 and December 2005 . After assessment , 26 % were eligible for therapy , while 74 % received counselling and education . Wait times decreased annually , with one-half of all referrals assessed within 30 days . Combination antiviral therapy was initiated in 363 clients with interferon plus ribavirin ( n=36 ) or pegylated interferon plus ribavirin ( n=327 ) . Treatment outcomes were available for 205 individuals . The overall rate of sustained virological response was 61 % ( 126 of 205 individuals ) . The number of individuals assessed at each site represented , on average , 20 % of the total cumulative reported HCV cases in the catchment areas . DISCUSSION The study findings illustrate how a public health nurse and physician partnership can service a population with complex medical needs while simultaneously increasing local capacity . Treatment outcomes were comparable with published clinical trials Background : Individuals with psychiatric disease , substance abuse , and /or housing instability have a high prevalence of chronic hepatitis C virus ( HCV ) infection . However , such individuals are often excluded from treatment for HCV infection because of a perceived inability to adhere to the rigorous medication regimen required . Methods : A pilot program using a multidisciplinary group medical visit model to treat HCV infection in the aforementioned population was created . Medication adherence and virologic response rates were prospect ively followed . Results : Approximately 80 % of patients were adherent to their HCV infection treatment regimen , as measured by attendance at group medical visits and by medication adherence . A sustained virologic response rate of 55 % among individuals with genotype 1 infection and 80 % among individuals with genotype 2 or 3 infections was observed . These results compare favorably with those seen in large , r and omized controlled trials . Rates of discontinuation and adverse effects were similar to those seen in other studies . Conclusions : An intensive , multidisciplinary treatment approach toward HCV infection treatment can achieve favorable results even in persons traditionally considered to be “ poor treatment c and i date s. ” Programs aim ed at bringing HCV infection treatment to this population are needed Objectives Injection drug users are often denied hepatitis C ( HCV ) treatment due to concerns about adherence , despite limited data about the impact of such common issues as psychiatric illness and intercurrent drug use . We sought to define the impact of these and other potential adherence barriers in a real-world sample of recovering drug users . Methods We conducted a prospect i ve observational study of 71 methadone-maintained patients who received interferon and ribavirin combination therapy in a community-based clinic with expertise in treating addictive disorders . Adherence measures were conducted with monthly interview , medication counts , and urine toxicology testing . Results Overall , 48 ( 68 % ) were adherent , and adherent patients were significantly more likely to achieve a sustained virologic response ( 42 vs. 4 % in nonadherent patients ) . Patients with and without a prior psychiatric history were similarly adherent ( 64 vs. 72 % , respectively , P>0.5 ) , and the initiation of new psychiatric medications during HCV treatment was associated with improved adherence overall ( P=0.02 ) and in patients that did not report a preexisting psychiatric diagnosis ( P=0.04 ) . Trend towards reduced adherence in patients without a period of abstinence was seen before initiating HCV treatment , 46 vs. 72 % of those who had been abstinent for at least 1 month ( P=0.10 ) . Although occasional drug users were similarly adherent to those who were completely abstinent , patients who relapsed to regular drug use showed a significantly lower level of adherence ( P=0.03 ) . Conclusions We conclude that the majority of methadone-maintained drug users can adhere to HCV treatment , even those with psychiatric illness and relatively limited pretreatment drug abstinence . Lack of pre-HCV treatment drug abstinence and regular drug use during HCV treatment may be relative barriers to medication adherence , but the initiation of psychiatric medications during HCV treatment may be a helpful intervention . This report provides further evidence for an individualized approach to HCV treatment that does not categorically exclude patients with potential barriers such as mental illness and limited drug abstinence BACKGROUND AND AIM There are few studies investigating the treatment of hepatitis C virus ( HCV ) infection in current and former drug users . With this in mind , we sought to evaluate the antiviral efficacy of interferon alpha-2b ( IFN alpha-2b ) or pegylated-interferon alpha-2b ( PEG-IFN alpha-2b ) and ribavirin ( RBV ) in injection drug users ( IDU ) enrolled in a directly observed therapy ( DOT ) program , as measured by sustained virologic response ( SVR ) . METHODS Viremic HCV-infected IDU , with alanine aminotransferase ( ALT ) > 1.5x upper limit of normal ( ULN ) were offered 24 - 48 week ( based on HCV genotype ) therapy with RBV ( 800 - 1200 mg/day , based on weight ) along with IFN alpha-2b ( 3 million IU thrice weekly ) replaced by PEG-IFN alpha-2b ( 1.5 ìg/kg once weekly ) as it became available . All injections were directly observed . The primary endpoint was SVR . RESULTS Overall , 40 patients ( 33 males ) received IFN alpha-2b ( 12 ) or PEG-IFN alpha-2b ( 28 ) , 55 % with HCV genotypes 2 or 3 . Only 14 discontinued therapy , 5 due to toxicity , 6 due to illicit drug use and 3 did not achieve an early virologic response . In an intent-to-treat analysis , the overall SVR was 55 % ( 22/40 ) , 64 % ( 14/22 ) in subjects with genotypes 2/3 . There was no significant difference in response rates among those with > 6 ( 50 % ) or < or=6 months ( 64 % ) drug abstinence ( P = 0.51 ) or among those with ( 53 % ) and without ( 57 % ) intercurrent drug use ( P = 0.99 ) ; however , frequent users ( n = 9 ) had a decreased SVR ( 22 % ) when compared with occasional users ( n = 10 , 80 % , P = 0.12 ) . CONCLUSION Treatment of HCV in current and former IDU within a multidisciplinary DOT program can be successfully undertaken , result ing in SVR similar to those in r and omized controlled trials Background Injecting drug use is the main risk factor for hepatitis C virus ( HCV ) infection . Secondary ‐care‐based strategies for the management of HCV do not effectively target this vulnerable population Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus ( HCV ) infection . However , very few injection drug users ( IDUs ) have received treatment for this condition given issues of medical or psychiatric co-morbidity , ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy , including regular medical follow-up . With this in mind , we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy . Utilizing the existing infrastructure for the management of addictive disease , we have developed a model of " one-stop shopping " whereby the treatment of addiction , HCV and other medical conditions are fully integrated , with the collaboration of nurses , counsellors , addiction specialists , infectious disease specialists , primary care physicians and research ers . Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment . Patients received therapy with pegylated interferon-alpha2a or -alpha2b , both in combination with ribavirin . All injections were directly observed . Overall , we observed a high uptake of HCV treatment among attendees , with 51 percent either receiving or about to receive therapy . To date , 18 patients have initiated treatment for HCV infection and 12 have completed therapy . Overall , 8/12 ( 67 percent ) subjects achieved an end of treatment response ( genotype 1 , 67 percent ; genotypes 2/3 , 67 percent ) , despite ongoing drug use in 75 percent of patients during treatment . These data demonstrate that with the appropriate programs in place , a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group . Moreover , the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken , result ing in ETRs similar to those reported in r and omized controlled trials The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear . Patients attending a community‐based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy . The first 50 patients to commence HCV therapy and complete at least 6 months follow‐up were prospect ively studied . ETR response ( HCV PCR negative ) was 34/50 ( 68 % ) and SVR 6 months post‐treatment was 31/50 ( 62 % ) . Viral eradication was maintained in those 22 patients that have had 12 months or more post‐treatment follow‐up . Eleven ( 22 % ) patients stopped therapy early due to side effects or poor compliance . Only two patients with an ETR likely reinfected due to unsafe injection practice s. One was re‐treated and achieved an SVR . Of the patients achieving a 6‐month SVR , 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation . 46 % of patients received antidepressant and /or antipsychotic medication during treatment . Conclusion : This study of HCV treatment in a community‐based subcutaneous naltrexone implant clinic found antiviral therapy result ed in a 62 % SVR . This result is comparable to that reported in hospital‐based clinics in non‐IDU patients . The side effect profile and compliance was also similar . HCV antiviral therapy should be offered to this large and currently under treated group . ( HEPATOLOGY 2007;45:111–117 . BACKGROUND Direct acting antiviral ( DAA ) treatments for Hepatitis C ( HCV ) are now widely available with sustained virologic response ( SVR ) rates of > 90 % . A major predictor of response to DAAs is adherence , yet few real-world studies evaluating adherence among marginalized people who use drugs and /or alcohol exist . This study evaluates patterns and factors associated with non-adherence among marginalized people with a history of drug use who were receiving care through a primary care , community-based HCV treatment program where opiate substitution is not offered on-site . METHODS Prospect i ve evaluation of chronic HCV patients initiating DAA treatment . Self-report medication adherence question naires were completed weekly . Pre/post treatment question naires examined socio-demographics , program engagement and substance use . Missing adherence data was counted as a missed dose . RESULTS Of the 74 participants , who initiated treatment , 76 % were male , the average age was 54 years , 69 % reported income from disability benefits , 30 % did not have stable housing and only 24 % received opiate substitution therapy . Substance use was common in the month prior to treatment initiation with , 11 % reported injection drug use , 30 % reported non-injection drug use and 18 % moderate to heavy alcohol use . The majority ( 85 % ) were treatment naïve , with 76 % receiving sofosbuvir/ledipasvir ( 8 - 24 weeks ) and 22 % Sofosbuvir/Ribarvin ( 12 - 24 weeks ) . The intention to treat proportion with SVR12 was 87 % ( 60/69 ) . In a modified ITT analysis ( excluding those with undetectable RNA at end of treatment ) , 91 % ( 60/66 ) achieved SVR12 . Overall , 89 % of treatment weeks had no missed doses . 41 % of participants had at least one missed dose . In multivariate analysis the only factor independently associated with weeks with missed doses was moderate to heavy alcohol use ( p=0.05 ) . CONCLUSION This study demonstrates that strong adherence and SVR with DAAs is achievable , with appropriate supports , even in the context of substance use , and complex health/social issues BACKGROUND The Extension for Community Healthcare Outcomes ( ECHO ) model was developed to improve access to care for underserved population s with complex health problems such as hepatitis C virus ( HCV ) infection . With the use of video-conferencing technology , the ECHO program trains primary care providers to treat complex diseases . METHODS We conducted a prospect i ve cohort study comparing treatment for HCV infection at the University of New Mexico ( UNM ) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico . A total of 407 patients with chronic HCV infection who had received no previous treatment for the infection were enrolled . The primary end point was a sustained virologic response . RESULTS A total of 57.5 % of the patients treated at the UNM HCV clinic ( 84 of 146 patients ) and 58.2 % of those treated at ECHO sites ( 152 of 261 patients ) had a sustained viral response ( difference in rates between sites , 0.7 percentage points ; 95 % confidence interval , -9.2 to 10.7 ; P=0.89 ) . Among patients with HCV genotype 1 infection , the rate of sustained viral response was 45.8 % ( 38 of 83 patients ) at the UNM HCV clinic and 49.7 % ( 73 of 147 patients ) at ECHO sites ( P=0.57 ) . Serious adverse events occurred in 13.7 % of the patients at the UNM HCV clinic and in 6.9 % of the patients at ECHO sites . CONCLUSIONS The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities . Implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat . ( Funded by the Agency for Healthcare Research and Quality and others . ) Although injection drug users represent the majority of incident and prevalent cases of hepatitis C , most lack access to treatment because of concerns about adherence , treatment efficacy , and reinfection . On the basis of an increasing body of evidence suggesting that injection drug users can successfully undergo treatment for hepatitis C virus ( HCV ) infection , the 2002 National Institutes of Health Consensus Statement on Hepatitis C has recommended that substance users , even those with ongoing drug use , be considered for treatment for HCV infection on a case-by-case basis . However , the criteria on which these treatment decisions should be based are unclear : The duration of pretreatment drug abstinence , comorbid psychiatric illness , intercurrent drug use , and the potential for injected interferon to cause relapse of drug use may all influence results of treatment for HCV infection . This overview summarizes my group 's current data about treatment for HCV infection in substance users and the effect of these potential barriers on outcomes of treatment Background Chronic hepatitis C is common in people who inject drugs ( PWID ) and this population serves as a reservoir for infection . Treatment levels are low among this group , ranging from 1 to 19 % . We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies . Methods This was a cluster r and omized trial of nurse-initiated versus physician-initiated antiviral therapy with pegylated interferon and ribavirin for hepatitis C virus in community clinics ( trial registration : IS RCT N07774040 ) . Results The proportion of participants initiating treatment during follow-up was 10 % with nurse-initiated ( 6/62 ) and 9 % with physician-initiated ( 6/76 ) therapy . Adherence was similar in both groups , with only one patient in each arm not adhering to therapy . There were no serious adverse events , but interferon-related side effects were common . Drug and alcohol use did not change during therapy . Conclusion Despite easy access to antiviral therapy , uptake of treatment was poor , with no significant difference between the groups . Nurse-led initiation of interferon-based antiviral therapy in PWID did not lead to increased uptake of , response to or adherence with treatment . Further service improvement is unlikely to increase the proportion of PWID undergoing antiviral therapy for hepatitis C virus and early adoption of interferon-free regimens may increase the proportion initiating and completing treatment BACKGROUND Though direct acting antivirals ( DAAs ) promise high cure rates , many providers and payers remain concerned about successful treatment for people who use drugs ( PWUD ) , even among those engaged in opioid agonist treatment ( OAT ) . The efficacy of DAAs among PWUD in real-world setting s is unclear . METHODS We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 ( n=89 ) at a primary care clinic in the Bronx , NY . Onsite HCV treatment with DAAs was performed by an HCV specialist , with support from a care coordinator funded by the NYC Department of Health . We identified four categories of drug use and drug treatment : ( 1 ) no active drug use/not receiving OAT ( defined as non-PWUD ) ; ( 2 ) no active drug use/receiving OAT ; ( 3 ) active drug use/not receiving OAT ; and ( 4 ) active drug use/receiving OAT . The primary outcome was SVR at 12 weeks post-treatment . RESULTS Overall SVR rates were 95 % ( n=41/43 ) for non-PWUD and 96 % ( n=44/46 ) for patients actively using drugs and /or receiving OAT [ p=0.95 ] . There were no differences in SVR rates by drug use or drug treatment category . Compared to non-PWUD , those with no active drug use/receiving OAT had 100 % SVR ( n=15/15 ; p=1.0 ) , those actively using drugs/not receiving OAT had 90 % SVR ( n=9/10 ; p=0.47 ) , and those actively using drugs/receiving OAT had 95 % SVR ( 20/21 ; p=1.0 ) . CONCLUSION Regardless of active drug use or OAT , patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates . We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and /or receiving OAT |
13,059 | 22,419,287 | The trials did not show that progesterone is an effective treatment for PMS nor that it is not .
Neither trial distinguished a subgroup of women who benefited , nor examined cl aim ed success with high doses | BACKGROUND About 5 % of women experience severe symptoms called premenstrual syndrome ( PMS ) , only in the two weeks before their menstrual periods .
Treatment with progesterone may restore a deficiency , balance menstrual hormone levels or reduce effects of falling progesterone levels on the brain or on electrolytes in the blood .
OBJECTIVES The objectives were to determine if progesterone has been found to be an effective treatment for all or some premenstrual symptoms and if adverse events associated with this treatment have been reported . | Purpose To further investigate the efficacy of progesterone in the treatment of the symptoms of premenstrual syndrome ( PMS ) . Material s and Methods From an initial cohort of 25 subjects diagnosed with moderate to severe PMS , 17 reproductive age females completed the 7-month , doubleblind , placebo controlled trial using 200-mg vaginal progestone suppositories . Multiple modalities for evaluating symptoms were employed , including the Spielberger self-evaluation rating , the Beck depression inventory , and the Hamilton anxiety scale . In addition , each subject was interviewed by a psychiatrist on a monthly basis ; ovulation was determined monthly using a basal body temperature chart ; serum hormonal assays included beta endorphin , progesterone , follicle stimulating hormone , luteinizing hormone , estradiol , and prolactin . Results Hormonal assays confirmed no differences between treatment and control groups . Overall scores on all test vehicles were likewise not significantly different between the two groups ; however , in the subcategory of nervous symptoms , a significant improvement was found in symptoms relating to tension , mood swings , irritability , anxiety and lack of control . Conclusions Metabolites of progesterone ( pregnanolone and allopregnanolone ) may play a physiologic role as anxiolytic agents , perhaps modifying mood and anxiety ; the current study confirms the utility of twice daily , 200-mg progesterone vaginal suppositories , in the alleviation of some PMS symptoms relating to anxiety and irritability . Further evaluation may be warranted to ascertain which patients in the known heterogeneous PMS population may be most likely to benefit from such treatment Background Given an observed test statistic and its degrees of freedom , one may compute the observed P value with most statistical packages . It is unknown to what extent test statistics and P values are congruent in published medical papers . Methods We checked the congruence of statistical results reported in all the papers of volumes 409–412 of Nature ( 2001 ) and a r and om sample of 63 results from volumes 322–323 of BMJ ( 2001 ) . We also tested whether the frequencies of the last digit of a sample of 610 test statistics deviated from a uniform distribution ( i.e. , equally probable digits ) . Results 11.6 % ( 21 of 181 ) and 11.1 % ( 7 of 63 ) of the statistical results published in Nature and BMJ respectively during 2001 were incongruent , probably mostly due to rounding , transcription , or type- setting errors . At least one such error appeared in 38 % and 25 % of the papers of Nature and BMJ , respectively . In 12 % of the cases , the significance level might change one or more orders of magnitude . The frequencies of the last digit of statistics deviated from the uniform distribution and suggested digit preference in rounding and reporting . Conclusions This incongruence of test statistics and P values is another example that statistical practice is generally poor , even in the most renowned scientific journals , and that quality of papers should be more controlled and valued CONTEXT Over the years , different hypotheses involving the ovarian steroid hormones have been proposed to explain the luteal phase occurrence of severe premenstrual syndrome symptoms . Although it had been strongly suspected that differences in the concentrations of the ovarian steroids may underlie the mood and psychological imbalance of this disorder , the evidence for this hypothesis has been inconsistent and remains controversial . OBJECTIVE Our objective was to measure the ovarian steroid hormones across the menstrual cycle in women with and without luteal phase symptoms consistent with premenstrual dysphoric disorder ( PMDD ) . DESIGN We measured estradiol ( E2 ) , progesterone , and SHBG in women with and without PMDD using a cross-sectional and prospect i ve experimental design . Participating women underwent 2-month self- assessment symptom screening and 1-month hormonal evaluation . RESULTS Overall means for LH , progesterone , E2 , peak E2 , and free E2 were not different between groups . Across the menstrual cycle , overall percent free E2 was significantly lower and SHBG significantly greater in the PMDD group compared with controls ( 1.39 + /- 0.26 vs. 1.50 + /- 0.28 , P = 0.03 ; 61.4 + /- 25.1 vs. 52.4 + /- 21.3 nmol/liter , P = 0.046 , respectively ) . During the luteal phase , free E2 was significantly lower in the PMDD group compared with controls ( PMDD 7.6 + /- 7.0 vs. controls 8.9 + /- 8.4 pmol/liter ; P = 0.032 ) . For both follicular and luteal phases , SHBG was significantly higher in the PMDD group ( follicular phase 60.5 + /- 31.7 vs. 51.4 + /- 38.2 nmol/liter , P = 0.047 ; luteal phase 65.1 + /- 32.3 vs. 55.1 + /- 38.9 nmol/liter , P = 0.03 ) . In both groups , SHBG significantly increased from the follicular to luteal phase . CONCLUSION Luteal phase concentrations of free E2 , percent free E2 , and SHBG differ significantly between women with and without PMDD The present study extends a previous report of lower plasma ACTH levels in women with premenstrual syndrome ( PMS ) compared with asymptomatic controls . Plasma levels of estradiol and progesterone were measured daily in 10 women with confirmed PMS and 8 asymptomatic women . Daily symptom reports were maintained during the same menstrual cycle . Both estradiol and progesterone levels were consistently , but not significantly , higher throughout the cycle in PMS subjects compared with controls . From the follicular to the early luteal phase , estradiol levels were significantly higher in a previously defined PMS subgroup 2 with more severe symptoms throughout the cycle compared with both the less severe PMS subgroup 1 and controls . Progesterone levels were significantly and positively correlated with PMS symptoms along the entire menstrual cycle , preceding the symptoms by 5 - 7 days . These preliminary results provide support for the hypothesis that the presence of progesterone at early luteal phase levels is required for PMS symptoms to occur A covert method of assessing perception of health in relation to menstruation was applied prospect ively to a group of women aged 20 to 40 years . Of the 1386 r and omly selected women contacted , 838 ( 60 % ) provided information for the full study period of six weeks and 608 of these respondents menstruated during that time . A clear excess of women demonstrated premenstrual deterioration in perceived health . This rose to a peak at the onset of menstruation and subsided rapidly during menstruation , thus reflecting the conventionally defined pattern of the premenstrual syndrome . When , on completion of prospect i ve recording , the same women were asked to return an overt and retrospective assessment of paramenstrual symptoms , the overall pattern of results was similar but , for individual women , there was little correspondence between similar data obtained by the two different methods A double blind , r and omised , crossover trial of oral micronised progesterone ( two months ) and placebo ( two months ) was conducted to determine whether progesterone alleviated premenstrual complaints . Twenty three women were interviewed premenstrually before treatment and in each month of treatment . They completed Moos 's menstrual distress question naire , Beck et al 's depression inventory , Spielberger et al 's state anxiety inventory , the mood adjective checklist , and a daily symptom record . Analyses of data found an overall beneficial effect of being treated for all variables except restlessness , positive moods , and interest in sex . Maximum improvement occurred in the first month of treatment with progesterone . Nevertheless , an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment . Further studies are needed to determine the optimum duration of treatment OBJECTIVES To explore the possible role of natriuretic peptides and vasopressin in luteal phase fluid retention in premenstrual syndrome ( PMS ) and to determine the effect of progesterone therapy on these hormones . DESIGN Self-controlled prospect i ve study . SETTING University-based medical research centre . PATIENTS Six patients with PMS were studied during the symptomatic luteal and asymptomatic follicular phases . The follicular phase response was used as the control for each subject . INTERVENTIONS An intravenous infusion of 3 % saline solution was administered on an early follicular and a late luteal phase day in 2 menstrual cycles . Progesterone was administered orally during the second luteal phase . OUTCOME MEASURES Osmolality , arginine vasopressin ( AVP ) , atrial natriuretic factor ( ANF ) , and brain natriuretic peptide ( BNP ) levels in plasma , osmolality , sodium , potassium , cyclic adenosine monophosphate ( cAMP ) and cyclic guanosine 5'-phosphate ( cGMP ) concentrations in urine , and thirst sensation . RESULTS Mean basal plasma ANF and osmolality levels and the threshold for AVP release and thirst were lower , and mean urinary cyclic nucleotide levels and AVP sensitivity ( amount of AVP secreted per unit rise in plasma osmolality ) were higher , in the luteal phase than in the follicular phase . With saline loading , there was an increase in plasma osmolality , AVP and ANF and in urinary sodium and cyclic nucleotide levels . Plasma ANF and osmolality levels remained lower in the luteal phase compared with the follicular phase , but AVP levels at the end of the saline infusion were higher in the luteal phase than in the follicular phase . Progesterone therapy caused an increase in plasma ANF and osmolality levels and the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic nucleotide levels . BNP levels did not change with phase or treatment . The differences in AVP threshold with phase and treatment were statistically significant ( p < 0.001 ) . There was a significant phase effect for plasma ANF ( p = 0.02 ) and a significant or near-significant interaction effect of phase and treatment for plasma ANF ( p = 0.06 ) and urinary cAMP ( p = 0.047 ) and cGMP ( p = 0.066 ) . The effect of phase and treatment was not significant for the other measurements . CONCLUSIONS Luteal phase fluid retention may be due to a relative deficiency of ANF and a lower threshold for AVP release . The symptomatic improvement produced by progesterone treatment may be due to its stimulation of ANF and inhibition of AVP release or synthesis BACKGROUND A variety of definitions have been applied to premenstrual syndrome . The severity of the syndrome is also variable . AIM A study was undertaken to compare progesterone pessaries with placebo in the relief of symptoms of premenstrual syndrome . In this study the condition was characterized by a wide range of symptoms recurring in the late luteal phase but absent in the follicular phase ( that is , the specific definition published by Dalton in 1953 ) . METHOD A multicentre , prospect i ve , double-blind , r and omized , parallel group study was undertaken by 45 general practitioners . Patients were deemed eligible after two prospect i ve menstrual cycles of observation ( selection phase ) in which a precise definition of symptoms was applied . Patients were r and omized to use either progesterone pessaries ( 400 mg twice a day ) or matching placebo , by vaginal or rectal administration , from 14 days before the expected onset of menstruation until the onset of vaginal bleeding , for four consecutive cycles . Baseline data for the outcome variables were determined in the selection phase . The main outcome variables were changes in the severity ( categorized as none , mild , moderate or severe ) of each patient 's most severe symptom , and in the average score of all the patient 's symptoms characteristic of premenstrual syndrome . Spontaneous reports of adverse events were recorded . RESULTS A total of 281 patients were screened for premenstrual syndrome ; of these , 141 patients were r and omized to treatment or placebo groups . Efficacy was evaluated in 93 patients . Reductions in the scores of the highest scoring , most severe , symptoms and in the average symptom score , were consistently observed in patients receiving progesterone pessaries and in those receiving placebo . The response to progesterone was greater than to placebo during each cycle ; the differences were clinical ly and statistically significant . Adverse events were reported by 51 % of patients in the progesterone treatment group and by 43 % in the placebo group . Irregularity of menstruation , vaginal pruritus and headache were reported more frequently by patients taking active therapy . CONCLUSION In this study , progesterone , given as pessaries by vaginal or rectal administration , was more effective than placebo in the relief of symptoms of premenstrual syndrome in a population of patients selected by strict entry criteria Plasma levels of prolactin , FSH , LH , progesterone and 17–β‐oestradiol in twenty women with premenstrual tension were compared with those in twenty controls . The former group was studied also during treatment with bromocriptine . The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase ( P < 0.±01 ) , but there was no difference between the PMT and control group in the luteal phase . No differences were found between the controls and the PMT group in FSH , LH , 17–β‐oestradiol and progesterone levels in the luteal phase . Bromocriptine suppressed prolactin concentrations ( P < 0.±01 ) , but had no effect on the FSH , LH , 17‐B‐oestradiol or progesterone levels Fifteen women with moderate to severe premenstrual symptoms , defined and grade d according to a recently developed scoring system , took part in a double blind study of the effect of progesterone on premenstrual symptoms . The dosage was 100 mg progesterone twice daily delivered in vaginal pessaries . The women were improved with a statistically significant decrease in their scores by progesterone as well as by placebo treatment . There was no statistically significant difference between the two regimes OBJECTIVE Patients from a r and omized , double-blind , placebo-controlled study of progesterone suppository treatment for premenstrual syndrome ( PMS ) were followed up to determine post study PMS symptom levels and medication use . METHOD An average of 1 year after the end of the treatment study , 129 subjects were contacted for telephone interviews . All subjects met criteria for PMS before the progesterone suppository treatment , and their symptoms were confirmed by daily symptom reports throughout the study . The outcome measure at follow-up was the patient 's global assessment of symptom severity , which was also rated by the subjects during the treatment study . The ratings at enrollment , end of study , and follow-up were compared . RESULTS Only 27 % of the subjects ( N = 35 ) were taking medications for PMS at follow-up . Symptom severity at follow-up was less than at enrollment but greater than at the end of the study . CONCLUSIONS Some of the improvement gained during treatment was maintained , but overall the subjects remained moderately symptomatic . Validation of the PMS condition , education , and support and caring may account for the symptom decreases during treatment , and the end of treatment and withdrawal of these conditions may account for the moderate return of symptoms Previous studies have indicated that the addition of progestins during sequential hormonal replacement therapy ( HRT ) causes negative mood and physical symptoms . History of premenstrual syndrome , type of progestin , and dose of progestin have thus far been shown to influence the progestin-induced adverse mood symptoms during HRT . The aim of this study was to compare adverse mood effects of two different doses of estradiol , in combination with a progestin , during postmenopausal HRT . Twenty-eight perimenopausal women were included in this r and omized , double-blind , crossover study comparing 2- or 3-mg continuous estradiol , with an addition of 10 mg medroxyprogesterone acetate on d 17 - 28 during each treatment cycle . The main outcome measures were mood and physical symptoms kept on a daily rating scale . Together with the progestin , the higher dose of estrogen caused significantly more negative mood symptoms than the lower dose . Tension , irritability , and depressed mood were all significantly augmented during the progestin phase of cycles with 3 mg estradiol ( P < 0.001 ) . Physical symptoms also increased during the progestin phase of 3-mg estradiol cycles ( P < 0.001 ) , whereas positive mood symptoms were less affected . The only positive mood that changed with estrogen dose was friendliness , which decreased during the progestin phase of high estradiol cycles compared with cycles with lower estradiol ( P < 0.05 ) . Our conclusion is that an increase of the estrogen dose accentuates negative mood and physical symptoms during the progestin phase of sequential hormonal therapy OBJECTIVE This study characterizes the responses to placebo medication of patients with premenstrual syndrome ( PMS ) who were r and omly assigned in controlled treatment trials . Possible predictors of placebo response were also examined . METHOD Subjects from two r and omized controlled trials were pooled . The 101 subjects met defined criteria for severe PMS , remained eligible after 1 month of single-blind placebo lead-in treatment , and were r and omly assigned to 3 months of double-blind placebo treatment . Improvement in the current study was defined as a decrease of at least 50 % in premenstrual symptom score from the pretreatment baseline . RESULTS At endpoint , 20 ( 20 % ) of the placebo-treated subjects showed sustained improvement , 18 of these in at least 3 of the 4 months of placebo medication . Another 42 % of subjects partially improved , and 39 % were clearly unimproved throughout the study period . CONCLUSIONS Some patients with severe PMS experience significant and sustained improvement with placebo medication , but the majority report only partial or no improvement . Patients who sustain improvement for at least 2 consecutive months are likely to remain improved , indicating the importance of nondrug factors in clinical care OBJECTIVE To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome ( PMS ) compared with age-matched phase-matched controls . DESIGN Prospect i ve , repeated measures , two-group study . SETTING Human volunteers in an academic research environment . PARTICIPANTS Six women with rigorously defined prospect ively determined PMS ; six age-matched phase-matched controls . MAIN OUTCOME MEASURES Frequency , amplitude , concentration , and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase . RESULTS No significant between-group differences in frequency , amplitude , or concentration were found . In pooled data , significant coincident pulsing between LH and P was demonstrated . The length of time between LH and P pulses systematic ally increased across the luteal phase , a finding not previously reported . In the PMS group only , significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day . CONCLUSION A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum . Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation Some studies suggest that patients suffering from premenstrual syndrome ( PMS ) may be affected by an endogenous opioid dysfunction . Since opioids are the main modulators of the pulsatile LH secretion , we evaluated plasma LH pulsatility in 13 patients with PMS ( aged 33.1 yr ) and in six asymptomatic control volunteers ( aged 31.5 yr ) , in the late luteal phase ( -7 , -5 days before their next menses ) . The patients were prospect ively evaluated for two menstrual cycles with the Menstrual Distress Question naire ; the main symptoms which worsened during the premenstrual period were mood swings and water retention . The pulsatility of plasma LH secretion was studied by collecting blood sample s every 10 min for 12 hr , starting at 0800h . The presence of LH pulses was estimated using the program DETECT on the raw data . This program also allows the computation of the instantaneous secretory rate ( ISR ) . Ovulation was ascertained in all the controls and in nine PMS patients by means of urinary LH assay and luteal progesterone ( P ) determination . The remaining four patients did not ovulate . Both the ovulatory and the anovulatory PMS patients had an increased number of LH pulses/12 hr ( 10.3 + /- 2.4 and 11.5 + /- 4.4 , mean + /- SD , respectively ) in comparison with the controls ( 7.0 + /- 1.3 pulses , p less than 0.01 ) , together with a reduced amplitude and duration . Similar findings were obtained with the ISR computation . Plasma P levels were similar in both the ovulatory patients and controls . The increased frequency and reduced amplitude of LH pulses in the PMS patients most likely reflect a dysfunction of hypothalamic Gn-RH release , possibly linked to a reduction of opioid inhibition OBJECTIVE To determine the effectiveness of oral micronized progesterone , alprazolam , and placebo in premenstrual syndrome ( PMS ) treatment and the effect of clinical contact on treatment responses . DESIGN R and omized , double-blind , placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact r and omized within each treatment group . SETTING University hospital PMS medical treatment outpatient program in obstetrics/gynecology department . SUBJECTS Among volunteers for PMS treatment , 444 were evaluated and 185 meeting defined PMS criteria were r and omized to treatment ; treatment data are available for 170 . There were no medical withdrawals for adverse events . INTERVENTION A double-blinded protocol in which 300 mg of oral micronized progesterone , 0.25 mg of alprazolam , or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle , including taper . The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam . Subjects were r and omized to brief ( < 20 minutes ) or extended ( 50 minutes ) visits . MAIN OUTCOME MEASURES Daily symptom report ( DSR ) scored for total DSR symptoms , four DSR factors . RESULTS Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function , pain , and mood . Thirty-seven percent of the alprazolam group experienced a 50 % reduction in total DSR scores . There were no clinical ly significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase . Oral micronized progesterone therapy was no better than placebo . Brief vs extended visits had no effect on treatment outcome . Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables . CONCLUSIONS Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase . Oral micronized progesterone is ineffective for PMS This essay traces the history of premenstrual syndrome ( PMS ) in French , British , and American medical literature from 1950 to 2004 . Aetiological theories , treatments and diagnostic criteria have varied over time and place , reflecting local conditions and changing notions of objectivity and evidence . During the 1970s research ers in each nation utilised different research strategies to overcome variation and contradictory results characteristic of PMS research . Since the 1980s , attempts have been made to st and ardise research internationally through prospect i ve daily rating question naires that diagnose and measure PMS . Amidst controversy , a psychiatric reformulation of the syndrome was included in the Diagnostic and Statistical Manual of Mental Disorders ( DSM ) . While the diagnostic criteria for this psychiatric category , now called premenstrual dysphoric disorder ( PMDD ) , are widely accepted for research purpose s , efforts to transfer them to medical practice have been less successful . PMDD remains a contested disease construct Patients with premenstrual syndrome recorded their symptoms daily using menstrual distress question naires . These were analysed by a least mean square method of fitting sine waves . After recording an untreated cycle , patients were given progesterone 200 mg b.d . and placebo in a double-blind crossover manner ; 75 per cent of patients were then given progesterone 400 mg b.d . and placebo in a similar manner . Treated cycles were rated by both daily menstrual distress question naires and retrospective self- assessment . Both rating methods showed there was no significant difference between progesterone and placebo in reducing symptoms of premenstrual syndrome , and in the majority of cases placebo was more effective , although never significantly so A review of measures of menstrual cycle symptoms is provided . This will enable research ers and clinicians to make the appropriate choice of method for their study requirements . In recent years , these measures have taken the form of retrospective question naires ( rating severity of symptoms from memory ) and prospect i ve diaries ( daily checklists of symptoms ) . Many of these draw on aspects of the well-known retrospective question naires , the Menstrual Distress Question naire and Premenstrual Assessment Form , in their development and validation . Each measure will be briefly described , followed by comments on its development , psychometric properties and finally an evaluation of its strengths and weaknesses . It concludes with an examination of the implication s arising from the review , and some recommendations that menstrual cycle research ers and clinicians may wish to consider , as they decide upon the most appropriate measure for their needs In the only Icel and ic study on premenstrual symptoms , a retrospective one conducted in 1991 , investigators found 30 % of the sample to have severe premenstrual changes . In light of critique that retrospective data primarily reflect socioculturally held beliefs about menstruation , the present study was undertaken in order to assess prospect ively Icel and ic women 's premenstrual and menstrual symptoms and experiences . A total of 211 menstrual cycles were recorded by 83 women using a daily health diary . A symptom pattern was defined for each woman . A small majority of the women ( 51.8 % ) displayed a low symptom pattern . Two women ( 2.4 % ) demonstrated a premenstrual syndrome pattern , and 5 women ( 6.0 % ) exhibited a premenstrual magnification pattern . The remaining women displayed mixed symptom patterns indicating wide variability in women 's experiences . These findings differ from the Icel and ic retrospective study and from a USA study using prospect i ve data . Therefore , it is concluded that menstrual socialization influences symptoms expectation and reporting The present study evaluates the luteal progesterone ( P ) and LH secretions in 14 patients affected by premenstrual syndrome ( PMS ) and in 14 asymptomatic controls through the evaluation of their episodic release . PMS was prospect ively confirmed in two consecutive menstrual cycles using Moos ' Menstrual Distress Question naire . A pulsatility study was performed during the luteal phase . Blood sample s were drawn every 10 min for 12 h , beginning at 0800 h. Statistically significant pulses were detected using the Detect program , and the degree of concordance of LH and P pulses was estimated . Similar mean 12-h P levels were found in controls ( mean + /- SD , 13.9 + /- 9.3 nmol/L ) and patients ( 14.2 + /- 10.1 ) . LH levels were also similar in the two groups . Patients showed a higher P pulse frequency ( 13.4 + /- 1.8 vs. 11.4 + /- 2.3 ; P < 0.02 ) and a reduced amplitude of secretory episodes ( 126.5 + /- 61.6 % vs. 187.1 + /- 126.7 % ; P < 0.03 ) than controls . Similarly , PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls . A significant degree of concordance between LH and P pulses was observed in both groups , with a time lag of 0 - 10 min ; that is , P secretory episodes follow LH with a delay of 0 - 10 min . These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects , the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude . This phenomenon is temporally related to LH secretion , thus reinforcing the concept of PMS as a neuroendocrine disorder Depressed mood is a salient feature of Premenstrual Syndrome ( PMS ) . Fourteen women with prospect ively documented PMS and ten without PMS completed the short form of the Beck Depression Inventory ( BDI ) and the Zung Self-Rating Scale for Depression ( Zung-D ) during the follicular and late luteal phases of two consecutive menstrual cycles . The short form of the BDI assesses the more cognitive symptoms of depression , while the Zung-D identifies primarily vegetative symptoms . The short form of the BDI was sensitive to cyclic changes in the PMS women , while the Zung-D was not . The BDI items uniquely endorsed by the PMS women during the late luteal phase were pessimism , sense of failure , dissatisfaction , guilt , self-dislike , and indecision . The premenstrual dysphoria experienced by PMS women thus appears to be more cognitive than vegetative in nature . Finally , differential utility of st and ardized mood measures to detect premenstrual depression is suggested . The BDI proved to be the more sensitive measure We carried out a r and omized , double-blind , crossover study of 85 women , design ed to investigate the dose-response of daily Mg supplementation on premenstrual symptoms . Each woman took one of four treatments : Mg ( 200 , 350 or 500 mg/day ) or sorbitol ( placebo ) for 2 months . This was followed by a washout of 1 month , and then each woman received one of the three remaining treatments for a further 2 months . Unexpectedly , sorbitol ( 1305 mg ) reduced anxiety-related and total premenstrual symptoms after 2 months compared with Mg treatments ( P<0.001 and P<0.001 , respectively ) . We conclude that low-dose sorbitol reduces premenstrual symptoms beyond that expected of a placebo . After 2 months of treatment , sorbitol also reduced urinary Mg excretion compared to baseline ( no intervention ) and Mg treatments ( P=0.005 ) . A follow-up study on 17 healthy volunteers confirmed lack of effect on urinary Mg output of a similar sorbitol intervention regime compared with either baseline or cellulose placebo . It appears that sorbitol may influence Mg homeostasis in women suffering premenstrual symptoms , but not in healthy individuals . Implication s for placebo choice in RCTs are discussed Rigorous criteria were used to select women with severe premenstrual syndrome for inclusion in an 8-month double-blind placebo-controlled clinical trial of progesterone vaginal suppositories . Following a control month without treatment , progesterone ( 200 mg in polyethylene glycol base ) or placebo was self administered twice daily by vaginal suppository for a minimum of 12 days before the onset of menstruation for 3 months . Crossover to the opposite medication for a further 3 months was followed by a final control cycle without treatment in month 8 . Physician contact was minimized throughout the study to avoid any possible positive effects of psychological support which may have confounded past investigations . Detailed self-report question naires were completed every 3 days for the duration of the study . Although the attrition rate was high , 20 women completed the trial and their records are analyzed here . The results of this trial indicate that the response to vaginal progesterone in these dosages is , at best , marginal and not significantly different from response with placebo use |
13,060 | 27,087,257 | Serious adverse events were not reported separately from the exacerbation outcomes .There was no difference in asthma control measured by the Asthma Control Question naire ( ACQ ) or in quality of life measured on the Asthma Quality of Life Question naire ( AQLQ ) between remote and face-to-face check-ups .
We could rule out significant harm of remote check-ups for these outcomes but we were less confident because these outcomes are more prone to bias from lack of blinding .
The larger implementation study that compared two general practice population s demonstrated that offering telephone check-ups and proactively phoning participants increased the number of people with asthma who received a review .
However , we do not know whether the additional participants who had a telephone check-up subsequently benefited in asthma outcomes .
Current r and omised evidence does not demonstrate any important differences between face-to-face and remote asthma check-ups in terms of exacerbations , asthma control or quality of life .
There is insufficient information to rule out differences in efficacy , or to say whether or not remote asthma check-ups are a safe alternative to being seen face-to-face | BACKGROUND Asthma remains a significant cause of avoidable morbidity and mortality .
Regular check-ups with a healthcare professional are essential to monitor symptoms and adjust medication .
Health services worldwide are considering telephone and internet technologies as a way to manage the rising number of people with asthma and other long-term health conditions .
This may serve to improve health and reduce the burden on emergency and inpatient services .
Remote check-ups may represent an unobtrusive and efficient way of maintaining contact with patients , but it is uncertain whether conducting check-ups in this way is effective or whether it may have unexpected negative consequences .
OBJECTIVES To assess the safety and efficacy of conducting asthma check-ups remotely versus usual face-to-face consultations . | OBJECTIVE To determine whether an asthma coaching program can improve parent and child asthma-related quality of life ( QOL ) and reduce urgent care events . DESIGN R and omized controlled trial of usual care vs usual care with coaching . Comparisons were made between groups using mixed models . SETTING A Midwest city . PARTICIPANTS A community-based sample of 362 families with a child aged 5 to 12 years with persistent asthma . INTERVENTION A 12-month structured telephone coaching program in which trained coaches provided education and support to parents for 4 key asthma management behaviors . MAIN OUTCOME MEASURES Parental and child QOL measured with a vali date d , interview-administered , 7-point instrument and urgent care events in a year ( unscheduled office visits , after-hours calls , emergency department visits , or hospitalizations ) determined by record audit . RESULTS Parental asthma-related QOL scores improved by an average of 0.67 units ( 95 % confidence interval [ CI ] , 0.49 to 0.84 ) in the intervention group and 0.28 units ( 95 % CI , 0.10 to 0.46 ) in the control group . The difference between study groups was statistically significant ( difference , 0.38 ; 95 % CI , 0.14 to 0.63 ) . No between-group difference was found in the change in the child 's QOL ( difference , -0.17 ; 95 % CI , -0.47 to 0.12 ) or in the mean number of urgent care events per year ( difference , 1.15 ; 95 % CI , 0.82 to 1.61 ) . The proportion of children with very poorly controlled asthma in the intervention group decreased compared with the control group ( difference , 0.34 ; 95 % CI , 0.21 to 0.48 ) . CONCLUSIONS A telephone coaching program can improve parental QOL and can be implemented without additional physician training or practice re design 263 participants completing a r and omised controlled trial comparing telephone vs. face-to-face asthma consultations were asked about preferences for future review s. Qualitative analysis of data from 209 respondents identified divergent views . Clear opinions were expressed about the respective roles of the two modes of consulting ; telephone consultations were considered convenient for review ing ' well controlled ' asthma , whereas face-to-face consultations were perceived as allowing in-depth assessment of problems in those with more symptomatic asthma . Practice s may consider offering patients the choice of a telephone or face-to-face review Background In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects . However , the optimal strategy for tapering oral corticosteroids is unknown . Objective To investigate whether an internet-based management tool including home monitoring of symptoms , lung function and fraction of exhaled nitric oxide ( FENO ) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life . Methods In a 6-month pragmatic r and omised prospect i ve multicentre study , 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies : according to conventional treatment ( n=43 ) or guided by a novel internet-based monitoring system ( internet strategy ) ( n=52 ) . Primary outcomes were cumulative sparing of prednisone , asthma control and asthma-related quality of life . Secondary outcomes were forced expiratory volume in 1 s ( FEV1 ) , exacerbations , hospitalisations and patient 's satisfaction with the tapering strategy . Results Median cumulative sparing of prednisone was 205 ( 25–75th percentile −221 to 777 ) mg in the internet strategy group compared with 0 ( −497 to 282 ) mg in the conventional treatment group ( p=0.02 ) . Changes in prednisone dose ( mixed effect regression model ) from baseline were −4.79 mg/day and + 1.59 mg/day , respectively ( p<0.001 ) . Asthma control , asthma-related quality of life , FEV1 , exacerbations , hospitalisations and satisfaction with the strategy were not different between groups . Conclusions An internet-based management tool including home monitoring of symptoms , lung function and FENO in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life . Clinical trial registration number Clinical trial registered with http://www.trialregister.nl ( Netherl and s Trial Register number 1146 ) Background : No r and omised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists . Most r and omised trials of asthma self-management have recruited participants from secondary care ; there is uncertainty regarding its effectiveness in primary care . A r and omised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy . Methods : Twenty four adults attending a community pharmacy in Tower Hamlets , east London for routine asthma medication were r and omised into two groups : the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist . Participants self-completed the North of Engl and asthma symptom scale at baseline and 3 months later . Results : The groups were well matched at baseline for demographic characteristics and mean ( SD ) symptom scores ( 26.3 ( 4.8 ) and 27.8 ( 3.7 ) in the intervention and control groups , respectively ) . Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 ( 4.2 ) and 28.1 ( 3.5 ) , respectively ( p<0.001 ; difference adjusted for baseline scores = 7.0 ( 95 % CI 4.4 to 9.5 ) . Conclusions : A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy . Further studies should attempt to confirm these findings using larger sample s and a wider range of outcome measures Background Many children with asthma do not have sufficient asthma control , which leads to increased healthcare costs and productivity loss of parents . One of the causative factors are adherence problems . Effective interventions improving medication adherence may therefore improve asthma control and reduce costs . A promising solution is sending real time text-messages via the mobile phone network , when a medicine is about to be forgotten . As the effect of real time text-messages in children with asthma is unknown , the primary aim of this study is to determine the effect of a Real Time Medication Monitoring system ( RTMM ) with text-messages on adherence to inhaled corticosteroids ( ICS ) . The secondary objective is to study the effects of RTMM on asthma control , quality of life and cost-effectiveness of treatment . Methods A multicenter , r and omized controlled trial involving 220 children ( 4–11 years ) using ICS for asthma . All children receive an RTMM-device for one year , which registers time and date of ICS doses . Children in the intervention group also receive tailored text-messages , sent only when a dose is at risk of omission . Primary outcome measure is the proportion of ICS dosages taken within the individually predefined time-interval . Secondary outcome measures include asthma control ( monthly Asthma Control Tests ) , asthma exacerbations , healthcare use ( collected from hospital records , patient reports and pharmacy record data ) , and disease-specific quality of life ( PAQLQ question naire ) . Parental and children ’s acceptance of RTMM is evaluated with online focus groups and patient question naires . An economic evaluation is performed adopting a societal perspective , including relevant healthcare costs and parental productivity loss . Furthermore , a decision-analytic model is developed in which different levels of adherence are associated with clinical and financial outcomes . Also , sensitivity analyses are carried out on different price levels for RTMM . Discussion If RTMM with tailored text-message reminders proves to be effective , this technique can be used in daily practice , which would support children with suboptimal adherence in their asthma (self)management and in achieving better asthma control and better quality of life . Trial registration Netherl and s Trial Register NTR2583 Background Asthma is a chronic lung disease in which recurrent asthma symptoms create a substantial burden to individuals and their families . At the same time the economic burden associated with asthma is considerable . Methods The cost-effectiveness study was part of a single centre prospect i ve r and omised controlled trial comparing a nurse-led telemonitoring programme to usual care in a population of asthmatic out patients . The study included 109 asthmatic out patients ( 56 children ; 53 adults ) . The duration of follow-up was 12 months , and measurements were performed at baseline , 4 , 8 , and 12 months . Patients were asked to transfer their monitor data at least twice daily and by judging the received data and following a stepwise intervention protocol a nurse was able to act as the main caregiver in the intervention group . In both groups the EQ-5D and the SF-6D were used to obtain estimates of health state utilities . One year health care costs , patient and family costs , and productivity losses were calculated . The mean incremental costs were weighted against the mean incremental effect in terms of QALY . Results The study population generally represented mild to moderate asthmatics . No significant differences were found between the groups with regard to the generic quality of life . Overall , the mean health care costs per patient were higher in the intervention group than in the control group . The intervention costs mainly caused the cost difference between the groups . The intervention costs the society € 31,035/QALY gained with regard to adults and with regard to children € 59,071/QALY gained . Conclusion If the outcome is measured by generic quality of life the nurse-led telemonitoring programme is of limited cost-effectiveness in the study population . From the societal perspective the probability of the programme being cost-effective compared to regular care was 85 % at a ceiling ratio of € 80,000/QALY gained among the adults and 68 % among the children . A decrease in the price of the asthma monitor will substantial increase the probability of the programme to be cost-effective . Trial registration Number : Background Asthma is a prevalent and costly disease result ing in reduced quality of life for a large proportion of individuals . Effective patient self-management is critical for improving health outcomes . However , key aspects of self-management such as self-monitoring of behaviours and symptoms , coupled with regular feedback from the health care team , are rarely addressed or integrated into ongoing care . Health information technology ( HIT ) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team , and access to their health information , presented in personalized ways that can alert them when there is a need for action . The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system , My Asthma Portal ( MAP ) , linked to a case-management system on asthma control , and asthma health-related quality of life . Methods The trial is a parallel multi-centered 2-arm pilot r and omized controlled trial . Participants are r and omly assigned to one of two conditions : a ) MAP and usual care ; or b ) usual care alone . Individuals will be included if they are between 18 and 70 , have a confirmed asthma diagnosis , and their asthma is classified as not well controlled by their physician . Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug data base , and asthma quality of life using the Mini Asthma Related Quality of Life Question naire . Power calculations indicated a needed total sample size of 80 subjects . Data are collected at baseline , 3 , 6 , and 9 months post r and omization . Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010 . Discussion Self-management support from the care team is critical for improving chronic disease outcomes . Given the high volume of patients and time constraints during clinical visits , primary care physicians have limited time to teach and reinforce use of proven self-management strategies . HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change . Trial Registration Current Controlled Trials IS RCT N34326236 Background Internet-based self-management has shown to improve asthma control and asthma related quality of life , but the improvements were only marginally clinical ly relevant for the group as a whole . We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma . Methods In a 1-year r and omised controlled trial involving 200 adults ( 18 - 50 years ) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Question naire ( ACQ ) . Participants were assigned either to the Internet group ( n = 101 ) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group ( UC ) ( n = 99 ) . We analysed 3 subgroups : patients with well controlled ( ACQ ≤ 0.75 ) , partly controlled ( 0.75>ACQ ≤ 1.5 ) or uncontrolled ( ACQ>1.5 ) asthma at baseline . Results Overall monitoring adherence was 67 % ( 95 % CI , 60 % to 74 % ) . Improvements in ACQ score after 12 months were -0.14 ( p = 0.23 ) , -0.52 ( p < 0.001 ) and -0.82 ( p < 0.001 ) in the Internet group compared to usual care for patients with well , partly and uncontrolled asthma at baseline , respectively . Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma ( + 278 μg , p = 0.001 ) , but not in patients with well or partly controlled asthma . After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care . Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients ' needs . Trial registration Current Controlled Trials IS RCT BACKGROUND Attendance for routine asthma review s is poor . A recent r and omised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates ; however , concerns have been expressed about the generalisability and implementation of the trial 's findings . AIM To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service . DESIGN OF STUDY Phase IV controlled before- and -after implementation study . SETTING A large UK general practice . METHOD Using existing administrative groups , all patients with active asthma ( n = 1809 ) received one of three asthma review services : structured recall with a telephone-option for review s versus structured recall with face-to-face-only review s , or usual-care ( to assess secular trends ) . Main outcome measures were : proportion of patients with active asthma review ed within the previous 15 months ( Quality and Outcomes Framework target ) , mode of review , enablement , morbidity , and costs to the practice . RESULTS A routine asthma review was provided for 397/598 ( 66.4 % ) patients in the telephone-option group compared with 352/654 ( 53.8 % ) in the face-to-face-only review group : risk difference 12.6 % ( 95 % confidence interval [ CI ] = 7.2 to 17.9 , P<0.001 ) . The usual-care group achieved a review rate of 282/557 ( 50.6 % ) . Morbidity was equivalent in the three groups ; however , enablement ( P = 0.03 ) and confidence ( P = 0.007 ) in asthma management were greater in the telephone-option versus face-to-face-only group . The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service ( 10.03 pounds versus 12.74 pounds , mean difference 2.71 pounds ; 95 % CI = 1.92 to 3.50 , P<0.001 ) ; usual-care costs were 11.85 pounds per review achieved . CONCLUSION Routinely offering telephone review s cost-effectively increased asthma review rates , enhancing patient enablement and confidence with management , with no detriment to asthma morbidity . Practice s should consider a telephone option for their asthma review service A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88 participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers Background Asthma is a common medical condition caused by chronic inflammation of the airways . Characteristic symptoms of the illness include attacks of shortness of breath , wheezing , tightness in the chest , and cough . Asthma is commonly treated by inhaled corticosteroids , which help to suppress inflammation of the airways and reduce the frequency of severe symptoms and attacks . This medication in the form of inhalers is known as preventer or controller medication and many patients also take short-acting bronchodilators to control acute symptoms ( reliever medication ) . In order to provide therapeutic benefit , preventer medication needs to be taken regularly on a daily basis . However , non-adherence to preventer medication is a common problem in patients diagnosed with asthma and these results in the overuse of reliever medication , increased asthma symptoms , more frequent asthma attacks , and hospital admissions ( Stern et al. , 2006 ) . Optimal adherence to inhaled corticosteroids requires patients to take their preventer medication on 80 % or more occasions , as this is associated with greatest asthma control ( Lasmar et al. , 2009 ) . Objective While effective preventative medication is readily available for asthma , adherence is a major problem due to patients ’ beliefs about their illness and medication . We investigated whether a text message programme targeted at changing patients ’ illness and medication beliefs would improve adherence in young adult asthma patients . Methods Two hundred and sixteen patients aged between 16 and 45 on asthma preventer medication were recruited from pamphlets dispensed with medication and e-mails sent to members of a targeted marketing website . Participants were r and omized to receive individually tailored text messages based on their illness and medication beliefs over 18 weeks or no text messages . Illness and medication beliefs were assessed at baseline and at 18 weeks . Adherence rates were assessed by phone calls to participants at 6 , 12 , and 18 weeks and at 6 and 9 months . Results At 18 weeks , the intervention group had increased their perceived necessity of preventer medication , increased their belief in the long-term nature of their asthma , and their perceived control over their asthma relative to control group ( all p<0.05 ) . The intervention group also significantly improved adherence over the follow-up period compared to the control group with a relative average increase in adherence over the follow-up period of 10 % ( p<0.001 ) . The percentage taking over 80 % of prescribed inhaler doses was 23.9 % in the control group compared to 37.7 % in the intervention group ( p<0.05 ) . Conclusion A targeted text message programme increases adherence to asthma preventer inhaler and may be useful for other illnesses where adherence is a major issue Abstract Introduction : Originally , the Asthma Control Test ( ACT ) was design ed for English-speaking patients using a paper- and -pencil format . The Turkish version of the ACT was recently vali date d. This article compares the paper- and -pencil and web-based texting formats of the Turkish version of the ACT and evaluates the compatibility of these ACT scores with GINA-based physician assessment s of asthma control . Methods : This multicentre prospect i ve study included 431 asthma patients from outpatient clinics in Turkey . The patients were r and omized into a paper- and -pencil group ( n = 220 ) and a text messaging group ( n = 211 ) . Patients completed the ACT at Visit 1 , after 10 ± 2 days , and at 5 ± 1 week to demonstrate the reliability and responsiveness of the test . At each visit , physicians assessed patients ’ asthma control levels . Results : The ACT administered via texting showed an internal consistency of 0.82 . For the texting group , we found a significant correlation between the ACT and physician assessment s at Visit 1 ( r = 0.60 , p < 0.001 ) . The AUC was 0.87 , with a sensitivity of 78.0 % and a specificity of 77.5 % for a score of ≤19 for screening “ uncontrolled ” asthma in the texting group . Conclusion : When the Turkish version of the ACT was administered via either the paper- and -pencil or text messaging test , scores were closely associated with physician assessment s of asthma control Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 OBJECTIVES To test the hypothesis that reinforcement of the advice given at the time of discharge from the emergency department by telephone consultation would improve asthma outcomes . METHODS A r and omized controlled trial of the parents of 310 children who had been discharged from the emergency department with asthma was undertaken . The parents were r and omized to receive either st and ard care ( 155 children ) or st and ard care plus education by telephone ( 155 children ) from a trained asthma educator . Symptoms , parental asthma knowledge , parental quality of life and use of asthma action plans and preventer therapy were collected at baseline and 6 months later . The primary measure was days of wheeze in last 3 months ; intermediate measures were regular use of preventer medications , possession and use of written asthma action plan , parental asthma knowledge scores and parental quality of life scores . RESULTS A total of 266 parents ( 136 intervention ) completed the follow-up question naires after 6 months . Both groups showed similar symptoms and process measures at baseline , apart from more regular use of preventer medication in the control children . At follow up , the intervention group children were significantly more likely than controls to possess ( 87.5 % vs 72.3 % ; P = 0.002 ) a written asthma action plan . Possession of action plans increased from baseline in the intervention group but tended to decrease in the control group . Use of action plans was greater in the intervention group but decreased from baseline in both groups . Both intervention and control groups showed significant decreases in asthma symptoms . CONCLUSIONS Reinforcement by telephone consultation did not improve the primary outcome of wheeze in the last 3 months . However , it increased the possession and regular use of written asthma action plans in the intervention group Objective To assess the effect of home based telehealth interventions on the use of secondary healthcare and mortality . Design Pragmatic , multisite , cluster r and omised trial comparing telehealth with usual care , using data from routine administrative data sets . General practice was the unit of r and omisation . We allocated practice s using a minimisation algorithm , and did analyses by intention to treat . Setting 179 general practice s in three areas in Engl and . Participants 3230 people with diabetes , chronic obstructive pulmonary disease , or heart failure recruited from practice s between May 2008 and November 2009 . Interventions Telehealth involved remote exchange of data between patients and healthcare professionals as part of patients ’ diagnosis and management . Usual care reflected the range of services available in the trial sites , excluding telehealth . Main outcome measure Proportion of patients admitted to hospital during 12 month trial period . Results Patient characteristics were similar at baseline . Compared with controls , the intervention group had a lower admission proportion within 12 month follow-up ( odds ratio 0.82 , 95 % confidence interval 0.70 to 0.97 , P=0.017 ) . Mortality at 12 months was also lower for intervention patients than for controls ( 4.6 % v 8.3 % ; odds ratio 0.54 , 0.39 to 0.75 , P<0.001 ) . These differences in admissions and mortality remained significant after adjustment . The mean number of emergency admissions per head also differed between groups ( crude rates , intervention 0.54 v control 0.68 ) ; these changes were significant in unadjusted comparisons ( incidence rate ratio 0.81 , 0.65 to 1.00 , P=0.046 ) and after adjusting for a predictive risk score , but not after adjusting for baseline characteristics . Length of hospital stay was shorter for intervention patients than for controls ( mean bed days per head 4.87 v 5.68 ; geometric mean difference −0.64 days , −1.14 to −0.10 , P=0.023 , which remained significant after adjustment ) . Observed differences in other forms of hospital use , including notional costs , were not significant in general . Differences in emergency admissions were greatest at the beginning of the trial , during which we observed a particularly large increase for the control group . Conclusions Telehealth is associated with lower mortality and emergency admission rates . The reasons for the short term increases in admissions for the control group are not clear , but the trial recruitment processes could have had an effect . Trial registration number International St and ard R and omised Controlled Trial Number Register IS RCT N43002091 OBJECTIVE Low-income and minority adolescents are at high risk for poor asthma outcomes , due in part to adherence . We tested acceptability , feasibility , and effect sizes of an adherence intervention for low socioeconomic status ( SES ) minority youth with moderate- and severe-persistent asthma . Design and Methods Single-site r and omized pilot trial : intervention ( n = 12 ; asthma education , motivational interviewing , problem-solving skills training , 1 month cell-phone with tailored text messaging ) versus control ( n = 14 ; asthma education ; cell-phone without tailored messaging ) . Calculated effect-sizes of relative change from baseline ( 1 and 3 months ) . RESULTS Intervention was judged acceptable and feasible by participants . Participants ( 12 - 18 years , mean = 15.1 , SD = 1.67 ) were 76.9 % African-American , 80.7 % public/no insurance . At 1 and 3 months , asthma symptoms ( Cohen 's d 's = 0.40 , 0.96 ) and HRQOL ( PedsQL ™ ; Cohen 's d 's = 0.23 , 1.25 ) had clinical ly meaningful medium to large effect sizes . CONCLUSIONS This intervention appears promising for at-risk youth with moderate- and severe-persistent asthma Background Internet-based self-management ( IBSM ) support cost-effectively improves asthma control , asthma related quality of life , number of symptom-free days , and lung function in patients with mild to moderate persistent asthma . The current challenge is to implement IBSM in clinical practice . Methods / design This study is a three-arm cluster r and omized trial with a cluster pre-r and omisation design and 12 months follow-up per practice comparing the following three IBSM implementation strategies : minimum strategy ( MS ) : dissemination of the IBSM program ; intermediate strategy ( IS ) : MS + start-up support for professionals ( i.e. , support in selection of the appropriate population and training of professionals ) ; and extended strategy ( ES ) : IS + additional training and ongoing support for professionals . Because the implementation strategies ( interventions ) are primarily targeted at general practice s , r and omisation will occur at practice level . In this study , we aim to evaluate 14 primary care practice s per strategy in the Leiden-The Hague region , involving 140 patients per arm . Patients aged 18 to 50 years , with a physician diagnosis of asthma , prescription of inhaled corticosteroids , and /or montelukast for ≥3 months in the previous year are eligible to participate . Primary outcome measures are the proportion of referred patients that participate in IBSM , and the proportion of patients that have clinical ly relevant improvement in the asthma-related quality of life . The secondary effect measures are clinical outcomes ( asthma control , lung function , usage of airway treatment , and presence of exacerbations ) ; self-management related outcomes ( health education impact , medication adherence , and illness perceptions ) ; and patient utilities . Process measures are the proportion of practice s that participate in IBSM and adherence of professionals to implementation strategies . Cost-effective measurements are medical costs and healthcare consumption . Follow-up is six months per patient . Discussion This study provides insight in the amount of support that is required by general practice s for cost-effective implementation of IBSM . Additionally , design and results can be beneficial for implementation of other self-management initiatives in clinical practice .Trial registration the Netherl and s National Trial Register Background Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients . Pharmacists are suited to impact medication adherence given their training , skills , and frequent contact with patients . The Empowering pharmacists in asthma management through interactive SMS ( EmPhAsIS ) trial involves an intervention leveraging mobile health ( mHealth ) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma . Methods / Design This study is a pragmatic pharmacy-based , cluster , r and omized controlled trial with 12 months of intervention delivery and follow-up . Pharmacies ( the clusters ) will be r and omized at a 1:1 ratio to provide intervention or usual care . The EmPhAsIS intervention consists of patient asthma education , short message service (SMS)-based monthly assessment of adherence , and follow-up of non-adherent individuals by community pharmacists . There are no inclusion or exclusion criteria for pharmacies . Patients are eligible if they : are 14 years of age or older , fill a prescription for inhaled corticosteroid ( either monotherapy or in a combination inhaler with long-acting beta-agonists ) , have been diagnosed with asthma , possess a mobile phone with SMS capabilities , and have no communication difficulties such as inability to communicate in English , or significant impairment in vision , hearing , or speech . The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio , the ratio of the days of medication supplied to days in a given time interval . This study will also evaluate secondary outcomes including : asthma control , asthma-related quality of life , asthma-related hospital admissions , and use of reliever medications during the follow-up period . A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon . Discussion Considering the prevalence of asthma , the extent of the non-adherence problem in this disease , and the availability of effective treatments , there is a tremendous potential to reduce the burden of asthma through improving adherence . This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management . Trial registration Clinical Trials.gov identifier : NCT02170883 ; date of registration : 19 June 2014 OBJECTIVES . Parents and children often overreport adherence to treatment regimens , which in turn complicates interpretation and application of clinical trial findings . The objective of this investigation was to test the effect of reporting mode on accuracy of inhaled corticosteroid-adherence reporting in children with asthma and their parents under conditions similar to those of an asthma clinical trial . PATIENTS AND METHODS . Participants included 104 children who were being treated with an inhaled corticosteroid delivered by a metered-dose inhaler for asthma diagnosed by their health care provider . Each parent and child dyad was r and omly assigned to 1 of 3 self-report adherence- assessment modes : ( 1 ) audio computer-assisted self-interviewing ; ( 2 ) face-to-face interview with study staff ; or ( 3 ) self-administered paper- and -pencil question naire . At the 4 monthly visits , the parent and child were interviewed separately and asked questions about adherence on the previous day and in the past week . Electronic devices were attached to the each participant 's metered-dose inhaler to provide an objective record of actual daily medication activations . RESULTS . Both children and parents greatly overreported their inhaled corticosteroid adherence when queried about either time frame ( 1 day or 1 week ) in any of the 3 interview modes . One of 3 responses reported full adherence when no medication had been taken . Inconsistent with the study hypothesis , discrepancy between self-report and objective ly measured adherence was greatest in the computer-interview condition . In the optimal circumstance where children were interviewed by study staff about their adherence within the previous 24 hours , reported adherence was within the ±25 % accuracy range for only half of the participants . Larger discrepancy scores were observed for both parents and children when reporting by computer or question naire . CONCLUSIONS . Under the best of conditions in this study , accuracy of self-report was insufficient to provide a st and -alone measure of adherence . Verification of treatment adherence by objective measures remains necessary Some children with severe asthma develop frequent exacerbations despite intensive treatment . We sought to assess the outcome ( severe exacerbations and healthcare use , lung function , quality of life and maintenance treatment ) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy . 50 children with severe uncontrolled asthma were enrolled in a 12-month prospect i ve study and were r and omised into two groups : 1 ) treatment managed with daily home spirometry and medical feedback ( HM ) and 2 ) conventional treatment ( CT ) . The children ’s mean age was 10.9 yrs ( 95 % confidence interval 10.2–11.6 ) . 44 children completed the study ( 21 in the HM group and 23 in the CT group ) . The median number of severe exacerbations per patient was 2.0 ( interquartile range 1.0–4.0 ) in the HM group and 3.0 ( 1.0–4.0 ) in the CT group ( p=0.38 with adjustment for age ) . There were no significant differences between the two groups for unscheduled visits ( HM 5.0 ( 3.0–7.0 ) , CT 3.0 ( 2.0–7.0 ) ; p=0.30 ) , lung function ( pre-&bgr;2-agonist forced expiratory volume in 1 s ( FEV1 ) p=0.13 ) , Paediatric Asthma Quality of Life Question naire scores ( p=0.61 ) and median daily dose of inhaled corticosteroids ( p=0.86 ) . A treatment strategy based on daily FEV1 monitoring with medical feedback did not reduce severe asthma exacerbations Background The financial costs associated with asthma care continue to increase while care remains suboptimal . Promoting optimal self-management , including the use of asthma action plans , along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally . Despite evidence of benefit , guided self-management remains underused , however the potential for online re sources to promote self-management behaviors is gaining increasing recognition . The aim of this paper is to describe the protocol for a pilot evaluation of a website ‘ Living well with asthma ’ which has been developed with the aim of promoting self-management behaviors shown to improve outcomes . Methods / Design The study is a parallel r and omized controlled trial , where adults with asthma are r and omly assigned to either access to the website for 12 weeks , or usual asthma care for 12 weeks ( followed by access to the website if desired ) . Individuals are included if they are over 16-years-old , have a diagnosis of asthma with an Asthma Control Question naire ( ACQ ) score of greater than , or equal to 1 , and have access to the internet . Primary outcomes for this evaluation include recruitment and retention rates , changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Question naire ( AQLQ ) scores , and quantitative data describing website usage ( number of times logged on , length of time logged on , number of times individual pages looked at , and for how long ) . Secondary outcomes include clinical outcomes ( medication use , health services use , lung function ) and patient reported outcomes ( including adherence , patient activation measures , and health status ) . Discussion Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale r and omized controlled trial to successfully recruit and be able to report on necessary outcomes . Here we will provide results across a range of outcomes which will provide estimates of efficacy to inform the design of a future full-scale r and omized controlled trial of the ‘ Living well with asthma ’ website . Trial registration This trial is registered with Current Controlled Trials IS RCT N78556552 on 18/06/13 Background Among adults in the United States , asthma prevalence is disproportionately high among African American women ; this group also experiences the highest levels of asthma-linked mortality and asthma-related health care utilization . Factors linked to biological sex ( e.g. , hormonal fluctuations ) , gender roles ( e.g. , exposure to certain triggers ) and race ( e.g. , inadequate access to care ) all contribute to the excess asthma burden in this group , and also shape the context within which African American women manage their condition . No prior interventions for improving asthma self-management have specifically targeted this vulnerable group of asthma patients . The current study aims to evaluate the efficacy of a culturally- and gender-relevant asthma-management intervention among African American women . Methods / Design A r and omized controlled trial will be used to compare a five-session asthma-management intervention with usual care . This intervention is delivered over the telephone by a trained health educator . Intervention content is informed by the principles of self-regulation for disease management , and all program activities and material s are design ed to be responsive to the specific needs of African American women . We will recruit 420 female participants who self-identify as African American , and who have seen a clinician for persistent asthma in the last year . Half of these will receive the intervention . The primary outcomes , upon which the target sample size is based , are number of asthma-related emergency department visits and overnight hospitalizations in the last 12 months . We will also assess the effect of the intervention on asthma symptoms and asthma-related quality of life . Data will be collected via telephone survey and medical record review at baseline , and 12 and 24 months from baseline . Discussion We seek to decrease asthma-related health care utilization and improve asthma-related quality of life in African American women with asthma , by offering them a culturally- and gender-relevant program to enhance asthma management . The results of this study will provide important information about the feasibility and value of this program in helping to address persistent racial and gender disparities in asthma outcomes .Trial Registration Clinical Trials.gov : This study compared results from Internet and written question naires about respiratory symptoms in order to find out if both forms of the survey yielded the same answers . One thous and seventy-one students , ages 13 to 17 , were asked to complete either an Internet or a written question naire . The demographic characteristics of the participants equalled those of the general Dutch adolescent population . Participants were r and omly assigned to fill out an electronic or written question naire . In addition to eight items from the International Study of Asthma and Allergies in Childhood ( ISAAC ) question naire , two items on doctor visits ( medical attention ) regarding asthma or allergic disease during the past 12 months were included . The participation rate was 87 % . The Internet version of the question naire showed fewer missing answers than the written version , but this was not statistically significant . The respiratory items did not show statistically significant score differences between the Internet and written modes of administration , and there was no visible trend for higher respectively lower scores by either mode of question naire administration . From these results , we conclude that respiratory question naires may be provided to adolescents electronically rather than on paper , since both approaches yielded equal results . To generalize these findings , we recommend repeated studies in other setting Background Effectiveness of Internet-based self-management in patients with asthma has been shown , but its cost-effectiveness is unknown . We conducted a cost-effectiveness analysis of Internet-based asthma self-management compared with usual care . Methodology and Principal Findings Cost-effectiveness analysis alongside a r and omized controlled trial , with 12 months follow-up . Patients were aged 18 to 50 year and had physician diagnosed asthma . The Internet-based self-management program involved weekly on-line monitoring of asthma control with self-treatment advice , remote Web communications , and Internet-based information . We determined quality adjusted life years ( QALYs ) as measured by the EuroQol-5D and costs for health care use and absenteeism . We performed a detailed cost price analysis for the primary intervention . QALYs did not statistically significantly differ between the Internet group and usual care : difference 0.024 ( 95 % CI , −0.016 to 0.065 ) . Costs of the Internet-based intervention were $ 254 ( 95 % CI , $ 243 to $ 265 ) during the period of 1 year . From a societal perspective , the cost difference was $ 641 ( 95 % CI , $ −1957 to $ 3240 ) . From a health care perspective , the cost difference was $ 37 ( 95 % CI , $ −874 to $ 950 ) . At a willingness-to-pay of $ 50000 per QALY , the probability that Internet-based self-management was cost-effective compared to usual care was 62 % and 82 % from a societal and health care perspective , respectively . Conclusions Internet-based self-management of asthma can be as effective as current asthma care and costs are similar . Trial Registration Current Controlled Trials IS RCT The self-management of asthma can improve clinical outcomes . Recently , mobile telephones have been widely used as an efficient , instant personal communication tool . This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme . This was a prospect i ve , controlled study in outpatient clinics . From 120 consecutive patients with moderate-to-severe persistent asthma , 89 were eventually recruited for the study , with 43 in the mobile telephone group ( with a mobile telephone-based interactive asthma self-care system ) . In the mobile telephone group , mean±sem peak expiratory flow rate significantly increased at 4 ( 378.2±9.3 L·min−1 ; n = 43 ; p = 0.020 ) , 5 ( 378.2±9.2 L·min−1 ; n = 43 ; p = 0.008 ) and 6 months ( 382.7±8.6 L·min−1 ; n = 43 ; p = 0.001 ) compared to the control group . Mean±sem forced expiratory volume in 1 s significantly increased at 6 months ( 65.2±3.2 % predicted ; n = 43 ; p<0.05 ) . Patients in the mobile telephone group had better quality of life after 3 months , as determined using the Short Form-12 ® physical component score , and fewer episodes of exacerbation and unscheduled visits than the control group . Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group . The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma , and improves asthma control To determine whether a clinical decision support system can favorably impact the delivery of emergency department and hospital services . R and omized clinical trial of three clinical decision support delivery modalities : email messages to care managers ( email ) , printed reports to clinic administrators ( report ) and letters to patients ( letter ) conducted among 20,180 Medicaid beneficiaries in Durham County , North Carolina with follow-up through 9 months . Patients in the email group had fewer low-severity emergency department encounters vs. controls ( 8.1 vs. 10.6/100 enrollees , p < 0.001 ) with no increase in outpatient encounters or medical costs . Patients in the letter group had more outpatient encounters and greater outpatient and total medical costs . There were no treatment-related differences for patients in the reports group . Among patients < 18 years , those in the email group had fewer low severity ( 7.6 vs. 10.6/100 enrollees , p < 0.001 ) and total emergency department encounters ( 18.3 vs. 23.5/100 enrollees , p < 0.001 ) , and lower emergency department ( $ 63 vs. $ 89 , p = 0.002 ) and total medical costs ( $ 1,736 vs. $ 2,207 , p = 0.009 ) . Patients who were ≥18 years in the letter group had greater outpatient medical costs . There were no intervention-related differences in patient-reported assessment s of quality of life and medical care received . The effectiveness of clinical decision support messaging depended upon the delivery modality and patient age . Health IT interventions must be carefully evaluated to ensure that the result ant outcomes are aligned with expectations as interventions can have differing effects on clinical and economic outcomes Background Long-term asthma management falls short of the goals set by international guidelines . The Internet is proposed as an attractive medium to support guided self-management in asthma . Recently , in a multicenter , pragmatic r and omized controlled parallel trial with a follow-up period of 1 year , patients were allocated Internet-based self-management ( IBSM ) support ( Internet group [ IG ] ) or usual care ( UC ) alone . IBSM support was automatically terminated after 12 months of follow-up . In this study , IBSM support has been demonstrated to improve asthma-related quality of life , asthma control , lung function , and the number of symptom-free days as compared to UC . IBSM support was based on known key components for effective self-management and included weekly asthma control monitoring and treatment advice , online and group education , and communication ( both online and offline ) with a respiratory nurse . Objective The objective of the study was to assess the long-term effects of providing patients 1 year of IBSM support as compared to UC alone . Methods Two hundred adults with physician-diagnosed asthma ( 3 or more months of inhaled corticosteroids prescribed in the past year ) from 37 general practice s and 1 academic outpatient department who previously participated were invited by letter for additional follow-up at 1.5 years after finishing the study . The Asthma Control Question naire ( ACQ ) and the Asthma Quality of Life Question naire ( AQLQ ) were completed by 107 participants ( 60 UC participants and 47 IG participants ) . A minimal clinical important difference in both question naires is 0.5 on a 7-point scale . Results At 30 months after baseline , a sustained and significant difference in terms of asthma-related quality of life of 0.29 ( 95 % CI 0.01 - 0.57 ) and asthma control of -0.33 ( 95 % CI -0.61 to -0.05 ) was found in favor of the IBSM group . No such differences were found for inhaled corticosteroid dosage or for lung function , measured as forced expiratory volume in 1 second . Conclusions Improvements in asthma-related quality of life and asthma control were sustained in patients who received IBSM support for 1 year , even up to 1.5 years after terminating support . Future research should be focused on implementation of IBSM on a wider scale within routine asthma care . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 79864465 ; http://www.controlled-trials.com/IS RCT N79864465 ( Archived by WebCite at http://www.webcitation.org/6J4VHhPk4 ) BACKGROUND Asthma is an important cause of morbidity , absence from school , and use of health services among children . Computer-based educational programs can be design ed to enhance children 's self-management skills and to reduce adverse outcomes . OBJECTIVE To assess the effectiveness of an interactive device programmed for the management of pediatric asthma . DESIGN A r and omized controlled trial ( 66 participants were in the intervention group and 68 were in the control group ) . SETTING Interventions conducted at home and in an outpatient hospital clinic . PARTICIPANTS Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician . INTERVENTION An asthma self-management and education program , the Health Buddy , design ed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers ( physicians , nurses , or other case managers ) through a secure Web site . Control group participants used an asthma diary . MAIN OUTCOME MEASURES Any limitation in activity was the primary outcome . Secondary outcomes included perceived asthma symptoms , absence from school , any peak flow reading in the yellow or red zone , and use of health services . RESULTS After adjusting for covariates , the odds of having any limitation in activity during the 90-day trial were significantly ( P = .03 ) lower for children r and omized to the Health Buddy . The intervention group also was significantly ( P = .01 ) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital ( P = .05 ) . Self-care behaviors , which were important correlates of asthma outcomes , also improved far more for the intervention group . CONCLUSION Compared with the asthma diary , monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence . In a prospect i ve , multicenter , interventional clinical trial with parallel groups , asthmatics were r and omized into an intervention group or a control group . Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization . After that , biweekly telephone calls were made to promote treatment adherence . Asthmatics included in the control group received only the initial and final telephone calls . Both groups received three packages of salmeterol/fluticasone for 3 months . The main outcome measure was the percentage of participants who took the prescribed doses of the drug . A total of 271 patients were included . The overall adherence rate was 51.9 % for the control group and 74.3 % for the intervention group . This meant a reduction of relative risk ( RRR ) of 47 % ( p < 0.001 ) . The number needed to treat ( NNT ) was 4.5 . The only variable associated with better adherence was severe persistent asthma . A low-cost easily implemented intervention , tailored to each individual , enhanced the adherence rate among Brazilian asthmatic patients OBJECTIVE To test the feasibility and preliminary effectiveness of the School-Based Preventive Asthma Care Technology ( SB-PACT ) program , which includes directly observed therapy of preventive asthma medications in school facilitated by Web-based technology for systematic symptom screening , electronic report generation , and medication authorization from providers . STUDY DESIGN We conducted a pilot r and omized trial of SB-PACT versus usual care with 100 children ( aged 3 - 10 years ) from 19 inner-city schools in Rochester , New York . Outcomes were assessed longitudinally by blinded interviewers . Analyses included bivariate statistics and linear regression models , adjusting for baseline symptoms . RESULTS There were data for 99 subjects for analysis . We screened all children using the Web-based system , and 44 of 49 treatment group children received directly observed therapy as authorized by their providers . Treatment group children received preventive medications 98 % of the time they were in school . Over the school year , children in the treatment group experienced nearly 1 additional symptom-free day over 2 weeks versus the usual care group ( 11.33 vs 10.40 , P = .13 ) . Treatment children also experienced fewer nights with symptoms ( 1.68 vs 2.20 , P = .02 ) , days requiring rescue medications ( 1.66 vs 2.44 , P = .01 ) , and days absent from school due to asthma ( 0.37 vs 0.85 , P = .03 ) compared with usual care . Further , treatment children had a greater decrease in exhaled nitric oxide ( -9.62 vs -0.39 , P = .03 ) , suggesting reduction in airway inflammation . CONCLUSION The SB-PACT intervention demonstrated feasibility and improved outcomes across multiple measures in this pilot study . Future work will focus on further integration of preventive care delivery across community and primary care systems OBJECTIVES To evaluate a self-regulation intervention for asthma for older adults . DESIGN A blinded r and omized controlled trial . SETTING Single-center tertiary care academic center . PARTICIPANTS Seventy older adults aged 65 and older with persistent asthma r and omized to an intervention or control group . INTERVENTION Participants participate in a six-session program conducted over the telephone and in group sessions . Participants selected an asthma-specific goal , identified problems , and addressed potential barriers . MEASUREMENTS Outcomes were assessed at 1 , 6 , and 12 months and included the mini-Asthma Quality of Life Question naire ( mAQLQ ) , Asthma Control Question naire ( ACQ ) , healthcare utilization , exhaled nitric oxide ( FENO ) , and percentage of predicted forced expiratory volume in 1 second ( FEV1 % ) . RESULTS The mAQLQ score was significantly higher in the intervention group at 1 , 6 , and 12 months , even after controlling for confounding factors . The between-group difference decreased over time , although at 12 months , it remained greater than 0.5 points . The ACQ was better in the intervention group than in the control group at 1 , 6 , and 12 months . At 12 months , those in the intervention group were 4.2 times as likely as those in the control group to have an ACQ score in the controlled range . Healthcare utilization was lower in the intervention group , although no difference was observed in FENO or predicted FEV1 % . CONCLUSION A self-regulation intervention can improve asthma control , quality of life , and healthcare utilization in older adults Asthma morbidity is high among inner-city minority adults . Improving access to care and patient-provider communication are believed to be essential for improving outcomes . Access and communication in turn increasingly rely on information technology including features of the Electronic Health Record . Its patient portal offers web-based communication with providers and practice s. How patients with limited re sources and educational opportunities can benefit from this portal is unclear . In contrast , home visits by community health workers ( CHWs ) have improved access to care for asthmatic children and promoted caretaker-clinician communication . We describe the planning , design , and methodology of an ongoing r and omized controlled trial for 300 adults , predominantly African American and Hispanic/Latino , with uncontrolled asthma recruited from low income urban neighborhoods who are directed to the most convenient internet access and taught to use the portal , with and without home visits from a CHW . The study 1 ) compares the effects of the 1-year interventions on asthma outcomes ( improved asthma control , quality of life ; fewer ED visits and hospitalizations for asthma or any cause ) , 2 ) evaluates whether communication ( portal use ) and access ( appointments made/kept ) mediate the interventions ' effects on asthma outcomes , and 3 ) investigates effect modification by literacy level , primary language , and convenience of internet access . In home visits , CHWs 1 ) train patients to competency in portal use , 2 ) enhance care coordination , 3 ) communicate the complex social circumstances of patients ' lives to providers , and 4 ) compensate for differences in patients ' health literacy skills . The practical challenges to design and implementation in the targeted population are presented CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits OBJECTIVE . The purpose of this study was to evaluate the impact and acceptability of an educational multimedia program design ed to promote self-management skills in children with asthma . METHODS . We conducted a r and omized , controlled trial with measures at baseline and 1- and 6-month follow-up . The trial was conducted in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals . Participants included 101 children aged 7 to 14 years under the care of hospital-based asthma services . The children were r and omly assigned to receive an asthma information booklet alone or the booklet plus The Asthma Files , an interactive CD-ROM for children with asthma . Asthma knowledge was the primary outcome measure . Other measures included asthma locus of control , lung function , use of oral steroids , and school absence . RESULTS . At the 1-month follow-up ( n = 99 ) , children in the computer group had improved knowledge compared with the control group and a more internal locus of control . There were no differences in objective lung-function measures , hospitalizations , or oral steroid use . The study participants were positive in their evaluation of the intervention . At the 6-month follow-up ( n = 90 ) , significantly fewer children in the intervention group had required oral steroids and had had time off school for asthma in the previous 6 months . The difference did not reach statistical significance in the intention-to-treat analysis for both steroid use and school absence . CONCLUSION . The Asthma Files was found to be an effective and popular health education tool for promoting asthma self-management skills within pediatric care Long recognizing that asthma , one of the most common chronic childhood diseases , is difficult to manage , the National Asthma Education Prevention Program developed clinical practice guidelines to assist health care providers , particularly those in the primary care setting . Yet , maintenance asthma care still fails to meet national st and ards . Therefore , in an attempt to improve and support asthma self-management behaviors for parents of children 5 to 12 years of age with persistent asthma , a novel nurse telephone coaching intervention was tested in a r and omized , controlled trial . A detailed description of the intervention is provided along with parent satisfaction results , an overview of the training used to prepare the nurses , and a discussion of the challenges experienced and lessons learned Objective : This study was conducted to test the effectiveness of a theory-based interactive voice response ( IVR ) intervention to improve adherence to controller medications among adults with asthma . Methods : Fifty participants aged 18 to 65 years who had a physician diagnosis of asthma and a prescription for a daily inhaled corticosteroid , attended a baseline visit and a final visit 10 weeks later . Participants r and omized to the intervention group received 2 automated IVR telephone calls separated by one month , with one additional call if they reported recent symptoms of poorly controlled disease or failure to fill a prescription . Calls were completed in less than 5 minutes and included content design ed to inquire about asthma symptoms , deliver core educational messages , encourage refilling of inhaled corticosteroid prescriptions , and increase communication with providers . Adherence was tracked during 10 weeks , with objective measures that included either electronic monitors or calculation of canister weight . Participants completed the Asthma Quality of Life Question naire , the Asthma Control Test , and the Beliefs in Medications Question naire ( BMQ ) during both visits . Results : Adherence was 32 % higher among patients in the IVR group than those in the control group ( P = .003 ) . A more favorable shift in perception of inhaled corticosteroids was seen on BMQ scores of patients in the IVR group ( P = .003 ) , which in turn correlated with degree of adherence change ( r = 0.342 ; P = .0152 ) . No differences emerged for the Asthma Quality of Life Question naire or Asthma Control Test . Conclusions : The IVR intervention result ed in a significant increase in adherence to inhaled corticosteroid treatment and improved BMQ scores during the study interval . The association of increased adherence with increased BMQ scores suggests that the intervention succeeded in helping participants adopt a more favorable perception of their controller medication , leading in turn to improved adherence INTRODUCTION Asthma control often is poor in adolescents and this causes considerable morbidity . Internet-based self-management ( IBSM ) improves asthma-related quality of life in adults . We hypothesized that IBSM improves asthma-related quality of life in adolescents . METHODS Adolescents ( 12 - 18 years ) with persistent and not well-controlled asthma participated in a r and omized controlled trial with 1 year follow-up and were allocated to IBSM ( n = 46 ) or usual care ( UC , n = 44 ) . IBSM consisted of weekly asthma control monitoring with treatment advice by a web-based algorithm . Outcomes included asthma-related quality of life ( Pediatric Asthma Quality of Life Question naire , PAQLQ ) and asthma control ( Asthma Control Question naire , ACQ ) and were analyzed by a linear mixed-effects model . RESULTS At 3 months , PAQLQ improved with 0.40 points ( 95 % CI : 0.17 - 0.62 , P < 0.01 ) , by IBSM compared to 0.0 points for UC ( P = 0.02 for the difference ) . At 12 months the between-group difference was -0.05 ( 95 % CI : -0.50 to 0.41 , P = 0.85 ) . At 3 months ACQ improved more in IBSM than in UC ( difference : -0.32 points ; 95 % CI : -0.56 to -0.079 , P < 0.01 ) . At 12 months the difference was -0.05 ( 95 % CI : -0.35 to 0.25 , P = 0.75 ) . CONCLUSION IBSM improved asthma-related quality of life and asthma control in adolescents with not well-controlled asthma after 3 months , but not after 12 months BACKGROUND Self management programs have been advocated for adults who have recently been admitted to hospital or have recently attended an emergency department because of asthma . A new telephone based approach has already been trialled for the management of a number of other chronic conditions . This study sought to determine the effect of a telephone based asthma management program for adults with asthma . METHODS Adults with one or more previous admissions for asthma to either or both of two tertiary hospitals between 1 May 2001 and 30 November 2003 were invited to participate . All participants received one face-to-face session with an asthma educator . Participants were r and omised to intervention ( six telephone calls over 6 months ) or control ( usual care ) groups . Measures of health care utilisation and morbidity were collected weekly for 12 months . RESULTS Seventy-one adults ( 54 females ) with a mean age of 36.2 years were recruited to the study . Twenty hospital re-admissions were recorded for the control group and one for the intervention group at 12 months . Re-admission was significantly associated with allocation to control group ( p=0.05 ) . The control group was significantly more likely to report being woken by asthma on more than half the nights of the week ( p=0.03 ) . DISCUSSION Telephone based self management intervention results in clinical ly important reductions in hospital re-admission in adults previously hospitalised with asthma BACKGROUND Experience from other fields of internal medicine shows that Internet-based technology can be used to monitor various diseases . The new technology h and les complex calculation programs easily , and it is a unique way of communicating . These advantages might be used in optimizing the treatment for asthmatic subjects because undertreatment is a common problem found in European asthmatic subjects . OBJECTIVE We sought to investigate the outcome of monitoring and treatment using a physician-managed online interactive asthma monitoring tool and to assess whether the outcome differs from that of monitoring and treatment in an outpatient respiratory clinic or in primary care . METHODS Three hundred asthmatic subjects were r and omized to 3 parallel groups in a 6-month prospect i ve study : ( 1 ) Internet-based monitoring ( n = 100 ) ; ( 2 ) specialist monitoring ( n = 100 ) ; and ( 3 ) general practitioner ( GP ) monitoring ( n = 100 ) . All the patients were examined on entry into the study and after 6 months of treatment . RESULTS The treatment and monitoring with the Internet-based management tool lead to significantly better improvement in the Internet group than in the other 2 groups regarding asthma symptoms ( Internet vs specialist : odds ratio of 2.64 , P = .002 ; Internet vs GP : odds ratio of 3.26 ; P < .001 ) , quality of life ( Internet vs specialist : odds ratio of 2.21 , P = .03 ; Internet vs GP : odds ratio of 2.10 , P = .04 ) , lung function ( Internet vs specialist : odds ratio of 3.26 , P = .002 ; Internet vs GP : odds ratio of 4.86 , P < .001 ) , and airway responsiveness ( Internet vs GP : odds ratio of 3.06 , P = .02 ) . CONCLUSION When physicians and patients used an interactive Internet-based asthma monitoring tool , better asthma control was achieved OBJECTIVE To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization . STUDY DESIGN R and omized clinical trial . METHODS Patients with persistent asthma were r and omly assigned to telephone outreach ( automated = 3389 , live caller = 192 ) or usual care ( n = 3367 ) . Intervention participants received 3 outreach calls over a 10-month period . The intervention provided brief , supportive information and flagged individuals with poor asthma control for follow-up by a provider . A survey was mailed to 792 intervention participants and 236 providers after the intervention . Additional feedback was obtained as part of the final intervention contact . RESULTS The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use , healthcare utilization , asthma control , or quality of life . Post hoc analyses found that , compared with the control group , individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists . They also reported higher satisfaction with their asthma care and better asthma-specific quality of life . Of surveyed providers , 59 % stated the program helped them to clinical ly manage their asthma patients and 70 % thought the program should be continued . CONCLUSIONS This study did not find improved health outcomes in the primary analyses . The intervention was well accepted by providers , however , and the individuals who participated in the calls appeared to have benefited from them . These findings suggest that further studies of automated telephone outreach interventions seem warranted BACKGROUND Guided self-management is an important component of asthma care . Most trials have evaluated paper-based strategies . The effectiveness of new communication technologies remains uncertain . OBJECTIVES To compare the feasibility and clinical outcomes of a st and ard paper-based asthma self-management strategy with web-based strategies . METHODS In a crossover trial , 21 patients using inhaled corticosteroids and long-acting B2-agonists ( mean [ SD ] age 29 [ 10 ] years ) were r and omly assigned to use a sequence of web-based and paper-based diary and action plan . Quality of life , asthma control , lung function , and airway inflammation were assessed using the Asthma Life Quality Question naire ( ALQ ) , Asthma Control Question naire ( ACQ-5 ) , Mini Asthma Quality of Life Question naire ( Mini AQLQ ) , and office spirometry . The ratio of forced expiratory volume in the first second of expiration ( FEV1 ) to peak expiratory flow ( PEF ) rate ( PiKo-1 ) and fraction of exhaled nitric oxide ( FE(NO ) ) were monitored . The main clinical outcomes were asthma control and FE(NO ) . Quality of data and adherence to monitoring tools were the main process outcomes . RESULTS Significant improvements were observed in the AQL and ACQ scores , although lung function did not change . FE(NO ) was significantly reduced only after a web-based strategy but a significant period effect occurred ( P = .006 ) . There were no differences in clinical outcomes between web-based and paper-based management . No intervention-related adverse effects were observed . Adherence seemed higher with the paper-based strategy ( P < .001 ) . However , paper data were unreliable when compared to automatic daily electronic FEV1/PEF records . Twelve patients were very interested in continuing self-management with the web-based approach compared with 2 in using paper tools ( P = .002 ) . CONCLUSIONS Web-based management was feasible , safe , and preferred by patients . Short-term outcomes were at least as good , and data quality was improved Asthma prevalence is increasing among poor and minority children . We examined the effectiveness of a novel interactive device programmed for self-management of pediatric asthma in reducing asthma control problems and hospitalizations . A r and omized controlled trial ( 66 children in the intervention group and 68 in the control group ) was conducted at home and in an outpatient hospital clinic with 8 - 16-year-old inner-city children with physician-diagnosed asthma . During a 12-week period , children in the experimental group received an asthma self-management and education program , the Health Buddy ( Health Hero Network ) , design ed to enable them to monitor their symptoms and transmit this information to a case manager through a secure website . Control group participants used an asthma diary . After adjusting for baseline asthma control problems , asthma severity , and seasonality , children r and omized to automated self-management had a significantly lower mean number of asthma control problems at 6 weeks ( 2.0 , SD = 1.6 ) as compared to children assigned to the asthma diary ( 2.7 , SD = 1.6 ) ( p = 0.03 ) . By 12 weeks , after adjusting for time and the other covariates , asthma control problems dropped markedly in both groups , and did not differ by intervention modality ( p = .07 ) . The intervention modality was not a significant predictor of hospitalization . Educational interventions that encourage children 's active involvement in their own care and symptom monitoring would help children increase their control of asthma problems . Compared to the asthma diary , the automated self-management had a significant short-term impact on asthma control problems . Its initial effectiveness and more consistent use suggest that remote monitoring may be successfully used in short-term interventions and in setting s where staffing for case management is weak We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma , whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians . We examined the effectiveness of this system with a r and omized control study . Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and r and omly assigned to either the tele-medicine or control group . After six months of participation in the program , the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group . Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow ( PEF ) value successfully , and at six months had noticed an improvement in PEF . We therefore conclude that the system effectively contributes to the management of poorly controlled asthma . In addition , further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously BACKGROUND There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice . Alternative methods of providing routine asthma care need to be examined . AIM To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage , compared to usual clinic care . DESIGN OF STUDY An open r and omised controlled trial . SETTING A single semi-rural practice in the southwest of Engl and . METHOD Adult patients with asthma were r and omised to receive either their routine asthma care in the surgery or care by telephone triage . Asthma control parameters , health status and NHS re source utilisation were measured over the 12-month study period . RESULTS One hundred and ninety-four patients were r and omised and 35 % per cent more patients ( n = 84 versus n = 62 ) received more than one consultation in the telephone group . Asthma control as measured by the asthma control question naire ( ACQ ) was similar in the clinic and telephone groups : mean change in ACQ = -0.11 ( 95 % CI = -0.32 to 0.11 ) versus -0.18 ( 95 % CI = -0.38 to 0.02 ) . Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group ( P-value of bootstrapped difference = 0.071 ) . CONCLUSION Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being review ed , at less cost per patient and without loss of asthma control compared to usual routine care in the surgery We have evaluated the feasibility of using the mobile phone short message service ( SMS ) for symptom monitoring in patients with asthma . All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrolment ( n = 497 ) . Those meeting the inclusion criteria were r and omized into a control ( n = 60 ) and intervention group ( n = 60 ) . Patients in the intervention group received SMS messages according to a structured workflow , while patients in the control group had no SMS support . In the intervention group , the mean response rate to the messages was 82 % . There was an improvement in the Asthma Control Test ( ACT ) scores in 36 subjects in the intervention group compared to 28 subjects in the control group . There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group , and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group . However , none of these differences were significant . There was no reduction in admission rates in either group ( P = 0.5 ) . The service was accepted by most patients , but its long-term effectiveness on the management of asthma remains to be determined Methods We conducted an open-label r and omized controlled trial to investigate the impact of support intervention to the outcome of parents of asthmatic children . The constructed supporting program includes scheduled one-by-one and group asthma knowledge education , treatment adherence reinforcement , family support course , and telephone follow-up . The differences of parental knowledge of asthma , medication adherence , hospital re-admission , and health care re source usage between two groups were compared This pilot clinical investigation was conducted to compare a home therapeutic drug-monitoring ( TDM ) method for theophylline blood levels and a traditional TDM method with respect to various patient outcome factors . Out patients with chronic obstructive pulmonary diseases ( COPD ) or asthma who were receiving long-term theophylline therapy were r and omized to one of two groups : home TDM or traditional TDM ( controls ) . Patients in the former group monitored their serum theophylline levels at home over 6 months . Patients in both groups completed survey instruments , including question naires , visual analog scales , and other psychosocial measures , at design ated times throughout the study period . Pulmonary function tests and dyspnea index scores were evaluated at each clinic visit . Results indicated a significantly lower ( p less than 0.05 ) number of changes in concomitant drug therapy in the home TDM group compared with controls . Other indicators that showed a trend toward more favorable outcomes in the home TDM group included symptomology , percentage of levels within the therapeutic range , patient attitudes regarding participation in health care management , and pulmonary function test results . Home monitoring prevented unnecessary clinic visits in several instances when theophylline dosage adjustments were based on telephone reports from patients . The utility of a home TDM method for theophylline has not been reported previously despite potential for broad applications . Findings from this preliminary study may support the use and feasibility of state-of-the-art method ologies in carefully selected sub population s outside the confines of the hospital or clinic setting BACKGROUND Only about a third of people with asthma attend an annual review . Clinicians need to identify cost-effective ways to improve access and ensure regular review . AIM To compare the cost-effectiveness of nurse-led telephone with face-to-face asthma review s. DESIGN OF STUDY Cost-effectiveness analysis based on a 3-month r and omised controlled trial . SETTING Four general practice s in Engl and . METHOD Adults due an asthma review were r and omised to telephone or face-to-face consultations . Trial nurses recorded proportion review ed , duration of consultation , and abortive calls/missed appointments . Data on use of healthcare re sources were extracted from GP records . Cost-effectiveness was assessed from the health service perspective ; sensitivity analyses were based on proportion review ed and duration of consultation . RESULTS A total of 278 people with asthma were r and omised to surgery ( n = 141 ) or telephone ( n = 137 ) review . Onehundred- and -one ( 74 % ) of those with asthma in the telephone group were review ed versus 68 ( 48 % ) in the surgery group ( P < 0.001 ) . Telephone consultations were significantly shorter ( mean duration telephone = 11.19 minutes [ st and ard deviation { SD } = 4.79 ] versus surgery = 21.87 minutes [ SD = 6.85 ] , P < 0.001 ) . Total respiratory healthcare costs per patient over 3 months were similar ( telephone = pounds sterling 64.49 [ SD = 73.33 ] versus surgery = pounds sterling 59.48 [ SD = 66.02 ] , P = 0.55 ) . Total costs of providing 101 telephone versus 68 face-to-face asthma review s were also similar ( telephone = pounds sterling 725.84 versus surgery = pounds sterling 755.70 ) , but mean cost per consultation achieved was lower in the telephone arm ( telephone = pounds sterling 7.19 [ SD = 2.49 ] versus surgery = pounds sterling 11.11 [ SD = 3.50 ] ; mean difference = - pounds sterling 3.92 [ 95 % confidence interval = - pounds sterling 4.84 to pounds sterling 3.01 ] , P < 0.001 ) . CONCLUSIONS Telephone consultations enable a greater proportion of asthma patients to be review ed at no additional cost to the health service . This mode of delivering care improves access and reduces cost per consultation achieved The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population OBJECTIVE . The goal was to determine whether home asthma telemonitoring with store- and -forward technology improved outcomes , compared with in-person , office-based visits . METHODS . A total of 120 patients , 6 to 17 years of age , with persistent asthma were assigned r and omly to the office-based or virtual group . The 2 groups followed the same ambulatory clinical pathway for 12 months . Office-based group patients received traditional in-person education and case management . Virtual group patients received computers , Internet connections , and in-home , Internet-based case management and received education through the study Web site . Disease control outcome measures included quality of life , utilization of services , and symptom control . RESULTS . A total of 120 volunteers ( 45 female ) were enrolled . The groups were clinical ly comparable ( office-based : 22 female/38 male ; mean age : 9.0 ± 3.0 years ; virtual : 23 female/37 male ; mean age : 10.2 ± 3.1 years ) . Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks ( 94 % vs 89 % ) , had greater adherence to daily asthma symptom diary su bmi ssion ( 35.4 % vs 20.8 % ) , had less participant time ( 636 vs 713 patient-months ) , and were older . Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline . There were no other differences in therapeutic or disease control outcome measures . CONCLUSIONS . Virtual group patients achieved excellent asthma therapeutic and disease control outcomes . Compared with those who received st and ardized office-based care , they were more adherent to diary su bmi ssion and had better inhaler scores at 52 weeks . Store- and -forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma UNLABELLED The use of communication technologies may overcome some of the difficulties of conventional , paper-based , self-management of chronic diseases . This paper aims to describe and evaluate the use of P'ASMA - a web based asthma self-management support tool regarding the opinion of patients and their adherence to monitoring in comparison to st and ard paper-based tools . SYSTEM DESCRIPTION P'ASMA allows the collection of asthma monitoring data and provides , to both patient and doctor , immediate feedback about patient 's condition . For each patient a set of forms and scheduling options can be chosen . EVALUATION METHODS Twenty-one adults with previous medical diagnosis of asthma were included in an exploratory r and omized crossover study . Patients used P'ASMA or a paper asthma diary and action-plan each during 4 weeks in a r and om sequence . RESULTS The number of patients who wrote negative remarks regarding P'ASMA was 2 and regarding paper-tools was 11 ; positive comments were 6 and 1 respectively for P'ASMA and Paper-based . Twelve patients were very interested to continue to monitor their asthma using P'ASMA whereas only 2 with Paper-based ( p=0.002 ) . Of the 19 problems reported with P'ASMA , 9 were related to the Internet connection , 5 to the user interface , 3 to internal system errors and 2 to the questions interpretation . The completeness of paper diary records was better ; however , 10 patients reported filling it several days at once which was not allowed in P'ASMA . CONCLUSIONS The intervention was feasible , safe and the problems detected in the web-application can be corrected . With P'ASMA data quality improved as the integrity features increase the reliability of the data . Moreover , patients preferred the web-based application to monitor their asthma Abstract Objective : To determine whether routine review by telephone of patients with asthma improves access and is a good alternative to face to face review s in general practice s. Design : Pragmatic , r and omised controlled trial . Setting : Four general practice s in Engl and . Participants : 278 adults who had not been review ed in the previous 11 months . Intervention : Participants were r and omised to either telephone review or face to face consultation with the asthma nurse . Main outcome measures : Primary outcome measures were the proportion of participants who were review ed within three months of r and omisation and disease specific quality of life , as measured by the Juniper mini asthma quality of life question naire . Secondary outcome measures included the vali date d “ short Q ” asthma morbidity score , nursing care satisfaction question naire score , and length of consultation . Results : Of 137 people r and omised to telephone consultation , 101 ( 74 % ) were review ed , compared with 68 review ed ( 48 % ) of the 141 people in the surgery group , a difference of 26 % ( 95 % confidence interval 14 % to 37 % ; P<0.001 ; number needed to treat 3.8 ) . Three months after r and omisation the two groups did not differ in the Juniper score ( risk difference −0.07 ( 95 % confidence interval −0.40 to 0.27 ) or in satisfaction with the consultation ( risk difference −0.07 ( −0.27 to 0.13 ) ) . Telephone consultations were on average 10 minutes shorter than review s held in the surgery ( mean difference 10.7 minutes ( 12.6 to 8.8 ; P<0.001 ) ) . Conclusions : Compared with face to face consultations in the surgery , telephone consultations enable more people with asthma to be review ed , without clinical disadvantage or loss of satisfaction . A shorter duration means that telephone consultations are likely to be an efficient option in primary care for routine review of asthma . What is already known on the topic Regular review of patients with asthma reduces morbidity and is endorsed as good practice by UK and international guidelines , but only about a third of patients attend for their annual review Most studies of telephone consultation in primary care have focused on consultations requested by patients rather than their use in the routine review of chronic disease What this study adds Telephone consultations enable more people with asthma to be review ed Telephone consultations are shorter than face to face consultations , without any apparent clinical disadvantage Patients are satisfied with telephone Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p < 0.05 ) and night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p < 0.05 ) . There was no significant difference between the groups in daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up BACKGROUND Women with asthma have greater mortality and morbidity than men in the United States . To date , there has been no rigorous evaluation of an intervention focused on the particular problems in asthma management faced by women . This study was a r and omized clinical trial of a self-regulation , telephone counseling intervention emphasizing women 's concerns , and sex and gender role factors in their management of asthma . METHODS A total of 808 women with diagnosed asthma were r and omly assigned to the intervention group or a usual-care control group , including conventional asthma education . Interviews and medical record data were collected to assess psychosocial factors , and the behavioral factors of functioning , quality of life , symptoms , and health-care use at baseline and the subsequent 1 year . Generalized estimating equations , identity link , logit link , and log link were employed to analyze the data . RESULTS Compared to control subjects , the women receiving treatment had greater annual reductions in the average number of nights with asthma symptoms ( p = 0.04 ) , days of missed work/school ( p = 0.03 ) , emergency department visits ( p = 0.04 ) , unscheduled office visits ( p = 0.01 ) , and scheduled office visits ( p = 0.04 ) . They had greater recognition of asthma symptoms during the menstrual cycle ( p = 0.0003 ) , had decreased asthma symptoms with sexual activity ( p = 0.008 ) , and had greater improvement in quality of life ( p = 0.0005 ) , self-regulation ( p = 0.03 ) , and self-confidence to manage asthma ( p = 0.001 ) . CONCLUSION The intervention improved women 's clinical status , functioning , quality of life , and health-care use . A program with a focus on asthma management problems particular to women can significantly assist female asthma patients Background Asthma is the most common pediatric illness in the United States , burdening low-income and minority families disproportionately and contributing to high health care costs . Clinic-based asthma education and telephone case management have had mixed results on asthma control , as have eHealth programs and online games . Objectives To test the effects of ( 1 ) CHESS+CM , a system for parents and children ages 4–12 years with poorly controlled asthma , on asthma control and medication adherence , and ( 2 ) competence , self-efficacy , and social support as mediators . CHESS+CM included a fully automated eHealth component ( Comprehensive Health Enhancement Support System [ CHESS ] ) plus monthly nurse case management ( CM ) via phone . CHESS , based on self-determination theory , was design ed to improve competence , social support , and intrinsic motivation of parents and children . Methods We identified eligible parent – child dyads from files of managed care organizations in Madison and Milwaukee , Wisconsin , USA , sent them recruitment letters , and r and omly assigned them ( unblinded ) to a control group of treatment as usual plus asthma information or to CHESS+CM . Asthma control was measured by the Asthma Control Question naire ( ACQ ) and self-reported symptom-free days . Medication adherence was a composite of pharmacy refill data and medication taking . Social support , information competence , and self-efficacy were self-assessed in question naires . All data were collected at 0 , 3 , 6 , 9 , and 12 months . Asthma diaries kept during a 3-week run-in period before r and omization provided baseline data . Results Of 305 parent – child dyads enrolled , 301 were r and omly assigned , 153 to the control group and 148 to CHESS+CM . Most parents were female ( 283/301 , 94 % ) , African American ( 150/301 , 49.8 % ) , and had a low income as indicated by child ’s Medicaid status ( 154/301 , 51.2 % ) ; 146 ( 48.5 % ) were single and 96 of 301 ( 31.9 % ) had a high school education or less . Completion rates were 127 of 153 control group dyads ( 83.0 % ) and 132 of 148 CHESS+CM group dyads ( 89.2 % ) . CHESS+CM group children had significantly better asthma control on the ACQ ( d = –0.31 , 95 % confidence limits [ CL ] –0.56 , –0.06 , P = .011 ) , but not as measured by symptom-free days ( d = 0.18 , 95 % CL –0.88 , 1.60 , P = 1.00 ) . The composite adherence scores did not differ significantly between groups ( d = 1.48 % , 95 % CL –8.15 , 11.11 , P = .76 ) . Social support was a significant mediator for CHESS+CM ’s effect on asthma control ( alpha = .200 , P = .01 ; beta = .210 , P = .03 ) . Self-efficacy was not significant ( alpha = .080 , P = .14 ; beta = .476 , P = .01 ) ; neither was information competence ( alpha = .079 , P = .09 ; beta = .063 , P = .64 ) . Conclusions Integrating telephone case management with eHealth benefited pediatric asthma control , though not medication adherence . Improved methods of measuring medication adherence are needed . Social support appears to be more effective than information in improving pediatric asthma control . Trial Registration Clinical trials.gov NCT00214383 ; http:// clinical trials.gov/ct2/show/NCT00214383 ( Archived by WebCite at http://www.webcitation.org/68OVwqMPz RATIONALE , AIMS AND OBJECTIVES The aim of the study was to evaluate the effects on , and the relationship between , asthma symptoms , asthma-specific quality of life and medical consumption of a nurse-led telemonitoring intervention compared with regular care in asthma in the Netherl and s. METHODS One hundred and nine asthmatic out patients ( 56 children ; 53 adults ) were r and omly assigned to the treatment arms ( 12-month follow-up ) . The control group received regular outpatient care , while the intervention group used an asthma monitor with modem at home with an asthma nurse as the main caregiver . Clinical asthma symptoms and medical consumption were measured by using diaries . Asthma-specific quality of life was measured by the ( Paediatric ) Asthma Quality of Life Question naire . RESULTS The study population generally represented mild to moderate asthmatics . The results show improvement in follow-up , but no statistically significant difference between the groups was observed . Moderate to high correlations were found within the outcome parameters , but the most remarkable was the low and statistically significant correlation between asthma-specific quality of life ( daily functioning ) and the self-reported beta-2 agonists . CONCLUSION Overall , the telemonitoring programme evaluated in this study did not significantly decrease asthma symptoms or medical consumption , or improve asthma-specific quality of life . The results showed that a telemonitoring programme on its own is not a guarantee of success . The patients ' perception of asthma-specific quality of life ( daily functioning ) should be a key element in asthma telemonitoring programmes Practical problems and patients or doctors low compliance has been hampering a wider use of self-management in asthma . Mobile or web technologies for supporting selfmanagement may improve patient – doctor communication and patient self-efficacy ( 1 , 2 ) . Furthermore , recent evidence suggests that interactive Internet-based asthma monitoring improves asthma control ( 3 ) . However , patients may not be willing to use a web asthma diary for more than short periods , possibly because it does not fit into their everyday lives ( 4 ) . The use of mobile phones has been suggested to overcome this problem ( 4 , 5 ) , but , to our knowledge , no data are available on the willingness of patients to use mobile phones , and very few data have been reported on their willingness to use the web for asthma self-management ( 6 ) . In the framework of a running r and omized controlled trial on psycho-educational interventions in asthma , 74 adults with moderate to severe asthma were r and omly allocated to fill a symptoms diary for 1 month . Of these , 37 dropped-out of the trial and the remaining 47 ( 63 % ) completed a self-administered question naire about asthma monitoring . These two groups did not differ significantly regarding age , education , socio-economic status , and asthma severity . Approximately one-third was younger than 31 years and half was older than 40 years ; 84 % were female ; nearly 70 % had low socio-economic background ( class IV and V ) and 44 % had 5 or fewer years of formal education . FEV1 predicted % was below 80 % in 53 % , while 64 % were treated with high-dose inhaled steroids . During the previous year , 56 % had at least one exacerbation requiring oral steroids and one in five was admitted to a hospital because of their asthma . Only 28 % had ever self-monitored asthma before entering the study . However , none of the patients referred unwillingness to monitor their asthma in the future , and 56 % of them were strongly in favor to its use ; furthermore , one-third of patients were happy to monitor their symptoms daily , whereas another third preferred to do it less than once a week . Also , one in five considered it was easy to forget to register symptoms in the paper diary , and all patients considered it to help them better underst and their disease . The proportions of referred willingness to use mobile or web technologies to support self-management are described in Table 1 . There were no significant associations between willingness to use mobile or web technologies and patient ’s sex , age , education level , socio-economic status , tobacco usage , other chronic diseases , and duration and severity of asthma . Caution is needed in the generalization of these results as the patients who were studied were mostly middle-aged women with low education , and low socio-economic background , who had moderate to severe asthma followed at secondary care . Nevertheless , a large majority of patients seem willing and ready to use communication technologies such as mobile phones and the Web to help them manage their asthma . Are the doctors and the health administrators also ready to test the effectiveness of this AL LERGY 2 0 0 6 : 6 1 : 3 8 9 – 3 9 5 • COPYR IGHT a 2006 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REVIEW , BUT WILL BE REV IEWED BY THE ASSOCIATE EDITORS We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site r and omized control study . In this program , a nurse under physician supervision monitors the patient 's airway status at home and provides instructions to individuals via the telephone , helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan . Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and r and omly assigned to either the telemedicine or control group . After a six-month study period , an 83 % reduction in hospitalization was demonstrated in the telemedicine group versus the control group , with a P value of 0.01 . Improvement of peak expiratory flow and symptoms were also shown in the study group . We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring , compliance with prescribed daily prophylactic anti-inflammatory steroid medications , and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration This article reports on the development of a personalized , Web-based asthma-education program for parents whose 4- to 12-year-old children have moderate to severe asthma . Personalization includes computer-based tailored messages and a human coach to build asthma self-management skills . Computerized features include the Asthma Manager , My Calendar/Reminder , My Goals , and a tailored home page . These are integrated with monthly asthma-education phone calls from an asthma-nurse case manager . The authors discuss the development process and issues and describe the current r and omized evaluation study to test whether the year-long integrated intervention can improve adherence to a daily asthma controller medication , asthma control , and parent quality of life to reduce asthma-related healthcare utilization . Implication s for health education for chronic disease management are raised The adherence and disease-control outcomes associated with the use of an Internet-based store- and -forward video home telehealth system to manage asthma in children were studied . Pediatric patients with persistent asthma were provided with home computers and Internet access and monitored biweekly over the Internet . All patients were seen in the pediatric clinic at 0 , 2 , 6 , 12 , and 24 weeks . Half of the patients received asthma education in person and half via an interactive Web site . Adherence measures were assessed by therapeutic and diagnostic monitoring . Therapeutic monitoring included digital videos of patients using their controller medication inhaler . Diagnostic monitoring included an asthma symptom diary and a video of peak flow meter use . Videos were su bmi tted electronically twice a week by using in-home telemonitoring with store- and -forward technology . Feedback was provided electronically to each patient . Disease control was assessed by examining quality of life , utilization of services , rescue-therapy use , symptom control , satisfaction with home telemonitoring , and retention of asthma knowledge . Patients were r and omly assigned to an asthma education group ( Internet versus office ) , and the data were analyzed by comparing results for study days 0 - 90 and 91 - 180 . Ten children participated . A total of 321 videos of inhaler use and 309 videos of peak flow meter use were su bmi tted . Inhaler technique scores improved significantly in the second study period . Su bmi ssion of diagnostic monitoring videos and asthma diary entries decreased significantly . Peak flow values as a percentage of personal best values increased significantly . Overall , there was no change in quality of life reported by patients . However , the caregivers in the virtual-education group reported an increase in the patients ' quality -of-life survey scores . Emergency department visits and hospital admissions for asthma were avoided . Rescue therapy was infrequent . A high rate of satisfaction with home telemonitoring was reported . Internet-based , store- and -forward video assessment of children 's use of asthma medications and monitoring tools in their homes appeared effective and well accepted Objective . We previously conducted the School-Based Asthma Therapy trial to improve adherence to national asthma guidelines for urban children through directly observed administration of preventive asthma medications in school . The trial successfully improved outcomes among these children ; however , several factors limit its potential for dissemination . To enhance sustainability , we subsequently developed a new model of care using web-based guides for efficient communications and integration within school and community systems . This article describes the development of the School-Based Preventive Asthma Care Technology ( SB-PACT ) trial . Method . We developed the SB-PACT web-based system based on stakeholder feedback , and conducted a pilot r and omized trial with 100 children to establish its feasibility in facilitating preventive asthma care for high-risk children . The SB-PACT system represents a new model of care using web-based guides for asthma symptom screening , follow-up control assessment s , and electronic communications with providers . Result . We enrolled and successfully screened all children using the web-based system . Most providers used the electronic communication system without difficulty , and the majority of children in the intervention group received preventive medications through school as planned and dose adjustments as needed . Several challenges to implementation also were encountered . Conclusions . This program is design ed to promote sustainability of school-based asthma care , reduce program costs , and ultimately succeed in a real-world setting . With further refinements , it has the potential to be implemented nationally in schools Objectives . To evaluate the effects of an automated interactive voice response system ( IVR ) and Specialist Nurse Support to reduce health care utilization and improve health-related quality of life in children with asthma . Study Design . A r and omized controlled trial in 121 children with doctor-diagnosed asthma and an acute presentation with asthma in the previous 12 months aged between 3 and 16 years . Children were r and omized to one of three groups for a 6-month intervention receiving asthma education and management support from a Specialist Nurse by telephone or e-mail ( N = 41 ) , from IVR ( N = 39 ) , or receiving usual care ( control group ; N = 41 ) . Outcomes included health care utilization and use of oral steroid rescue . Health-related quality of life ( HRQOL ) data using the Pediatric Asthma Quality of Life Question naire and Pediatric Quality of Life Inventory were collected at baseline and at the end of the study . Results : There was no statistically significant benefit identified for either the IVR or the Nurse Support interventions for health care utilization , use of oral steroid rescue , or HRQOL compared with controls . Relative to controls , the incremental costs were −A$225.73 ( 95 % confidence interval [ CI ] : −A$840 , A$ 391 ) per child for the Nurse Support intervention and −A$451.45 ( −A$1075 , A$ 173 ) per child for IVR . The results were most sensitive to the frequency of admissions to hospital . Conclusion . This study suggested that both IVR and Nurse Support interventions may be cost-saving from a health system perspective , with IVR providing the greatest benefit and this pilot study provides a strong basis for developing larger trials with longer follow-up Background . Although regular follow-up is recommended for patients with asthma , the optimal frequency of such follow-up has not been defined . The purpose of this study was to evaluate the relationship of the interval between routine physician visits to asthma outcomes in patients with moderate persistent asthma . Methods . The study population was a volunteer sample of subjects aged 18 years or older with moderate persistent asthma requiring at least moderate doses of inhaled corticosteroids who were followed for at least 6 months by one of two allergists in a large staff model HMO . Subjects were r and omized to one of three groups : 1 ) monthly physician visits , 2 ) semi-annual physician visits , and 3 ) semiannual physician visits and monthly nurse phone calls . All subjects were advised to call their physician for questions or increased symptoms . The primary outcome variable was total asthma quality of life measured at baseline , 6 months and 12 months . Other outcome variables included specific asthma quality of life domains , spirometry , global asthma rating , satisfaction with treatment rating , and asthma re source and medication utilization during the one year of follow-up . Results . The final cohort included 29 patients per group . There were no significant differences between groups in baseline demographics , smoking history , spirometry , asthma quality of life , global rating , or satisfaction with treatment rating . As per the protocol , patients in the monthly physician visit group made significantly more routine visits during the study than other patients ( P<.0001 ) , but there were no other significant differences between groups in any of the other outcome variables at 6 months , 12 months , or during the year of the study . Conclusion . Patients with the characteristics of those in this study do not need routine follow-up visits more often than every 6 months . Further studies will be necessary to determine optimal follow-up intervals for patients with other degrees of asthma severity and for those followed in other setting BACKGROUND Asthma morbidity and mortality rates are high among young inner-city children . Lack of routine primary care provider visits , poor access to care , and poor patient-physician communication might be contributing factors . OBJECTIVE This study evaluated the effects of providing Breathmobile services only , a Facilitated Asthma Communication Intervention ( FACI ) only , or both Breathmobile plus FACI on asthma outcomes relative to st and ard care . METHODS Children with asthma ( n = 322 ; mean age , 4 years ; 53 % male ; 97 % African American ) were recruited from Head Start programs in Baltimore City and r and omized into 4 groups . Outcome measures included symptom-free days ( SFDs ) , urgent care use ( emergency department visits and hospitalizations ) , and medication use ( courses of oral steroids and proportion taking an asthma controller medication ) , as reported by caregivers at baseline , 6-month , and 12-month assessment s. Generalized estimating equations models were conducted to examine the differential treatment effects of the Breathmobile and FACI compared with st and ard care . RESULTS Children in the combined treatment group ( Breathmobile plus FACI ) had an increase of 1.7 ( 6.6 % ) SFDs that was not maintained at 12 months . In intent-to-treat analyses the FACI-only group had an increase in the number of emergency department visits at 6 months , which was not present at 12 months or in the post hoc as-treated analyses . No significant differences were found between the intervention groups compared with those receiving st and ard care on all other outcome measures . CONCLUSIONS Other than a slight improvement in SFDs at 6 months in the Breathmobile plus FACI group , the intervention components did not result in any significant improvements in asthma management or asthma morbidity Objectives . Asthmatic children and their parents constantly need to adjust their lifestyles due to asthma attacks . We evaluated the effectiveness of a self-management interactive support ( SMIS ) program for caregivers of asthmatic children . Methods . Children with persistent asthma were r and omized into two groups , one receiving SMIS and the other receiving usual care ( the control group ) . The SMIS program involved a three-month multifaceted behavioral intervention . Changes in the caregivers ’ knowledge and attitude regarding self-management , children ’s lung function , and number of emergency department visits and hospital admissions were examined at 12 months post-enrollment . Results . Sixty-five asthmatic children and caregivers ( 78 % follow-up ) completed the study . Primary caregivers in the SMIS group had significant improvements in knowledge and attitude regarding asthma compared to those in the control group ( p < .05 ) . Most importantly , knowledge about asthma medications and exacerbations significantly improved and attitudes toward medication adherence and dealing with asthma care became more positive in the SMIS group . The forced expiratory volume in one second was significantly improved in the SMIS group after 12 months ( p < .05 ) , and performance in the methacholine challenge test at the end of the study was significantly better in the SMIS group ( p < .05 ) . Participants in the SMIS group also had a lower rate of emergency room use ( p < .05 ) . Conclusion . The SMIS program for the self-management of asthma in children by their caregivers improved lung function and reduced the number of visits to the emergency departments . Interactive support interventions reinforce learning incentives and encourage self-care and maintenance of therapeutic regimens Context Patient self-management is an essential component of asthma care , and the Internet is a medium to potentially support patients in self-management . Contribution This r and omized trial compared Internet-based asthma self-management with usual care and found modest improvements in asthma control and lung function with the Internet intervention , but found no reduction in exacerbations and changes in asthma-related quality of life that were less than clinical ly significant at 12 months . Implication Although Internet-based self management can improve some asthma outcomes , the improvements were small and the program did not reduce the number of exacerbations . The Editors Asthma is a chronic disorder of the airways that is characterized by recurring respiratory symptoms , variable airflow obstruction , airway hyperresponsiveness , and underlying inflammation ( 1 , 2 ) . Recent clinical guidelines for the management of asthma distinguish 4 essential components of asthma care : assessment and monitoring , patient education , control of environmental and comorbid factors that affect asthma , and drug treatment . With appropriate medical care , well-informed and empowered patients can control their asthma and live full , active lives ( 1 , 2 ) . However , despite the availability of monitoring tools and effective therapy , asthma control is suboptimal in many patients worldwide , and long-term management falls far short of the goals set in the guidelines ( 3 ) . Self-monitoring , education , and specific medical care are important aspects in improving the lives of patients with asthma ( 1 , 2 ) . However , many patients with mild or moderate persistent asthma do not attend checkups regularly or visit their physician with symptoms of the disease ( 4 ) . In addition , in practice , both patients and their health care providers are reluctant to use written self-management plans ( 5 ) . Internet technology is increasingly seen as an appealing tool to support self-management for patients with chronic disease in remote and underserved population s ( 68 ) . However , to date , studies on Internet-based asthma self-management show only short-term improvements in asthma control , lung function , and quality of life ( 911 ) . Long-term studies on the effect of Internet-based self-management , including all its essential features , are not available . Therefore , we developed a guided self-management tool for adult patients with asthma that included Internet-based home monitoring and treatment advice ( action plan ) , online education , and remote Web communication with a specialized asthma nurse . The goal of our study was to assess the long-term clinical effectiveness of Internet-based self-management education compared with usual physician-provided care alone . Methods Design Overview We conducted a 12-month , multicenter , nonblinded , r and omized , controlled trial . We r and omly assigned patients to Internet-based self-management ( Internet group ) as an adjunct to usual care or to usual physician-provided care alone ( usual care group ) . The Internet-based self-management program included weekly asthma control monitoring and treatment advice , online and group education , and remote Web communications with a specialized asthma nurse . The intervention continued for 12 months after enrollment . The Medical Ethics Committee of the Leiden University Medical Center , Leiden , the Netherl and s , approved the study . Setting and Participants We recruited patients from 37 general practice s ( 69 general practitioners ) in the Leiden and The Hague area and the Outpatient Clinic of the Department of Pulmonology at the Leiden University Medical Center from September 2005 to September 2006 . Inclusion criteria were physician-diagnosed asthma coded according to the International Classification of Primary Care in the electronic medical record ( 12 ) , age 18 to 50 years , prescription of inhaled corticosteroids for at least 3 months in the previous year , no serious comorbid conditions that interfered with asthma treatment , access to the Internet at home , and mastery of the Dutch language . We excluded patients who were receiving maintenance oral glucocorticosteroid treatment . On the basis of diagnosis , age , prescribed asthma medication , and comorbid conditions , we sent eligible patients an invitation letter followed by 1 reminder letter after 2 to 4 weeks if they did not respond to the first . We continued this process until a total of 200 patients had entered the study ( September 2006 ) . All participants gave written consent . R and omization and Intervention In a 2-week baseline period before r and omization , we collected data on patient demographic characteristics , asthma-related quality of life , symptom control , lung function , and medication level . We provided basic education about core information on asthma , action of medications , and inhaler technique instructions to all patients . We trained all participants to measure FEV1 daily with a h and -held electronic spirometer ( PiKo-1 , Ferraris Respiratory , Hertford , United Kingdom ) and to report the highest value of 3 measurements in the morning before taking medication ( 2 , 13 ) . They were shown how to report these values on a personal page on a secure Web application by using a login password ( or how to report by mobile telephone text message ) . Patients were also asked to report their nighttime and daytime asthma symptom scores on this Internet page or by text message . We asked all participants to complete the Asthma Control Question naire on their personal Internet page each week ( 14 ) . We did not give any patients feedback about lung function or asthma control . After the 2-week baseline period , we r and omly assigned participants to either the Internet group or the usual care group . We stratified according to care provider ( primary vs. subspecialty care ) and asthma control at baseline ( 15 ) . We r and omly assigned patients to the 2 groups ( 1:1 ratio ) by using a computer-generated , permuted-block scheme . Allocation took place by computer after collection of the baseline data , ensuring concealment of allocation . The Internet-based self-management program consisted of the 4 principal components of asthma self-management and was accessed through the specially design ed Web site , which allowed monitoring through the Web site ( or text message on a mobile telephone ) , use of an Internet-based treatment plan , online education , and Web communications with a specialized asthma nurse ( 16 ) . Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Question naire on the Web site and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan ( Table 1 and Appendix Figures 1 , 2 , 3 , 4 , and 5 ) . Depending on the scores su bmi tted , patients received 4 types of self-treatment advice . When 4 consecutive Asthma Control Question naire scores were 0.5 or less , patients were advised to decrease treatment according to treatment plan . When 2 consecutive scores were greater than 0.5 but less than 1.0 , patients were advised to increase treatment according to treatment plan . When 1 score was 1.0 or more but less than 1.5 , patients were advised to immediately increase treatment according to treatment plan . Finally , when 1 score was 1.5 or more , patients were advised to immediately increase treatment and contact the asthma nurse . Table 1 . Treatment Plan Appendix Figure 1 . Algorithm based on consecutive ACQ scores to adjust medical treatment . * ACQ = Asthma Control Question naire . At entry of the algorithm , the evaluation period is bypassed . The evaluation period starts after treatment was stepped up . The optimal control period starts after 1 ACQ score 0.5 and ends after 1 ACQ score > 0.5 . Appendix Figure 2 . Screen shot of daily lung function and symptom monitoring . Appendix Figure 3 . Screen shot of feedback on daily lung function and symptom monitoring . Appendix Figure 4 . Screen shot of weekly Asthma Control Question naire monitoring . Appendix Figure 5 . Screen shot of feedback on Asthma Control Question naire , treatment advice according to personalized treatment plan , and results of past 6 months . We advised no medication changes during the 4 weeks after treatment was stepped up ( evaluation period ) . In addition to weekly assessment s , patients could optionally report daily symptoms and lung function and were able to contact our asthma nurse though the Web or by telephone . Thus , any acute deterioration warranting a visit to the general practitioner or hospital could be detected ( Appendix Figures 2 and 3 ) . We aim ed to empower patients to use the Internet-based self-management tool and to develop a patientprovider partnership in asthma care ( 2 ) . Self-management education consisted of both Web-based and face-to-face , group-based education . Web-based education included asthma information , news , frequently asked questions , and interactive communication with a respiratory nurse specialist . We scheduled 2 group-based education sessions , which lasted 45 to 60 minutes , for patients in the Internet-based self-management group within 6 weeks after entering the trial . Both sessions included exploration of a patient 's interests and previous knowledge ( negotiating an agenda and patient-centered education ) , personalized feedback , and empowerment of self-management ( self-efficacy and implementing a plan for change ) ( 2 , 17 ) . The first educational session also included pathophysiology of asthma , information on the Web-based action plan , and information and review of inhalation technique . The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance . Patients in the usual care group received asthma care according to the Dutch general practice guidelines on asthma management in adults , which recommend a medical review and treatment adjustment every 2 to 4 weeks in unstable asthma and medical review once or twice Background The rising prevalence of chronic conditions constitutes a major burden for patients and healthcare systems and is predicted to increase in the upcoming decades . Improving the self-management skills of patients is a strategy to steer against this burden . This could lead to better outcomes and lower healthcare costs . Health coaching is one method for enhancing the self-management of patients and can be delivered by phone . The effects of telephone-based health coaching are promising , but still inconclusive . Economic evaluations and studies examining the transferability of effects to different healthcare systems are still rare . Aim of this study is to evaluate telephone-based health coaching for chronically ill patients in Germany . Methods / Design The study is a prospect i ve r and omized controlled trial comparing the effects of telephone-based health coaching with usual care during a 4-year time period . Data are collected at baseline and after 12 , 24 and 36 months . Patients are selected based on one of the following chronic conditions : diabetes , coronary artery disease , asthma , hypertension , heart failure , COPD , chronic depression or schizophrenia . The health coaching intervention is carried out by trained nurses employed by a German statutory health insurance . The frequency and the topics of the health coaching are manual-based but tailored to the patients ’ needs and medical condition , following the concepts of motivational interviewing , shared decision-making and evidence -based-medicine . Approximately 12,000 insurants will be enrolled and r and omized into intervention and control groups . Primary outcome is the time until hospital readmission within two years after enrolling in the health coaching , assessed by routine data . Secondary outcomes are patient-reported outcomes like changes in quality of life , depression and anxiety and clinical values assessed with question naires . Additional secondary outcomes are further economic evaluations like health service use as well as costs and hospital readmission rates . The statistical analyses includes intention-to-treat and as-treated principles . The recruitment will be completed in September 2014 . Discussion This study will provide evidence regarding economic and clinical effects of telephone-delivered health coaching . Additionally , this study will show whether health coaching is an adequate option for the German healthcare system to address the growing burden of chronic diseases . Trial registration German Clinical Trials Register ( Deutsches Register Klinischer Studien ; DRKS ) DRKS00000584 OBJECTIVE To assess the feasibility , acceptability , and preliminary impact of a telepharmacy intervention in an underserved , rural asthma patient population . SUBJECTS AND METHODS Patients with asthma were r and omized to receive either st and ard care or telephone consultations from pharmacists regarding asthma self-management over a 3-month period . Qualitative interviews were conducted to identify participants ' attitudes/opinions regarding the intervention . Baseline and follow-up surveys assessed asthma control , patient activation , and medication utilization . RESULTS Ninety-eight adults were recruited ( 78 % accrual ) ; 83 completed the study ( 15 % dropout ) . Participants reported positive opinions and believed the intervention improved their asthma self-management . The intervention group had significantly higher patient activation compared with the control ( p<0.05 ) . There were no significant between-group differences regarding asthma control . However , within-group analyses of the intervention group showed an improvement in asthma control ( p<0.01 ) and medication adherence ( p<0.01 ) . No within-group differences were found for the control group . CONCLUSIONS This telepharmacy intervention is feasible and showed indicators of effectiveness , suggesting the design is well suited for a robust study to evaluate its impact in uncontrolled asthma patients . Pharmacists helping patients manage asthma through telecommunications may resolve access barriers and improve care BACKGROUND We examined the feasibility of self-directed Triple P ' Positive Parenting Programme ' for optimizing parents ' management of childhood asthma and behaviour . METHODS Eligible families were invited to access asthma-specific web-based Triple P as part of a preliminary r and omized controlled study . RESULTS Initial study information and introductory website pages received considerable interest but intervention uptake was poor with high rates of attrition . CONCLUSIONS Although parents of children with asthma show willingness to access web-based parenting support , further work is necessary to develop engaging websites and determine barriers to uptake , and adherence to online parenting interventions with this population The CYMPLA trial . Mobile phone-based str rct rred intervention to achieve asthma control in patients with rncontrolled persistent asthma : a pragmatic r and omised controlled OBJECTIVE To describe medication therapy management ( MTM ) services via videoconferencing . DESIGN A descriptive , cross-sectional analysis of an ongoing prospect i ve , r and omized-controlled study . SETTING A secured seven-pharmacy network connected by computers , webcams , telephones , and electronic medical records . PARTICIPANTS Patients 18 years of age or older ; taking four or more chronic medications ; and with diabetes , hypertension , hyperlipidemia , asthma/chronic obstructive pulmonary disease , multiple sclerosis , and /or Parkinson 's disease . INTERVENTIONS Chart review s and videoconferencing interviews to identify medication-related problems ( MRP ) and provide patient education and recommendations to providers . MAIN OUTCOME MEASURES Patient demographics , identified MRPs , interventions , and patient satisfaction . RESULTS During April to July 2010 , 43 patients were interviewed ( mean age 50.8 ± 11.5 years ) ; of these , 12 patients ( 27.9 % ) were older adults , mean age 69.5 ± 5.0 years . Prevalent health conditions were hypertension ( 31/43 , 72 % ) , hyperlipidemia ( 28/43 , 65 % ) , and diabetes ( 19/43 , 44 % ) . A mean number of 3.5 ± 2.3 MRP/patient was identified . Compared with charted numbers , patients significantly under-reported their health conditions ( selfreported mean number 4.0 ± 1.6 , compared with 6.9 ± 3.3 , P < 0.0001 ) and medications used ( self-reported mean number 7.7 ± 3.4 , charted number 9.4 ± 2.3 , P < 0.005 ) . Providers accepted a mean number of 2.2 ± 1.6 ( out of 2.8 ± 1.3 ) pharmacist-provided recommendations ( acceptance rate 78.6 % ) . All patients interviewed agreed or strongly agreed that the MTM interview with pharmacist and the information provided were helpful . CONCLUSION Webcam-enabled videoconferencing allows effective interactions between pharmacists and patients to identify MRP and improve access to MTM services . Provider acceptance of pharmacist-provided recommendations and patient satisfaction with videoconferencing MTM services are high |
13,061 | 24,703,918 | All studies of early myocardial changes with chemotherapy demonstrate that alterations of myocardial deformation precede significant change in left ventricular ejection fraction ( LVEF ) .
Using tissue Doppler-based strain imaging , peak systolic longitudinal strain rate has most consistently detected early myocardial changes during therapy , whereas with speckle tracking echocardiography ( STE ) , peak systolic global longitudinal strain ( GLS ) appears to be the best measure .
A 10 % to 15 % early reduction in GLS by STE during therapy appears to be the most useful parameter for the prediction of cardiotoxicity , defined as a drop in LVEF or heart failure .
In late survivors of cancer , measures of global radial and circumferential strain are consistently abnormal , even in the context of normal LVEF , but their clinical value in predicting subsequent ventricular dysfunction or heart failure has not been explored .
Thus , this systematic review confirms the value of echocardiographic myocardial deformation parameters for the early detection of myocardial changes and prediction of cardiotoxicity in patients receiving cancer therapy | The literature exploring the utility of advanced echocardiographic techniques ( such as deformation imaging ) in the diagnosis and prognostication of patients receiving potentially cardiotoxic cancer therapy has involved relatively small trials in the research setting .
In this systematic review of the current literature , we describe echocardiographic myocardial deformation parameters in 1,504 patients during or after cancer chemotherapy for 3 clinical ly-relevant scenarios . | PURPOSE This study sought to estimate cardiac dysfunction ( CD ) risk for patients receiving trastuzumab ; to characterize observed CD by severity , treatment , and clinical outcome ; to assess effects of baseline clinical risk factors on CD ; and to assess effects of cumulative doses of anthracyclines and trastuzumab on CD . PATIENTS AND METHODS A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumab clinical trials was performed . Predefined criteria were used for the diagnosis , and the New York Heart Association functional classification system was used to document CD severity . Product-limit estimates were used to summarize the cumulative anthracycline and trastuzumab doses at the time of CD onset . RESULTS Patients treated with trastuzumab were found to be at an increased risk for CD . The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide ( 27 % ) . The risk was substantially lower in patients receiving paclitaxel and trastuzumab ( 13 % ) or trastuzumab alone ( 3 % to 7 % ) ; however , most of these patients had received prior anthracycline therapy . CD was noted in 8 % of patients receiving anthracycline plus cyclophosphamide and 1 % receiving paclitaxel alone . Most trastuzumab-treated patients developing CD were symptomatic ( 75 % ) , and most improved with st and ard treatment for congestive heart failure ( 79 % ) . CONCLUSION Trastuzumab is associated with an increased risk of CD , which is greatest in patients receiving concurrent anthracyclines . In most patients with metastatic breast cancer , the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab BACKGROUND The aim of this case-control study was to assess the usefulness of three-dimensional ( 3D ) speckle-tracking echocardiography in the evaluation of global left ventricular ( LV ) myocardial performance in adolescent and adult survivors of childhood cancers . METHODS Fifty-three anthracycline-treated survivors of childhood cancers ( mean age , 18.6 ± 5.1 years ) and 38 controls were studied . Three-dimensional speckle-tracking echocardiography was performed to assess LV 3D global and segmental strain , time to peak segmental 3D strain , LV torsion , and ejection fraction . LV systolic dyssynchrony index ( SDI ) was calculated as the percentage of the st and ard deviation of times to peak strain of the 16 segments divided by the RR interval . A global performance index ( GPI ) was calculated as ( global 3D strain × torsion)/SDI . The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic indices to discriminate between patients and controls . RESULTS Compared with controls , patients had significantly reduced LV global 3D strain ( P < .001 ) , torsion ( P < .001 ) , and GPI ( P < .001 ) and greater SDI ( P < .001 ) . All except the basal anteroseptal segment in patients had reduced regional 3D strain compared with controls ( P < .05 for all ) . Global 3D strain ( P = .018 ) , SDI ( P = .003 ) , and GPI ( P = .02 ) were correlated with cumulative anthracycline dose . The areas under the curves for GPI , global 3D strain , 1/SDI , torsion , and ejection fraction were 0.92 , 0.79 , 0.79 , 0.79 , and 0.78 , respectively . A GPI cutoff of 10.6 ° /cm had sensitivity of 84.9 % and specificity of 81.6 % of differentiating patients from controls . CONCLUSIONS Three-dimensional speckle-tracking echocardiography enables the derivation of an index of LV global performance that incorporates LV 3D strain , dyssynchrony , and torsion for the sensitive detection of altered LV mechanics in childhood cancer survivors Background Salidroside [ 2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside ] , one of the most potent ingredients extracted from the plant Rhodiola rosea L. , has been shown to have a cardiovascular protective effect as an antioxidant , and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer . However , the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity , especially early left ventricular regional systolic dysfunction , have to date been sparsely investigated . Objective The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin . Methods Sixty patients with histologically confirmed breast cancer were enrolled . Eligible patients were r and omized to receive salidroside ( 600 mg/day ; n= 30 ) or placebo ( n = 30 ) starting 1 week before chemotherapy . Patients were investigated by means of echocardiography and strain rate ( SR ) imaging . We also measured plasma concentrations of reactive oxygen species ( ROS ) . All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2 . Results A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2 , with no significant differences between salidroside and placebo ( 1.35 ± 0.36 vs 1.42 ± 0.49/second ) . At growing cumulative doses of epirubicin , the SR normalized only with salidroside , showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 ( 1.67 ± 0.43 vs 1.32 ± 0.53/second , p < 0.05 ) and 400 mg/m2 ( 1.68±0.29 vs 1.40 ± 0.23/second , p < 0.05 ) . Moreover , a significant increase in plasma concentrations of ROS was found with placebo , but they remained unchanged with salidroside . ConclusionS alidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer BACKGROUND The occurrence of chronic anthracycline cardiotoxicity leading to heart failure and even death is a major concern in the treatment of childhood malignancies . Currently , most treatment protocol s use reduced anthracycline doses compared with historical exposure . The long-term effect of these reduced doses on myocardial function has not been well studied . METHODS We examined 56 asymptomatic patients . They all had been treated with anthracyclines at a cumulative dose less than 300 mg/m2 5.2 ( range : 2.0 - 15.2 ) years before the current evaluation . In all patients , st and ard two-dimensional , Doppler echocardiographic measurements , end-systolic wall stress calculation , and color Doppler myocardial imaging data were obtained . From the color Doppler myocardial imaging data , peak systolic myocardial velocities , peak systolic strain rate , and peak systolic strain [ symbol : see text ] were computed . The myocardial acceleration during isovolumetric contraction was measured at the basal left ventricular ( LV ) lateral and right ventricular free wall . Data were compared with 32 age-matched normal controls . RESULTS In asymptomatic patients previously exposed to low-dose anthracycline treatment , several changes in cardiac function were noted : 1 . LV diastolic function was abnormal with a prolonged isovolumetric relaxation time and abnormal pulmonary venous flow patterns . 2 . End-systolic wall stress was increased . 3 . LV annular motion was reduced . 4 . Systolic myocardial deformation was reduced with a significant decrease in both radial and longitudinal peak systolic strain rate and [ symbol : see text ] . CONCLUSIONS Changes in systolic and diastolic function are noted in asymptomatic patients with normal ejection fraction late after low-dose anthracycline treatment . This confirms that sub clinical LV dysfunction is present in patients after low-dose anthracycline treatment during childhood . The long-term significance of these findings warrants further follow-up BACKGROUND Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity . Telmisartan , an angiotensin II type 1 receptor blocker , inhibits activation of superoxide sources and induces anti-inflammatory effects . METHODS The possible role of telmisartan in preventing myocardial damage induced by epirubicin ( EPI ) was investigated . Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined . Eligible patients were r and omized to receive telmisartan ( 40 mg/d ; TEL , n = 25 ) or placebo ( PLA , n = 24 ) starting 1 week before chemotherapy . Patients were studied by means of echocardiography , tissue Doppler , and strain and strain rate ( SR ) imaging . We also measured plasma levels of inflammatory and oxidative stress markers . All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m(2 ) . RESULTS An impairment of the SR peak was observed at the EPI dose of 200 mg/m(2 ) , with no significant differences between TEL and PLA ( 1.41 + /- 0.31 vs 1.59 + /- 0.36/s ) . At growing cumulative doses of EPI , SR normalized only in TEL , showing a significant difference in comparison to PLA at EPI doses of 300 mg/m(2 ) ( 1.69 + /- 0.42 vs 1.34 + /- 0.18/s , P < .001 ) and 400 mg/m(2 ) ( 1.74 + /- 0.27 vs 1.38 + /- 0.24/s , P < .001 ) . Moreover , a significant increase in reactive oxygen species and interleukin-6 was found in PLA ; but these remained unchanged in TEL . CONCLUSIONS We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses . In addition , we showed that telmisartan can reduce EPI-induced radical species , antagonize the inflammation , and reverse the early myocardial impairment AIMS The benefits from anthracycline chemotherapy are undermined by potentially life-threatening cardiotoxicity . Transthoracic echocardiography is the most commonly used method for monitoring cardiotoxicity , and centres on the measurement of left ventricular systolic function . The aim of this study was to utilize two-dimensional speckle tracking echocardiography ( 2DSTE ) at baseline and immediately after anthracycline chemotherapy to investigate whether patients with significant changes in systolic function after anthracycline therapy would also develop alterations in diastolic parameters . METHODS AND RESULTS Fifty-two women with histologically confirmed breast cancer were prospect ively recruited . Echocardiograms were performed 1 week prior to and 1 week following chemotherapy ( always before adjuvant trastuzumab or thoracic radiotherapy ) . Conventional Doppler , tissue velocity imaging ( TVI ) , and 2DSTE were used to measure diastolic function . 2DSTE measurements included longitudinal diastolic strain , early ( E-Sr ) , and late ( A-Sr ) myocardial strain rate . 2DSTE and left ventricular ejection fraction ( LVEF ) were used to measure longitudinal systolic function . Altered LV diastolic function ( including E-Sr ) was observed in the entire cohort after chemotherapy , with a differential reduction in participants with a post therapy LVEF < 55 % . Pre-chemotherapy systolic strain was found to predict reduced E-Sr post therapy ( P = 0.04 ) . Univariate predictors of E-Sr were LVEF post therapy ( P = 0.049 ) and systolic strain post-therapy ( P = 0.01 ) . In a multivariate analysis , systolic strain after chemotherapy was the strongest independent predictor ( P = 0.001 ) . CONCLUSION Altered LV diastolic function was observed immediately after the administration of therapeutic doses of anthracycline chemotherapy . Furthermore , our analysis indicates that the changes in diastolic function are associated with reduced systolic function The aim of this study was to describe the acute effects of anthracyclines on left ventricular systolic and diastolic function using different echocardiographic modalities . Thirteen children scheduled to receive anthracyclines were prospect ively studied . They underwent complete 2-dimensional and Doppler echocardiographic evaluations , including tissue Doppler imaging , before the first dose and < 2 hours after each of the first 3 doses of anthracyclines ( dose range 30 to 75 mg/m2 ) . After the first dose , increased end-diastolic wall thickness , decreased wall thickening , and a prolonged myocardial performance index were noted . Parameters of diastolic function changed significantly , with a lower mitral E wave , a decreased E/A ratio , and prolonged isovolumic relaxation time . Also , reduced longitudinal early diastolic myocardial velocity and myocardial velocity acceleration during isovolumic contraction as well as reduced peak longitudinal and radial systolic strain rate and strain were noted . All these parameters remained significantly lower after subsequent doses . After the second dose , significant changes in the shortening fraction and the ejection fraction compared with baseline became apparent . After the third dose , further deterioration in radial peak systolic strain was seen . In conclusion , low to moderate doses of anthracyclines acutely induce cardiac diastolic and systolic dysfunction A phase II , open , nonr and omized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early pre clinical changes that are predictive of the risk for heart failure . Thirty-one patients ( male/female ratio , 8/23 ; mean age + /- st and ard deviation , 59 + /- 14 years ) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen , were enrolled . We prospect ively evaluated the acute ( 1 week after ) and late ( 3 , 6 , 12 , and 18 months of follow-up ) effects of epirubicin administration . A significant impairment in systolic left ventricular ( LV ) function was observed at a cumulative epirubicin dose of 200 mg/m(2 ) . This was shown by a reduction in the strain rate ( SR ) peak in comparison with baseline and persisted throughout the treatment and follow-up , up to 18 months ; strain ( Sigma ) remained unchanged . The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up . On TDI the E(m)/A(m ) ratio declined at the 200-mg/m(2 ) cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up . On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m(2 ) cumulative epirubicin dose . Interleukin (IL)-6 , soluble IL-6 receptor , and reactive oxygen species ( ROS ) increased significantly at the 200-mg/m(2 ) dose , and IL-6 was persistently high at the 300- and 400-mg/m(2 ) doses , returning to within baseline values during follow-up . ROS , after the peak reached at the 200-mg/m(2 ) dose , returned to within baseline values . A significant inverse correlation between DeltaSR and the increase in both IL-6 and ROS was observed . A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of DeltaSR . The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up AIMS The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia ( ALL ) during and shortly after treatment with anthracyclines . METHODS AND RESULTS Cardiac function of 60 children with ALL was prospect ively studied with measurements of cardiac troponin T ( cTnT ) and N-terminal-pro-brain natriuretic peptide ( NT-pro-BNP ) and conventional and myocardial 2D strain echocardiography before start ( T = 0 ) , after 3 months ( T = 1 ) , and after 1 year ( T = 2 ) , and were compared with 60 healthy age-matched controls . None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening . Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls . Cardiac troponin T levels were abnormal in 11 % of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 ( P = 0.003 ) . N-terminal-pro-brain natriuretic peptide levels were abnormal in 13 % of patients at T = 1 and in 20 % at T = 2 , absolute values increased throughout treatment in 59 % . Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1 , for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline . CONCLUSION Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography . N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore , the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines We studied the role of global myocardial strain and strain rate in monitoring sub clinical heart failure in a large group of asymptomatic long-term survivors of childhood cancer . Global strain ( rate ) parameters of survivors were compared with those in healthy controls and were related to conventional echocardiographic parameters , N-terminal-pro-natriuretic peptide ( NT-pro-BNP ) levels and clinical parameters . Two-dimensional ( 2-D ) echocardiography was performed in 111 survivors and 107 healthy controls . Blood sample s were taken from survivors to determine NT-pro-BNP levels . We showed that global myocardial strain , strain rate and time to peak systolic strain in asymptomatic survivors of childhood cancer were significantly lower compared with healthy controls ( p values < 0.0001 ) and were significantly related to several systolic and diastolic left ventricular parameters . Whether myocardial strain and strain rate are superior to conventional echocardiography in the early detection of sub clinical heart failure needs to be explored in further longitudinal prospect i ve studies PURPOSE Strain rate imaging ( SRI ) is a new echocardiographic modality that enables accurate measurement of regional myocardial function . We investigated the role of SRI and troponin I ( TnI ) in the detection of sub clinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients . METHODS AND MATERIAL S This study prospect ively included 75 women ( 51 left-sided and 24 right-sided ) receiving adjuvant RT to the breast/chest wall and regional lymph nodes . Sequential echocardiographs with SRI were obtained before RT , immediately after RT , and 8 and 14 months after RT . TnI levels were measured on the first and last day of RT . RESULTS Mean heart and left ventricle ( LV ) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy , respectively , for the right-sided patients . A decrease in strain was observed at all post-RT time points for left-sided patients ( -17.5 % ± 1.9 % immediately after RT , -16.6 % ± 1.4 % at 8 months , and -17.7 % ± 1.9 % at 14 months vs -19.4 % ± 2.4 % before RT , P<.01 ) but not for right-sided patients . When we considered left-sided patients only , the highest mean dose was given to the anterior left ventricular ( LV ) wall ( 25 ± 14 Gy ) and the lowest to the inferior LV wall ( 3 ± 3 Gy ) . Strain of the anterior wall was reduced after RT ( -16.6 % ± 2.3 % immediately after RT , -16 % ± 2.6 % at 8 months , and -16.8 % ± 3 % at 14 months vs -19 % ± 3.5 % before RT , P<.05 ) , whereas strain of the inferior wall showed no significant change . No changes were observed with conventional echocardiography . Furthermore , mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT , whereas TnI levels of the right-sided patients remained unaffected . CONCLUSIONS In contrast to conventional echocardiography , SRI detected a regional , sub clinical decline in cardiac function up to 14 months after breast RT . It remains to be determined whether these changes are related to clinical outcome . In the meantime , we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients BACKGROUND Pediatric cancer survivors who have been exposed to anthracycline ( ANT ) chemotherapy are an ever increasing population at risk for premature cardiac disease . Studies have shown that ANT is associated with impaired left ventricular ( LV ) myocardial deformation , but this has not been shown to be associated with traditional echocardiographic measures of LV systolic dysfunction . The aim of this study was to test the hypothesis that changes in LV longitudinal peak systolic strain ( LPSS ) would correlate with parameters of LV systolic dysfunction . METHODS This study included 19 prospect ively enrolled pediatric patients receiving ANT ( mean dose , 296 ± 103 mg/m(2 ) ) and 19 controls matched for age , gender , and body surface area . For ANT patients , echocardiography was performed at baseline , mid , and final treatment points ( 0 , 4 , and 8 months ) . St and ard echocardiographic parameters and two-dimensional speckle tracking-derived longitudinal strain parameters were obtained and compared with baseline measurements in controls . Associations between changes in LV global LPSS and st and ard echocardiographic indices were explored . RESULTS Within the ANT group , the change in LV global LPSS showed a significant decrease compared with baseline at 4 months ( 8.7 ± 0.2 % , P = .033 ) and 8 months ( 9.2 ± 0.3 % , P = .015 ) , while the percentage change in ejection fraction ( EF ) showed a statistically significant decrease at 8 months ( 4.3 ± 0.1 % , P = .044 ) . LV global LPSS was decreased in the ANT group compared with controls at 4 months ( 18.1 ± 2.5 % vs 20.5 ± 1.5 % , P = .011 ) and 8 months ( 18.1 ± 2.8 % , P = .032 ) . Segmental changes in mid and apical LV LPSS average were significantly correlated with change in EF ( mid : r = -0.49 , β = -0.645 , P = 0.039 ; apical : r = -0.48 , β = -0.4126 , P = .046 ) . CONCLUSIONS In adolescents who receive ANT therapy , changes in two-dimensional LV global LPSS precede decreases in EF , and segmental changes in mid and apical LV LPSS suggest an increased likelihood that depressed LV EF will be observed later in follow-up . Two-dimensional speckle tracking-derived LV LPSS is potentially useful in the serial clinical monitoring of ANT cardiotoxicity AIMS The efficacy of anthracyclines is undermined by potential life-threatening cardiotoxicity . Cardiotoxicity is dependent upon several factors and the timing to its development is variable . Moreover , as adjuvant therapy with trastuzumab often follows , a close monitoring of cardiac function in those treated with anthracyclines is m and atory . Left ventricular ejection fraction ( LVEF ) by echocardiography is currently used for monitoring cardiotoxicity ; however , LVEF has numerous limitations . Two-dimensional strain imaging may provide a more sensitive measure of altered LV systolic function , so the aim of the present study was to compare LVEF and LV systolic strain before and after anthracyclines . METHODS AND RESULTS Fifty-two women with histologically confirmed breast cancer were prospect ively studied . Echocardiographic LVEF ( by Simpson 's method ) , global and regional peak longitudinal , radial , and circumferential 2D systolic strain were measured 1 week before and 1 week after chemotherapy . Global and regional longitudinal LV systolic strain was significantly reduced after treatment ; global longitudinal strain decreased from -17.7 to -16.3 % ( P < 0.01 ) with 48 % of global measurements reduced by > 10 % . Global and regional radial LV systolic strain after treatment was also significantly reduced ; global radial strain dropped from 40.5 to 34.5 % ( P < 0.01 ) with 59 % of global measurements reduced by > 10 % . In contrast , no reduction in LVEF > 10 % after chemotherapy was observed . CONCLUSION Reduced LV systolic strain immediately after anthracycline treatment may indicate early impairment of myocardial function before detectable change in LVEF Anthracyclines are important anticancer drugs , but their use is limited by cardiotoxicity . Left ventricular ejection fraction ( LVEF ) is often inadequate to detect myocardial disease induced by chemotherapy . Tissue Doppler and bidimensional-strain imaging could detect LV myocardial dysfunction earlier than LVEF . In drug-induced cardiotoxicity , torsional and longitudinal LV deformations [ LV twist ( LVtw ) , radial strain ( GRS ) , global longitudinal strain ( GLS ) ] are damaged . We assessed whether a new index , GLS × LVtw , could predict future anthracycline-induced cardiomyopathy . Echocardiography , troponin , and natriuretic peptide determination were prospect ively performed in 74 patients before and after 6 , 12 , 24 , and 52 weeks of anthracycline treatment . These patients were treated for breast cancer , Hodgkin 's or non-Hodgkin 's lymphoma , acute lymphoblastic or myeloblastic leukaemia , or osteosarcoma . At 6 weeks after initiation of chemotherapy , isovolumic relaxation time , systolic mitral annular velocity , LVGLS , LVGRS , LV apical rotation , LVtw , and GLS × LVtw deteriorated , and troponin levels became elevated ( all p < 0.05 by ANOVA ) before LVEF decreased . The receiver operating characteristic curves identified early deterioration of GLS × LVtw as the best predictor of later cardiotoxicity ( area under curve = 0.93 ) , followed by GLS ( 0.84 ) and LV apical rotation ( 0.81 ) deterioration . In conclusion , early change in the GLS × LVtw index seems to be a good predictor of future development of anthracycline-induced cardiotoxicity A phase II , open , nonr and omized trial was carried out in a group of epirubicin-treated patients with cancer at different sites with the aim of detecting early pre clinical changes that are predictive of the risk for heart failure . All patients underwent conventional echocardiography , as well as tissue Doppler imaging ( TDI ) with strain ( sigma ) and strain rate ( SR ) , a very accurate technique for detecting minimal changes in cardiac left ventricular ( LV ) function . Moreover , echocardiographic changes identified during epirubicin treatment were compared with those of a series of biochemical markers of both myocardial damage and inflammation/oxidative stress . Sixteen patients ( male-to-female ratio , 3:13 ; mean age + /- st and ard deviation , 56 + /-3 years ; range , 27 - 75 years ) with histologically confirmed tumors at different sites , scheduled to be treated with an epirubicin-based chemotherapy regimen , were enrolled in the study . A significant impairment in systolic LV function was observed after 200 mg/m2 of epirubicin ; this was shown by a lower SR peak compared with baseline ( 1.82 + /- 0.57/second versus 1.45 + /- 0.44/second ) , whereas sigma remained unchanged . The following significant changes in LV diastolic function occurred only after 300 mg/m2 of epirubicin : a decrease in conventional early/late diastolic ( E/A ) velocities ( 1.16 + /- 0.31 versus 0.93 + /- 0.24 ) and a reduction in both the E(m ) wave in the basal portion of the interventricular septum ( 8.86 + /- 1.73 cm/second versus 7.51 + /- 2.30 cm/second ) and in the E(m)/A(m ) ratio ( 1.09 + /- 0.51 versus 0.83 + /- 0.51 ) , as measured using the TDI technique . No significant changes in LV ejection fraction were observed . Baseline values of brain natriuretic peptide , troponin I , myoglobin , and creatine kinase-myocardial subfraction were within the normal range and no significant changes were observed throughout the study . Levels of interleukin (IL)-6 and its soluble receptor ( sIL-6R ) and reactive oxygen species increased significantly , whereas glutathione peroxidase ( GPx ) levels decreased significantly , after 200 mg/m2 of epirubicin . Significant correlations between the reduction in the SR peak ( deltaSR ) after 200 mg/m2 of epirubicin and the increase in IL-6 and ROS and decrease in GPx were observed . The multiple regression analysis showed that the only independent predictive variable for deltaSR was ROS level . Our data show that : ( a ) subtle cardiac abnormalities may occur at epirubicin doses significantly below those known to be potentially clinical ly harmful and ( b ) the earliest myocardial impairment affects LV systolic rather than diastolic function . Early contractility impairment during epirubicin treatment was associated with high levels of ROS and markers of inflammation . The clinical meaningfulness of our findings warrants further investigations in a larger number of patients for a longer period of follow-up OBJECTIVES The purpose of this study was to evaluate the clinical relevance of anthracycline-induced cardiomyopathy ( AC-CMP ) and its response to heart failure ( HF ) therapy . BACKGROUND The natural history of AC-CMP , as well as its response to modern HF therapy , remains poorly defined . Hence , evidence -based recommendations for management of this form of cardiomyopathy are still lacking . METHODS We included in the study 201 consecutive patients with a left ventricular ejection fraction ( LVEF ) < or=45 % due to AC-CMP . Enalapril and , when possible , carvedilol were promptly initiated after detection of LVEF impairment . LVEF was measured at enrollment , every month for the first 3 months , every 3 months during the first 2 following years , and every 6 months afterward ( mean follow-up 36 + /- 27 months ) . Patients were considered responders , partial responders , or nonresponders according to complete , partial , or no recovery in LVEF , respectively . Major adverse cardiac events during follow-up were also evaluated . RESULTS Eighty-five patients ( 42 % ) were responders ; 26 patients ( 13 % ) were partial responders , and 90 patients ( 45 % ) were nonresponders . The percentage of responders progressively decreased as the time from the end of chemotherapy to the start of HF treatment increased ; no complete recovery of LVEF was observed after 6 months . Responders showed a lower rate of cumulative cardiac events than partial and nonresponders ( 5 % , 31 % , and 29 % , respectively ; p < 0.001 ) . CONCLUSIONS In cancer patients developing AC-CMP , LVEF recovery and cardiac event reduction may be achieved when cardiac dysfunction is detected early and a modern HF treatment is promptly initiated OBJECTIVES The aim of this study was to evaluate whether cardiac biomarkers , tissue velocity ( TVI ) and strain imaging , and cardiac magnetic resonance imaging can predict early left ventricular ( LV ) dysfunction in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting . BACKGROUND Early indexes of LV systolic dysfunction with noninvasive cardiac imaging would be useful for addressing the cardiac safety profile of trastuzumab , potentially avoiding the detrimental effects of heart failure . METHODS We used cardiac biomarkers , TVI and strain imaging , and cardiac magnetic resonance imaging to detect pre- clinical changes in LV systolic function , before conventional changes in left ventricular ejection fraction ( LVEF ) in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting . RESULTS Of 42 patients ( mean age 47 ± 9 years ) prospect ively followed between 2007 and 2009 , 10 ( 25 % ) developed trastuzumab-mediated cardiomyopathy ( CM ) . Troponin T , C-reactive protein , and brain natriuretic peptide did not change over time . Within 3 months of adjuvant therapy with trastuzumab , there was a significant difference in the lateral S ' between the normal cohort and the CM group ( 9.1 ± 1.6 cm/s and 6.4 ± 0.6 cm/s , respectively , p < 0.05 ) . Similarly , the peak global longitudinal and radial strain decreased as early as 3 months in the trastuzumab-mediated cardiotoxicity group . As compared with both global longitudinal and radial strain , only S ' was able to identify all 10 patients who developed trastuzumab-mediated CM . The LVEF subsequently decreased at 6 months of follow-up in all 10 patients , necessitating discontinuation of the drug . All 10 patients demonstrated delayed enhancement of the lateral wall of the LV within the mid-myocardial portion , consistent with trastuzumab-induced CM . CONCLUSIONS Both TVI and strain imaging were able to detect pre- clinical changes in LV systolic function , before conventional changes in LVEF , in patients receiving trastuzumab in the adjuvant setting |
13,062 | 25,501,448 | A small preventive effect of endovascular therapy may exist , particularly if the 30 day postprocedural risk is reduced | BACKGROUND A recent r and omized trial of patients with primarily anterior circulation intracranial artery stenosis showed that intensive medical therapy was superior to intracranial stenting in preventing recurrent stroke .
The rate of stroke recurrence or death in symptomatic intracranial vertebrobasilar stenosis with medical therapy alone may be especially high , and rates compared with endovascular therapy need further study . | Eighteen patients underwent stenting for symptomatic basilar artery stenosis . There were three major periprocedural complications ( 16.7 % ) without fatality . At a mean 26.7 ± 12.1-month follow-up , 15 patients ( 83.3 % ) had an excellent long-term outcome . Only one patient ( 5.6 % ) had moderate disability from recurrent stroke , and two patients died of medical illness at 30 and 36 months after stenting . In this uncontrolled study , stenting appeared to be effective in reducing stroke risk and death and worthy of further scrupulous trial BACKGROUND AND PURPOSE There are limited data on the prognosis of patients with angiographically proved symptomatic stenosis of the intracranial vertebral artery or basilar artery . METHODS We studied 68 patients with 50 % to 99 % stenosis of one of the following arteries : intracranial vertebral ( n = 31 ) , basilar ( n = 28 ) , posterior cerebral ( PCA ) ( n = 6 ) , or posterior inferior cerebellar ( PICA ) ( n = 3 ) . All patients had previous transient ischemic attack or stroke in the territory of the stenotic artery and were treated with warfarin ( n = 42 ) or aspirin ( n = 26 ) . Follow-up was by chart review and personal or telephone interview . RESULTS During a median follow-up of 13.8 months , 15 patients ( 22 % ) had an ischemic stroke ( 4 fatal ) , 3 patients ( 4.5 % ) had a fatal myocardial infa rct ion ( MI ) or sudden death , and 6 patients ( 9 % ) had a nonfatal MI . Stroke rates in any vascular territory ( per 100 patient-years of follow-up ) were 15.0 in patients with basilar artery stenosis , 13.7 in patients with vertebral artery stenosis , and 6.0 in patients with PCA or PICA stenosis . Stroke rates in the same territory as the stenotic artery ( per 100 patient-years of follow-up ) were 10.7 in patients with basilar artery stenosis , 7.8 in patients with vertebral artery stenosis , and 6.0 in patients with PCA or PICA stenosis . CONCLUSIONS Patients with symptomatic intracranial vertebral artery or basilar stenosis are at high risk of stroke , MI , or sudden death . Further studies are needed to clarify optimal therapy for these patients Background — Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease ( WASID ) trial . A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy . Methods and Results — WASID was a r and omized , double-blinded , multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50 % to 99 % stenosis of a major intracranial artery . Median time from qualifying event to r and omization was 17 days , and mean follow-up was 1.8 years . Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery . Subsequent ischemic stroke occurred in 106 patients ( 19.0 % ) ; 77 ( 73 % ) of these strokes were in the territory of the stenotic artery . Risk of stroke in the territory of the stenotic artery was highest with severe stenosis ≥70 % ( hazard ratio 2.03 ; 95 % confidence interval 1.29 to 3.22 ; P=0.0025 ) and in patients enrolled early ( ≤17 days ) after the qualifying event ( hazard ratio 1.69 ; 95 % confidence interval 1.06 to 2.72 ; P=0.028 ) . Women were also at increased risk , although this was of borderline significance ( hazard ratio 1.59 ; 95 % confidence interval 1.00 to 2.55 ; P=0.051 ) . Location of stenosis , type of qualifying event , and prior use of antithrombotic medications were not associated with increased risk . Conclusions — Among patients with symptomatic intracranial stenosis , the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis ≥70 % , after recent symptoms , and in women Background and aim Posterior circulation stenosis may be a risk factor associated with stroke after intracranial stenting as compared with anterior circulation stenosis . Our aim was to test our hypothesis that there was no difference in clinical outcome poststenting between patients with severe stenosis of the basilar artery ( BA ) and intracranial vertebral artery ( VA ) . Methods Using the Cox proportional hazards regression model adjusted for prespecified factors ( qualifying event , and timing of stenting after the qualifying event ) , we compared primary endpoint ( ischemic stroke in the vertebrobasilar territory , including any stroke or death within 30 days of stenting ) between patients with severe symptomatic atherosclerotic BA and VA stenosis who underwent elective stenting in our prospect i ve data base . Analysis was by intention-to-treat principle . Results Primary endpoint event occurred in 13 ( 18.8 % ) of 69 patients with BA stenosis during a mean 23.4 months ( 9 within 30 days and 4 afterward ) and 3 ( 4.3 % ) of 70 patients with VA stenosis during a mean 26.4 months ( 2 within 30 days and 1 afterward ) . Patients with BA stenosis had a significantly higher risk of the primary endpoint ( adjusted HR=4.87 , 95 % CI 1.37 to 17.29 ; p=0.014 ) or any stroke or death within 30 days of stenting ( adjusted HR=5.13 , 95 % CI 1.10 to 23.96 ; p=0.038 ) than those with VA stenosis . Conclusion A significantly higher stroke risk poststenting exists in patients with severe BA stenosis than those with VA stenosis . The discrepancy in clinical outcome after stenting between patients with BA and VA stenosis should be considered in clinical practice and stenting trials Background : Symptomatic intracranial atherothrombotic stenoses ( ICAS ) are associated with high rates of cerebrovascular ischemic events . Objective : To conduct a prospect i ve multicenter study to evaluate the natural history of ICAS and , in those patients refractory to medical treatment , the outcomes associated with intracranial angioplasty . Methods : Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50 % . Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator . Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy . Neurologic and ultrasonographic examinations were performed at study inclusion , 3 months after enrollment , and every 6 months of follow-up thereafter , for 36 months . Results : One hundred two patients were included , with a mean age of 63.3 ± 10.4 years . Intracranial artery stenoses involved the vertebral artery in 22.5 % , the basilar artery in 25.5 % , the middle cerebral artery in 26.5 % , and the internal carotid artery in 25.5 % . In 27.4 % of the patients , the stenoses had clinical hemodynamic characteristics . During a mean follow-up of 23.4 months , 38.2 % of the patients had a cerebrovascular event : ischemic stroke in 13.7 % and TIA in 24.5 % . Among patients with a hemodynamically significant stenosis , 60.7 % had a recurrent stroke or TIA in the territory of the stenotic artery ; this association was significant in univariate analysis . Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2 % . The overall vascular death rate was 8.8 % . Conclusions : Despite medical treatment , the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2 % . Cardiovascular events occurred in 18.6 % of patients . Clinical ly significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients Background and Purpose — 20 % of ischemic stroke is in the posterior circulation , but there is little prospect i ve data on early recurrent stroke risk and whether vertebrobasilar stenosis predicts a high recurrence risk . This natural history data are important as it is technically possible to stent such lesions . Contrast enhanced MRA ( CE-MRA ) and CT angiography ( CTA ) now allow noninvasive identification of vertebrobasilar stenosis . Methods — 216 consecutive patients presenting with posterior circulation TIA or stroke were recruited and prospect ively followed for 90 days . 8 patients with vertebral dissection were excluded . CE-MRA or CTA at presentation and 90-day follow-up was available in 182 . Any posterior circulation TIA/stroke in the month before the presenting episode was recorded . Results — Taking the first event ( including TIA/stroke in the previous month ) as the index case recurrent stroke risk in patients with stenosis was 30.5 % versus 8.9 % in those without ; RR 3.4 ( 95 % CI 1.7 to 7.0 ) , P<0.001 ) . Taking the presenting episode as the index case the risk was 13.8 % versus 4.1 % ; RR 3.4 ( 95 % CI 1.1 to 10.5 ) P=0.0274 . The probability of recurrence was highest soon after the initial event . Conclusions — The presence of vertebro-basilar stenosis identifies a group of patients with posterior circulation stroke who have a high early recurrent stroke risk . Early intervention might reduce recurrent stroke risk . Vertebral stenosis can now be treated by stenting , but determining whether this reduces the early stoke risk requires r and omized controlled trials Objective : To determine the prognosis of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy . Background : The outcome of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy is unknown . These patients may represent the target group for investigation of more aggressive therapies such as intracranial angioplasty . Methods : The authors performed a chart review and telephone interview of patients with symptomatic intracranial atherosclerosis identified in the Stanford Stroke Center clinical data base . A Cox regression model was created to identify factors predictive of failure of antithrombotic therapy . The authors generated Kaplan – Meier survival curves to determine the timing of recurrent TIA , stroke , or death after failure of antithrombotic therapy . Results : Fifty-two patients had symptomatic intracranial atherosclerosis and fulfilled entry criteria . Twenty-nine of the 52 patients ( 55.8 % ) had cerebral ischemic events while receiving an antithrombotic agent ( antiplatelet agents [ 55 % ] , warfarin [ 31 % ] , or heparin [ 14 % ] ) . In a Cox regression model , older age was an independent predictor of failure of antithrombotic therapy , and warfarin use was associated with a decrease in risk . Recurrent TIA ( n = 7 ) , nonfatal/fatal stroke ( n = 6/1 ) , or death ( n = 1 ) occurred in 15 of 29 ( 51.7 % ) of the patients who failed antithrombotic therapy . The median time to recurrent TIA , stroke , or death was 36 days ( 95 % CI 13 to 59 ) . Conclusions : Patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy have extremely high rates of recurrent TIA/stroke or death . Recurrent ischemic events typically occur within a few months after failure of st and ard medical therapy . The high recurrence risk observed warrants testing of alternative treatment strategies such as intracranial angioplasty We conducted a retrospective , multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events ( ischemic stroke , myocardial infa rct ion , or sudden death ) in patients with symptomatic stenosis of a major intracranial artery . Patients with 50 to 99 % stenosis of an intracranial artery ( carotid ; anterior , middle , or posterior cerebral ; vertebral ; or basilar ) were identified by review ing the results of consecutive angiograms performed at participating centers between 1985 and 1991 . Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study . Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview . Seven centers enrolled 151 patients ; 88 were treated with warfarin and 63 were treated with aspirin . Median follow-up was 14.7 months ( warfarin group ) and 19.3 months ( aspirin group ) . Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups , yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group ( stroke rate , 10.4/100 patient-years ; myocardial infa rct ion or sudden death rate , 7.7/100 patient-years ) compared with 8.4 per 100 patient-years of follow-up in the warfarin group ( stroke rate , 3.6/100 patient-years ; myocardial infa rct ion or sudden death rate , 4.8/100 patient-years ) . Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin ( p equals 0.01 ) . The relative risk of a major vascular event in those treated with warfarin was 0.46 ( 95 % CI , 0.23 to 0.86 ) compared with patients treated with aspirin . Major hemorrhagic complications occurred in three patients on warfarin ( including two deaths ) during 166 patient-years of follow-up and in none of the patients on aspirin during 143 patient-years of follow-up . This study suggests a favorable risk/benefit ratio for warfarin compared with aspirin for the prevention of major vascular events in patients with symptomatic intracranial large-artery stenosis . A prospect i ve , r and omized study is needed to confirm these findings . NEUROLOGY 1995;45 : 1488 - We report our experience with stenting for symptomatic vertebrobasilar artery stenosis . One hundred and sixteen patients with vertebrobasilar artery stenosis ( 101 vertebral ostial stenosis , 15 intracranial vertebrobasilar artery stenosis ) were treated with stenting . Indication criteria of treatment were 1 ) symptomatic lesion , 2 ) angiographical stenosis more than 60 % . Under local anesthesia , pre-dilatation was first performed , then stents were placed to the lesion . Successful dilatation was obtained in 115 cases . The stenosis rate reduced to 2 % post-stenting in ostial lesions and 16 % in intracranial lesions . Transient neurological complications developed in 2 patients . Follow-up angiographies more than 6 months after stenting were performed in 94 patients with ostial lesions and all patients with intracranial lesions . Of these , 8 patients ( 9.5 % ) with ostial lesions and 4 patients ( 27 % ) with intracranial lesions developed restenosis . All patients with restenosis were treated successfully with PTA ( percutaneous transluminal angioplasty ) . During the follow-up period , 3 patients developed recurrence of VBI ( vertebro-basilar insufficiency ) symptoms due to restenosis . One patient developed brain stem infa rct ion due to in-stent occlusion 8 months after stenting . Conclusion . Stenting for vertebrobasilar artery stenoses is feasible and safe . Prevention of restenosis , especially in intracranial arteries , is the next problem to be solved OBJECTIVE Balloon-mounted coronary stents ( BMC S ) have been adapted for use in the intracranial circulation for the treatment of symptomatic intracranial atheromatous disease ( ICAD ) . We performed a retrospective analysis of our 7-year experience with these devices in an attempt to quantify the periprocedural risks and long-term outcomes in patients with symptomatic ICAD of the vertebrobasilar ( VB ) system treated with BMC S. METHODS A retrospective review of a prospect ively maintained data base was performed to determine the neurological and non-neurological periprocedural risks of BMC S treatment of ICAD . Patients were followed with serial transcranial Doppler ( TCD ) and , in some cases , angiographic imaging . The clinical status was determined based on clinic visits and by telephone interviews when possible . RESULTS Over the 6-year period from March 1999 to May 2005 , 44 patients ( 35 men , 9 women ; average age , 64.8 yr ) with 47 symptomatic atheromatous lesions of the VB system were treated with BMC S. In two patients , the BMSC could not be delivered across the target lesion . Treatment of the remaining 45 lesions was technically successful ( 95.7 % ) . The periprocedural neurological morbidity and mortality was 26.1 % ( 10 clinical ly evident strokes , 2 deaths ) . One additional patient experienced a periprocedural transient ischemic attack ( TIA ) . Two patients died of non-neurological causes within 6 months ( 4.3 % , myocardial infa rct ion and cholecystitis ) . The average stenosis measured 82.5 % , declining to 10.0 % stenosis after BMC S. TCD examinations showed a preprocedural velocity of 127.7 cm/second ( n = 43 ; st and ard deviation , 63.7 cm/s ) , which declined to 54.0 cm/s immediately after the procedure ( n = 42 ; st and ard deviation , 22.7 cm/s ) . In patients with serial TCD evaluations , velocities were typically constant over years of follow-up ( six patients with > 5 yr of follow-up ; average velocity , 52.2 cm/s ) . Angiographic follow-up was available for 11 patients . Three patients had stent occlusion ( all symptomatic with TIAs ) , one patient had greater than 50 % in-stent restenosis ( ISR ) ( symptomatic with TIA ) and seven had no significant ( < 50 % ) stenosis . The overall ISR/occlusion rate was 12.5 % ( 4 out of 32 lesions with angiographic and /or TCD follow-up > 6 mo ) . Of the 42 patients who successfully underwent BMC S , clinical follow-up was available for 33 ( 78.6 % , average follow-up period , 43.5 mo ) , three patients died before any follow-up could be performed , and seven were lost to follow-up . Of the patients with follow-up , five had recurrent vertebrobasilar ischemic symptoms ( 15 % ; four TIA , one stroke ) . Four out of five patients with recurrent symptoms had ISR or occlusion verified on conventional angiography . At the time of the last follow-up examination , seven patients of 44 patients who underwent attempted treatment were dead ( modified Rankin Scale [ mRS ] score , 6 ) ; four had an mRS score of 3 to 5 , 16 had an mRS score of 1 or 2 , and 10 had an mRS score of 0 . CONCLUSION Percutaneous transluminal angioplasty and stenting using BMC S for the treatment of symptomatic VB ICAD can be carried out with high rates of technical success and excellent immediate angiographic results . However , the procedure carries with it a very high rate of periprocedural morbidity and mortality . Greater than 50 % ISR or stent occlusion occurred in 12.5 % of the patients and was associated with recurrent TIAs . In the absence of ISR/occlusion , patients who tolerated the initial procedure did well neurologically and did not typically experience recurrent ischemic symptoms Background and Purpose — Stroke rates in patients with symptomatic intracranial stenosis may be as high as 10 % to 24 % per year on medical therapy . This multicenter , nonr and omized , prospect i ve feasibility study evaluated the NEUROLINK System for treatment of vertebral or intracranial artery stenosis . Methods — Patients were 18 to 80 years old with symptoms attributed to a single target lesion of ≥50 % stenosis . Patients received 5 neurological examinations before and in the year after the procedure , and another angiogram at 6 months . Results — In 61 patients enrolled , 43 ( 70.5 % ) intracranial arteries ( 15 internal carotid , 5 middle cerebral , 1 posterior cerebral , 17 basilar , 5 vertebral ) and 18 ( 29.5 % ) extracranial vertebral arteries ( 6 ostia , 12 proximal to the posterior inferior cerebellar artery [ PICA ] ) were treated . In the first 30 days , 4 patients ( 6.6 % ) had strokes and no deaths occurred . Successful stent placement was achieved in 58/61 cases ( 95 % ) . At 6 months , stenosis of > 50 % occurred in 12/37 ( 32.4 % ) intracranial arteries and 6/14 ( 42.9 % ) extracranial vertebrals , 4 in the vertebral ostia . Seven ( 39 % ) recurrent stenoses were symptomatic . Four of 55 patients ( 7.3 % ) had strokes later than 30 days , 1 of which was in the only patient not stented . Conclusions — The NEUROLINK System is associated with a high rate of successful stent deployment . Strokes occurred in 6.6 % of patients within 30 days and in 7.3 % between 30 days and 1 year . Although restenoses occurred in 35 % of patients , 61 % were asymptomatic . Further trials involving the NEUROLINK System are warranted OBJECTIVE To study the frequency , clinical course , and functional outcome of perforator stroke ( PS ) result ing from elective stenting of symptomatic intracranial stenosis . METHODS Between September 2001 and November 2004 , 169 consecutive patients with 181 symptomatic intracranial stenoses underwent stenting procedure at our institute . The preoperative perforator infa rct adjacent to the stenotic segment ( PIAS ) on MRI was evaluated blindly . Patients who developed PS after stenting were enrolled . Each patient was assessed by an experienced stroke neurologist by neurologic examination and NIH Stroke Scale score every day until discharge and at day 30 , and by modified Rankin Scale ( mRS ) score at the end of the first , third , and sixth month , and then at intervals of 6 months . RESULTS PS frequency was 3.0 % ( 5/169 patients ) . The patients with preoperative PIAS had a higher frequency of PS and PS exacerbation , result ing from intracranial stenting ( 8.2 % , 4/49 ) , vs patients without preoperative PIAS ( 0.8 % , 1/120 ; p = 0.031 ) . Four PSs occurred during the procedure and one 10 hours after stenting . Four PSs reached the maximum deficit almost at once , and one after 2 hours from onset . All five patients were functionally independent ( mRS < or= 1 ) within 12 months . CONCLUSION Patients with preoperative perforator infa rct adjacent to the stenotic segment have a higher perforator stroke frequency after elective stenting of intracranial stenosis . Most perforator strokes occur during the procedure and reach the maximum deficit almost immediately . Functional outcomes are relatively good |
13,063 | 29,480,025 | Aerobic exercise alone was not significantly associated with aerobic capacity and quality of life improvement .
Conclusion : The results provide support to interventions that combine intradialytic aerobic and resistance exercises to improve physical functioning and quality of life in end-stage renal disease patients undergoing hemodialysis | Objective : To determine the effects of different intradialytic exercise training modalities on physical functioning and health-related quality of life of maintenance hemodialysis patients . | Previous studies have suggested that exercise during hemodialysis ( HD ) could increase the efficacy of solute removal , although this hypothesis has not been conclusively evaluated . The goal of this study was to compare the removal of low‐molecular weight solutes between HD sessions , with and without aerobic exercise . It was a controlled clinical trial , including HD patients in a r and omly cross‐over design , such that each patient received a HD session with exercise ( intervention ) and the next one without exercise ( control ) , three times each . In the exercise sessions , patients pedaled on a cycle ergometer for 60 minutes . The total mass of removed urea , potassium , creatinine , and phosphate were calculated from the solutes concentration in dialysate ( continuous spent sampling of dialysate ) . This was evaluated in a total of 132 HD sessions of patients with a mean age of 54 ± 15 years , 75 % male and HD vintage of 3 ( 2–13 ) years . Phosphate removal in dialysate during intervention sessions was significantly higher ( 5.6 [ 2.5–18.9 ] vs. 5.1 [ 1.5–11.2 ] mg/min ) than during control sessions , P = 0.04 . The median mass of phosphate removed during control HD session was 1226 ( 367.8–2697.2 ) vs. 1348.6 ( 613.0–4536.2 ) mg/session during intervention sessions . The exercise did not modify the removal of urea ( control 122.6 [ 61.3–286.0 ] vs. exercise 112.4 [ 51.1–250.3 ] mg/min , P = 0.44 ) , creatinine ( control 5.6 [ 2.5–13.8 ] vs. exercise 5.6 [ 2.5–12.8 ] mg/min , P = 0.49 ) , or potassium ( control 13.3 [ 11.2–15.8 ] vs. exercise 13.8 [ 6.6–15.8 ] mEq/min , P = 0.49 ) . Aerobic exercise during HD increases the efficacy of phosphate removal , without changing urea , creatinine and potassium removal . The implication s of this finding in mineral and bone disease and cardiovascular disease need to be evaluated on future clinical trials INTRODUCTION Cardiovascular disease is the major cause of death in hemodialysis patients . Regular aerobic or intradialytic exercise may play a role in reducing cardiovascular mortality in these patients . The aim of this study was to evaluate the relationship between intradialytic exercise and echocardiographic findings . METHODS AND MATERIAL S Forty patients were enrolled in the study from Shahrekord Hemodialysis Center . They were r and omly assigned into the exercise and control groups . In the exercise group , the patients had a 30-minute exercise program per dialysis session , 3 times a week , for 3 months . Electrocardiography and echocardiography were done at the beginning of the study and 3 months later . RESULTS The mean age and body mass index of the patients were 43.2 + /- 10.5 years and 21.7 + /- 5.4 kg/m2 , respectively . Left ventricular ejection fraction increased and systolic pulmonary artery pressure and right ventricular size decreased significantly after the study in the exercise group patients . CONCLUSIONS Our results showed the improvement of cardiac systolic and diastolic function in patients who had physical exercise during dialysis sessions . Regular intradialysis exercise can be suggested for hemodialysis patients without cardiac disease Background The anabolic response to progressive resistance exercise training ( PRET ) in haemodialysis patients is unclear . This pilot efficacy study aim ed to determine whether high-intensity intradialytic PRET could reverse atrophy and consequently improve strength and physical function in haemodialysis patients . A second aim was to compare any anabolic response to that of healthy participants completing the same program . Methods In a single blind controlled study , 23 haemodialysis patients and 9 healthy individuals were r and omly allocated to PRET or an attention control ( SHAM ) group . PRET completed high-intensity exercise leg extensions using novel equipment . SHAM completed low-intensity lower body stretching activities using ultra light resistance b and s. Exercises were completed thrice weekly for 12 weeks , during dialysis in the haemodialysis patients . Outcomes included knee extensor muscle volume by magnetic resonance imaging , knee extensor strength by isometric dynamometer and lower body tests of physical function . Data were analysed by a per protocol method using between-group comparisons . Results PRET elicited a statistically and clinical ly significant anabolic response in haemodialysis patients ( PRET — SHAM , mean difference [ 95 % CI ] : 193[63 to 324 ] cm3 ) that was very similar to the response in healthy participants ( PRET — SHAM , 169[−41 to 379 ] cm3 ) . PRET increased strength in both haemodialysis patients and healthy participants . In contrast , PRET only enhanced lower body functional capacity in the healthy participants . Conclusions Intradialytic PRET elicited a normal anabolic and strength response in haemodialysis patients . The lack of a change in functional capacity was surprising and warrants further investigation Background Functional limitations , altered cardiac autonomic activity , and psychological distress are known disorders in chronic hemodialysis ( HD ) patients , relating to increased morbidity and mortality . The aim of this study was to examine the influence of an exercise training program on emotional parameters and heart rate variability ( HRV ) indices , as well as to determine whether emotional stress contributes to autonomic dysfunction in these patients . Methods Forty-four HD patients were r and omly assigned into group A ( 24 patients , aged 46.3 ± 11.2 years ) , who participated in a 1-year intradialytic exercise training program and group B ( 20 patients , aged 45.8 ± 10.8 years ) , who were used as controls . At baseline and a year after , measures of HRV were obtained for the estimation of st and ard deviation of RR intervals , the mean square successive differences , percentage of RR intervals differing by more than 50 ms from the preceding RR interval ( pNN50 ) , and low to high frequency components . Emotional parameters ( Beck Depression Inventory – BDI and Hospital Anxiety and Depression Scale – HADS ) were also assessed by vali date d question naires . Moreover , all patients performed a spiroergometric study for the estimation of VO2peak . Results At baseline , all measurements were similar in the two groups and remained almost unchanged after a year in group B. After a year of training , VO2peak increased from 16.79 ± 5.24 to 22.33 ± 4.90 ml/kg per min ( P > 0.001 ) in group A. Trained patients also showed an increase in st and ard deviation of RR intervals by 58.8 % ( P > 0.001 ) , the mean square successive differences by 68.1 % ( P > 0.001 ) , pNN50 by 23.5 % ( P > 0.001 ) , and a low to high frequency ratio by 17.3 % ( P > 0.001 ) . Finally , at the end of the study , group A showed a decrease in BDI score by 34.5 % ( P > 0.001 ) and HADS by 23.9 % ( P > 0.001 ) . Canonical correlation revealed significant inverse correlation among depression ( in BDI and HADS ) and HRV indices before and after exercise training . Conclusion Cardiac autonomic modulation seemed to be sensitive to the experience of persistent depression in HD patients . Significantly , exercise training reduced emotional distress and concomitantly improved HRV OBJECTIVES Regular exercise is known to reduce arterial stiffness ( AS ) in hemodialysis patients . However , the impact of a more realistic intradialytic form of exercise , such as pedaling , is unclear . We aim ed to examine ( i ) the effect of intradialytic pedaling exercise on AS over 4 months and ( ii ) the longer term effect of pedaling on AS 4 months after exercise cessation . METHODS Patients on stable in-center hemodialysis ( 3 x/week ) were r and omly assigned 1:1 to either intradialytic pedaling exercise ( EX ) or to a control group receiving usual hemodialysis ( nonEX ) for 4 months . At baseline and 4 months , peripheral and central blood pressure ( BP ) indices , heart rate ( HR ) , augmentation index HR corrected ( AIx75 ) , and carotid-femoral pulse wave velocity ( cfPWV ) were assessed ( applanation tonometry ) . Measurements were repeated in the EX group 4 months postexercise cessation . RESULTS As per protocol analysis was completed in 10 EX group participants ( 58 ± 17 years , body mass index 26 ± 4 kg/m2 ) and 10 nonEX group participants ( 53 ± 15 years , body mass index 27 ± 6 kg/m2 ) . Peripheral and central BP was unchanged in both groups . AIx75 was unchanged in the EX group , however , a significant median increase of 3.5 % [ interquartile range , IQR 1.0 , 8.5 ] was noted in the nonEX group ( P = 0.009 ) . We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls : -1.00 [ IQR -1.95 , 0.05 ] vs. 0.20 [ IQR -0.10 , 0.90 ] ( P = 0.033 ) . Interestingly , the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation . CONCLUSION Intradialytic pedaling exercise has a beneficial impact on AS . This relationship warrants further investigation . CLINICAL TRIALS REGISTRATION Trial Number # NCT03027778 ( clinical trials.gov ) BACKGROUND Protein-energy wasting ( PEW ) is common in patients undergoing hemodialysis ( HD ) . Studies have assessed the positive effect of oral nutritional supplementation ( ONS ) or resistance exercise ( RE ) on nutritional status ( NS ) markers in patients undergoing HD . METHODS The aim of this study was to assess the effect of ONS and RE on NS and the quality of life ( QOL ) of 36 patients undergoing HD . In a r and omized clinical trial , patients were divided into the following two groups : a control group ( ONS ) that received a can of ONS during their HD sessions and an intervention group ( ONS + RE ) that received a can of ONS and underwent a 40-min session of RE during their HD sessions . Both interventions lasted 12 weeks . The patients ' anthropometric , biochemical , dietetic and bioelectrical impedance measurements as well as their QOL , evaluated using the Kidney Disease Quality of Life Short Form , were recorded . RESULTS At baseline , 55.5 % of patients presented with PEW according to International Society of Renal Nutrition and Metabolism criteria ( 20 patients ) . We found statistically significant changes from baseline in both groups , such as increases in body weight , body mass index , midarm circumference , midarm muscle circumference , triceps skinfold thickness , fat mass percentage , h and grip strength , phase angle and serum albumin . A decrease in the prevalence of PEW was observed in both groups at the end of the intervention . A delta comparison between groups showed no statistically significant differences in the anthropometric and biochemical parameters . No significant improvement was observed in QOL and body composition measured by bioimpedance vector analysis . Dietary energy and protein intake increased significantly during the study period for all patients . CONCLUSION Oral nutritional supplementation during HD improves NS . The addition of RE during HD does not seem to augment the acute anabolic effects of intradialytic ONS on NS Background Exercise during hemodialysis treatments improves physical function , markers of cardiovascular disease and quality of life . However , exercise programs are not a part of st and ard therapy in the vast majority of hemodialysis clinics internationally . Hemodialysis unit-based accredited exercise physiologists may contribute to an increased intradialytic exercise uptake and improved physical function . Methods and design This is a stepped wedge cluster r and omised controlled trial design . A total of 180 participants will be recruited from 15 community satellite hemodialysis clinics in a large metropolitan Australian city . Each clinic will represent a cluster unit . The stepped wedge design will consist of three groups each containing five r and omly allocated cluster units , allocated to either 12 , 24 or 36 weeks of the intervention . The intervention will consist of an accredited exercise physiologist-coordinated program consisting of six lower body resistance exercises using resistance elastic b and s and tubing . The resistance exercises will include leg abduction , plantar flexion , dorsi flexion , straight-leg/bent-knee raise , knee extension and knee flexion . The resistance training will incorporate the principle of progressive overload and completed in a seated position during the first hour of hemodialysis treatment . The primary outcome measure is objective physical function measured by the 30-second sit to st and test . Secondary outcome measures include the 8-foot timed-up- and -go test , the four square step test , quality of life , cost-utility analysis , uptake and involvement in community activity , self-reported falls , fall ’s confidence , medication use , blood pressure and morbidity ( hospital admissions ) . Discussion The results of this study are expected to determine the efficacy of an accredited exercise physiologist supervised resistance training on the physical function of people receiving hemodialysis and the cost-utility of exercise physiologists in hemodialysis centres . This may contribute to intradialytic exercise as st and ard therapy using an exercise physiologist workforce model . Trial registration Current Controlled Trials ACTRN12612001223820 OBJECTIVE Abnormalities in mineral and bone metabolism are frequent in chronic kidney disease patients . Physical exercise can improve many indicators of physical functioning , and recent studies showed beneficial effects on bone mineral density in the general population . The aim of this study was to evaluate the effects of resistance exercise training on bone markers and body composition in hemodialysis ( HD ) patients . DESIGN This was a r and omized controlled trial . SUBJECTS The study included 13 HD patients ( 46.2 % men ) . INTERVENTION Patients were divided into a control group and an exercise group , which performed 8 weeks of intradialytic resistance exercise . Serum sclerostin , bone alkaline phosphatase ( BAP ) , insulin , leptin , 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , and body composition were measured before and after the exercise period . RESULTS In the exercise group , BAP levels increased from 11.4 ± 6.5 to 14.6 ± 6.4 U/L ( P < .05 ) and serum 1,25-dihydroxyvitamin D levels from 46.0 ± 23.5 to 87.2 ± 31.8 ng/mL ( P < .05 ) . After exercise , serum BAP levels were inversely correlated with serum sclerostin ( r = -0.96 , P < .05 ) . There was no change in body composition in either group . CONCLUSION Resistance exercise training appears to be an interesting approach for stimulating BAP production in HD patients and may prevent bone loss and stimulate bone formation BACKGROUND Cardiovascular disease ( CVD ) mortality rates are greatly elevated in chronic kidney disease patients receiving maintenance haemodialysis therapy . The purpose of this study was to evaluate the efficacy of intradialytic endurance exercise training on novel risk factors that may contribute to this excessive CVD risk . METHODS Seventeen haemodialysis patients were r and omized to either an intradialytic exercise training ( cycling ) group ( EX ; n = 8) or a non-exercising control group ( CON ; n = 9 ) for 4 months . At baseline and following the intervention , we measured serum parameters related to CVD risk and renal function , used echocardiography to measure variables related to cardiac structure and function and assessed physical performance by a vali date d shuttle walk test . RESULTS Performance on the shuttle walk test increased by 17 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in serum lipids or inflammatory markers ( C-reactive protein , interleukin-6 ) in either group . Serum thiobarbituric acid reactive substances , a marker of oxidative stress , were reduced by 38 % in EX ( P < 0.05 ) , but did not change in CON . In addition , serum alkaline phosphatase ( ALP ) , a putative risk factor for vascular calcification , was reduced by 27 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in left atrial volume , left ventricular mass or myocardial performance index in either group . However , the thickness of the epicardial fat layer was reduced by 11 % in EX ( P < 0.05 ) , but did not change in CON . Furthermore , the change in physical performance was inversely correlated to the change in epicardial fat ( r = -0.63 ; P = 0.03 ) . CONCLUSIONS These results suggest that endurance exercise training may improve CVD risk in haemodialysis patients by decreasing novel risk factors including serum oxidative stress , ALP and epicardial fat PURPOSE To investigate the effect of progressive resistance training ( PRT ) on body composition , physical fitness , quality of life , lipid and nutritional profile of patients on hemodialysis ( HD ) . METHODS A non equivalent comparison group pretest and posttest design study was used with 40 participants who were r and omly assigned to the exercise group ( 20 participants ) and the comparison group ( 20 participants ) . The exercise group received PRT for 30 minutes per session , 3 sessions a week , for 12 weeks , while the comparison group received usual care . The PRT consisted of upper and lower body exercises using elastic b and s and s and bags . Outcome measures evaluated were : body composition , physical fitness , quality of life , and lipid profile . RESULTS Skeletal muscle mass , grip , leg muscle strength , and quality of life all improved significantly in the exercise group . Body fat rate , total cholesterol and triglyceride rate decreased significantly in the exercise group . CONCLUSION These results suggest that PRT improves body composition , physical fitness , quality of life , and lipid profile of patients on HD . PRT using elastic b and s and s and bags can be utilized as part of a regular care plan for these patients Abstract . Maximal strength-training with an emphasis on maximal mobilization during cross-country skiing increases exercise economy when double-poling . The aim of this experiment was to investigate whether the mechanism of this increase is a change in the force-velocity relationship and the mechanical power output . A group of 19 cross-country skiers having an average peak oxygen uptake of 255 ml·kg–0.67 body mass·min–1 or 61 ml·kg–1·min–1 were r and omly assigned to either a high resistance-training group ( n=10 ) or a control group ( n=9 ) . Upper body endurance was tested on a ski ergometer . The high-resistance-training group trained for 15 min on three occasions a week for 9 weeks . Training consisted of three series of five repetitions using 85 % of one repetition maximum ( 1RM ) , with emphasis on high velocity in the concentric part of the movement . Upper body exercise economy , 1RM and time to exhaustion increased significantly in the high resistance-training group , but was unchanged in the control group . Peak power and the velocities for a given load increased significantly , except for the two lowest loads . We conclude that the increased exercise economy after a period of upper body high resistance-training can be partly explained by a specific change in the force-velocity relationship and the mechanical power output BACKGROUND Kidney failure is associated with muscle wasting and physical impairment . Moderate- to high-intensity strength training improves physical performance , nutritional status and quality of life in people with chronic kidney disease and in dialysis patients . However , the effect of low-intensity strength training has not been well documented , thus representing the objective of this pilot study . METHODS Fifty participants ( mean + /- SD , age 69 + /- 13 years ) receiving long-term haemodialysis ( 3.7 + /- 4.2 years ) were r and omized to intra-dialytic low-intensity strength training or stretching ( attention-control ) exercises twice weekly for a total of 48 exercise sessions . The primary study outcome was physical performance assessed by the Short Physical Performance Battery score ( SPPB ) after 36 sessions , if available , or carried forward from 24 sessions . Secondary outcomes included lower body strength , body composition and quality of life . Measurements were obtained at baseline and at completion of 24 ( mid ) , 36 ( post ) and 48 ( final ) exercise sessions . RESULTS Baseline median ( IQR ) SPPB score was 6.0 ( 5.0 ) , with 57 % of the participants having SPPB scores below 7 . Exercise adherence was 89 + /- 15 % . The primary outcome could be computed in 44 participants . SPPB improved in the strength training group compared to the attention-control group [ 21.1 % ( 43.1 % ) vs. 0.2 % ( 38.4 % ) , respectively , P = 0.03 ] . Similarly , strength training participants exhibited significant improvements from baseline compared to the control group in knee extensor strength , leisure-time physical activity and self-reported physical function and activities of daily living ( ADL ) disability ; all P < 0.02 . Adverse events were common but not related to study participation . CONCLUSIONS Intra-dialytic , low-intensity progressive strength training was safe and effective among maintenance dialysis patients . Further studies are needed to establish the generalizability of this strength training program in dialysis patients The purpose of this study was to evaluate the effect of a 12-week intradialytic progressive resistance training ( PRT ) regimen on circulating pro- and anti-inflammatory cytokines . Forty-nine patients ( 62.6 ± 14.2 years ) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital , Sydney , Australia . Patients were r and omized to : PRT + usual care ( n = 24 ) or usual care control ( n = 25 ) . The PRT group performed two sets of 10 exercises at high intensity using free-weights , 3 times per week for 12 weeks during dialysis , while the control group did not exercise . Tumor necrosis factor-alpha , interleukin-1b , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , interleukin-10 , and interleukin-12 were measured in serum before and after the intervention period . Muscle cross-sectional area ( CSA ) , intramuscular lipid , intermuscular adipose tissue , and subcutaneous and total thigh fat , evaluated via computed tomography of the non-dominant mid-thigh , were also collected at both time points . All cytokines were significantly elevated in the total cohort at baseline compared with normative data . There were no cytokine changes over time or between groups ( p > 0.05 ) . In secondary analyses pooling the groups , changes in logIL-6 and IL-8 were inversely related to changes subcutaneous thigh fat ( p < 0.05 ) while changes in logIL-6 were also inversely related to changes in thigh muscle CSA , and total thigh fat ( p < 0.03 ) . These data suggest that 12 weeks of intradialytic progressive resistance training does not improve circulating pro- and anti-inflammatory markers . Further research is required to eluci date the implication s and mechanisms of the relationships between IL-6 and IL-8 and body composition in ESRD Objective : To assess the effects of intradialytic exercise training on health-related quality of life indices in haemodialysis patients . Subjects/ patients : Thirty-five patients on haemodialysis , with a mean ( SD ) age of 48.8 ( 13.9 ) years , volunteered to participate in the study . They were r and omized either to rehabilitation group ( group A : 19 patients ) , following a 10-month intradialytic exercise training programme or to control group ( group B : 14 patients ) . After the r and omization , two of the patients , one of each group , withdrew from the study for reasons unrelated to exercise training . Method : All patients at the beginning and the end of the study underwent clinical examination , laboratory tests and a treadmill exercise testing with spiroergometric study for the evaluation of their aerobic capacity ( Vo2peak ) . A formal psychosocial assessment , which included affective ( Beck Depression Inventory ) , health-related quality of life ( Quality of Life Index , Living Question naire of Minnesota , Life Satisfaction Index and Short Form-36 question naire ) and personality ( Eysenck Personality Question naire ) parameters , was evaluated at beginning and end of the study . The dose of erythropoietin was changed as needed , according to the level of the haemoglobin , aim ing to keep it at 11 ( 2 ) g/dL during the study . Results : Baseline values were similar between the two groups . After training in group A , Vo2peak was increased by 21.1 % ( P<0.05 ) and exercise time by 23.6 % ( P<0.05 ) . Moreover , group A showed a decrease in self-reported depression ( Beck Depression Index ) of 39.4 % ( P<0.001 ) . In addition , trained patients demonstrated a significant improvement in Quality of Life Index ( from 6.5 ( 1.8 ) to 9.0 ( 1.3 ) , P<0.001 ) and Life Satisfaction Index ( from 44.8 ( 8.6 ) to 53.0 ( 5.6 ) , P<0.001 ) , and an increase in the Physical Component Scale of the SF-36 ( from 40.5 ( 5.6 ) to 44.5 ( 5.5 ) , P<0.05 ) , while the Mental Component Scale remained unchanged . Multiple regression analysis indicated that the improvement in quality of life depended on the participation in exercise programmes , the effects of training and the reduction in the level of depression . No changes were observed in Eysenck Personality Question naire by the end of the study , while all the above parameters remained almost unchanged in the controls . Conclusion : The results demonstrated that intradialytic exercise training improves both physical functioning and psychological status in haemodialysis patients , leading to an improvement of patients ' quality of life Background / Aims : Patients requiring haemodialysis have cardiovascular and immune dysfunction . Little is known about the acute effects of exercise during haemodialysis . Exercise has numerous health benefits but in other population s has a profound impact upon blood pressure , inflammation and immune function ; therefore having the potential to exacerbate cardiovascular and immune dysfunction in this vulnerable population . Methods : Fifteen patients took part in a r and omised-crossover study investigating the effect of a 30-min bout of exercise during haemodialysis compared to resting haemodialysis . We assessed blood pressure , plasma markers of cardiac injury and systemic inflammation and neutrophil degranulation . Results : Exercise increased blood pressure immediately post-exercise ; however , 1 hour after exercise blood pressure was lower than resting levels ( 106±22 vs. 117±25 mm Hg ) . No differences in h-FABP , cTnI , myoglobin or CKMB were observed between trial arms . Exercise did not alter circulating concentrations of IL-6 , TNF-α or IL-1ra nor clearly suppress neutrophil function . Conclusions : This study demonstrates fluctuations in blood pressure during haemodialysis in response to exercise . However , since the fall in blood pressure occurred without evidence of cardiac injury , we regard it as a normal response to exercise superimposed onto the haemodynamic response to haemodialysis . Importantly , exercise did not exacerbate systemic inflammation or immune dysfunction ; intradialytic exercise was well tolerated OBJECTIVE : Depression is the most important neuropsychiatric complication in chronic kidney disease because it reduces quality of life and increases mortality . Evidence demonstrating the association between dialysis shift and depression is lacking ; thus , obtaining such evidence was the main objective of this study . METHOD : This cross-sectional study included patients attending a hemodialysis program . Depression was diagnosed using Beck 's Depression Inventory . Excessive daytime sleepiness was evaluated using the Epworth Sleepiness Scale . RESULTS : A total of 96 patients were enrolled ( 55 males , age 48±14 years ) . Depression and excessive daytime sleepiness were observed in 42.7 % and 49 % of the patients , respectively . When comparing variables among the three dialysis shifts , there were no differences in age , dialysis vintage , employment status , excessive daytime sleepiness , hemoglobin , phosphorus levels , or albumin levels . Patients in the morning shift were more likely to live in rural areas ( p<0.0001 ) , although patients in rural areas did not have a higher prevalence of depression ( p = 0.30 ) . Patients with depression were more likely to be dialyzed during the morning shift ( p = 0.008 ) . Independent risk factors for depression were age ( p<0.03 ) , lower levels of hemoglobin ( p<0.01 ) and phosphorus ( p<0.01 ) , and dialysis during the morning shift ( p = 0.0009 ) . The hospitalization risk of depressive patients was 4.5 times higher than that of nondepressive patients ( p<0.008 ) . CONCLUSION : These data suggest that depression is associated with dialysis shift , higher levels of phosphorus , and lower levels of hemoglobin . The results highlight the need for r and omized trials to determine whether this association occurs by chance or whether circadian rhythm disorders may play a role BACKGROUND Individuals on hemodialysis have low physical function and activity levels . Clinical trials have shown improvements in these parameters with exercise programming . Pedometers have not been extensively evaluated in individuals on hemodialysis . This r and omized clinical trial compared the effects of intradialytic cycling versus a pedometer program on physical function , physical activity and quality of life . METHODS Sixty patients were r and omly assigned to two study groups . The ergometer group cycled during each hemodialysis session for 24 weeks . Pedometer participants followed a home-based walking program for 24 weeks . The primary outcome was aerobic capacity [ VO2peak and 6-minute walk ( 6MW ) test ] . Secondary outcomes included lower extremity strength [ sit-to-st and ( SS ) test ] , flexibility [ sit- and -reach ( SR ) test ] , physical activity ( accelerometer ) and health-related quality of life . Measurements were collected at baseline and at 12 and 24 weeks . RESULTS At 12 and 24 weeks , there was no significant change in the VO2peak or 6MW test between or within study groups . SS testing in the ergometer group improved from 10.2 ( SD 3.4 ) to 11.4 ( SD 2.5 ) cycles from baseline to 24 weeks ( P < 0.005 ) . Similarly , in the pedometer group , SS cycles improved from 10.1 ( SD 3.3 ) to 12.2 ( SD 3.5 ) ( P < 0.005 ) . The SR test also significantly improved over time in both the study groups . No significant changes were noted for other secondary outcomes . CONCLUSIONS Both intradialytic cycling and pedometer programming improved aspects of physical function . Neither intervention had a significant effect on aerobic capacity . No significant differences in any outcomes were identified between interventions groups Background . Restless leg syndrome ( RLS ) is one of the prevalent complaints of patients with end stage renal diseases suffering chronic hemodialysis . Although there are some known pharmacological managements for this syndrome , the adverse effect of drugs causes a limitation for using them . In this r and omized clinical trial we aim ed to find a nonpharmacological way to improve signs of restless leg syndrome and patients ' quality of life . Material and Methods . Twenty-six patients were included in the study and divided into 2 groups of control and exercise . The exercise group used aerobic exercise during their hemodialysis for 16 weeks . The quality of life and severity of restless leg syndrome were assessed at the first week of study and final week . Data were analyzed using SPSS software . Results . The difference of means of RLS signs at the first week of study and final week was −5.5 ± 4.96 in exercise group and −0.53 ± 2.3 in control group . There was not any statistical difference between control group and exercise group in quality of life at the first week of study and final week . Conclusions . We suggest using aerobic exercise for improving signs of restless leg syndrome , but no evidence was found for its efficacy on patient 's quality of life INTRODUCTION Sleep disorders are common in hemodialysis patients . They can affect their quality of life . The purpose of this study was to evaluate the effects of aerobic training on sleep quality , inflammatory status , and serum leptin levels in hemodialysis patients . MATERIAL S AND METHODS Twenty-eight men in the age range of 28 to 74 years who were on maintenance hemodialysis and had sleep problems were enrolled in this study . They were r and omly assigned into control and training groups ( 14 patients in each group ) . Patients in the training group performed a 10- to 30-minute stationary cycling , 3 times a week , during the 1st two hours of every dialysis session , for 8 weeks . The Pittsburgh Sleep Quality Index and the Baecke question naire on physical activity were filled out for all participants . To assess serum leptin and C-reactive protein levels , blood sample s were drawn before the beginning and at the end of the eighth week . RESULTS At the end of the study , serum leptin and C-reactive protein levels were significantly reduced ( P < .001 and P < .001 , respectively ) . Furthermore , the Pittsburgh Sleep Quality Index scores of the training group declined significantly after 8 weeks ( P < .001 ) . There was a positive correlation between sleep quality and serum levels of leptin and C-reactive protein ( P = .03 and P = .04 , respectively ) . CONCLUSIONS Aerobic exercise with moderate intensity during the first two hours of a dialysis session could improve sleep quality and inflammatory status of hemodialysis patients , which predicts morbidity , mortality , and quality of life . However , additional research is needed to confirm these effects OBJECTIVES The purpose of this study is to determine whether a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling could improve behavioural change , physical fitness , physiological condition and health-related quality of life of sedentary haemodialysis patients in The Netherl and s. METHODS Ninety-six haemodialysis patients of the Groningen Dialysis Center were r and omized into an exercise group ( n = 53 ) and a control group ( n = 43 ) . The exercise programme consists of cycling during dialysis together with a pre-dialysis strength training programme lasting 12 weeks . The intensity of the exercise programme is condition level 12 - 16 according to the rate of perceived exertion ( RPE ) . Motivational interviewing techniques were used for exercise counselling . Before and after the intervention , both groups were tested on behavioural change and physical fitness components such as reaction time , manual dexterity , lower extremity muscle strength and VO2 peak . Physiological conditions such as weight , blood pressure , haemoglobin and haematocrit values , cholesterol and Kt/V were obtained from the medical records . Health-related quality of life assessment included R AND -36 scores , symptoms and depression . RESULTS A group x time analysis with MANOVA ( repeated measures ) demonstrates that participation in a low-to-moderate intensity exercise programme linked with exercise counselling yields a significant increase in behavioural change , reaction time , lower extremity muscle strength , Kt/V and three components of quality of life , and no significant effects in the control group . CONCLUSION Participating in a low-to-moderate intensity pre-conditioning exercise programme showed beneficial effects on behavioural change , physical fitness , physiological conditions and health-related quality of life Abstract Inflammation , endothelial dysfunction , and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis ( HD ) patients . Physical exercise alleviates inflammation and increases bone density . Here , we investigated the effects of intradialytic aerobic cycling exercise on HD patients . Forty end-stage renal disease patients undergoing HD were r and omly assigned to either an exercise or control group . The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up , 20 minutes of cycling at the desired workload , and a 5-minute cool down during 3 HD sessions per week for 3 months . Biochemical markers , inflammatory cytokines , nutritional status , the serum endothelial progenitor cell ( EPC ) count , bone mineral density , and functional capacity were analyzed . After 3 months of exercise , the patients in the exercise group showed significant improvements in serum albumin levels , the body mass index , inflammatory cytokine levels , and the number of cells positive for CD133 , CD34 , and kinase insert domain-conjugating receptor . Compared with the exercise group , the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs . The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program . Furthermore , the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program . Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition , bone mineral density , and exercise tolerance in HD patients BACKGROUND Uraemic restless legs syndrome ( RLS ) affects a significant proportion of patients receiving haemodialysis ( HD ) therapy . Exercise training has been shown to improve RLS symptoms in uraemic RLS patients ; however , the mechanism of exercise-induced changes in RLS severity is still unknown . The aim of the current r and omized controlled exercise trial was to investigate whether the reduction of RLS severity , often seen after training , is due to expected systemic exercise adaptations or it is mainly due to the relief that leg movements confer during exercise training on a cycle ergometer . This is the first r and omized controlled exercise study in uraemic RLS patients . METHODS Twenty-four RLS HD patients were r and omly assigned to two groups : the progressive exercise training group ( n = 12 ) and the control exercise with no resistance group ( n = 12 ) . The exercise session in both groups included intradialytic cycling for 45 min at 50 rpm . However , only in the progressive exercise training group was resistance applied , at 60 - 65 % of maximum exercise capacity , which was reassessed every 4 weeks to account for the patients ' improvement . The severity of RLS symptoms was evaluated using the IRLSSG severity scale , functional capacity by a battery of tests , while sleep quality , depression levels and daily sleepiness status were assessed via vali date d question naires , before and after the intervention period . RESULTS All patients completed the exercise programme with no adverse effects . RLS symptom severity declined by 58 % ( P = 0.003 ) in the progressive exercise training group , while a no statistically significant decline was observed in the control group ( 17 % change , P = 0.124 ) . Exercise training was also effective in terms of improving functional capacity ( P = 0.04 ) , sleep quality ( P = 0.038 ) and depression score ( P = 0.000 ) in HD patients , while no significant changes were observed in the control group . After 6 months of the intervention , RLS severity ( P = 0.017 ) , depression score ( P = 0.002 ) and daily sleepiness status ( P = 0.05 ) appeared to be significantly better in the progressive exercise group compared with the control group . CONCLUSION A 6-month intradialytic progressive exercise training programme appears to be a safe and effective approach in reducing RLS symptom severity in HD patients . It seems that exercise-induced adaptations to the whole body are mostly responsible for the reduction in RLS severity score , since the exercise with no applied resistance protocol failed to improve the RLS severity status of the patients Protein-energy wasting ( PEW ) , defined as a loss of body protein mass and fuel reserves , is a powerful predictor of adverse outcomes in haemodialysis ( HD ) patients . Robust arguments suggest that intra-dialytic exercise , combined with oral/parenteral nutrition , enhances the effect of nutritional interventions in HD patients . This pilot r and omized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW , physical functioning ( gait , balance , muscle strength ) and quality of life ( QoL ) in older HD patients ( mean age 69.7 ± 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were r and omly assigned to Nutrition-Exercise group ( GN-Ex , n = 10 ) or Nutrition group ( GN , n = 11 ) . Both groups received nutritional supplements in order to reach recommended protein and energy intake goals . In addition GN-Ex completed a cycling program . No significant difference between groups was found in the number of patients having reached remission of PEW . Likewise , no change was observed in serum-albumin , -prealbumin , C-reactive protein , body mass index , lean- and fat-tissue index , or quadriceps force . Interestingly , we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidence d by a significant improvement in the 6-min walk test ( + 22 % ) , the absence of decline in balance ( unlike the GN ) , and a noteworthy increase in QoL ( + 53 % ) . Combining intra-dialytic exercise and nutrition in HD patients is feasible , and well accepted , improves physical function and QoL but it appears not to have the potential to reverse PEW INTRODUCTION We aim ed determine the impact of an 8-week intradialytic exercise program , consisting of 15 minutes of cumulative duration low-intensity exercise during the first 2 hours of dialysis on serum electrolytes levels and hemoglobin . MATERIAL S AND METHODS In a r and omized controlled trial of in an outpatient hemodialysis unit , clinical ly stable hemodialysis patients ( n = 47 ) were included and assigned into the aerobic exercise group ( n = 25 ) and the control group ( n = 23 ) . Aerobic exercises were done in groups , 15 min/d , 3 times a week , for 2 months . The main outcome measures were biochemical variables including serum levels of calcium , phosphate , and potassium levels and hemoglobin level . RESULTS After an 8-week intervention , significant improvements were seen in serum phosphate levels ( decreased by 1.84 mg/dL ) and serum potassium levels ( decreased by 0.69 mg/dL ) . No side-effects were observed . Serum calcium and hemoglobin levels did not change significantly in the exercise group . CONCLUSIONS A simplified aerobic exercise program is a complementary , safe , and effective clinical treatment modality in patients with end-stage renal disease on dialysis Cardiovascular ( CV ) disease is the most common cause of mortality in end‐stage kidney disease ( ESKD ) , and arterial stiffness , measured by pulse wave velocity ( PWV ) , is an independent predictor of all‐cause and CV mortality . B‐type natriuretic peptide ( BNP ) levels are high in patients with CV disease and ESKD , and increases in BNP may also be a marker of CV risk . Regular exercise has many benefits on quality of life and physical strength and may also improve CV risk , but few studies have addressed the impact of exercise on CV risk in ESKD . We performed a prospect i ve cross‐over trial in 19 hemodialysis ( HD ) patients to assess the impact of regular exercise on surrogate markers of CV risk‐arterial compliance and BNP levels . Exercise involved the use of a bicycle ergometer for minimum 30 min at each HD session for 3 months , with a 1‐month washout period . Group A ( n=9 ) exercised for the first 3 months only , while group B ( n=10 ) performed no intradialytic exercise initially and exercised for 3 months at cross‐over ( month 4 ) . Pulse wave velocity was performed using a SphygmoCor device , with concurrent measurements of BNP and other serum markers , at the commencement of the study , at 3 months , and on completion . The mean PWV ( A : 10.4±3.1 m/s , B : 9.8±3.8 at baseline ) showed a trend toward improvement with exercise ( A : 8.7±2.7 , p=0.07 ) , and no significant change without ( B : 10.5±3.6 , p=0.31 ) . After cross‐over , there was an increase in PWV in group A with cessation of exercise ( 9.75±2.4 , p=0.01 vs. 3 months ) and an improvement in group B with exercise ( 9.33±2.3 , p=0.11 vs. 3 months ) . When comparing PWV after 3 months of exercise vs. 3 months of no exercise ( paired t test ) , there was a significant difference in favor of exercise ( 9.04±0.59 vs. 10.16±0.74 , p=0.008 ) . The mean BNP levels following 3 months of exercise were also lower than those after 3 months of no exercise ( 504.4±101.2 vs. 809.4±196.1[N<100 ] , p=0.047 ) . There was an overall improvement in PWV , and to a lesser extent BNP levels , with 3 months of intradialytic exercise compared with no exercise , suggesting that regular exercise in ESKD may be associated with improvements in arterial compliance and a reduction in CV risk Rational : Patients under regular dialysis can also present alterations in the cardiovascular , musculoskeletal , and metabolic systems . Objectives : The aim of this study is to compare the effects of strength and aerobic exercises performed during hemodialysis ( HD ) in individuals with chronic renal disease . Material s and Methods : R and omized clinical trial . It was developed as a program of exercises three times a week , in the first 2 h of HD for 8 weeks . The patients were divided into three groups : control ( Group 1 , n : 11 ) , strength ( Group 2 , n : 11 ) , and aerobic ( Group 3 , n : 10 ) . G1 has not developed any type of physical training ; G2 utilized a training load of 40 % of one repetition maximum ( 1RM ) with anklets , and developed three series of 15 repetitions . G3 pedaled seated in the dialysis seat , during 20 min , in an ergometric bicycle , with intensity regulated by the perceived effort scale . Before and after 8 weeks , the following variables were evaluated : respiratory muscular strength , pulmonary function , functional capacity , blood biochemistry , and quality of life . Main Findings : In the pre- and post-training comparison , there was statistically significant improvement ( p < 0.05 ) in the maximal inspiratory pressure ( MIP ) , number of steps achieved ( NSA ) , and quality of life ( QoL ) in the trained groups , as compared to the non-exercised group ( G1 ) . Conclusions : The strength and aerobic exercises developed during HD can improve the respiratory muscular strength , functional performance , and quality of life , when compared to individuals presenting the disease who have not developed any type of physical training Background Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes ’ severity and quality of life . Methods In this r and omized , partially double blind , placebo controlled trial , thirty two hemodialysis patients with restless legs syndrome were r and omly assigned into three groups : 1 ) the exercise training group ( N = 16 ) , 2 ) the dopamine agonists group ( ropinirole 0.25 mg/d ) ( N = 8) and 3 ) the placebo group ( N = 8) . The intervention programs lasted 6 months . Restless Legs Syndrome severity was assessed using the international severity scale , physical performance by a battery of tests , muscle size and composition by computed tomography , body composition by Dual Energy X Ray Absorptiometry , while depression score , sleep quality , daily sleepiness and quality of life were assessed through question naires . Results Exercise training and dopamine agonists were effective in reducing syndrome ’s symptoms by 46 % ( P = 0.009 ) and 54 % ( P = 0.001 ) respectively . Within group changes revealed that both approaches significantly improved quality of life ( P < 0.05 ) , however , only the dopamine agonists significantly improved sleep quality ( P = 0.009 ) . Within group changes showed a tendency for lean body mass improvements with dopamine agonists , this reached statistical significance only with the exercise training ( P = 0.014 ) , which also reduced fat infiltration in muscles ( P = 0.044 ) and improved physical performance ( P > 0.05 ) in various tests . Between group changes detect significant improvements with both exercise and dopamine agonists in depression score ( P = 0.003 ) , while only the dopamine agonist treatment was able to significantly improve sleep quality , compared to exercise and placebo ( P = 0.016 ) . Conclusions A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients . Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.Trial registration 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 ABSTRACT Purpose : To determine if 16 weeks of strength training can improve the cardiovascular function of older men during sub‐maximum aerobic exercise . Methods : Twenty four men aged 70‐80 yr were r and omly assigned to a strength training ( ST ; n = 12 ) and control group ( C ; n = 12 ) . Training consisted of 3 sets of 6 ‐ 10 repetitions at 70 % to 90 % of 1RM , 3 times per week , on an incline squat machine for 16 weeks , followed by 4 weeks detraining . Leg strength and maximum oxygen consumption ( VO2 max ) were assessed every 4 weeks of the 20‐week study . Cardiovascular function was assessed during submaximum cycle exercise at 40 Watts , 50 % and 70 % of VO2 max before training , after 16 weeks training , and after 4 weeks detraining . Results : At 40 Watts , heart rate ( HR ) , systolic blood pressure , and rate pressure product ( RPP ) were lower and stroke volume ( SV ) significantly higher after 16 weeks training and 4 weeks detraining : at 50 % VO2 max , HR and RPP were lower after 16 weeks training and 4 weeks detraining : at 70 % VO2 max , cycle ergometry power , VO2 and arterio‐venous oxygen difference ( a ‐ & OV0456;O2 ) were higher after 16 weeks training . Leg strength and VO2 max increased after 16 weeks training , with leg strength remaining above pre‐training levels after 4‐weeks detraining . Conclusions : Sixteen weeks of strength training significantly improves the cardiovascular function of older men . Therefore strength training not only increases muscular strength and hypertrophy but also provides significant cardiovascular benefits for older individuals BACKGROUND Individuals with end-stage renal disease on hemodialysis therapy have reduced aerobic exercise capacity and reduced muscle strength . METHODS This was a single-blind , r and omized , placebo-controlled trial of an exercise intervention in hemodialysis patients administered erythropoietin . The intervention consisted of progressive resisted isotonic quadriceps and hamstrings exercise and training on a cycle ergometer three times weekly for 12 weeks . Individuals in the control group underwent a nonprogressive program of range-of-motion exercises . Both groups were observed for an additional 5 months without intervention . Outcomes were assessed without knowledge of treatment assignment at baseline , 12 weeks , and 5 months . A healthy age- and sex-matched sample provided comparative data . RESULTS Our sample was relatively high functioning , with a mean score on the Physical Function subscale of the Short Form 36 ( SF-36 ) of 76 of 100 . At 12 weeks , there were large and statistically significant differences in favor of the experimental group on the submaximal exercise test ( 14 W ; 95 % confidence interval , 2 to 26 ) and muscle strength ( 45 lb ; 95 % confidence interval , 9 to 81 ) , but not in the 6-minute walk , symptoms question naire , or SF-36 . Differences between the intervention and control groups at 12 weeks were not evident on retesting 5 months after the end of the intervention . Compared with the healthy sample , patients were significantly lower functioning on the submaximal exercise test , muscle strength , and 6-minute walk test at baseline . CONCLUSION In this high-functioning sample , the exercise program improved physical impairment measures , but had no effect on symptoms or health-related quality of life . The impact on patients with a greater degree of physical dysfunction needs to be rigorously studied In chronic kidney disease ( CKD ) , oxidative stress ( OS ) plays a central role in the development of cardiovascular diseases . This pilot program aim ed to determine whether an intradialytic aerobic cycling training protocol , by increasing physical fitness , could reduce OS and improve other CKD-related disorders such as altered body composition and lipid profile . Eighteen hemodialysis patients were r and omly assigned to either an intradialytic training ( cycling : 30 min , 55%-60 % peak power , 3 days/week ) group ( EX ; n = 8) or a control group ( CON ; n = 10 ) for 3 months . Body composition ( from dual-energy X-ray absorptiometry ) , physical fitness ( peak oxygen uptake and the 6-minute walk test ( 6MWT ) ) , lipid profile ( triglycerides ( TG ) , total cholesterol , high-density lipoprotein , and low-density lipoprotein ( LDL ) ) , and pro/antioxidant status ( 15-F2α-isoprostanes ( F2-IsoP ) and oxidized LDL in plasma ; superoxide dismutase , glutathione peroxidase , and reduced/oxidized glutathione in erythrocytes ) were determined at baseline and 3 months later . The intradialytic training protocol did not modify body composition but had significant effects on physical fitness , lipid profile , and pro/antioxidant status . Indeed , at 3 months : ( i ) performance on the 6MWT was increased in EX ( + 23.4 % , p < 0.001 ) but did not change in CON , ( ii ) plasma TG were reduced in EX ( -23 % , p < 0.03 ) but were not modified in CON , and ( iii ) plasma F2-IsoP concentrations were lower in EX than in CON ( -35.7 % , p = 0.02 ) . In conclusion , our results show that 30 min of intradialytic training , 3 times per week for 3 months , are enough to exert beneficial effects on the most sensitive and reliable marker of lipid peroxidation ( IsoP ) while improving CKD-associated disorders ( lipid profile and physical fitness ) . Intradialytic aerobic cycling training represents a useful and easy strategy to reduce CKD-associated disorders . These results need to be confirmed with a larger r and omized study AIMS The objective of this study was to determine whether 24 weeks resistance training during hemodialysis could improve exercise capacity , muscle strength , physical functioning and health-related quality of life compared to a low intensity aerobic program . MATERIAL AND METHODS 27 patients ( 55.6 + /- 17.6 years ) were recruited from two hemodialysis clinics in Valencia ( Spain ) . Patients were r and omized to resistance training ( n = 19 ) or low-intensity aerobic training ( n = 8) . Resistance training consisted of three sets of 4 exercises at an intensity of 12 - 15 out of 20 at the rate of perceived exertion scale ( Borg scale measuring self-rated exercise intensity ) using weights and elastic b and s on every session during 24 weeks . Primary outcomes included physical performance tests , evaluated by the " sit-to-st and -to-sit tests " and the 6 minutes walking test , and knee extensor muscles strength , evaluated by isometric dynamometry . Secondary outcomes included cardiorespiratory fitness , measured by time and METs ( measure of energy expenditure as ml of oxygen per kg of weight and per minute ; 1 MET is equal to 3.5 ml O(2)/kg/min ) achieved on a grade d exercise test , and quality of life , measured by the SF-36 question naire . RESULTS No differences were noted in change-over-time between the two groups in any of the physical performance tests . However , a significant change was found in change-over-time in right knee extensor muscles dynamometry , and intragroup analysis showed a significant improvement in resistance training groups in the physical performance tests and METs . CONCLUSIONS These findings suggest that resistance training during hemodialysis improves patient 's physical functioning BACKGROUND Exercise training during the dialytical procedure may have positive cardiovascular effects and prevent or revert muscle wasting in patients undergoing chronic hemodialysis . AIM To evaluate the effects of an exercise training program in patients undergoing chronic hemodialysis . MATERIAL AND METHODS Fifteen patients on chronic hemodialysis aged 21 to 69 years ( three females ) were included in the study . Nine of these were included in an exercise training program . During 16 weeks , exercise sessions were carried out during each dialytical procedure that included a warm-up period , aerobic exercises done using st and ing cycles , and resistance exercises , performed using Thera-B and ( ® ) elastic b and s and loops . Borg scale was used to control the intensity of training . At baseline and at the end of the study , a blood sample prior and after the dialytical procedure was obtained to measure C reactive protein , tumor necrosis factor α and interleukin 6 . Quadriceps muscle strength , six minutes ' walk and quality of life using the SF-36 question naire , were also measured . RESULTS Four experimental subjects did not complete the study period , two that withdrew before starting , one due to problems with the venous access and one that decided to withdraw after 1 month of training . Among the five patients that finished the training period , significant improvements in the six minutes ' walk and quadriceps strength were observed in the experimental group . No significant changes were observed among controls . No changes were observed in either group in C reactive protein , tumor necrosis factor and interleukin 6 levels or quality of life . CONCLUSIONS Among patients undergoing chronic hemodialysis exercise training improves endurance and muscle strength Background End-stage renal disease is associated with several hemodynamic and peripheral muscle abnormalities that could slow the rate of change in oxygen uptake ( V · O2 ) at the onset and at the end of exercise . This study was performed to determine whether an intra-dialytic aerobic training program would speed V · O2 kinetics at the transition to and from moderate and high-intensity exercise . Design This study was a r and omized controlled trial . Methods Twenty-four patients with end-stage renal disease ( 14 females ; 47.0 ± 11.9 years ) were r and omly assigned to either 12-week cycle ergometer-based training at moderate exertion or a similar control period . At initial and final evaluations , patients underwent 6 min moderate and high-intensity tests to exercise intolerance ( Tlim ) . Results Training improved Tlim by ∼90 % ( median ( inter-quartile range ) = 232 ( 59 ) s to 445 ( 451 ) s , p < 0.05 ) ; in contrast , Tlim decreased by ∼30 % in controls ( 291 ( 134 ) s to 202 ( 131 ) s ) . V · O2 kinetics at the onset of moderate-intensity exercise were significantly accelerated with training leading to lower oxygen ( O2 ) deficit ( mean ± st and ard deviation ( SD ) = 3.2 ± 1.3 l vs 2.3 ± 1.2 l ) . Similar positive effects were found at the high-intensity test either at the onset of , or recovery from , exercise ( p < 0.05 ) . “ Excess ” V · O2 at the high-intensity test was also lessened with training . Changes in Tlim correlated with faster V · O2 kinetics and lower “ excess ” V · O2 ( Spearman 's ρ = –0.56 and –0.75 , respectively ; p < 0.01 ) . Conclusions A symptom-targeted intra-dialytic training program improved sub-maximal aerobic metabolism and endurance exercise capacity . V · O2 kinetics are valuable in providing relatively effort-independent information on the efficacy of exercise interventions in this patient population BACKGROUND Urea rebound results as urea re-equilibrates between intracellular and intravascular compartments post haemodialysis . The mechanism of the rebound is thought to be due to either a reduced diffusion rate or blood flow . It is hypothesized that low blood flow in the skeletal muscles might be responsible . We tested this by study ing the effect of exercise during dialysis on the removal of urea , creatinine and potassium . METHODS Eleven patients ( aged 32 - 78 years ) on haemodialysis ( 4 - 58 months ) were studied on paired dialysis sessions ; one with exercise and the other as a control . Patients pedalled on a cycle for 5 - 20 min at submaximal workload followed by 10 min rest to achieve a total of 60 min exercise . Plasma concentrations of urea , creatinine and potassium were measured pre- , post- and 30-min post dialysis . The post-dialysis rebound ( % rebound ) and reduction ratios ( RR ) of the solutes and equilibrated ( two-pool ) urea Kt/V were calculated for comparison . RESULTS The rebound of all three solutes was reduced significantly following exercise . The rebound of urea decreased from 12.4 to 10.9 % ( median , P<0.01 Wilcoxon signed rank test ) , creatinine from 21.2 to 17.2 % ( P<0.001 ) and potassium from 62 to 44 % ( P<0.05 ) . Kt/V and RR increased significantly as a result : Kt/V urea from 1.00 to 1.15 ( P=0.001 ) , RR urea from 0.63 to 0.68 ( P<0.001 ) ; Kt/V creatinine from 0.71 to 0.84 ( P<0.01 ) ; and RR creatinine from 0.51 to 0.57 ( P<0.05 ) . CONCLUSION Exercise increased the efficiency of dialysis by reducing the rebound of solutes due to increased perfusion of the skeletal muscles Hemodialyzed ( HD ) patients with end-stage renal disease ( ESRD ) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural , metabolic , and functional abnormalities in skeletal muscles . The aim of this r and omized study was to compare the effect of rehabilitation ( RHB ) training on a bicycle ergometer and electromyostimulation ( EMS ) of leg extensors in HD patients with ESRD . Thirty-two HD patients ( 18 men/14 women ; mean age 61.1 ± 8.8 years ) were r and omized into three groups : ( i ) exercise training ( ET ; n = 11 ) on bicycle ergometer 2 × 20 min ; ( ii ) EMS ( n = 11 ) where stimulation ( 10 Hz ) of leg extensors was applied for 60 min ; and ( iii ) controls ( CON ; n = 10 ) without exercise . Exercising was performed between the 2nd and the 3rd hour of HD , three times a week , 20 weeks in total . Ergometric test was performed in order to evaluate peak workload ( W(peak ) ) , 6-min corridor walking test ( CWT ) to evaluate the distance walked , and dynamometry of leg extensors to assess muscle power ( F(max ) ) . Urea clearance was monitored and expressed as st and ard parameters : spKt/V , spKt/V equilibrated ( spKt/V-e ) , and the urea removal ratio ( URR ) . Quality of life ( QoL ) was assessed by the question naire SF-36 . A significant increase of F(max ) ( P = 0.040 in group ET ; P = 0.032 in group EMS ) , of 6-min CWT ( P < 0.001 in ET group ; P = 0.042 in EMS group ) , and of W(peak ) ( P = 0.041 in ET group ) was observed . In both exercising groups , significant increase of spKt/V , spKt/V-e , and URR was found as compared with initial values ( P < 0.05 ) . In both exercising groups , highly significant changes in summarized mental functions were found ( P = 0.001 ) ; in summarized physical components , significant improvement was observed in the ET group ( P = 0.006 ) . Intradialytic RHB showed comparable positive effects on functional parameters , urea clearance , and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To investigate if high-intensity constant work rate ( CWR ) would constitute a more appropriate testing strategy compared with incremental work rate ( IWR ) to assess the effectiveness of intradialytic aerobic training in patients with end-stage renal disease ( ESRD ) . DESIGN R and omized controlled trial . SETTING Nephrology unit at the university hospital . PARTICIPANTS Patients ( N=28 ; 47.0±11.9y ) under hemodialysis ( 4.4±4.3y ) were r and omly assigned to exercise and control groups . INTERVENTION Patients included in the exercise group underwent a moderate-intensity intradialytic aerobic training program 3 times per week for 12 weeks . MAIN OUTCOME MEASURES Cardiopulmonary and perceptual responses were obtained during an IWR and a high-intensity CWR test to the limit of tolerance on a cycle ergometer . RESULTS Training-induced increases in peak oxygen uptake ( Vo(2)peak ) and time to exercise intolerance ( Tlim ) . Mean improvement in Tlim ( 97.4%±75.6 % ) was significantly higher than increases in Vo(2)peak ( 12%±11.3 % ) ( P<.01 ) ; in fact , while Tlim improved 50 % to 200 % in 9 of 12 patients , Vo(2)peak increases were typically in the 15 % to 20 % range . CWR test revealed lower metabolic , ventilatory , cardiovascular , and subjective stresses at isotime ; in contrast , submaximal responses during the incremental work rate ( at the gas exchange threshold ) remained unaltered after training . CONCLUSIONS A laboratory-based measure of endurance exercise capacity ( high-intensity CWR test to Tlim ) was substantially more sensitive than oxygen uptake at the peak IWR test to unravel the physiologic benefits of an intradialytic aerobic training program in mildly impaired patients with ESRD Both exercise training and treatment with dopamine agonists ( DA ) have been used with success for the amelioration of uremic restless legs syndrome ( RLS ) symptoms . However , no data are available combining those two approaches . The aim of the current r and omized , double-blind , placebo-controlled study was to investigate the effects of a 6 month intradialytic exercise training in combination with a low dose of DA in patients suffering from uremic RLS symptoms . Fourteen stable patients with RLS on hemodialysis were r and omly assigned to the exercise training plus DA group and the exercise training plus placebo group . Both combinations were found to equally reduce uremic RLS symptoms by approximately 60 % . The combination of low dose of DA with aerobic exercise training could be considered an alternative approach to high DA dosage regimes in reducing RLS symptoms ’ severity OBJECTIVE This study was conducted to determine the impact of an 8-week intradialytic exercise program ( consisting of 15 minutes low-intensity exercise during the first 2 hours of dialysis ) on dialysis efficacy . METHODS In an open r and omized controlled trial , a total of 50 clinical ly stable hemodialysis patients were enrolled into the study and r and omly allocated into two groups : the aerobic exercise group ( n=25 ) and the control group ( n=25 ) . Aerobic exercises were done in the intervention group for 15 min/day , three times a week for 2 months . The dialysis efficacy was assessed prior to and at the end of each month of the program . RESULTS The efficacy of dialysis increased at the end of the first month and remained elevated for the duration of the program in the exercise group ( p<0.05 ) . CONCLUSION A simplified aerobic exercise program has increased the efficacy of dialysis and may be considered as a safe , complementary and effective modality for hemodialysis patients We present the first study on the influence of exercise training on restless legs syndrome ( RLS ) in patients on hemodialysis ( HD ) . Restless legs syndrome has been treated pharmacologically with satisfactory results ; however , side effects and rebound phenomena have been reported . Intradialytic exercise training effectively counteracts uremia-induced catabolism ; nevertheless , it remains unknown whether patients with RLS undergoing HD benefit from such programs . The aims of the current study were to evaluate the effect of 16-weeks aerobic exercise training in the severity of RLS and in the functional capacity and the quality of life of patients with RLS on HD . Fourteen patients on HD ( four female , mean age 59 ± 16 years ) with untreated RLS were assigned , according to their will , to either the exercise group ( Ex-group , n = 7 ) , and participated in a 16-week supervised intradialytic aerobic exercise training , or to the control group ( Con-group , n = 7 ) , and continued usual activities . Primary aim was to compare the International RLS ( IRLS ) study group rating scale , functional ability , and quality of life in baseline and the end of the 16 weeks . Exercise training reduced IRLS score by 42 % ( p = 0.02 ) . Furthermore , it significantly improved indices of functional ability ( p = 0.02 ) , exercise capacity ( p = 0.01 ) , quality of life ( p = 0.03 ) , and sleep quality ( p = 0.01 ) . In the Con-group no changes were observed . In conclusion , aerobic exercise training is safe and efficacious in reducing RLS symptoms and improving quality of life in patients with RLS on HD BACKGROUND Physical performance measures , particularly gait speed , have been useful as predictors of loss of independence , institutionalization , and mortality in older nonuremic individuals . Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis , nor have the determinants of gait speed in the dialysis population been studied . METHODS We performed a cross-sectional analysis to determine whether demographic , clinical , or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units . Three physical performance measures were examined , including gait speed , time to climb stairs , and time to rise from a chair five times in succession . Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following c and i date predictor variables : age , gender , body mass index , dialysis vintage , Kt/V , albumin , blood urea nitrogen , creatinine , hematocrit , lean body mass , phase angle , ferritin , and the following comorbidities : hypertension , diabetes mellitus , coronary artery disease , peripheral vascular disease , and cerebrovascular disease . RESULTS Subjects included 31 men and 15 women aged 22 to 87 years ( mean + /- SD , 52 + /- 17 ) . The mean gait speed for the group was 113.1 + /- 34.5 cm/s ( low compared with norms established for persons of similar age ) . Results of multivariable regression showed that age , albumin , and Kt/V were important determinants of gait speed in this population . Overall , the model explained 52 % of the variability in gait speed ( r = 0.72 , P < 0.0001 ) . Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables , except that comorbidity was more important than age for stair climbing . The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance . CONCLUSIONS Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age , serum albumin , and dialysis dose . Prospect i ve studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis BACKGROUND Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients . We assessed the prevalence of depressive symptoms and physician-diagnosed depression , their variations by country , and associations with treatment by antidepressants among hemodialysis patients . We also assessed whether depressive symptoms were independently associated with mortality , hospitalization , and dialysis withdrawal . METHODS The sample was represented by 9382 hemodialysis patients r and omly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study ( DOPPS II ) . Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index ( CES-D ) , using > or = 10 CES-D score as the cut-off value . RESULTS Overall prevalence of physician-diagnosed depression was 13.9 % , and percentage of CES-D score > or = 10 43.0 % . While the smallest prevalence of physician-diagnosed depression was observed in Japan ( 2.0 % ) and France ( 10.6 % ) , the percentage of CES-D score > or = 10 in these counties was similar to the whole sample . Patients on antidepressants also varied by country , 34.9 % and 17.3 % among those with physician-diagnosed depression and CES-D scores > or = 10 , respectively . In Cox models adjusted for several comorbidities , CES-D scores > or = 10 were associated with significantly higher relative risks ( RR ) of death ( RR = 1.42 ; 95 % CI = 1.29 to 1.57 ) , hospitalization ( RR = 1.12 ; 95 % CI = 1.03 to 1.22 ) , and dialysis withdrawal ( RR = 1.55 ; 95 % CI = 1.29 to 1.85 ) . CONCLUSION The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients . CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization . Interventions should target these patients with the goal to improve survival and reduce hospitalizations Background : The number of chronic renal failure patients treated by hemodialysis ( HD ) is continuously increasing . Most patients have reduced physical capacity and have a high risk of cardiac and vascular diseases . The aim of this study was to determine the effects of 5 months physical exercise of HD patients ’ physical capacity , self-rated health and risk factors for cardiovascular disease . Methods : 33 HD patients were included in the study . Inclusion criteria : HD for more than 3 months , age > 18 years . Exclusion criteria : Diabetes mellitus , symptomatic cardiovascular disease , musculoskeletal limitations , severe peripheral polyneuropathy , inability to speak Danish or English , dementia or other mental disorders . The patients were r and omly assigned to an exercise group ( EG , n = 22 ) or a control group ( CG , n = 11 ) . Prior to r and omization , baseline testing was performed . The effects were measured by aerobic capacity , ‘ 2-min stair climbing ’ , ‘ squat test ’ , self-rated health ( SF36 ) , blood pressure and lipids . All tests were carried out by blinded testers . The intervention consisted of 1 h of physical exercise twice a week for 5 months . Results : 20 patients completed the intervention . Attendance was 74 % of all sessions . There were no dropouts caused by complications related to the intervention . The EG had a significant increase in aerobic capacity , ‘ squat test ’ and Physical Function and Physical Component Scale ( SF36 ) . No significant changes were observed in any of the parameters in the CG . Conclusion : Physical exercise twice a week for 5 months increases physical function and aerobic capacity in HD patients . An exercise program with only two exercise sessions per week seems easy to implement in clinical practice with high attendance among participants . Further investigation is needed to determine the effects on blood pressure and lipids . There were no medical complications related to the exercise program BACKGROUND Noninvasive screening studies may identify hemodialysis ( HD ) patients at increased risk of sudden cardiac death . Interventions that improve the findings of such screening studies may reduce sudden cardiac death . STUDY DESIGN R and omized and controlled clinical trial . SETTING & PARTICIPANTS 59 HD patients were r and omly assigned to an exercise training group ( group A ; 30 patients ) or control group ( group B ; 29 patients ) . INTERVENTION Group A participated in a 10-month supervised exercise training program during the HD sessions ( 3 times weekly ) . OUTCOMES Each risk factor separately and the composite risk score . Patients were considered high risk according to the criteria ( aerobic capacity : peak oxygen consumption [ Vo(2)peak ] < or = 14 mL/kg/min , left ventricular ejection fraction < or = 30 % , SD of normal RR intervals [ SDNN ] < or = 70 milliseconds , positive T-wave alternans , or positive late potentials ) . Statistical analysis included a 2-group comparison of change scores and analysis of covariance adjusting for baseline . MEASUREMENTS At entry and end of the study , Vo(2)peak and left ventricular ejection fraction were estimated , heart rate variability was calculated ( measurement of SDNN , mean RR intervals ) , and the ratio between low- ( LF ) to high-frequency ( HF ) components ( LF/HF ) and late potentials and T-wave alternans were detected . RESULTS Baseline measurements were similar between the 2 groups . At follow-up , 9 patients from group A and 20 from group B ( P = 0.003 ) were considered high risk . The change in number of risk markers over time was significantly different between groups ( -0.5 + /- 0.7 in group A versus 0.07 + /- 0.3 in group B ; P < 0.001 ) . Additionally , the change in Vo(2)peak over time was 3.5 + /- 3.2 in group A and -0.2 + /- 3.5 mL/kg/min in group B ( P < 0.001 ) , left ventricular ejection fractions were 3.4 % + /- 3.9 % and 0.2 % + /- 7.7 % ( P < 0.05 ) , SDNNs were 12.6 + /- 16.3 and -1.1 + /- 10.2 milliseconds ( P < 0.001 ) , and LF/HF ratios were 0.3 + /- 0.4 and -0.1 + /- 0.3 ( P < 0.001 ) , respectively . Change in numerical score of the signal-averaged electrocardiogram also was found to be statistically different ( P < 0.05 ) between groups . LIMITATIONS Clinical outcomes , including survival , were not assessed . CONCLUSIONS Exercise training improves aerobic capacity and ameliorates some indicators of risk of sudden cardiac death in HD patients BACKGROUND Arterial baroreflex sensitivity ( BRS ) evaluation has been increasingly used as an index of cardiac autonomic control . Cardiac autonomic dysfunction leading to depressed BRS has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with chronic kidney disease ( CKD ) on hemodialysis ( HD ) . AIM The purpose of this study was to investigate the effects of an exercise training program during hemodialysis on BRS in CKD patients . PATIENTS AND METHODS 43 HD patients participated in the study . They were r and omly assigned into either a 7-month exercise training program during HD ( Group A : n=22 patients ) or a sedentary control group ( Group B : n=21 patients ) . Additionally , 20 sex- and age-matched sedentary individuals comprised a healthy control group ( Group C ) . All patients at the beginning and the end of the study underwent a tilt test for evaluation of BRS and an exercise testing with spiroergometric study for cardiorespiratory capacity estimation . The level of Hb , medications and the HD procedure remained stable during the study . RESULTS At baseline BRS was found to be reduced by 51.5 % ( p<0.05 ) and baroreflex effectiveness index ( BEI ) by 36.4 % ( p<0.05 ) in Group A compared with Group C. Initially , all HD patients had also significantly lower exercise time and VO2 peak than the healthy subjects . After training , Group A showed a significant improvement in BRS by 23.0 % ( p<0.05 ) , in BEI by 27.0 % ( p<0.05 ) , in event and ramp count by 35.0 % ( p<0.05 ) and 29.0 % ( p<0.05 ) , respectively as well as in VO2 peak by 22.4 % ( p<0.05 ) and in exercise time by 40.9 % ( p<0.05 ) . Significant correlations were found between BRS and METs ( r=0.476 , p<0.05 ) , BRS and VO2 peak ( r=0.443 , p<0.05 ) , BEI and METs ( r = 0.492 , p<0.05 ) , BEI and VO2 peak ( r=0.467 , p<0.05 ) , event count and VO2 peak ( r=0.715 , p<0.01 ) , event count and exercise time ( r=0.799 , p<0.01 ) , in Group A at the end of the study . CONCLUSIONS Our results indicate that HD patients had considerably reduced cardiorespiratory capacity and impaired cardiac BRS compared to healthy sedentary individuals . Importantly , exercise training during HD yielded a marked increase of the indices representing baroreflex activity in association to the improvement of their functional capacity Physical function limitation is a common disorder in chronic hemodialysis ( HD ) patients , relating to increased morbidity and mortality . The aim of this study was to determine the effects of aerobic and resistance trainings on blood lipids and inflammation status in HD patients . Out of 30 volunteer males who had been undergoing conventional maintenance HD within an HD unit in Tehran , 21 subjects were enrolled . They were r and omly assigned into aerobic exercise group – resistance training group undergoing an 8-week intradialytic exercise program ( three times/week ) and control group ( n = 7 , each ) . Training program consisted of 10 - 30 min stationary cycling at an intensity of 12–16 out of 20 at the rate of perceived exertion ( RPE ) of Borg scale in aerobic group and using ankle weights for knee extension , hip abduction and flexions at an intensity of 15–17 out of 20 at the RPE of Borg scale in resistance group . Fasting blood sample s for serum biochemistry were drawn at baseline and 8 weeks . The age , HD duration , and physical activity score were 51.6±18.9yrs ; 25.1±13.9 mo , and 19.2±7.6 , respectively . Diabetes mellitus ( 43 % ) , hypertension ( 28 % ) , and obstructive uropathy ( 14 % ) were the most common underlying diseases . Aerobic and resistance exercises were correlated with serum creatinine ( P < 0.0001 and P<0.001 ) and hs-CRP levels ( P=0.005 and P=0.036 ) reduction so that aerobic exercise induced more reduction . These exercises had no influence on weight , Kt/V values , serum urea , albumin , hemoglobin , and lipid levels ( P>0.05 ) . Both intradialytic aerobic and resistance exercises showed beneficial effects on inflammation status without any influences on serum lipid levels probably due to short duration of the study which was not accompanied with body weight changes . Solute removal had no change during exercise programs . There is a need for more investigation on the role of exercise in HD patients Studies have shown that nuclear factor erythroid 2-related factor 2 ( Nrf2 ) can be modulated by physical exercise . However , the impact of resistance exercise has never been investigated in patients with chronic kidney disease ( CKD ) . The aim of this study was to evaluate the effects of resistance exercise programs on the expression of transcription factors Nrf2 and nuclear factor κB ( NF-κB ) in CKD patients on hemodialysis ( HD ) . Patients on an HD program were r and omly assigned to an exercise group of 25 patients ( 54.5 % women , aged 45.7±15.2years and time on dialysis=71.2±45.5months ) or a control group of 19 patients who had no exercise intervention ( 61.5 % women , aged 42.5±13.5years and time on dialysis=70.1±49.9months ) . A strength exercise program was performed 3 times a week during the HD sessions . Peripheral blood mononuclear cells were isolated and processed for the expression of Nrf2 and NF-κB by quantitative real-time polymerase chain reaction 3months before and after the exercise program . Using an enzyme-linked immunosorbent assay , the activity of glutathione peroxidase ( GPx ) as well as the products of high-sensitivity C-reactive protein and nitric oxide ( NO ) were assessed . Nrf2 expression ( ranging from 0.86±0.4 to 1.76±0.8 ) and GPx activity were significantly increased after exercise intervention . In the exercise group , no difference in the levels of NO was observed ; however , there was a significant reduction in the control group . In conclusion , these data suggest that resistance exercises seem to be capable of inducing Nrf2 activation in CKD patients on HD Functional capacity of end-stage renal disease patients is dramatically impaired . Although exercise training programs appear to have beneficial morphological , functional and psychosocial effects in end-stage renal disease patients on hemodialysis ( HD ) , the adherence rate is high . The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable , efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs . Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population . The 48 patients who completed the study protocol were r and omly assigned either to one of the three training groups or to a control group . Sixteen of them ( Group A - mean age 46.4+/-13.9 years ) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days ; 10 ( Group B - mean age 48.3+/-12.1 years ) completed a 6-month exercise program during HD ; 10 ( Group C - mean age 51.4+/-12.5 years ) followed an unsupervised moderate exercise program at home , and 12 patients ( Group D-mean age 50.2+/-7.9 years ) were used as patient controls . The level of anemia , the medications and the HD prescription remained stable during the study . Fifteen sex- and age-matched sedentary individuals ( Group E - mean age 46.9+/-6.4 years ) comprised a healthy control group for baseline data . All subjects at the beginning and end of the study underwent clinical examination , laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity . Group A had a higher dropout rate ( 24 % ) compared to groups B ( 17 % ) and C ( 17 % ) . Peak oxygen consumption ( VO2 peak ) increased by 43 % ( p < 0.05 ) , anaerobic threshold ( VO2AT ) by 37 % ( p < 0.05 ) and exercise time by 33 % ( p < 0.05 ) after training in Group A ; by 24 % ( p < 0.05 ) , 18 % ( p < 0.05 ) and 22 % ( p < 0.05 ) , respectively , in B ; and by 17 % ( p < 0.05 ) , 8 % ( p < 0.05 ) and 14 % ( p < 0.05 ) , respectively , in C ; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training , whereas exercise during HD is also effective and preferable The limitation to exercise capacity in hemodialysis patients has been attributed to anemia . We report the effects of normalization of hematocrit levels by using r-hu-recombinant erythropoietin and exercise training on exercise capacity and self-reported physical functioning in hemodialysis patients . Sixty-five patients were r and omized into 1 of 4 groups : usual hematocrit ( 30%-33 % ) with no exercise training ( UH ) ; usual hematocrit ( 30%-33 % ) plus exercise training ( UHX ) ; normalized hematocrit ( 40%-42 % ) with no exercise training ( NH ) ; and normalized hematocrit ( 40%-42 % ) plus exercise training ( NHX ) . Treadmill exercise testing was conducted at baseline and at 5 months after the initiation of the interventions . Analysis was performed on the data collapsed for 48 patients who met the criteria for hematocrit and exercise adherence and completed both baseline and post intervention ( 5.6 + /- 1.6 months ) testing . Significant effects of exercise were found in peak oxygen uptake measurements ( P = 0.03 ) and in self-reported physical functioning as measured by the Short Form-36 question naire ( P = 0.01 ) . There was a significant effect of hematocrit on the General Health scale on the SF-36 ( P = 0.03 ) . The changes in peak oxygen uptake with exercise training were small and levels remained lower than age-predicted values at the end of the study . These results indicate that there are other physiologic limitations to exercise capacity that are not overcome by exercise training or normalization of hematocrit . The effects of exercise training on self-reported physical functioning may be of clinical importance because these scores have been shown to be highly predictive of outcomes such as hospitalizations and mortality in hemodialysis patients BACKGROUND To determine whether prolonged ( 24 weeks ) intradialytic progressive resistance training ( PRT ) could counteract muscle wasting more effectively than short- duration training ( 12 weeks ) in patients with end-stage renal disease . STUDY DESIGN R and omized controlled trial . SETTING & PARTICIPANTS 49 patients ( age , 62.6 + /- 14.2 years ; 0.3 to 16.7 years on hemodialysis therapy ) were r and omly assigned to PRT plus usual care for 24 weeks ( 24WK group ) or a crossover control group that received usual care for the first 12 weeks , then PRT plus usual care for the latter 12 weeks ( 12WK group ) . INTERVENTION Two sets of 10 free-weight PRT exercises were performed at a high intensity during routine thrice-weekly hemodialysis treatment under direct supervision . OUTCOMES & MEASUREMENTS Primary outcomes include thigh muscle cross-sectional area by means of computed tomography and intramuscular lipid content estimated through attenuation . Secondary outcomes include muscular strength , exercise capacity , and C-reactive protein level . RESULTS The 24WK group increased muscle cross-sectional area ( + 1.82 + /- 3.25 cm(2 ) ) compared with losses in the 12WK group ( -1.37 + /- 6.87 cm(2 ) ; relative effect size , 0.59 ; 95 % confidence interval [ CI ] , -0.27 to 6.65 ; P = 0.04 ) . However , this outcome did not achieve the level of statistical significance required ( P = 0.025 ) after Bonferroni correction for multiple primary outcomes . There was no significant change in intramuscular lipid content between groups ( + 0.19 + /- 1.32 versus + 0.16 + /- 1.69 Hounsfield units in the 24WK and 12WK groups , respectively ; P = 0.31 ) . Log C-reactive protein level tended to decrease in the 24WK group compared with the 12WK group ( relative effect size , -0.63 ; 95 % CI , -0.27 [ -0.54 to 0.00 ] ; P = 0.05 ) . The 24WK group improved muscular strength measures and exercise capacity throughout the trial . LIMITATIONS Single geographic site used ; no control group without exercise exposure ; unblinded assessment of some secondary outcome measures . CONCLUSIONS Prolonged intradialytic PRT did not significantly improve muscle cross-sectional area or intramuscular lipid content compared with a shorter duration of exercise . Future trials are required to more thoroughly investigate the clinical importance and magnitude of myogenic adaptations to PRT in this cohort BACKGROUND Depression is not uncommon among patients with end-stage renal disease ( ESRD ) being treated by hemodialysis . We investigated whether risk of mortality and rate of hospitalization may be predicted from physician-diagnosed depression and patients ' self-reports of depressive symptoms . METHODS Data were analyzed from the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) for r and omly selected ESRD patients being treated by hemodialysis in the United States ( 142 facilities , 2855 patients ) and five European countries ( 101 facilities , 2401 patients ) . The diagnosis of depression during the past year was abstract ed from the medical records . In addition , the patients were asked to indicate how much of their time over the previous four weeks they had felt ( 1 ) " so down in the dumps that nothing could cheer you up " and ( 2 ) " downhearted and blue . " A response of " a good bit,""most , " or " all " of the time were classified as depressed . RESULTS The prevalence of depression was nearly 20 % . The relative risks of mortality and hospitalization among depressed ( vs. non-depressed ) , adjusted for time on dialysis , age , race , socioeconomic status , comorbid indicators and country were , respectively : 1.23 and 1.11 for physician-diagnosed depression , 1.48 and 1.15 for the " so down in the dumps " question , and 1.35 and 1.11 for the " downhearted and blue " question ( P < 0.05 for all six relative risks ) . These associations were not significantly different between US and European patients . CONCLUSIONS Self-reported depression by two simple questions was associated with increased risks of mortality and hospitalization for hemodialysis patients . Future research needs to assess whether early identification and treatment of depression may help to improve quality of life and survival in hemodialysis patients The aim was to assess the effects of exercise training on aerobic and functional capacity of patients with end‐stage renal disease ( ESRD ) . Patients completed an incremental exercise test on a cycle ergometer to determine VO2 peak and VO2 at ventilatory threshold ( VT ; V‐slope ) . On a separate day they performed two constant load exercise tests on a cycle ergometer at 90 % of VT and at a workload of 33 W , to determine VO2 kinetics . Functional capacity was assessed using measurements of sit‐to‐st and s ( STS‐5 , STS‐60 ) and a walk test . Dialysis patients were r and omly allocated to an exercise ( ET : n=18 , age=57·3 years ) or control ( C : n=15 , age=50·5 years ) group . The ET group participated in an exercise training programme involving cycling for 3 months . Repeated measures ANOVA revealed significant time by group interactions ( P < 0·05 ) following training for VO2 peak ( ET : 17 ± 6·1 versus 19·9 ± 6·3 , C : 19·5 ± 4·7 versus 18·8 ± 4·9 ml kg min–1 ) and VO2–VT ( ET : 10·7 ± 3·5 versus 11·8 ± 3·3 , C:12·9 ± 3·2 versus 11·9 ± 3·5 ml kg min–1 ) . VO2 kinetics remained unchanged in both groups at 90 % ‐VT , but a trend ( P=0·059 ) towards faster kinetics at the 33 W was observed ( ET : 49·6 ± 19·5 versus 37·8 ± 12·7 , C : 42·8 ± 13 versus 49·4 ± 20·2 s ) . Significant time by group interactions ( P < 0·05 ) were also observed for STS‐5 ( ET : 14·7 ± 6·2 versus 11·0 ± 3·3 , C : 12·8 ± 4·4 versus 12·7 ± 4·8 s ) and STS‐60 measurements ( ET : 21·2 ± 7·2 versus 26·9 ± 6·2 , C : 23·7 ± 6·8 versus 24·1 ± 7·2 ) . Three months of exercise rehabilitation significantly improves peak exercise capacity of patients with ESRD . Measurements of VO2 kinetics and functional capacity suggest that longer time might be needed to induce peripheral adaptations Patients who are on hemodialysis commonly experience muscle wasting and weakness , which have a negative effect on physical functioning and quality of life . The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis . A r and omized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California , San Francisco-affiliated dialysis units . Interventions included double-blinded weekly n and rolone decanoate ( 100 mg for women ; 200 mg for men ) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights . Primary outcomes included change in lean body mass ( LBM ) measured by dual-energy x-ray absorptiometry , quadriceps muscle cross-sectional area measured by magnetic resonance imaging , and knee extensor muscle strength . Secondary outcomes included changes in physical performance , self-reported physical functioning , and physical activity . Sixty-eight patients completed the study . Patients who received n and rolone decanoate increased their LBM by 3.1 + /- 2.2 kg ( P < 0.0001 ) . Exercise did not result in a significant increase in LBM . Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise ( P = 0.01 ) and to n and rolone ( P < 0.0001 ) in an additive manner . Patients who exercised increased their strength in a training-specific fashion , and exercise was associated with an improvement in self-reported physical functioning ( P = 0.04 compared with nonexercising groups ) . N and rolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis . Further studies are needed to determine whether these interventions improve survival To determine the effects of 12 wk of strength training on lactate threshold ( LT ) and endurance performance , 18 healthy untrained males between 25 and 34 yr of age were r and omly assigned to either strength training ( N = 10 ) or control ( N = 8) groups . Despite no changes in treadmill VO2max or cycle peak VO2 , a 33 + /- 5 % increase ( P less than 0.001 ) in cycling time to exhaustion at 75 % of peak VO2 was observed following training . No significant changes in cycling time were observed in the control group . There were significant reductions in plasma lactate concentration at all relative exercise intensities ranging between 55 and 75 % of peak VO2 training . The improved endurance performance was associated with a 12 % increase in LT ( r = 0.78 , P less than 0.001 ) . The strength training program result ed in significant improvements ( P less than 0.001 ) of 31 + /- 5 % and 35 + /- 7 % in isokinetic peak torque values for leg extension and flexion , respectively , at a velocity of 30 degrees.s-1 . There were also significant increases in 1-RM values of 30 + /- 4 % ( P less than 0.001 ) for leg extension , 52 + /- 6 % ( P less than 0.001 ) for leg flexion , and 20 + /- 4 % ( P less than 0.001 ) for the bench press . These findings indicate that strength training improves cycle endurance performance independently of changes in VO2max . This improved performance appears to be related to increases in LT and leg strength Background : Exercise during dialysis ( EDD ) in End-Stage Renal Disease ( ESRD ) has been documented as an effective intervention to improving a patient 's aerobic capacity . Aims : This pilot study aim ed to confirm physiological improvements , to establish its safety and practicality and to form guidelines for a long-term study , leading to the integration of EDD in ESRD therapy . Methods : A total of 17 patients on hospital haemodialysis were recruited : ten exercisers ( age 42.4 ± 12.6 ) and six controls ( age 41.0 ± 8.3 ) . Both groups were initially tested for estimated VO2max , heart rate , blood pressure , leg extension peak torque , anxiety and depression levels , as well as biochemical and haematological values . The exercisers then underwent cycling ergometer exercise sessions during dialysis , twice weekly , for a total of 12 sessions . Both groups were re-tested after this period . Results : All test and exercise sessions were completed without complication . Compliance was high with only 1 exerciser failing to complete all 12 sessions . The exercisers showed a statistically significant increase ( p < 0.05 ) in EDD workrates ( 44.3 to 52.1 watts ) during the 12 sessions and a reduction in anxiety ( p < 0.05 ) . Statistical analysis showed no other significant changes in either group after the 6-week period . Conclusion : This pilot study has confirmed that aerobic EDD is feasible and well accepted by patients on hospital haemodialysis . EDD reduced anxiety scores and showed a trend for an improved level of aerobic fitness Skeletal muscle wasting is common and insidious in patients who receive maintenance hemodialysis treatment for the management of ESRD . The objective of this study was to determine whether 12 wk of high-intensity , progressive resistance training ( PRT ) administered during routine hemodialysis treatment could improve skeletal muscle quantity and quality versus usual care . Forty-nine patients ( 62.6 + /- 14.2 yr ; 0.3 to 16.7 yr on dialysis ) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital ( Sydney , Australia ) . Patients were r and omized to PRT + usual care ( n = 24 ) or usual care control only ( n = 25 ) . The PRT group performed two sets of 10 exercises at a high intensity ( 15 to 17/20 on the Borg Scale ) using free weights , three times per week for 12 wk during routine hemodialysis treatment . Primary outcomes included thigh muscle quantity ( cross-sectional area [ CSA ] ) and quality ( intramuscular lipid content via attenuation ) evaluated by computed tomography scan . Secondary outcomes included muscle strength , exercise capacity , body circumference measures , proinflammatory cytokine C-reactive protein , and quality of life . There was no statistically significant difference in muscle CSA change between groups . However , there were statistically significant improvements in muscle attenuation , muscle strength , mid-thigh and mid-arm circumference , body weight , and C-reactive protein in the PRT group relative to the nonexercising control group . These findings suggest that patients with ESRD can improve skeletal muscle quality and derive other health-related adaptations solely by engaging in a 12-wk high-intensity PRT regimen during routine hemodialysis treatment sessions . Longer training duration s or more sensitive analysis techniques may be required to document alterations in muscle CSA OBJECTIVE Although resistance exercise has been associated with improvement in the muscle reserves , muscle strength and quality of life in end-stage renal disease patients , the objective of this paper is to evaluate the effect of resistance exercise performed during hemodialysis sessions on the anthropometric indicators of muscle reserve and h and grip strength in sedentary malnourished patients with end-stage renal disease . METHODS Patients were r and omized to perform resistance exercise during hemodialysis sessions with ankle weights and resistance b and s. The exercises were performed twice a week over the course of 12 weeks . The control group underwent a hemodialysis session alone . The outcomes measures were the following anthropometric measurements : arm muscle circumference and arm muscle area . Dynamometry was used to measure the h and grip strength . RESULTS Sixty-one sedentary patients with a median age of 29 years ( interquartile range [ IQR ] 21 - 39 years ) , and 83 % presenting with some grade of malnutrition were equally r and omized to either the intervention or control group . In the resistance exercise group , there was an increase in the arm muscle circumference from 233.6 ( IQR 202 - 254 ) mm to 241.4 ( IQR 203 - 264 ) mm ( P= .001 ) , arm muscle area from 35.9 ( 26 - 41 ) cm(2 ) to 36.6 ( IQR 26 - 46 ) cm(2 ) ( P= .002 ) , and h and grip strength from 19.6 ( IQR 11 - 28 ) kg to 21.2 ( IQR 13 - 32 ) kg between the basal and final measurements ( P < .05 ) . The tolerance to exercise was adequate , and no adverse events were reported during the practical exercise . CONCLUSIONS Resistance exercise at least twice a week is safe and represents an opportunity for improving the muscle mass and strength in adult patients who are on hemodialysis , including in those with malnutrition Patients on hemodialysis ( HD ) show changes in muscle structure and function reducing their functional capacity . This study was conduted to assess the effects of respiratory muscle training ( RMT ) and peripheral muscle training ( PMT ) during dialysis on functional parameters , inflammatory state , and quality of life ( QoL ) in patients on HD . R and omized controlled trial included 39 patients on HD , and they were divided into three groups : RMT ( n = 11 ) , PMT ( n = 14 ) , and controls ( C , n = 14 ) . Training was performed during the HD session for 10 weeks . Maximal inspiratory pressure ( PImax ) , maximal expiratory pressure ( PEmax ) , forced vital capacity ( FVC ) , six-minute walk test ( 6MWT ) , Kt/Vsp , biochemical parameters , and inflammatory state ( i.e. , level of high sensitivity C-reactive protein ) were evaluated . Variation from baseline was calculated by Analysis of Covariance ( ANCOVA ) . The ΔPImax was 22.5 ± 3.2 , 9.1 ± 2.9 , and −4.9 ± 2.8 cmH2O in the RMT , PMT and C , respectively ( p < 0.001 ) ; ΔPEmax was 10.8 ± 6.6 , 3.7 ± 5.9 , and −15.6 ± 5.9 cmH2O respectively ( p = 0.014 ) . The Δ6MWT was significantly greater in RMT and PMT ( 65.5 ± 9 ; 30.8 ± 8 m ) than in C ( −0.5 ± 8.1 m ) , p < 0.001 . Although biochemical parameters decreased after training , Kt/V remained unchanged . CRP decreased only in the RMT and PMT groups . There was a significant increase in QoL scores in the training groups ( vs. C ) in energy/fatigue ( p = 0.002 ) , sleep ( p < 0.001 ) , pain ( p < 0.001 ) , and list of symptoms/problems ( p = 0.014 ) . A short period of RMT or PMT during HD significantly improved functional capacity , with RMT showing greater effect than PMT . Muscle training improved biochemical and inflammatory markers , but a direct cause and effect relationship could not be established by this study |
13,064 | 23,873,003 | ConclusionS MSR PET has good diagnostic performance for evaluation of NET in the thorax and abdomen , better than SRS which has been the previous st and ard method .
This meta- analysis gives further support for switching to SMSR PET | Purpose Neuroendocrine tumours ( NET ) are uncommon and may be localized in many different places in the body .
Traditional imaging has mainly been performed with CT and somatostatin receptor scintigraphy ( SRS ) .
Recently , it has become possible to use somatostatin receptor PET/CT ( SMSR PET ) instead , which might improve diagnostic quality .
To evaluate the diagnostic quality of SMSR PET we performed a meta- analysis as an up date of a previous study published in 2012 . | The aim of this study was to evaluate the diagnostic value of a new somatostatin analog , 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N , N′,N″,N″′-tetraacetic acid-d-Phe1-Tyr3-octreotide ( 68Ga-DOTA-TOC ) , for PET in patients with known or suspected neuroendocrine tumors . PET was compared with conventional scintigraphy and dedicated CT . Methods : Eighty-four patients ( 48 men , 36 women ; age range , 28–79 y ; mean age ± SD , 58.2 ± 12.2 y ) were prospect ively studied . For analysis , patients were divided into 3 groups : detection of unknown primary tumor in the presence of clinical or biochemical suspicion of neuroendocrine malignancy ( n = 13 patients ) , initial tumor staging ( n = 36 patients ) , and follow-up after therapy ( n = 35 patients ) . Each patient received 100–150 MBq 68Ga-DOTA-TOC . Imaging results of PET were compared with 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide ( 99mTc-HYNIC-TOC ) and 111In-DOTA-TOC . CT was also performed on every patient using a multidetector scanner . Each imaging modality was interpreted separately by observers who were unaware of imaging findings before comparison with PET . The gold st and ard for defining true-positive ( TP ) , true-negative ( TN ) , false-positive ( FP ) , and false-negative ( FN ) results was based on all available histologic , imaging , and follow-up findings . Results : PET was TP in 69 patients , TN in 12 patients , FP in 1 patient , and FN in 2 patients , indicating a sensitivity of 97 % , a specificity of 92 % , and an accuracy of 96 % . The FP finding was caused by enhanced tracer accumulation in the pancreatic head , and the FN results were obtained in patients with a tumor of the gastrointestinal tract displaying liver metastases . 68Ga-DOTA-TOC showed higher diagnostic efficacy compared with SPECT ( TP in 37 patients , TN in 12 patients , FP in 1 patient , and FN in 34 patients ) and diagnostic CT ( TP in 41 patients , TN in 12 patients , FP in 5 patients , and FN in 26 patients ) . This difference was of statistical significance ( P < 0.001 ) . However , the combined use of PET and CT showed the highest overall accuracy . Conclusion : 68Ga-DOTA-TOC PET shows a significantly higher detection rate compared with conventional somatostatin receptor scintigraphy and diagnostic CT with clinical impact in a considerable number of patients BACKGROUND : Endoscopic ultrasonography ( EUS ) and somatostatin receptor scintigraphy ( SRS ) can detect a high percentage of gastroenteropancreatic neuroendocrine tumours especially in the upper gastrointestinal tract . The ability of these procedures to localise primary tumour lesions and metastases of gastrinomas and insulinomas was evaluated in comparison with transabdominal ultrasonography ( US ) , computed tomography ( CT ) and magnetic resonance imaging ( MRI ) . PATIENTS AND METHODS : In a prospect i ve trial , patients with gastrinomas ( n = 10 ) and insulinomas ( n = 10 ) diagnosed by clinical signs and laboratory tests were assessed by EUS , SRS , US , CT and MRI . RESULTS : In 10 patients with gastrinoma and 10 patients with insulinoma , a total of 14 separate primary tumour lesions were histologically confirmed for each of the tumour entities . The mean diameter was 2.1 cm for gastrinomas and 1.5 cm for insulinomas . All insulinomas and nine gastrinoma lesions were located in the pancreas . Three gastrinomas were found in the duodenal wall , one in a periduodenal lymph node , and one in the liver , For gastrinomas , sensitivities were 79 % with EUS , 86 % with SRS and 29 % with CT , US , and MRI . For insulinomas , sensitivities were 93 % with EUS , 14 % with SRS , 21 % with CT and 7 % with US and MRI . CONCLUSIONS : EUS is of high value for localising primary lesions of both tumour entities . SRS is a very sensitive procedure for diagnosing of gastrinomas but not insulinomas . CT , US and MRI are primarily useful for visualising metastases Purpose Neuroendocrine tumours ( NETs ) can be imaged with scintigraphy using radiolabelled somatostatin analogues . The aim of our study was to compare the value of 68Ga-DOTATOC PET and 111In-DTPAOC SPECT ( Octreoscan ) in the detection of NET manifestations . Methods Twenty-seven NET patients were prospect ively examined . 68Ga-DOTATOC PET and 111In-DTPAOC SPECT were performed using st and ard techniques . Treatment was not applied in between . Mean and maximum st and ardised uptake values ( SUVs ) were calculated for PET findings . Tumour/non-tumour ratios were calculated for SPECT findings . Findings were compared by a region-by-region analysis and verified with histopathology , CT and MRI within 21 days . Results SUVs of positive lesions on 68Ga-DOTATOC PET ranged from 0.7 to 29.3 ( mean SUV ) and from 0.9 to 34.4 ( maximum SUV ) . Tumour/non-tumour ratios on 111In-DTPAOC SPECT ranged from 1.8 to 7.3 . In imaging lung and skeletal manifestations , 68Ga-DOTATOC PET was more efficient than 111In-DTPAOC SPECT . All discrepant lung findings and 77.8 % of discrepant osseous findings were verified as true positive PET interpretations . In regional comparison of liver and brain , 68Ga-DOTATOC PET and 111In-DTPAOC SPECT were identical . In lymph nodes , the pancreas and the gastro-intestinal system , different values of the two techniques were not indicated in regional analyses . In a single patient , surgical interventions were changed on the basis of 68Ga-DOTATOC PET findings . Conclusion 68Ga-DOTATOC PET is superior to 111In-DTPAOC SPECT in the detection of NET manifestations in the lung and skeleton and similar for the detection of NET manifestations in the liver and brain . 68Ga-DOTATOC PET is advantageous in guiding the clinical management Radiolabeled somatostatin analogs represent valuable tools for both in vivo diagnosis and therapy of neuroendocrine tumors ( NETs ) because of the frequent tumoral overexpression of somatostatin receptors ( sst ) . The 2 compounds most often used in functional imaging with PET are 68Ga-DOTATATE and 68Ga-DOTATOC . Both lig and s share a quite similar sst binding profile . However , the in vitro affinity of 68Ga-DOTATATE in binding the sst subtype 2 ( sst2 ) is approximately 10-fold higher than that of 68Ga-DOTATOC . This difference may affect their efficiency in the detection of NET lesions because it is the sst2 that is predominantly overexpressed in NET . We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ( 68Ga-DOTATATE and 68Ga-DOTATOC ) in the same NET patients . Methods : Forty patients with metastatic NETs underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT as part of the work-up before prospect i ve peptide receptor radionuclide therapy . The performance of both imaging methods was analyzed and compared for the detection of individual lesions per patient and for 8 defined body regions . A region was regarded positive if at least 1 lesion was detected in that region . In addition , radiopeptide uptake in terms of the maximal st and ardized uptake value ( SUVmax ) was compared for concordant lesions and renal parenchyma . Results : Seventy-eight regions were found positive with 68Ga-DOTATATE versus 79 regions with 68Ga-DOTATOC ( not significant ) . Overall , however , significantly fewer lesions were detected with 68Ga-DOTATATE than with 68Ga-DOTATOC ( 254 vs. 262 , P < 0.05 ) . Mean 68Ga-DOTATATE SUVmax across all lesions was significantly lower than 68Ga-DOTATOC ( 16.0 ± 10.8 vs. 20.4 ± 14.7 , P < 0.01 ) . Mean SUVmax for renal parenchyma was not significantly different between 68Ga-DOTATATE and 68Ga-DOTATOC ( 12.7 ± 3.0 vs. 13.2 ± 3.3 ) . Conclusion : 68Ga-DOTATOC and 68Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions , with 68Ga-DOTATOC having a potential advantage . The approximately 10-fold higher affinity for the sst2 of 68Ga-DOTATATE does not prove to be clinical ly relevant . Quite unexpectedly , SUVmax of 68Ga-DOTATOC scans tended to be higher than their 68Ga-DOTATATE counterparts Abstract . Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging ( SRI ) . However , there may be differences in sensitivity depending on the site of the primary tumour and /or its metastases . We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic ( GEP ) tract . A pathological diagnosis was obtained in 116 patients , while in 15 the diagnosis was based on instrumental results and follow-up . Fifty-one patients were examined for staging purpose s , 80 were in follow-up . Images were acquired 24 and 48 h after the injection of 150–220 MBq of indium-111 pentetreotide . Whole-body and SPET images were obtained in all patients . Patients were also studied with computed tomography ( CT ) , ultrasound ( US ) , and other procedures . Tumours were classified according to their site of origin : pancreas n = 39 , ileum n = 32 , stomach n = 16 , appendix n = 9 , duodenum n = 5 , jejunum n = 5 , rectum n = 3 , biliary tract n = 2 , colon n = 2 , caecum n = 1 , liver metastases from unknown primary = 15 , widespread metastases from unknown primary = 2 . Sensitivity for primary tumour localisation was as follows : SRI = 62 % ; CT = 43 % ; US = 36 % ; other procedures = 45 % . Sensitivity for liver metastases : SRI = 90 % ; CT = 78 % ; US = 88 % ; other procedures = 71 % . Sensitivity for the detection of extrahepatic soft tissue lesions was : SRI = 90 % ; CT = 66 % ; US = 47 % ; other procedures = 61 % . Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites : SRI 4/17 ; CT 0/13 ; US 0/12 ; other procedures 1/10 . In 28 % of the patients SRI revealed previously unknown lesions , and in 21 % it determined a modification of the scheduled therapy . Our study confirms the important role of SRI in the management of GEP tumours . However , we feel that a critical investigation should address its role in locating primary tumours , in particular in patients with metastases from unknown primary sites Abstract Objective To evaluate the role of 68Ga-labelled [ 1 , 4 , 7 , 10-tetraazacyclododecane-1 , 4 , 7 , 10-tetraacetic acid]-1-NaI3-Octreotide ( 68Ga-DOTA-NOC ) whole body positron emission tomography-computed tomography ( PET-CT ) as a functional imaging approach for phaeochromocytoma and paraganglioma . Methods Thirty-five unrelated patients ( Median age-34.4 years ; range : 15–71 ) were evaluated in this prospect i ve study . PET-CT was performed after injection of 132–222 MBq of 68Ga-DOTA-NOC . Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively ( st and ardised uptake value-SUVmax ) . In addition we compared the findings with 131I Metaiodobenzylguanidine ( MIBG ) scintigraphy , which was available for 25 patients . Histopathology and /or conventional imaging with biochemical markers were taken as the reference st and ard . Results 44 lesions were detected on 68Ga-DOTA-NOC PET-CT imaging with an additional detection of 12 lesions not previously known , leading to a change in management of 6 patients . Sensitivity , specificity and accuracy were 100 % , 85.7 % , and 97.1 % on a per patient basis and 100 % , 85.7 % and 98 % on per lesion basis , respectively.131I MIBG scintigraphy was concordant with 68Ga-DOTA-NOC PET-CT in 16 patients and false negative in 9 patients . Conclusion 68Ga-DOTA-NOC PET-CT is highly sensitive and specific for the detection of phaeochromoctyomas and paragangliomas . It seems better than 131I MIBG scintigraphy for this purpose .Key Points• 68Ga-DOTA-NOC PET-CT seems useful in patients with phaeochromocytoma and paraganglioma . • This prospect i ve single centre study showed that it has high diagnostic accuracy . • 68Ga-DOTA-NOC PET-CT seems superior to131I-MIBG in these patients BACKGROUND & AIMS Duodenal gastrinomas and peripancreatic lymph nodes are difficult to localize . The aim of this study was to evaluate the ability of Octreoscan scintigraphy to detect such tumors . METHODS Results of Octreoscan scintigraphy in 21 consecutive patients with Zollinger-Ellison syndrome were compared with those of conventional imaging techniques , including endoscopic ultrasonography , and with the surgical findings . RESULTS Surgical exploration found 27 duodenal and /or lymph node gastrinomas in 19 patients . None had pancreatic gastrinoma . Octreoscan scintigraphy was the only positive preoperative technique in 32 % of the patients . The sensitivities of conventional techniques , Octreoscan scintigraphy , and their association were 58 % , 58 % , and 90 % , respectively , for all resected gastrinomas . The smallest duodenal gastrinoma detected by Octreoscan scintigraphy measured 3 mm . Endoscopic ultrasonography detected all the tumors visualized by any other conventional technique and was considered falsely positive , as was Octreoscan scintigraphy , in 1 patient . Follow-up and comparison between the number of resected gastrinomas and the number of preoperative hot spots suggested that surgeons should find at least as many tumors as the number of hot spots . CONCLUSIONS Octreoscan scintigraphy improved the preoperative detection of extrapancreatic gastrinomas , mainly by endoscopic ultrasonography . Surgeons should find at least as many gastrinomas as the number of hot spots Purpose 18F-FDG positron emission tomography ( PET ) value for the assessment of neuro-endocrine tumours ( NET ) is limited . Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy . At present , there are no comparative studies investigating their role in NET . Aim The aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours . Material s and methods Thirteen patients with biopsy-proven NET ( gastro-entero-pancreatic or pulmonary ) were prospect ively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET . PET results obtained with both tracers were compared with each other , with other conventional diagnostic procedures ( CT , ultrasound ) and with follow-up ( clinical , imaging ) . Results The most common primary tumour site was the pancreas ( 8/13 ) followed by the ileum ( 2/13 ) , the lung ( 2/13 ) and the duodenum ( 1/13 ) . The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases . 68Ga-DOTA-NOC PET was positive , showing at least one lesion , in 13/13 cases while 18F-DOPA PET was positive in 9/13 . On a lesions basis , 68Ga-DOTA-NOC identified more lesions than 18F-DOPA ( 71 vs 45 ) , especially at liver , lung and lymph node level . 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases ( in five cases , the primary was surgically removed before PET ) , while 18F-DOPA identified the primary only in two of eight cases . Conclusions Although the patients studied are few and heterogeneous , our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA BACKGROUND & AIMS Recently [111In-DTPA-D-Phe1]-octreotide was approved for somatostatin receptor scintigraphy ( SRS ) of gastroenteropancreatic tumors . SRS and other tumor localization methods can be time consuming , expensive , and involve patient inconvenience . The role of SRS in comparison to other tumor localization modalities remains undefined because the relative effects of these methods on management have not been studied . The aim of this study was to determine whether SRS alters clinical management in Zollinger-Ellison syndrome . METHODS One hundred twenty-two consecutive patients were studied prospect ively . Each patient was assigned to one of five different clinical categories . Conventional imaging studies ( ultrasonography , computerized tomography , magnetic resonance image , angiography , and bone scan ) were performed , and the management was proposed . SRS was then performed . Clinical management was reassessed , and whether SRS altered management was determined based on six criteria . RESULTS SRS was superior to any single imaging study . SRS altered management in 47 % overall and in 22%-60 % of patients in the five different clinical categories . Primary tumor localization and clarification of equivocal localization results from conventional studies were the principal reasons for altering management . SRS was equally useful in patients with or without metastatic liver disease . CONCLUSIONS Because of the ability of SRS to alter clinical management combined with its superior sensitivity , high specificity , simplicity , and cost-effectiveness , SRS should be the initial imaging modality for patients with gastrinomas Purpose Recent data have indicated that 68Ga-DOTA-NOC positron emission tomography/X-ray computed tomography ( PET/CT ) may yield improved images in a shorter acquisition protocol than 111In-DTPA-octreotide ( OctreoScan ® , OCT ) . Therefore , we performed a prospect i ve comparison of 68Ga-DOTA-NOC and OCT for the detection of neuroendocrine tumors ( NETs ) . Methods Nineteen patients ( eight carcinoid , nine pancreatic NETs , and two NE carcinoma of unknown origin ) with previous positive OCT scans underwent 68Ga-DOTA-NOC PET/CT and OCT single-photon emission computed tomography imaging for staging or follow-up . Findings were compared by region and verified with conventional imaging . Results All images of both modalities demonstrated focal uptake , often at multiple sites . 68Ga-DOTA-NOC images were clearer than OCT images , facilitating interpretation . Similar foci were identified with both modalities in 41 regions , with additional foci on 68Ga-DOTA-NOC in 21 and on OCT in 15 regions . CT , magnetic resonance imaging , or ultrasound confirmed the concordant findings in 31 of 41 regions and findings seen with 68Ga-DOTA-NOC only in 15 of 21 regions . Findings seen with OCT only were less clear and were only confirmed in 4 of 15 regions . 68Ga-DOTA-NOC had impact on staging in four patients and on management in three patients . Conclusions Although 68Ga-DOTA-NOC and OCT images were similar , in this study , 68Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients . This direct comparison supports replacement of OCT with 68Ga-DOTA-NOC-PET/CT in the evaluation of NETs UNLABELLED Somatostatin receptor scintigraphy ( SRS ) has been used for the detection of gastroenteropancreatic ( GEP ) tumors . This study evaluates the clinical impact of SRS in GEP tumor detection and its therapeutic implication s on patient management . METHODS We prospect ively studied 160 patients with biologically and /or histologically proven GEP tumors . Before SRS , patients were classified into three groups : gastrointestinal ( Group 1 ; n = 90 ) patients without known metastases ; ( Group 2 ; n = 59 ) patients with metastases limited to the liver ; ( Group 3 ; n = 11 ) patients with known extrahepatic metastases . The scintigraphic data were compared to the radiological findings . RESULTS In Group 1 , without known metastases , conventional imaging detected 53 primary sites in 44 patients : SRS was positive in 68 % of these sites and discovered 4 additional primary tumors in 3 patients and 16 metastases in 14 patients . Conventional imaging was negative in 46 patients : SRS discovered 47 new sites in 36 patients . In Group 2 , SRS confirmed liver metastases in 95 % of patients and discovered 45 new sites in 36 of these patients . In Group 3 , SRS disclosed 11 new sites in 7 patients . These results modified patient classification in 38 cases ( 24 % ) . Surgical therapeutic strategy was changed in 40 patients ( 25 % ) . CONCLUSION Somatostatin receptor scintigraphy improves tumor detection , has major clinical significance and should be performed systematic ally for staging and therapeutic decision making in patients with GEP tumors UNLABELLED The use of positron emitter-labeled compounds for somatostatin receptor imaging ( SRI ) has become attractive because of the prospect of improved spatial resolution , accelerated imaging procedures , and the ability to quantify tissue radioactivity concentrations . This paper provides results from first-in-humans use of (64)Cu-DOTATATE , an avidly binding somatostatin receptor lig and linked to a radioisotope with intermediate half-life and favorable positron energy ( half-life , 12.7 h ; maximum positron energy , 0.653 MeV ) . METHODS In a prospect i ve setup , 14 patients with a history of neuroendocrine tumors underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with our current routine imaging agent (111)In-diethylenetriaminepentaacetic acid-octreotide . After intravenous injection of 193 - 232 MBq of (64)Cu-DOTATATE , whole-body PET scans were acquired at 1 h ( n = 14 ) , 3 h ( n = 12 ) , and 24 h ( n = 5 ) after administration . Tissue radioactivity concentrations for normal organs and lesions were quantified , and st and ardized uptake values were calculated for the early ( 1 h ) and delayed ( 3 h ) scans . Using the data for 5 patients , we assessed the radiation dose with OLINDA/EXM software . Furthermore , the clinical performance of (64)Cu-DOTATATE with respect to lesion detection was compared with conventional SRI . RESULTS SRI with (64)Cu-DOTATATE produced images of excellent quality and high spatial resolution . Images were characterized by high and stable tumor-to- background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy , (64)Cu-DOTATATE PET identified additional lesions in 6 of 14 patients ( 43 % ) . In 5 patients , lesions were localized in organs and organ systems not previously known as metastatic sites , including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene . All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo . Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of (64)Cu-DOTATATE , with the liver being the organ with the highest absorbed radiation dose ( 0.16 mGy/MBq ) . CONCLUSION This first-in-humans study supports the clinical use of (64)Cu-DOTATATE for SRI with excellent imaging quality , reduced radiation burden , and increased lesion detection rate when compared with (111)In-diethylenetriaminepentaacetic acid-octreotide OBJECTIVE To determine the relative abilities of somatostatin receptor scintigraphy ( SRS ) and conventional imaging studies ( computed tomography , magnetic resonance imaging , ultrasound , angiography ) to localize gastrinomas before surgery in patients with Zollinger-Ellison syndrome ( ZES ) subsequently found at surgery , and to determine the effect of SRS on the disease-free rate . SUMMARY BACKGROUND DATA Recent studies demonstrate that SRS is the most sensitive imaging modality for localizing neuroendocrine tumors such as gastrinomas . Because of conflicting results in small series , it is unclear in ZES whether SRS will alter the disease-free rate , which gastrinomas are not detected , what factors contribute to failure to detect a gastrinoma , or whether the SRS result should be used to determine operability in patients without hepatic metastases , as recently recommended by some investigators . METHODS Thirty-five consecutive patients with ZES undergoing 37 exploratory laparotomies for possible cure were prospect ively studied . All had SRS and conventional imaging studies before surgery . Imaging results were determined by an independent investigator depending on surgical findings . All patients underwent an identical surgical protocol ( palpation after an extensive Kocher maneuver , ultrasound during surgery , duodenal transillumination , and 3 cm duodenotomy ) and postoperative assessment of disease status ( fasting gastrin , secretin test imaging within 2 weeks , at 3 to 6 months , and yearly ) , as used in pre-SRS studies previously . RESULTS Gastrinomas were detected in all patients at each surgery . Seventy-four gastrinomas were found : 22 duodenal , 8 pancreatic , 3 primaries in other sites , and 41 lymph node metastases . The relative detection order on a per-patient or per-lesion basis was SRS > angiography , magnetic resonance imaging , computed tomography > ultrasound . On a per-lesion basis , SRS had greater sensitivity than all conventional studies combined . SRS missed one third of all lesions found at surgery . SRS detected 30 % of gastrinomas < or = 1.1 cm , 64 % of those 1.1 to 2 cm , and 96 % of those > 2 cm and missed primarily small duodenal tumors . Tumor size correlated closely with SRS rate of detection . SRS did not increase the disease-free rate immediately after surgery or at 2 years mean follow-up . CONCLUSIONS SRS is the most sensitive preoperative imaging study for extrahepatic gastrinomas in patients with ZES and should replace conventional imaging studies as the preoperative study of choice . Negative results of SRS for localizing extrahepatic gastrinomas should not be used to decide operability , because a surgical procedure will detect 33 % more gastrinomas than SRS . SRS does not increase the disease-free rate . In the future , more sensitive methods to detect small gastrinomas , especially in the duodenum and in periduodenal lymph nodes , or more extensive surgery will be needed to improve the postoperative disease-free rate in ZES In patients with the Zollinger-Ellison syndrome , which is either sporadic or integrated into multiple endocrine neoplasia type 1 , accurate localization of all the tumours is difficult and may have therapeutic implication s. In an attempt to improve this localization , somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide was performed prospect ively in 48 consecutive patients with the Zollinger-Ellison syndrome . Thirty of them had the sporadic type of this disease . Scintigraphic data were compared with data obtained by conventional imaging methods , and also , in 32 selected patients , with those obtained by endoscopic ultrasonography . Somatostatin receptor scintigraphy showed abnormal tracer uptake in 39 patients ( 81 % ) , in whom it correctly identified 50 of the 60 tumoral sites ( 83 % ) previously localized by the other imaging methods . In 17 patients ( 35 % ) somatostatin receptor scintigraphy disclosed abnormal tracer uptake at 18 different tumoral sites : 14 were located in the abdomen , including four in the liver and eight in the duodenopancreatic area , and four outside the abdomen , including two in the mediastinum . Six of the ten tumoral sites which were not correctly identified by somatostatin receptor scintigraphy were located in the duodenopancreatic area . However , in the 20 patients for whom conventional techniques failed to visualize any tumour in the duodenopancreatic area , somatostatin receptor scintigraphy was positive in ten ( 50 % ) whereas endoscopic ultrasonography was only positive in five ( 25 % ) . In our patients with the Zollinger-Ellison syndrome , somatostatin receptor scintigraphy appeared to be a useful new addition to the battery of tests used for tumour detection |
13,065 | 14,583,963 | MAIN RESULTS None of the six studies reporting cognitive training interventions demonstrated any statistically significant effects in any domain , although there were indications of some modest , non-significant effects in various domains of cognitive functioning . | BACKGROUND Memory problems are a defining feature of the early stages of Alzheimer 's disease ( AD ) and vascular dementia .
Cognitive training and cognitive rehabilitation are specific approaches design ed to address everyday memory difficulties .
OBJECTIVES The main aim was to evaluate the effectiveness and impact of cognitive training and cognitive rehabilitation interventions aim ed at improving memory functioning for people in the early stages of Alzheimer 's disease or vascular dementia .
The two types of intervention were considered separately . | BACKGROUND A recent Cochrane review of reality orientation therapy identified the need for large , well- design ed , multi-centre trials . AIMS To test the hypothesis that cognitive stimulation therapy ( CST ) for older people with dementia would benefit cognition and quality of life . METHOD A single-blind , multi-centre , r and omised controlled trial recruited 201 older people with dementia . The main outcome measures were change in cognitive function and quality of life . An intention-to-treat analysis used analysis of covariance to control for potential variability in baseline measures . RESULTS One hundred and fifteen people were r and omised within centres to the intervention group and 86 to the control group . At follow-up the intervention group had significantly improved relative to the control group on the Mini-Mental State Examination ( P=0.044 ) , the Alzheimer 's Disease Assessment Scale - Cognition ( ADAS-Cog ) ( P=0.014 ) and Quality of Life - Alzheimer 's Disease scales ( P=0.028 ) . Using criteria of 4 points or more improvement on the ADAS-Cog the number needed to treat was 6 for the intervention group . CONCLUSION The results compare favourably with trials of drugs for dementia . CST groups may have worthwhile benefits for many people with dementia The efficacy of a cognitive intervention consisting of training in face-name associations , spaced retrieval , and cognitive stimulation was tested in a sample of 37 patients ( 16 men , 21 women ) with probable Alzheimer disease ( AD ) . Patients with AD were r and omly assigned to receive either the cognitive intervention or a mock ( placebo ) intervention for 5 weeks . The placebo group then crossed over to receive the intervention . During the intervention , AD patients showed significant improvement in recall of personal information , face-name recall , and performance on the Verbal Series Attention Test . Improvement did not generalize to additional neuropsychologic measures of dementia severity , verbal memory , visual memory , word generation , or motor speed , or to caregiver-assessed patient quality of life . Results suggest that although face-name training , spaced retrieval , and cognitive stimulation may produce small gains in learning personal information and on a measure of attention , improvement does not generalize to overall neuropsychologic functioning or patient quality of life OBJECTIVE The authors evaluated the efficacy of a new cognitive rehabilitation program on memory and functional performance of mildly impaired Alzheimer disease ( AD ) patients receiving a cholinesterase inhibitor . METHODS Twenty-five participants in the Cognitive Rehabilitation ( CR ) condition participated in two 45-minute sessions twice per week for 24 total sessions . CR training included face-name association tasks , object recall training , functional tasks ( e.g. , making change , paying bills ) , orientation to time and place , visuo-motor speed of processing , and the use of a memory notebook . Nineteen participants in the Mental Stimulation ( MS ) condition had equivalent therapist contact and number of sessions , which consisted of interactive computer games involving memory , concentration , and problem-solving skills . RESULTS Compared with the MS condition , participants in CR demonstrated improved performance on tasks that were similar to those used in training . Gains in recall of face-name associations , orientation , cognitive processing speed , and specific functional tasks were present post-intervention and at a 3-month follow-up . CONCLUSION A systematic program of cognitive rehabilitation can result in maintained improvement in performance on specific cognitive and functional tasks in mildly impaired AD patients OBJECTIVE --To reduce the psychological stress and improve the skills in coping of people who care for relatives with dementia . DESIGN -- Assessment and suitability of carers by question naire ; assessment of patients and carers in a hospital outpatient clinic ; allocation to groups according to date of application to study . Linkage of groups of four carers and programme coordinator by telephone conference calls over 12 months after programmes . Re assessment at three , six , 12 , and , for those in the " wait list " group , 18 months . SETTING --The programmes were conducted in the psychiatry unit of a Sydney teaching hospital . SUBJECTS -- Eligible patients were less than 80 years old , had mild to moderate dementia , and lived at home with their carer . Of the 96 patient-carer pairs in the study , 33 were in the dementia carers ' programme group , 31 were in the memory retraining group , and 32 were in the wait list group . INTERVENTIONS --Carers in the dementia carers ' programme received training in coping with the difficulties of looking after patients with dementia while the patients had sessions in subjects such as memory retraining . In the memory retraining programme patients were admitted and received the patient component of the carers ' programme while their carers had 10 days ' respite . In the wait list group carers waited six months before undertaking the carers ' programme . MAIN OUTCOME MEASURES --Effect of the programmes on carers ' general health question naire scores and the rate of placement of patients in institutions . RESULTS --At 12 months ' follow up the carers ' programme had result ed in significantly lower psychological stress among carers than the memory retraining programme ( mean ( SD ) general health question naire scores at 0 months were 6.31 ( 6.23 ) and 3.60 ( 6.25 ) respectively , and at 12 months were 4.69 ( 5.58 ) and 7.40 ( 9.39 ) ; p less than 0.05 . ) In the wait list group distress scores remained stable , even after the carers and patients had undertaken the carers ' programme . Patients deteriorated over 12 months regardless of group allocation , but at 30 months , allowing for patients who died and could not be included in the analysis , 65 % of patients in the carers ' programme group were still living at home compared with 26 % in the memory retraining programme group . CONCLUSION --The intensive intervention programme described for carers of patients with dementia can reduce the psychological morbidity of the carer and delay the placement of the patient in an institution without increasing the use of health services by either patient or carer This r and omized study evaluated the combined effect of a cognitive-communication program plus an acetylcholinesterase inhibitor ( donepezil ; donepezil-plus-stimulation group ; n = 26 ) , as compared with donepezil alone ( donepezil-only group ; n = 28 ) in 54 patients with mild to moderate Alzheimer 's disease ( AD ; Mini-Mental Status Examination score of 12- 28 ) ranging in age from 54 to 91 years . It was hypothesized that cognitive-communication stimulation in combination with donepezil would positively affect the following : ( a ) relevance of discourse , ( b ) performance of functional abilities , ( c ) emotional symptoms , ( d ) quality of life , and ( e ) overall global function , as measured by caregiver and participant report and st and ardized measures . Cognitive-communication , neuropsychiatric , functional performance , and quality of life evaluations were conducted at baseline and Month 4 , the month after the 2-month active stimulation period . Follow-up evaluations were performed at Months 8 and 12 . The stimulation program consisted of 12 hr of intervention over an 8-week period and involved participant-led discussion s requiring homework , interactive sessions about AD , and discussion s using salient life stories . Additive effects of active stimulation with donepezil were examined in 2 ways : ( 1 ) comparing mean group performance over time and ( 2 ) evaluating change scores from baseline . A Group x Time interaction was found for the donepezil-plus-stimulation group in the emotional symptoms of apathy and irritability as compared with the donepezil-only group . Evaluation of change scores from baseline to 12 months revealed a positive effect for the donepezil-plus-stimulation group on discourse and functional abilities with a trend on apathy , irritability , and patient-reported quality of life . In sum , the research revealed benefits to the donepezil-plus-stimulation group in the areas of discourse abilities , functional abilities , emotional symptoms , and overall global performance . This study adds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors , indicating a need to advance research in the area of cognitive treatments . The fact that AD is a progressive brain disease should not preclude ameliorative treatment The Advanced Cognitive Training for Independent and Vital Elderly ( ACTIVE ) trial is a r and omized , controlled , single-masked trial design ed to determine whether cognitive training interventions ( memory , reasoning , and speed of information processing ) , which have previously been found to be successful at improving mental abilities under laboratory or small-scale field conditions , can affect cognitively based measures of daily functioning . Enrollment began during 1998 ; 2-year follow-up will be completed by January 2002 . Primary outcomes focus on measures of cognitively dem and ing everyday functioning , including financial management , food preparation , medication use , and driving . Secondary outcomes include health-related quality of life , mobility , and health-service utilization . Trial participants ( n = 2832 ) are aged 65 and over , and at entry into the trial , did not have significant cognitive , physical , or functional decline . Because of its size and the carefully developed rigor , ACTIVE may serve as a guide for future behavioral medicine trials of this nature To evaluate nonpharmacologic interventions , caregivers ( 65 women , 38 men ) and their dementia-diagnosed spouses ( patients ) were r and omized to one of four treatment programs ( cognitive stimulation , dyadic counseling , dual supportive seminar , and early-stage day care ) or to a wait-list control group . Assessment s occurred initially and at postintervention ( 3 months ) . Patients were evaluated on memory , verbal fluency , and problem-solving ability , and caregivers were assessed on marital interaction , emotional status , and physical health , along with stress , coping , and social support . Caregivers also completed a program evaluation . Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes , and caregivers decreased in depressive symptoms . Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies , respectively . Although qualitatively derived benefits differed across groups , similarities in program content reduced the potential for quantitative differentiation among the groups The efficacy of a memory-training program to improve word-list recall and recognition was evaluated in 34 patients with probable Alzheimer 's disease ( AD ) . The patients , who were all taking donepezil throughout the 6-week intervention , were r and omly assigned to a cognitive intervention group or a control group . The Control group received didactic presentations but no formal memory training . Patients were assessed on neuropsychological tests before the 6-week training program , immediately after the training , and 8 weeks after completion of the training . Caregivers , who were blind to group assignment , completed activities of daily living ( ADLs ) and everyday memory question naires at all three timepoints . No significant main effects of group ( training vs. control ) or time were observed on any outcome measures , nor were any significant interactions found . In terms of " process " measures during the 6-week training program , the patients demonstrated modest improvement on recall and recognition of test material presented during the training sessions . These results suggest that although modest gains in learning and memory may be evident in AD patients who are taught specific strategies , the benefits do not generalize to other measures of neuropsychological functioning after a brief intervention A study was performed on patients with Alzheimer ’s disease ( AD ) in order to evaluate the efficacy of a combined treatment ( donepezil plus cognitive training ) in both cognitive processes and affective states . Eighty-six subjects , 25 men and 61 women , with an average age of 75.58 years , were studied . Almost all the subjects had a basic educational level . Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music ; the sessions took place on Monday to Friday and lasted three quarters of an hour . The study lasted 12 months . Subjects underwent test-retest with the following tests : Mini-Mental State Examination ( MMSE ) , the cognitive subscale of the Alzheimer ’s Disease Assessment Scale ( ADAS-cog ) ; the Geriatric Depression Scale ( GDS ) and the overall deterioration scale ( FAST ) . The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training . These subjects ’ MMSE score decreased by 3.24 on average . The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not Awareness of difficulties may have an important impact on functioning and response to intervention in early-stage Alzheimer ’s disease ( AD ) . Clinical reports and retrospective studies suggest an association , but this has not previously been tested in a prospect i ve study . Using a new measure of awareness , the Memory Awareness Rating Scale ( MARS ) , which was design ed to take account of method ological limitations identified in a review of previous studies , the present study explored the relationship between awareness of difficulties and outcome of a cognitive rehabilitation ( CR ) intervention in 12 participants with a diagnosis of early-stage Alzheimer ’s disease . The relationship between awareness and mood , behaviour and executive function was also assessed . The results provide the first demonstration in a prospect i ve study that higher levels of awareness are related to better CR outcomes . Awareness was associated with depression and reported behaviour problems , but not with performance on tests of executive function . These results suggest that variations in level of awareness in early-stage AD are influenced by psychological factors , and that explanatory models need to take these factors into account . Awareness of difficulties may serve as a useful predictor of the likely effectiveness of CR , and this may assist clinicians in selecting appropriate interventions for individuals with early-stage AD A cognitive remediation intervention was tested for its effect on functional outcomes of older care recipients with the diagnosis of dementia of the Alzbeimer 's type . The 78 community-dwelling care recipients were assessed on cognitive and behavioral functioning and r and omly assigned to one of three conditions . Care recipients were expected to benefit most from active cognitive stimulation training as compared to placebo ( passive ) activity or wait-list control conditions . Following each weekly instruction session , the intervention was executed in the home by the family caregiver . Care recipients in the experimental group improved in cognitive and behavioral performance with treatment , but returned to former level of functioning by the 9th month . In contrast , the control group declined , while the placebo group remained static on these variables . These findings support the viability of remediation interventions in dementia despite the trajectory of cognitive decline Accurate clinical staging of dementia in older subjects has not previously been achieved despite the use of such methods as psychometric testing , behavioural rating , and various combinations of simpler psychometric and behavioural evaluations . The Clinical Dementia Rating ( CRD ) , a global rating device , was developed for a prospect i ve study of mild senile dementia -- Alzheimer type ( SDAT ) . Reliability , validity , and correlational data are discussed . The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function , from healthy to severely impaired OBJECTIVE To describe the theory , elements and practice of a successful caregiver training programme ; and report the 8-year outcome . DESIGN Prospect i ve , r and omized control trial and longitudinal follow-up over approximately 8 years . SETTING Psychiatry unit , general teaching hospital , Sydney , Australia . PARTICIPANTS 96 persons less than 80 years old with mild to moderate dementia and their cohabiting caregivers . INTERVENTIONS All patients received a 10-day structured memory retraining and activity programme . Caregivers in the immediate and wait-list caregiver training groups received a structured , residential , intensive 10-day training programme , boosted by follow-ups and telephone conferences over 12 months . Those in the wait-list group entered the programme after waiting 6 months . The third group of caregivers received 10 days ' respite ( while patients underwent their memory retraining programme ) and 12 months booster sessions as for the other groups . MAIN OUTCOME MEASURES Nursing home admission ; time until patient death . MAIN RESULTS 64 % of patients whose caregivers were in the immediate training group , 53 % of wait-list group patients and 70 % of memory retraining patients had died . Nursing home admission had occurred in 79 % of the immediate training , 83 % of the delayed and 90 % of the memory retraining group . Eight-year survival analysis indicated that patients whose caregivers received training stayed at home significantly longer ( p = 0.037 ) and tended to live longer ( p = 0.08 ) . CONCLUSIONS Caregiver training programmes demonstrably can delay institutionalization of people with dementia Forty patients with probable Alzheimer 's disease ( AD ) were selected from a pool of 80 patients and assigned to 4 groups . Each received either social support , cognitive training only , or cognitive training in combination with pyritinol or phosphatidylserine . Treatment duration was 6 months . Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography ( PET ) and 2[18F]-fluoro-2-deoxy-D-glucose ( FDG ) . Before treatment , the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task . They did not differ in scores of a neuropsychological test battery . After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions , and an improvement in cognitive functioning compared to the other groups . The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone Objectives : Our purpose was to evaluate the adequacy of a stress adaptation framework for guiding intervention research on caregivers and patients coping with Alzheimer ’s disease , and to test the effect of a cognitive stimulation intervention as an interactive outcome . Methods : Using a repeated measures design , 87 caregiverpatient dyads were r and omized to one of three conditions : active cognitive stimulation , passive stimulation , or control . Assessment s occurred at preintervention , postintervention ( 3 months ) , and 9 months . Results : The LISREL model was entirely satisfactory by the chi-square goodness-of-fit criteria . However , the coefficients associated with the paths between the mediating concepts and the dyadic interaction differed significantly at 3 months and 9 months . The intervention group caregivers were shown to be more satisfied with their interaction with the impaired member . Discussion : The improvement in caregiver satisfactionwas attributed to an attenuation of the behavioral stressor effects through increased use of a problem-focused coping strategy , namely , positive re appraisal of the stressful situation |
13,066 | 26,159,942 | Our findings suggest that , in patients with the first CHD , work stress is associated with an increased relative risk of recurrent CHD events by 65 % . | Though much evidence indicates that work stress increases the risk of incident of coronary heart disease ( CHD ) , little is known about the role of work stress in the development of recurrent CHD events .
The objective of this study was to review and synthesize the existing epidemiological evidence on whether work stress increases the risk of recurrent CHD events in patients with the first CHD . | Aims Cortisol is associated with increased cardiovascular morbidity and mortality in patients with chronic heart failure and in the general population . The negative predictive effect of cortisol on survival in non-diabetic patients who have suffered an acute myocardial infa rct ion ( AMI ) has been shown . We aim ed to determine the prognostic significance of cortisol in a general group of AMI patients , as this is not well known . Methods Plasma cortisol levels were measured in 955 consecutive patients admitted with AMI . We prospect ively evaluated the relationship between cortisol and major adverse cardiovascular event ( MACE ) , which was a composite of all-cause mortality , and combination all-cause mortality and re-hospitalization for heart failure , in post-AMI patients . Results During the 2-year follow-up , MACE occurred in 261 patients ( 27.3 % ) . Patients with MACE had significantly higher median levels of cortisol than those without ( 609.4 versus 549.4 pmol/ml , P = 0.0073 ) . Log cortisol was independently predictive of MACE after adjusting for covariates with hazard ratio ( 95 % confidence interval ) of 1.55 ( 1.05–2.27 ) , P = 0.027 . Patients in the highest quartile of cortisol had significantly more risk of MACE compared with those in the lowest quartile , with an adjusted hazard ratio ( 95 % confidence interval ) of 1.91(1.16–3.15 ) , P = 0.0120 . Kaplan – Meier survival estimates for MACE were lower in patients with plasma cortisol levels in the highest quartile compared with those in the first three quartiles ( Log rank test & khgr;2 for survival = 10.41 , P = 0.0013 ) . Conclusion This study has shown the prognostic significance of cortisol in 955 post-AMI patients from a single centre AIM Interleukin (IL)-17 pathway is being clinical ly targeted in immune-mediated diseases , most of which are associated with a significant cardiovascular risk . We investigated the relationship between serum levels of IL-17 and the risk of cardiovascular events in patients with acute myocardial infa rct ion . METHODS AND RESULTS We used data from 981 patients enrolled in the prospect i ve , multicentre French registry of Acute ST elevation , or non-ST-elevation Myocardial Infa rct ion ( Fast-MI , NCT00673036 ) . Serum levels of IL-17 were associated with the risk of all-cause death and recurrent MI at 2 years , with levels of IL-17 below the median indicative of a worse outcome . The impact of IL-17 remained significant after adjustment for known cardiovascular risk factors , C-reactive protein , and treatments including statins : hazard ratio ( HR ) = 1.40 ( 1.03 - 1.91 ) ; P = 0.03 . IL-17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial vascular cell adhesion molecule ( VCAM-1 ) expression . Patients with low ( below the median ) IL-17 levels and high ( above the median ) soluble VCAM-1 ( sVCAM-1 ) levels were at particularly increased risk of death and MI : adjusted HR = 2.22 ( 1.32 - 3.75 ) compared with the high IL-17/low sVCAM-1 group ( P = 0.002 ) . CONCLUSIONS Low serum levels of IL-17 are associated with a higher risk of major cardiovascular events in Caucasian patients with acute MI . Our results raise possible concern about the use of inhibitors of the IL-17 pathway in clinical setting s associated with a high cardiovascular risk . CLINICAL TRIALS REGISTRATION NCT00673036 BACKGROUND Justice is a fundamental value in human societies , but its effect on health is poorly described . We examined justice at work as a predictor of coronary heart disease ( CHD ) . METHODS Prospect i ve occupational cohort study of 6442 male British civil servants aged 35 to 55 years without prevalent CHD at baseline in phase 1 ( 1985 - 1988 ) . Baseline screening included measurements of conventional risk factors . Perceived justice at work and other work-related psychosocial factors were determined by means of question naire at phases 1 and 2 ( 1989 - 1990 ) . Follow-up for CHD death , first nonfatal myocardial infa rct ion , or definite angina occurring from phase 2 through 1999 was based on medical records ( mean follow-up , 8.7 years ) . RESULTS Cox proportional hazard models adjusted for age and employment grade showed that employees who experienced a high level of justice at work had a lower risk of incident CHD than employees with a low or an intermediate level of justice ( hazard ratio , 0.65 ; 95 % confidence interval , 0.47 - 0.89 ) . The hazard ratio did not material ly change after additional adjustment for baseline cholesterol concentration , body mass index , hypertension , smoking , alcohol consumption , and physical activity . Although other psychosocial models such as job strain and effort-reward imbalance predicted CHD in these data , the level of justice remained an independent predictor of incident CHD after adjustment for these factors . CONCLUSION Justice at work may have benefits for heart health among employees CONTEXT There is evidence that job strain increases the risk of a first coronary heart disease ( CHD ) event . However , little is known about its association with the risk of recurrent CHD events after a first myocardial infa rct ion ( MI ) . OBJECTIVE To determine whether job strain increases the risk of recurrent CHD events . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 972 men and women aged 35 to 59 years who returned to work after a first MI and were then followed up between February 10 , 1996 , and June 22 , 2005 . Patients were interviewed at baseline ( on average , 6 weeks after their return to work ) , then after 2 and 6 years subsequently . Job strain , a combination of high psychological dem and s and low decision latitude , was evaluated in 4 quadrants : high strain ( high dem and s and low latitude ) , active ( high dem and s and high latitude ) , passive ( low dem and s and low latitude ) , and low strain . A chronic job strain variable was constructed based on the first 2 interviews , and patients were divided into those exposed to high strain at both interviews and those unexposed to high strain at 1 or both interviews . The survival analyses were presented separately for 2 periods : before 2.2 years and at 2.2 years and beyond . MAIN OUTCOME MEASURE The outcome was a composite of fatal CHD , nonfatal MI , and unstable angina . RESULTS The outcome was documented in 206 patients . In the unadjusted analysis , chronic job strain was associated with recurrent CHD in the second period after 2.2 years of follow-up ( hazard ratio [ HR ] , 2.20 ; 95 % CI , 1.32 - 3.66 ; respective event rates for patients exposed and unexposed to chronic job strain , 6.18 and 2.81 per 100 person-years ) . Chronic job strain remained an independent predictor of recurrent CHD in a multivariate model adjusted for 26 potentially confounding factors ( HR , 2.00 ; 95 % CI , 1.08 - 3.72 ) . CONCLUSION Chronic job strain after a first MI was associated with an increased risk of recurrent CHD Objective : Evidence regarding the status of job strain as a risk factor for coronary heart disease ( CHD ) is mixed , including both results supporting the risk status and null findings . However , previous studies have typically assessed job strain at one point in time only . We examined whether the failure of such measurement to reflect long-term job strain could contribute to false null findings . Methods : Job strain and its components , as stress indicators , were assessed twice ( 3-year time lag ) for 5043 men and 2210 women who were free of apparent CHD at baseline . Incident CHD after the stress measurement comprised CHD death , a first nonfatal myocardial infa rct ion , or definite angina ( mean follow-up , 10.4 years ) . The data analysis was based on Cox proportional-hazard models adjusted for age , sex , and employment grade and corrected using regression dilution ratios calculated from short-term repeat data in a r and om sub sample . Results : In the total cohort , incidence of new CHD was higher for higher levels of job strain and dem and s. For these stress indicators , the corrected excess CHD risk was 30 % and 29 % higher than the corresponding uncorrected estimates , whereas the corresponding increase for job control was only 13 % . Effects of job strain and work dem and s , but not job control , were stronger for a subgroup , with consistent exposure measurements over time than for the total cohort . Conclusion : This evidence suggests that use of single-time exposure measures may underestimate the status of long-term job strain as a CHD risk factor . CHD = coronary heart disease ; ECG = electrocardiogram BACKGROUND Return to work is an important indicator of recovery after acute cardiac events . This study aim ed to determine rates of work resumption and identify predictors of non-return to work and delayed resumption of work . METHODS 401 currently employed patients consecutively admitted after acute coronary syndrome or to undergo coronary artery bypass graft surgery were recruited . Patient characteristics , perceptions and occupational outcomes were investigated via interviews and self-report question naires . RESULTS Twenty-three patients were lost to follow-up . Of the 378 completers , 343 ( 90.7 % ) patients resumed work , while 35 ( 9.3 % ) did not . By four months , 309 ( 91.1 % ) patients had returned to work . At 12 months , 302 ( 79.9 % ) of the 378 patients were employed , 32 ( 8.5 % ) unemployed and 20 ( 5.3 % ) retired . The employment status of 24 ( 6.3 % ) patients was unknown . Non-return to work was significantly more likely if patients were not intending to return to work or were uncertain , had a negative perception of health , had a comorbidity other than diabetes and reported financial stress . Significant predictors of delayed return to work were cardiac rehabilitation attendance , longer hospital stay , past angina , having a manual job , physically active work , job dissatisfaction , no confidante and depression . CONCLUSIONS Patients at risk of poor occupational outcomes can be identified early . Strategies to improve vocational rehabilitation require further investigation OBJECTIVE The usual assessment of coronary angiograms by st and ard visual analysis was compared with the assessment by quantitative computer analysis to provide evidence of the consequences of measurement errors attributable to visual assessment in the evaluation of coronary stenoses in clinical trials . METHODS Angiograms obtained in 151 patients enrolled in a double-blind r and omized controlled trial assessing the effect of fish oil supplementation on restenosis were evaluated by both visual and quantitative methods . Proportions of patients with unsuccessful angioplasty and proportions of patients with restenosis according to visual and quantitative methods were compared by st and ard statistical methods . RESULTS Of the 151 patients who were considered successfully dilated by visual interpretation , 32 were not considered successfully dilated by quantitative analysis . With quantitative computer analysis , evaluation of restenosis on the 119 successfully dilated patients documented a protective effect of fish oil against restenosis ( 30.5 % of treated patients versus 48.3 % of control patients , P < 0.05 ) . Visual evaluation of restenosis six months after angioplasty misclassified 10 % of patients in each treatment group and failed to demonstrate a protective effect of fish oil against restenosis . CONCLUSIONS Misclassification by visual assessment of both success and restenosis in the present trial led to underestimating the true effect of fish oil in the prevention of restenosis . Accurate and objective methods , such as quantitative computer analysis , are thus required for evaluating the effects of interventions on coronary arteries Using comparative data from five countries , this study investigates the psychometric properties of the effort-reward imbalance ( ERI ) at work model . In this model , chronic work-related stress is identified as non-reciprocity or imbalance between high efforts spent and low rewards received . Health-adverse effects of this imbalance were documented in several prospect i ve and cross-sectional investigations . The internal consistency , discriminant validity and factorial structure of ' effort ' , ' reward ' , and ' overcommitment ' scales are evaluated , using confirmatory factor analysis . Moreover , content ( or external ) validity is explored with respect to a measure of self-reported health . Data for the analysis is derived from epidemiologic studies conducted in five European countries : the Somstress Study ( Belgium ; n = 3796 ) , the GAZEL-Cohort Study ( France ; n = 10,174 ) , the WOLF-Norrl and Study ( Sweden ; n = 960 ) , the Whitehall II Study ( UK ; n = 3697 ) and the Public Transport Employees Study ( Germany ; n = 316 ) . Internal consistency of the scales was satisfactory in all sample s , and the factorial structure of the scales was consistently confirmed ( all goodness of fit measures were > 0.92 ) . Moreover , in 12 of 14 analyses , significantly elevated odds ratios of poor health were observed in employees scoring high on the ERI scales . In conclusion , a psychometrically well-justified measure of work-related stress ( ERI ) grounded in sociological theory is available for comparative socioepidemiologic investigations . In the light of the importance of work for adult health such investigations are crucial in advanced societies within and beyond Europe Objective : Prospect i ve studies have shown that effort-reward imbalance ( ERI ) at work is associated with the incidence of a first coronary heart disease ( CHD ) event . However , it is unknown whether ERI at work increases the risk of recurrent CHD events . The objective of this study was to determine whether ERI at work and its components ( effort and reward ) increase the risk of recurrent CHD in post-myocardial infa rct ion ( post-MI ) workers . Methods : We carried out a prospect i ve cohort study of 669 men and 69 women who returned to work after a first MI . ERI at work was assessed by telephone interview using vali date d scales of reward and psychological dem and s. The outcome was a composite of fatal CHD , nonfatal MI , and unstable angina . CHD risk factors were documented in medical files and by interview . The participants were followed up for a mean period of 4.0 years ( 1998 - 2005 ) . Results : During the follow-up , 96 CHD events were documented . High ERI and low reward were associated with recurrent CHD ( respective adjusted hazard ratios [ HRs ] = 1.75 , 95 % confidence interval [ CI ] = 0.99 - 3.08 , and HR = 1.77 , 95 % CI = 1.16 - 2.71 ) . There was a gender interaction showing stronger effects among women ( respective adjusted HRs for high ERI and low reward : HR = 3.95 , 95 % CI = 0.93 - 16.79 , and HR = 9.53 , 95 % CI = 1.15 - 78.68 ) . Conclusions : Post-MI workers holding jobs that involved ERI or low reward had increased risk of recurrent CHD . BMI = body mass index ; CHD = coronary heart disease ; CI = confidence interval ; ERI = effort-reward imbalance ; HR = hazard ratio ; MI = myocardial infa rct ion |
13,067 | 23,552,825 | It appears that resistance training alone or in combination with impact-loading activities are most osteogenic for this population , whereas the walking trials had limited effect on BMD . | Although trials have shown that exercise has positive effects on bone mineral density ( BMD ) , the majority of exercise trials have been conducted in older women .
The aim of this study was to systematic ally review trials examining the effect of weight-bearing and resistance-based exercise modalities on the BMD of hip and lumbar spine of middle-aged and older men . | Abstract : We performed a prospect i ve study to evaluate the normal changes in bone mineral density ( BMD ) in the forearm , hip , spine and total body , and to study the agreement between changes in BMD estimated from cross-sectional data and the actual longitudinal changes . Six hundred and twenty subjects ( 398 women , 222 men ; age 20–89 years ) without diseases or medication known to affect bone metabolism undertook baseline evaluations , and 525 ( 336 women , 189 men ) completed the study . BMD was measured twice 2 years apart by dual-energy X-ray absorptiometry . From cross-sectional evaluations the only premenopausal bone loss ( < 0.003 g/cm2/year ) was found in the hip . In women after menopause and in men an age-related bone loss ( 0.002–0.006 g/cm2/year ) was found at all sites . The data from the longitudinal evaluation showed a small bone loss in women before menopause at the hip and lumbar spine ( < 0.4%/year ( < 0.004 g/cm2/year ) ) ; this bone loss nearly tripled in the early postmenopausal years ( < 10 years since menopause ) , and thereafter decreased to the premenopausal rate for the hip , and to zero for the lumbar spine . The most pronounced bone loss after menopause occurred in the forearm ( 1.2 % /year ( 0.006 g/cm2/year ) ) , and it remained constant throughout life . In men there was a small longitudinal bone loss in the hip throughout life , and a small bone loss in the distal forearm after the age of 50 years . In all groups , except for the early postmenopausal women , we found a small increase in total body BMD with age . When comparing the changes in BMD estimated from cross-sectional data with the longitudinal changes , only the hip and forearm generally displayed agreement , whereas the changes in the total body and spine generally were incongruous . In conclusion , the hip and forearm appear to be the sites with the best agreement between the cross-sectional estimated and the longitudinal age-related changes in BMD Summary Our r and omized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for > 1 year . Introduction Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors ( BCS ) . We investigated whether impact + resistance training could improve bone mineral density ( BMD ) , reduce bone turnover , build muscle , and decrease fat mass in BCS with premature menopause . Methods We conducted a r and omized controlled trial in 71 BCS ( mean age , 46.5 years ) within 5 years of treatment-related menopause . Women were r and omly assigned to one of two groups : ( 1 ) impact + resistance training ( prevent osteoporosis with impact + resistance ( POWIR ) ) or ( 2 ) exercise placebo ( FLEX ) 3 × /week for 1 year . Outcomes were hip and spine BMD ( in grams per square centimeter ) and body composition ( percent body fat ( % BF ) and lean and fat mass ( in kilograms ) ) by DXA and bone turnover markers ( serum osteocalcin ( in nanograms per milliliter ) and urinary deoxypryrodinoline ( in nanomoles per milliliter ) . Results There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample . In analyses restricted to BCS who were menopausal for ≥1 year , POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX ( femoral neck — POWIR , 0.004 ± 0.093 g/cm2 vs. FLEX , −0.010 ± 0.089 g/cm2 ; p < 0.01 ; spine — POWIR , −0.003 ± 0.114 g/cm2 vs. FLEX , −0.020 ± 0.110 g/cm2 ; p = 0.03 ) . POWIR prevented increases in % BF ( POWIR , 0.01 % vs. FLEX , 1.3 % ; p < 0.04 ) . Women with attendance to POWIR at ≥64 % had better improvements in % BF than women attending less often ( p < 0.03 ) . Conclusion Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS INTRODUCTION Exercise can increase bone strength , but to be effective in reducing fracture risk , exercise must be feasible enough to be adopted into daily life and influence potentially vulnerable skeletal sites such as the superolateral cortex of the femoral neck , where thinning is associated with increased fracture risk . Brief , high-impact exercise increases femoral neck bone density but the optimal frequency of such exercise and the location of bone accrual is unknown . This study thus examined ( 1 ) the effectiveness of different weekly frequencies of exercise on femoral neck BMD and ( 2 ) whether BMD change differed between hip sites using a high-impact , unilateral intervention . METHODS Healthy premenopausal women were r and omly assigned to exercise 0 , 2 , 4 , or 7 days/week for 6 months . The exercise intervention incorporated 50 multidirectional hops on one r and omly selected leg . BMD was measured by DXA at baseline and after 6 months of exercise . Changes in the exercise leg were compared between groups using ANCOVA , with change in the control leg and baseline BMD as covariates . RM-MANOVA was conducted to determine whether bone changes from exercise differed between hip sites . RESULTS 61 women ( age 33.6+/-11.1 years ) completed the intervention . Compliance amongst exercisers was 86.7+/-10.6 % . Peak ground reaction forces during exercise increased from 2.5 to 2.8 times body weight . The change in femoral neck BMD in the exercise limb ( adjusted for change in the control limb and baseline BMD ) differed between groups ( p=0.015 ) , being -0.3 % ( -1.2 to 0.6 ) , 0.0 % ( -1.0 to 1.0 ) , 0.9 % ( -0.1 to 2.0 ) and 1.8 % ( 0.8 to 2.8 ) in those exercising 0 , 2 , 4 and 7 days per week , respectively . When BMD changes at upper neck , lower neck and trochanter were compared using RM-MANOVA , a significant exercise effect was observed ( p=0.048 ) , but this did not differ significantly between sites ( p=0.439 ) despite greatest mean increases at the upper femoral neck . CONCLUSIONS Brief , daily hopping exercises increased femoral neck BMD in premenopausal women but less frequent exercise was not effective . Brief high-impact exercise may have a role in reducing hip fragility , but may need to be performed frequently for optimal response PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P < 0.001 ) and muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P < 0.001 ) increased significantly after training . Significant improvement ( P < 0.05 ) occurred in the 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P < 0.05 ) by 15.7 % at the quadriceps site . Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects This work analyses the short-term physiological and neurophysiological effects of a brisk walking programme in ageing , healthy , active men . Twenty-one men 63 to 72 years of age were recruited and separated into 2 groups . One group performed a walking programme ( WP ) ( n = 11 ) and another served as control ( C ) group ( n = 10 ) . The walking programme lasted for twelve weeks and included five sessions per week . Several parameters were assessed before and after the programme for the WP group . The same tests were performed ( separated by twelve weeks ) in group C. During each assessment , the subjects were put through static and dynamic balance tests , spatio-temporal gait analysis , body composition measurements and determination of aerobic capacity and bone mineral density . The statistic analysis showed a significant improvement in dynamic balance performance , especially in lateral sway when the subjects kept their eyes open , an increase of VO(2 ) max and loss of fat mass in the WP group . However , no alterations appeared in spatiotemporal gait characteristics , static balance performance , lean mass or bone mineral density ( total body and hip ) . According to these results , this walking programme may have positive effects on preventing ageing subjects from falling BACKGROUND The beneficial role of exercise in improving bone mineral density , muscle strength and balance , has been documented predominantly in younger population s. These findings may not apply to elderly population s with limited ability to perform exercises of high intensity . OBJECTIVE To examine the effects of Tai Chi ( TC ) and resistance exercise ( RTE ) on bone mineral density ( BMD ) , muscle strength , balance and flexibility in community living elderly people . DESIGN R and omised controlled trial , using blocked r and omization with stratification by sex . SETTING A community in the New Territories Region of Hong Kong , China . SUBJECTS One hundred eighty subjects ( 90 men , 90 women ) aged 65 - 74 , were recruited through advertisements in community centres . METHODS Subjects were assigned to participate in TC , RTE three times a week , or no intervention ( C ) for 12 months . Measurements were carried out at baseline , 6 and 12 months . Analyses of covariance ( ANCOVA ) adjusted for age , and baseline values of variables that were significantly different between groups : i.e. smoking and flexibility for men ; quadriceps strength for women . RESULTS Compliance was high ( TC 81 % , RTE 76 % ) . In women , both TC and RTE groups had less BMD loss at total hip compared with controls . No effect was observed in men . No difference in either balance , flexibility or the number of falls was observed between either intervention or controls after 12 months . CONCLUSION The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes Summary A 1-year r and omized controlled trial of resistance training compared with a control group was undertaken in 143 men aged 55–80 years . Although hip bone mineral density , lean body mass , and function increased in both groups , lean body mass and function but not bone density increased more in the resistance group . Introduction Previous studies have demonstrated a positive effect of resistance training on bone mineral density ( BMD ) in postmenopausal women , but the effect in men is unclear . The aim was to examine the effect of a 1-year resistance training program on bone and lean body mass in 143 men aged 55–80 years , r and omized to either resistance training or active control . Methods Resistance exercises were selected to provide loading at the hips . Measurements were taken at 0 , 6 , and 12 months for BMD ( whole body , hip , and spine ) , lean body mass , strength , and functional fitness . Results The intervention showed a significant increase in total hip BMD for both groups at 12 months ( active control , 1,014–1,050 mg/cm2 ; resistance , 1,045–1,054 mg/cm2 , p < 0.05 ) with no increased effect of resistance training compared to active control . However , compared to the active control group , the resistance group increased their lean body mass ( active control , 0.1 ± 2.1 % ; resistance , 1.5 ± 2.7 % , p < 0.05 ) , fitness ( active control , 4.6 ± 11.1 % ; resistance , 13.0 ± 13.4 % , p < 0.05 ) , and lower limb muscle strength ( active control , 14.3 ± 16.8 % ; resistance , 39.4 ± 30.87 % , p < 0.05 ) . Conclusions In contrast to previous findings in older women , in older men , a resistance training program does not increase hip bone mass more than walking 30 min three times a week Summary We examined the independent and combined effects of a multi-component exercise program and calcium – vitamin-D3-fortified milk on bone mineral density ( BMD ) in older men . Exercise result ed in a 1.8 % net gain in femoral neck BMD , but additional calcium – vitamin D3 did not enhance the response in this group of older well-nourished men . Introduction This 12-month r and omised controlled trial assessed whether calcium – vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men . Methods Men ( n = 180 ) aged 50–79 years were r and omised into : ( 1 ) exercise + fortified milk ; ( 2 ) exercise ; ( 3 ) fortified milk ; or ( 4 ) controls . Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise . Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3 . Femoral neck ( FN ) , total hip , lumbar spine and trochanter BMD and body composition ( DXA ) , muscle strength 25-hydroxyvitamin D and parathyroid hormone ( PTH ) were assessed . Results There were no exercise-by-fortified milk interactions at any skeletal site . Exercise result ed in a 1.8 % net gain in FN BMD relative to no-exercise ( p < 0.001 ) ; lean mass ( 0.6 kg , p < 0.05 ) and muscle strength ( 20–52 % , p < 0.001 ) also increased in response to exercise . For lumbar spine BMD , there was a net 1.4–1.5 % increase in all treatment groups relative to controls ( all p < 0.01 ) . There were no main effects of fortified milk at any skeletal site . Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men , but additional calcium – vitamin D3 did not enhance the osteogenic response 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 The effects of a 16-wk strength-training program on bone mineral density ( BMD ) was assessed by dual-energy X-ray absorptiometry in 21 men [ age 61 + /- 1 ( SE ) yr ] . Sixteen men ( age 59 + /- 2 yr ) served as control subjects . To investigate the possible hormonal relationships underlying the effects on BMD , serum concentrations of growth hormone , insulin-like growth factor I , and testosterone were determined before and after training . In addition , osteocalcin and skeletal alkaline phosphatase ( markers of bone formation ) and tartrate-resistant acid phosphatase ( a marker of bone resorption ) were measured before and after training to assess bone turnover . The training program result ed in a 2.8 + /- 0.6 % increase in femoral neck BMD ( 1.004 + /- 0.037 vs. 1.031 + /- 0.037 g/cm2 ; P < 0.001 ) . However , there were no significant changes in total body , anterioposterior spine , lateral spine , Ward 's triangle , or greater trochanter BMD . Moreover , there were no significant changes in growth hormone , insulin-like growth factor I , testosterone , osteocalcin , or skeletal alkaline phosphatase . There were no changes in the control group . Thus , strength training can increase femoral neck BMD , and this effect does not appear to be accompanied by changes in anabolic hormones or markers of bone formation and resorption Abstract : The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density ( BMD ) in middle-aged men . A population based sample of 140 men ( 53–62 years ) was r and omly assigned into the exercise and reference groups . BMD and apparent volumetric BMD ( BMDvol ) of the proximal femur and lumbar spine ( dual-energy X-ray absorptiometry , DXA ) and anthropomorphic measurements were performed at the r and omization and 2 and up to 4 years later . The participation rate was 97 % and 94 % at the second and third BMD measurements , respectively . As another indication of excellent adherence and compliance , the cardiorespiratory fitness ( aerobic threshold ) increased by 13 % in the exercise group . The 2 % decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness . Regardless of the group , there was no association between the increase in aerobic threshold and change in BMD . In the entire group , age-related bone loss was seen in the femoral neck BMD and BMDvol ( p<0.01 ) . BMD and BMDvol values increased with age in L2–L4 ( p<0.004 ) . An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake ( p = 0.003 ) . Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck ( p = 0.040 ) . A decrease in body height associated with decreased total femoral BMD ( r= 0.19 , p = 0.04 ) and the change in body height was a predictor of bone loss in the femoral neck ( β= 0.201 ) . Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD . On the other h and , possible structural alterations , which are also essential for the mechanical strength of bone , can not be detected by the DXA measurements used in this study . The increase seen in lumbar BMD reflects age-related changes in the spine , thus making it an unreliable site for BMD follow-up in men Summary The ability of combined step aerobic- and circuit-training to prevent bone loss after breast cancer treatments was related to skeletal site and patients ’ menopausal status . Among premenopausal breast cancer survivors , a 12-month exercise intervention completely prevented bone loss at the femoral neck , whereas no exercise effect was seen at lumbar spine or at neither site in postmenopausal women . Introduction The primary objective of this r and omised clinical trial was to determine the preventive effect of supervised weight-bearing jumping exercises and circuit training on bone loss among breast cancer patients . Methods Of 573 breast cancer survivors aged 35–68 years r and omly allocated into exercise or control group after adjuvant treatments , 498 ( 87 % ) were included in the final analysis . The 12-month exercise intervention comprised weekly supervised step aerobic- and circuit-exercises and similar home training . Bone mineral density ( BMD ) at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry . Physical performance was assessed by 2-km walking and figure-8 running tests , and the amount of physical activity was estimated in metabolic equivalent-hours/week . Results In premenopausal women , bone loss at the femoral neck was prevented by exercise , the mean BMD changes being −0.2 % among the trainees vs. −1.4 % among the controls ( p = 0.01 ) . Lumbar bone loss could not be prevented ( −1.9 % vs. −2.2 % ) . In postmenopausal women , no significant exercise-effect on BMD was found either at the lumbar spine ( −1.6 % vs. −2.1 % ) or femoral neck ( −1.1 % vs. −1.1 % ) . Conclusions This 12-month aerobic jumping and circuit training intervention completely prevented femoral neck bone loss in premenopausal breast cancer patients , whereas no effect on BMD was seen in postmenopausal women The effects of a vertical jumping exercise regime on bone mineral density ( BMD ) have been assessed using r and omized controlled trials in both pre- and postmenopausal women , the latter stratified for hormone replacement therapy ( HRT ) . Women were screened for contraindications or medication likely to influence bone . The premenopausal women were at least 12 months postpartum and not lactating ; the postmenopausal women had been stable on , or off , HRT for the previous 12 months and throughout the study . BMD was measured blind using dual-energy X-ray absorptiometry at the spine ( L2-L4 ) and the proximal femur . The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm , which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women . In the premenopausal women , the exercise result ed in a significant increase of 2.8 % in femoral BMD after 5 months ( p < 0.001 , n = 31 ) . This change was significantly greater ( p < 0.05 ) than that found in the control group ( n = 26 ) . In the postmenopausal women , there was no significant difference between the exercise and control groups after 12 months ( total n = 123 ) nor after 18 months ( total n = 38 ) . HRT status did not affect this outcome , at least up to 12 months . It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not CONTEXT Exercise and calcium-vitamin D are independently recognized as important strategies to prevent osteoporosis , but their combined effects on bone strength and its determinants remain uncertain . OBJECTIVE To assess whether calcium-vitamin D(3 ) fortified milk could enhance the effects of exercise on bone strength , structure , and mineral density in middle-aged and older men . DESIGN , SETTING , PARTICIPANTS An 18-month factorial design r and omized controlled trial in which 180 men aged 50 - 79 years were r and omized to the following : exercise + fortified milk ; exercise ; fortified milk ; or controls . Exercise consisted of progressive resistance training with weight-bearing impact activities performed 3 d/week . Men assigned to fortified milk consumed 400 ml/d of 1 % fat milk containing 1000 mg/d calcium and 800 IU/d vitamin D(3 ) . MAIN OUTCOME MEASURES Changes in bone mineral density ( BMD ) , bone structure , and strength at the lumbar spine ( LS ) , proximal femur , mid-femur , and mid-tibia measured by dual energy x-ray absorptiometry and /or quantitative computed tomography . RESULTS There were no exercise-by-fortified milk interactions at any skeletal site . Main effect analysis showed that exercise led to a 2.1 % ( 95 % confidence interval , 0.5 - 3.6 ) net gain in femoral neck section modulus , which was associated with an approximately 1.9 % gain in areal BMD and cross-sectional area . Exercise also improved LS trabecular BMD [ net gain 2.2 % ( 95 % confidence interval , 0.2 - 4.1 ) ] , but had no effect on mid-femur or mid-tibia BMD , structure , or strength . There were no main effects of the fortified milk at any skeletal site . CONCLUSION A community-based multi-component exercise program successfully improved LS and femoral neck BMD and strength in healthy older men , but providing additional calcium-vitamin D(3 ) to these replete men did not enhance the osteogenic response OBJECTIVES This was a prospect i ve , r and omized , controlled study design ed to determine the effect of resistance exercise training on bone metabolism in heart transplant recipients . BACKGROUND Osteoporosis frequently complicates heart transplantation . No preventative strategy is generally accepted for glucocorticoid-induced bone loss . METHODS Sixteen male heart transplant recipients were r and omly assigned to a resistance exercise group that trained for 6 months ( mean [ + /- SD ] age 56 + /- 6 years ) or a control group ( mean age 52 + /- 10 years ) that did not perform resistance exercise . Bone mineral density ( BMD ) of the total body , femur neck and lumbar spine ( L2 to L3 ) was measured by dual-energy X-ray absorptiometry before and 2 months after transplantation and after 3 and 6 months of resistance exercise or a control period . The exercise regimen consisted of lumbar extension exercise ( MedX ) performed 1 day/week and variable resistance exercises ( Nautilus ) performed 2 days/week . Each exercise consisted of one set of 10 to 15 repetitions performed to volitional fatigue . RESULTS Pretransplantation baseline values for regional BMD did not differ in the control and training groups . Bone mineral density of the total body , femur neck and lumbar vertebra ( L2 to L3 ) were significantly decreased below baseline at 2 months after transplantation in both the control ( -3.3 + /- 1.3 % , -4.5 + /- 2.8 % , -12.7 + /- 3.2 % , -14.8 + /- 3.1 % , respectively ) . Six months of resistance exercise restored BMD of the whole body , femur neck and lumbar vertebra to within 1 % , 1.9 % and 3.6 % of pretransplantation levels , respectively . Bone mineral density of the control group remained unchanged from the 2-month posttransplantation levels . CONCLUSIONS Within 2 months after heart transplantation , approximately 3 % of whole-body BMD is lost , mostly due to decreases in trabecular bone ( -12 % to -15 % of lumbar vertebra ) . Six months of resistance exercise , consisting of low back exercise that isolates the lumbar spine and a regimen of variable resistance exercises , restores BMD toward pretransplantation levels . Our results suggest that resistance exercise is osteogenic and should be initiated early after heart transplantation |
13,068 | 19,389,745 | Conclusions : Strong recommendations support the use of physical exercise training to improve health-related quality of life and functional exercise capacity . | Purpose : Up date of a clinical practice guideline for the physiotherapy management of patients with chronic obstructive pulmonary disease supporting the clinical decision-making process . | Long-term treatment of chronic bronchitis with chest physiotherapy with or without positive expiratory pressure ( PEP ) by mask was studied in 43 patients r and omly allocated to PEP treatment ( PEP group , 20 patients ) and conventional chest physiotherapy ( control group , 23 patients ) . After instruction , the treatments were self-administered twice daily for 12 months ( 34 patients ) and 5 months ( 9 patients ) . Twice weekly , patients filled in a diary concerning symptoms . The PEP group had significantly less cough and less mucus production . The number of acute exacerbations were calculated from the diaries and were lower in the PEP group compared to the control group , and 85 percent of the patients in the PEP group were free from acute exacerbations versus 48 percent in the control group . The PEP group also used less antibiotics and mucolytics . The PEP group had a small increase in FEV1 of mean 62 ml compared to a small decrease of 43 ml for the control group . Treatment with a simple PEP device can reduce morbidity in patients with chronic bronchitis and may preserve lung function from a more rapid decline BACKGROUND Supplemental oxygen in patients with chronic obstructive pulmonary disease ( COPD ) and exercise hypoxaemia improves exercise capacity and dyspnoea . However , the benefit of oxygen during pulmonary rehabilitation in these patients is still unknown . METHODS Twenty five patients with stable COPD ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 0.76 ( 0.29 ) l and 30.0 (9.89)% predicted , arterial oxygen tension ( Pao 2 ) 8.46 ( 1.22 ) kPa , arterial carbon dioxide tension ( Paco 2 ) 6.32 ( 1.01 ) kPa ) and significant arterial desaturation on exercise ( 82.0 (10.4)% ) were entered onto a pulmonary rehabilitation programme . Patients were r and omised to train whilst breathing oxygen ( OT ) ( n = 13 ) or air ( AT ) ( n = 12 ) , both at 4 l/min . Assessment s included exercise tolerance and associated dyspnoea using the shuttle walk test ( SWT ) and Borg dyspnoea score , health status , mood state , and performance during daily activities . RESULTS The OT group showed a significant reduction in dyspnoea after rehabilitation compared with the AT group ( Borg mean difference –1.46 ( 95 % CI –2.72 to –0.19 ) ) but there were no differences in other outcome measures : SWT difference –23.6 m ( 95 % CI –70.7 to 23.5 ) , Chronic Respiratory Disease Question naire 3.67 ( 95 % CI –7.70 to 15.1 ) , Hospital Anxiety and Depression Scale 1.73 ( 95 % CI –2.32 to 5.78 ) , and London Chest Activity of Daily Living Scale –2.18 ( 95 % CI –7.15 to 2.79 ) . At baseline oxygen significantly improved SWT ( mean difference 27.3 m ( 95 % CI 14.7 to 39.8 ) and dyspnoea ( –0.68 ( 95 % CI –1.05 to –0.31 ) ) compared with placebo air . CONCLUSIONS This study suggests that supplemental oxygen during training does little to enhance exercise tolerance although there is a small benefit in terms of dyspnoea . Patients with severe disabling dyspnoea may find symptomatic relief with supplemental oxygen Limited information is available regarding the physiological responses to different types of exercise training in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was two fold : firstly , to investigate the physiological response to training at 60 % of achieved peak load in patients with severe COPD ; and secondly to study the effects of interval ( I ) versus continuous ( C ) training in these patients . Twenty-one patients with COPD ( mean+/-SD forced expiratory volume in one second : 37+/-15 % of predicted , normoxaemic at rest ) were evaluated at baseline and after 8 weeks ' training . Patients were r and omly allocated to either I or C training . The training was performed on a cycle ergometer , 5 days a week , 30 min daily . The total work load was the same for both training programmes . C training result ed in a significant increase in oxygen consumption ( V'O2 ) ( 17 % , p<0.05 ) and a decrease in minute ventilation (V'E)/V'O2 ( p<0.01 ) and V'E/carbon dioxide production ( V'CO2 ) ( p<0.05 ) at peak exercise capacity , while no changes in these measures were observed after interval training . During submaximal exercise a significant decrease was observed in lactic acid production , being most pronounced in the C-trained group ( -31 % , p<0.01 versus -20 % , p<0.05 ) . Only in the I-trained group did a significant increase in peak work load ( 17 % , p<0.05 ) and a decrease in leg pain ( p<0.05 ) occur . Training did not result in a significant improvement in lung function , but maximal inspiratory mouth pressure increased in both groups by 10 % ( C : p<0.05 ) and 23 % ( I : p<0.01 ) . The present study shows a different physiological response pattern to interval or continuous training in chronic obstruction pulmonary disease , which might be a reflection of specific training effects in either oxidative or glycolytic muscle metabolic pathways . Further work is required to determine the role of the different exercise programmes and the particular category of patients for whom this might be beneficial Pulmonary rehabilitation is beneficial for patients with chronic lung disease . However , long-term maintenance has been difficult to achieve after short-term treatment . We evaluated a telephone-based maintenance program after pulmonary rehabilitation in 172 patients with chronic lung disease recruited from pulmonary rehabilitation graduates . Subjects were r and omly assigned to a 12-month maintenance intervention with weekly telephone contacts and monthly supervised reinforcement sessions ( n = 87 ) or st and ard care ( n = 85 ) and followed for 24 months . Except for a slight imbalance between sexes , experimental and control groups were equivalent at baseline and showed similar improvements after rehabilitation . During the 12-month intervention , exercise tolerance ( maximum treadmill workload and 6-minute walk distance ) and overall health status ratings were better maintained in the experimental group together with a reduction in hospital days . There were no group differences for other measures of pulmonary function , dyspnea , self-efficacy , generic and disease-specific quality of life , and health care use . By 24 months , there were no significant group differences . Patients returned to levels close to but above prerehabilitation measures . We conclude that a maintenance program of weekly telephone calls and monthly supervised sessions produced only modest improvements in the maintenance of benefits after pulmonary rehabilitation The purpose of this study was to test the effectiveness of a taped relaxation message in reducing dyspnea and anxiety in chronic obstructive pulmonary disease ( COPD ) patients . Twenty-six adult COPD patients with dyspnea were r and omly assigned to two groups . The treatment group was taught relaxation using a prerecorded tape while the control group was instructed to sit quietly . Skin temperature , heart rate , and respiratory rate were recorded for all subjects during a total of four weekly sessions . Anxiety , dyspnea , and airway obstruction were measured at the beginning and end of the study . The relaxation group achieved the preset relaxation criteria . Dyspnea , anxiety , and airway obstruction were induced in the relaxation group while the control group remained the same or became worse This study poses two questions : 1 ) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease ( COPD ) ? and 2 ) what is the effect of a r and omized , controlled , 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance ? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients ( age 49+/-11 yrs ) , mean forced expiratory volume in one second ( FEV1 ) 77+/-23 % pred and 52 healthy , sedentary subjects ( age 51 ( 10 ) yrs ) , mean FEV1 109+/-16 % pred . The 43 COPD patients were r and omly allocated into training ( n=26 ) and control ( n=17 ) groups . Isokinetic and isotonic muscle function , whole body endurance , maximal exercise capacity and lung function were measured . The COPD patients had reduced isokinetic muscle function ( with the exception of sustained upper limb strength ) as compared with healthy sedentary subjects . Muscle function improved after weight training in the COPD patients . Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption . A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which can not be explained by factors such as hypoxaemia and malnutrition . Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning On theoretical grounds it is assumed that positive expiratory pressure mask physiotherapy ( PEP ) as a means of promoting mucus clearance is especially effective in the more distal airways . In a r and omized cross-over trial including a control measurement the effect of PEP and of the forced expiration technique combined with postural drainage ( FET/PD ) on regional lung clearance was evaluated in seven patients with chronic bronchitis and abundant sputum production ( mean 32 g.day-1 ) . PEP consisted of positive expiratory pressure mask breathing interspersed with breathing exercises , forced expiration manoeuvres ( huffing ) and , if necessary , coughing . FET consisted of breathing exercises , huffing and also , if necessary , coughing . FET was combined with PD . Following inhalation of a radio-aerosol regional lung clearance was estimated by means of gamma camera imaging . The results after PEP appeared to be not significantly different from control . The mean clearance in all three lung zones ( peripheral , intermediate and inner ) was largest after FET/PD as compared with PEP and control . Statistical significance ( p less than 0.02 ) was reached only for clearance in the inner region . It is concluded that PEP has no demonstrable effect on regional lung clearance in these patients Supplemental oxygen improves exercise tolerance of normoxemic and hypoxemic chronic obstructive pulmonary disease ( COPD ) patients . We determined whether nonhypoxemic COPD patients undergoing exercise training while breathing supplemental oxygen achieve higher intensity and therefore improve exercise capacity more than patients breathing air . A double-blinded trial was performed involving 29 nonhypoxemic patients ( 67 years , exercise SaO2 > 88 % ) with COPD ( FEV1 = 36 % predicted ) . All exercised on cycle ergometers for 45 minutes , 3 times per week for 7 weeks at high-intensity targets . During exercise , they received oxygen ( 3 L/minute ) ( n = 14 ) or compressed air ( 3 L/minute ) ( n = 15 ) . Both groups had a higher exercise tolerance after training and when breathing oxygen . However , the oxygen-trained group increased the training work rate more rapidly than the air-trained group . The mean + /- SD work rate during the last week was 62 + /- 19 W ( oxygen-trained group ) and 52 + /- 22 W ( air-trained group ) ( p < 0.01 ) . After training , endurance in constant work rate tests increased more in the oxygen-trained group ( 14.5 minutes ) than in the air-trained group ( 10.5 minutes ) ( p < 0.05 ) . At isotime , the breathing rate decreased four breaths per minute in the oxygen-trained group and one breath per minute in the air-trained group ( p = 0.001 ) . We conclude that supplemental oxygen provided during high-intensity training yields higher training intensity and evidence of gains in exercise tolerance in laboratory testing BACKGROUND PATIENTS : with chronic airflow obstruction are often limited by muscle fatigue and weakness . As exercise rehabilitation programmes have produced modest improvements at best a study was design ed to determine whether specific muscle training techniques are helpful . METHODS : Thirty four patients with chronic airflow limitation ( forced expiratory volume in one second ( FEV1 ) 38 % of predicted values ) were stratified for FEV1 to vital capacity ( VC ) ratio less than 40 % and arterial oxygen desaturation during exercise and r and omised to a control or weightlifting training group . In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only . It was carried out three times a week for eight weeks . RESULTS : Three subjects dropped out of each group ; results in the remaining 14 patients in each group were analysed . Adherence in the training group was 90 % . In the trained subjects muscle strength and endurance time during cycling at 80 % of maximum power output increased by 73 % from 518 ( SE69 ) to 898 ( 95 ) s , with control subjects showing no change ( 506 ( 86 ) s before training and 479 ( 89 ) s after training ) . No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group . Responses to a chronic respiratory question naire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group . CONCLUSIONS : Weightlifting training may be successfully used in patients with chronic airflow limitation , with benefits in muscle strength , exercise endurance , and subjective responses to some of the dem and s of daily living OBJECTIVE To compare the short-term effects of postural drainage ( PD ) , oscillating positive expiratory pressure ( using the FLUTTER device ) , and expiration with the glottis open in the lateral posture ( ELTGOL ) on oxygen saturation , pulmonary function , and sputum production in patients with an acute exacerbation of chronic bronchitis . DESIGN A prospect i ve , r and omized study . SETTING A clinical ward . PATIENTS Ten patients with chronic bronchitis exacerbation received PD , FLUTTER , and ELTGOL by the same respiratory therapist at about the same time of day on separate days and in r and om order . MAIN OUTCOME MEASURES Oxygen saturation and pulmonary function were measured before , immediately after , and 15 minutes and 1 hour after each treatment . Improvement in sputum production was measured by total sputum wet weight immediately after and for 1 hour after treatment . INTERVENTIONS PD consisted of positioning the patients in a posture that allows bronchial drainage by gravity . FLUTTER is a device that is cl aim ed to combine oscillating positive expiratory pressure with oscillations of the airflow . ELTGOL is an airway clearance technique that uses lateral posture and different lung volumes to control expiratory flow rate to avoid airway compression . The total time spent for treatments was 30 minutes . RESULTS All techniques were well tolerated , and oxygen saturation and pulmonary function did not change significantly during and after treatments . Thirty minutes after the beginning of treatment , sputum production increased significantly with all techniques , but during the 1 hour after the end of treatment , it was significantly larger with FLUTTER ( from 15.0 + /- 8.6 g to 19.0 + /- 9.3 g , p < .01 ) and ELTGOL ( from 17.0 + /- 7.0 g to 20.6 + /- 6.9 g , p < .02 ) than with PD ( from 15.5 + /- 4.0 g to 17.5 + /- 3.7 g , NS ) . CONCLUSIONS All three treatments were safe and effective in removing secretions without causing undesirable effects on oxygen saturation , but FLUTTER and ELTGOL techniques were more effective in prolonging secretion removal in chronic bronchitis exacerbation than was the PD method This r and omized , controlled study investigated the physiological effects of a specially design ed 12 week programme of isolated conditioning of peripheral skeletal muscle groups . The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital . Forty eight patients , aged 40 - 72 yrs with chronic obstructive pulmonary disease ( COPD ) ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 61 (27)% of predicted normal ) were r and omly allocated into training ( n = 32 ) and control ( n = 16 ) groups . Physiological assessment s were performed before and after the 12 week study period , and included peripheral muscle endurance and strength , whole body endurance , maximal exercise capacity ( maximum oxygen consumption ( V'O2,max ) ) and lung function . The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance , with no additional breathlessness . Whole body endurance measured by free arm treadmill walking increased by 6,372 ( 3,932 - 8,812 ) 3 ( p < 0.001 ) . Symptom-limited maximal V'O2 was unchanged . However , the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide , both at peak exercise and at equivalent work rate ( Wmax ) . In summary , low intensity isolated peripheral muscle conditioning is well-tolerated , simple and easy to perform at home . The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning Background : Passive training of specific locomotor muscle groups by means of neuromuscular electrical stimulation ( NMES ) might be better tolerated than whole body exercise in patients with severe chronic obstructive pulmonary disease ( COPD ) . It was hypothesised that this novel strategy would be particularly effective in improving functional impairment and the consequent disability which characterises patients with end stage COPD . Methods : Fifteen patients with advanced COPD ( nine men ) were r and omly assigned to either a home based 6 week quadriceps femoris NMES training programme ( group 1 , n=9 , FEV1=38.0 (9.6)% of predicted ) or a 6 week control period before receiving NMES ( group 2 , n=6 , FEV1=39.5 (13.3)% of predicted ) . Knee extensor strength and endurance , whole body exercise capacity , and health related quality of life ( Chronic Respiratory Disease Question naire , CRDQ ) were assessed . Results : All patients were able to complete the NMES training programme successfully , even in the presence of exacerbations ( n=4 ) . Training was associated with significant improvements in muscle function , maximal and endurance exercise tolerance , and the dyspnoea domain of the CRDQ ( p<0.05 ) . Improvements in muscle performance and exercise capacity after NMES correlated well with a reduction in perception of leg effort corrected for exercise intensity ( p<0.01 ) . Conclusions : For severely disabled COPD patients with incapacitating dyspnoea , short term electrical stimulation of selected lower limb muscles involved in ambulation can improve muscle strength and endurance , whole body exercise tolerance , and breathlessness during activities of daily living A r and omized , controlled , single-blind study was performed on 20 patients with chronic obstructive pulmonary disease and exercise-induced hypoxaemia . Ten patients each were r and omly assigned to one of two groups , one training with air and the other training with oxygen . There were no significant differences between the groups regarding values measured prior to the study . The patients trained 3 times per week for 30 minutes each time for a duration of 8 weeks . The training consisted of interval walking on a treadmill ( intensity set according to Borg ratings ) with either air or oxygen administered through a nasal cannula at a rate of 5 l/min . Training significantly improved the 6-minute walking distance by 20 % and 14 % in the air and oxygen group , respectively , when the patients were tested on air . In the same test the air group significantly decreased Borg ratings for perceived exertion . Borg ratings for dyspnoea and perceived exertion significantly decreased in the oxygen group when they were tested on oxygen . It was concluded that oxygen supplementation did not further improve the training effect , compared with training with air , in patients with chronic obstructive pulmonary disease and exercise-induced hypoxaemia Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD . A r and omized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise ( arterial oxygen saturation ( Sa , O2 ) < 90 % at peak exercise ) . All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration . They were assigned either to general exercise training while breathing room air ( GET/RA group : forced expiratory volume in one second ( FEV1 ) 38 % of predicted ; arterial oxygen tension ( Pa , O2 ) 10.5 kPa at rest ; Pa , O2 7.3 kPa at peak exercise ) , or to GET while breathing supplemental oxygen ( GET/O2 group : FEV1 29 % pred ; Pa , O2 10.2 kPa at rest ; Pa , O2 7.2 kPa at peak exercise ) . Sa , O2 was not allowed to fall below 90 % during the training . The effects on exercise performance while breathing air and oxygen , and on quality of life were compared . Maximum workload ( Wmax ) significantly increased in the GET/RA group ( mean ( SD ) 17 ( 15 ) W , p<0.01 ) , but not in the GET/O2 group ( 7 ( 25 ) W ) . Six minute walking distance ( 6MWD ) , stair-climbing , weight-lifting exercise ( all while breathing room air ) and quality of life significantly increased in both groups . Acute administration of oxygen improved exercise performance before and after training . Training significantly increased Wmax , peak carbon dioxide production ( V'CO2 ) and 6MWD while breathing oxygen in both groups . Differences between groups were not significant . Pulmonary rehabilitation improved exercise performance and quality of life in both groups . Supplementation of oxygen during the training did not add to the effects of training on room air OBJECTIVES To have a group of COPD patients undergo a simple program of home-based exercise training , using the shuttle walking test ( SWT ) to st and ardize the intensity of training . METHODS Sixty patients participated , r and omly distributed into two groups ( rehabilitation and control ) of 30 patients each . The following evaluations were carried out at baseline and at 12 weeks : ( 1 ) pulmonary function studies ; ( 2 ) SWT ; ( 3 ) submaximal intensity resistance test ; ( 4 ) cycle ergometer test ; ( 5 ) quality of life ; and ( 6 ) dyspnea . The rehabilitation group underwent a lower-extremity training program . Walking was selected as the type of exercise . The intensity of training was set at 70 % of the maximum speed attained on the SWT . Divided sessions were held , lasting 1 h , 6 days/wk , at home , with a checkup every 2 weeks . The duration of the program was 12 weeks . RESULTS The following patients completed the study : 20 patients ( 66.6 % ) from the rehabilitation group ( mean [ + /- SD ] ) age , 64.3 + /- 8.3 years ; mean FEV(1 ) , 41.7 + /- 15.6 % of predicted ) ; and 17 patients ( 56.6 % ) from the control group ( mean age , 63.1 + /- 6.9 years ; mean FEV(1 ) , 40 + /- 16.4 % of predicted ) . We found no changes in pulmonary function or effort parameters ( SWT or cycle ergometer ) in the rehabilitation group at 12 weeks . A twofold increase ( 1,274 + /- 980 to 2,651 + /- 2,056 m ; p < 0.001 ) was achieved in the submaximal intensity resistance test , with less dyspnea at the conclusion of the test ( p = 0.05 ) . Significant improvement also was achieved in basal dyspnea and , both statistically and clinical ly , in the quality of life . Significant changes were not achieved in the control group patients . CONCLUSIONS A simple home-based program of exercise training achieved improvement in exercise tolerance , posteffort dyspnea , basal dyspnea , and quality of life in COPD patients STUDY OBJECTIVES We sought to determine whether breathing heliox or using nasal noninvasive positive pressure ventilation ( NIPPV ) would produce immediate improvements in exercise capability in patients with COPD , and whether training for 6 weeks with one of these modalities would result in greater exercise improvement than with training unassisted . SETTING US military medical center . METHODS Thirty-nine patients with severe COPD ( mean FEV1 of 33.5 % predicted ) underwent three incremental treadmill tests to exhaustion unassisted , breathing heliox , or breathing with NIPPV . They were then r and omized to undergo 6 weeks of twice-weekly rehabilitation with unassisted exercise training ( UT group ) , training while breathing heliox ( HT group ) , or training while breathing with NIPPV ( NT group ) . The three exercise tests were then repeated . RESULTS Heliox treatment did not produce any immediate benefit in exercise time or maximum workload in the 39 patients initially tested , the 32 patients who completed the protocol , or the HT group . Furthermore , no training advantage was evident in the HT group ( n = 10 ) compared to the UT group ( n = 11 ) . NIPPV did not produce an immediate benefit in the initial tests , but produced a small increase in exercise time in the 32 patients completing the protocol in the final tests . This effect was primarily because of the NT group , who exercised significantly longer ( mean + /- SD , 16.8 + /- 4.9 min vs 14.2 + /- 5.6 min , p = 0.0045 ) and to a higher workload ( 4.46 + /- 1.55 metabolic equivalents [ METs ] vs 4.09 + /- 1.75 METs , respectively ; p = 0.038 ) when tested using the ventilator . Compared to the UT group , the NT group started out with a lower exercise time ( 7.9 + /- 3.5 min vs 12.3 + /- 5.2 min , p = 0.031 ) in preliminary testing , but the statistical difference was eliminated in the final tests ( 14.2 + /- 5.6 min vs 16.0 + /- 5.8 min , respectively ; p = 0.451 ) . The NT group actually slightly exceeded the UT group when they used the ventilator in final testing , although this was not statistically significant ( 16.8 + /- 4.9 min vs 16.0 + /- 5.8 min , respectively ) . CONCLUSION Heliox treatment does not appear to offer an immediate or training advantage with exercise in patients with COPD . For patients who have undergone regular exercise conditioning with NIPPV , use of the ventilator produces an immediate improvement in both exercise time and maximum workload attained , and it may confer a training advantage In patients with chronic obstructive pulmonary disease ( COPD ) the intensity of aerobic training is limited by dyspnea . Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea . We examined effects of home-based inspiratory muscle training ( IMT ) and cycle ergometry training ( CET ) in 53 patients with moderate to severe COPD ( FEV(1)% pred , 50 + /- 17 [ mean + /- SD ] ) . Patients were r and omly assigned to 4 mo of training in one of four groups : IMT , CET , CET + IMT , or health education ( ED ) . Patients were encouraged to train to the limits of their dyspnea . Inspiratory muscle strength and endurance increased in IMT and CET + IMT groups compared with CET and ED groups ( p < 0 . 01 ) . Peak oxygen uptake increased and heart rate , minute ventilation , dyspnea , and leg fatigue decreased at submaximal work rates in the CET and CET + IMT groups compared with the IMT and ED groups ( p < 0 . 01 ) . There were no differences between the CET and CET + IMT groups . Home-based CET produced a physiological training effect and reduced exercise-related symptoms while IMT increased respiratory muscle strength and endurance . The combination of CET and IMT did not produce additional benefits in exercise performance and exercise-related symptoms . This is the first study to demonstrate a physiological training effect with home-based exercise training PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program Twenty-one patients with severe chronic irreversible airflow obstruction ( FEV1 consistently less than 1.2 l ) were allocated r and omly to one of two training programmes design ed to reduce respiratory disability or a placebo training control group . Daily structured physical exercise , twice daily inspiratory muscle training by resistive breathing , or daily placebo training were undertaken for 10 weeks , and the effects on lung function , exercise capacity , respiratory symptoms and psychological state compared . Maximal work achieved on a progressive bicycle exercise test was significantly increased in all groups ( 36 % , 23 % and 34 % respectively ) and global improvement in mood also occurred . There was no significant change in respiratory symptom score , static lung function tests or 12 min walking distance . Neither form of active treatment showed superiority over placebo training STUDY OBJECTIVES To compare the effectiveness of two forms of exercise training in pulmonary rehabilitation . DESIGN A prospect i ve , r and omized , unblinded , 8-week trial . SETTING A hospital-based outpatient pulmonary rehabilitation program . PATIENTS Forty patients ( 20 patients in each group ) with COPD who were referred for pulmonary rehabilitation . INTERVENTIONS We compared the short-term effectiveness of a high-intensity , lower-extremity endurance program with a low-intensity , multicomponent calisthenics program for the rehabilitation of patients with COPD . The high-intensity group trained predominately on the stationary bicycle and treadmill , with a goal of exercising at > or = 80 % of maximal level determined from incremental testing for 30 min per session . The low-intensity group performed predominately classroom exercises for approximately 30 min per session . For both groups , twice-weekly sessions were held for 8 weeks . The primary outcome measure was health status , measured using the Chronic Respiratory Disease Question naire . Other outcomes included peak oxygen consumption on incremental treadmill exercise testing , exertional dyspnea , treadmill endurance time , the number of sit-to-st and repetitions and arm lifts in 1 min , overall dyspnea , and question naire-rated functional status . MEASUREMENTS AND RESULTS Both groups showed significant postrehabilitation improvement in exercise variables , exertional and overall dyspnea , functional performance , and health status . Patients in the high-intensity group showed greater increases in treadmill endurance and greater reductions in exertional dyspnea , whereas those in the low-intensity group showed greater increases in arm-endurance testing . Both groups had similar improvements in overall dyspnea , functional performance , and health status . CONCLUSIONS Despite differences in exercise performance , both high-intensity , lower-extremity endurance training and low-intensity calisthenics led to similar short-term improvements in question naire-rated dyspnea , functional performance , and health status Underst and ing of what constitutes a training load adequate to induce training effects in patients with chronic obstructive pulmonary disease ( COPD ) is still evolving . The present study investigated whether interval training ( IT ) is effective in terms of inducing measurable improvements in physiological response and compared its effects on exercise tolerance ( ET ) and quality of life to those of continuous training ( CT ) . Thirty-six COPD patients , with a forced expiratory volume in one second of 45±4 % of the predicted value ( mean±sem ) , were r and omly assigned to CT ( exercise at 50 % of baseline peak work-rate ) or IT ( work for 30 s at 100 % of peak work-rate alternating with 30‐s rest intervals ) groups that cycled 40 min·day−1 and 2 days·week−1 for 12 weeks . After training , both groups showed significantly improved ET ( IT , 57±6 to 71±8 W ; CT , 57±5 to 70±6 W ) and total quality -of-life score of the Chronic Respiratory Disease Question naire ( IT , 77±3 to 88±2 ; CT , 78±3 to 93±2 ) . At identical levels of exercise , minute ventilation was significantly reduced ( IT , 35.8±2.5 to 31.7±2.5 L·min−1 ; CT , 36.4±2.7 to 32.5±2.7 L·min−1 ) . The magnitude of improvement in these variables was not significantly different among groups . The present data exp and on the principles of exercise prescription for chronic obstructive pulmonary disease patients by demonstrating that interval training elicits substantial training effects , which are similar in magnitude to those produced by continuous training at half the exercise intensity but double the exercise time The effects of two 8 week programmes of reconditioning in chronic obstructive pulmonary disease ( COPD ) patients were studied . Forty one subjects ( mean+/-SD ) 644.5 ) yrs ; forced expiratory volume in one second ( FEV1 ) 1.09+/-0.16 L ; 40.6+/-6.2 % predicted were r and omly assigned either to supervised training on a treadmill , 4 days x week(-1 ) ( group S ; n=21 ) or walking 3 or 4 km in 1 h 4 days x week(-1 ) , self-monitored with a pedometer , with weekly visits to encourage adherence ( group SM ; n=20 ) . Patients were evaluated with the chronic respiratory diseases question naire ( CRQ ) and two exercise tests on a treadmill : incremental ( IT ) and constant ( CT ) , above lactic threshold or 70 % of maximal oxygen uptake ( VO2 , max ) with arterial blood lactate determinations . Estimated mean work rate of training was 69+/-27 W and 25+/-5 W respectively for groups S and SM . Both types of training produced similar changes in the four dimensions of the CRQ . In group S reconditioning yielded significant ( p<0.05 ) increases in VO2 , max and increases in duration , with decreased lactate accumulation , ventilation , CO2 output ( VCO2 ) , heart rate ( HR ) and diastolic blood pressure ( DBP ) at the end of CT . They also adopted a deeper slower pattern of breathing during exercise . The SM group showed significant ( p<0.05 ) increases in duration , lower HR and DBP at the end of CT . Significantly ( p<0.05 ) different effects between S and SM programmes were changes in VO2 , max 100+/-101 mL x min(-1 ) versus 5+/-101 mL x min(-1 ) ) , duration of the CT ( 8.1+/-4.4 min versus 3.9+/-4.7 min ) , VCO2 ( -94+/-153 mL x min(-1 ) versus 48+/-252 mL x min(-1 ) ) , lactate accumulation ( -1.3+/-2.2 mmol x L(-1 ) versus 0+/-1.2 mmol x L(-1 ) and respiratory rate at the end of CT ( 4.3+/-3.4 min(-1 ) versus -1+/-4.2 min(-1 ) ) . Supervised , intense training yields physiological improvements in severe chronic obstructive pulmonary disease patients not induced by self-monitored training . The self-monitored , less intense training , increases submaximal exercise endurance , although to a lesser degree The effects of endurance training on exercise capacity and health-related quality of life ( HRQL ) in chronic obstructive pulmonary disease ( COPD ) patients have been studied thoroughly , while resistance training has been rarely evaluated . This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness ( isometric knee extension peak torque < 75 % predicted ) . Forty-eight patients ( age 64±8 yrs , forced expiratory volume in one second 38±17 % pred ) were r and omly assigned to resistance training ( RT , n=24 ) or endurance training ( ET , n=24 ) . The former consisted of dynamic strengthening exercises . The latter consisted of walking , cycling and arm cranking . Respiratory and peripheral muscle force , exercise capacity , and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation ( RT n=14 , ET n=16 ) . Statistically significant increases in knee extension peak torque ( RT 20±21 % , ET 42±21 % ) , maximal knee flexion force ( RT 31±39 % , ET 28±37 % ) , elbow flexion force ( RT 24±19 % , ET 33±25 % ) , 6-min walking distance ( 6MWD ) ( RT 79±74 m , ET 95±57 m ) , maximum workload ( RT 15±16 Watt , ET 14±13 Watt ) and HRQL ( RT 16±25 points , ET 16±15 points ) were observed . No significant differences in changes in HRQL and 6MWD were seen between the two treatments . Resistance training and endurance training have similar effects on peripheral muscle force , exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness STUDY OBJECTIVE To compare the effects of active limb mobilization ( ALM ) with or without electrical stimulation ( ES ) on muscle strength , respiratory rate ( RR ) , heart rate , oxygen saturation , and time needed to transfer from bed to chair in two groups of patients with COPD . DESIGN R and omized , controlled study . SETTING Respiratory high-dependency care unit . PATIENTS Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy . METHODS Patients were r and omly assigned either to ALM alone or to ALM plus ES ( ALM/ES ) . ES was applied using square-wave alternate , symmetric , and compensated impulses for 30 min bid . The duration of treatment was 28 days for all patients . RESULTS Muscle strength improved significantly in the overall group of patients ( from 1.75 + /- 0.73 to 3.44 + /- 0.65 , p < 0.05 ) . Comparing the change ( end minus beginning ) of the analyzed variables , ALM/ES significantly improved muscle strength ( 2.16 + /- 1.02 vs 1.25 + /- 0.75 , p = 0.02 ) and RR ( - 1.91 + /- 1.72 vs 0.41 + /- 1.88 , p = 0.004 ) , and decreased the number of days needed to transfer from bed to chair ( 10.75 + /- 2.41 days vs 14.33 + /- 2.53 days , p = 0.001 ) . CONCLUSION In bed-bound patients with COPD receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy , application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair This study evaluates the effects of training with noninvasive ventilatory support in patients with chronic obstructive pulmonary disease in a r and omised , controlled , observer-blinded trial . Twenty-nine patients with chronic obstructive pulmonary disease and with a ventilatory limited exercise capacity ( forced expiratory volume in one second < 60 % predicted , breathing reserve at maximal exercise < 20 % of maximally voluntary ventilation , resting arterial oxygen tension ≥8 kPa ( 60 mmHg ) , end-exercise arterial oxygen saturation measured by pulse oximetry ≥85 % ) completed an 8-week supervised outpatient cycle exercise programme . Fourteen patients were r and omised to training with inspiratory pressure support of 10 cmH2O and 15 patients to training with control ( sham ) inspiratory pressure support of 5 cmH2O . Outcome measures were the incremental shuttle walking test and a constant-load cycle endurance test at 75 % of peak work rate including the measurement of physiological responses , and health status measured using the St. George 's Respiratory Question naire . Statistically significant between-group differences were found in favour of the inspiratory pressure support of 10 cmH2O group for improvement in shuttle walking distance ( 16±17 versus 3±13 % ) , cycle endurance ( 164±124 versus 88±128 % ) , and the reduction in minute ventilation during exercise ( -11±10 versus -2±9 % ) . It was concluded that exercise training with inspiratory pressure support of 10 cmH2O result ed in statistically significantly larger improvements in exercise performance than training with inspiratory pressure support of 5 cmH2O in patients with chronic obstructive pulmonary disease suffering from a ventilatory limited exercise capacity . Inspiratory pressure support of 10 cmH2O may be considered as adjunct during high-intensity exercise training Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels Pursed lips breathing ( PLB ) training is often used in the management of patients with chronic obstructive lung disease ( COLD ) . Previous clinical studies have demonstrated that PLB improves arterial oxygen saturation ( SaO2 ) and CO2 removal as well as relieving dyspnea . Twelve hypoxemic subjects with stable COLD were r and omly assigned to either the pursed lips ( P ) or control group consisting of general relaxation ( R ) . The SaO2 was monitored via ear oximetry , and respiratory rate and tidal volume were monitored using a strain gage transducer and the minute volume was calculated . The PLB was taught by an experienced instructor using the ear oximeter as a monitoring display with a goal toward increasing SaO2 . The subject was taught general relaxation ( Rlx ) with the aid of pleasant music . We compared PLB and Rlx treatments using an A-B-A crossover study design . In both groups , PLB significantly improved SaO2 over baseline ( p less than 0.001 ) whereas Rlx did not . We conclude that patients can learn to increase their SaO2 by PLB using ear oximetry adjunctively Inspiratory muscle training may have beneficial effects in certain patients with chronic obstructive pulmonary disease ( COPD ) . Because of the lack of a home training device , normocapnic hyperpnea has rarely been used as a training mode for patients with COPD , and is generally considered unsuitable to large-scale application . To study the effects of hyperpnea training , we r and omized 30 patients with COPD and ventilatory limitation to respiratory muscle training ( RMT ; n = 15 ) with a new portable device or to breathing exercises with an incentive spirometer ( controls ; n = 15 ) . Both groups trained twice daily for 15 min for 5 d per week for 8 wk . Training-induced changes were significantly greater in the RMT than in the control group for the following variables : respiratory muscle endurance measured through sustained ventilation ( + 825 + /- 170 s [ mean + /- SEM ] versus -27 + /- 61 s , p < 0.001 ) , inspiratory muscle endurance measured through incremental inspiratory threshold loading ( + 58 + /- 10 g versus + 21.7 + /- 9.5 g , p = 0.016 ) , maximal expiratory pressure ( + 20 + /- 7 cm H(2)O versus -6 + /- 6 cm H(2)O , p = 0.009 ) , 6-min walking distance ( + 58 + /- 11 m versus + 11 + /- 11 m , p = 0.002 ) , V O(2peak ) ( + 2.5 + /- 0.6 ml/kg/min versus -0.3 + /- 0.9 ml/kg/min , p = 0.015 ) , and the SF-12 physical component score ( + 9.9 + /- 2.7 versus + 1.8 + /- 2.4 , p = 0.03 ) . Changes in dyspnea , maximal inspiratory pressure , treadmill endurance , and the SF-12 mental component score did not differ significantly between the RMT and control groups . In conclusion , home-based respiratory muscle endurance training with the new device used in this study is feasible and has beneficial effects in subjects with COPD and ventilatory limitation BACKGROUND Disability in patients with chronic obstructive pulmonary disease has led to the development of rehabilitation programs to increase exercise tolerance . OBJECTIVE To determine , if the effect of training can be improved by giving supplemental oxygen during exercise . MEASUREMENTS Ten male patients with COPD ( mean FEV1 = 43.2 + /- 17.1 % pred ) underwent a five day per week cycle ergometer training program for four weeks at least 45 minutes per day at a constant workload of 80 % of their highest achieved workrate -- measured in an incremental exercise test before training . At this workrate all patients performed exercise above their anaerobic threshold . Five patients were breathing 35 % oxygen during exercise , five were breathing roomair ( r and omised , single blind ) . To evaluate and compare the results of training before and after the program all patients performed an incremental exercise test ( continuously increasing workrate ) with roomair . RESULTS In the group breathing 35 % O2 during training the maximally achieved power in the incremental exercise test after training was 15.9 % higher . In the group breathing roomair during training the maximally achieved power after training was 36.3 % higher than before ( p < 0.05 ) . This group also showed significant reductions in lactate levels ( p < 0.05 ) after training at the maximum workload achieved in the pre-training test . CONCLUSIONS Training in the roomair-group result ed in a significant increase in the maximum power and total amount of work . In this group training could induce a physiologic response ( increase of aerobic capacity ) , which was shown by significantly lower lactate levels at a comparable workload Disability and exertional dyspnea associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and relief of dyspnea . To evaluate whether aerobic training ( training groups P1 and P4 ) , strength training ( P2 and P5 ) or a combination of both ( P4 and P6 ) is useful , 69 patients ( 44 m/25 f ) with moderate to severe COPD were r and omised to a three week inpatient training program . The training consisted of three weekly twenty minute exercise sessions without ( P1 - P3 ) or with supplemental oxygen ( P4 - P6 ) on a calibrated ergocycle ( 70 % W(max ) ) or three weekly sessions of 20 - 25 repetitions of 2 - 4 training series ( 40 % W(max ) ) or a combination of both . In general , the programme failed to demonstrate significant changes in lung function and arterial blood gases . Evaluation of exercise capacity via the six-minute-walking test ( 6MT ) yielded a significant increase of the walking distance in all groups except P2 ( 60 - 83 m ) , The time to finish a test-set of daily activities ( TAF ) was reduced in all groups ( 5 - 58 sec ) and reached significance in P1 , P3 , P5 and P6 . After the 6MT , exertional dyspnea improved in all groups except P4 and was significant in P1 and P3 ; after the TAF , dyspnea again was reduced in all groups with a significant change in P2 and P5 . These data support the hypotheses that a short term inpatient training programme is suitable to improve exercise-capacity and dyspnea . Patients with advanced disease ( P4 - P6 ) show greater benefits with strength training ( alone or in combination with aerobic training ) while for patients with moderate disease ( P1 - P3 ) aerobic training is favourable . These changes may translate into improved performance of daily activities and general well-being Background : Although exercise training improves exercise tolerance in most patients with chronic obstructive pulmonary disease ( COPD ) , some patients with severe disease may not be able to tolerate exercise training due to incapacitating breathlessness . Transcutaneous electrical muscle stimulation ( TCEMS ) has been shown to improve muscle strength , muscle mass , and performance in paraplegics , patients with knee ligament injury , and patients with peripheral vascular disease . We hypothesised that TCEMS of the lower extremities can improve muscle strength and exercise tolerance in patients with moderate to severe COPD . Methods : A r and omised controlled trial of TCEMS of the lower extremities was performed in 18 medically stable patients of mean ( SD ) age 60.0 ( 1.5 ) years with a mean forced expiratory volume in 1 second ( FEV1 ) of 1.03 ( 0.10 ) l ( 38 % predicted ) and residual volume/total lung capacity ( RV/TLC ) of 59 (2)% . Stimulation of the lower extremities was performed three times a week , 20 minutes each session , for six continuous weeks . Quadriceps and hamstring muscle strength , exercise capacity , and peak oxygen uptake were measured at baseline and after 6 weeks of stimulation . Results : TCEMS improved both the quadriceps strength ( by 39.0 (20.4)% v 9.0 (8.1)% , p=0.046 ) and hamstring muscle strength ( by 33.9 (13.0)% v 2.9 (4.7)% , p=0.038 ) in the treated ( n=9 ) and sham treated ( n=9 ) groups , respectively . The improvement in muscle strength carried over to better performance in the shuttle walk test in the treated group ( 36.1 % v 1.6 % in the treated and sham groups respectively , p=0.007 , Mann-Whitney U test ) . There was no significant change in lung function , peak workload , or peak oxygen consumption in either group . Muscle stimulation was well tolerated by the patients with no dropouts and better than 95 % compliance with the protocol . Conclusions : TCEMS of peripheral muscles can be a useful adjunct to the comprehensive pulmonary rehabilitation of patients with COPD Study objectives The aims of this study were to establish whether pulmonary rehabilitation ( PR ) improves domestic function and daily activity levels in COPD and whether individually targeted exercise is more effective than general exercise . Design Prospect i ve r and omized , controlled trial . Setting Outpatient PR program in secondary care . Participants One-hundred eighty patients ( mean [ ±SD ] age , 68.3 ± 8.6 years ; FEV 1 , 0.95 ± 0.4 L ; FEV 1 /FVC ratio , 0.51 ± 0.15 ; 111 male patients ; 69 female patients ) with stable COPD . One hundred twenty-one patients completed the study . Interventions Patients were r and omized to a conventional 7-week general exercise program ( [ GEP ] n=90 ) or an individually targeted exercise program ( [ ITEP ] n=90 ) . Measurement and results Daily activity was measured using ambulatory activity monitors ( Z80 –32k V1 Int ; Gaehwiler Electronics ; Hombrechtikon , Switzerl and ) . These were lightweight devices , which contained a uniaxial accelerometer . Domestic function was assessed by the Canadian Occupational Performance Measure ( COPM ) . Exercise performance was assessed by the incremental shuttle walk test ( ISWT ) and the endurance shuttle walk test and health status by the chronic respiratory question naire – self-reported . Activity monitor counts increased by 29.18 % ( 95 % confidence interval [ CI ] , 3.19 to 55.17 ; p=0.03 ) for the GEP and 40.63 % ( 95 % CI , 7.42 to 73.83 ; p=0.02 ) for the ITEP . Mean COPM performance scores increased by 1.71 ( 95 % CI , 1.37 to 2.05 ; p=0.0001 ) for the GEP and 1.46 ( 95 % CI , 1.05 to 1.87 ; p=0.0001 ) for the ITEP . Mean COPM satisfaction scores increased by 2.27 ( 95 % CI , 1.74 to 2.81 ; p=0.0001 ) for the GEP and 2.04 ( 95 % CI , 1.56 to 2.52 ; p=0.0001 ) for the ITEP . ISWT scores increased by 81.72 m ( range , 63.83 to 99.62 ) for the GEP and by 85.52 m ( range , 67.62 to 103.42 ) for the ITEP . No statistically significant difference was found between the general exercise group and the individually targeted exercise group for any outcome measure . Conclusions Pulmonary rehabilitation improves domestic function and physical activity . This study also demonstrates that general exercise training is as effective as individually targeted training STUDY OBJECTIVE We analyzed the effects of the use of a rollator on walking distance and physiologic variables : pulmonary gas exchange , heart rate , minute ventilation ( Ve ) , oxygen saturation , and symptoms during the 6-min walk test ( 6MWT ) in patients with COPD . SETTING Outpatient clinic at university hospital . PATIENTS Fourteen patients with COPD in stable clinical condition . One patient had mild COPD , five patients had moderate COPD , six patients had severe COPD , and two patients had very severe COPD . INTERVENTIONS Two 6MWTs were performed with a portable metabolic system ( VmaxST 1.0 ; Viasys Healthcare ; MEDA ; Aartselaar , Belgium ) with a rollator and without a rollator , in r and om order . In addition , maximal voluntary ventilation ( MVV ) was measured with and without a rollator , r and omly . RESULTS The median 6MWT distance increased significantly with a rollator : 416 m without a rollator ( interquartile range [ IQR ] , 396 to 435 m ) , vs 462 m with a rollator ( IQR , 424 to 477 m ) [ p = 0.04 ] . Significant increases were also seen in oxygen uptake ( 0.04 L/min [ IQR , - 0.002 to 0.09 L/min ] ) ; tidal volume ( 0.06 L/min [ IQR , - 0.001 to 0.11 L/min ] ) ; and Ve ( 0.95 L/min [ IQR , - 0.67 to 7.1 L/min ] ) , recorded in the last minute of the 6MWT ; as well as in MVV ( 3 L/min [ IQR , 0 to 12 L/min ] ) [ p < 0.05 for all ] . Borg dyspnea scores tended to be lower with a rollator : 6 ( IQR , 4 to 7 ) without a rollator , vs 5 ( IQR , 4 to 7 ) with a rollator ( p = 0.10 ) . The variation in the 6MWT was explained by individual changes in walking efficiency ( partial R(2 ) = 0.31 ) and changes in Ve ( partial R(2 ) = 0.36 ) [ p model < 0.04 ] . CONCLUSION The use of a rollator improves walking distance of patients with COPD through an increased ventilatory capacity and /or better walking efficiency The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p < 0.05 ) , but the improvement was greater in the AERO + ST group ( 20 + /- 12 % versus 8 + /- 10 % [ mean + /- SD ] in the AERO group , p < 0.005 ) . The thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p < 0.001 ) , but not in the AERO group ( 3 + /- 6 % and 2 + /- 10 % , respectively , p > 0.05 ) . These changes were significantly different in the two study groups ( p < 0.01 ) . The increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life BACKGROUND There are several reports showing that expiratory muscle strength and endurance can be impaired in patients with COPD . This muscle weakness may have clinical ly relevant implication s. Expiratory muscle training tended to improve cough and to reduce the sensation of respiratory effort during exercise in patients other than those with COPD . METHODS Twenty-six patients with COPD ( FEV(1 ) 38 % predicted ) were recruited for the study . The patients were r and omized into two groups : group 1 , 13 patients were assigned to receive specific expiratory muscle training ( SEMT ) daily , six times a week , each session consisting of 1/2 h of training , for 3 months ; and group 2 , 13 patients were assigned to be a control group and received training with very low load . Spirometry , respiratory muscle strength and endurance , 6-min walk test , Mahler baseline dyspnea index ( before ) , and the transitional dyspnea index ( after ) were measured before and after training . RESULTS The training-induced changes were significantly greater in the SEMT group than in the control group for the following variables : expiratory muscle strength ( from 86 + /- 4.1 to 104 + /- 4.9 cm H(2)O , p < 0.005 ; mean difference from the control group , 24 % ; 95 % confidence interval , 18 to 32 % ) , expiratory muscle endurance ( from 57 + /- 2.9 % to 76 + /- 4.0 % , p < 0.001 ; mean difference from the control group , 29 % ; 95 % confidence interval , 21 to 39 % ) , and in the distance walked in 6 min ( from 262 + /- 38 to 312 + /- 47 m , p < 0.05 ; mean difference from the control group , 14 % ; 95 % confidence interval , 9 to 20 % ) . There was also a small but not significant increase ( from 5.1 + /- 0.9 to 5.6 + /- 0.7 , p = 0.14 ) in the dyspnea index . CONCLUSIONS The expiratory muscles can be specifically trained with improvement of both strength and endurance in patients with COPD . This improvement is associated with increase in exercise performance and no significant change in the sensation of dyspnea in daily activities BACKGROUND Impaired exercise tolerance is frequently observed in patients with COPD . Respiratory muscle endurance training ( RMET ) by means of normocapnic hyperpnea can be used to improve respiratory muscle function and probably exercise capacity . RMET is not applied on a large scale because complicated equipment is needed to maintain carbon dioxide homeostasis during hyperpnea , which can also be done by enlarging the dead space of the ventilatory system by breathing through a tube . Therefore , tube breathing might be a new , inexpensive method for home-based RMET . The aim of this study was to assess whether home-based RMET by means of tube breathing improves endurance exercise performance in patients with COPD . METHODS We r and omized 36 patients with moderate-to-severe COPD to RMET by paced tube breathing ( n = 18 ) or sham training ( control , n = 18 ) . Both groups trained twice daily for 15 min , 7 days per week , for 5 weeks . RESULTS Patients receiving RMET showed significant improvements in endurance exercise capacity ( constant-load exercise on cycle ergometry ; 18 min vs 28 min , p < 0.001 ) , in perception of dyspnea ( Borg score ; 8.4 vs 5.4 , p < 0.001 ) , and respiratory muscle endurance capacity ( sustainable inspiratory pressure ; 25 cm H(2)O vs 31 cm H(2)O , p = 0.005 ) . Quality of life ( chronic respiratory disease question naire ) also improved ( 78.7 to 86.6 , p = 0.001 ) . The control group showed no significant changes . CONCLUSION Home-based RMET by means of tube breathing leads to a significant improvement of endurance exercise capacity , a reduction in perception of dyspnea , and an improvement in quality of life in patients with moderate-to-severe COPD Background : The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease ( COPD ) during a high intensity outpatient cycle exercise programme were examined . Methods : Nineteen patients ( 17 men ) with severe COPD ( mean ( SD ) forced expiratory volume in 1 second ( FEV1 ) 27 (7)% predicted ) underwent a 6 week supervised outpatient cycle exercise programme . Ten patients were r and omised to exercise with ventilatory assistance using proportional assist ventilation ( PAV ) and nine ( two women ) to exercise unaided . Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate ( Wpeak ) followed by a constant work rate ( CWR ) test at 70 % of Wpeak achieved in the baseline incremental test . Minute ventilation ( Ve ) , heart rate , and arterialised venous plasma lactate concentration [ La+ ] were measured before and after each test . Results : Mean training intensity ( Wt/Wpeak ) at 6 weeks was 15.2 % ( 95 % CI 3.2 to 27.1 ) higher in the group that used ventilatory assistance ( p=0.016 ) . Peak work rate after training was 18.4 % ( 95 % CI 6.4 to 30.5 ) higher ( p=0.005 ) in the assisted group ( p=0.09 ) . [ La+ ] at an identical workload after training was reduced by 30 % ( 95 % CI 16 to 44 ) in the assisted group ( p=0.002 compared with baseline ) and by 11 % ( 95 % CI –7 to 31 ) ( p=0.08 compared with baseline ) in the unassisted group ( mean difference 18.4 % ( 95 % CI 3.3 to 40 ) , p=0.09 ) . A significant inverse relationship was found between reduction in plasma lactate concentration ( ΔL ) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training ( r=–0.7 , p=0.0006 ) . Conclusions : PAV enables a higher intensity of training in patients with severe COPD , leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation In a r and omized cross-over trial , including a control measurement the effect of positive expiratory pressure ( PEP ) and forced expiration technique ( FET ) on tracheobronchial clearance was evaluated in eight chronic bronchitics with abundant sputum production ( mean , 32 g/day ) . PEP consisted of PEP-mask breathing interspersed with breathing exercises , huffing , and coughing . FET consisted of postural drainage , breathing exercises , huffing , and coughing . Clearance was measured with a radio-aerosol technique . At 40 min after the start of therapy the mean clearance , expressed as percentage of the amount of radioactivity present at the start of therapy , was 32 % after PEP , 53 % after FET , and 15 % in the control run . The difference between PEP , FET , and control was statistically significant ( p less than 0.02 ) . Sputum production during PEP and FET was larger than during the equivalent period of time in the control run . It is concluded that FET is more effective than PEP in enhancing tracheobronchial clearance Many patients with chronic obstructive pulmonary disease ( COPD ) report greater limitation for activities involving the upper extremities than the lower extremities . Exercise training has generally emphasized lower-extremity exercise . We design ed and evaluated two simple , practical , and widely applicable upper-extremity training programs in 45 patients with COPD participating concurrently in a comprehensive , multidisciplinary pulmonary rehabilitation program . Patients were r and omly assigned to one of the following three groups : ( 1 ) gravity-resistance ( GR ) upper-extremity training ; ( 2 ) modified proprioceptive neuromuscular facilitation ( PNF ) upper-extremity training ; or ( 3 ) no upper-extremity training ( control ) . Patients were evaluated before and after at least six weeks of uninterrupted training . Twenty-eight patients completed the study . Compared to controls , both GR and PNF patients demonstrated improved performance on tests specific to the training performed ( upper-extremity performance test , maximal level and endurance on isokinetic arm cycle ) . There were no significant changes on isotonic arm cycle , ventilatory muscle endurance , or simulated activities of daily-living tests . Ratings of perceived breathlessness and fatigue decreased significantly in all groups for several tests . We conclude that specific upper-extremity training may be beneficial in the rehabilitation of patients with COPD and warrants further investigation The addition of noninvasive positive pressure ventilation ( NPPV ) to an exercise training ( ET ) program in severe chronic obstructive pulmonary disease ( COPD ) may produce greater benefits in exercise tolerance and quality of life than after training alone . Forty-five patients with severe stable COPD -mean ( SD ) FEV(1 ) 0.96 ( 0.31 ) L , Pa(O(2 ) ) 65.4 ( 9.07 ) mm Hg , Pa(CO(2 ) ) 45.6 ( 7.89 ) mm Hg-were r and omized to domiciliary NPPV + ET ( n = 23 ) or ET alone ( n = 22 ) . Exercise capacity and health status were assessed at baseline and after an 8-wk training program . There was a significant improvement in mean shuttle walk test ( SWT ) in the NPPV + ET group : from 169 ( 112 ) to 269 ( 124 ) m ( p = 0.001 ) , compared with the ET group : 205 ( 100 ) to 233 ( 123 ) m ( p = 0.19 ) ; mean difference ( 95 % confidence interval [ CI ] ) : 72 ( 12.9 to 131 ) m. Repeated measures analysis of variance ( ANOVA ) showed that the differences between the two groups became evident only in the final 4 wk of the training program with a mean end study difference ( 95 % 1CI ) of 65.8 ( 17.1 to 114 ) m. There was a significant improvement in the Chronic Respiratory Disease Question naire ( CRDQ ) of mean ( SD ) 24.0 ( 17.4 ) ( p = < 0.001 ) in the NPPV + ET group and 11.8 ( 15.8 ) ( p = 0.003 ) points in the ET group ; mean difference : 12.3 ( 1.19 to 23.4 ) . Only the NPPV + ET group demonstrated a significant improvement in arterial oxygenation ; mean difference : 3.70 mm Hg ( 0.37 to 7.27 ) . This study suggests that domiciliary NPPV can be used successfully to augment the effects of rehabilitation in severe COPD BACKGROUND Over the last 10 years ' exercise referral schemes ' have been popular even though the evidence for effectiveness of any one-to-one intervention in primary care is deficient . We report the results of a primary care based one-to-one intervention that compared the effect of two communication styles with a no-intervention control group on self-reported physical activity at 12 months . METHODS In all , 1658 middle-aged men and women were r and omly assigned to 30 minutes of brief negotiation or direct advice in primary care or a no-intervention control group . The main outcome was self-reported physical activity at 12 months . Secondary outcome measures included change in blood pressure and body mass index . RESULTS Intention-to-treat analysis revealed no significant differences in physical activity between groups . Brief negotiation group participants who completed the study increased their physical activity significantly more than controls . There was no change in body mass index in any group . The brief negotiation group produced a greater reduction in diastolic blood pressure than direct advice . CONCLUSION If patients whose health may benefit from increased physical activity seek advice in primary care , 20 - 30 minutes of brief negotiation to increase physical activity is probably more effective than similar attempts to persuade or coerce . However , blanket physical activity promotion in primary care is not effective . The most effective way of increasing physical activity in primary care has yet to be determined BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . STUDY OBJECTIVES To investigate the response to interval exercise ( IE ) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle , and to compare these changes to those incurred after constant-load exercise ( CLE ) training . DESIGN R and omized , controlled , parallel , two-group study ( IE vs CLE training ) . SETTING Multidisciplinary , outpatient , hospital-based , pulmonary rehabilitation program . PATIENTS Nineteen patients with stable advanced COPD ( mean + /- SEM FEV1 , 40 + /- 4 % predicted ) . INTERVENTIONS Patients ( n = 10 ) assigned to IE training exercised at a mean intensity of 124 + /- 15 % of baseline peak exercise capacity ( peak work rate [ Wpeak ] ) with 30-s work periods interspersed with 30-s rest periods for 45 min/d . Patients ( n = 9 ) allocated to CLE training exercised at a mean intensity of 75 + /- 5 % Wpeak for 30 min/d . Patients exercised 3 d/wk for 10 weeks . MEASUREMENTS AND RESULTS Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation . After IE training , the cross-sectional areas of type I and IIa fibers were significantly increased ( type I before , 3,972 + /- 455 microm2 ; after , 4,934 + /- 467 microm2 [ p = 0.004 ] ; type IIa before , 3,695 + /- 372 microm2 ; after , 4,486 + /- 346 microm2 [ p = 0.008 ] ) , whereas the capillary-to-fiber ratio was significantly enlarged ( from 1.13 + /- 0.08 to 1.24 + /- 0.07 [ p = 0.013 ] ) . Citrate synthase activity increased ( from 14.3 + /- 1.4 to 20.5 + /- 4.2 micromol/min/g ) , albeit not significantly ( p = 0.097 ) . There was also a significant improvement in Wpeak ( by 19 + /- 5 % ; p = 0.04 ) and in lactate threshold ( by 17 + /- 5 % ; p = 0.02 ) . The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training . During training sessions , however , ratings of dyspnea and leg discomfort , expressed as fraction of values achieved at baseline Wpeak , were significantly lower ( p < 0.05 ) for IE training ( 73 + /- 9 % and 60 + /- 8 % , respectively ) compared to CLE training ( 83 + /- 10 % and 87 + /- 13 % , respectively ) . CONCLUSIONS High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations ; however , IE is associated with fewer training symptoms BACKGROUND Patients with severe chronic obstructive pulmonary disease ( COPD ) may develop dyspnea with minimal arm activity , thoracoabdominal dyssynchrony with unsupported arm exercise ( UAEX ) and increased oxygen uptake ( VO2 ) , and minute ventilation ( VE ) with simple unsupported arm elevation ( UAE ) and UAEX . We investigated whether unsupported arm training , as the only form of exercise , could decrease the VO2 and VE cost ( percentage increase from resting baseline ) associated with unsupported arm elevation and exercise , respectively . METHODS Twenty-six patients with severe COPD were r and omized to 21 - 24 sessions of unsupported arm ( ARMT ) or low-intensity resistive breathing ( RBT ) training as the only form of exercise . Patients were studied before and after training using a metabolic cart and esophageal and gastric pressures to evaluate metabolic and respiratory muscle function . RESULTS After ARMT , the VO2 ( 58 % vs 38 % increase , P < 0.05 ) and VE ( 41 % v. 21 % increase , P < 0.05 ) cost for UAEX at exercise isotime decreased and endurance time increased . Similarly the VO2 ( 25 % vs 18 % increase , P < 0.05 ) cost decreased and VE no longer increased in response to 2 minutes of UAE after ARMT . The RBT group showed no such change . No improvement in ventilatory load or respiratory muscle function could be identified to explain the physiologic changes observed . After ARMT , mean inspiratory flow ( VT/TL ) , a measure of central respiratory drive , was reduced during UAEX and the expected increase during UAE did not occur . CONCLUSION We conclude that arm training reduces the VO2 and VE cost of UAE and UAEX , possibly through improved synchronization and coordination of accessory muscle action during unsupported arm activity The effect of manual chest percussion was studied in 10 patients recovering from an acute exacerbation of chronic bronchitis . All patients were studied on 2 consecutive days . Physiotherapy consisting of postural drainage and instructed coughing was given on both days . Chest percussion was included in a r and omized way on either day . Percussion was associated with a small but statistically significant increase in airflow obstruction , measured as a reduction in FEV1 after the treatment . There were no differences in the deposition or clearance of inhaled radiolabelled particles between the 2 forms of treatment . Changes in oxygen saturation were small and insignificant during both forms of treatment . The study indicates that manual chest percussion is of little value as an adjunct to postural drainage and instructed coughing in the treatment of patients with chronic bronchitis BACKGROUND Respiratory muscle weakness may contribute to dyspnea and exercise limitation in patients with significant COPD . In an attempt to reduce the severity of breathlessness and to improve exercise tolerance , inspiratory muscle training has been applied in many COPD patients . On the other h and , there is a paucity of data related to expiratory muscle performance and training in COPD . METHODS Thirty-two patients with significant COPD ( ie , mean FEV(1 ) , 37 % of predicted ) were recruited for the study . The patients were r and omized into four groups : eight patients were assigned to receive specific expiratory muscle training ( SEMT ) ; eight patients received specific inspiratory muscle training ( SIMT ) ; eight patients received SEMT and SIMT ( ie , the SEMT + SIMT group ) ; and eight patients who were assigned to a control group received training with very low load . All patients trained daily , six times a week , with each session consisting of one half hour of training , for 3 months . Spirometry , respiratory muscle strength and endurance , 6-min walk test distance , the perception of dyspnea , and the Mahler baseline dyspnea index ( BDI ) were measured before and following training . RESULTS Training caused a statistically significant specific increase in the expiratory muscle strength and endurance ( in the SEMT and SEMT + SIMT groups ) and in the inspiratory muscle strength and endurance ( in the SIMT and SEMT + SIMT groups ) . There was significant increase in the distance walked in 6 min in the SEMT , SIMT , and SEMT + SIMT groups . However , the increase in the SIMT and SEMT + SIMT groups was significantly greater than that in the SEMT group . There was a statistically significant increase in the BDI , and a decrease in the mean Borg score during breathing against resistance in the SIMT and SEMT + SIMT groups , with no changes in the SEMT and control groups . CONCLUSIONS The inspiratory and expiratory muscles can be specifically trained with improvement of both muscle strength and endurance . The improvement in the inspiratory muscle performance is associated with an increase in the 6-min walk test distance and the sensation of dyspnea . There is no additional benefit gained by combining SIMT with SEMT , compared to using SIMT alone A r and omised controlled study of the effects of exercise training in 39 patients with chronic respiratory disability was performed . Exercise training began with six weeks in a rehabilitation centre and was continued at home . The original control group attended the rehabilitation centre after the controlled part of the study . The treated group experienced subjective benefit from rehabilitation . The 12-minute walking distance increased on average from 523 m to 643 m in the treatment group and from 564 m to 607 m in the control group . The treatment effect of 77 m ( SE 33 m ) was significant at the 5 % level . Treadmill exercise performance changed little and resting lung function was unaltered after rehabilitation . The treatment group maintained most of their improvement seven months later and the original control subjects improved after their rehabilitation . The study confirms the beneficial effects of exercise training in the chronically breathless and it suggests that the 12-minute walking distance is a useful index of changes in everyday exercise tolerance PURPOSE Many patients with chronic obstructive pulmonary disease ( COPD ) report dyspnea and fatigue when performing upper limb activities . Unsupported upper limb training has been shown to improve upper limb endurance , but its effects on symptoms and quality of life have not been examined . The aim of this study was to compare the effects of upper limb and lower limb training with lower limb training alone on exercise capacity , symptoms , and quality of life with COPD . METHODS For this study , 38 patients with moderate to severe COPD were r and omly allocated to unsupported upper limb endurance training or to a control group that completed a sham training task . All the patients underwent lower limb endurance training . The 6-minute walk test , the Incremental Unsupported Upper Limb Exercise Test , and the Chronic Respiratory Disease Question naire ( CRQ ) were completed before training and then 6 weeks afterward . Both patients and assessors were blinded to group allocation . RESULTS All the patients reported symptoms associated with upper limb activities on the initial CRQ . Both groups showed significant improvements in all domains of the CRQ and in the 6-minute walk test after training . Only the upper limb training group showed improvement in upper limb endurance time ( 57 + /- 75 vs 2 + /- 58 seconds ; P = .02 ) . There were no significant differences between the groups for 6-minute walk test or any domain of the CRQ . CONCLUSIONS Unsupported upper limb training for patients COPD improves upper limb exercise capacity , but has no additional effect on symptoms or quality of life , as compared with leg training alone . This type of upper limb training may not adequately address the complex interaction between respiratory mechanics and upper limb function OBJECTIVE Compare unsupported ( UAEx ) vs supported ( SAEx ) arm exercise in training of patients with severe chronic airflow obstruction ( CAO ) . DESIGN R and omized trial of UAEx vs SAEx training added to a 10-week outpatient program of lower extremity ( LE ) exercise training , respiratory muscle training , breathing retraining , psychological support , and teaching . SETTING The Lahey Clinic Medical Center , a tertiary referral center . PATIENTS Forty patients with CAO entered the rehabilitation program with 32 completing training and testing . INTERVENTIONS All underwent progressive bicycle ergometer and treadmill training and respiratory muscle training using a threshold inspiratory pressure trainer . Patients were r and omized to progressive SAEx training ( arm cycle ergometer , n = 17 ) or UAEx training ( raising weighted dowel , n = 18 ) . MAIN OUTCOME MEASURES AND RESULTS There was no significant difference in disease severity or exercise capacity between the two groups . Twelve-min walk test , bicycle ergometer power output , and respiratory muscle function improved with no significant difference in improvement between the two groups . Both groups showed similar improvements in arm ergometer testing while those trained with UAEx showed greater improvement in dowel testing ( UAEx > SAEx , p = 0.002 ) . In 17 patients VO2isotime ( time at which patient performed pre-training and post-training tests ) was measured during dowel testing . Only those trained with UAEx showed decreases in VO2isotime ( UAEx trained , p = 0.02 ; SAEx , p = 0.18 ) . VO2 during the last minute of a 2-min period of simple arm elevation was also measured in 17 patients . Only those trained with UAEx showed decreases in VO2 ( UAEx , p = 0.02 ; SAEx , p = 0.20 ) . CONCLUSION We confirm that a pulmonary rehabilitation program incorporating exercise training improves LE and respiratory muscle function . Arm exercise training improved arm activity with greater increases in unsupported arm activity seen in those trained with unsupported arm training . Metabolic cost of UAEx decreased only in those trained with UAEx . As UAEx is typical of activities of daily living in patients with CAO , the changes seen with UAEx training may be of greater clinical significance . Arm training should be incorporated in exercise training and a simple program of UAEx appears the optimal format Different modalities of assisted ventilation improve breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . The aim of this study was to evaluate the effects of the addition of assisted ventilation during exercise training on the outcome of a structured pulmonary rehabilitation programme ( PRP ) in COPD patients . Thirty-three male patients with stable COPD ( mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) 44 ( 16 ) % pred ) , without chronic ventilatory failure , undergoing a 6-week multidisciplinary outpatient PRP including exercise training , were r and omised to training during either mask proportional assist ventilation ( PAV : 18 patients ) or spontaneous breathing ( SB : 15 patients ) . Assessment included exercise tolerance , dyspnoea , leg fatigue , and health-related quality of life ( HRQL ) . Five out of 18 patients ( 28 % ) in the PAV group dropped out due to lack of compliance with the equipment . Both groups showed significant post-PRP improvements in exercise tolerance ( peak work rate difference : 20 ( 95 % Cl 2.4 - 37.6 ) and 14 ( 3.8 % CI to 24.2 ) W in PAV and SB group , respectively ) , dyspnoea and leg fatigue , but not in HRQL , without any significant difference between groups . It is concluded that with the modality and in the patients assessed in this study assisted ventilation during training sessions included in a multidisciplinary PRP was not well tolerated by all patients and gave no additional physiological benefit in comparison with exercise training alone BACKGROUND Exercise training is being promoted increasingly for patients with chronic obstructive pulmonary disease ( COPD ) . Many of these patients experience exercise related arterial desaturation but the clinical importance of these hypoxaemic episodes is not known . QTc dispersion is a marker of myocardial repolarisation abnormalities and there has been much interest in its role as a non-invasive predictor of cardiac arrhythmias and sudden death . However , little is known about the dynamic effects that exercise and hypoxaemia have on QTc dispersion in patients with COPD . METHODS 20 patients with severe COPD ( FEV1 < 40 % predicted ) undertook two 15 minute treadmill tests at a speed calculated to produce a constant workload of 50 % maximum oxygen consumption ( VO2max ) during which they were blindly given either air or 35 % oxygen in r and om order . Physiological measurements taken throughout exercise included 12 lead electrocardiograms from which QTc dispersion values were calculated according to st and ard criteria . Nine of the patients who desaturated with exercise were studied further . A similar degree of hypoxaemia was induced at rest by giving them a titrated mixture of air and oxygen and the changes in QTc dispersion were recorded . RESULTS 11 of the 20 patients developed significant hypoxaemia ( desaturation by > or = 5 % to < 90 % ) with exercise breathing air . There were no significant changes in QTc dispersion with either exercise or hypoxaemia . There were no significant changes in QTc dispersion when comparing those who did and did not desaturate , and those with and without a high baseline QTc dispersion values ( 60 ms ) . Induced hypoxaemia without exercise also failed to worsen QTc dispersion . CONCLUSIONS No evidence was found to suggest that exercise , even when associated with hypoxaemia , causes myocardial repolarisation abnormalities in patients with COPD PURPOSE To compare the effects on exercise capacity and health related quality of life ( HRQoL ) of two exercise programmes ; one programme including endurance training and one including only resistance training and callisthenics . A second purpose was to find out whether the severity of chronic obstructive pulmonary disease ( COPD ) affected the training response and whether the interventions had a long-term effect . METHODS Sixty-three patients were stratified according to severity of COPD and r and omised to two training groups . Group A had a mixed programme including endurance training . Group B had resistance training and callisthenics . All trained twice weekly for 8 weeks . A symptom-limited ergometer test , 12-min walking test , dynamic spirometry , blood gas analysis at rest and HRQoL were measured before and after the training period . Follow-up tests were conducted at 6 and 12 months after training . RESULTS Forty-two patients fulfilled the trial . In group A ( n=20 ) peak exercise capacity increased by 7W ( P<0.001 ) and 12-min walking distance ( 12MWD ) by 50 m ( P<0.01 ) , whereas group B ( n=22 ) did not change in any of these variables . HRQoL did not change significantly in either group . Training response was similar in patients with moderate and severe disease . One year post-training 12MWD had returned to pre-training level in group A , and below pre-training level in group B ( P<0.05 ) . CONCLUSIONS Exercise capacity in patients with severe and moderate COPD improved by intensive endurance training , two sessions a week for 8 weeks . The improvement was however small and HRQoL did not improve . Severity of illness did not affect response to training . The results indicated that the effects of a short endurance training intervention slowed down decline in baseline functional exercise capacity for 1 year Prior studies demonstrate the ability of upper extremity training to increase arm strength and endurance when incorporated into a pulmonary rehabilitation program . However , patients with severe chronic obstructive pulmonary disease ( COPD ) may have transportation or mobility problems that make it difficult to travel to a rehabilitation site to obtain this training . This pilot study was design ed to determine whether a home-based , upper-arm exercise program could increase arm strength and endurance , and decrease perceptions of breathlessness and fatigue during five activities of daily living . Twenty patients with severe COPD ( FEV1 0.80 + /- 0.42 ) were r and omized to an experimental ( n = 10 ) or control group ( n = 10 ) . The experimental-group training included three upper arm exercises five times a week for 8 weeks , with training level incremented during weekly home visits . Control-group subjects were contacted weekly to equalize attention from health care providers . During the upper-extremity endurance test for number of rings moved , no significant differences between groups were seen for interaction or treatment . However , there was a significant interaction between treatment and time for perceived fatigue ( p = 0.0012 ) , with the experimental group perceiving less fatigue during upper arm work than did the control group . No change was seen in perceived breathlessness . Findings of this study suggest that a home-based , upper-arm exercise program can reduce perceptions of fatigue for patients with severe COPD during activities involving upper arm work . Testing in a larger sample is indicated to determine whether this training can also improve ability to perform unsupported arm work |
13,069 | 27,955,685 | Meta-regression analysis showed that duration of follow-up did not have a significant effect on the magnitude of the placebo response and that the strongest predictor of placebo response was subjectivity of the outcome .
Conclusions This is the first study to investigate the temporal changes of placebo response in surgical trials and the first to investigate the sources of heterogeneity of placebo response .
Placebo response in surgical trials was large for subjective outcomes , persisting as a time-invariant effect throughout blinded follow-up .
Therefore , placebo response can not be minimized in these types of outcomes through their appraisal at alternative time points .
The analyses suggest that objective outcomes may be preferable as trial end-points . | Background Underst and ing changes in the placebo arm is essential for correct design and interpretation of r and omized controlled trials ( RCTs ) .
It is assumed that placebo response , defined as the total improvement in the placebo arm of surgical trials , is large ; however , its precise magnitude and properties remain to be characterized .
To the best of our knowledge , the temporal changes in the placebo arm have not been investigated .
The aim of this paper was to determine , in surgical RCTs , the magnitude of placebo response and how it is affected by duration of follow-up . | BACKGROUND Laparoscopic adhesiolysis for chronic abdominal pain is controversial and is not evidence based . We aim ed to test our hypothesis that laparoscopic adhesiolysis leads to substantial pain relief and improvement in quality of life in patients with adhesions and chronic abdominal pain . METHODS Patients had diagnostic laparoscopy for chronic abdominal pain attributed to adhesions ; other causes for their pain had been excluded . If adhesions were confirmed during diagnostic laparoscopy , patients were r and omly assigned either to laparoscopic adhesiolysis or no treatment . Treatment allocation was concealed from patients , and assessors were unaware of patients ' treatment and outcome . Pain was assessed for 1 year by visual analogue score ( VAS ) score ( scale 0 - 100 ) , pain change score , use of analgesics , and quality of life score . Analysis was by intention to treat . FINDINGS Of 116 patients enrolled for diagnostic laparoscopy , 100 were r and omly allocated either laparoscopic adhesiolysis ( 52 ) or no treatment ( 48 ) . Both groups reported substantial pain relief and a significantly improved quality of life , but there was no difference between the groups ( mean change from baseline of VAS score at 12 months : difference 3 points , p=0.53 ; 95 % CI -7 to 13 ) . INTERPRETATION Although laparoscopic adhesiolysis relieves chronic abdominal pain , it is not more beneficial than diagnostic laparoscopy alone . Therefore , laparoscopic adhesiolysis can not be recommended as a treatment for adhesions in patients with chronic abdominal pain Background It is an inherent assumption in r and omised controlled trials that the drug effect can be estimated by subtracting the response during placebo from the response during active drug treatment . Objective To test the assumption of additivity . The primary hypothesis was that the total treatment effect is smaller than the sum of the drug effect and the placebo effect . The secondary hypothesis was that non-additivity was most pronounced in participants with large placebo effects . Methods We used a within-subject r and omised blinded balanced placebo design and included 48 healthy volunteers ( 50 % males ) , mean ( SD ) age 23.4 ( 6.2 ) years . Experimental pain was induced by injections of hypertonic saline into the masseter muscle . Participants received four injections with hypertonic saline along with lidocaine or matching placebo in r and omised order : A : received hypertonic saline/told hypertonic saline ; B : received hypertonic saline+lidocaine/told hypertonic saline ; C : received hypertonic saline+placebo/told hypertonic saline+pain killer ; D : received hypertonic saline+lidocaine/told hypertonic saline+pain killer . The primary outcome measure was the area under the curve ( AUC , mm2 ) of pain intensity during injections . Results There was a significant difference between the sum of the drug effect and the placebo effect ( mean AUC 6279 mm2 ( 95 % CI , 4936–7622 ) ) and the total treatment effect ( mean AUC 5455 mm2 ( 95 % CI , 4585–6324 ) ) ( P = 0.049 ) . This difference was larger for participants with large versus small placebo effects ( P = 0.015 ) , and the difference correlated significantly with the size of the placebo effect ( r = 0.65 , P = 0.006 ) . Conclusion Although this study examined placebo effects and not the whole placebo response as in r and omised controlled trials , it does suggest that the additivity assumption may be incorrect , and that the estimated drug effects in r and omised controlled trials may be underestimated , particularly in studies reporting large placebo responses . The implication s for r and omised controlled trials and systematic review s need to be discussed Background : Endoscopic treatment for gastro-oesophageal reflux disease ( GORD ) is rapidly emerging , but there is a great need for r and omised controlled trials to evaluate the efficacy . Design and setting : A single-centre , double-blind , r and omised , sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system . Patients and interventions : 60 patients with GORD were r and omly assigned to three endoscopic gastroplications ( n = 20 ) , a sham procedure ( n = 20 ) or observation ( n = 20 ) . The research nurse and patients in the active and sham groups were blinded to the procedure assignment . After 3 months , open-label active treatment was offered to all patients . Outcome measures : The primary outcome measures were proton pump inhibitor ( PPI ) use and GORD symptoms , and secondary measures were quality of life , 24-h oesophageal acid exposure , oesophageal manometry and adverse events . Follow-up assessment s were performed at 3 , 6 and 12 months . Results : At 3 months , the percentage of patients who had reduced drug use by ⩾50 % was greater in the active treatment group ( 65 % ) than in the sham ( 25 % ) or observation groups ( 0 % ) ( p<0.02 ) . Symptoms ( heartburn and to a lesser extent regurgitation ) improved more in the active group than in the sham group . Three Short Form-20 quality of life subscales ( role function , general health and bodily pain perception ) improved in the active group versus sham . Oesophageal acid exposure was modestly decreased after active treatment ( p<0.02 ) , but not significantly greater than after the sham procedure ( p = 0.61 ) . The active treatment effects on PPI use , symptoms and quality of life persisted after 6 and 12 months of open-label follow-up ( n = 41 ) , but 29 % of patients were retreated in this period . No serious adverse events occurred . Conclusions : Endoscopic gastroplication , using the Endocinch device , reduced acid-inhibitory drug use , improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure . The effects persisted up to 12 months . However , the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure 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 & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo . Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained with placebo is one‐third of the maximum possible ( and does not vary ) , and that one‐third of patients respond to placebo . The results show that the amount of relief obtained with placebo varies considerably between patients , that 38 % of patients obtained more than 10 % of the maximum possible relief , and 16 % obtained greater than 50 % . In double‐blind , r and omised parallel‐group studies of high quality placebo scores should not vary . Despite these conditions being met the placebo scores did vary . The previous explanation , of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported BACKGROUND Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures , but there is limited evidence to support its use . METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months ' duration and unhealed , as confirmed by magnetic resonance imaging , were r and omly assigned to undergo vertebroplasty or a sham procedure . Participants were stratified according to treatment center , sex , and duration of symptoms ( < 6 weeks or > or = 6 weeks ) . Outcomes were assessed at 1 week and at 1 , 3 , and 6 months . The primary outcome was overall pain ( on a scale of 0 to 10 , with 10 being the maximum imaginable pain ) at 3 months . RESULTS A total of 78 participants were enrolled , and 71 ( 35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group ) completed the 6-month follow-up ( 91 % ) . Vertebroplasty did not result in a significant advantage in any measured outcome at any time point . There were significant reductions in overall pain in both study groups at each follow-up assessment . At 3 months , the mean ( + /-SD ) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3 , respectively ( adjusted between-group difference , 0.6 ; 95 % confidence interval , -0.7 to 1.8 ) . Similar improvements were seen in both groups with respect to pain at night and at rest , physical functioning , quality of life , and perceived improvement . Seven incident vertebral fractures ( three in the vertebroplasty group and four in the placebo group ) occurred during the 6-month follow-up period . CONCLUSIONS We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures , at 1 week or at 1 , 3 , or 6 months after treatment . ( Australian New Zeal and Clinical Trials Registry number , ACTRN012605000079640 . Abstract Objective To investigate whether a sham device ( a vali date d sham acupuncture needle ) has a greater placebo effect than an inert pill in patients with persistent arm pain . Design A single blind r and omised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls . Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study . Setting Academic medical centre . Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale . Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks . Main outcome measures Arm pain measured on a 10 point pain scale . Secondary outcomes were symptoms measured by the Levine symptom severity scale , function measured by Pransky 's upper extremity function scale , and grip strength . Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups , but changes were not different between the groups ( −0.14 , 95 % confidence interval −0.52 to 0.25 , P = 0.49 ) . Changes in severity scores for arm symptoms and grip strength were similar between groups , but arm function improved more in the placebo pill group ( 2.0 , 0.06 to 3.92 , P = 0.04 ) . Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group ( −0.33 ( −0.40 to −0.26 ) v −0.15 ( −0.21 to −0.09 ) , P = 0.0001 ) and on the symptom severity scale ( −0.07 ( −0.09 to −0.05 ) v −0.05 ( −0.06 to −0.03 ) , P = 0.02 ) . Differences were not significant , however , on the function scale or for grip strength . Reported adverse effects were different in the two groups . Conclusions The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in . Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals BACKGROUND Vertebroplasty is commonly used to treat painful , osteoporotic vertebral compression fractures . METHODS In this multicenter trial , we r and omly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement ( control group ) . The primary outcomes were scores on the modified Rol and -Morris Disability Question naire ( RDQ ) ( on a scale of 0 to 23 , with higher scores indicating greater disability ) and patients ' ratings of average pain intensity during the preceding 24 hours at 1 month ( on a scale of 0 to 10 , with higher scores indicating more severe pain ) . Patients were allowed to cross over to the other study group after 1 month . RESULTS All patients underwent the assigned intervention ( 68 vertebroplasties and 63 simulated procedures ) . The baseline characteristics were similar in the two groups . At 1 month , there was no significant difference between the vertebroplasty group and the control group in either the RDQ score ( difference , 0.7 ; 95 % confidence interval [ CI ] , -1.3 to 2.8 ; P=0.49 ) or the pain rating ( difference , 0.7 ; 95 % CI , -0.3 to 1.7 ; P=0.19 ) . Both groups had immediate improvement in disability and pain scores after the intervention . Although the two groups did not differ significantly on any secondary outcome measure at 1 month , there was a trend toward a higher rate of clinical ly meaningful improvement in pain ( a 30 % decrease from baseline ) in the vertebroplasty group ( 64 % vs. 48 % , P=0.06 ) . At 3 months , there was a higher crossover rate in the control group than in the vertebroplasty group ( 51 % vs. 13 % , P<0.001 ) [ corrected ] . There was one serious adverse event in each group . CONCLUSIONS Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group . ( Clinical Trials.gov number , NCT00068822 . Thirty‐four patients with advanced Parkinson 's disease participated in a prospect i ve 24‐month double‐blind , placebo‐controlled trial of fetal nigral transplantation . Patients were r and omized to receive bilateral transplantation with one or four donors per side or a placebo procedure . The primary end point was change between baseline and final visits in motor component of the Unified Parkinson 's Disease Rating Scale in the practically defined off state . There was no significant overall treatment effect ( p = 0.244 ) . Patients in the placebo and one‐donor groups deteriorated by 9.4 ± 4.25 and 3.5 ± 4.23 points , respectively , whereas those in the four‐donor group improved by 0.72 ± 4.05 points . Pairwise comparisons were not significant , although the four‐donor versus placebo groups yielded a p value of 0.096 . Stratification based on disease severity showed a treatment effect in milder patients ( p = 0.006 ) . Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination . Fifty‐six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ( “ off”‐medication dyskinesia ) . Fetal nigral transplantation currently can not be recommended as a therapy for PD based on these results .Ann Neurol IMPORTANCE Revisional laparoscopic surgery after Roux-en-Y gastric bypass ( RYGB ) has been linked to substantial complications and morbidity . OBJECTIVE To investigate the safety and effectiveness of endoscopic gastric plication with the StomaphyX device vs a sham procedure for revisional surgery in RYGB patients to reduce regained weight . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , single-center , r and omized , single-blinded study from July 2009 through February 2011 , evaluating revisional surgery using StomaphyX was conducted in patients with initial weight loss after RYGB performed at least 2 years earlier . We planned for 120 patients to be r and omized 2:1 to multiple full-thickness plications within the gastric pouch and stoma using the StomaphyX device with SerosFuse fasteners or a sham endoscopic procedure and followed up for 1 year . The primary efficacy end point was reduction in pre-RYGB excess weight by 15 % or more excess body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) loss and BMI less than 35 at 12 months after the procedure . Adverse events were recorded . RESULTS Enrollment was closed prematurely because preliminary results indicated failure to achieve the primary efficacy end point in at least 50 % of StomaphyX-treated patients . One-year follow-up was completed by 45 patients treated with StomaphyX and 29 patients in the sham treatment group . Primary efficacy outcome was achieved by 22.2 % ( 10 ) with StomaphyX vs 3.4 % ( 1 ) with the sham procedure ( P < .01 ) . Patients undergoing StomaphyX treatment experienced significantly greater reduction in weight and BMI at 3 , 6 , and 12 months ( P ≤ .05 ) . There was one causally related adverse event with StomaphyX , that required laparoscopic exploration and repair . CONCLUSIONS AND RELEVANCE StomaphyX treatment failed to achieve the primary efficacy target and result ed in early termination of the study . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00939055 While r and omized , placebo-controlled double-blinded trials have become the pharmacological st and ard over the last 60 years , the gain in knowledge of the mechanisms behind the placebo response in recent years has raised substantial concerns about the appropriateness of some of its underlying assumptions . The following questions will be addressed : Is the assumed model of drug and placebo being additive ( still ) valid ? Does the likelihood of receiving active treatment affect the placebo response ? What is the size of the placebo response in " active comparator studies " ? Minimizing the placebo response/maximizing the drug-placebo difference ? How to maximize the placebo response in daily medicine ? What is the placebo response with personalized medicines in the future ? This and other questions require answers that can only be generated with more experimental studies on the placebo response and with thorough meta- and re-analyses of placebo responses in clinical trials OBJECTIVE To evaluate the effectiveness of tidal irrigation ( TI ) in comparison with a well-matched sham irrigation ( SI ) procedure as a treatment for knee osteoarthritis ( OA ) . METHODS One hundred eighty subjects with knee OA were r and omized to receive TI or SI , with clinical followup over the ensuing 12 months . The primary outcomes of interest were change in pain and function , as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Subjects and the nurse assessor were blinded , and success of blinding was assessed . RESULTS Although the study groups were otherwise comparable , the baseline WOMAC pain and physical functioning scores were higher ( worse ) in the SI group . After adjustment for baseline , there were no differences between the effects Palatal implants have been used to treat snoring and mild to moderate obstructive sleep apnea ( OSA ) . Two previous controlled trials have published conflicting results regarding the effects of palatal implants on objective outcome measures , although they both could demonstrate superiority over placebo . The aim of the present study was to assess the effects of palatal implants in patients with mild to moderate sleep apnea in a r and omised , placebo-controlled trial . Twenty-two patients with mild to moderate OSA ( AHI 18 ± 5 , BMI 28 ± 3 , age 51 ± 13 years ) due to palatal obstruction were enrolled in this r and omised , double-blind , placebo-controlled trial . Respiratory parameters and sleep efficiency ( evaluated by polysomnography ) , snoring ( evaluated by the bed partner ) , and daytime sleepiness ( evaluated by ESS ) were assessed before and 90 days after surgery . One patient in each group did not show up for follow-up . The AHI , HI and LSAT showed statistically significant improvement in the treatment group ( p < 0.05 ) . Snoring as rated by bed partners also showed statistically significant improvement within the treatment group ( p = 0.025 ) . There was no statistical difference when comparing the means of the treatment group with the placebo group . There were no peri- or post-operative complications and no extrusions during the follow-up period . The study supports the idea that palatal implants lead to a reduction in respiratory events in patients with mild to moderate OSA , although a statistically significant superiority of palatal implants over placebo could not be demonstrated in this trial & NA ; A study was conducted to determine whether changes in expected pain levels , desire for pain relief , or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms . Twenty‐six women with IBS were exposed to rectal stimulation ( 35 or 55 mmHg for 30 s ) and tested under natural history ( NH ) , rectal placebo ( RP ) and rectal lidocaine ( RL ) conditions . During all conditions , 16 patients were given saline intravenously ( to test for a placebo effect ) and 10 patients were given naloxone intravenously ( to test naloxone antagonism of the placebo effect ) on a double blind basis . Patients rated expected pain level , desire for pain relief and anxiety at 2 and 22 min after the onset of NH , RP , and RL conditions and they rated actual pain intensity at 5‐min intervals for 40 min . There was a large and significant placebo effect ( P<0.001 ) that increased over time . Ratings of expected pain levels , desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session . These changes suggest that a reduction in negative emotions may be central to placebo effects . There was no significant difference between psychological mediators ( desire , expectation , anxiety ) or the placebo effect in the saline and naloxone groups , indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinical ly related paradigm Subjects were given varying doses of a placebo , consisting of decaffeinated coffee , with double-blind or deceptive instructions . Deceptive administration simulated clinical situations in that subjects were led to believe that they were receiving an active drug . In contrast , subjects in double-blind conditions were aware that they might receive a placebo . Double-blind and deceptive administration of the placebo produced different , and in some instances , opposite effects on pulse rate , systolic blood pressure , and subjective mood . Deceptive administration produced an increase in pulse rate , whereas double-blind administration did not . A theoretically predicted curvilinear effect on systolic blood pressure , alertness , tension , and certainty of having consumed caffeine was confirmed with deceptive administration , but not with double-blind administration . Double-blind administration produced curves in the opposite direction on each of these variables . The effects of the placebo on motor performance varied as a function of subject 's beliefs about the effects of caffeine . These data challenge the validity of double-blind experimental design s and suggest that this common method of drug assessment may lead to spurious conclusions BACKGROUND Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis , but it is unclear how the procedure achieves this result . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee . METHODS A total of 180 patients with osteoarthritis of the knee were r and omly assigned to receive arthroscopic débridement , arthroscopic lavage , or placebo surgery . Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope . Patients and assessors of outcome were blinded to the treatment-group assignment . Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores -- three on scales for pain and two on scales for function-- and one objective test of walking and stair climbing . A total of 165 patients completed the trial . RESULTS At no point did either of the intervention groups report less pain or better function than the placebo group . For example , mean ( + /-SD ) scores on the Knee-Specific Pain Scale ( range , 0 to 100 , with higher scores indicating more severe pain ) were similar in the placebo , lavage , and débridement groups : 48.9+/-21.9 , 54.8+/-19.8 , and 51.7+/-22.4 , respectively , at one year ( P=0.14 for the comparison between placebo and lavage ; P=0.51 for the comparison between placebo and débridement ) and 51.6+/-23.7 , 53.7+/-23.7 , and 51.4+/-23.2 , respectively , at two years ( P=0.64 and P=0.96 , respectively ) . Furthermore , the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinical ly meaningful difference . CONCLUSIONS In this controlled trial involving patients with osteoarthritis of the knee , the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure In order to investigate external factors that may influence the magnitude of placebo analgesia as well as psychological factors that mediate placebo analgesia , 13 irritable bowl syndrome ( IBS ) patients rated evoked rectal distension and cutaneous heat pain under the conditions of natural history ( NH ) , rectal placebo ( RP ) , rectal nocebo ( RN ) , rectal lidocaine ( RL ) and oral lidocaine ( OL ) . Patients were given verbal suggestions for pain relief and rated expected pain levels and desire for pain relief for both evoked visceral and cutaneous pain , respectively . Large reductions in pain intensity and pain unpleasantness ratings were found in the RP , RL and OL condition as compared to the natural history condition , whereas no significant difference in pain reduction between the three treatment conditions was found . Ratings during RN and NH were not statistically different . Compared to a previous study , which shows that rectal lidocaine reverses visceral and cutaneous hyperalgesia , these results suggest that adding a verbal suggestion for pain relief can increase the magnitude of placebo analgesia to that of an active agent . Since IBS patients rate these stimuli as much higher than do normal control subjects and since placebo effects were very large , they probably reflect anti‐hyperalgesic mechanisms to a major extent . Expected pain levels and desire for pain relief accounted for large amounts of the variance in visceral pain intensity in the RP , RL , and OL condition ( up to 81 % ) , and for lower amounts of the variance in cutaneous pain intensity . Hence , the combination of expected pain levels and desire for pain relief may offer an alternative means of assessing the contribution of placebo factors during analgesia Background : Plantar calluses are a common cause of foot pain , which can have a detrimental impact on the mobility and independence of older people . Scalpel debridement is often the first treatment used for this condition . Our aim was to evaluate the effectiveness of scalpel debridement of painful plantar calluses in older people . Methods : This study was a parallel-group , participant and assessor-blinded r and omized trial . Eighty participants aged 65 years and older with painful forefoot plantar calluses were recruited . Participants were r and omly allocated to one of two groups : either real or sham scalpel debridement . Participants were followed for six weeks after their initial intervention appointment . The primary outcomes measured were the difference between groups in pain ( measured on a 100-mm visual analogue scale ) immediately post-intervention , and at one , three and six weeks post-intervention . Results : Both the real debridement and sham debridement groups experienced a reduction in pain when compared with baseline . Small , systematic between-group differences in pain scores were found at each time point ( between 2 and 7 mm favoring real scalpel debridement ) ; however , none of these were statistically significant and none reached a level that could be considered clinical ly worthwhile . Scalpel debridement caused no adverse events . Conclusions : The benefits of real scalpel debridement for reducing pain associated with forefoot plantar calluses in older people are small and not statistically significant compared with sham scalpel debridement . When used alone , scalpel debridement has a limited effect in the short term , although it is relatively inexpensive and causes few complications . However , these findings do not preclude the possibility of cumulative benefits over a longer time period or additive effects when combined with other interventions . Trial registration : Australian Clinical Trials Registry ( ACTRN012606000176561 ) |
13,070 | 22,209,349 | In general , more intensive interventions and those with combined approaches including medications and follow-up counseling achieved the best outcomes .
The quit rates from these studies and the relative effectiveness of different intervention approaches are consistent with the general smoking cessation literature .
However , in most studies , treatment effects were of short duration , and absolute quit rates were low , leaving the vast majority of older smokers at high risk for smoking-related health conditions . | OBJECTIVES Cigarette smoking poses substantial health risks at any age , but is particularly dangerous for older smokers , who are already at heightened risk for various health conditions .
Studies suggest that older smokers are motivated to quit and succeed , but few of these have been r and omized controlled trials .
There is a need to systematic ally evaluate the research on effective interventions in older smokers . | Background : The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large r and omised controlled trials . Methods : This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial ( DLCST ) , a 5-year r and omised controlled trial comprising 4104 subjects ; 2052 subjects received annual low-dose CT scan ( CT group ) and 2052 received no intervention ( control group ) . Participants were healthy current and former smokers ( > 4 weeks since smoking cessation ) with a tobacco consumption of > 20 pack years . Smoking habits were determined at baseline and at annual screening . Smoking status was verified using exhaled carbon monoxide levels . Lung function tests , nicotine dependency and motivation to quit smoking were assessed . Quit rates and relapse rates were determined at 1-year follow-up for all subjects . Results : At 1 year the quit rates among smokers were 11.9 % in the CT group and 11.8 % in the control group ( p = 0.95 ) . Relapse rates for former smokers were 10.0 % and 10.5 % in the CT and control groups , respectively ( p = 0.81 ) . Significant predictors ( p<0.05 ) for smoking cessation were : high motivation to quit , low dependency , low ratio of forced expiratory volume in 1 s to forced vital capacity , low pack years , higher age , longer period of abstinence and CT findings necessitating 3-month repeat CT scans . Conclusions : Overall , quit rates were similar in the CT and control group at 1-year follow-up , with a net quit rate of 6.0 % . Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later AIMS Tobacco dependence treatments achieve abstinence rates of 25 - 30 % at 1 year . Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder . The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age , and to determine if gender differences in efficacy existed . DESIGN Open r and omized clinical trial . SETTING A free-st and ing , smoking treatment research clinic . PARTICIPANTS A total of 402 smokers of > or = 10 cigarettes per day , all 50 years of age or older . INTERVENTION Participants completed a 12-week treatment that included group counseling , nicotine replacement therapy ( NRT ) and bupropion . Participants , independent of smoking status , were then assigned r and omly to follow-up conditions : ( i ) st and ard treatment ( ST ; no further treatment ) ; ( ii ) extended NRT ( E-NRT ; 40 weeks of nicotine gum availability ) ; ( iii ) extended cognitive behavioral therapy ( E-CBT ; 11 cognitive behavioral sessions over a 40-week period ) ; or ( iv ) E-CBT plus E-NRT ( E-combined ; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability ) . MEASUREMENTS Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24 , 52 , 64 and 104 . FINDINGS The most clinical ly important findings were significant main effects for treatment condition , time and the treatment x time interaction . The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [ ( week 24 ( 58 % ) , 52 ( 55 % ) , 64 ( 55 % ) and 104 ( 55 % ) ] , and was significantly more effective than E-NRT and ST across that period . No other treatment condition was significantly different to ST . No effects for gender were found . CONCLUSIONS Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women . NRT does not add to the efficacy of extended CBT , and may hamper its efficacy . Research is needed to determine if these results can be replicated in a sample with a greater range of ages , and improved upon with the addition of medications other than NRT BACKGROUND Although older adults can achieve significant health benefits from smoking cessation , few programs have specifically targeted this population . This study tested the effectiveness of an office-based smoking cessation program tailored to midlife and older smokers . METHODS This paper describes a r and omized controlled trial comparing usual care with physician-delivered brief quit-smoking advice and counseling for midlife and older smokers ( ages 50 - 74 ) . Outpatient medical practice s assigned to the Immediate Intervention ( experimental ) condition were trained to deliver brief quit-smoking advice and counseling . Delayed Intervention ( control ) practice s followed usual care procedures . Thirty-nine practice s accruing five or more patients per practice were included in the analyses . RESULTS Using conservative measure of quitting , self-reported quit rates at 6-month follow-up were 15.41 % for the Immediate Intervention group versus 8.16 % of subjects in the Delayed Intervention group ( P < 0.005 ) . Baseline subject ( N = 659 ) characteristics related to 6-month abstinence included number of previous quit attempts , quitting for 24 hr in the past year , desire to quit , confidence in quitting , perceived health benefits , and lower nicotine dependence . CONCLUSIONS Smoking abstinence was significantly increased by training physicians and key office and clinical staff to intervene with older smokers . Brief interventions are tailored to this age cohort can be successfully and efficaciously integrated into routine care The impact of smoking cessation on coronary heart disease ( CHD ) and lung cancer was assessed after 10.5 years of follow-up in the 12,866 men in the Multiple Risk Factor Intervention Trial ( MRFIT ) . Those men who died of lung cancer ( n = 119 ) were either cigarette smokers at entry or ex-smokers ; no lung cancer deaths occurred among the 1,859 men who reported never smoking cigarettes . The risk of lung cancer for smokers , adjusted for selected baseline variables using a Cox proportional hazards model , increased as the number of cigarettes smoked increased ( B = 0.0203 , SE = 0.0076 ) . There was not the same grade d response for CHD among smokers at entry . The risk of CHD death was greater among smokers than nonsmokers ( RR = 1.57 ) ( B = -0.0034 , S.E. = 0.0048 ) . After one year of cessation , the relative risk of dying of CHD for the quitters as compared to non-quitters ( RR = 0.63 ) was significantly lower even after adjusting for baseline differences and changes in other risk factors . The relative risk for smokers who quit for at least the first three years of the trial was even lower compared to non-quitters ( RR = 0.38 ) . However , the relative risk for lung cancer for quitters versus non-quitters was close to 1 both for quitters at 12 months and at three years . These data support the benefits of cessation in relation to CHD and are consistent with other epidemiologic studies which suggest that the lag time for a beneficial effect of smoking cessation on lung cancer may be as long as 20 years OBJECTIVE : To evaluate the relative effectiveness of two self-help smoking interventions as adjuncts to a self-help manual and telephone support service ( hotline ) for older smokers . DESIGN : Subjects were stratified on baseline variables and r and omised to one of two treatment conditions in a methods development study . SUBJECTS : 177 community-dwelling smokers aged 60 years and older . INTERVENTIONS : All subjects received a self-help manual and access to a smokers ' telephone hotline . Subjects also received either mailings ( Letters condition ) or counselling telephone calls ( Proactive condition ) at four and eight weeks after enrollment . MAIN OUTCOME MEASURES : Use of the hotline and prevalence of abstinence lasting at least 48 hours ( verified by a " significant other " ) were assessed at three and six months for the full sample . Seven-day abstinence was calculated for comparison with previous research . A sub sample of 91 subjects was followed up at 12 months . RESULTS : Overall abstinence rates for the two conditions were in the range of typical self-help interventions . Men were more likely to be abstinent than women at follow up at three and six months . A significant gender x treatment interaction was found , with abstinence rates higher for men in the Letters condition , and women in the Proactive condition . Hotline use was high , with nearly half of subjects calling by 12 months . CONCLUSION : Both interventions appear promising for older smokers , but may be differentially effective for men and women . Older smokers will use a hotline ; whether Letters and Proactive interventions can improve on manual and hotline effectiveness rates alone is being tested in a subsequent controlled trial CONTEXT Most smokers with mental illness do not receive tobacco cessation treatment . OBJECTIVE To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder ( PTSD ) improves long-term smoking abstinence rates . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009 . INTERVENTION Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians ( integrated care [ IC ] ) vs referral to Veterans Affairs smoking cessation clinics ( SCC ) . Patients received smoking cessation treatment within 3 months of study enrollment . MAIN OUTCOME MEASURES Smoking outcomes included 12-month bioverified prolonged abstinence ( primary outcome ) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals . Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome . Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Question naire 9 , respectively , to determine if IC participation or quitting smoking worsened psychiatric status . RESULTS Integrated care was better than SCC on prolonged abstinence ( 8.9 % vs 4.5 % ; adjusted odds ratio , 2.26 ; 95 % confidence interval [ CI ] , 1.30 - 3.91 ; P = .004 ) . Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence ( 78/472 [ 16.5 % ] vs 34/471 [ 7.2 % ] , P < .001 ) and remained significant at 18 months ( 86/472 [ 18.2 % ] vs 51/471 [ 10.8 % ] , P < .001 ) . Number of counseling sessions received and days of cessation medication used explained 39.1 % of the treatment effect . Between baseline and 18 months , psychiatric status did not differ between treatment conditions . Posttraumatic stress disorder symptoms for quitters and nonquitters improved . Nonquitters worsened slightly on the Patient Health Question naire 9 relative to quitters ( differences ranged between 0.4 and 2.1 , P = .03 ) , whose scores did not change over time . CONCLUSION Among smokers with military-related PTSD , integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment result ed in greater prolonged abstinence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118534 There is new evidence that smokers of all ages benefit from cessation of smoking . Although most older smokers , like younger smokers , prefer to quit on their own , at the time this project was started , there were no material s or programs targeted to older smokers . Using the literature , focus groups with older smokers and a national survey of older smokers , we created Clear Horizons , a self-help guide for older smokers , and a telephone counseling protocol tailored to the needs of older smokers ( age 50 - 74 ) . Smokers were recruited from around the United States and assigned r and omly to a control guide , Clearing the Air , Clear Horizons alone or Clear Horizons and two counselor calls . Follow-up of nearly 2000 smokers was conducted by telephone 3 , 6 , 12 and 24 months after delivery of the self-help guides . This report focuses primarily on results at 3 months because that was the measurement for reactions to the interventions . At the 3 month interview , those in the tailored interventions rated their guides more highly than did those in the control group . They also read more of their guides and were more likely to reread them . Quit rates were significantly higher among smokers who received a combination of the tailored guide and telephone counseling . At 3 months , the combination of the guide and telephone counseling was most effective in helping smokers to quit . By 12 months , both the tailored guide alone and the tailored guide and calls groups had higher quit rates than the control guide but were not statistically different from one another BACKGROUND Smoking has a well-documented detrimental effect on risk for myocardial infa rct ion and stroke , but less information is available regarding peripheral artery disease ( PAD ) , particularly among women . OBJECTIVE To prospect ively assess the association of current smoking status , cumulative smoking exposure , and smoking cessation with incident symptomatic PAD in women . DESIGN Prospect i ve cohort study . SETTING U.S. female health care professionals in the Women 's Health Study . PARTICIPANTS 39,825 women with no cardiovascular disease who were prospect ively followed for a median of 12.7 years . MEASUREMENTS Incidence of symptomatic PAD . Cox proportional hazards models were used to compare PAD risk across smoking categories . RESULTS 178 confirmed PAD events occurred . Across the 4 smoking categories ( never , former , < 15 cigarettes/d , and ≥15 cigarettes/d ) , age-adjusted incidence rates were 0.12 , 0.34 , 0.95 , and 1.63 per 1000 person-years of follow-up , respectively . Multivariate adjustment had little effect on this relationship ( adjusted hazard ratios [ HRs ] , 3.14 [ 95 % CI , 2.01 to 4.90 ] , 8.93 [ CI , 5.02 to 15.89 ] , and 16.95 [ CI , 10.77 to 26.67 ] , respectively , vs. women who never smoked ) . Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels among women with available blood sample s ( 28,314 participants , 117 events ) attenuated risk estimates ( HR , 5.58 [ CI , 2.61 to 11.93 ] for smoking < 15 cigarettes/d and 9.52 [ CI , 5.17 to 17.53 ] for smoking ≥15 cigarettes/d ) . Lifetime exposure showed a strong dose-response relationship ; fully adjusted HRs for smoking abstinence of fewer than 10 , 10 to 29 , and 30 or more pack-years were 2.52 ( CI , 1.49 to 4.25 ) , 6.75 ( CI , 4.33 to 10.52 ) , and 11.09 ( CI , 6.94 to 17.72 ) , respectively . Compared with current smokers , the adjusted HRs for fewer than 10 years , 10 to 20 years , more than 20 years , or lifelong abstinence were 0.39 ( CI , 0.24 to 0.66 ) , 0.28 ( CI , 0.17 to 0.46 ) , 0.16 ( CI , 0.10 to 0.26 ) , and 0.08 ( CI , 0.05 to 0.12 ) , respectively . LIMITATION The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease . CONCLUSION Among initially healthy women , smoking is a potent risk factor for symptomatic PAD and was associated with sub clinical inflammation . Smoking cessation substantially reduces risk for PAD , but an increased occurrence of PAD persists even among former smokers who maintain abstinence . PRIMARY FUNDING SOURCE The National Heart , Lung , and Blood Institute and National Cancer Institute This study was undertaken to evaluate a tailored smoking cessation intervention , which is applicable to Korean culture , using the Agency for Health Care Policy and Research ( AHCPR ) guideline . On-site counselors provided brief nurse-assisted smoking cessation counseling , including follow-up telephone support , to prevent a relapse in 200 r and omly assigned smoking patients . These patients were referred by their physicians regardless of their willingness in smoking cessation in the outpatient department at a university hospital . Nicotine replacement therapy was not provided . Another 201 patients served as a control . After 5 months , current smoking cessation was self-reported on the phone and vali date d later by a portable carbon monoxide analyzer . After 5 months , the participants in the intervention group were no more likely to quit smoking than the control group . A subgroup analysis by age showed that the intervention among 166 younger smokers ( aged 49 or less ) was significantly more likely to be effective { risk ratio = 5.76 [ 95 % confidence interval ( CI ) 1.34 - 24.74 ] } than it was among 235 older smokers ( aged 50 or more ) [ risk ratio = 1.03 ( 95 % CI 0.53 - 1.99 ) ] . This study suggests a smoking cessation intervention using the AHCPR guideline tailored for Koreans , is effective for assisting out patients aged 49 or younger to quit smoking This study aim ed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking . Using a single general practitioner visit backed up by a practice nurse , 14 % of the smokers had discontinued the habit 6 months after the intervention period . The intervention group also showed some improvements in a st and ardized measure of breathlessness Data from a r and om sample of 8,191 men and women from 6 U.S. cities are used to fit a model describing the effects of cumulative and current cigarette smoking on pulmonary function . The data show that smokers suffer an irreversible loss of FVC and FEV1 , which is described by a linear function of their cumulative cigarette smoking as measured in pack-years . For a typical male 173 cm tall , the estimated loss of FEV1 is 7.4 ml for each pack-year smoked . For a typical woman , 161 cm tall , the estimated effect is 4.4 ml per pack-year . Current cigarette smoking adds an acute deficit over and above the cumulative effect of lifetime smoking . For any lifetime pack-years , exsmokers have higher levels of FEV1 , 123 ml for a typical man , 107 ml for a typical woman , than do current smokers of a pack per day ( p less than 0.001 ) . A man who starts smoking one pack of cigarettes per day at 25 yr of age would at age 60 , after 35 pack-years of exposure , have an expected FEV1 equal to that of a man 69.4 yr of age who had never smoked . If he stopped smoking at 60 yr of age , his expected level would increase to that of a 66.5-yr-old never-smoker . This model therefore estimates how much lung function is irreversibly lost by smoking , estimates how much could be regained with cessation of smoking , and predicts the future loss of lung function in both cases OBJECTIVE To prospect ively examine the relationship of time since stopping smoking with risk of stroke in middle-aged women . DESIGN An ongoing prospect i ve cohort of women with 12 years ' follow-up data ( 1976 to 1988 ) , in which information on smoking habits was up date d every 2 years by postal question naire . POPULATION STUDIED A total of 117,006 female registered nurses aged 30 to 55 years in 1976 and free of coronary heart disease , stroke , and cancer at baseline . MAIN OUTCOME MEASURES Incident strokes ( fatal and nonfatal ) , further subdivided into ischemic stroke , subarachnoid hemorrhage , and cerebral hemorrhage . RESULTS The age-adjusted relative risk of total stroke among current smokers compared with never smokers was 2.58 ( 95 % confidence interval , 2.08 to 3.19 ) . The corresponding relative risk among former smokers was 1.34 ( 95 % confidence interval , 1.04 to 1.73 ) . For total and ischemic stroke , the excess risks among former smokers largely disappeared from 2 to 4 years after cessation . The same patterns of decline were observed regardless of number of cigarettes smoked , the age at starting , or the presence of other risk factors for stroke . CONCLUSIONS The risk of suffering among cigarette smokers declines soon after cessation and the benefits are independent of the age at starting and the number of cigarettes smoked per day This paper presents inital outcomes of a r and omised controlled trial evaluating the efficacy of a self help intervention combining a quit smoking guide design ed for older adults with a series of personalised computer tailored cessation messages . These messages were delivered through a state prescription plan , similar to the prescription and pharmacy benefit management plans widely used by managed care organisations to control pharmacy costs and improve appropriate drug use . Prescription plans offer a channel which is especially appropriate for older adults since they consume a disproportionate share of medications.1 A previous study showed that the Clear Horizons guide,2 targeted to the special quitting needs and barriers of older adults , was more OBJECTIVE To investigate relationships between cigarette smoking and pulmonary function in elderly men and women . DESIGN Cross-sectional analysis of baseline data from a prospect i ve , population -based study of risk factors , pre clinical , and overt cardiovascular and pulmonary disease . SETTING Defined communities in Forsyth County , North Carolina ; Pittsburgh , Pa ; Sacramento County , California ; and Washington County , Maryl and . POPULATION A total of 5201 noninstitutionalized men and women 65 years of age and older . MAIN OUTCOME MEASURES Pulmonary function ; means of forced expiratory volume in 1 second ( FEV1 ) and forced vital capacity and prevalence of low FEV1 levels . RESULTS Prevalence of cigarette smoking was 10 % to 20 % and higher in women than men and in blacks than whites . Forced vital capacity and FEV1 levels were related positively to height and white race and negatively to age and waist girth . Age- and height-adjusted FEV1 means were 23 % and 18 % lower in male and female current smokers , respectively , than in never smokers but not reduced in never smokers currently living with a smoker . Smokers who quit before age 40 years had FEV1 levels similar to never smokers , but FEV1 levels were lower by 7 % and 14 % in smokers who quit at ages 40 to 60 years and older than 60 years , respectively . Lung function was related inversely to pack-years of cigarette use . Prevalence rates of impaired lung function were highest in current smokers and lowest in never smokers . Regression coefficients for the smoking variables were smaller in persons without cardiovascular or respiratory conditions than in the total cohort . CONCLUSIONS Cigarette smoking is associated with reduced pulmonary function in elderly men and women . However , smokers who quit , even after age 60 years , have better pulmonary function than continuing smokers Smoking cessation has immediate health benefits ; however , the efficacy of smoking cessation interventions among older adults and women has received limited research attention . The original Women 's Initiative for Nonsmoking ( WINS ) study was a r and omized controlled trial that tested the efficacy of a smoking cessation intervention for Bay Area women hospitalized with cardiovascular disease . The current study , which used the WINS data set , compares participants 62 and older with those younger than 62 years . The sample ( n=277 ) contained 136 older smokers and 141 younger smokers . At the 6-month follow-up , 52.1 % of older smokers had quit smoking compared with 40.6 % of younger smokers . At the 12-month follow-up , 52.0 % of older smokers had quit smoking compared with 38.1 % of younger smokers . The difference at 12 months was statistically significant , and a Kaplan-Meier survival analysis further supported these findings . Clinicians should be sure to also include older smokers in smoking assessment s and smoking cessation interventions OBJECTIVE To examine whether reimbursement for Provider Counseling , Pharmacotherapies , and a telephone Quitline increase smoking cessation relative to Usual Care . STUDY DESIGN R and omized comparison trial testing the effectiveness of four smoking cessation benefits . SETTING Seven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate . PARTICIPANTS There were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months . INTERVENTION(S ) ( 1 ) Usual Care , ( 2 ) reimbursement for Provider Counseling , ( 3 ) reimbursement for Provider Counseling with Pharmacotherapy , and ( 4 ) telephone counseling Quitline with nicotine patch . MAIN OUTCOME MEASURE Seven-day self-reported cessation at 6- and 12-month follow-ups . PRINCIPAL FINDINGS Unadjusted quit rates assuming missing data = smoking were 10.2 percent ( 9.0 - 11.5 ) , 14.1 percent ( 11.7 - 16.5 ) , 15.8 percent ( 14.4 - 17.2 ) , and 19.3 percent ( 17.4 - 21.2 ) at 12 months for the Usual Care , Provider Counseling , Provider Counseling + Pharmacotherapy , and Quitline arms , respectively . Results were robust to sociodemographics , smoking history , motivation , health status , and survey nonresponse . The additional cost per quitter ( relative to Usual Care ) ranged from several hundred dollars to $ 6,450 . CONCLUSIONS A telephone Quitline in conjunction with low-cost Pharmacotherapy was the most effective means of reducing smoking in the elderly |
13,071 | 28,164,026 | This study demonstrates the accuracy of crowdsourcing for systematic review citations screening , with retention of all eligible articles and a significant reduction in the work required from the investigative team .
Together , these two findings suggest that crowdsourcing could represent a significant advancement in the area of systematic review . | BACKGROUND Completing large systematic review s and maintaining them up to date poses significant challenges .
This is mainly due to the toll required of a small group of experts to screen and extract potentially eligible citations .
Automated approaches have failed so far in providing an accessible and adaptable tool to the research community .
Over the past decade , crowdsourcing has become attractive in the scientific field , and implementing it in citation screening could save the investigative team significant work and decrease the time to publication . | 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 ) < 30 ng/ml , mean 24.2 ± 4.8 ng/ml ) 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 < .001 ) , yet only 48 % of the vitamin group became vitamin D sufficient with this dosing . No between-group differences were found in the changes of 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 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 Objectives : Vitamin D is critical for skeletal health ; hypovitaminosis D is common in pediatric inflammatory bowel disease ( IBD ) , yet optimal repletion therapy is not well studied . We aim ed to conduct a pilot trial comparing the efficacy of 2 vitamin D regimens of weekly dosing for the repletion of hypovitaminosis D in pediatric IBD . Methods : Subjects identified from our IBD clinic with 25-hydroxyvitamin D ( 25[OH]D ) concentrations < 30 ng/mL were r and omized to 10,000 ( n = 18 ) or 5000 ( n = 14 ) IU of oral vitamin D3/10 kg body weight per week for 6 weeks . Serum 25(OH)D , Ca , and parathyroid hormone concentrations were measured at baseline , week 8 , and week 12 . Results : In the higher dosing group , serum 25(OH)D increased from 23.7 ± 8.5 ng/mL at baseline to 49.2 ± 13.6 ng/mL at 8 weeks ; P < 0.001 . In the lower dosing group , serum 25(OH)D increased from 24.0 ± 7.0 ng/mL at baseline to 41.5 ± 9.6 ng/mL at 8 weeks ; P < 0.001 . At 12 weeks , serum 25(OH)D concentrations were 35.1 ± 8.4 and 30.8 ± 4.2 ng/mL for the higher and lower dose regimens , respectively . Mean serum Ca and parathyroid hormone concentrations did not significantly change during the study . No patient exhibited hypercalcemia , and no serious adverse events occurred . Conclusions : Both treatment arms were safe and effective at normalizing vitamin D nutriture in pediatric IBD . Although significant repletion of 25(OH)D concentration was achieved in both dosing groups at 8 weeks , this effect was lost by the 12-week follow-up . Maintenance vitamin D therapy following initial repletion is likely required to maintain long-term normalized vitamin D status Objectives : The aim of this study was to investigate the 25-hydroxyvitamin D [ 25(OH)D ] status of children with growing pains and to evaluate the efficacy of vitamin D treatment on the resolution of pain symptoms . Subjects and Methods : One hundred and twenty children with growing pains were included in a prospect i ve cohort study . Serum 25(OH)D and bone mineral levels were measured in all subjects at the time of enrollment . The pain intensity of those with vitamin D deficiency was measured using a pain visual analog scale ( VAS ) . After a single oral dose of vitamin D , the pain intensity was remeasured by means of the VAS at 3 months . The 25(OH)D levels and VAS scores before and after oral vitamin D administration were compared by means of a paired Student 's t test . Results : In the 120 children with growing pains , vitamin D insufficiency was noted in 104 ( 86.6 % ) . Following vitamin D supplementation , the mean 25(OH)D levels increased from 13.4 ± 7.2 to 44.5 ± 16.4 ng/ml , the mean pain VAS score decreased from 6.8 ± 1.9 to 2.9 ± 2.5 cm ( a mean reduction of -3.8 ± 2.1 , p < 0.001 ) and the difference was statistically significant . Conclusion : Supplementation with oral vitamin D result ed in a significant reduction in pain intensity among these children with growing pains who had hypovitaminosis Abstract Objective : The objective of this study was to evaluate the relationship between 25(OH)D , Vitamin D Binding Protein ( DBP ) , and free vitamin D in premature infants . Methods : Thirty-two infants < 32 weeks ’ gestation were r and omized to two different levels of vitamin D3 supplementation ( 400 vs. 800 IU/day ) . 25(OH)D levels were measured by LC-MS/MS ; DBP was measured by vali date d ELISA . Free vitamin D was calculated using molar ratios of 25(OH)D and DBP . The Wilcoxon signed rank test was used to compare DBP , free D and 25(OH)D levels ; Spearman ’s correlation coefficients were used to assess correlations . Results : The mean gestational age at birth was 30.5 weeks ; mean birth weight was 1405 g. Mean 25(OH)D levels at birth were 17.3 ng/mL ; DBP levels were 297 mg/L , and estimated free vitamin D levels were 18.9 . There was a statistically significant change in 25(OH)D levels after 8 weeks ( 24.6 vs. 39.1 ng/mL in the 400 vs. 800 group , respectively , p=0.02 ) . DBP levels from birth to 8 weeks showed a statistically significant decrease ( 267 vs. 208 , p=0.04 ) . Estimated free 25(OH)D concentrations increased over the study period , from 18.9 at birth to 64.7 at 8 weeks of age ( p=0.0001 ) . Free vitamin D levels at birth were associated with global DEXA bone mineral content at discharge from the NICU ( r=0.58 , p=0.05 ) . Conclusion : Supplementation with vitamin D3 increased the free portion of the vitamin D metabolite , providing increased bioavailable substrate . Improved free vitamin D levels may improve measurable outcomes such as bone mineral content and deserve further evaluation In recognition of the benefits of transparent reporting , many peer- review ed journals require that their authors be prepared to share their raw , unprocessed data with other scientists and /or state the availability of raw data in published articles . But little information on how data should be prepared for publication - or sharing - has emerged . In clinical research patient privacy and consent for use of personal health information are key considerations , but agreed-upon definitions of what constitutes anonymised patient information do not appear to have been established . We aim to address this issue by providing practical guidance for those involved in the publication process , by proposing a minimum st and ard for de-identifying data sets for the purpose s of publication in a peer- review ed biomedical journal , or sharing with other research ers . Basic advice on file preparation is provided along with procedural guidance on prospect i ve and retrospective publication of raw data , with an emphasis on r and omised controlled trials . In order to encourage its wide dissemination this article is freely accessible on the BMJ and Trials journal web sites The purpose of this study was to investigate the effect of supplementary vitamin D therapy in addition to amitriptyline on the frequency of migraine attacks in pediatric migraine patients . Fifty-three children 8 - 16 years of age and diagnosed with migraine following the International Headache Society 2005 definition , which includes childhood criteria , were enrolled . Patients were classified into four groups on the basis of their 25-hydroxyvitamin D [ 25(OH)D ] levels . Group 1 had normal 25(OH)D levels and received amitriptyline therapy alone ; group 2 had normal 25(OH)D levels and received vitamin D supplementation ( 400 IU/day ) plus amitriptyline ; group 3 had mildly deficient 25(OH)D levels and received amitriptyline plus vitamin D ( 800 IU/day ) ; and group 4 had severely deficient 25(OH)D levels and was given amitriptyline plus vitamin D ( 5000 IU/day ) . All groups were monitored for 6 months , and the number of migraine attacks before and during treatment was determined . Calcium , phosphorus alkaline phosphatase , parathormone , and 25(OH)D levels were also determined before and during treatment . Results were compared between the groups . Data obtained from the groups were analyzed using one-way analysis of variance . The number of pretreatment attacks in groups 1 to 4 was 7±0.12 , 6.8±0.2 , 7.3±0.4 , and 7.2±0.3 for 6 months , respectively ( all P>0.05 ) . The number of attacks during treatment was 3±0.25 , 1.76±0.37 ( P<0.05 ) , 2.14±0.29 ( P<0.05 ) , and 1.15±0.15 ( P<0.05 ) , respectively . No statistically significant differences in calcium , phosphorus , alkaline phosphatase , or parathormone levels were observed ( P>0.05 ) . Vitamin D given in addition to anti-migraine treatment reduced the number of migraine attacks BACKGROUND Eczema is one of the most common chronic inflammatory skin diseases , affecting about 20 % of children . The pathogenic mechanisms of eczema are still not fully understood , and current treatment of moderate-severe eczema is often difficult . Recently , it has been suggested that Vitamin D plays a key role in this disease , even if mechanisms are only partially known . OBJECTIVE The purpose of our study was to assess the 25-Hydroxyvitamin D serum levels in a pediatric population suffering from chronic eczema ( IgE-mediated and non-IgE-mediated ) , and to correlate these phenotypes with the SCORAD severity and selected clinical and biological parameters . Moreover , we aim ed to evaluate whether a supplementation of Vitamin D3 could affect the same clinical and laboratory parameters . METHODS 89 children with chronic eczema were enrolled in the study . Severity of eczema was assessed with the SCORAD index . Past and present history was taken , and patients were divided into two groups according to the state of sensitization . According to a r and omization schedule , the enrolled children were assigned to the following groups : supplementation group , which received a daily oral Vitamin D3 supplementation ( 2000 IUs ) for 3 months ; control group which received no supplementation . RESULTS Vitamin D concentrations in patients with moderate and severe eczema were not statistically different from Vitamin D concentration detected in the serum of patients with mild eczema . Furthermore , we did not find any correlation between Vitamin D levels , total IgEs and SCORAD index , both in the Sensitized and in the Not-Sensitized group . The Vitamin D3 supplementation did not influence the SCORAD severity or the total IgEs concentration . CONCLUSION To our knowledge , our study is the first one that shows no correlation between serum levels of Vitamin D , eczema severity and IgE sensitization in a pediatric population suffering from chronic eczema Background Multiple treatments are frequently available for a given condition , and clinicians and patients need a comprehensive , up-to- date synthesis of evidence for all competing treatments . We aim ed to quantify the waste of research related to the failure of systematic review s to provide a complete and up-to- date evidence synthesis over time . Methods We performed a series of systematic overviews and networks of r and omized trials assessing the gap between evidence covered by systematic review s and available trials of second-line treatments for advanced non-small cell lung cancer . We search ed the Cochrane Data base of Systematic Review s , Data base of Abstract s of Review s of Effects , MEDLINE , EMBASE , and other re sources sequentially by year from 2009 to March 2 , 2015 . We sequentially compared the amount of evidence missing from systematic review s to the r and omized evidence available for inclusion each year . We constructed cumulative networks of r and omized evidence over time and evaluated the proportion of trials , patients , treatments , and treatment comparisons not covered by systematic review s on December 31 each year from 2009 to 2015 . Results We identified 77 trials ( 28,636 patients ) assessing 47 treatments with 54 comparisons and 29 systematic review s ( 13 published after 2013 ) . From 2009 to 2015 , the evidence covered by existing systematic review s was consistently incomplete : 45 % to 70 % of trials ; 30 % to 58 % of patients ; 40 % to 66 % of treatments ; and 38 % to 71 % of comparisons were missing . In the cumulative networks of r and omized evidence , 10 % to 17 % of treatment comparisons were partially covered by systematic review s and 55 % to 85 % were partially or not covered . Conclusions We illustrate how systematic review s of a given condition provide a fragmented , out-of- date panorama of the evidence for all treatments . This waste of research might be reduced by the development of live cumulative network meta-analyses Abstract This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana , Mexico and determined the effect of a single oral dose of 50 000 IU vitamin D3 at birth on 25-hydroxyvitamin D ( 25[OH]D ) levels during infancy . Healthy infants were r and omized to receive vitamin D3 or placebo at birth . At birth 23 % of infants were vitamin D deficient and 77 % had vitamin D insufficiency ( mean 25[OH]D level 18.9 ng/ml ) ; 10 % of mothers were vitamin D deficient and 61 % were insufficient . Infants receiving vitamin D3 had higher 25(OH)D levels at two months ( N = 29 ; 33.9 versus 24.2 ng/ml ) and six months ( N = 21 ; 36.5 versus 27.4 ng/ml ) . Exclusively breastfed infants had lower 25(OH)D levels at two months ( 14.9 versus 33.4 ng/ml ) . Vitamin D deficiency is common in infants and mothers in Tijuana , Mexico . A single dose of vitamin D3 at birth was safe and significantly increased 25(OH)D levels during infancy Background Vitamin D is a pleiotropic hormone important for the recovery of organ systems after critical illness . Recent observational studies have suggested that three out of every four children are vitamin D deficient following cardiac surgery , with inadequate preoperative intake and surgical losses playing important contributory roles . Observed associations between postoperative levels , cardiovascular dysfunction and clinical course suggest that perioperative optimization of vitamin D status could improve outcome . With this two-arm , parallel , double blind , r and omized controlled trial ( RCT ) , we aim to compare immediate postoperative vitamin D status in children requiring cardiopulmonary bypass for congenital heart disease who receive preoperative daily high dose vitamin D supplementation ( high-dose arm ) with those who receive usual intake ( low-dose arm ) . Methods / Design Eligibility requirements include age ( > 36 weeks , < 18 years ) and a congenital heart defect requiring cardiopulmonary bypass surgical correction . Enrollment of 62 participants will take place at a single Canadian tertiary care center over a period of 2 years . Children r and omized to the high-dose group will receive age-based dosing that was informed by the Institute of Medicine ( IOM ) daily tolerable upper intake level ( < 1 year old = 1,600 IU/day , > 1 year old = 2,400 IU/day ) . Children in the low-dose arm will receive usual care based on IOM recommendations ( < 1 year old = 400 IU , > 1 year old = 600 IU ) . The primary outcome measure is immediate postoperative vitamin D status , using blood 25(OH)D. Discussion Maintaining adequate postoperative vitamin D levels following surgery could represent an effective therapy to speed recovery following CHD surgery . The proposed research project will determine whether preoperative supplementation with a dosing regimen based on the IOM recommended daily upper tolerable intake will prevent postoperative vitamin-D deficiency in the majority of children . The results will then be used to inform the design of a large international RCT exploring whether preoperative optimization of vitamin D status might improve short and long-term outcomes in this vulnerable population .Trial Registration Clinical trials.gov Identifier - NCT01838447 Date of registration : 11 April BACKGROUND Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections ( URI ) . T lymphocytes have a major anti-viral role , are affected by vitamin D metabolism , and may mediate the link between vitamin D and URIs . Competitive swimmers have a relatively high rate of URIs , alongside a high prevalence of low vitamin D concentration . OBJECTIVES To examine the associations linking T cell receptor excision circles ( TREC , markers of thymus activity ) , circulating 25(OH)D concentrations and the effect of vitamin D supplementation , and URI symptoms in young competitive swimmers . METHODS We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency . R and omized supplementation of either vitamin D3 or placebo was given for 12 winter weeks . URI symptoms were recorded weekly . The associations between TREC copy numbers , vitamin D and URI burden were examined . RESULTS TREC concentrations decreased with the participants ' age ( r = -0.346 , P = 0.003 ) , with no significant between-gender difference . TREC concentrations did not material ly differ among subjects with normal , insufficient or deficient vitamin D status , and were not affected by vitamin D supplementation . No significant correlations were found between TREC levels or their changes during the study period , and mean URI severity or duration . CONCLUSIONS Thymus activity , represented by higher TREC levels , was not related to vitamin D concentrations or status , and was not affected by vitamin D supplementation in adolescent swimmers . TREC concentrations were not associated with URI severity or duration in this population AIM The prevalence of vitamin D deficiency has risen in countries with a high ultraviolet index and sunny environment such as Australia . There is lack of information on vitamin D status and best possible therapy in Australian Aboriginal children . We aim to ( i ) describe the vitamin D status in an opportunistic sample of Aboriginal children in Western Australia and ( ii ) compare the efficacy of oral daily vitamin D with oral stoss vitamin D therapy in this sample . METHOD Participants were recruited from a metropolitan area ( 31 ' S ) and a rural area ( 17 ' S ) . Those with a 25(OH)D level less than 78 nmol/L were r and omised to receive daily or stoss vitamin D therapy with follow-up at 4 - 6 months and 9 - 12 months . Biochemical and clinical parameters such as 25(OH)D , alkaline phosphatase , calcium and sun exposure were collected . RESULTS Seventy-three participants were enrolled ( 61 from a metropolitan and 12 from a rural area ) . 25(OH)D levels were greater than 78 nmol/L in 9/12 ( 75 % ) participants in the rural group and 21/61 ( 34 % ) in the metropolitan group . 25(OH)D levels were less than 78 nmol/L in 43/73 ( 59 % ) participants . Of these , 34/43 ( 79 % ) were insufficient ( 50 - 78 nmol/L ) , 8/43 ( 19 % ) mildly deficient ( 27.5 - 50 nmol/L ) and 1/43 ( 2 % ) deficient ( < 27.5 nmol/L ) . Daily vitamin D therapy had a higher average increase in 25(OH)D levels from baseline than stoss therapy ; however , this was not significant . CONCLUSION Vitamin D insufficiency is common in Aboriginal children of Western Australia and stoss therapy is a safe alternative to daily vitamin D therapy but requires further evaluation of timing and doses PURPOSE Vitamin D deficiency and cardiometabolic risk factors are common in obese adolescents . Observational studies demonstrate an inverse relationship among serum 25-hydroxyvitamin D ( 25OHD ) and obesity , insulin resistance , and inflammatory cytokines . This pilot study explores if vitamin D supplementation could reduce serum concentrations of inflammatory cytokines ( interleukin [ IL ] 6 , IL-10 , tumor necrosis factor α ) , adiponectin , lipids , hemoglobin A1C , and high-sensitivity C-reactive protein ( hs-CRP ) . A secondary aim was to determine the associations between baseline serum 25OHD concentrations and body mass index ( BMI ) , hs-CRP , inflammatory cytokines , and lipids . METHODS Overweight and obese adolescents enrolled in this 24-week , r and omized , double-blind study were given 150,000 IU ergocalciferol or placebo at baseline and 12 weeks . Outcome measurements included serum 25OHD , inflammatory cytokines , adiponectin , hs-CRP , lipids , hemoglobin A1C , and BMI at baseline , 12 , and 24 weeks . RESULTS Of 40 participants , 31 ( 78 % ) completed the study . Mean ± st and ard error 25OHD levels were similar in vitamin D and placebo groups at baseline ( 19.6 ± 5.3 vs. 25.8 ± 10.8 ng/mL ) and 24 weeks ( 20.1 ± 3.4 vs. 24.6 ± 8.4 ng/mL ) . Inflammatory and cardiovascular markers were not significantly different between groups at 24 weeks . Serum 25OHD at baseline was associated with BMI ( r = -.44 [ 95 % confidence interval , -.66 to -.15 ] ) but not with other outcome measures . CONCLUSIONS Supplementation with vitamin D at 150,000 IU every 3 months failed to increase serum 25OHD or alter inflammatory markers and lipids in overweight and obese youth . Further studies are needed to establish the dose of vitamin D required to increase 25OHD and determine potential effects on metabolic risk factors in obese teens BACKGROUND The effect of supplemental vitamin D on fracture occurrence following burn injuries is unclear . The objective of this study was to evaluate postintervention incidence of fractures in children during the rehabilitative phase postburn ( PB ) following participation in a r and omized clinical trial of vitamin D supplementation . MATERIAL S AND METHODS Follow-up for fracture evaluation was obtained in 39 of 50 patients r and omized to daily enteral vitamin D2 , D3 , or placebo throughout the acute burn course . Serum 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , D2 , D3 , calcitonin , and bone alkaline phosphatase ( BAP ) measurements were obtained PB day 7 , midpoint , discharge , and 1-year PB . Urinary calcium was obtained PB day 7 and midpoint . Dual-energy x-ray absorptiometry ( DXA ) was performed at discharge and 1-year PB . RESULTS Fractures were reported in 6 of 39 respondents . Four fractures occurred in the placebo group , 2 in the D2 group , and none in the D3 group . Serum vitamin D , calcitonin , BAP , and urinary calcium were similar between fracture groups . The group with fracture morbidity had larger burn size ( 83.8 % ± 4.9 % vs 53.0 % ± 2.9 % , P < .0001 ) , greater full-thickness burn ( 69.7 % ± 9.4 % vs 39.4 % ± 4.1 % , P = .02 ) , and increased incidence of inhalation injury ( 33 % vs 6 % , P = .04 ) . Decreased bone mineral density z score was noted at discharge in the placebo fracture compared with no-fracture group ( P < .05 ) . CONCLUSION This preliminary report suggests there may be benefit of vitamin D3 in reducing postdischarge fracture risk . Results reaffirm the importance of monitoring bone health in pediatric patients postburn Observational studies identified associations between vitamin D insufficiency ( serum 25(OH)D < 30ng·ml-1 ) and 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 < .001 ) , and moderately associated with 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 |
13,072 | 26,553,497 | Conclusions RSS training is a novel training method with potential for the improvement of sprint performance , but its performance benefits over URS training remain to be conclusively demonstrated . | Background Based on recent findings regarding the mechanical determinants of sprint performance , resisted sled sprint ( RSS ) training may provide an effective tool for the improvement of sprint acceleration and maximal velocity .
However , the volume and intensity for effective RSS training in different population s is unclear .
Objectives The primary objective was to evaluate the effectiveness of RSS training compared with unresisted sprint ( URS ) training , and the differential effects of sled load on RSS training outcomes . | The aim of this study was to compare sprint performance over 10 and 20 m when participants ran while towing resistances , weighing between 0 and 30 % of body mass . The sample of 33 participants consisted of male rugby and soccer players ( age 21.1 ± 1.8 years , body mass 83.6 ± 13.1 kg , height 1.82 ± 0.1 m ; mean ± s ) . Each participant performed two sets of seven sprints over 20 m using a Latin rectangular design . The times were recorded at 10 and 20 m using electronic speed gates . The sprints of 13 players were video-recorded to allow calculation of stride length and frequency . For both sprints , a quadratic relationship was observed between sprint time and resistance as sprint time increased from 2.94 s to 3.80 s from 0 to 30 % resistance . This relationship was statistically significant but considered not to be meaningful for performance because , over the range of resistances used in this study , the quadratic model was never more than 1 % ( in terms of sprint time ) from the linear model . As resistance increased , the stride length shortened , with mean values of 1.63 ± 0.13 m at 0 % body mass and 1.33 ± 0.13 m at 30 % of body mass . There was no significant change in stride frequency with increasing resistance . The results show that in general there is an increase in sprint time with an increase in resistance . No particular resistance in the range tested ( 0 – 30 % ) can be recommended for practice The purpose of this study was to compare changes in velocity-specific adaptations in moderately resistance-trained athletes who trained with either low or high resistances . The study used tests of sport-specific skills across an intermediate-to high-velocity spectrum . Thirty NCAA Division I baseball players were r and omly assigned to either a low-resistance ( 40–60 % 1 repetition maximum [ 1RM ] ) training group or a high-resistance ( 70–90 % 1RM ) training group . Both of the training groups intended to maximally accelerate each repetition during the concentric phase ( IMCA ) . The 10 weeks of training consisted of 4 training sessions a week using basic core exercises . Peak force , velocity and power were evaluated during set angle and depth jumps as well as weighted jumps using 30 and 50 % 1RM . Squat 1RMs were also tested . Although no interactions for any of the jump tests were found , trends supported the hypothesis of velocity-specific training . Percentage gains suggest that the combined use of heavier training loads ( 70–90 % 1RM ) and IMCA tend to increase peak force in the lower-body leg and hip extensors . Trends also show that the combined use of lighter training loads ( 40–60 % 1RM ) and IMCA tend to increase peak power and peak velocity in the lower-body leg and hip extensors . The high-resistance group improved squats more than the low-resistance group ( p < 0.05 ; + 22.7 vs. + 16.1 kg ) . The results of this study support the use of a combination of heavier training loads and IMCA to increase 1RM strength in the lower bodies of resistance-trained athletes OBJECTIVES To investigate the physical dem and s of professional rugby league match-play using microtechnology , and to compare these dem and s with typical training activities used to prepare players for competition . DESIGN Prospect i ve cohort study . METHODS Thirty elite rugby league players participated in this study . Seven hundred and eighty-six . training data sets and 104 data sets from National Rugby League matches were collected over one playing season . Movement was recorded using a commercially available microtechnology unit ( minimaxX , Catapult Innovations ) , which provided information on speeds , distances , accelerations , physical collisions and repeated high-intensity efforts . RESULTS Mean distances covered during match-play by the hit-up forwards , wide-running forwards , adjustables , and outside backs were 3,569 m , 5,561 m , 6,411 m , and 6,819 m , respectively . Hit-up forwards and wide-running forwards were engaged in a greater number of moderate and heavy collisions than the adjustables and outside backs , and more repeated high-intensity effort bouts per minute of play ( 1 bout every 4.8 - 6.3 min ) . The physical dem and s of traditional conditioning , repeated high-intensity effort exercise , and skill training activities were all lower than the physical dem and s of competition . CONCLUSIONS These results demonstrate that absolute distances covered during professional rugby league matches are greater for outside backs , while the collision and repeated high-intensity effort dem and s are higher for hit-up forwards and wide-running forwards . The specific physical dem and s of competitive play , especially those dem and s associated with collisions and repeated high-intensity efforts , were not well matched by those observed in traditional conditioning , repeated high-intensity effort exercise , and skills training activities . Further research is required to investigate whether modifications need to be made to these training activities to better prepare players for the dem and s of National Rugby League competition UNLABELLED Fast acceleration is an important performance factor in h and ball . In addition to traditional sprint training ( TST ) , resisted-sprint training ( RST ) is a method often used to improve acceleration . However , studies on RST show conflicting results , and underlying mechanisms have not been studied . PURPOSE To compare the effects of RST , by sled towing , against TST on sprint performance and muscle architecture . METHODS Participants ( n=18 ) were assigned to either RST or TST and completed 2 training sessions of RST or TST per week ( 10 wk ) , in addition to their normal team training . Sprint tests ( 10 and 30 m ) and measurements of muscle architecture were performed pre- and posttraining . RESULTS Beneficial effects were found in the 30-m-sprint test for both groups ( mean ; ±90 % CL : TST=-0.31 ; ±0.19 s , RST=-0.16 ; ±0.13 s ) , with unclear differences between the groups . Only TST had a beneficial effect on 10-m time ( -0.04 ; ±0.04 s ) , with a likely difference between the 2 groups ( 85 % , ES=0.60 ) . Both groups had a decrease in pennation angle ( -6.0 ; ±3.3 % for TST and -2.8 ; ±2.0 % for RST ) , which had a nearly perfect correlation with percentage change in 10-m-sprint performance ( r=.92 ) . A small increase in fascicle length ( 5.3 ; ±3.9 % and 4.0 ; ±2.1 % for TST and RST , respectively ) was found , with unclear differences between groups . DISCUSSION TST appears to be more effective than RST in enhancing 10-m-sprint time . Both groups showed similar effects in 30-m-sprint time . A similar , yet small , effect of sprint training on muscle architecture was observed in both groups The purpose of this study was to compare the effects of combined strength and plyometric training with strength training alone on power-related measurements in professional soccer players . Subjects in the intervention team were r and omly divided into 2 groups . Group ST ( n = 6 ) performed heavy strength training twice a week for 7 weeks in addition to 6 to 8 soccer sessions a week . Group ST+P ( n = 8) performed a plyometric training program in addition to the same training as the ST group . The control group ( n = 7 ) performed 6 to 8 soccer sessions a week . Pretests and posttests were 1 repetition maximum ( 1RM ) half squat , countermovement jump ( CMJ ) , squat jump ( SJ ) , 4-bounce test ( 4BT ) , peak power in half squat with 20 kg , 35 kg , and 50 kg ( PP20 , PP35 , and PP50 , respectively ) , sprint acceleration , peak sprint velocity , and total time on 40-m sprint . There were no significant differences between the ST+P group and ST group . Thus , the groups were pooled into 1 intervention group . The intervention group significantly improved in all measurements except CMJ , while the control group showed significant improvements only in PP20 . There was a significant difference in relative improvement between the intervention group and control group in 1RM half squat , 4BT , and SJ . However , a significant difference between groups was not observed in PP20 , PP35 , sprint acceleration , peak sprinting velocity , and total time on 40-m sprint . The results suggest that there are no significant performance-enhancing effects of combining strength and plyometric training in professional soccer players concurrently performing 6 to 8 soccer sessions a week compared to strength training alone . However , heavy strength training leads to significant gains in strength and power-related measurements in professional soccer players UNLABELLED A " negative interaction " between step length and step rate refers to an increase in one factor result ing in a decrease in the other . PURPOSE S There were three main purpose s : a ) to investigate the relative influence of the determinants of step length and step rate , b ) to determine the sources of negative interaction between step length and step rate , and c ) to investigate the effects of manipulation of this interaction . METHODS Thirty-six athletes performed maximal-effort sprints . Video and ground reaction force data were collected at the 16-m mark . Sprint velocity , step length , step rate , and their underlying determinants were calculated . Analyses included correlations , multiple linear regressions , paired t-tests , and a simple simulation based on alterations in flight determining parameters . RESULTS A wide range of step length and step rate combinations was evident , even for subgroups of athletes with similar sprint velocities . This was partly due to a negative interaction that existed between step length and step rate ; that is , those athletes who used a longer step length tended to have a lower step rate and vice versa . Vertical velocity of takeoff was the most prominent source of the negative interaction . CONCLUSIONS Leg length , height of takeoff , and vertical velocity of takeoff are all possible sources of a negative interaction between step length and step rate . The very high step lengths and step rates achieved by elite sprinters may be possible only by a technique that involves a high horizontal and low vertical velocity of takeoff . However , a greater vertical velocity of takeoff might be of advantage when an athlete is fatigued and struggling to maintain a high step rate The purpose of this investigation was to examine the effect of an 8-week training program with heavy- vs. light-load jump squats on various physical performance measures and electromyography ( EMG ) . Twenty-six athletic men with varying levels of resistance training experience performed sessions of jump squats with either 30 % ( JS30 , n = 9 ) or 80 % ( JS80 , n = 10 ) of their one repetition maximum in the squat ( 1RM ) or served as a control ( C , n = 7 ) . An agility test , 20-m sprint , and jump squats with 30 % ( 30J ) , 55 % ( 55J ) , and 80 % ( 80J ) of their 1RM were performed before and after training . Peak force , peak velocity ( PV ) , peak power ( PP ) , jump height , and average EMG ( concentric phase ) were calculated for the jumps . There were significant increases in PP and PV in the 30J , 55J , and 80J for the JS30 group ( p < 0.05 ) . The JS30 group also significantly increased in the 1RM with a trend towards improved 20-m sprint times . In contrast , the JS80 group significantly increased both PF and PP in the 55J and 80J and significantly increased in the 1RM but ran significantly slower in the 20-m sprint . In the 30J the JS30 group 's percentage increase in EMG activity was significantly different from the C group . In the 80J the JS80 group 's percentage increase in EMG activity was significantly different from the C group . This investigation indicates that training with light-load jump squats results in increased movement velocity capabilities and that velocity-specific changes in muscle activity may play a key role in this adaptation The literature contains some hypotheses regarding the most favorable ground reaction force ( GRF ) for sprint running and how it might be achieved . This study tested the relevance of these hypotheses to the acceleration phase of a sprint , using GRF impulse as the GRF variable of interest . Thirty-six athletes performed maximal-effort sprints from which video and GRF data were collected at the 16-m mark . Associations between GRF impulse ( expressed relative to body mass ) and various kinematic measures were explored with simple and multiple linear regressions and paired t-tests . The regression results showed that relative propulsive impulse accounted for 57 % of variance in sprint velocity . Relative braking impulse accounted for only 7 % of variance in sprint velocity . In addition , the faster athletes tended to produce only moderate magnitudes of relative vertical impulse . Paired t-tests revealed that lower magnitudes of relative braking impulse were associated with a smaller touchdown distance ( p < 0.01 ) and a more active touchdown ( p < 0.001 ) . Also , greater magnitudes of relative propulsive impulse were associated with a high mean hip extension velocity of the stance limb ( p < 0.05 ) . In conclusion , it is likely that high magnitudes of propulsion are required to achieve high acceleration . Although there was a weak trend for faster athletes to produce lower magnitudes of braking , the possibility of braking having some advantages could not be ruled out . Further research is required to see if braking , propulsive , and vertical impulses can be modified with specific training . This will also provide insight into how a change in one GRF component might affect the others PURPOSE The aim of this study was to compare the effects of 2 strength and conditioning programs involving either purely vertically oriented or combining vertically and horizontally oriented exercises on soccer-relevant performance variables ( ie , acceleration , jumping ability , peak power , and endurance ) . METHODS Twenty-two professional male soccer players were r and omly assigned to 2 training groups : vertical strength ( VS , n = 11 ) and vertical and horizontal strength ( VHS , n = 11 ) . Players trained 2 times per week during all the preseason ( 5 wk ) and 3 weeks of the competitive season . The effect of the training protocol s was assessed using double- and single-leg vertical countermovement jumps ( CMJ ) , half-squat peak power ( PP ) , sprint performance over 5 and 15 m , and blood lactate concentration at selected running speeds . RESULTS Both groups obtained significant improvements in PP ( P < .05 ; ES = 0.87 and 0.80 for VS and VHS , respectively ) and small practical improvements in 5-m- ( P < .05 ; ES = 0.27 and 0.25 for VS and VHS , respectively ) and 15-m-sprint time ( P < .05 ; ES = 0.19 and 0.24 for VS and VHS , respectively ) . The CMJ performance showed a small improvement ( P < .05 , ES = 0.34 ) only in the VHS group . Submaximal aerobic-fitness changes were similar in both groups ( P < .05 ; ES = 1.89 and 0 .71 for VS and VHS , respectively ) . CONCLUSION This study provided a small amount of practical evidence for the consideration of preseason training protocol s that combine exercises for vertical- and horizontal-axis strength development in professional male soccer players . Further studies using more aggressive training protocol s involving horizontally oriented conditioning exercises are warranted Abstract Byrne , PJ , Kenny , J , and O ’ Rourke , B. Acute potentiating effect of depth jumps on sprint performance . J Strength Cond Res 28(3 ) : 610–615 , 2014—The purpose of this investigation was to determine whether the addition of 3 depth jumps to a dynamic warm-up ( DYNDJ ) protocol would significantly improve 20-m sprint performance when compared with a cardiovascular ( C ) warm-up protocol or a dynamic ( DYN ) stretching protocol alone . The first part of the study identified optimal drop height for all subjects using the maximum jump height method . The identified optimal drop heights were later used during the DYNDJ protocol . The second part compared the 3 warm-up protocol s above to determine their effect on 20-m sprint performance . Twenty-nine subjects ( age , 20.8 ± 4.4 years ; weight , 82.6 ± 9.9 kg ; height , 180.3 ± 6.2 cm ) performed 3 protocol s of a C protocol , a DYN protocol , and a DYNDJ protocol in a r and omized order . A 20-m sprint was performed 1 minute after the completion of each of the 3 protocol s. Results displayed significant differences between each of the 3 protocol s. A significant improvement ( p = 0.001 ) of 2.2 % was obtained in sprint time between the C protocol ( 3.300 ± 0.105 seconds ) and the DYN protocol ( 3.227 ± 0.116 seconds ) , a further significant improvement of 5.01 % was attained between the C and the DYNDJ protocol s ( 3.300 ± 0.10 vs. 3.132 ± 0.120 seconds ; p = 0.001 ) . In addition , a significant improvement ( p = 0.001 ) of 2.93 % was observed between the DYN protocol ( 3.227 ± 0.116 seconds ) and the DYNDJ protocol ( 3.132 ± 0.116 seconds ) . The data from this study advocate the use of DYNDJ protocol as a means of significantly improving 20-m sprint performance 1 minute after the DYNDJ protocol Abstract West , DJ , Cunningham , DJ , Bracken , RM , Bevan , HR , Crewther , BT , Cook , CJ , and Kilduff , LP . Effects of resisted sprint training on acceleration in professional rugby union players . J Strength Cond Res 27(4 ) : 1014–1018 , 2013—The use of weighted sled towing as a training tool to improve athlete acceleration has received considerable attention ; however , its effectiveness for developing acceleration is equivocal . This study compared the effects of combined weighted sled towing and sprint training against traditional sprint training on 10 and 30 m speed in professional rugby union players ( n = 20 ) . After baseline testing of 10 and 30 m speed , participants were assigned to either the combined sled towing and sprint training ( SLED ) or traditional sprint training ( TRAD ) groups , matched for 10-m sprint times . Each group completed 2 training sessions per week for 6 weeks , with performance reassessed post-training . Both training programmes improved participants ' 10 and 30 m speed ( p < 0.001 ) , but the performance changes ( from pre to post ) in 10 m ( SLED −0.04 ± 0.01 vs. TRAD −0.02 ± 0.01 seconds ; p < 0.001 ) and 30 m ( SLED −0.10 ± 0.03 vs. TRAD −0.05 ± 0.03 seconds ; p = 0.003 ) sprint times were significantly greater in the SLED training group . Similarly , the percent change within the SLED group for the 10 m ( SLED −2.43 ± 0.67 vs. TRAD −1.06 ± 0.80 seconds ; p = 0.003 ) and 30 m ( SLED −2.46 ± 0.63 vs. TRAD −1.15 ± 0.72 seconds ; p = 0.003 ) tests were greater than the TRAD group . In conclusion , sprint training alone or combined with weighted sled towing can improve 10 and 30 m sprint times ; however , the latter training method promoted greater improvements in a group of professional rugby players Abstract Kawamori , N , Newton , RU , Hori , N , and Nosaka , K. Effects of weighted sled towing with heavy versus light load on sprint acceleration ability . J Strength Cond Res 28(10 ) : 2738–2745 , 2014—Weighted sled towing is used by athletes to improve sprint acceleration ability . The typical coaching recommendation is to use relatively light loads , as excessively heavy loads are hypothesized to disrupt running mechanics and be detrimental to sprint performance . However , this coaching recommendation has not been empirically tested . This study compared the effects of weighted sled towing with 2 different external loads on sprint acceleration ability . Twenty-one physically active men were r and omly allocated to heavy- ( n = 10 ) or light-load weighted sled towing ( n = 11 ) groups . All subjects participated in 2 training sessions per week for 8 weeks . The subjects in the heavy and light groups performed weighted sled towing using external loads that reduced sprint velocity by approximately 30 and 10 % , respectively . Before and after the training , the subjects performed a 10-m sprint test , in which split time was measured at 5 and 10 m from the start . The heavy group significantly improved both the 5- and 10-m sprint time by 5.7 ± 5.7 and 5.0 ± 3.5 % , respectively ( P < 0.05 ) , whereas only 10-m sprint time was improved significantly by 3.0 ± 3.5 % ( P < 0.05 ) in the light group . No significant differences were found between the groups in the changes in 5-m and 10-m sprint time from pre- to posttraining . These results question the notion that training loads that induce greater than 10 % reduction in sprint velocity would negatively affect sprint performance and point out the potential benefit of using a heavier load for weighted sled towing Hermassi , S , Chelly , MS , Tabka , Z , Shephard , RJ , and Chamari , K. Effects of 8-week in-season upper and lower limb heavy resistance training on the peak power , throwing velocity , and sprint performance of elite male h and ball players . J Strength Cond Res 25(9 ) : 2424 - 2433 , 2011—The aims of this study were to test the potential of in-season heavy upper and lower limb strength training to enhance peak power output ( Wpeak ) , vertical jump , and h and ball related field performance in elite male h and ball players who were apparently already well trained , and to assess any adverse effects on sprint velocity . Twenty-four competitors were divided r and omly between a heavy resistance ( HR ) group ( age 20 ± 0.7 years ) and a control group ( C ; age 20 ± 0.1 years ) . Resistance training sessions were performed twice a week for 8 weeks . Performance was assessed before and after conditioning . Peak power ( Wpeak ) was determined by cycle ergometer ; vertical squat jump ( SJ ) and countermovement jump ( CMJ ) ; video analyses assessed velocities during the first step ( V1S ) , the first 5 m ( V5 m ) , and between 25 and 30 m ( Vpeak ) of a 30-m sprint . Upper limb bench press and pull-over exercises and lower limb back half squats were performed to 1-repetition maximum ( 1RM ) . Upper limb , leg , and thigh muscle volumes and mean thigh cross-sectional area ( CSA ) were assessed by anthropometry . Wpeak ( W ) for both limbs ( p < 0.001 ) , vertical jump height ( p < 0.01 for both SJ and CMJ ) , 1RM ( p < 0.001 for both upper and lower limbs ) and sprint velocities ( p < 0.01 for V1S and V5 m ; p < 0.001 for Vpeak ) improved in the HR group . Upper body , leg , and thigh muscle volumes and thigh CSA also increased significantly after strength training . We conclude that in-season biweekly heavy back half-squat , pull-over , and bench-press exercises can be commended to elite male h and ball players as improving many measures of h and ball-related performance without adverse effects upon speed of movement Clark , KP , Stearne , DJ , Walts , CT , and Miller , AD . The longitudinal effects of resisted sprint training using weighted sleds vs. weighted vests . J Strength Cond Res 24(12 ) : 3287 - 3295 , 2010-The purpose of this study was to determine the longitudinal effects of weighted sled ( WS ) and weighted vest ( WV ) sprint training on maximum velocity sprint performance and kinematics . Twenty male collegiate lacrosse players were r and omly assigned to a WS group ( n = 7 ) towing 10 % body mass , a WV group ( n = 6 ) loaded with 18.5 % body mass , or an unresisted ( UR ) active control group ( n = 7 ) . All subjects completed 13 training sessions over 7 weeks . Pre- and post-test measures of sprint time and average velocity across the distance interval of 18.3 to 54.9 m were used to assess sprint performance , whereas high-speed video ( 300 Hz ) and motion- analysis software were used to analyze stride length , stride rate , ground contact time , and flight time . A 3 × 2 repeated measures analysis of variance was performed for each dependent variable and revealed no significant between-group differences for any of the sprint performance or kinematic stride cycle measures . Effect size statistics suggested small improvements in 18.3- to 54.9-m sprint time and average velocity for the UR group but only trivial improvements for the WS and WV groups . With regard to sprint performance , the results indicate that WS and WV training had no beneficial effect compared with UR training . In fact , for the loads used by WS and WV in this study , UR training may actually be superior for improving sprint performance in the 18.3- to 54.9-m interval Acceleration is a significant feature of game-deciding situations in the various codes of football . However little is known about the acceleration characteristics of football players , the effects of acceleration training , or the effectiveness of different training modalities . This study examined the effects of resisted sprint ( RS ) training ( weighted sled towing ) on acceleration performance ( 0–15 m ) , leg power ( countermovement jump [ CMJ ] , 5-bound test [ 5BT ] , and 50-cm drop jump [ 50DJ ] ) , gait ( foot contact time , stride length , stride frequency , step length , and flight time ) , and joint ( shoulder , elbow , hip , and knee ) kinematics in men ( N = 30 ) currently playing soccer , rugby union , or Australian football . Gait and kinematic measurements were derived from the first and second strides of an acceleration effort . Participants were r and omly assigned to 1 of 3 treatment conditions : ( a ) 8-week sprint training of two 1-h sessions·wk−1 plus RS training ( RS group , n = 10 ) , ( b ) 8-week nonresisted sprint training program of two 1-h sessions·wk−1 ( NRS group , n = 10 ) , or ( c ) control ( n = 10 ) . The results indicated that an 8-week RS training program ( a ) significantly improves acceleration and leg power ( CMJ and 5BT ) performance but is no more effective than an 8-week NRS training program , ( b ) significantly improves reactive strength ( 50DJ ) , and ( c ) has minimal impact on gait and upper- and lower-body kinematics during acceleration performance compared to an 8-week NRS training program . These findings suggest that RS training will not adversely affect acceleration kinematics and gait . Although apparently no more effective than NRS training , this training modality provides an overload stimulus to acceleration mechanics and recruitment of the hip and knee extensors , result ing in greater application of horizontal power The purpose of the present study was to investigate the effects of performing heavy back squats ( HBS ) and heavy front squats ( HFS ) on the average speed during each 10-m interval of 40-m sprint trials . In a r and omized , cross-over design , 10 strength-trained men performed a HBS , HFS , or control treatment before performing three 40-m sprint trials separated by 3 minutes . The HBS and HFS treatments consisted of performing parallel back or front squats with 30 % , 50 % , and 70 % of the subject 's 1 repetition maximum after 5 minutes of cycling . The control treatment consisted of cycling for 5 minutes . The sprint trials were performed 4 minutes after completing the HBS , HFS , or control treatments . Significant increases in speed were found during the 10- to 20-m interval for the HBS compared with the control treatment ( mean difference , 0.12 m·s−1 ; 95 % likely range , 0.05 - 0.18 m·s−1 ; P = 0.001 ) . During the 30- to 40-m interval , HBS produced significantly greater speeds compared with the HFS treatment ( mean difference , 0.24 m·s−1 ; 95 % likely range , 0.02 - 0.45 m·s−1 ; P = 0.034 ) and the control treatment ( mean difference , 0.18 m·s−1 ; 95 % likely range , 0.03 - 0.32 m·s−1 ; P = 0.021 ) . The differing effects of the treatments may reflect different levels of muscular activation or different mechanical aspects of the squat exercises . Similarly , the multidimensional nature of sprint running means that other specific exercises may confer improvements in sprinting performance during other intervals . It is suggested that coaches could incorporate HBS into the warm-up procedure of athletes to improve sprinting performance The purpose of this investigation was to determine whether performing high force or explosive force movements prior to sprinting would improve running speed . Fifteen NCAA Division III football players performed a heavy-load squat ( HS ) , loaded countermovement jump ( LCMJ ) , or control ( C ) warm-up condition in a counterbalanced r and omized order over the course of 3 weeks . The HS protocol consisted of 1 set of 3 repetitions at 90 % of the subject 's 1 repetition maximum ( 1RM ) . The LCMJ protocol was 1 set of 3 repetitions at 30 % of the subject 's 1RM . At 4 minutes post – warm-up , subjects completed a timed 40-m dash with time measured at 10 , 30 , and 40 m. The results of the study indicated that when preceded by a set of HS , subjects ran 0.87 % faster ( p ≤ 0.05 ) in the 40-m dash ( 5.35 ± 0.32 vs. 5.30 ± 0.34 seconds ) in comparison to C. No significant differences were observed in the 10-m or 30-m split times between the 3 conditions . The data from this study suggest that an acute bout of low-volume heavy lifting with the lower body may improve 40-m sprint times , but that loaded countermovement jumps appear to have no significant effect The purpose of this study was to investigate the effect of a combined heavy-resistance and running-speed training program performed in the same training session on strength , running velocity ( RV ) , and vertical-jump performance ( VJ ) of soccer players . Thirty-five individuals were divided into 3 groups . The first group ( n = 12 , COM group ) performed a combined resistance and speed training program at the same training session , and the second one ( n = 11 , STR group ) performed the same resistance training without speed training . The third group was the control group ( n = 12 , CON group ) . Three jump tests were used for the evaluation of vertical jump performance : squat jump , countermovement jump , and drop jump . The 30-m dash and 1 repetition maximum ( 1RM ) tests were used for running speed and strength evaluation , respectively . After training , both experimental groups significantly improved their 1RM of all tested exercises . Furthermore , the COM group performed significantly better than the STR and the CON groups in the 30-m dash , squat jump , and countermovement jump . It is concluded that the combined resistance and running-speed program provides better results than the conventional resistance training , regarding the power performance of soccer players Various studies have demonstrated that resistance sprint ( RS ) training can produce significant changes in running speed and running kinematics . The longer-term training adaptations after RS training remain unclear . The purpose of this study was to investigate whether an RS training intervention would enhance the running speed and dynamic strength measures in male rugby players . Fifteen male rugby players aged 20.5 ( + /- 2.8 ) years who were proficient in resisted sledge training took part in the study . The subjects were r and omly assigned to control or RS groups . The RS group performed two sessions per week of RS training for 6 weeks , and the control group did no RS training . Pre- and postintervention tests were carried out for 30-m sprint , drop , squat , and rebound jumps on a force sledge system . A laser measurement device was used to obtain velocities and distance measures during all running trials . The results show a statistically significant decrease in time to 5 m for the 30-m sprint for the RS group ( p = 0.02 ) . The squat jump and drop jump variables also showed significant increases in starting strength ( p = 0.004 ) and height jumped ( p = 0.018 ) for the RS group from pre- to post-testing sessions . The results suggest that it may be beneficial to employ an RS training intervention with the aim of increasing initial acceleration from a static start for sprinting |
13,073 | 29,957,086 | The main results showed that participants report low-to-moderate FA .
Higher levels of FA were shown by women , highly educated individuals , people who reported difficulties with conceiving , and those who had planned their pregnancies .
Having or desiring to have children was not related to FA level . | INTRODUCTION Recent evidence indicates that reproductive-age people have inadequate fertility awareness ( FA ) concerning fertility , infertility risk factors , and consequences of delaying childbearing .
However , no study has tried to summarize these studies and to clarify the variables associated with FA , namely the role of gender , age , education , and reproductive status on FA . | OBJECTIVE To estimate the probability of medical consultation for infertility during the course of a pregnancy attempt and to study its determinants . DESIGN Pregnancy-based retrospective telephone survey analyzed with a discrete time Cox model . SETTING Two rural counties in Brittany and Norm and y , France . PATIENT(S ) A r and om sample of 901 women from the general population aged 18 - 60 years reporting 1,460 pregnancy attempts result ing in a live birth between 1985 and 2000 ( participation rate , 73 % ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Probability of medical consultation for involuntary infertility cumulated over time . RESULT ( S ) The cumulative probability of medical consultation for involuntary infertility among nulligravid women was 45 % after 12 months of involuntary infertility and 75 % after 24 months . The probability of medical consultation at any time was half that for parous women ( odds ratio 0.4 , 95 % confidence interval 0.2 - 0.6 ) . More highly educated women were more likely to have sought medical help for infertility . Only 45 % of women who had sought medical advice received infertility treatment . CONCLUSION ( S ) Our survival approach provides a description of infertility service use during the course of a pregnancy attempt , and confirms that parity and educational level are strong predictors of medical help-seeking behaviors BACKGROUND Women age 35 and older account for an increasing proportion of births and are at increased risk of having difficulties conceiving and of delivering a multiple birth , low birth weight infant , and /or preterm infant . Little is known about men 's and women 's underst and ing of the maternal age related risks to pregnancy . OBJECTIVES 1 ) To determine the factors influencing the timing of childbearing for non-parenting men and women , 2 ) to determine knowledge among non-parenting men and women about maternal age-related reproductive risks , the consequences of low birth weight and multiple birth , and issues related to infertility , and 3 ) to determine characteristics associated with limited knowledge of these reproductive risks . METHODS An age-stratified r and om sample of individuals , aged 20 - 45 years and without children , completed a computer-assisted telephone interview from two urban regions of Alberta , Canada ( 1006 women and 500 men ) . RESULTS Factors that influenced timing of childbearing for both men and women included : financial security ( 85.8 % ) and partner suitability to parent ( 80.2 % ) . Over 70 % of men and women recognized the direct relationship between older maternal age and conception difficulties . Less than half knew that advanced maternal age increased the risk of stillbirth , caesarean delivery , multiple birth and preterm delivery . CONCLUSIONS Poor underst and ing of the links between childbearing after age 35 , pregnancy complications and increased risk of adverse infant outcomes limits adults ' ability to make informed decisions about timing of childbearing Women of reproductive age have insufficient fertility knowledge and awareness . Reproductive lifespan and assisted reproduction are the primary areas in which awareness is lacking . Relatively simple interventions can be used to increase knowledge among university students ; however , no intervention has been tested to date in a population with more varied education levels . The aim of this study was to evaluate which intervention most improved fertility knowledge in women attending a fertility centre for oocyte donation . A r and omized controlled trial was conducted with three intervention groups : tailored , untailored and control . A question naire was administered on the day of the first consultation , and again at the oocyte retrieval . Two hundred and one women were enrolled and completed the pre-test , 109 started the cycle and 90 completed the post-test . The effect of the intervention was measured as the difference between the groups in their score from the pre-test to the post test . Only the tailored group showed a significant increase ( + 2.5 ; 95 % CI [ 1.8 , 3.3 ] ; P = 0.001 ) . Information relating to a woman 's most fertile age and limits for childbearing were the most useful . Tailored oral education , therefore , increases fertility knowledge in young women , particularly in relation to their fertility lifespan Objective Fertility declines as women age . Advancing maternal age increases pregnancy risks such as diabetes or hypertension . Studies suggest women are not aware of the risks of aging on fertility and pregnancy . The study objective was to assess women 's knowledge of fertility and reproductive outcomes affected by aging . Methods Prospect i ve IRB approved survey of women ( n=94 ) attending an obstetrics and gynecology ( OB/GYN ) clinic . Data collected included demographics , pregnancy history , and knowledge of age-related fertility decline and pregnancy risks . Statistical analysis performed using JMP Pro11.0 . Results Ages ranged from 18 to 67 . One third ( 30.5 % ) were aware fertility begins to decline at age 35 , however this varied among groups depending on prior history of infertility or requiring fertility treatment . Nulliparous women were more unaware of the health risks of pregnancy over age 35 ( 1.4 % vs 13.6 % , P 0.02 ) . African Americans ( AA ) women were less likely to think obesity ( 76 % Caucasian vs 47.8 % AA vs 66.7 % other , P < 0.05 ) and older age ( 88 % Caucasian vs 60.9 % AA vs 82.7 % other , P 0.02 ) affected fertility . Conclusion Knowledge regarding fertility and reproduction related to aging was variable and differed by age and race . Difficulty conceiving appears to be associated with higher knowledge levels . Public education will increase awareness of age-related fertility declines . Increased contact during pregnancy is an excellent opportunity to educate women in a nondirective way STUDY QUESTION What are the effects of fertility education on knowledge , childbearing desires and anxiety ? SUMMARY ANSWER Providing fertility information contributed to greater knowledge , but increased anxiety . WHAT IS KNOWN ALREADY Past studies have found that exposure to educational material improved fertility awareness and changed desires toward childbearing and its timing . Existing educational websites with evidence -based medical information provided in a non-judgmental manner have received favorable responses from reproductive-aged men and women . STUDY DESIGN , SIZE , DURATION This three-armed ( one intervention and two control groups ) , r and omized controlled trial was conducted using online social research panels ( SRPs ) in Japan in January 2015 . PARTICIPANTS / MATERIAL S , SETTING , METHODS A total of 1455 participants ( 726 men and 729 women ) between 20 and 39 years of age who hoped to have ( more ) children in the future were block-r and omized and exposed to one of three information brochures : fertility education ( intervention group ) , intake of folic acid during pregnancy ( control group 1 ) or governmental financial support for pregnancy and childbirth ( control group 2 ) . Fertility knowledge was measured with the Japanese version of the Cardiff Fertility Knowledge Scale ( CFKS-J ) . Knowledge , child-number and child-timing desires , subjective anxiety ( i.e. whether participants felt anxiety [ primary outcome ] ) , and scores on the State-Trait Anxiety Inventory were assessed immediately after exposure . Non-inferiority comparisons were performed on subjective anxiety with non-inferiority declared if the upper limit of the two-sided 95 % confidence interval ( CI ) for risk difference did not exceed a margin of 0.15 . This test for non-inferiority was only performed for subjective anxiety ; all the other variables were tests of superiority . MAIN RESULTS AND THE ROLE OF CHANCE Posttest scores on the CFKS-J ( mean , SD ) were higher in the intervention group than that of the control groups : intervention versus Control 1 and versus Control 2 : 52.8 ( 28.8 ) versus 40.9 ( 26.2 ) ( P < 0.001 ) versus 45.1 ( 27.1 ) ( P = 0.003 ) among men and 64.6 ( 26.0 ) versus 50.8 ( 26.9 ) ( P < 0.001 ) versus 53.0 ( 26.4 ) ( P < 0.001 ) among women . The percentage of participants who felt subjective anxiety after exposure to the intervention brochure was significantly higher than that of the control groups : intervention versus Control 1 and versus Control 2 : 32.6 versus 17.8 % ( risk difference [ RD ] = 0.149 , 95 % CI : 0.073–0.225 ) versus 14.5 % ( RD = 0.182 , 95 % CI : 0.108–0.256 ) among men , and 50.2 versus 26.3 % ( RD = 0.239 , 95 % CI : 0.155–0.322 ) versus 14.0 % ( RD = 0.362 , 95 % CI : 0.286–0.439 ) among women . Non-inferiority of the intervention was inconclusive ( i.e. the CI included 0.15 ) among men whereas inferiority was declared among women . The incidence of anxiety was higher in the intervention group than that of the control groups especially among men aged 30 and older and among women aged 25 and older . No difference existed in childbearing desires between groups after exposure . LIMITATIONS , REASONS FOR CAUTION The possibility of selection bias associated with the use of SRPs ( higher socioeconomic status and education ) and volunteer bias toward those more interested in fertility may limit the generalizability of these findings . WIDER IMPLICATION S OF THE FINDINGS In addition to education targeting a younger generation , psychological approaches are needed to alleviate possible anxiety caused by fertility information . STUDY FUNDING /COMPETING INTEREST(S ) This study was funded by National Center for Child Health and Development , Seiiku Medical Study Grant ( 24 - 6 ) , the Daiwa Foundation Small Grants and Grant-in-Aid for JSPS Fellows ( 26 - 1591 ) . No competing interest declared . TRIAL REGISTRATION NUMBER UMIN Clinical Trials Registry . Trial registration number , 000016168 . TRIAL REGISTRATION DATE 13 January 2015 . DATE OF FIRST PATIENT 'S ENROLMENT 15 January 2015 Abstract Background : An emerging pattern of increasing median age at first birth among women has been well documented in Western countries . A similar but less remarkable trend is being experienced in sub-Saharan Africa . There is a paucity of information in Sub-Saharan Africa about awareness of age-related fertility decline . The aim of this study was to assess the perception of fertility , childbirth intentions and parenting attitudes among university students . Material s and methods : A cross-sectional survey of 231 female and 158 male students r and omly selected university undergraduates in Nigeria using a self-reported question naire . Results : The respondents overestimated the ages of slight ( 92.1 % ) and marked decline ( 89.4 % ) in female fertility . The chance of pregnancy after unprotected sex during ovulation was overestimated by 93.1 % of the respondents . Over three-quarters of them overestimated the success rate of in-vitro fertilization . The sources of information regarding fertility issues were mainly school ( 40.1 % ) , the media ( 20.6 % ) and family members ( 18.8 % ) . About 98.7 % of the childless respondents reported an intention to have children in the future . The mean number of children desired was 3.29±1.14 . Females desire to have their first and last children earlier than males ( p=0.000 ) . The perceived potential obstacles to having the desired children were the pursuit of career aspirations ( 35.5 % ) and the pursuit of personal interests ( 20.8 % ) . Conclusions : Misconceptions about fertility issues have grave implication s for involuntary childlessness and secondary infertility . Comprehensive family planning education that will address the misconceptions about female fecundity and parenting issues are required OBJECTIVE To assess knowledge and attitudes about infertility through a survey . DESIGN Descriptive study with stratified r and om sampling . SETTING Eighteen high schools were selected in Toronto , Ontario , Canada . PATIENT(S ) Seven hundred seventy-two students participated in the study . The mean age of students was 17.5 + /- 0.98 years . Females were 49.02 % ( n = 377 ) of the sample . The sample was ethnically diverse , consisting of > 13 groups . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) The main outcome was infertility knowledge and attitudes . Secondary analysis compared gender and socioeconomic status . RESULT ( S ) The majority ( 608 ; 79 % ) of high school students were familiar with the term infertility ( 95 % confidence interval : 76 % , 82 % ) . More than 94 % did not know that chlamydia or gonorrhea could lead to infertility . Seventy percent felt that protecting their fertility was important to them , with significantly more females feeling this way . There was a higher proportion of students from schools with low socioeconomic status who gave incorrect answers to knowledge-related questions and were unaware of the association between sexually transmitted infections and infertility . CONCLUSION ( S ) Although the majority of students value their fertility , knowledge about preventable factors causing infertility was limited . Increased efforts are needed to educate students on factors that may affect their fertility STUDY QUESTION Can reproductive life plan (RLP)-based information in contraceptive counselling before pregnancy increase women 's knowledge of reproduction , and of the importance of folic acid intake in particular ? SUMMARY ANSWER The RLP-based information increased women 's knowledge of reproduction including knowledge of folic acid intake . WHAT IS KNOWN ALREADY Many women have insufficient knowledge of reproduction , including a health-promoting lifestyle prior to conception , and highly educated women in particular postpone childbearing until an age when their fertile capacity has started to decrease . STUDY DESIGN , SIZE , DURATION The study was an r and omized controlled trial with one intervention group ( IG ) and two control groups ( CG1 , CG2 ) . A sample size calculation indicated that 82 women per group would be adequate . Recruitment took place during 3 months in 2012 and 299 women were included . The women were r and omized in blocks of three . All groups received st and ard care ( contraceptive counselling , Chlamydia testing , cervical screening ) . In addition , women in the IG were given oral and written RLP-based information about reproduction . PARTICIPANTS / MATERIAL S , SETTING , METHODS A total of 299 out of 338 ( 88 % ) Swedish-speaking women visiting a Student Health Centre were included ( mean age 23 years ) ; response rate was 88 % . Before the counselling , women in the IG and the CG1 completed a baseline question naire , including questions about lifestyle changes in connection to pregnancy planning , family planning intentions and knowledge of reproduction ( e.g. the fecundity of an ovum ) . At follow-up 2 months after inclusion , a structured telephone interview was performed in all groups ( n = 262 , 88 % participation rate ) . MAIN RESULTS AND THE ROLE OF CHANCE There was no difference between the groups regarding the mean knowledge score at baseline . The IG scored higher at follow-up than at baseline ( P < 0.001 ) ; the mean increased from 6.4 to 9.0 out of a maximum 20 points . The women in the CG1 scored no differently at follow-up than at baseline . The difference in the knowledge score between the IG and the two CGs was significant ( P < 0.001 ) , whereas no difference was shown between the two CGs . There was no difference between the groups at baseline regarding how many women could mention folic acid intake among the things to do when planning to get pregnant . At follow-up , 22 % in the IG , 3 % in CG1 and 1 % in CG2 mentioned folic acid intake ( P < 0.001 ) . At follow-up , more women in the IG also wished to have their last child earlier in life ( P < 0.001 ) than at baseline , while there was no difference in the CG1 . LIMITATIONS , REASONS FOR CAUTION As the study sample consisted of university students , it is possible that the effect of the intervention was connected to a high level of education and conclusions for all women of reproductive age should be drawn with caution . WIDER IMPLICATION S OF THE FINDINGS The provision of RLP-based information seems to be a feasible tool for promoting reproductive health . STUDY FUNDING /COMPETING INTEREST(S ) Study funding was received from the Faculty of Medicine , Uppsala University , Sweden . There are no conflicts of interest . TRIAL REGISTRATION NUMBER Clinical Trial.gov Identifier NCT01739101 ABSTRACT Objectives : The aim of our study was to investigate Ukrainian medical students ’ intentions and attitudes in relation to future parenthood , and their knowledge about fertility . Methods : A classroom survey was carried out of r and omly selected groups among 3568 Russian-speaking medical students . The response rate was 88.8 % ; 858 were female and 407 were male ; the mean age was 20.6 ( st and ard deviation [ SD ] 2.4 ) years . Results : One in four male and 16 % of female respondents did not want to have children , 3.3 % had children and 17 % wanted one child only . Female respondents wished to have their first child when they were 24.4 ( SD 2.4 ) years of age , and male respondents when they were 26.8 ( SD 3.4 ) years of age . Around 60 % of respondents reported there was a pronounced decline in female fertility after the age of 45 years . Conclusions : The desire to have children in the future is not apparent among medical students , especially not among men . Gaps in students ’ knowledge about fertility need to be addressed by sexual and reproductive education OBJECTIVE To examine the effectiveness of an educational intervention in increasing knowledge of fertility and the effectiveness of IVF among university students in Australia . DESIGN Two-group , pretest-posttest design . SETTING A large metropolitan university in Queensl and , Australia . PATIENT(S ) One hundred thirty-seven male and female undergraduate students . INTERVENTION(S ) Online information brochure on fertility ( intervention group ) , or an online information brochure on home ownership ( control group ) . MAIN OUTCOME MEASURE(S ) Knowledge of fertility , knowledge of IVF effectiveness , and desired age at commencement and completion of childbearing , assessed immediately before and after exposure to the brochure . RESULT ( S ) Exposure to the brochure result ed in significant increases in knowledge of fertility and knowledge of IVF effectiveness in the intervention group and significant decreases in desired age at commencement and completion of childbearing . No changes were observed in the control group . CONCLUSION ( S ) Educational intervention is a worthwhile endeavor that can increase knowledge of fertility and IVF effectiveness in the short-term . Further research is needed to evaluate whether increased knowledge persists and affects intentions in the longer-term . Because the determinants of timing of childbearing are highly multifactorial , fertility education should be paired with policies and practice s that support men and women to make informed decisions about the timing of childbearing Background To compare the underst and ing and perceptions of fertility issues among medical and non-medical University students . Methods In a prospect i ve case-control study , using a 43 item question naire with 5 sections and 43 questions regarding personal data ( 8 questions ) , lifestyle factors ( 9 questions ) , plans on having children ( 5 questions ) , age and fertility ( 5 questions ) , and lifestyle and fertility ( 16 questions ) , knowledge of fertility and influencing factors , desired age at commencement and completion of childbearing , among male and female medical and non-medical students in their first academic year at Vienna University , Vienna , Austria were evaluated . Results 340 students were included . 262/340 ( 77 % ) participants planned to have children in the future . Medical students ( n = 170 ) planned to have fewer and later children and had a higher awareness of the impact of age on fertility than non-medical students ( n = 170 ; estimated knowledge probability 0.55 [ medical students ] vs. 0.47 [ non-medical students ] ; F ( 1 , 336 ) = 5.18 and p = .024 ( η p = .015 ) . Gender did not independently affect estimated knowledge probability ( F ( 1 , 336 ) = 1.50 and p = .221 ) . More female and male medical students had a positive attitude towards Assisted Reproductive Technology in case of infertility than non-medical students ( 47 and 55 % vs. 23 and 29 % , respectively ; p = < .001 ) . Medical students had a healthier lifestyle than non-medical students . A healthy lifestyle and female gender were associated with higher fertility awareness . Conclusions Medical students have a higher awareness of fertility issues than non-medical students . Choice of academic study , gender , and personal life style are important factors affecting fertility awareness . These data may be helpful to address knowledge gaps among young non-medical Academics ABSTRACT Objective To explore attitudes towards family formation and fertility awareness among Danish female healthcare professionals . Methods We collected cross-sectional baseline data from a prospect i ve cohort study of 863 women , ranging in age from 20 to 40 years , working at a hospital in Denmark . Information about participants ’ intentions and attitudes towards family formation and fertility knowledge was gathered by means of a question naire . Results Only 2 % of the respondents did not want children . Most women believed that motherhood is important , and hoped to have two to three children . About half of the respondents intended to have their last child after the age of 35 years . The most important prerequisites for family formation included : living in a stable relationship , having completed one 's studies , a sound financial situation , a job that can be kept when having children , access to public child day care , and the possibility of travelling . As many as 50 % of women underrated the impact of a woman 's age on fertility , and overestimated the success rates of assisted reproductive technology ( ART ) treatments . Conclusions Many female healthcare professionals contemplated giving birth after the age of 35 years . Knowledge of fertility and ART success rates is needed to make well-informed decisions about when to have children STUDY QUESTION Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children ? SUMMARY ANSWER The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs . WHAT IS KNOWN ALREADY It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age . However , research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child . STUDY DESIGN , SIZE , DURATION An established computer simulation model of fertility , up date d with recent IVF success rates , was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one- , two- or three-child family , for different female ages at which the couple starts trying to conceive . PARTICIPANTS / MATERIAL S , SETTING , METHODS The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI . In order to focus the discussion , we single out three levels of importance that couples could attach to realizing a desired family size : ( i ) Very important ( equated with aim ing for at least a 90 % success chance ) . ( ii ) Important but not at all costs ( equated with a 75 % success chance ) ( iii ) Good to have children , but a life without children is also fine ( equated with a 50 % success chance ) . MAIN RESULTS AND THE ROLE OF CHANCE In order to have a chance of at least 90 % to realize a one-child family , couples should start trying to conceive when the female partner is 35 years of age or younger , in case IVF is an acceptable option . For two children , the latest starting age is 31 years , and for three children 28 years . Without IVF , couples should start no later than age 32 years for a one-child family , at 27 years for a two-child family , and at 23 years for three children . When couples accept 75 % or lower chances of family completion , they can start 4–11 years later . The results appeared to be robust for plausible changes in model assumptions . LIMITATIONS , REASONS FOR CAUTION Our conclusions would have been more persuasive if derived directly from large-scale prospect i ve studies . An evidence -based simulation study ( as we did ) is the next best option . We recommend that the simulations should be up date d every 5–10 years with new evidence because , owing to improvements in IVF technology , the assumptions on IVF success chances in particular run the risk of becoming out date d. WIDER IMPLICATION S OF THE FINDINGS Information on the chance of family completion at different starting ages is important for prospect i ve parents in planning their family , for preconception counselling , for inclusion in educational courses in human biology , and for increasing public awareness on human reproductive possibilities and limitations . STUDY FUNDING /COMPETING INTEREST(S ) No external funding was either sought or obtained for this study . There are no conflicts of interest to be declared BACKGROUND In the USA , the postponement of childbearing reflects contemporary social norms of delaying marriage , pursing educational goals and securing economic stability prior to attempting conception . Although university students are more likely to delay childbearing , it is unclear to what extent they are aware of age-related fertility decline . The current study is the first of its kind to assess fertility awareness and parenting attitudes of American undergraduate university students . METHODS Two-hundred forty-six r and omly selected undergraduate university students ( 138 females and 108 males ) completed an online self-report survey adapted from the Swedish Fertility Awareness Question naire . Students were evenly distributed between the freshman , sophomore , junior and senior classes with a mean age of 20.4 years . RESULTS Participants wanted to have their first and last child within the window of a woman 's fertility . However , participants demonstrated a lack of fertility awareness by vastly overestimating the age at which women experience declines in fertility , the likelihood of pregnancy following unprotected intercourse and the chances that IVF treatments would be successful in the case of infertility . Nearly 9 in 10 participants want to have children in the future and viewed parenthood as a highly important aspect of their future lives . CONCLUSIONS Delaying childbearing based on incorrect perceptions of female fertility could lead to involuntary childlessness . Education regarding fertility issues is necessary to help men and women make informed reproductive decisions that are based on accurate information rather than incorrect perceptions BACKGROUND Postponing childbirth is becoming increasingly common in Western countries , especially among women with higher education . OBJECTIVE The aim of the present study was to investigate female and male postgraduate students ' attitudes toward parenthood , their intentions to have children , perceived obstacles to having or raising children during postgraduate studies , and their awareness of fertility issues . METHODS A 52- question survey was mailed to r and omly selected postgraduate students attending a Swedish university . The question naire was developed based on earlier research by , and the professional experience of , the authors . Three pilot studies were conducted to test the question naire 's reliability and validity . The t , x2 , and Mann-Whitney U tests were used , as appropriate , to analyze responses . RESULTS Two hundred female and 200 male postgraduate students aged < or=40 years received question naires . The response rate was 71 % ( n=141 ) among women and 58 % ( n=116 ) among men . Most childless respondents had positive attitudes toward parenthood and wanted to have 2 or 3 children , and a majority of women wanted to have their last child after age 35 . Compared with men , women were more pessimistic about the effects of parenthood on their postgraduate studies , and perceived more problems related to balancing work and family life . One of 4 respondents overestimated a woman 's ability to become pregnant between 35 and 40 years of age , and about half had overly optimistic perceptions of the chances to have a baby by means of in vitro fertilization . CONCLUSIONS Most postgraduate students wanted to have children in the future . More women than men perceived that having children while completing postgraduate studies was or would be difficult , and that parenthood would negatively affect their status in the labor market . Because many female postgraduate students intend to have children at an age when female fecundity is decreased , information on fertility issues would help them make informed decisions regarding family planning OBJECTIVE To determine the impact of the initial infertility visit on treatment-related knowledge , patient anxiety , and appraisal s of treatment . DESIGN Prospect i ve survey . SETTING Academic medical center . PATIENT(S ) Two hundred thirty-four English-speaking women aged 18 - 50 years attending their first infertility visit . INTERVENTION(S ) Participants completed a survey assessing health literacy , knowledge , anxiety , and appraisal s of the treatment process before and after their infertility visit . MAIN OUTCOME MEASURE(S ) Knowledge of infertility and treatment and anxiety and appraisal scores . RESULT ( S ) Most participants were white and earned > $ 100,000/year and had at least a college education . Baseline knowledge of reproductive anatomy , assisted reproductive technology ( ART ) , and fertility factors was modest but improved after the initial visit . Factors associated with higher knowledge included higher education and income , white or Asian ethnicity , and English as a primary language . Patient appraisal s of treatment represented by the positive ( Challenge ) and negative ( Threat and Loss ) subscale scores on the Appraisal of Life Events ( ALE ) scale changed over time Negative appraisal s of treatment and anxiety scores decreased and positive appraisal s of treatment increased after the initial visit . Lower knowledge was associated with higher positive appraisal scores ; lower health literacy was associated with higher anxiety and appraisal scores ( positive and negative ) after the visit . Black women had higher Challenge scores compared with white and Asian women . Hispanic women had higher anxiety scores than non-Hispanic women . CONCLUSION ( S ) Infertility patients have modest baseline knowledge of fertility and infertility treatment . The initial infertility visit can improve this knowledge and decrease both negative appraisal s of treatment and anxiety levels . Differences in knowledge and appraisal were seen across ethnic groups and other demographic variables . Physicians should individualize patient counseling to improve patients ' knowledge and provide realistic treatment expectations while also reducing patient anxiety OBJECTIVE : To estimate the effects of aging on the percentage of outwardly healthy couples who are sterile ( completely unable to conceive without assisted reproduction ) or infertile ( unable to conceive within a year of unprotected intercourse ) . METHODS : A prospect i ve fecundability study was conducted in a sample of 782 couples recruited from 7 European centers for natural family planning . Women aged 18–40 years were eligible . Daily intercourse records were used to adjust for timing and frequency of intercourse when estimating the per-menstrual-cycle probability of conception . The number of menstrual cycles required to conceive a clinical pregnancy and the probability of sterility and infertility were derived from the estimated fecundability distributions for men and women of different ages . RESULTS : Sterility was estimated at about 1 % ; this percent did not change with age . The percentage infertility was estimated at 8 % for women aged 19–26 years , 13–14 % for women aged 27–34 years and 18 % for women aged 35–39 years . Starting in the late 30s , male age was an important factor , with the percentage failing to conceive within 12 cycles increasing from an estimated 18–28 % between ages 35 and 40 years . The estimated percentage of infertile couples that would be able to conceive after an additional 12 cycles of trying varied from 43–63 % depending on age . CONCLUSION : Increased infertility in older couples is attributable primarily to declines in fertility rates rather than to absolute sterility . Many infertile couples will conceive if they try for an additional year . LEVEL OF EVIDENCE : Abstract Objectives To explore older ( 35 years + ) primigravid women 's knowledge of the risks of delayed childbearing and to identify the characteristics of those with limited knowledge . Methods A cross-sectional survey involving 675 primigravid women in Tehran , Iran , using a cluster r and om sampling method at the first prenatal visit . A vali date d question naire assessed the women 's awareness of delayed-childbearing risks . Results Women variously identified conception difficulties , gestational diabetes , hypertension , multiple birth , caesarean section , preterm delivery , stillbirth , Down 's syndrome , congenital abnormality , and low birth weight , as associated with delayed childbearing . Awareness of infant risks ranged between 10 and 72 % . Awareness of maternal risks were independently related to the women ’s educational levels ( odds ratio [ OR ] : 1.95 ; 95 % confidence interval [ CI ] : 1.12–3.38 ) , planned pregnancy ( OR : 1.87 ; 95 % CI : 1.25–2.78 ) and maternal age ≥ 40 ( OR : 1.24 ; 95 % CI : 1.14–2.53 ) . Women aware of infant risks were significantly likely to be aged ≥ 40 ( OR : 1.87 ; 95 % CI : 0.01–5.12 ) , have post-graduate education ( OR : 2 ; 95 % CI : 1.90–4.42 ) , and have a planned pregnancy ( OR : 1.99 ; 95 % CI : 1.03–5.12 ) . Conclusion Women are largely unaware of the potential complications of delayed childbirth . Underst and ing the risks is important for reproductive healthcare providers and policy makers in providing appropriate information to enable women to make informed decisions on the timing of conception BACKGROUND Couples seeking infertility treatment are generally hungry for information about available therapeutic options and how to help themselves achieve pregnancy . This study examined couples ' perceptions of the information available from various sources in the context of achieved pregnancy or continuing treatment . METHODS A 3 year prospect i ve interview study started in April 2004 , following couples undergoing infertility treatment at a tertiary fertility clinic at Aberdeen Maternity Hospital . Fifty-four couples were invited to participate . Up to three semi-structured interviews took place , and were analysed thematically using a variation of grounded theory . RESULTS Twenty-seven couples agreed to participate and of the 25 couples followed up , 11 were diagnosed with unexplained infertility . The age range of the women was 22 - 41 years . All hoped to be given information on helping themselves to achieve pregnancy , spontaneous or assisted , and 19 of the 25 couples became pregnant . Most couples were dissatisfied with the written and verbal information routinely provided by the fertility clinic because it suggested lifestyle changes they had already attempted to adopt . They sought additional information from the internet , books and magazines . Those who became pregnant were generally empowered by the experience and thought that it had helped them to conceive . Women who were still undergoing treatment however , sometimes became distressed , blaming themselves for failing to follow the lifestyle advice provided . CONCLUSIONS Couples , especially those diagnosed with unexplained infertility , seek information to help themselves conceive , but only those who succeed find it an empowering experience STUDY QUESTION How good is fertility knowledge and what are treatment beliefs in an international sample of men and women currently trying to conceive ? SUMMARY ANSWER The study population had a modest level of fertility knowledge and held positive and negative views of treatment . WHAT IS KNOWN ALREADY Few studies have examined general fertility treatment attitudes but studies of specific interventions show that attitudes are related to characteristics of the patient , doctor and context . Further , research shows that fertility knowledge is poor . However , the majority of these studies have examined the prevalence of infertility , the optimal fertile period and /or age-related infertility in women , in university students and /or people from high-re source countries making it difficult to generalize findings . STUDY DESIGN , SIZE , DURATION A cross-sectional sample completed the International Fertility Decision-making Study ( IFDMS ) over a 9-month period , online or via social research panels and in fertility clinics . PARTICIPANTS / MATERIAL S , SETTING , METHODS Participants were 10 045 people ( 8355 women , 1690 men ) who were on average 31.8 years old , had been trying to conceive for 2.8 years with 53.9 % university educated . From a total of 79 countries , sample size was > 100 in 18 countries . All 79 countries were assigned to either a very high Human Development Index ( VH HDI ) or a not very high HDI ( NVH HDI ) . The IFDMS was a 45-min , 64-item English survey translated into 12 language s. The inclusion criteria were the age between 18 and 50 years and currently trying to conceive for at least 6 months . Fertility knowledge was assessed using a 13-item correct/incorrect scale concerned with risk factors , misconceptions and basic fertility facts ( range : 0 - 100 % correct ) . Treatment beliefs were assessed with positive and negative statements about fertility treatment rated on a five-point agree/disagree response scale . MAIN RESULTS AND THE ROLE OF CHANCE Average correct score for Fertility Knowledge was 56.9 % , with greater knowledge significantly related to female gender , university education , paid employment , VH HDI and prior medical consultation for infertility ( all P < 0.001 ) . The mean agreement scores for treatment beliefs showed that agreement for positive items ( safety , efficacy ) was correlated with agreement for negative items ( short/long-term physical/emotional effects ) ( P > 0.001 ) . People who had given birth/fathered a child , been trying to conceive for less than 12 months , who had never consulted for a fertility problem and who lived in a country with an NVH HDI agreed less with negative beliefs . HDI , duration of trying to conceive and help-seeking were also correlates of higher positive beliefs , alongside younger age , living in an urban area and having stepchildren . Greater fertility knowledge was associated with stronger agreement on negative treatment beliefs items ( P < 0.001 ) but was unrelated to positive treatment beliefs items . LIMITATIONS , REASONS FOR CAUTION There was volunteer bias insofar as more women , people of higher education and people with fertility problems ( i.e. met criteria for infertility , had consulted a medical doctor , had conceived with fertility treatment ) participated and this was true in VH and NVH HDI countries . The bias may mean that people in this sample had better fertility knowledge and less favourable treatment beliefs than is the case in the general population . WIDER IMPLICATION S OF THE FINDINGS Educational interventions should be directed at improving knowledge of fertility health . Future prospect i ve research should be aim ed at investigating how fertility knowledge and treatment beliefs affect childbearing and help-seeking decision-making BACKGROUND Postponing childbirth is becoming increasingly common in Western countries , especially among groups with higher education qualifications . It is relatively unknown to what extent women and men are aware of the age-related decline in female fertility . The aim was to investigate university students ' intentions and attitudes to future parenthood and their awareness regarding female fertility . METHODS Postal survey of a r and omly selected sample of 222 female ( 74 % response ) and 179 male ( 60 % response ) university students . RESULTS Female and male university students in Sweden have largely positive attitudes towards parenthood and want to have children . Women , in comparison to men , were significantly more concerned about problems related to combining work and children . Both women and men had overly optimistic perceptions of women 's chances of becoming pregnant . About half of women intended to have children after age 35 years and were not sufficiently aware of the age-related decline of female fecundity in the late 30s . CONCLUSIONS University students plan to have children at ages when female fertility is decreased without being sufficiently aware of the age-related decline in fertility . This increases the risk of involuntary infertility in this group , which is alarming in view of the great importance they put on parenthood OBJECTIVE Societal influence on infertile couples usually stems from what is known or perceived about the causes , risk factors and treatment of infertility in the population . This study aim ed to investigate perceptions of infertility among urbanresidents of Port Harcourt . MATERIAL S AND METHODS A cross-sectional , household-based survey was conducted in the Borikiri area of Port Harcourt in 2003 . A sample of 150 adults , aged 20 years and above was drawn by multi-staged r and om sampling involving the selection of streets , houses , households and finally individuals , as sampling units at different stages . Households were visited period of two days , and all eligible subjects wer interviewed using a pre-tested , interviewer administered , structured question naire . RESULTS Sixty ( 40.0 % ) of the respondents were females ; 105 ( 70 % ) were 20 - 29 years ; 58.7 % were unmarried ; and 66.7 % possessed tertiary education . Only 48 ( 32.0 % ) correctly identified a three-fold medical definition of infertility ( 2 = 38.88 , p-value = 0.00 ) . Between 88 % and 100 % were aware of a selection of factors perceived to increase the risk of infertility . About two-thirds ( 93 , 63.3 % ) felt that a woman was more likely to be responsible for infertility . Majority , 106 ( 70.7 % ) were aware of in-vitro fertilization , and 92 ( 61.3 % ) knew of artificial insemination by husb and and artificial insemination by donor respectively . Over 80 % were in support of artificial insemination by husb and and in-vitro fertilization , but only about 25 % and 10 % supported adoption and artificial insemination by donor , respectively . CONCLUSION Our study showed that most of Port Harcourt residents ' perception of the definition of infertility differed from its commonly used medical context . However many recognized some known risk factors of infertility and were aware of assisted reproductive technologies . But they were selective in the options they support . Patients ' level of knowledge and differences in perceptions between a biomedical and lay concept of infertility are important for health workers ' management decisions Background : Women aged 35 and older account for an increasing proportion of births and are at increased risk of pregnancy complications and poor infant outcomes . The objectives of the study were : 1 ) to determine what women know about delayed childbearing , including pregnancy complications and outcomes associated with low birthweight ( LBW , < 2500 grams ) , preterm delivery ( < 37 weeks ) and multiple birth , and 2 ) to assess the characteristics of women with limited knowledge of risks . Methods : A computer-assisted telephone interview survey was conducted with 1,044 r and omly selected women who delivered their first live-born infant , between July 2002 and September 2003 , in two urban centres , Calgary and Edmonton , in Alberta , Canada . Results : The proportion of women aware of specific childbearing risks associated with advanced maternal age were as follows : conception difficulties ( 85.3 % ) , multiple birth ( 24.0 % ) , caesarean section ( 18.8 % ) , preterm delivery ( 21.8 % ) , and LBW ( 11.2 % ) . Knowledge of specific developmental and health-related risks of suboptimal infant outcomes ranged between 18.0 % and 46.5 % . Logistic regression revealed that limited knowledge of maternal age-related pregnancy risks were associated with unplanned pregnancy ( OR , 1.48 ; 95 % CI , 1.03–2.14 ) , smoking ( OR , 1.83 ; 95 % CI , 1.29–2.60 ) and non-use of fertility treatment ( OR , 2.15 ; 95 % CI , 1.44–3.19 ) . Characteristics associated with limited knowledge of the risks associated with suboptimal birth outcomes were : age 35–39 years ( OR , 2.98 ; 95 % CI , 1.35–6.58 ) , less than post-graduate education ( < high school OR , 2.14 ; 95 % CI , 1.20–3.82 ) , and not currently enrolled as a student ( OR , 1.75 ; 95 % CI , 1.02–3.00 ) . Conclusions : Many women are generally unaware of the potential consequences of delayed childbearing . There are missed opportunities in preconception counselling and education , which should be addressed to allow for more informed decision-making about family planning . Résumé Context e : Une proportion croissante de bébés naissent de femmes de 35 ans et plus , lesquelles risquent davantage d’avoir des complications durant la grossesse et d’accoucher de nourrissons d’un poids sous-optimal . Notre étude visait : 1 ) à déterminer ce que les femmes savent au sujet de la procréation tardive , notamment des complications de la grossesse et des résultats associés à l’insuffisance de poids à la naissance ( IPN , < 2 500 g ) , à l’accouchement prématuré ( < 37 semaines ) et à l’accouchement multiple , et 2 ) à évaluer les caractéristiques des femmes qui connaissent mal ces risques . Méthode : Nous avons mené un sondage téléphonique assisté par ordinateur auprès de 1 044 femmes , sélectionnées au hasard , ayant accouché d’un premier enfant vivant entre juillet 2002 et septembre 2003 dans deux centres urbains de l’Alberta ( Calgary et Edmonton).Résultats : Les femmes connaissaient les risques de la procréation à un âge avancé dans les proportions suivantes : difficultés à concevoir ( 85,3 % ) , accouchement multiple ( 24 % ) , accouchement par césarienne ( 18,8 % ) , accouchement prématuré ( 21,8 % ) , et IPN ( 11,2 % ) . Entre 18 % et 46,5 % des répondantes connaissaient les risques développementaux et sanitaires auxquels est exposé un nouveau-né de poids sous-optimal . Une analyse de régression logistique a montré que la connaissance limitée des risques de la grossesse à un âge maternel avancé était associée à la grossesse non planifiée ( RC = 1,48 ; IC de 95 % = 1,03–2,14 ) , au tabagisme ( RC = 1,83 ; IC de 95 % = 1,29–2,60 ) et au fait de ne pas avoir subi de traitement de l’infertilité ( RC = 2,15 ; IC de 95 % = 1,44–3,19 ) . Les caractéristiques associées à la connaissance limitée des risques de l’IPN étaient les suivantes : avoir entre 35 et 39 ans ( RC = 2,98 ; IC de 95 % = 1,35–6,58 ) , ne pas avoir fait d’études postsecondaires ( moins qu’un diplôme d’études secondaires : RC = 2,14 ; IC de 95 % = 1,20–3,82 ) , et ne pas être inscrite en tant qu’étudiante ( RC = 1,75 ; IC de 95 % = 1,02–3,00 ) . Conclusions : Nombre de femmes ont peu conscience des répercussions possibles de la procréation tardive . Il y aurait des lacunes à combler sur le plan du counselling et de l’éducation avant la grossesse pour favoriser une prise de décisions plus éclairée en matière de planning familial OBJECTIVE To investigate the long-term effects of alcohol consumption on female fertility . DESIGN Prospect i ve study of a r and om sample of 7,393 women , selected from the 445,000 inhabitants of Stockholm County , Sweden , in 1969 . Self-estimated alcohol consumption was obtained from postal question naires . Data on hospitalizations for pregnancy outcomes including infertility examinations were analyzed until 1987 . SETTING Healthy women in Stockholm County , Sweden . PATIENT(S ) Seven thous and three hundred ninety-three women in the age range 18 - 28 years . MAIN OUTCOME MEASURE(S ) Rates of hospitalization for deliveries , miscarriages , legal abortions , extrauterine pregnancies , pelvic inflammatory disease , endometriosis , and infertility examinations were analyzed in relation to the intake of alcohol . RESULT ( S ) Two hundred fifty-two women underwent infertility examinations . High consumers had an increased risk for such examinations , as compared with moderate consumers : relative risk ratio ( RR ) = 1.59 ( 95 % confidence interval [ CI ] : 1.09 - 2.31 ) ; and low consumers had a decreased risk ( RR = 0.64 ; CI : 0.46 - 0.90 ) . Moreover , for both high and low consumers we observed a significantly lower number of first and second partus . Rates of miscarriage , extrauterine pregnancy , and pelvic inflammatory disease did not differ between high and low consumers of alcohol . CONCLUSION ( S ) High alcohol consumption was associated with increased risk of infertility examinations at hospitals and with lower numbers of first and second partus . It may be important for the female partner in an infertile couple to limit alcohol intake or to not drink at all OBJECTIVE To examine the effects of alcohol and caffeine on conception . DESIGN Prospect i ve observational study . SETTING Healthy volunteers in two manufacturing facilities . PATIENT(S ) One hundred twenty-four women who provided daily urine sample s for measurement of steroid hormones and hCG , and prospect i ve information about alcohol and caffeine consumption . MAIN OUTCOME MEASURE(S ) Probability of conception per 100 menstrual cycles . RESULT ( S ) There was > 50 % reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol . Caffeine consumption did not independently affect the probability of conception but may enhance alcohol 's negative effect . Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day . CONCLUSIONS This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive . Our results suggest that women who are attempting to conceive should abstain from consuming alcohol Abstract Objectives : Recent evidence has shown that young adults have poor knowledge about reproductive health and fertility , and that interventions are needed to increase fertility awareness . The aim of this study was to assess the effectiveness of a brief video in increasing knowledge about fertility and infertility in young adults . Methods : We carried out a two-arm , parallel-group , r and omised controlled trial with a pre-test/post-test design ( NCT02607761 , Clinical Trials.gov ) . The sample was composed of 173 undergraduates who completed a self-report question naire . Participants were r and omly assigned to exposure or no exposure to an educational video about reproductive health and infertility ( intervention group , n = 89 ; control group , n = 84 ) . Results : At baseline , participants revealed poor knowledge of infertility risk factors and fertility issues , and average knowledge of the definition of infertility . Interaction effects between group and time were found for all variables targeted in the video . Participants in the intervention group significantly increased their knowledge of fertility issues , infertility risk factors and the definition of infertility . No significant differences in post-test knowledge were observed in the control group , except for the age at which there is a marked decrease in female fertility . Conclusions : A short video intervention is effective in increasing short-term knowledge about reproductive health and infertility . If future research using longer intervals corroborates our findings , video intervention could be a useful tool in public health prevention campaigns |
13,074 | 30,420,407 | Conclusion Despite its poor predictive value , our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse , particularly in re source -limited setting . | Background Relapse continues to place significant burden on patients and tuberculosis ( TB ) programmes worldwide .
We aim ed to determine clinical and microbiological factors associated with relapse in patients treated with the WHO st and ard 6-month regimen and then evaluate the accuracy of each factor at predicting an outcome of relapse . | BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) RATIONALE Cavitary disease and delayed culture conversion have been associated with relapse . Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients . OBJECTIVES To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months . METHODS This study was a r and omized , open-label equivalence trial . HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid , rifampin , pyrazinamide , and ethambutol for 2 months , followed by 2 months of isoniazid and rifampin . After 4 months , patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were r and omly assigned to continue treatment for 2 more months or to stop treatment . Patients were followed for relapse for 30 months after beginning treatment . MEASUREMENTS AND MAIN RESULTS Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm . A total of 370 patients were eligible for per protocol analysis . Thirteen patients in the 4-month arm relapsed , compared with three subjects in the 6-month arm ( 7.0 vs. 1.6 % ; risk difference , 0.054 ; 95 % confidence interval with Hauck- And erson correction , 0.01 - 0.10 ) . CONCLUSION Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs result ed in a greater relapse rate . The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse BACKGROUND Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control . This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis . METHODS We conducted a noninferiority , r and omized , open-label , controlled trial involving patients 18 to 65 years of age with smear-positive , rifampin-sensitive , newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries . A st and ard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin ( 400 mg per day ) was substituted for ethambutol during the intensive phase and was continued , along with rifampin and isoniazid , during the continuation phase . The primary efficacy end point was an unfavorable outcome ( treatment failure , recurrence , or death or study dropout during treatment ) measured 24 months after the end of treatment , with a noninferiority margin of 6 percentage points , adjusted for country . RESULTS A total of 1836 patients were assigned to the 4-month regimen ( experimental group ) or the st and ard regimen ( control group ) . Baseline characteristics were well balanced between the groups . At 24 months after the end of treatment , the adjusted difference in the risk of an unfavorable outcome ( experimental group [ 21.0 % ] minus control group [ 17.2 % ] ) in the modified intention-to-treat population ( 1356 patients ) was 3.5 percentage points ( 95 % confidence interval , -0.7 to 7.7 ) . There was heterogeneity across countries ( P=0.02 for interaction , with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal ) and in baseline cavitary status ( P=0.04 for interaction ) and body-mass index ( P=0.10 for interaction ) . The st and ard regimen , as compared with the 4-month regimen , was associated with a higher dropout rate during treatment ( 5.0 % vs. 2.7 % ) and more treatment failures ( 2.4 % vs. 1.7 % ) but fewer recurrences ( 7.1 % vs. 14.6 % ) . There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen . CONCLUSIONS Noninferiority of the 4-month regimen to the st and ard regimen with respect to the primary efficacy end point was not shown . ( Funded by the Special Program for Research and Training in Tropical Diseases and others ; Clinical Trials.gov number , NCT00216385 . ) BACKGROUND WHO guidelines recommend early initiation of antiretroviral therapy ( ART ) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV , but evidence supporting this approach is poor quality . We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more . METHODS We did this r and omised , placebo-controlled trial between Jan 1 , 2008 , and April 31 , 2013 at 26 treatment centres in South Africa , Tanzania , Ug and a , and Zambia . We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy . Participants were r and omly allocated ( 1:1 ) to early ART ( starting after 2 weeks of tuberculosis treatment ) or delayed ART ( placebo , then starting ART at the end of 6 months of tuberculosis treatment ) . R and omisation was computer generated , with permuted blocks of size eight , and stratified by CD4 count ( 220 - 349 cells per μL vs ≥350 cells per μL ) . Patients and investigators were masked to treatment allocation until completion of 6-months ' tuberculosis treatment , after which the study was open label . The primary endpoint was a composite of failure of tuberculosis treatment , tuberculosis recurrence , and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population . Secondary endpoints included mortality . The study is registered with controlled-trials.com ( IS RCT N77861053 ) . FINDINGS We screened 13,588 patients and enrolled 1675 : 834 assigned early ART , 841 delayed ART . The primary endpoint was reached by 65 ( 8·5 % ) of 767 patients in the early ART group versus 71 ( 9·2 % ) of 771 in the delayed ART group ( relative risk [ RR ] 0·91 , 95 % CI 0·64 - 1·30 ; p=0·9 ) . Of patients with a CD4 cell count of 220 - 349 cells per μL , 26 ( 7·9 % ) of 331 patients versus 33 ( 9·6 % ) of 342 reached the primary endpoint ( RR 0·80 , 95 % CI 0·46 - 1·39 ; p=0·6 ) . For those with 350 cells per μL or more , 39 ( 8·9 % ) of 436 versus 38 ( 8·9 % ) of 429 reached the primary endpoint ( RR 1·01 , 95 % CI 0·63 - 1·62 ; p=0·4 ) . Mortality did not differ significantly between treatment groups ( RR 1·4 , 95 % CI 0·8 - 2·3 ; p=0·23 ) . Grade 3 and 4 adverse events occurred in 149 ( 18 % ) of 834 patients assigned early ART versus 174 ( 21 % ) of 841 assigned delayed ART ( p=0·37 ) . 87 ( 10 % ) of 834 versus 84 ( 10 % ) of 841 had immune reconstitution inflammatory syndrome ( p=0·56 ) . INTERPRETATION ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be up date d accordingly . FUNDING USAID , Zambia Ministry of Health , Tanzania Commission for Science and Technology , WHO-TDR The impact of smoking on tuberculosis outcome was evaluated in a territory-wide treatment programme . 16 345 consecutive patients undergoing chemotherapy for active tuberculosis in government chest clinics in Hong Kong from 2001 to 2003 were followed up prospect ively for 2 years for treatment outcome and subsequently tracked through the territory-wide tuberculosis notification registry for relapse until the end of 2012 . Smoking was associated with more extensive lung disease , lung cavitation and positive sputum smear and culture at the baseline . In both current smokers and ex-smokers , sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment . Both categories of smokers were significantly less likely to achieve cure or treatment completion within 2 years . Overall , 16.7 % of unsuccessful treatment outcomes were attributable to smoking , with the key contributor being default in current smokers and death in ex-smokers . Among successful treatment completers , there was a clear gradient ( hazard ratios of 1.00 , 1.33 and 1.63 ) of relapse risk from never-smokers to ex-smokers and current smokers , with an overall population attributable risk of 19.4 % ( current smokers : 12.2 % ; ex-smokers : 7.2 % ) . Smoking adversely affects baseline disease severity , bacteriological response , treatment outcome and relapse in tuberculosis . Smoking cessation likely reduces relapse and secondary transmission . Smoking adversely affects treatment response in TB . Smoking cessation reduces relapse and secondary transmission . BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed . METHODS We r and omly assigned patients with newly diagnosed , smear-positive , drug-sensitive tuberculosis to one of three regimens : a control regimen that included 2 months of ethambutol , isoniazid , rifampicin , and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin ; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months ; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months . Sputum specimens were examined on microscopy and after culture at regular intervals . The primary end point was a composite treatment failure and relapse , with noninferiority based on a margin of 6 percentage points and 90 % confidence intervals . RESULTS We enrolled a total of 827 patients from South Africa , Zimbabwe , Botswana , and Zambia ; 28 % of patients were coinfected with the human immunodefiency virus . In the per- protocol analysis , the proportion of patients with an unfavorable response was 4.9 % in the control group , 3.2 % in the 6-month group ( adjusted difference from control , -1.8 percentage points ; 90 % confidence interval [ CI ] , -6.1 to 2.4 ) , and 18.2 % in the 4-month group ( adjusted difference from control , 13.6 percentage points ; 90 % CI , 8.1 to 19.1 ) . In the modified intention-to-treat analysis these proportions were 14.4 % in the control group , 13.7 % in the 6-month group ( adjusted difference from control , 0.4 percentage points ; 90 % CI , -4.7 to 5.6 ) , and 26.9 % in the 4-month group ( adjusted difference from control , 13.1 percentage points ; 90 % CI , 6.8 to 19.4 ) . CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen . The 4-month regimen was not noninferior to the control regimen . ( Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust ; RIFAQUIN Current Controlled Trials number , IS RCT N44153044 . ) Background Despite recent increased clinical trials activity , no regimen has proved able to replace the st and ard 6-month regimen for drug-sensitive tuberculosis . Underst and ing the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials . Methods Using data from the r and omized controlled phase III trial REMoxTB , we evaluated sputum-based markers of speed of clearance of bacilli : time to smear negative status ; time to culture negative status on LJ or in MGIT ; daily rate of change of log10(TTP ) to day 56 ; and smear or culture results at weeks 6 , 8 or 12 ; as individual- and trial-level surrogate endpoints for long-term clinical outcome . Results Time to culture negative status on LJ or in MGIT , time to smear negative status and daily rate of change in log10(TTP ) were each independent predictors of clinical outcome , adjusted for treatment ( p < 0.001 ) . However , discrimination between low and high risk patients , as measured by the c-statistic , was modest and not much higher than the reference model adjusted for BMI , history of smoking , HIV status , cavitation , gender and MGIT TTP . Conclusions Culture conversion during treatment for tuberculosis , however measured , has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients . REMoxTB Clinical Trials.gov number : NCT00864383 RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various duration s in HIV-associated tuberculosis is unclear . OBJECTIVES To compare the efficacy of an intermittent 6-month regimen ( Reg6 M : 2EHRZ(3)/4HR(3 ) [ ethambutol , 1,200 mg ; isoniazid , 600 mg ; rifampicin , 450 or 600 mg depending on body weight < 60 or > or = 60 kg ; and pyrazinamide , 1,500 mg for 2 mo ; followed by 4 mo of isoniazid and rifampicin at the same doses ] ) versus a 9-month regimen ( Reg9 M : 2EHRZ(3)/7HR(3 ) ) in HIV/tuberculosis ( TB ) . METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were r and omly assigned to Reg6 M ( n = 167 ) or Reg9 M ( n = 160 ) and monitored by determination of clinical , immunological , and bacteriological parameters for 36 months . Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up , whereas the secondary outcome was death . Intent-to-treat and on-treatment analyses were performed . All patients were antiretroviral treatment-naive during treatment . MEASUREMENTS AND MAIN RESULTS Of the patients , 70 % had culture-positive pulmonary TB ; the median viral load was 155,000 copies/ml and the CD4(+ ) cell count was 160 cells/mm(3 ) . Favorable response to antituberculosis treatment was similar by intent to treat ( Reg6 M , 83 % and Reg9 M , 76 % ; P = not significant ) . Bacteriological recurrences occurred significantly more often in Reg6 M than in Reg9 M ( 15 vs. 7 % ; P < 0.05 ) although overall recurrences were not significantly different ( Reg6 M , 19 % vs. Reg9 M , 13 % ) . By 36 months , 36 % of patients undergoing Reg6 M and 35 % undergoing Reg9 M had died , with no significant difference between regimens . All 19 patients who failed treatment developed acquired rifamycin resistance ( ARR ) , the main risk factor being baseline isoniazid resistance . CONCLUSIONS Among antiretroviral treatment-naive HIV-infected patients with TB , a 9-month regimen result ed in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen . ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment . Clinical Trials Registry Information : ID # NCT00376012 registered at www . clinical trials.gov BACKGROUND Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus ( HIV ) . Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy ( ART ) in relation to the start of antituberculosis therapy . METHODS We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4 + T-cell counts of 200 per cubic millimeter or lower . After beginning the st and ard , 6-month treatment for tuberculosis , patients were r and omly assigned to either earlier treatment ( 2 weeks after beginning tuberculosis treatment ) or later treatment ( 8 weeks after ) with stavudine , lamivudine , and efavirenz . The primary end point was survival . RESULTS A total of 661 patients were enrolled and were followed for a median of 25 months . The median CD4 + T-cell count was 25 per cubic millimeter , and the median viral load was 5.64 log(10 ) copies per milliliter . The risk of death was significantly reduced in the group that received ART earlier , with 59 deaths among 332 patients ( 18 % ) , as compared with 90 deaths among 329 patients ( 27 % ) in the later-ART group ( hazard ratio , 0.62 ; 95 % confidence interval [ CI ] ; 0.44 to 0.86 ; P=0.006 ) . The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group ( hazard ratio , 2.51 ; 95 % CI , 1.78 to 3.59 ; P<0.001 ) . Irrespective of the study group , the median gain in the CD4 + T-cell count was 114 per cubic millimeter , and the viral load was undetectable at week 50 in 96.5 % of the patients . CONCLUSIONS Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4 + T-cell counts of 200 per cubic millimeter or lower . ( Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health ; CAMELIA Clinical Trials.gov number , NCT01300481 . ) BACKGROUND Rifapentine has a long half-life in serum , which suggests a possible treatment once a week for tuberculosis . We aim ed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week . METHODS We did a r and omised , multicentre , open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen . We r and omly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week . Primary outcome was failure/relapse . Analysis was by intention to treat . FINDINGS 1004 patients were enrolled ( 502 per treatment group ) . 928 successfully completed treatment , and 803 completed the 2-year 4-month study . Crude rates of failure/relapse were 46/502 ( 9.2 % ) in those on rifapentine once a week , and 28/502 ( 5.6 % ) in those given rifampicin twice a week ( relative risk 1.64 , 95 % CI 1.04 - 2.58 , p=0.04 ) . By proportional hazards regression , five characteristics were independently associated with increased risk of failure/relapse : sputum culture positive at 2 months ( hazard ratio 2.8 , 95 % CI 1.7 - 4.6 ) ; cavitation on chest radiography ( 3.0 , 1.6 - 5.9 ) ; being underweight ( 3.0 , 1.8 - 4.9 ) ; bilateral pulmonary involvement ( 1.8 , 1.0 - 3.1 ) ; and being a non-Hispanic white person ( 1.8 , 1.1 - 3.0 ) . Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome ( 1.34 ; 0.83 - 2.18 ; p=0.23 ) . Of participants without cavitation , rates of failure/relapse were 6/210 ( 2.9 % ) in the once a week group and 6/241 ( 2.5 % ) in the twice a week group ( relative risk 1.15 ; 95 % CI 0.38 - 3.50 ; p=0.81 ) . Rates of adverse events and death were similar in the two treatment groups . INTERPRETATION Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography . Clinical , radiographic , and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen CONTEXT Fixed-dose combinations ( FDCs ) of drugs for treatment of tuberculosis have been advocated to prevent the emergence of drug resistance . OBJECTIVE To assess the efficacy and safety of a 4-drug FDC for the treatment of tuberculosis . DESIGN , SETTING , AND PATIENTS The Study C trial , a parallel-group , open-label , noninferiority , r and omized controlled trial conducted in 11 sites in Africa , Asia , and Latin America between 2003 and 2008 . Patients were 1585 adults with newly diagnosed smear-positive pulmonary tuberculosis . INTERVENTIONS Patients were r and omized to receive daily treatment with 4 drugs ( rifampicin , isoniazid , pyrazinamide , ethambutol ) given as an FDC ( n = 798 patients ) or separately ( n = 787 ) in the 8-week intensive phase of treatment . MAIN OUTCOME MEASURE Favorable treatment outcome , defined as negative culture result at 18 months post r and omization and not having already been classified as unfavorable . Noninferiority was dependent on consistent results from a per- protocol and modified intention-to-treat analysis , using 2 different models for the latter , classifying all changes of treatment or refusal to continue treatment ( eg , bacteriological failure/relapse , adverse event , default , drug resistance ) as unfavorable ( model 1 ) and classifying changes of treatment for reasons other than therapeutic outcomes according to their 18-month bacteriological outcome if available ( post hoc model 2 ) . The prespecified noninferiority margin was 4 % . RESULTS In the per- protocol analysis , 555 of 591 patients ( 93.9 % ) had a favorable outcome in the FDC group vs 548 of 579 ( 94.6 % ) in the separate-drugs group ( risk difference , -0.7 % [ 90 % confidence interval { CI } , -3.0 % to 1.5 % ] ) . In the model 1 analysis , 570 of 684 patients ( 83.3 % ) had a favorable outcome in the FDC group vs 563 of 664 ( 84.8 % ) in the separate-drugs group ( risk difference , -1.5 % [ 90 % CI , -4.7 % to 1.8 % ] ) . In the post hoc model 2 analysis , 591 of 658 patients ( 89.8 % ) in the FDC group and 589 of 647 ( 91.0 % ) in the separate-drugs group had a favorable outcome ( risk difference , -1.2 % [ 90 % CI , -3.9 % to 1.5 % ] ) . Adverse events related to trial drugs were similarly distributed among treatment groups . CONCLUSIONS Compared with a regimen of separately administered drugs , a 4-drug FDC regimen for treatment of tuberculosis satisfied prespecified noninferiority criteria in 2 of 3 analyses . Although the results do not demonstrate full noninferiority of the FDCs compared with single drugs given separately using the strict definition applied in this trial , use of FDCs is preferred because of potential advantages associated with the administration of FDCs compared with separate-drug formulations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00216333 |
13,075 | 31,118,753 | Clinical trials also showed beneficial effects on nerve conduction parameters and nerve fiber regeneration , with a good safety profile .
These data indicate that ALC provides an effective and safe treatment in patients with painful peripheral neuropathy . | Abstract Acetyl-L-carnitine ( ALC ) has shown a neuroprotective effect in patients with peripheral neuropathies of different etiologies .
Pre clinical studies demonstrated a central anti-nociceptive action , both in neuropathic and nociceptive pain models .
The present review aims to provide the knowledge on the efficacy of ALC in patients with painful peripheral neuropathy , based on the evidence . | Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus ( HIV ) patients under dideoxynucleoside therapy , benefits only partially from medical therapy , and often leads to drug discontinuation . Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism , eventually related to a reduction of mitochondrial DNA content , and interference with nerve growth factor activity . Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions . Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation . The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients . Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period . Efficacy was evaluated by means of the modified Short Form McGill Pain Question naire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit . Mean pain intensity score was significantly reduced during the study , changing from 7.35 + /- 1.98 ( mean + /- SD ) at baseline to 5.80 + /- 2.63 at week 4 ( p = 0.0001 ) . Electrophysiological parameters did not significantly change between baseline and week 4 . In this study , acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity . On the contrary , no effect was noted on neurophysiological parameters Acetyl-L-carnitine ( ALC ) improves non-oncological neuropathies . We tested oral ALC ( 1 g tid ) for 8 weeks in 25 patients with neuropathy grade 3 ( common toxicity criteria --CTC ) during paclitaxel or cisplatin therapy , or grade 2 persisting for at least three months after discontinuing the drugs . An independent neurologist assessed patients before and after ALC . All patients except one reported symptomatic relief , and only two described grade 1 nausea . The sensory neuropathy grade improved in 15 of 25 ( 60 % ) , and motor neuropathy in 11 of 14 patients ( 79 % ) . Total neuropathy score ( TNS ) that included neurophysiological measures improved in 23 ( 92 % ) . Amelioration of sensory amplitude and conduction velocity ( sural and peroneal nerves ) was measured in 22 and 21 patients , respectively . Symptomatic improvement persisted in 12 of 13 evaluable patients at median 13 months after ALC . In view of its effect in improving established paclitaxel- and cisplatin-neuropathy , we recommend ALC testing in preventing progression or revert symptoms during neurotoxic chemotherapy Purpose Retreatment with bortezomib ( B ) is often considered for patients with relapsed multiple myeloma ( MM ) , but this strategy is hindered by uncertainty of response and emergence of B-induced peripheral neuropathy ( PN ) . We incorporated acetyl-l-carnitine ( ALCAR ) to prevent PN and allow for adequate dosing . We also investigated the correlation between B-inducible NF-κB activation and response to therapy . Methods Nineteen patients with relapsed/refractory MM received up to 8 cycles of intravenous bortezomib , doxorubicin and oral low-dose dexamethasone ( BDD ) to evaluate response and toxicity . Thirteen additional patients received prophylactic ALCAR ( BDD-A ) . Patients receiving BDD-A were evaluated by FACT-GOG-TX , FACIT-Fatigue , Neuropathic Pain index ( NPI ) and Grooved Pegboard ( GP ) testing . Primary MM cells from 11 patients were tested for B-inducible NF-κB activation . Results Seventy-six percent of subjects were refractory to previous treatment , 39 % refractory to bortezomib . Median cycles received were 5 . CR + PR for the entire group were 53 % and did not differ between groups . Incidence of ≥3 PN was 32 % in the BDD group versus 15 % in the BDD-A group ( p = ns ) . Patient-reported fatigue and PN measured by FACT-GOG-TX increased throughout the treatment period in the BDD-A group , although time to complete GP testing declined . In a sub- study examining constitutive bortezomib-inducible NF-κB activity in primary subject-specific MM cells , the presence of NF-κB activation correlated with lower likelihood of response . Conclusions Addition of ALCAR to BDD did not alter the incidence or severity of PN in relapsed MM patients receiving a B-based regimen . Bortezomib-inducible NF-κB activation in patient-derived primary MM cells may be associated with poorer response The aim of this study was to investigate the antioxidant effect of acetyl-L-carnitine ( ALC ) against gamma-irradiation-induced oxidative damage in liver and lung tissue after total body irradiation with a single dose of 6Gy . To achieve the ultimate goal of this study , 40 adult rats were r and omly divided into 4 groups of 10 animals each . Group I was injected intraperitoneally with saline solution for 5 consecutive days and served as control group . Group II was irradiated with a single dose of 6Gy . Group III was daily injected with ALC ( 250 mg kg(-1 ) , i.p . ) for 5 consecutive days . Group IV received a daily i.p . injection of ALC ( 250 mg kg(-1 ) , i.p . ) for 5 consecutive days and 1h after the last dose , rats were irradiated with a single dose ( 6Gy ) . The animals were sacrified after 24h . Administration of ALC for 5 consecutive days result ed in a significant increase in the activities of both superoxide dismutase ( SOD ) and glutathione peroxidase ( GSHPx ) and the level of reduced glutathione ( GSH ) , in lung and liver tissues which were reduced by radiation treatment . Also , ALC result ed in a significant decrease in total nitrate/nitrite ( NO(x ) ) and malondialdehyde ( MDA ) levels in both lung and liver tissues and a significant decrease in triglycerides , low-density lipoprotein-cholesterol ( LDL ) , high-density lipoprotein-cholesterol ( HDL ) , total cholesterol , Serum alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) levels and Gamma glutamyl transpeptidase ( GGTP ) compared to irradiated group . In conclusion , data obtained from this study indicate that ALC could increase the endogenous antioxidant defense mechanism in rat and there by protect the animals from radiation-induced organs toxicity Abstract Aims / Introduction To assess the efficacy and safety of acetyl‐L‐carnitine ( ALC ) on diabetic peripheral neuropathy compared with methylcobalamin ( MC ) . Material s and methods This was a multicenter , r and omized , parallel‐group , double‐blind , double‐dummy , positive‐controlled , non‐inferior phase II clinical trial . Diabetic patients with abnormal nerve conduction test results were r and omized in a 1:1 ratio to receive oral ALC 500 mg t.i.d . or MC 0.5 mg t.i.d . for 24 weeks . The neuropathy symptom score , neuropathy disability score and neurophysiological parameters were measured during follow up . Results A total of 232 patients were r and omized ( ALC n = 117 , MC n = 115 ) , 88 % of which completed the trial . At week 24 , patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups ( neuropathy symptom score reduction : ALC vs MC 2.35 ± 2.23 , P < 0.0001 vs 2.11 ± 2.48 , P < 0.0001 , intergroup P = 0.38 ; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90 , P < 0.0001 vs 1.35 ± 1.65 , P < 0.0001 , intergroup P = 0.23 ) . Neurophysiological parameters were also improved in both groups . No significant difference was found between groups in the development of adverse events . Conclusions ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24‐week period with good tolerance OBJECTIVE We evaluated frozen data bases from two 52-week r and omized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-L-carnitine ( ALC ) : 500 and 1,000 mg/day t.i.d . RESEARCH DESIGN AND METHODS Intention-to-treat patients amounted to 1,257 or 93 % of enrolled patients . Efficacy end points were sural nerve morphometry , nerve conduction velocities , vibration perception thresholds , clinical symptom scores , and a visual analogue scale for most bothersome symptom , most notably pain . The two studies were evaluated separately and combined . RESULTS Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters . Nerve conduction velocities and amplitudes did not improve , whereas vibration perception improved in both studies . Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC . CONCLUSIONS These studies demonstrate that ALC treatment is efficacious in alleviating symptoms , particularly pain , and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy Aims and background In addition to bone marrow suppression and renal toxicity , neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes , cisplatin and vinca alkaloids . Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification . The aim of the present exploratory study was to investigate the activity of acetyl-L-carnitine in reversing peripheral neuropathy in patients with chemotherapy-induced peripheral neuropathy . Methods and study design Twenty-seven patients ( 16 males and 11 females ) with paclitaxel and /or cisplatin-induced neuropathy ( according to WHO recommendations for the grading of acute and subacute toxic effects ) were enrolled . Patients received at least one cisplatin- ( n = 5 ) or one paclitaxel- ( n = 11 ) based regimen , or a combination of both ( n = 11 ) . Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die iv infusion over 1 - 2 h for at least 10 days . Results Twenty-six patients were evaluated for response having completed at least 10 days of acetyl-L-carnitine therapy ( median , 14 days ; range , 10 - 20 ) . At least one WHO grade improvement in the peripheral neuropathy severity was shown in 73 % of the patients . A case of insomnia related to ALC treatment was reported in one patient . Acetyl-L-carnitine seems to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy . Conclusions Our preliminary results should be confirmed in double-blind , placebo controlled studies Background : Nucleoside analogue reverse transcriptase inhibitors ( NRTI ) disrupt neuronal mitochondrial DNA synthesis , impairing energy metabolism and result ing in a distal symmetrical polyneuropathy ( DSP ) , an antiretroviral toxic neuropathy ( ATN ) that causes significant morbidity in HIV disease . Serum acetyl-l-carnitine ( ALCAR ) levels are decreased in neuropathy associated with NRTI therapy . ALCAR enhances neurotrophic support of sensory neurons and promotes energy metabolism , potentially causing nerve regeneration and symptom relief . Objective : To assess the efficacy of oral ALCAR ( 1500 mg twice daily ) for up to 33 months in an open cohort of 21 HIV-positive patients with established ATN . Methods : Skin biopsies were excised from the leg before ALCAR treatment , at 6–12 month intervals thereafter and from HIV-negative non-neuropathic controls . Fibre types in epidermal , dermal and sweat gl and innervation were quantified immunohistochemically . Results : After 6 month 's treatment , mean immunostaining area for small sensory fibres increased ( epidermis 100 % , P = 0.006 ; dermis 133 % , P < 0.05 ) by more than that for all fibre types ( epidermis 16 % , P = 0.04 ; dermis 49 % , P < 0.05 ; sweat gl and s 60 % , P < 0.001 ) or for sympathetic fibres ( sweat gl and s 41 % , P < 0.0003 ) . Compared with controls , epidermal , dermal and sweat gl and innervation reached 92 % , 80 % and 69 % , respectively , after 6 month 's treatment . Innervation improvements continued ( epidermis and dermis ) or stabilized ( sweat gl and s ) after 24 month 's treatment . Neuropathic grade improved in 76 % of patients and remained unchanged in 19 % . HIV RNA load , CD4 and CD8 cell counts did not alter significantly throughout the study . Conclusions : ALCAR treatment improves symptoms , causes peripheral nerve regeneration and is proposed as a pathogenesis-based treatment for DSP Objective : A severe dose-limiting axonal peripheral neuropathy may develop in subjects on treatment with the nucleoside analogues didanosine ( ddI ) , zalcitabine ( ddC ) , and stavudine ( d4 T ) . The impairment of mitrochondrial DNA synthesis is crucial to the pathogenesis of this disorder although other mechanisms have not been ruled out . The depletion of acetyl-carnitine , which regulates the metabolism and function of peripheral nerves , could contribute to the neurotoxicity of these compounds . Design : Non-r and omized , cross-sectional study of selected patients . Methods : We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues ( ddI , ddC , d4 T ) . Subjects who did not develop peripheral neuropathy while staying on treatment with ddI ( n = 10 ) or zidovudine ( n = 11 ) served as the control groups . HIV-negative subjects with axonal or demyelinating autoimmune neuropathies ( n = 10 ) and healthy individuals ( n = 13 ) were additional control groups . Results : Subjects experiencing axonal peripheral neuropathy on treatment with ddI , ddC and d4 T had significantly reduced levels of acetyl-carnitine in comparison to the control groups . No difference was observed in the levels of total carnitine between study subjects and the control groups . Conclusions : Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddI , ddC and d4 T had acetyl-carnitine deficiency . The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems . The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddI , ddC and d4 T , even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity We studied the effects of acetyl-L-carnitine on pain in 16 HIV+ patients affected by painful distal symmetrical neuropathy . Patients were treated with 0.5 - 1 gr per day of acetyl-L-carnitine either i.m . or i.v . for 3 weeks . Pain intensity was measured before and after the treatment by the Huskisson 's analogic scale . Ten patients ( 62.5 % ) reported an improvement of symptoms , five patients ( 31.25 % ) were unchanged , one patient worsened . The results of this open study show that acetyl-L-carnitine can have a role in the treatment of pain in distal symmetrical polyneuropathy related to HIV infection . However , further double-blind , placebo-controlled studies are needed to confirm these preliminary results The present study aim ed to evaluate the efficacy and safety of acetyl-L-carnitine ( ALC ) for the treatment of chemotherapy-induced peripheral neuropathy ( CIPN ) . The study was carried out as a prospect i ve , r and omized , double-blind , placebo-controlled and paralleled clinical study . A total of 239 patients with CIPN were selected as the study subjects . Of the 239 subjects , 118 subjects received 3 g/day ALC orally for 8 weeks and 121 received a placebo . The primary endpoint was improvement of peripheral neuropathy by at least one grade . Patient status was assessed at week 4 , 8 and 12 after enrollment into the study . In both the full analysis set ( FAS ) and the per- protocol set ( PPS ) , peripheral sensory neuropathy was significantly ameliorated in the ALC group with 50.5 and 51.6 % patients meeting the primary endpoint at week 8 , compared with 24.1 and 23.1 % of patients in the placebo group ( P<0.001 in both sets ) . Secondary endpoints , such as the nerve electrophysiological examination and the Karnofsky physical score were also significantly improved in patients receiving ALC treatment , as compared with the placebo group ( FAS , P=0.0463 and P=0.022 ; PPS , P=0.0076 and P=0.0064 , respectively ) . Cancer-associated fatigue was significantly alleviated following ALC treatment in the PPS ( P=0.0135 ) . In the safety analysis set , the difference in adverse events incidence between the two groups was not statistically significant ( P=0.3903 ) . There were only two severe adverse events in the ALC group , which were not associated with the effect of ALC . In conclusion , the results of the present study demonstrated that in Chinese patients with cancer , oral administration of ALC is effective at ameliorating peripheral sensory neuropathy induced by chemotherapy , as well as reducing of cancer-associated fatigue and improving physical conditions Summary 426 patients with peripheral motor or sensory neuropathies were recruited and r and omly assigned to 2 treatment groups in a double-blind , 30-day , prospect i ve trial comparing L-acetylcarnitine ( LAC ) [ 1000 mg/day intramuscularly for the first 10 days then 2000 mg/day orally for the remaining 20 days ] with placebo . Treatment efficacy was assessed by commonly employed electrophysiological tests performed at baseline and at the end of treatment . Safety and tolerability evaluations were performed on the entire patient population , although the statistical analysis for efficacy was restricted to the 298 patients with lower-than-normal nerve conduction velocities ( CVs ) at baseline . Among patients with impaired motor nerve function , a statistically significant improvement in mean CV ( p < 0.01 vs placebo ) was detected in LAC-treated individuals with mononeuropathies , whereas no statistical difference emerged between the LAC- and placebo-treated groups in patients with motor nerve poly neuropathies . In contrast , there were statistically significant differences between the LAC and placebo groups in terms of improvement in mean CV in patients with sensory nerve mononeuropathies ( p < 0.05 ) and in those with sensory nerve polyneuropathies ( p < 0.05 ) . Only 17 patients reported poor tolerability to treatment , and only 7 of the 32 patients who were withdrawn from the study did so because of adverse events . Our trial demonstrated the efficacy of LAC in improving electrophysiological nerve conduction properties in patients with sensory or motor neuropathies |
13,076 | 26,787,125 | The primary outcomes were reduction or cessation of substance use .
They also did not have a significant effect on delinquent-type behaviour outcomes among adolescents .
We found low- or very low- quality evidence that brief school-based interventions may be more effective in reducing alcohol and cannabis use than the assessment -only condition and that these reductions were sustained at long-term follow-up .
We found moderate- quality evidence that , when compared to information provision , brief interventions probably did not have a significant effect on substance use outcomes .
It is premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use . | BACKGROUND Adolescent substance use is a major problem in and of itself , and because it acts as a risk factor for other problem behaviours .
As substance use during adolescence can lead to adverse and often long-term health and social consequences , it is important to intervene early in order to prevent progression to more severe problems .
Brief interventions have been shown to reduce problematic substance use among adolescents and are especially useful for individuals who have moderately risky patterns of substance use .
Such interventions can be conducted in school setting s. This review set out to evaluate the effectiveness of brief school-based interventions for adolescent substance use .
OBJECTIVES To evaluate the effectiveness of brief school-based interventions in reducing substance use and other behavioural outcomes among adolescents compared to another intervention or assessment -only conditions . | AIMS Despite widespread prevention efforts to decrease adolescent risk-taking , substance use and driving after drinking ( DD ) are prevalent in the United States . The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education ( DARE-A ) to a new Risk Skills Training Program ( RSTP ) . DESIGN Adolescent participation in drinking , drug use , DD and riding with a drunk driver was examined longitudinally . After baseline assessment s , adolescents were r and omly assigned to the RSTP . DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessment s. SETTING Adolescents attended a mid-sized suburban high school . PARTICIPANTS The sample ( N = 300 ) was comprised of 58 % females and the age range was 14 - 19 years . INTERVENTION The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting . DARE-A focused on increasing knowledge and underst and ing the deleterious effects of substance use . MEASUREMENTS Risk-taking behavior , perception of peer risk-taking and positive and negative alcohol expectancies were assessed . FINDINGS RSTP participants decreased participation in several risk behaviors at post-test , but reductions were not maintained at 6-month follow-up . The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies . The control group increased their alcohol consumption . CONCLUSIONS Results suggest that a brief , personalized , group prevention program is a feasible approach to reducing adolescent risk-taking . Strategies must be developed to solidify these positive changes so that they are longer-lasting This study evaluated the short-term ( eight-week ) benefits of brief intervention ( BI ) in students aged 14 - 19 years old who met the DSM-IV diagnostic criteria for methamphetamine ( MA ) dependence or abuse . The participants were r and omly assigned to receive two 20-minute sessions of BI or one 15-minute session of psychoeducation ( PE ) . Primary outcomes of interest were the decrease of MA use in days of use ( per week ) units and MA tablets used ( per day when used ) . All outcomes were assessed at baseline ( week 0 ) , week 4 , and week 8 ( endpoint ) . A total of 48 participants were enrolled in the study ( 24 on BI and 24 on PE treatment ) . At week 4 , the numbers of dropouts in the BI and PE groups were 7 and 5 , respectively . The frequency and amount of MA use decreased significantly in both groups . At week 8 , the days of MA use had decreased in the BI group by a significantly larger number than in the PE group ( t=2 , df=34 , p=0.04 ) . BI appears to have some minimal short-term benefits for adolescents with MA use disorders . It may decrease the number of days that MA is used Group motivational interviewing ( MI ) interventions that target youth at-risk for alcohol and other drug ( AOD ) use may prevent future negative consequences . Youth in a teen court setting [ n=193 ; 67 % male , 45 % Hispanic ; mean age 16.6 ( SD=1.05 ) ] were r and omized to receive either a group MI intervention , Free Talk , or usual care ( UC ) . We examined client acceptance , and intervention feasibility and conducted a preliminary outcome evaluation . Free Talk teens reported higher quality and satisfaction ratings , and MI integrity scores were higher for Free Talk groups . AOD use and delinquency decreased for both groups at 3 months , and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC . Results contribute to emerging literature on MI in a group setting . A longer term follow-up is warranted The authors evaluated the efficacy of a brief image-based prevention intervention and assessed current drug use as a moderator of intervention effects . In a clinical trial , 416 high school-age adolescents were r and omized to either the brief intervention or usual care control , with data collected at baseline and 3-month follow-up . The brief intervention consisted of a tailored in-person communication and a series of parent/guardian print material s based on the behavior-image model . Health behavior goal setting increased for participants receiving the brief intervention , with an effect size in the small range ( d = 0.33 ) . Overall effect sizes for cigarette smoking frequency and quantity and alcohol use frequency and quantity were small ( ds = 0.16 - 0.21 ) and in favor of the brief intervention . However , adolescents reporting current substance use who received the brief intervention reduced their frequency and heavy use of alcohol , frequency and quantity of cigarette smoking , and reported fewer alcohol/drug problems , with larger effects ranging from small to approaching medium in size ( ds = 0.32 - 0.43 , ps < .01 ) . This study suggests that brief image-based messages may increase health behavior goal setting and reduce substance use , particularly among drug-using older adolescents This study investigated the effects of social-cognitive group intervention on violence avoidance beliefs among at-risk adolescents . Fifty high school students were r and omly assigned to an experimental or a control group . The experimental group participated in ten , 2-hour weekly sessions of a social-cognitive intervention . Both groups were administered a question naire before , immediately following , and 3 months after the intervention . Findings showed that the social-cognitive intervention did not result in significant differences between the groups on violence avoidance beliefs at posttest or follow-up . In addition , drug/alcohol users and nonusers , fighters and nonfighters , and students threatened at school and those not threatened were compared . Students who used drugs/alcohol and fought in school had significantly lower scores ( i.e. , a greater belief in using violence as a coping technique ) than did students who did not engage in those behaviors OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention OBJECTIVE Methamphetamine use has become a growing problem in a number of countries over the past two decades , but has only recently emerged in South Africa . This study investigated the prevalence of methamphetamine use among high-school students in Cape Town and whether students reporting methamphetamine use were more likely to be at risk for mental health and aggressive behavior problems . METHODS A cross-sectional survey of 15 r and omly selected high schools in Cape Town , of 1561 males and females grade 8 - 10 students ( mean age 14.9 ) , was conducted using the Problem Oriented Screening Instrument for Teenagers ( POSIT ) and the Beck Depression Inventory ( BDI ) . RESULTS Findings indicated that 9 % of the students had tried methamphetamine at least once . Ordinal logistic regression analyses showed that methamphetamine use in the past year was significantly associated with higher aggressive behavior scores ( OR=1.81 , 95 % CI : 1.04 - 3.15 , p<0.05 ) , mental health risk scores ( OR=2.04 , 95 % CI : 1.26 - 3.31 , p<0.01 ) and depression scores ( OR=2.65 , 95 % CI : 1.64 - 4.28 , p<0.001 ) . CONCLUSIONS Methamphetamine use has become a serious problem in Cape Town , particularly among adolescents . Screening adolescents in school setting s for methamphetamine use and behavior problems may be useful in identifying youth at risk for substance misuse , providing an opportunity for early intervention . These findings have implication s for other parts of the world where methamphetamine use may be occurring at younger ages and highlight the importance of looking at co-morbid issues related to methamphetamine use OBJECTIVE Alcohol consumption in adolescence is associated with problem drinking in later life , and there is a need to develop evidence -based interventions to reduce adolescent alcohol consumption . The aims of the present study were to test the ability of a very brief intervention based on self-affirmation theory to reduce alcohol consumption in a sample of adolescents and to examine potential mediators of the effects . METHOD 67 adolescents were r and omly allocated either to form a self-affirming implementation intention or to complete a distractor task . All participants were exposed to a threatening message concerning the health risks of alcohol consumption . The main outcome measure was subsequent alcohol intake , but message processing ( operationalized as perceived threat and message derogation ) , behavioral intention , and self-efficacy were also measured as potential mediators . RESULTS The intervention produced a significant decrease in alcohol consumption : Participants in the self-affirming implementation intention condition consumed 2.48 fewer grams of pure alcohol per day at the end of the study than adolescents who completed the distractor task . The effect was not mediated by perceived threat , message derogation , behavioral intention , or self-efficacy . CONCLUSIONS The findings provide support for the efficacy of the self-affirming implementation intention for promoting health behavior change and extend previous research by testing an adolescent sample and observing longer term effects . Further research is needed to find out what mediates the effects of self-affirming implementation intentions on health behavior change This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes AIM To test whether beneficial effects of a single session of Motivational Interviewing ( MI ) on alcohol , tobacco and illicit drug use apparent after 3 months were maintained until 12 months . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either MI ( n = 105 ) or to an assessment -only control condition ( n = 95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people who were current users of illegal drugs ( age range 16 - 20 years ) with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from MI in the form of a topic-based 1-hour single-session discussion . MEASUREMENTS Changes in cigarette , alcohol , cannabis and other drug use and perceptions of risk and harm between the time of recruitment and follow-up interviews after 3 and 12 months . FINDINGS A satisfactory follow-up rate ( 81 % ) was achieved . After 12 months , 3-month differences between MI and assessment -only groups have disappeared almost entirely . Unexpected improvements by the assessment -only control group on a number of outcomes suggest the possibility of reactivity to the research assessment at 3-month follow-up . CONCLUSION In the terms of the original experiment , there is little evidence of enduring intervention effectiveness shown by between-group differences after 12 months . Deterioration of effect is the most probable explanation , although reactivity to 3-month assessment , a late Hawthorne effect , can not be ruled out Evidence for negative effects of early-onset cannabis use has led to a need for effective interventions targeting adolescent cannabis users . A r and omized controlled trial of an Australian two-session intervention based on motivational interviewing ( the ACCU , or Weed-Check in Dutch ) was replicated in a larger Dutch sample of 119 non-treatment-seeking adolescent cannabis users . Outcome measures at the 3-month follow-up were quantity and frequency of cannabis use , symptoms of dependence , stage of change , and psychosocial functioning . Changes in all measures were in the expected direction , yet not significant . In moderation analyses , heavier cannabis users at baseline receiving the Weed-Check had greater reductions in cannabis use than those in the control condition . These results suggest that the Weed-Check might be beneficial for heavier cannabis-using adolescents . Further research is needed to confirm these results in a sample of adolescent heavy cannabis users and to examine the relationship between MI skills of prevention workers and outcome BACKGROUND Cluster r and omized trials increasingly are being used in health services research and in primary care , yet the majority of these trials do not account appropriately for the clustering in their analysis . OBJECTIVES We review the main implication s of adopting a cluster r and omized design in primary care and highlight the practical application of appropriate analytical techniques . METHODS The application of different analytical techniques is demonstrated through the use of empirical data from a primary care-based case study . CONCLUSION Inappropriate analysis of cluster trials can lead to the presentation of inaccurate results and hence potentially misleading conclusions . We have demonstrated that adjustment for clustering can be applied to real-life data and we encourage more routine adoption of appropriate analytical techniques Reconnecting Youth ( RY ) is a school-based drug prevention program design ed to address academic , substance use and mood management goals among youth at risk of dropping out of high school . This paper presents the organizational factors and RY program characteristics that either promoted or hindered the implementation of the program during a r and omized controlled effectiveness trial in 10 schools in two school districts in the United States . Data were collected using surveys and interviews from teachers and school and district staff who participated in the implementation of the RY program in these schools . Results suggest that certain RY program characteristics made it difficult to implement . Small class size , re source -intensive procedures for student selection and recruitment and special training , qualities and skills needed to be an effective RY teacher meant that schools had to significantly change their usual practice s to implement the program . Organizational barriers included a lack of financial re sources and leadership support for program implementation , and low priority for non-academic courses for high-risk students . Transient student population s , staff turnover and district-wide scheduling and curriculum changes all result ed in high levels of organizational turbulence at most schools , further hindering program implementation Cannabis use adversely affects adolescents and interventions that are attractive to adolescents are needed . This trial compared the effects of a brief motivational intervention for cannabis use with a brief educational feedback control and a no- assessment control . Participants were r and omized into one of three treatment conditions : Motivational Enhancement Therapy ( MET ) , Educational Feedback Control ( EFC ) , or Delayed Feedback Control ( DFC ) . Those who were assigned to MET and EFC were administered a computerized baseline assessment immediately following r and omization and completed assessment s at the 3- and 12-month follow-up periods . Participants in the DFC condition were not assessed until the 3-month follow-up . Following the completion of treatment sessions , all participants were offered up to four optional individual treatment sessions aim ed at cessation of cannabis use . The research was conducted in high schools in Seattle , Washington . The participant s included 310 self-referred adolescents who smoked cannabis regularly . The main outcome measures included days of cannabis use , associated negative consequences , and engagement in additional treatment . At the 3-month follow-up , participants in both the MET and EFC conditions reported significantly fewer days of cannabis use and negative consequences compared to those in the DFC . The frequency of cannabis use was less in MET relative to EFC at 3 months , but it did not translate to differences in negative consequences . Reductions in use and problems were sustained at 12 months , but there were no differences between MET and EFC interventions . Engagement in additional treatment was minimal and did not differ by condition . Brief interventions can attract adolescent cannabis users and have positive impacts on them , but the mechanisms of the effects are yet to be identified This r and omized controlled trial evaluated the use of two brief intervention conditions for adolescents ( aged 12 - 18 years ) who have been identified in a school setting as abusing alcohol and other drugs . Adolescents and their parents ( N = 315 ) were r and omly assigned to receive either a two-session adolescent-only ( BI-A ) , two-session adolescent and additional parent session ( BI-AP ) , or assessment -only control condition ( CON ) . Interventions were manually guided and delivered in a school setting by trained counselors . Adolescents and parents were assessed at intake and at 6 months following the completion of the intervention . Analyses of relative ( change from intake to 6 months ) and absolute ( status at 6 months ) outcome variables indicated that for the most part , adolescents in the BI-A and BI-AP conditions showed significantly more reductions in drug use behaviors compared with the CON group . In addition , youth receiving the BI-AP condition showed significantly better outcomes compared with the BI-A group on several variables . Problem-solving skills and use of additional counseling services mediated outcome . The value of a school-based brief intervention for students is discussed Surveys of risk behaviors have been hobbled by their reliance on respondents to report accurately about engaging in behaviors that are highly sensitive and may be illegal . An audio computer-assisted self-interviewing ( audio-CASI ) technology for measuring those behaviors was tested with 1690 respondents in the 1995 National Survey of Adolescent Males . The respondents were r and omly assigned to answer questions using either audio-CASI or a more traditional self-administered question naire . Estimates of the prevalence of male-male sex , injection drug use , and sexual contact with intravenous drug users were higher by factors of 3 or more when audio-CASI was used . Increased reporting was also found for several other risk behaviors AIM To test whether a single session of Motivational Interviewing ( MI ) focussing on drinking alcohol , and cigarette and cannabis smoking , would successfully lead to reductions in use or problems . METHODS Naturalistic quasi-experimental study , in 162 young people ( mean age 17 years ) who were daily cigarette smokers , weekly drinkers or weekly cannabis smokers , comparing 59 receiving MI with 103 non-intervention assessment -only controls . MI was delivered in a single session by youth workers or by the first author . Assessment was made of changes in self-reported cigarette , alcohol , cannabis use and related indicators of risk and problems between recruitment and after 3 months by self-completion question naire . RESULTS 87 % of subjects ( 141 of 162 ) were followed up . The most substantial evidence of benefit was achieved in relation to alcohol consumption , with those receiving MI drinking on average two days per month less than controls after 3 months . Weaker evidence s of impact on cigarette smoking , and no evidence of impact on cannabis use , were obtained . CONCLUSIONS Evidence of effectiveness for the delivery of MI by youth workers in routine conditions has been identified . However , the extent of benefit is much more modest than previously identified in efficacy studies AIM To test whether a single session of motivational interviewing ( discussing alcohol , tobacco and illicit drug use ) would lead successfully to reduction in use of these drugs or in perceptions of drug-related risk and harm among young people . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either motivational interviewing ( n=105 ) or non-intervention education-as-usual control condition ( n=95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people ( age range 16 - 20 years ) currently using illegal drugs , with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from the literature on motivational interviewing in the form of a 1-hour single-session face-to-face interview structured by a series of topics . MEASUREMENTS Changes in self-reported cigarette , alcohol , cannabis and other drug use and in a range of drug-specific perceptions and other indicators of risk and harm . Measurement at recruitment and follow-up interview 3 months later . FINDINGS A good follow-up rate ( 89.5 % ; 179 of 200 ) was achieved . In comparison to the control group , those r and omized to motivational interviewing reduced their of use of cigarettes , alcohol and cannabis , mainly through moderation of ongoing drug use rather than cessation . Effect sizes were 0.37 ( 0.15 - 0.6 ) , 0.34 ( 0.09 - 0.59 ) and 0.75 ( 0.45 - 1.0 ) for reductions in the use of cigarettes , alcohol and cannabis , respectively . For both alcohol and cannabis , the effect was greater among heavier users of these drugs and among heavier cigarette smokers . The reduced cannabis use effect was also greater among youth usually considered vulnerable or high-risk according to other criteria . Change was also evident in various indicators of risk and harm , but not as widely as the changes in drug consumption . CONCLUSIONS This study provides the first substantial evidence of non-treatment benefit to be derived among young people involved in illegal drug use in receipt of motivational interviewing . The targeting of multiple drug use in a generic fashion among young people has also been supported A brief motivational interviewing ( MI ) intervention may be a viable adjunct to school-based substance abuse prevention programs . This article describes the development and implementation of a brief MI intervention with 573 adolescents ( mean age 16.8 ; 40.3 % female , 68 % Latino ) enrolled in eight continuation high schools in Southern California . Study participants were assigned to the MI condition in a r and omized controlled trial of Project Toward No Drug Abuse . Data are provided on dosage , topics discussed , and quality of MI determined with the Motivational Interviewing Skill Code ( MISC ) . Results suggest that the protocol was feasible and implemented with adequate fidelity . The study 's limitations are noted Young marijuana abusers rarely seek treatment themselves and are difficult to engage in treatment when referred by social agencies . To evaluate treatment engagement strategies in this population , 65 young probation-referred marijuana abusers were r and omly assigned to either three-session motivational enhancement therapy ( MET alone ) or three-session MET plus contingency management ( MET/CM ) , with vouchers for treatment attendance . A significantly higher number of participants in the MET/CM condition completed the three-session intervention as compared with MET alone . Participants in both conditions reported significant reductions in marijuana use and improvement in legal problems . These findings suggest that young marijuana abusers benefit from scientifically vali date d treatments This study evaluated the use of 2 brief interventions ( BIs ) to reduce drug use among 14- to 17-year-olds identified in a school setting as drug abusers . Students ( N = 79 ) were r and omly assigned to receive 1 of 3 target conditions : 2 sessions with the adolescent only ( BI-A ) , 2 sessions with the adolescent and 1 with the parent ( BI-AP ) , or an assessment -only control condition ( CON ) . Follow-up assessment s of 78 participants done 6 months post-intervention showed that the adolescents in the BI-A and BI-AP conditions generally had superior outcomes on their drug use behaviors compared with the CON group . Also , those receiving the BI-AP had better outcomes on most outcome variables compared with adolescents receiving BI-A. The 6-month abstinence rates did not differ across groups . The potential value of a school-based BI for students with a substance abuse disorder is discussed CONTEXT Selective school-based alcohol prevention programs targeting youth with personality risk factors for addiction and mental health problems have been found to reduce substance use and misuse in those with elevated personality profiles . OBJECTIVES To report 24-month outcomes of the Teacher-Delivered Personality-Targeted Interventions for Substance Misuse Trial ( Adventure trial ) in which school staff were trained to provide interventions to students with 1 of 4 high-risk ( HR ) profiles : anxiety sensitivity , hopelessness , impulsivity , and sensation seeking and to examine the indirect herd effects of this program on the broader low-risk ( LR ) population of students who were not selected for intervention . DESIGN Cluster r and omized controlled trial . SETTING Secondary schools in London , United Kingdom . PARTICIPANTS A total of 1210 HR and 1433 LR students in the ninth grade ( mean [ SD ] age , 13.7 [ 0.33 ] years ) . INTERVENTION Schools were r and omized to provide brief personality-targeted interventions to HR youth or treatment as usual ( statutory drug education in class ) . MAIN OUTCOME MEASURES Participants were assessed for drinking , binge drinking , and problem drinking before r and omization and at 6-monthly intervals for 2 years . RESULTS Two-part latent growth models indicated long-term effects of the intervention on drinking rates ( β = -0.320 , SE = 0.145 , P = .03 ) and binge drinking rates ( β = -0.400 , SE = 0.179 , P = .03 ) and growth in binge drinking ( β = -0.716 , SE = 0.274 , P = .009 ) and problem drinking ( β = -0.452 , SE = 0.193 , P = .02 ) for HR youth . The HR youth were also found to benefit from the interventions during the 24-month follow-up on drinking quantity ( β = -0.098 , SE = 0.047 , P = .04 ) , growth in drinking quantity ( β = -0.176 , SE = 0.073 , P = .02 ) , and growth in binge drinking frequency ( β = -0.183 , SE = 0.092 , P = .047 ) . Some herd effects in LR youth were observed , specifically on drinking rates ( β = -0.259 , SE = 0.132 , P = .049 ) and growth of binge drinking ( β = -0.244 , SE = 0.073 , P = .001 ) , during the 24-month follow-up . CONCLUSIONS Findings further support the personality-targeted approach to alcohol prevention and its effectiveness when provided by trained school staff . Particularly novel are the findings of some mild herd effects that result from this selective prevention program . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00776685 OBJECTIVE Adolescent substance use and abuse is a pressing public health problem and is strongly related to interpersonal aggression . Such problems disproportionately impact minority youth , who have limited access to evidence -based interventions such as ecological family therapies , brief motivational interventions ( BMI s ) , and cognitive behavioral therapies ( CBTs ) . With a predominantly minority sample , our objective was to rigorously evaluate the efficacy of a school-based BMI /CBT , Guided Self-Change ( GSC ) , for addressing substance use and aggressive behavior . METHOD We conducted a school-based r and omized , controlled trial with 514 high school students ( mean age 16.24 years , 41 % female , 80 % minority ) reporting using substances and perpetrating aggression . We used structural equation modeling to compare participants r and omly assigned to receive GSC or st and ard care ( SC ; education/ assessment /referral-only ) at posttreatment and at 3 and 6 months posttreatment on alcohol use , drug use , and interpersonal aggression outcomes as assessed by the Timeline Follow-Back . RESULTS Compared with SC participants , GSC participants showed significant reductions ( p < .05 ) in total number of alcohol use days ( Cohen 's d = 0.45 at posttreatment and 0.20 at 3 months posttreatment ) , drug use days ( Cohen 's d = 0.22 at posttreatment and 0.20 at 3 months posttreatment ) , and aggressive behavior incidents ( Cohen 's d = 0.23 at posttreatment ) . Moreover , treatment effects did not vary by gender or ethnicity . CONCLUSIONS With minority youth experiencing mild to moderate problems with substance use and aggressive behavior , GSC holds promise as an early intervention approach that can be implemented with success in schools This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication The aim of this study was to evaluate the efficacy of a brief motivational enhancement therapy in reducing cannabis use and cannabis-related problems in a population of non-treatment-seeking adolescent cannabis users . In a r and omized controlled trial , 40 young people ( aged 14 - 19 years ) were r and omly assigned to either a two-session brief intervention or a 3-month delayed-treatment control condition . The intervention consisted of a detailed assessment and a session of motivational enhancement therapy . An additional optional discussion of skills for reducing or quitting cannabis use was offered if a participant was interested in discussing these issues . Primary outcome measures were changes in days of cannabis use , mean quantity of cannabis used weekly , and number of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition dependence symptoms reported . Significantly greater reductions on these measures were found in the Adolescent Cannabis Check-up group at 3-month follow-up . Between-group effect sizes were moderate . The approach is acceptable to participants and merits further evaluation with this difficult to reach population Two manually guided brief interventions were evaluated with a r and omized , controlled trial . Adolescents ( aged 13 - 17 years ) suspected of abusing alcohol and other drugs and their parent were r and omly assigned to receive either a 2-session adolescent only ( BI-A ) , 2-session adolescent and additional parent session ( BI-AP ) , or assessment only control condition ( CON ) . Adolescents were identified in a school setting , and the intervention was delivered by trained counselors . Outcome analyses ( N = 284 ; 90 % of those enrolled ) of relative change ( from intake to 12 months ) and absolute status ( at 12 months ) revealed a general pattern of reductions in drug use behaviors , particularly with the cannabis outcome measures , in both active conditions ( BI-A and BI-AP ) . Students in the control condition showed worse outcome compared with the BI-A and BI-AP groups . Among the 4 mediating variables measured at 6 months , use of additional services , motivation to change , and parenting practice s had significant influences on 12-month outcome ; problem-solving skills approached significance as a mediator . The potential value of a brief intervention for drug abusing adolescents is discussed This article presents the main outcome findings from two inter-related r and omized trials conducted at four sites to evaluate the effectiveness and cost-effectiveness of five short-term outpatient interventions for adolescents with cannabis use disorders . Trial 1 compared five sessions of Motivational Enhancement Therapy plus Cognitive Behavioral Therapy ( MET/CBT ) with a 12-session regimen of MET and CBT ( MET/CBT12 ) and another that included family education and therapy components ( Family Support Network [ FSN ] ) . Trial II compared the five-session MET/CBT with the Adolescent Community Reinforcement Approach ( ACRA ) and Multidimensional Family Therapy ( MDFT ) . The 600 cannabis users were predominately white males , aged 15 - 16 . All five CYT interventions demonstrated significant pre-post treatment during the 12 months after r and om assignment to a treatment intervention in the two main outcomes : days of abstinence and the percent of adolescents in recovery ( no use or abuse/dependence problems and living in the community ) . Overall , the clinical outcomes were very similar across sites and conditions ; however , after controlling for initial severity , the most cost-effective interventions were MET/CBT5 and MET/CBT12 in Trial 1 and ACRA and MET/CBT5 in Trial 2 . It is possible that the similar results occurred because outcomes were driven more by general factors beyond the treatment approaches tested in this study ; or because of shared , general helping factors across therapies that help these teens attend to and decrease their connection to cannabis and alcohol Abstract Objective : Reduce college student at-risk drinking ( ARD ) using a Web-based brief motivational alcohol prevention/intervention called Michigan Prevention and Alcohol Safety for Students ( M-PASS ) . Participants : Participants included 1,137 r and omly sample d first-year college students , including 59 % female , 80 % white , and averaged age 18.1 years . Methods : Intervention group participants ( n = 616 ) attended 4 online M-PASS sessions , receiving feedback tailored to individual drinking patterns and concepts from 4 behavior change theories . Control group participants ( n = 521 ) completed a mid-phase survey , and both groups were surveyed at baseline and posttest . Results : Evidence of M-PASS 's efficacy was found . The intervention was associated with advanced stage of change , lower tolerance of drinking and drink/driving , fewer reasons to drink , and use of more strategies to avoid ARD . Preliminary evidence of behavioral change was also found . Efficacy was greater for women than men . Conclusions : Web-based programs may be useful in reducing alcohol-related risk among college students . Further evaluation is needed AIMS To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young , regular users of MDMA ( ' ecstasy ' ) , cocaine powder and crack cocaine . DESIGN AND MEASUREMENTS A r and omized trial of the intervention versus a control group who received written health risk information material s only . All participants completed a baseline self- assessment question naire before r and omization . Outcome measures were self-reported period prevalence abstinence from ecstasy , cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days , recorded at 6-month follow-up via self-completion question naire and personal interview . PARTICIPANTS AND SETTING A total of 342 adolescent and young adult stimulant users ( aged 16 - 22 years ) were recruited and 87 % were followed-up . The intervention was delivered by a team of 12 agency youth drug workers and two research ers at five locations in Greater London and south-east Engl and . FINDINGS There were no significant differences in abstinence for ecstasy , cocaine powder or crack cocaine use between the experimental and control groups . Contrasting follow-up with baseline self-reports , there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use . Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants . CONCLUSIONS Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone . We hypothesize that research recruitment , baseline self- assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use This study evaluated the psycho-educational small-group component of the CASPAR Youth Services Student Assistance Program with a r and omized-controlled trial . Two cohorts of at-risk sixth grade rs from six schools in two communities were r and omly assigned to intervention or control conditions and tested one and a half years later at the end of the seventh grade . A generalized estimating equations model yielded a significant intervention effect on all three composite outcome variables . The results support the effectiveness of prevention strategies aim ed at promoting positive youth development and a social influence process for adolescents that creates trusting relationships as the foundation for helping youth improve key skills , exert greater control over their lives , and make informed decisions about substances . Editor 's Strategic Implication s : School administrators should be aware of this promising approach ( pending replication ) of using student assistance counselors to promote children 's intrinsic motivation and potential for positive decision making OBJECTIVE The objective of this study was to develop and test a brief , experimental alcohol preventive intervention matched to the use of specific alcohol beverages among adolescents . METHOD A total of 232 high school students who drank within the last year participated in this study . Participants were r and omly assigned to either the experimental intervention or a minimal intervention control . Four-month postintervention data are reported . RESULTS Overall multivariate analyses of covariance ( MANCOVAs ) were significant ( p 's < .05 ) on risk factors ( influenceability , perceived severity , perceived susceptibility and perceived peer prevalence ) for three of six beverages ( beer , wine and distilled spirits ) , with a fourth , malt liquor , approaching significance ( p = .06 ) . These tests showed intervention adolescents experiencing less risk for alcohol use than control adolescents . In addition , whereas the overall MANCOVA for malt liquor use was not significant , univariate analyses were significant for 30-day frequency ( F = 5.69 , 1/195 df , p = .01 ) and 30-day quantity of malt liquor use ( F = 4.03 , 1/195 df , p = .04 ) with intervention adolescents showing less consumption than control adolescents . A post hoc analysis examining differential intervention effects using preintervention drug use as a factor ( i.e. , 30-day cigarette or marijuana use ) showed a significant overall factorial MANCOVA interaction ( F = 6.90 , 4/189 df , p = .000 ) , with drug-using intervention adolescents consuming cigarettes and marijuana less frequently than drug-using control adolescents at postintervention . CONCLUSIONS The findings of this study suggest the brief , beverage-tailored intervention reduced certain risk factors mediating individual alcohol beverage use and consumption of malt liquor ( 4 months after intervention ) and may have reduced the frequency of cigarette and marijuana use among those already using drugs Attendance and grade point average ( GPA ) data are universally maintained in school records and can potentially aid in identifying students with concealed behavioral problems , such as substance use . Research ers evaluated attendance ( truancy ) and GPA as a means to identify high school students at risk for substance use , suicide behaviors , and delinquency in 10 high schools in San Antonio , Texas , and San Francisco , California , during the spring and fall of 2002 . A screening protocol identified students as “ high risk ” if ( 1 ) in the top quartile for absences and below the median GPA or ( 2 ) teacher referred . Survey responses of 930 high-risk students were compared with those from a r and om sample of 393 “ typical ” students not meeting the protocol . Bivariate and multivariate analyses assessed associations between the screening protocol variables and demographics , risk and protective factors , and problem outcomes . The individual contribution of each of the variables was also assessed . Students identified as high risk were significantly more likely than typical students to use cigarettes , alcohol , and marijuana , evidence suicide risk factors , and engage in delinquent behavior . Norms varied between the two districts ; nevertheless , high-risk students showed consistent differences in risk and protective factors , as well as problem behaviors , compared with typical students . Because of site differences in data collection and teacher participation , the comprehensive protocol is recommended , rather than individual indicators alone ( e.g. , truancy ) . Strengths of the screening protocol are the ready availability of school record data , the ease of use of the adapted protocol , and the option of including teacher referral . More research is recommended to test the generalizability of the protocol and to ensure that there are no unintended negative effects associated with identification of students as high risk PURPOSE To implement a brief intervention aim ed at reducing abuse of alcohol among adolescents , and to assess its effectiveness . METHODS One thous and 10th- grade students from seven high schools , chosen by r and om from the roster of all schools in southern Israel , were assigned to intervention and control groups . The intervention , which was based on Botvin 's social skills theory , was conducted over 3 days and included dissemination of information , workshops , lectures by guest experts , and activity areas . It was administered by the staff of the high schools and the Psychological Counseling Service in Israel . A self-administered question naire was answered anonymously by students in the 10th grade ( pretest ) and again in the 11th and 12th grade s ( posttests ) . It included questions on sociodemographic data , alcohol-related habits , smoking habits , use of illicit drugs , knowledge , and attitudes . Data were collected between 1994 and 1997 with a 76 % follow-up rate at 2 years . RESULTS At baseline there was no statistical difference in alcohol consumption between the intervention and control groups . At 1- and 2-year follow-up the rates of alcohol consumption did not change in the intervention group ( p > .05 ) but rose significantly in the control group ( p < .001 ) . In multiple regression analysis the variables male gender , positive attitudes , cigarette smoking , availability of illegal drugs , and intervention group were significant predictors of alcohol consumption . CONCLUSIONS The results of this study show the effectiveness of this intervention program , based on reduced alcohol consumption in the intervention group at 1- and 2-year follow-up , compared with the control group . Compared with other programs , the present intervention is brief , intensive , and relatively easy to implement Six-hundred and fifty 6th grade students were r and omly assigned with the intervention group receiving the STARS for Families Program , an alcohol reduction program consisting of st and ardized health consultations provided by nurses and mailed follow-up information . The control group received minimum information . Students in the study attended either a neighborhood or a bused inner-city middle school . Students receiving the intervention had significantly less intentions to use alcohol in the future and less alcohol quantity . The study suggests that brief , provider-involved interventions may be a viable school based approach to prevention Background There is a significant public health burden associated with substance use in Canada . The early detection and /or treatment of risky substance use has the potential to dramatically improve outcomes for those who experience harms from the non-medical use of psychoactive substances , particularly adolescents whose brains are still undergoing development . The Screening , Brief Intervention , and Referral to Treatment model is a comprehensive , integrated approach for the delivery of early intervention and treatment services for individuals experiencing substance use-related harms , as well as those who are at risk of experiencing such harm . Methods This article describes the protocol for a systematic review of the effectiveness of brief interventions as part of the Screening , Brief Intervention , and Referral to Treatment model for reducing the non-medical use of psychoactive substances . Studies will be selected in which brief interventions target non-medical psychoactive substance use ( excluding alcohol , nicotine , or caffeine ) among those 12 years and older who are opportunistically screened and deemed at risk of harms related to psychoactive substance use . We will include one-on-one verbal interventions and exclude non-verbal brief interventions ( for example , the provision of information such as a pamphlet or online interventions ) and group interventions . Primary , secondary and adverse outcomes of interest are prespecified . R and omized controlled trials will be included ; non-r and omized controlled trials , controlled before-after studies and interrupted time series design s will be considered in the absence of r and omized controlled trials . We will search several bibliographic data bases ( for example , MEDLINE , EMBASE , CINAHL , PsycINFO , CORK ) and search sources for grey literature . We will meta-analyze studies where possible . We will conduct subgroup analyses , if possible , according to drug class and intervention setting . Discussion This review will provide evidence on the effectiveness of brief interventions as part of the Screening , Brief Intervention , and Referral to Treatment protocol aim ed at the non-medical use of psychoactive substances and may provide guidance as to where future research might be most beneficial AIM To test the effectiveness of motivational interviewing ( MI ) in comparison with drug information and advice in opportunistically securing reductions in drug-related risk among young cannabis users not seeking help . DESIGN R and omized controlled trial . SETTING Eleven London Further Education colleges . PARTICIPANTS A total of 326 students aged 16 - 19 years who smoked cannabis weekly or more frequently . INTERVENTIONS Participants were r and omized to a single-session intervention of MI or drug information and advice-giving . MEASUREMENTS Cannabis use , cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months . FINDINGS No differences were found between MI and drug information and advice , although MI fidelity was not high . There were wide-ranging individual practitioner effects on observed outcomes and a practitioner-intervention interaction was detected in relation to cannabis cessation after 3 months . Change over time was more pronounced for cannabis use than for other drug use . CONCLUSIONS Further study of the nature and consequences of MI fidelity , and individual practitioner effects more generally , is needed . Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials |
13,077 | 31,807,093 | We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children .
Patients who experience these symptoms have worse quality of life , with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features , such as active joint count .
Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their child 's mental health and pain symptoms related to JIA . | Depression and anxiety are prevalent in children with rheumatologic diseases , including juvenile idiopathic arthritis ( JIA ) .
However , prevalence rates and the relationship with disease outcomes , including quality of life are conflicting in the early literature . | Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers Child depression is an impairing condition for which psychotherapies have shown modest effects . Parental depression is a risk factor for development of child depression and might also be negatively associated with child depression treatment outcomes . To explore this possibility , we analyzed data from a study in which children were treated for depression after parental depressive symptoms had been assessed at baseline . Among children treated for depression in a r and omized controlled trial , we identified 31 who had child- and parent-report pre- and post-treatment data on child symptoms and parent-report of pre-treatment parental depressive symptoms . Children were aged 8–13 , 77 % boys , and 52 % Caucasian , 13 % African-American , 6 % Latino , and 29 % multi-racial . Analyses focused on differences in trajectories of change ( across weekly measurements ) , and post-treatment symptoms among children whose parents did ( n = 12 ) versus did not ( n = 19 ) have elevated depressive symptoms at baseline . Growth curve analyses showed markedly different trajectories of change for the two groups , by both child-report ( p = 0.03 ) and parent-report ( p = 0.03 ) measures : children of parents with less severe depression showed steep symptom declines , but children of parents with more severe depression showed flat trajectories with little change in symptoms over time . ANCOVAs showed lower post-treatment child symptoms for children of parents with less severe depression versus parents with more severe depression ( p = 0.05 by child report , p = 0.01 by parent report ) . Parental depressive symptoms predict child symptom trajectories and poorer child treatment response , and may need to be addressed in treatment BACKGROUND We evaluated the safety and efficacy of etanercept , a soluble tumor necrosis factor receptor (p75):Fc fusion protein , in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate . METHODS Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial , open-label part of a multicenter trial . Those who responded to treatment then entered a double-blind study and were r and omly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred . A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity , with no more than one indicator worsening by more than 30 percent . RESULTS At the end of the open-label study , 51 of the 69 patients ( 74 percent ) had had responses to etanercept treatment . In the double-blind study , 21 of the 26 patients who received placebo ( 81 percent ) withdrew because of disease flare , as compared with 7 of the 25 patients who received etanercept ( 28 percent ) ( P=0.003 ) . The median time to disease flare with placebo was 28 days , as compared with more than 116 days with etanercept ( P<0.001 ) . In the double-blind study , there were no significant differences between the two treatment groups in the frequency of adverse events . CONCLUSIONS Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis . Etanercept is well tolerated by pediatric patients CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Objectives Method ologically , to assess the feasibility of participant recruitment and retention , as well as missing data in study ing mental disorder among children newly diagnosed with chronic physical conditions ( ie , multimorbidity ) . Substantively , to examine the prevalence of multimorbidity , identify sociodemographic correlates and model the influence of multimorbidity on changes in child quality of life and parental psychosocial outcomes over a 6-month follow-up . Design Prospect i ve pilot study . Setting Two children ’s tertiary-care hospitals . Participants Children aged 6–16 years diagnosed in the past 6 months with one of the following : asthma , diabetes , epilepsy , food allergy or juvenile arthritis , and their parents . Outcome measures Response , participation and retention rates . Child mental disorder using the Mini International Neuropsychiatric Interview at baseline and 6 months . Child quality of life , parental symptoms of stress , anxiety and depression , and family functioning . All outcomes were parent reported . Results Response , participation and retention rates were 90 % , 83 % and 88 % , respectively . Of the 50 children enrolled in the study , the prevalence of multimorbidity was 58 % at baseline and 42 % at 6 months . No sociodemographic characteristics were associated with multimorbidity . Multimorbidity at baseline was associated with declines over 6 months in the following quality of life domains : physical well-being , β=−4.82 ( –8.47 , –1.17 ) ; psychological well-being , β=−4.10 ( –7.62 , –0.58 ) and school environment , β=−4.17 ( –8.18 , –0.16 ) . There was no association with parental psychosocial outcomes over time . Conclusions Preliminary evidence suggests that mental disorder in children with a physical condition is very common and has a negative impact on quality of life over time . Based on the strong response rate and minimal attrition , our approach to study child multimorbidity appears feasible and suggests that multimorbidity is an important concern for families . Method ological and substantive findings from this pilot study have been used to implement a larger , more definitive study of child multimorbidity , which should lead to important clinical implication OBJECTIVE To describe the long-term psychosocial outcome in a prospect ively followed cohort of patients with juvenile chronic arthritis ( JCA ) , to assess the associations between psychosocial outcome and disease variables and to explore family stressors as predictors of long-term psychosocial and physical outcome . METHODS Fifty-two patients with JCA were assessed psychosocially at first admission to a pediatric rheumatology clinic and were reassessed 9 years later . Assessment methods included semi-structured psychiatric interviews and st and ardized parental question naires and self-reports . RESULTS At follow-up , 9 patients ( 17 % ) fulfilled the criteria for a psychiatric diagnosis and 8 ( 15 % ) had mild to moderate impairment in psychosocial functioning ( children 's or adult Global Assessment Scale ) . Mental health and psychosocial functioning were significantly improved from the first hospital admission to follow-up . In patients < 18 years of age ( n = 26 ) , psychosocial functioning at follow-up correlated with physical disability according to the Childhood Health Assessment Question naire ( r = -0.52 , p < 0.01 ) . Psychosocial outcome was unrelated to other measures of disease severity . Chronic family difficulties in the disease course predicted psychosocial functioning at follow-up in patients < 18 years old ( R2 = 0.22 ) . Chronic family difficulties at disease onset , together with gender and chronic family difficulties in the disease course , predicted psychosocial functioning at follow-up in patients > or = 18 years old ( R2 = 0.61 ) . Family stressors were unrelated to the physical outcome . CONCLUSION The long-term psychosocial outcome was favorable in most of the patients . Psychosocial outcome was predicted by chronic family difficulties , but was not closely related to disease severity at follow-up OBJECTIVE Children with arthritis experience frequent pain , but the predictors of daily pain variations are largely unidentified . The goal of this study was to examine sleep quality as a predictor of pain in children with arthritis and to determine whether mood moderates this relationship . METHOD In this prospect i ve , longitudinal study children with polyarticular arthritis ( n = 51 , ages 8 - 16 years ) tracked daily symptoms , including sleep quality over 2 months . Self-reported daily pain intensity , as indicated on a visual analog scale , was used as the primary outcome measure in multilevel models . RESULTS Poorer sleep quality was associated with higher next-day pain ratings ( p < .01 ) . Mood moderated this relationship such that as positive mood increased , the relationship between poor sleep quality and high pain weakened ( p < .01 ) . Daily pain did not predict nightly sleep quality ( p > .05 ) . CONCLUSIONS Sleep quality is an important predictor of pain in children with arthritis . These findings add to the growing body of literature on the use of daily diaries for analyzing patterns of pain , sleep , and mood in children with chronic painful conditions Studied children with mild to moderate juvenile rheumatoid arthritis who were massaged by their parents 15 minutes a day for 30 days ( and a control group engaged in relaxation therapy ) . The children 's anxiety and stress hormone ( cortisol ) levels were immediately decreased by the massage , and over the 30-day period their pain decreased on self-reports , parent reports , and their physician 's assessment of pain ( both the incidence and severity ) and pain-limiting activities Abstract Objectives To determine if depressive symptoms assessed near diagnosis associate with future measures of pain , disability and disease for adolescent patients diagnosed with JIA . Methods Data were analysed from JIA patients aged 11–16 years recruited to the Childhood Arthritis Prospect i ve Study , a UK-based inception cohort of childhood-onset arthritis . Depressive symptoms ( using the Mood and Feelings Question naire ; MFQ ) , active and limited joint count , disability score ( Childhood Health Assessment Question naire ) , pain visual analogue scale and patient ’s general evaluation visual analogue scale were collected . Associations between baseline measures ( first visit to paediatric rheumatologist ) were analysed using multiple linear regression . Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable . Results Data from 102 patients were analysed . At baseline , median ( IQR ) age was 13.2 years ( 11.9–14.2 years ) and 14.7 % scored over the MFQ cut-off for major depressive disorder . At baseline , depressive symptoms significantly associated with all clinical measures of disease ( P ⩽ 0.01 ) . High baseline depressive symptoms scores predicted worse pain ( P ⩽ 0.005 ) and disability ( P ⩽ 0.001 ) 12 months later but not active and limited joint counts . Conclusions Adolescent patients with JIA and depressive symptoms had more active joints , pain and disability at the time of their first specialist appointment . The associations between baseline depression and both pain and disability continued for at least one year , however , this was not the case for active joint count BACKGROUND : Cross-sectional studies link functional abdominal pain ( FAP ) to anxiety and depression in childhood , but no prospect i ve study has evaluated psychiatric status in adulthood or its relation to pain persistence . METHODS : Pediatric patients with FAP ( n = 332 ) and control subjects ( n = 147 ) were tracked prospect ively and evaluated for psychiatric disorders and functional gastrointestinal disorders ( FGIDs ) at follow-up in adolescence and young adulthood ( mean age = 20.01 years ) . Participants were classified according to presence ( FGID-POS ) or absence ( FGID-NEG ) of FGIDs at follow-up . RESULTS : Lifetime and current risk of anxiety disorders was higher in FAP than controls ( lifetime : 51 % vs 20 % ; current : 30 % vs 12 % ) . Controlling for gender and age , the odds ratio was 4.9 ( confidence interval = 2.83–7.43 ) for lifetime anxiety disorder and 3.57 ( confidence interval = 2.00–6.36 ) for current anxiety disorder at follow-up for FAP versus controls . Lifetime risk of depressive disorder was significantly higher in FAP versus controls ( 40 % vs. 16 % ) ; current risk did not differ . In most cases , initial onset of anxiety disorders was before pediatric FAP evaluation ; onset of depressive disorders was subsequent to FAP evaluation . Within the FAP group , risk of current anxiety disorders at follow-up was significantly higher for FGID-POS versus FGID-NEG ( 40 % vs 24 % ) , and both were higher than controls ( 12 % ) ; current depressive disorders did not differ across FGID-POS , FGID-NEG , and controls . CONCLUSIONS : Patients with FAP carry long-term vulnerability to anxiety that begins in childhood and persists into late adolescence and early adulthood , even if abdominal pain resolves Objective : To report adverse events ( AEs ) seen in a large cohort of patients with juvenile idiopathic arthritis ( JIA ) treated with tumour necrosis factor (TNF)α blockers ( infliximab and etanercept ) . Methods : All patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute ( Milan , Italy ) from November 1999 to February 2006 , were enrolled in an open , single-centre , long-term prospect i ve study Results : In all , 163 patients ( 68 infliximab , 95 etanercept ) were enrolled . Mean ( SD ) age of onset was 6.4 ( 4.8 ) years , mean age 17.1 ( 9.2 ) years , mean therapy duration 22.9 ( 17.6 ) months . A total of 45 patients ( 32 infliximab , 13 etanercept ) failed to respond to or did not tolerate the first therapy and switched to a second one . In all , 208 treatments ( 81 infliximab , 127 etanercept ) were performed . A total of 71 AEs occurred in 51 ( 62.9 % ) patients on infliximab and led to discontinuation in 26 ( 32.1 % ) ; 133 AEs occurred in 69 ( 54.3 % ) patients on etanercept and led to discontinuation in 18 ( 14.2 % ) . Some AEs , such as thrombocytopoenia , neuropsychiatric disorders , new onset of Crohn disease and new onset or flare-up of chronic iridocyclitis ( CIC ) , are unusual and have rarely been described before , yet proved to be significant in frequency and /or clinical ly noteworthy in the large population we followed . Conclusions : In our 6-year study , anti-TNFα agents infliximab and etanercept were well tolerated and safe , and were associated with only few serious , but all reversible , AEs . However , such inhibitors are associated with various and numerous AEs . Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFα therapy as much as possible OBJECTIVE Etanercept monotherapy has been studied and approved for treatment of polyarticular juvenile idiopathic arthritis ( JIA ) . The following study evaluates the safety and efficacy of combination therapy of etanercept and methotrexate compared to etanercept monotherapy in JIA . METHODS We perfomed an open , non-r and omised study on patients who had previously failed to respond to at least one disease-modifying antirheumatic drug ( DMARD ) . A total of 722 patients with JIA in whom at least 1 item of follow-up data was recorded were identified ; of these , 118 patients treated with further slow acting drugs were excluded . In all , 504 patients were treated with a combination of etanercept and methotrexate . A total of 100 patients treated with etanercept only were in the control group . Efficacy was calculated using the American College of Rheumatology paediatric scores for 30 , 50 and 70 % improvement ( PedACR30/50/70 ) . Adverse events ( AEs ) and serious adverse events ( SAEs ) were reported . RESULTS After 12 months 55 patients in the monotherapy group and 376 patients in the etanercept and methotrexate group were available for comparison . For the intention to treat analysis , 65 patients discontinuing treatment prematurely were included . All activity parameters decreased significantly in both treatment groups . After 12 months 81%/74%/62 % of patients of the etanercept and methotrexate group and 70%/63%/45 % of patients of the etanercept monotherapy group achieved PedACR30/50/70 scores , respectively ( p<0.05 for PedACR30 , p<0.01 for PedACR70 ) . The likelihood of achieving a PedACR70 increased with combination therapy with an odds ratio of 2.1 ( 95 % CI 1.2 to 3.5 ) . In total , 25 infectious and 23 non-infectious SAEs including 3 malignancies occurred in the etanercept and methotrexate group , and 1 infectious and 3 non-infectious SAEs occurred in the single etanercept group . CONCLUSIONS The patients ' disease activity improved during etanercept monotherapy and etanercept and methotrexate combination therapy . Tolerability in both treatment groups was comparable |
13,078 | 24,018,760 | Heartburn and regurgitation were less frequent after surgical intervention .
However , a considerable proportion of patients still needed antireflux medication after fundoplication .
Nevertheless , the surgical patients were significantly more satisfied with their symptom control and showed higher satisfaction with the treatment received .
Conclusions This systematic review showed that surgical management of GERD is more effective than medical management with respect to patient-relevant outcomes in the short and medium term .
However , long-term studies still are needed to determine whether antireflux surgery is an equivalent alternative to lifelong medical treatment | Background Medical , endoscopic , and open/laparoscopic surgical methods are used to treat gastroesophageal reflux disease ( GERD ) .
This study aim ed to perform a systematic review of r and omized controlled trials comparing medical and surgical treatments of GERD in adult patients . | Background : With the introduction of laparoscopic antireflux surgery ( LARS ) for gastro-oesophageal reflux disease ( GORD ) along with the increasing efficacy of modern medical treatment , a direct comparison is warranted . The 3-year interim results of a r and omised study comparing both the efficacy and safety of LARS and esomeprazole ( ESO ) are reported . Methods : LOTUS is an open , parallel-group multicentre , r and omised and controlled trial conducted in dedicated centres in 11 European countries . LARS was completed according to a st and ardised protocol , comprising a total fundoplication and a crural repair . Medical treatment comprised ESO 20 mg once daily , which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control . The primary outcome variable was time to treatment failure ( Kaplan – Meier analysis ) . Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol . Results : 554 patients were r and omised , of whom 288 were allocated to LARS and 266 to ESO . The two study arms were well matched . The proportions of patients who remained in remission after 3 years were similar for the two therapies : 90 % of surgical patients compared with 93 % medically treated for the intention to treat population , p = 0.25 ( 90 % vs 95 % per protocol ) . No major unexpected postoperative complications were experienced and ESO was well tolerated . However , postfundoplication complaints remain a problem after LARS . Conclusions : Over the first 3 years of this long-term study , both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD Background The fundoplication of choice for the surgical treatment of gastroesophageal reflux disease ( GERD ) still is debated . Multichannel intraluminal impedance monitoring ( MII ) has not been used to compare objective data , and comparative subjective data on laparoscopic Nissen and Toupet fundoplications are scarce . Methods This study r and omly allocated 125 patients with documented chronic GERD to either laparoscopic floppy Nissen fundoplication ( LNF ; n = 62 ) or laparoscopic Toupet fundoplication ( LTF ; n = 63 ) . The Gastrointestinal Quality of Life Index ( GIQLI ) , symptom grading , esophageal manometry , and MII data were documented preoperatively and 1 year after surgery . The pre- and postprocedure data were compared . Statistical significance was set at a p value lower than 0.01 ( NCT01321294 ) . Results Both procedures result ed in significantly improved GIQLI and GERD symptoms . Preoperative dysphagia improved in both groups , but the improvement reached significance only in the LTF group . The ability to belch was shown to be significantly more decreased after LNF than after LTF . Gas-bloat and “ atypical ” extraesophageal symptoms also were decreased after surgery ( p < 0.01 ) . However , bowel symptoms were virtually unchanged in both groups . Both procedures result ed in significantly improved lower esophageal sphincter pressures . The improvement was greater in the LNF group than in the LTF group ( p < 0.01 ) . The DeMeester score and the numbers of total , acid , proximal , upright , and recumbent reflux episodes decreased in both groups after surgery ( p < 0.01 ) . No significant difference between the procedures in terms of MII data was found . Six patients ( 4.8 % ) had to undergo reoperation because of intrathoracic slipping of the wrap . All the patients had undergone LNF . Conclusions Both procedures proved to be equally effective in improving quality of life and GERD symptoms . However , the reoperation and dysphagia rates were lower and the ability to belch was higher after LTF than after LNF BACKGROUND & AIMS It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease ( GERD ) . In a 12-year study , we compared the effects of therapy with omeprazole with those of antireflux surgery . METHODS This open , parallel group study included 310 patients with esophagitis enrolled from outpatient clinics in Nordic countries . Of the 155 patients r and omly assigned to each arm of the study , 154 received omeprazole ( 1 withdrew before therapy began ) , and 144 received surgery ( 11 withdrew before surgery ) . In patients who remained in remission after treatment , post-fundoplication complaints , other symptoms , and safety variables were assessed . RESULTS Of the patients enrolled in the study , 71 who were given omeprazole ( 46 % ) and 53 treated with surgery ( 37 % ) were followed for a 12-year follow-up period . At this time point , 53 % of patients who underwent surgery remained in continuous remission , compared with 45 % of patients given omeprazole with a dose adjustment ( P = .022 ) and 40 % without dose adjustment ( P = .002 ) . In addition , 38 % of surgical patients required a change in therapeutic strategy ( eg , to medical therapy or another operation ) , compared with 15 % of those on omeprazole . Heartburn and regurgitation were significantly more common in patients given omeprazole , whereas dysphagia , rectal flatulence , and the inability to belch or vomit were significantly more common in surgical patients . The therapies were otherwise well-tolerated . CONCLUSIONS As long-term therapeutic strategies for chronic GERD , surgery and omeprazole are effective and well-tolerated . Antireflux surgery is superior to omeprazole in controlling overall disease manifestations , but post-fundoplication complaints continue after surgery Objective To examine the association between chronic use of proton pump inhibitors ( PPIs ) and risk of hip fracture . Design Prospect i ve cohort study . Setting Nurses ’ Health Study , which originally recruited from the 11 most populous states in the US . Participants 79 899 postmenopausal women enrolled in the Nurses ’ Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008 . Main outcome measure Incident hip fracture Results During 565 786 person years of follow-up , we documented 893 incident hip fractures . The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years , compared with 1.51 events per 1000 person years among non-users . Compared with non-users , the risk of hip fracture among women who regularly used PPIs for at least two years was 35 % higher ( age adjusted hazard ratio 1.35 ( 95 % confidence interval 1.13 to 1.62 ) ) , with longer use associated with increasing risk ( Ptrend<0.01 ) . Adjustment for risk factors , including body mass index , physical activity , and intake of calcium did not material ly alter this association ( hazard ratio 1.36 ( 1.13 to 1.63 ) ) . These associations were also not changed after accounting for reasons for PPI use . The relation between PPI use and fracture differed by smoking history ( Pinteraction=0.03 ) . Among current and former smokers , PPI use was associated with greater than 50 % increase in risk of fracture , with a multivariate hazard ratio for fracture of 1.51 ( 1.20 to 1.91 ) . In contrast , among women who never smoked there was no association ( multivariate hazard ratio 1.06 ( 0.77 to 1.46 ) ) . In a meta- analysis of these results with 10 prior studies , the pooled odds ratio of hip fracture associated with PPI use was 1.30 ( 1.25 to 1.36 ) . Conclusion Chronic use of PPIs is associated with increased risk of hip fracture , particularly among women with a history of smoking Objectives To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease ( GORD ) . Design Five year follow-up of multicentre , pragmatic r and omised trial ( with parallel non-r and omised preference groups ) . Setting Initial recruitment in 21 UK hospitals . Participants Responders to annual question naires among 810 original participants . At entry , all had had GORD for > 12 months . Intervention The surgeon chose the type of fundoplication . Medical therapy was review ed and optimised by a specialist . Subsequent management was at the discretion of the clinician responsible for care , usually in primary care . Main outcome measures Primary outcome measure was self reported quality of life score on disease-specific REFLUX question naire . Other measures were health status ( with SF-36 and EuroQol EQ-5D question naires ) , use of antireflux medication , and complications . Results By five years , 63 % ( 112/178 ) of patients r and omised to surgery and 13 % ( 24/179 ) of those r and omised to medical management had received a fundoplication ( plus 85 % ( 222/261 ) and 3 % ( 6/192 ) of those who expressed a preference for surgery and for medical management ) . Among responders at 5 years , 44 % ( 56/127 ) of those r and omised to surgery were taking antireflux medication versus 82 % ( 98/119 ) of those r and omised to medical management . Differences in the REFLUX score significantly favoured the r and omised surgery group ( mean difference 8.5 ( 95 % CI 3.9 to 13.1 ) , P<0.001 , at five years ) . SF-36 and EQ-5D scores also favoured surgery , but were not statistically significant at five years . After fundoplication , 3 % ( 12/364 ) had surgical treatment for a complication and 4 % ( 16 ) had subsequent reflux-related operations — most often revision of the wrap . Long term rates of dysphagia , flatulence , and inability to vomit were similar in the two r and omised groups . Conclusions After five years , laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management . Adverse effects of surgery were uncommon and generally observed soon after surgery . A small proportion had re-operations . There was no evidence of long term adverse symptoms caused by surgery . Trial registration Current Controlled Trials IS RCT N15517081 Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease ( GORD ) . Design Multicentre , pragmatic r and omised trial ( with parallel preference groups ) . Setting 21 hospitals in the United Kingdom . Participants 357 r and omised participants ( 178 surgical , 179 medical ) and 453 preference participants ( 261 , 192 ) ; mean age 46 ; 66 % men . All participants had documented evidence of GORD and symptoms for > 12 months . Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon . Those allocated to medical treatment had their treatment review ed and adjusted as necessary by a local gastroenterologist , and subsequent clinical management was at the discretion of the clinician responsible for care . Main outcome measures The disease specific REFLUX quality of life score ( primary outcome ) , SF-36 , EQ-5D , and medication use , measured at time points equivalent to three and 12 months after surgery , and surgical complications . Main results R and omised participants had received drugs for GORD for median of 32 months before trial entry . Baseline REFLUX scores were 63.6 ( SD 24.1 ) and 66.8 ( SD 24.5 ) in the surgical and medical r and omised groups , respectively . Of those r and omised to surgery , 111 ( 62 % ) actually had total or partial fundoplication . Surgical complications were uncommon with a conversion rate of 0.6 % and no mortality . By 12 months , 38 % ( 59/154 ) r and omised to surgery ( 14 % ( 14/104 ) among those who had fundoplication ) were taking reflux medication versus 90 % ( 147/164 ) r and omised medical management . The REFLUX score favoured the r and omised surgical group ( 14.0 , 95 % confidence interval 9.6 to 18.4 ; P<0.001 ) . Differences of a third to half of 1 SD in other health status measures also favoured the r and omised surgical group . Baseline scores in the preference for surgery group were the worst ; by 12 months these were better than in the preference for medical treatment group . Conclusion At least up to 12 months after surgery , laparoscopic fundoplication significantly increased measures of health status in patients with GORD . Trial registration IS RCT N15517081 Background A r and omized controlled trial ( RCT ) investigated patients with gastroesophageal reflux disease ( GERD ) who were stable and symptomatically controlled with long-term medical therapy to compare ongoing optimized medical therapy with laparoscopic Nissen fundoplication ( LNF ) . Methods Of the 180 patients eligible for r and omization , 104 gave informed consent , and 3 withdrew from the study immediately after r and omization . The patients r and omized to medical therapy received optimized treatment with proton pump inhibitors ( PPIs ) using a st and ardized management protocol based on best evidence and published guidelines . The surgical patients underwent LNF by one of four surgeons using a previously published technique . The patients underwent symptom evaluation using the GERD symptom scale ( GERSS ) and the global visual analog scale ( VAS ) for overall symptom control . They had 24-h esophageal pH monitoring at baseline and after 3 years . The medical patients were evaluated receiving PPI , and the surgical patients were evaluated not receiving PPI . Results For the 3-year follow-up assessment , 93 patients were available . At 3 years , surgery was associated with more heartburn-free days , showing a mean difference of −1.35 days per week ( p = 0.0077 ) and a lower VAS score ( p = 0.0093 ) than medical management . Surgical patients reported improved quality of life on the general health subscore of the Medical Outcomes Survey Short Form 36 ( SF-36 ) at 3 years , with a mean difference of −12.19 ( p = 0.0124 ) . The groups did not differ significantly in terms of GERSS or acid exposure on 24-h esophageal pH monitoring at 3 years . There were six treatment failures ( 11.8 % ) in the surgical group and eight treatment failures ( 16 % ) in the medical group by 3 years . Conclusions For patients whose GERD symptoms are stable and controlled with PPI , continuing medical therapy and laparoscopic antireflux surgery are equally effective , although surgery may result in better symptom control and quality of life CONTEXT Severe gastroesophageal reflux disease ( GERD ) is a lifelong problem that can be complicated by peptic esophageal stricture and adenocarcinoma of the esophagus . OBJECTIVE To determine the long-term outcome of medical and surgical therapies for GERD . DESIGN AND SETTING Follow-up study conducted from October 1997 through October 1999 of a prospect i ve r and omized trial of medical and surgical antireflux treatments in patients with complicated GERD . Mean ( median ) duration of follow-up was 10.6 years ( 7.3 years ) for medical patients and 9.1 years ( 6.3 years ) for surgical patients . PARTICIPANTS Two hundred thirty-nine ( 97 % ) of the original 247 study patients were found ( 79 were confirmed dead ) . Among the 160 survivors ( 157 men and 3 women ; mean [ SD ] age , 67 [ 12 ] years ) , 129 ( 91 in the medical treatment group and 38 in the surgical treatment group ) participated in the follow-up . MAIN OUTCOME MEASURES Use of antireflux medication , Gastroesophageal Reflux Disease Activity Index ( GRACI ) scores , grade of esophagitis , frequency of treatment of esophageal stricture , frequency of subsequent antireflux operations , 36-item Short Form health survey ( SF-36 ) scores , satisfaction with antireflux therapy , survival , and incidence of esophageal adenocarcinoma , compared between the medical antireflux therapy group and the fundoplication surgery group . Information on cause of death was obtained from autopsy results , hospital records , and death certificates . RESULTS Eighty-three ( 92 % ) of 90 medical patients and 23 ( 62 % ) of 37 surgical patients reported that they used antireflux medications regularly ( P<.001 ) . During a 1-week period after discontinuation of medication , mean ( SD ) GRACI symptom scores were significantly lower in the surgical treatment group ( 82.6 [ 17.5 ] vs 96.7 [ 21.4 ] in the medical treatment group ; P = .003 ) . However , no significant differences between the groups were found in grade of esophagitis , frequency of treatment of esophageal stricture and subsequent antireflux operations , SF-36 st and ardized physical and mental component scale scores , and overall satisfaction with antireflux therapy . Survival during a period of 140 months was decreased significantly in the surgical vs the medical treatment group ( relative risk of death in the medical group , 1.57 ; 95 % confidence interval , 1.01 - 2.46 ; P = .047 ) , largely because of excess deaths from heart disease . Patients with Barrett esophagus at baseline developed esophageal adenocarcinomas at an annual rate of 0.4 % , whereas these cancers developed in patients without Barrett esophagus at an annual rate of only 0.07 % . There was no significant difference between groups in incidence of esophageal cancer . CONCLUSION This study suggests that antireflux surgery should not be advised with the expectation that patients with GERD will no longer need to take antisecretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett esophagus Laparoscopic Nissen fundoplication and proton pump inhibitor ( PPI ) therapy are both established treatments for gastroesophageal reflux disease ( GERD ) . We have performed a prospect i ve r and omized study comparing these two treatments and now have long-term follow-up data . Between July 1997 and August 2001 , 183 patients in Norwich took part in a r and omized controlled trial comparing laparoscopic Nissen fundoplication and PPI therapy for the treatment of GERD . In October 2005 , patients were followed up and asked to complete a reflux symptom question naire . Ninety-one patients were r and omized to have surgery and 92 to have optimized PPI therapy . After 12 months , those who had been r and omized to PPI were offered the opportunity to have surgery . Fifty-four patients went on to have antireflux surgery ; the remaining 38 did not . In all three groups , there was a significant improvement in symptom score after the initial 12 months ( P<0.01 ; Mann-Whitney U test ) . However , those who later had surgery despite having had optimal PPI treatment beforeh and experienced further symptomatic improvement ( P<0.01 ) at long-term follow-up ( median 6.9 years , range , 4.3–8.3 ) . Both optimal PPI therapy and laparoscopic Nissen fundoplication are effective treatments for GERD . However , surgery offers additional benefit for those who have only partial symptomatic relief whilst on PPIs BACKGROUND Proton pump inhibitor ( PPI ) medications have been inconsistently shown to be associated with osteoporotic fractures . We examined the association of PPI use with bone outcomes ( fracture , bone mineral density [ BMD ] ) . METHODS This prospect i ve analysis included 161 806 postmenopausal women 50 to 79 years old , without history of hip fracture , enrolled in the Women 's Health Initiative ( WHI ) Observational Study and Clinical Trials with a mean ( SD ) follow-up of 7.8 ( 1.6 ) years . Analyses were conducted for 130 487 women with complete information . Medication information was taken directly from drug containers during in-person interviews ( baseline , year 3 ) . The main outcome measures were self-reported fractures ( hip [ adjudicated ] , clinical spine , forearm or wrist , and total fractures ) and for a sub sample ( 3 densitometry sites ) , 3-year change in BMD . RESULTS During 1 005 126 person-years of follow-up , 1500 hip fractures , 4881 forearm or wrist fractures , 2315 clinical spine fractures , and 21 247 total fractures occurred . The multivariate-adjusted hazard ratios for current PPI use were 1.00 ( 95 % confidence interval [ CI ] , 0.71 - 1.40 ) for hip fracture , 1.47 ( 95 % CI , 1.18 - 1.82 ) for clinical spine fracture , 1.26 ( 95 % CI , 1.05 - 1.51 ) for forearm or wrist fracture , and 1.25 ( 95 % CI , 1.15 - 1.36 ) for total fractures . The BMD measurements did not vary between PPI users and nonusers at baseline . Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip ( P = .05 ) but not at other sites . CONCLUSION Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine , forearm or wrist , and total fractures OBJECTIVES : The prevalence of gastroesophageal reflux symptoms ( GERS ) in the population is high ; however , data on long-term follow-up and incidence of GERS in the population are sparse . This study describes the long-term natural history of GERS , the related health-care use , and quality of life in a population followed up for 5 years . METHODS : A total of 10,000 r and omly selected inhabitants , 40–65 years old , received , as a part of a controlled trial of Helicobacter pylori screening and treatment ( control group ) , a mailed question naire regarding demographic data , gastrointestinal symptoms ( the Gastrointestinal Symptom Rating Scale ( GSRS ) ) , and quality of life ( the Short-Form 36-Item Health Survey ( SF-36 ) ) at inclusion and after 5 years . GERS was defined as a mean score ≥2 in the reflux dimension in the GSRS . Information on use of health-care re sources was drawn from the question naires and registers . RESULTS : In all , 6,781 individuals answered the first question naire and 5-year symptom data were complete for 5,578 ( 82.3 % ) of them . The mean age at inclusion was 52.4 years , 48 % were men . At inclusion , 22 % reported GERS . During follow-up , symptoms resolved in 43 % , of whom 10 % received acid inhibitory treatment at 5-year follow-up . The incidence of GERS was 2.2 % per year . Health-care use during follow-up was significantly higher in individuals with GERS at baseline than in individuals without GERS . Quality of life at 5-year follow-up was lower in individuals with GERS at inclusion than in individuals without GERS at inclusion . CONCLUSIONS : GERS are prevalent , long lasting , and associated with an impaired quality of life and substantial health-care use The objective of this study was to determine the levels of evidence and grade s of recommendations available for techniques in antireflux surgery . Areas of technical controversy in antireflux surgery were identified and developed into eight answerable questions . The external evidence was surveyed using the data bases Medline and EMBASE . Abstract s and appropriate articles were identified from January 1966 to December 2005 . A set of search strategies was systematic ally employed to determine the levels of evidence available for each clinical question . Primary outcome measures included the determination of levels of evidence and grade of recommendation based on The Oxford Center for Evidence -Based Medicine . Secondary outcome measures included for r and omized controlled trials were Jadad scores , noting the presence of a sample size calculation , and the determination of an effect estimate and the reporting of a confidence interval . Higher quality r and omized controlled trials ( mostly level 2b , occasional level 1b ) existed to answer three questions : whether to complete a 360 degrees or partial wrap ; whether or not to divide the short gastric vessels ; and whether to perform laparoscopic or open surgery . Lower quality r and omized controlled trials were available to determine whether the use of mesh was helpful , whether or not to use a bougie catheter for calibration of the wrap , and whether an anterior or posterior wrap results in a superior outcome . This was deemed to be of inferior grade of recommendation due to the lack ( < 2 ) of trials available and the sole presence of level 2b evidence . The final two questions : whether to complete fundoplication using a thoracic or abdominal approach and whether to use intraoperative manometry relied exclusively upon level 4 evidence and thus received a lower grade of recommendation . A higher Jadad score seemed to be associated with studies having a higher level of evidence available to answer the question . Sample size calculations were given to answer three questions . Effect estimate was difficult to interpret given inconsistent findings , composite outcomes and lack of reported confidence intervals . In conclusion , antireflux surgery has many r and omized controlled trials available upon which to base clinical practice . Unfortunately , these are generally of poor quality . We recommend that esophageal surgeons determine consistent outcome measures and endeavor to improve the quality of r and omized controlled trials they perform A r and omized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor ( n = 52 ) with laparoscopic Nissen fundoplication ( n = 52 ) . Patients were monitored for 1 year . The primary end point was frequency of gastroesophageal reflux dis-ease symptoms . Surgical patients had improved symptoms , pH control , and overall quality of life health index after surgery at 1 year compared with the medical group . The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients , but improved in the surgical patients . Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose , but 6 had satisfactory symptom remission . No surgical patients required additional treatment for symptom control . Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical c and i date s and should experience improved symptom control after surgery at 1 year BACKGROUND Conventional medical treatment for gastroesophageal reflux disease involves life-style modifications and combination drug therapy , but few studies have included these features in their protocol s. Antireflux surgery has seldom been studied prospect ively , and there have been no trials comparing modern medical and surgical treatments for reflux disease . METHODS We conducted a long-term , r and omized trial of medical therapy ( lifestyle modifications and up to four medications ) and surgical therapy ( Nissen fundoplication ) in 247 patients ( 243 men and 4 women ) with peptic esophageal ulcer , stricture , erosive esophagitis , or Barrett 's esophagus . They received by r and om assignment either continuous medical therapy , medical therapy for symptoms only , or surgical therapy . Symptoms were assessed quarterly with a disease-activity index ; esophagoscopy was performed at base line and each year for two years . The outcomes evaluated at one and two years included the activity index , and the endoscopic grade of esophagitis . RESULTS Follow-up data were available for 176 patients at one year and for 106 patients at two years . The mean ( + /- SE ) activity-index score ( possible range , 74 to 172 ) decreased in one year from 108 + /- 3 to 87 + /- 2 in the group receiving continuous medical therapy , from 107 + /- 3 to 88 + /- 2 in the group receiving medical therapy for symptoms only , and from 109 + /- 3 to 78 + /- 2 in the surgical-therapy group ( P less than 0.0001 for the change from base line , for all comparisons ) . The mean ( + /- SE ) grade of esophagitis ( possible range , 1 to 4 ) decreased in the respective groups from 2.9 + /- 0.1 to 2.0 + /- 0.1 , from 2.9 + /- 0.1 to 2.3 + /- 0.1 , and from 2.9 + /- 0.1 to 1.4 + /- 0.1 ( P less than 0.005 vs. base line , for all comparisons ) . The mean activity-index score and the grade of esophagitis were significantly better in the surgical-therapy group than in either medical-therapy group during the two years of follow-up ( P less than 0.003 ) . CONCLUSIONS In men with complicated gastroesophageal reflux disease , surgery is significantly more effective than medical therapy in improving the symptoms and endoscopic signs of esophagitis for up to two years , although medical treatment is also effective BACKGROUND The efficacy of antireflux surgery ( ARS ) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established . A direct comparison between these therapies is warranted to assess the benefits of respective therapies . STUDY DESIGN There were 310 patients with erosive esophagitis enrolled in the trial . There were 155 patients r and omized to continuous omeprazole therapy and 155 to open antireflux surgery , of whom 144 later had an operation . Because of various withdrawals during the study course , 122 patients originally having an antireflux operation completed the 5-year followup ; the corresponding figure in the omeprazole group was 133 . Symptoms , endoscopy , and quality -of-life question naires were used to document clinical outcomes . Treatment failure was defined to occur if at least one of the following criteria were fulfilled : Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit ; Esophagitis of at least grade 2 ; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation ; If r and omized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms , or having a reoperation ; If r and omized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms ; If r and omized to omeprazole and the patient , for any reason , preferred antireflux surgery during the course of the study . Treatment failure was the primary outcomes variable . RESULTS When the time to treatment failure was analyzed by use of the intention to treat approach , applying the life table analysis technique , a highly significant difference between the two strategies was revealed ( p < 0.001 ) , with more treatment failures in patients who originally were r and omized to omeprazole treatment . The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence . The curves subsequently describing the failure rates still remained separated in favor of surgery , although the difference did not reach statistical significance ( p = 0.088 ) . Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years . CONCLUSIONS In this r and omized multicenter trial with a 5-year followup , we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates . But if the dose of omeprazole was adjusted in case of relapse , the two therapeutic strategies reached levels of efficacy that were not statistically different We compared the surgical and medical managements of reflux esophagitis in a prospect i ve managements of reflux esophagitis in a prospect i ve clinical trial . Patients wissigned to surgical ( 15 patients ) and medical ( 16 patients ) groups . A non-r and omized medical group ( 20 patients ) was also studied . Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response . A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients . Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy . The histologic appearance of the squamous mucosa , however , remained abnormal in all but one patient . In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux . The relative increases in pphincter pressure to grade d increases in gastric pressure , however , remained abnormal in all but one patient Both laparoscopic Nissen fundoplication ( LNF ) and proton‐pump inhibitor ( PPI ) therapy are established in the treatment of gastro‐oesophageal reflux disease ( GORD ) . The aim of this study was to compare these two treatments in a r and omized clinical trial |
13,079 | 28,371,878 | Conclusion Differences between clinical and pre clinical studies are evident and may affect the translation of pre clinical findings in the clinical setting | Background Acute kidney injury ( AKI ) is a common clinical condition directly associated with adverse outcomes .
Several AKI biomarkers have been discovered , but their use in clinical and pre clinical studies has not been well examined .
This study aims to investigate the differences between clinical and pre clinical studies on AKI biomarkers . | Background Experimentally , erythropoietin ( EPO ) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury . We tested the hypothesis that different doses of recombinant human EPO administered to patients after cardiac surgery would minimize kidney lesions and the systemic inflammatory response , thereby decreasing acute kidney injury ( AKI ) incidence . Methods In this double-blinded r and omized control study , 80 patients admitted to the ICU post-cardiac surgery were r and omized by computer to receive intravenously isotonic saline ( n = 40 ) versus α-Epoetin ( n = 40 ) : either 40000 IU ( n = 20 ) or 20000 IU ( n = 20 ) . The study lasted one year . The primary outcome was the change in urinary NGAL concentration from baseline and 48 h after EPO injection . Creatinine , cystatine C and urinary NGAL levels were measured on the day of r and omization and 2–4 days after EPO injection . To assess acute inflammatory response , serum cytokines ( IL6 and IL8 ) were measured at r and omization and four days after r-HuEPO injection . Patients and care-takers were blinded for the assignment . Results No patient was excluded after r and omization . Patient groups did not differ in terms of age , gender , comorbidities and renal function at r and omization . The rate of AKI assessed by AKIN criteria was 22.5 % in our population . EPO treatment did not significantly modify the difference in uNGAl between 48 hours and r and omization compared to placebo [ 2.5 ng/ml ( −17.3 ; 22.5 ) vs 0.7 ng/ml ( −31.77 ; 25.15 ) , p = 0.77 ] and the incidence of AKI was similar . Inflammatory cytokines levels were not influenced by EPO treatment . Mortality and hospital stays were similar between the groups and no adverse event was recorded . Conclusion In this r and omized-controlled trial , α-Epoetin administrated after cardiac surgery , although safe , demonstrated neither nephroprotective nor anti-inflammatory properties . Trial registration PURPOSE To evaluate the effect of parecoxib ( an NSAID ) on renal function by measuring plasma NGAL ( serum neutrophil gelatinase-associated lipocalin ) levels in an induced-ischemia rat model . METHODS Forty male Wistar rats were r and omly assigned to one of four groups : Ischemia ( I ) , Ischemia/parecoxib ( IP ) , No-ischemia ( NI ) , and No-ischemia/parecoxib ( NIP ) . Body weight , mean arterial pressure , heart rate , body temperature , NGAL levels , and renal histology were compared across groups . RESULTS The Ischemia ( I ) group , which did not receive parecoxib , showed the highest NGAL levels ( p=0.001 ) , while the IP group , which received the medication , had NGAL levels similar to those of the non-ischemic ( NI and NIP ) groups . CONCLUSION Parecoxib result ed in renal protection in this experimental model INTRODUCTION Delayed graft function ( DGF ) is a consequence of ischemia-reperfusion injuries in kidney allografts , for which no definite treatment is available . The neutrophil gelatinase-associated lipocalin ( NGAL ) and interleukin-18 ( IL-18 ) are introduced as the most promising urine biomarkers to detect DGF . N-acetylcysteine ( NAC ) and vitamin C , well-known potent antioxidants that scavenge free radicals , may alleviate kidney injury . This study investigated the protective effects of NAC alone and in combination with vitamin C on DGF , by measuring IL-18 and NGAL in living donor kidney transplantations . MATERIAL S AND METHODS Patients transplanted between January 2011 and February 2013 were r and omly divided into 3 groups to receive routine anti-rejection medication only ( n = 32 ) , NAC plus routine immunosuppressive regimen ( NAC group ; n = 33 ) , and NAC and vitamin C plus routine regimen ( NAC and vitamin C group ; n = 19 ) . Urine sample s were taken 4 hours and 24 hours after transplantation . Enzyme-linked immunosorbent assay kits were utilized for measuring urine NGAL and IL-18 . RESULTS There were no significant differences in the DGF prevalence and its duration between the study arms . Although the levels of NGAL and IL-18 decreased in the NAC and NAC and vitamin C groups , these reductions were not significant . Glomerular filtration rate at 30 and 60 days after transplantation were not significantly different between study groups , either . CONCLUSIONS Our results showed that NAC is a safe drug without significant adverse effects in kidney transplant recipients ; however , its potential useful effects on urinary biomarkers of DGF were not illustrated in the present study Background : Use of aprotinin has been associated with acute kidney injury after cardiac surgery . Neutrophil gelatinase-associated lipocalin ( NGAL ) is a novel , very sensitive marker for renal injury . Urinary NGAL may be able to detect renal injury caused by aprotinin . This study determined if the use of aprotinin is associated with an increased incidence of acute kidney injury and increased levels of urinary NGAL . Methods : In this prospect i ve , observational study 369 patients undergoing cardiac surgery were enrolled . 205 patients received aprotinin and 164 received epsilon amino-caproic acid intraoperatively . Urinary NGAL was measured before and immediately after cardiac surgery and 3 , 18 and 24 h later . The association of aprotinin use with the incidence of acute kidney injury ( increase of serum creatinine > 0.5 mg/dl ) and NGAL levels was determined using logistic and linear regression models . Results : 51 of 205 patients ( 25 % ) who received aprotinin developed acute kidney injury compared to 19 of 164 patients ( 12 % ) who received epsilon amino-caproic acid ( p = 0.0013 ) . Aprotinin use was associated with a two-fold higher risk of acute kidney injury when adjusted for potential confounders ( age , Parsonnet score , preoperative serum creatinine , cardiopulmonary bypass and cross-clamp times ; multiple logistic regression : OR = 2.164 ; CI ( 95 % ) = 1.102 to 4.249 ; p = 0.0249 . Urinary NGAL was 19 times higher immediately after cardiopulmonary bypass and 18 times higher 3 h later in patients who had received aprotinin ( postoperative : 19.23 ; CI ( 95 % ) = 12.60 to 29.33 ; p < 0.0001 ; 3 h post-cardiopulmonary bypass 18.67 ; CI ( 95 % ) = 11.45 to 30.43 ; p < 0.0001 ) . Conclusions : Postoperative urinary NGAL – a novel marker for renal injury – is increased in cardiac surgical patients receiving aprotinin compared to patients receiving epsilon amino-caproic acid . These results further support the hypothesis that aprotinin may cause renal injury . The substantial rise of urinary NGAL associated with aprotinin use may in part be due to aprotinin blocking the uptake of NGAL by megalin/gp330 receptors in the proximal tubules High-dose ibuprofen ( IBU ) may slow the decline of lung function in patients with cystic fibrosis ( CF ) , but its use has been limited due to concerns over renal and gastrointestinal toxicity . In this pilot study , we examined the association of IBU with markers of acute kidney injury ( AKI ) in patients with CF . The effect of aminoglycoside ( AG ) exposure on AKI biomarkers was also examined . The AKI markers , kidney injury molecule-1 ( KIM ) , N-acetyl-β-glucosaminidase ( NAG ) and urine protein , normalized for creatinine , were chosen as they are more sensitive indicators of kidney injury than changes in serum creatinine . Urine sample s from 52 patients , 26 from patients who were treated with IBU , were analyzed . There was no significant association between IBU treatment and KIM-1 , NAG or protein levels , compared to patients never treated with IBU . While there was an association between AG courses and KIM-1 levels , there were no differences in biomarker levels between IBU and non-IBU groups with respect to AG courses . These preliminary results suggest that IBU treatment in patients with CF may be safe with respect to renal toxicity Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease ( CKD ) . Remote ischemic preconditioning ( RIPC ) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI . We undertook a r and omized controlled trial of RIPC to prevent AKI in 86 patients with CKD ( estimated glomerular filtration rate under 60 ml/min per 1.73 m(2 ) ) undergoing coronary artery bypass graft ( CABG ) surgery . Forty-three patients each were r and omized to receive st and ard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion . The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery . Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C , neutrophil gelatinase-associated lipocalin ( NGAL ) , and interleukin-18 ( IL-18 ) , and urinary biomarkers including NGAL , IL-18 , and kidney injury molecule-1 measured at 6 , 12 , and 24 h after CABG , and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury . Clinical and operative characteristics were similar between the preconditioned and control groups . AKI developed in 12 patients in both groups within 48 h of CABG . There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG . Thus , RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD PURPOSE The main objective of this study was to compare the effect of two anaesthetic techniques ( general vs combined ) on plasma levels of NGAL ( Neutrophil Gelatinase Associated Lipocalin ) after robotic urogenital oncosurgery . The secondary objective was to correlate NGAL levels with the incidence of acute kidney injury ( AKI ) . METHODS This was a longitudinal prospect i ve study . Forty patients were included and r and omized in 2 groups : group C ( N=16 cases ; combined general-epidural anesthesia ) and group G ( N=24 cases ; control group with general anesthesia ) . Demographic data , Charlson Comorbidity Index , Apache II , SOFA and ASA scores were similar in both groups . Serum creatinine was determined preoperatively and every 24 hrs for 4 postoperative days to identify AKI according to RIFLE and AKIN criteria . Serum NGAL was determined at 6 and 12 hrs after induction of anesthesia . RESULTS Serum creatinine increased at 24 hrs postoperatively in both groups as compared to baseline , but significant changes were registered only in the G group ( p(control ) = 0.004 ) . Serum NGAL increased significantly in both groups as compared with baseline levels ( pcase=0.0034 vs p(control)=0.0001 ) . The incidence of AKI was 12.50 % ( 95 % CI 0.4 - 34 ) in the C group and 37.50 % ( 95 % CI 17 - 58 ) in the G group ( p=0.0909 ) , respectively . CONCLUSION Impaired renal function and AKI occurred in robot-assisted laparoscopic urogenital oncosurgery under both general and combined anaesthesia . The incidence of AKI was lower in patients undergoing combined anesthesia compared to general anaesthesia after robotic urogenital oncosurgery but the difference did not reach statistical significance . However , plasma levels of NGAL were significantly increased at 6 and 12 hrs in the general anaesthesia group as compared with combined anaesthesia . NGAL may be a better marker in detecting postoperative acute kidney injury . Further studies are needed The prevalence of type 1 cardiorenal syndrome ( CRS ) is increasing and strongly associated with long-term mortality . However , lack of reliable animal models and well-defined measures of renoprotection , made early diagnosis and therapy difficult . We previously successfully established the swine acute myocardial infa rct ion ( AMI ) model of ischemia-reperfusion by blocking left anterior descending branch ( LAD ) . Reperfusion was performed after 90-minute occlusion of the LAD . AMI was confirmed by ECG and left ventricular angiography ( LVG ) . Then those 52 survived AMI reperfusion swine , including ventricular fibrillation-cardiac arrest after restoration of blood flow , were r and omly divided into four groups ( four/group ) according to different interventions : resuscitation in room temperature , resuscitation with 500 ml saline in room temperature , resuscitation with 4 ° C 500 ml saline and normal control ( with no intervention of resuscitation ) . Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias : 1 , 3 , 5 , 10-minute reperfusion after ventricular arrhythmias . Plasma and r and om urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury ( AKI ) . Our swine AMI model of ischemia-reperfusion provoked sub clinical AKI with the elevation of the tubular damage biomarker , NGAL , IL-18 and L-FABP . Renal damage rapidly observed after hemodynamic instability , rather than observation after several hours as previously reported . The increasing rate of biological markers declined after interventions , however , its impact on the long-term prognosis remains to be further studied . These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS Previous studies reported the beneficial effect of erythropoietin ( EPO ) in acute injuries . We followed patients with and without acute kidney injury ( AKI ) after coronary artery bypass grafting ( CABG ) and evaluated the effect of EPO on long-term outcome . We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin ( uNGAL ) as a predictive marker of AKI . Seventy-one patients scheduled for elective CABG were r and omly given either 300 U/kg of EPO or saline before CABG . The primary outcome was AKI , and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease ( ESRD ) . Twenty-one patients had AKI , 14 ( 66.7 % ) in the placebo group and 7 ( 33.3 % ) in the EPO group ( P = 0.05 ) . Also , uNGAL was higher in the patients with AKI than in those without AKI at baseline , 2 , 4 , 24 , and 72 hr after CABG ( P = 0.011 ) . Among patients with AKI , 2-week creatinine ( Cr ) was not different from baseline Cr in the EPO group , but 2-week Cr was significantly higher than baseline Cr in the placebo group ( P = 0.009 ) . All-cause-mortality ( P = 0.022 ) and the composite of all-cause-mortality and ESRD ( P = 0.003 ) were reduced by EPO . EPO reduces all-cause-mortality and ESRD in patients with AKI , largely due to the beneficial effect of EPO on recovery after AKI BACKGROUND High-dose methotrexate ( HD-MTX ) is potentially nephrotoxic . The feasibility of novel biomarkers to indicate renal injury due to HD-MTX infusion was studied in children with acute lymphoblastic leukemia ( ALL ) . PROCEDURE Markers for glomerular and tubular injury were evaluated prospect ively after HD-MTX infusion in 20 children with ALL . Plasma creatinine , cystatin C , and neutrophil gelatinase-associated lipocalin ( NGAL ) were measured 24 - 48 hr before MTX-infusion and 24 , 36 , 48 , and 72 hr after starting the HD-MTX treatment , and thereafter daily until the MTX concentration was below 0.1 µmol/L. Urine NGAL , β2 -microglobulin , and creatinine concentrations as well as dipstick and urinalysis were performed at the same time points . RESULTS In children with ALL , HD-MTX treatment at 5 g/m(2 ) over 24 hr was well tolerated and none of the patients developed significant glomerular or tubular dysfunction . The mean plasma cystatin C level increased significantly ( P < 0.001 ) from 0.83 mg/L at baseline to 0.94 mg/L at 36 hr after starting the HD-MTX treatment . The cystatin C concentration remained within reference range in all but two patients ( 10 % ) . There was no significant change in plasma creatinine level during or after HD-MTX treatment , the values being normal in all patients . Plasma and urea NGAL did not increase during or after the HD-MTX treatment . CONCLUSIONS Our results suggest that plasma cystatin C concentration alone is a sensitive marker to monitor renal function during and after HD-MTX infusion in pediatric ALL patients . Plasma or urine NGAL do not provide any further advantage in the follow-up of these patients Background / Aims : Low-level laser therapy ( LLLT ) has been found to modulate biological activity . The aim of the present study was to investigate the possible beneficial effects of LLLT application to stem cells in the bone marrow ( BM ) , on the kidneys of rats that had undergone acute ischemia-reperfusion injury ( IRI ) . Methods : Injury to the kidneys was induced by the excision of the left kidney and 60 min of IRI to the right kidney in each rat . Rats were then divided r and omly into 2 groups : non-laser-treated and laser-treated . LLLT was applied to the BM 10 min and 24 h post-IRI and rats were sacrificed 4 days post-IRI . Blood was collected before the sacrifice and the kidney processed for histology . Results : Histological evaluation of kidney sections revealed the restored structural integrity of the renal tubules , and a significant reduction of 66 % of pathological score in the laser-treated rats as compared to the non-laser-treated ones . C-kit positive cell density in kidneys post-IRI and laser-treatment was ( p = 0.05 ) 2.4-fold higher compared to that of the non-laser treated group . Creatinine , blood urea nitrogen , and cystatin-C levels were significantly 55 , 48 , and 25 % lower respectively in the laser-treated rats as compared to non-treated ones . Conclusion : LLLT application to the BM causes induction of stem cells , which subsequently migrate and home in on the injured kidney . Consequently , a significant reduction in pathological features and improved kidney function post-IRI are evident . The results demonstrate a novel approach in cell-based therapy for acute ischemic injured kidneys . i 2014 S. Karger AG , BACKGROUND AND OBJECTIVES Delayed graft function ( DGF ) is associated with adverse long-term outcomes after deceased-donor kidney ( DDK ) transplantation . Ischemia-reperfusion injury plays a crucial role in the development of DGF . On the basis of promising animal data , this study evaluated any potential benefits of erythropoietin-alfa ( EPO-α ) given intra-arterially at the time of reperfusion of renal allograft on the degree of allograft function , as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial was conducted to evaluate the influence of EPO-α administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009 . RESULTS Seventy-two patients were r and omly assigned to EPO-α ( n=36 ) or placebo ( n=36 ) . The incidences of DGF , slow graft function , and immediate graft function did not significantly differ between the treatment and control groups ( 41.7 % versus 47.2 % , 25.0 % versus 36.1 % , and 33.3 % versus 16.7 % , respectively ; P=0.24 ) . The groups had similar levels of urinary biomarkers , including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation ; urinary output during the first 3 postoperative days ; 1-month renal function ; and BP readings , hemoglobin , and adverse effects during the first month . CONCLUSIONS This study did not show any clinical ly demonstrable beneficial effects of high-dose EPO-α given intra-arterially during the early reperfusion phase in DDK transplant recipients in terms of reducing the incidence of DGF or improving short-term allograft function Contrast-induced nephropathy limits the outcomes of percutaneous coronary intervention ( PCI ) . The present study compared the protective effects of different statin doses on renal function . A total of 228 patients with acute coronary syndrome undergoing selective PCI were r and omly divided into simvastatin 20-mg group ( S20 , n = 115 ) and simvastatin 80-mg group ( S80 , n = 113 ) . Serum creatinine was measured at admission , the day of PCI , and 24 and 48 hours after PCI . The creatinine clearance was calculated using the Cochcroft-Gault formula . High-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 were also measured before and after the procedure . Contrast-induced nephropathy was defined as a postprocedure increase in serum creatinine of > or = 0.5 mg/dl or > 25 % from baseline . The serum creatinine significantly increased after PCI , with the peak value occurring at 24 hours , and then began to decrease . At 48 hours , the serum creatinine had decreased to the baseline level in the S80 group , but it had failed to do so in the S20 group . At 24 and 48 hours after PCI , the serum creatinine was lower in the S80 group than in the S20 group ( p < 0.05 and p < 0.001 , respectively ) . The creatinine clearance significantly decreased after PCI , with the lowest value occurring at 24 hours , and then it began to increase . In the S80 group , the creatinine clearance recovered to baseline level at 48 hours , but it failed to do so in the S20 group . The creatinine clearance was greater at 24 and 48 hours in the S80 group than that in the S20 group . Although the procedure caused a significant increase in high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels , the value was lower in the S80 group than in the S20 group ( p < 0.001 ) . In conclusion , pretreatment with simvastatin 80 mg before PCI could further decrease the occurrence of contrast-induced nephropathy compared with simvastatin 20 mg . This benefit was associated with the lowering of high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels In a double-blinded r and omized controlled trial , Anja Haase-Fielitz and colleagues find that an infusion of sodium bicarbonate during open heart surgery did not reduce the risk for acute kidney injury , compared with saline control Purpose Acute kidney injury ( AKI ) is a common and serious adverse effect of cisplatin-based chemotherapy . However , traditional markers of kidney function , such as serum creatinine , are suboptimal , because they are not sensitive measures of proximal tubular injury . We aim ed to determine whether the new urinary biomarkers such as kidney injury molecule-1 ( KIM-1 ) , monocyte chemotactic protein-1 ( MCP-1 ) , and neutrophil gelatinase-associated lipocalin ( NGAL ) could detect cisplatin-induced AKI in lung cancer patients in comparison with the conventional urinary proteins such as N-acetyl-β-d-glucosaminidase ( NAG ) and β2-microglobulin . Methods We measured KIM-1 , MCP-1 , NGAL , NAG , and β2-microglobulin concentrations in urine sample s from 11 lung cancer patients , which were collected the day before cisplatin administration and on days 3 , 7 , and 14 . Subsequently , we evaluated these biomarkers by comparing their concentrations in 30 AKI positive ( + ) and 12 AKI negative ( − ) sample s and performing receiver operating characteristic ( ROC ) curve analyses . Results The urinary levels normalized with urine creatinine of KIM-1 and MCP-1 , but not NGAL , NAG , and β2-microglobulin in AKI ( + ) sample s were significantly higher than those in AKI ( − ) sample s. In addition , ROC curve analyses revealed that KIM-1 and MCP-1 , but not NGAL , could detect AKI with high accuracy ( area under the curve [ AUC ] = 0.858 , 0.850 , and 0.608 , respectively ) . The combination of KIM-1 and MCP-1 outperformed either biomarker alone ( AUC = 0.871 ) . Conclusions Urinary KIM-1 and MCP-1 , either alone or in combination , may represent biomarkers of cisplatin-induced AKI in lung cancer patients Background Based on Acute Kidney Injury Network ( AKIN ) criteria , we considered acute kidney injury ( AKI ) as an absolute increase in the serum creatinine ( sCr ) level of more than or equal to 0.3 mg/dl or 50 % . The introduction of Urinary neutrophil gelatinase-associated lipocalin ( UNGAL ) has conferred earlier diagnosis of AKI . Pentoxifylline ( PTX ) , a non-specific phosphodiesterase inhibitor , can suppress the production of some factors of inflammatory response and presumably prevent AKI . We examined the PTX on the development of AKI in cardiac surgery patients by measuring the levels of UNGAL . Material s and methods We performed a double blind r and omized clinical trial , enrolling 28 consecutive patients undergoing elective coronary artery bypass graft ( CABG ) surgery . Patients were divided into two groups , one to receive PTX 5 mg/kg intravenous bolus injection , followed by 1.5 mg/kg/h continuous intravenous infusion until 3 hours after cessation of CPB and the other group received placebo . UNGAL was measured before , 3 and 24 hours after surgery . In addition serum creatinine was measured before and 24 , 48 , 72 and 96 hours after surgery and C-reactive protein ( CRP ) only 24 hours postoperatively . Results Both groups did not differ in demographic and baseline characteristics . 12 patients developed AKI 48 hours after surgery ; 5 of them were in the intervention group and 7 in the control group ( p= 0.445 ) . There was an increase of UNGAL in both groups postoperatively , although not significant . Mean sCr was significantly increased in the control group at 24 and 48 hours after surgery ( 24-h mean : 0.79 ± 0.18 mg/dl vs. 1.03 ± 0.43 mg/dl , P value = 0.02 ; 48-h mean : 1.17 ± 0.24 mg/dl vs. 0.98 ± 0.20 mg/dl , P value = 0.03 , respectively ) . PTX had a positive effect in preventing AKI reflecting in changes in sCr , and the increase of UNGAL was consistent with the emergence of AKI ( Pearson 's correlation = 0.30 ) . Conclusion Our study demonstrates a weak correlation between UNGAL and sCr after cardiac surgery . The rise of UNGAL in these patients may be reduced by administration of PTX although we did not show significance . PTX could reduce the occurrence of AKI as determined by attenuation of sCr rise without causing hemodynamic instability or increased bleeding . Overall , we suggest future studies with larger sample sizes to eluci date this effect and determine the different aspects of administrating PTX.Trial Registration IS RCT N : I RCT Tacrolimus is widely used as an immunosuppressant in liver transplantation , and tacrolimus-induced acute kidney injury ( AKI ) is a serious complication of liver transplantation . For early detection of AKI , various urinary biomarkers such as monocyte chemotactic protein-1 , liver-type fatty acid-binding protein , interleukin-18 , osteopontin , cystatin C , clusterin and neutrophil gelatinase-associated lipocalin ( NGAL ) have been identified . Here , we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients . Urine sample s were collected from 31 patients after living-donor liver transplantation ( LDLT ) . Twenty recipients developed tacrolimus-induced AKI . After the initiation of tacrolimus therapy , urine sample s were collected on postoperative days 7 , 14 , and 21 . In patients who experienced AKI during postoperative day 21 , additional spot urine sample s were collected on postoperative days 28 , 35 , 42 , 49 , and 58 . The 8 healthy volunteers , whose renal and liver functions were normal , were asked to collect their blood and spot urine sample s. The urinary levels of NGAL , monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without , while those of interleukin-18 , osteopontin , cystatin C and clusterin did not differ between the 2 groups . The area under the receiver operating characteristics curve of urinary NGAL was 0.876 ( 95 % confidence interval , 0.800–0.951 ; P<0.0001 ) , which was better than those of the other six urinary biomarkers . In addition , the urinary levels of NGAL at postoperative day 1 ( p = 0.0446 ) and day 7 ( p = 0.0006 ) can be a good predictive marker for tacrolimus-induced AKI within next 6 days , respectively . In conclusion , urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI , and may help predict renal event caused by tacrolimus therapy in liver transplant patients Purpose : Protective effect of pulsatile flow cardiopulmonary bypass ( CPB ) on the occurrence of acute renal injury is still a matter of debate . The objective of this study was to compare the effects of pulsatile and non-pulsatile cardiopulmonary bypass on kidneys using Urinary neutrophil gelatinase-associated lipocalin ( NGAL ) and interleukin-18 ( IL-18 ) as the markers of renal injury . Methods : 85 consecutive patients with normal preoperative renal function were prospect ively enrolled in the study . Pulsatile perfusion ( Group P ) and non-pulsatile perfusion ( Group NP ) was used in 42 and 43 of the patients , respectively , during aortic cross-clamping period . NGAL and IL-18 were analyzed using ELISA in urine sample s obtained preoperatively , and at 2 , 12 , and 24 h after CPB . Results : There was no significant difference between the groups in terms of perioperative renal function tests . IL-18 levels measured at 12 h after CPB were significantly lower in Group P , compared to Group NP ( p<0.05 ) . Urinary NGAL levels measured at 2 and 12 h were higher in Group NP ; however , the difference was insignificant . In the subgroup of patients with a cross clamp time ≥45 minutes ( pulsatile CPB , group P1 , n = 33 ; non-pulsatile CPB , group NP1 , n = 33 ) , IL-18 levels measured at 12 hours after CPB were significantly lower in Group P1 . Urinary NGAL concentrations measured at 2 and 12 hours in Group P1 were also significantly lower than that in Group NP1 ( p = 0.048 and 0.043 , respectively ) . Conclusions : Low IL-18 and NGAL levels found in the pulsatile perfusion group might suggest the use of pulsatile flow result ed in better kidney protection Background / Aims : Contrast-induced nephropathy ( CIN ) is at present the third leading cause of hospital-acquired acute kidney injury ( AKI ) . Traditionally , it is diagnosed by measuring the increase of the serum creatinine concentration . However , in patients with acute changes in their glomerular filtration rate , serum creatinine is an insensitive marker . This clinical study was design ed to investigate whether human urinary interleukin-18 ( IL-18 ) and neutrophil gelatinase-associated lipocalin ( NGAL ) are early predictive markers for AKI after coronary angiography and their correlation with later cardiac events . Methods : Patients undergoing coronary angiography using low-osmolar contrast medium were enrolled and then followed up for at least 17 months . Urine sample s were collected before and 24 h after coronary angiography and IL-18 and NGAL levels measured by using an ELISA kit . Results : CIN was diagnosed in 13 of 150 ( 8.7 % ) patients ( CIN group ) ; 27 patients without CIN served as control group . At 24 h after the procedure , the urinary IL-18 and NGAL levels were significantly increased in the CIN group , but not in the control group ( p < 0.05 ) . The predictable time of AKI onset determined by IL-18 was 24 h earlier than determined by serum creatinine ( p < 0.01 ) . Receiver operating characteristic curve analysis showed that both IL-18 and NGAL showed a good performance in early diagnosis of CIN as compared with serum creatinine ( p < 0.05 ) . We also found that IL-18 is an independent predictive marker for later major cardiac events : relative risk = 2.09 ( p < 0.01 ) . Conclusions : We conclude that urinary IL-18 or NGAL could be early biomarkers of CIN and that urinary IL-18 is well associated with the later cardiac outcomes in patients after coronary angiography Background Cardiac surgery-associated acute kidney injury ( CSA-AKI ) is a common complication following coronary bypass graft ( CABG ) surgery . Multi-factorial causes of CSA-AKI involve oxidative stress and inflammation . Erythropoietin ( EPO ) has been shown from many studies to have a reno-protective effect . The present study was conducted to examine the role of EPO in preventing CSA-AKI . Methods This prospect i ve , r and omized , double-blind , placebo-controlled trial was conducted in the Cardiovascular and Thoracic Unit . One hundred patients r and omly received either 200 U/kg of rHuEPO ( n = 50 ) or saline ( n = 50 ) intravenously three days before operation , and rHuEPO 100 U/kg or saline at operation time . The serum creatinine ( SCr ) , estimated glomerular filtration rate ( eGFR ) and urine neutrophil gelatinase-associated lipocaline ( NGAL ) were measured in order to evaluate renal injury following CABG . Results The incidence of CSA-AKI was significantly lower in rHuEPO group ( 14 % ) when compared with the placebo group ( 38 % ; p < 0.01 ) . The mean intensive care unit ( ICU ) and hospital stays of the rHuEPO group were significantly shorter than the placebo group ( p < 0.01 ) . Postoperative increases in SCr and decreases in eGFR were significantly lower in the rHuEPO group than the placebo group ( p < 0.05 ) . The mean urine NGAL in rHuEPO group was significantly lower than the placebo group at 3 hr , 6 hr , 12 hr and 18 hr after CABG ( p < 0.05 ) , respectively . Conclusions Prophylaxis administration with intravenous rHuEPO before cardiac surgery decreased the incidence of CSA-AKI and urine NGAL with reduced days in ICU and hospital in elective CABG patients .Trial registration Clinical Trials.gov : Introduction Cystatin C could be a relevant residual glomerular filtration rate marker during hemodialysis ( HD ) , and a high cytokine plasma ( p ) rate is associated with an increase in mortality during sepsis . To the best of our knowledge , cytokines and cystatin C kinetics during and after HD during sepsis have never been studied . In this study , we described p cytokines and cystatin C variations during and after hemodialysis in septic-shock patients with acute kidney injury ( AKI ) . Methods Ten patients , from two tertiary ICUs , with septic shock-related AKI , according to RIFLE class F , were studied . In this prospect i ve observational study , blood sample s were collected at the start , after 1 hour , 2 hours , and at the end of HD with a polymethymethacrylate ( PMMA ) hemodialyzer ( D0 , D1 , D2 , and endD ) , and 30 , 60 , 90 , 120 , and 180 min after HD ( postD0.5 , postD1 , postD1.5 , postD2 , and postD3 ) . We measured p interleukins (IL)-6 , IL-8 , IL-10 , cystatin C , and albumin . Results are expressed as variations from D0 ( mean ± SD ) . Results During HD , p[IL-6 ] did not vary significantly , whereas p[IL-8 ] and p[IL-10 ] reductions by D1 were 31.8 ± 21.2 % and 36.3 ± 26 % , respectively ( P < 0.05 as compared with D0 ) . At postD3 , p[IL-8 ] and p[IL-10 ] returned to their initial values . p[Cystatin C ] was significantly reduced from D1 to postD1 , with a maximal reduction of 30 ± 6.7 % on D2 ( P < 0.05 ) . Norepinephrine infusion rate decreased from D0 to postD3 ( 0.65 ± 0.39 to 0.49 ± 0.37 μg/kg/min ; P < 0.05 ) . Conclusions HD allows a transient and selective decrease in p cytokines , which are known as being correlated with mortality during septic shock . Because of a significant decrease in p cystatin C during HD , this should not be considered as an accurate marker for residual glomerular filtration rate during septic acute renal failure when receiving HD with a PMMA hemodialyzer AIM Renal ischaemia-reperfusion ( I/R ) injury , a primary cause of acute renal failure , can induce high morbidity and mortality . This study aim ed to explore the effect of erythropoietin on renal I/R injury and its underlying mechanism . METHODS Fifty male Sprague-Dawley rats were r and omly allocated to three groups ( n = 10 ) : the sham group , the renal ischaemia-reperfusion-saline ( IRI ) group , and the IRI+-Erythropoietin ( EPO ) group . Erythropoietin ( 250 , 500 , 1000 U/kg ) was intraperitoneally injected 30 min before inducing I/R. Renal I/R injury were induced by clamping the left renal artery for 30 min followed by reperfusion , along with a contralateral nephrectomy . Renal function and histological damage were determined after 24 h reperfusion . The expression of pro-inflammatory cytokines interleukin-6 ( IL-6 ) , interleukin-1 β ( IL-1β ) , and tumour necrosis factor-α ( TNF-α ) in the serum and renal tissue were evaluated by enzyme linked immunosorbent assay ( ELISA ) and reverse transcription-polymerase chain reaction ( RT-PCR ) , respectively . Further , the effects of erythropoietin on PI3K/Akt signalling , erythropoietin receptor ( EPOR ) and nuclear factor (NF)-κB activation were measured by Western blotting . RESULTS Erythropoietin pretreatment can significantly decrease the level of renal dysfunction in a dose-dependent manner , attenuated the renal histological changes , the expression of TNF-α , IL-1β , and IL-6 , the levels of reactive oxygen species ( ROS ) production and NF-κB p65 phosphorylation in renal tissue upon IRI . Moreover , erythropoietin pretreatment could further activate the PI3K/Akt signalling and induced EPOR activity . CONCLUSIONS Erythropoietin pretreatment could attenuate renal I/R injury by suppressing inflammation , which was associated with activating PI3K/Akt signalling though EPOR activation . Our findings suggest that erythropoietin may be a novel practical strategy to prevent renal I/R injury Objective Circulating adhesion molecules appear to be excellent markers of endothelial activation in critically ill patients . Pentoxifylline ( PTX ) may limit sequelae of inflammation and subsequent endothelial activation by various mechanisms . The influence of PTX on the plasma levels of soluble adhesion molecules in critically ill patients undergoing continuous veno-venous hemofiltration ( CVVH ) was studied . Design Prospect i ve , r and omized , blinded study . Setting Clinical investigation in the surgical intensive care unit of a university hospital . Patients and participants Fourteen consecutive patients suffering from acute renal failure ( ARF ) with postoperative complications who received continuous pentoxifylline ( CVVH-PTX ) i.v . were compared with 14 patients with ARF who did not receive PTX ( CVVH control group ) . Interventions Pump-driven CVVH was carried out with a blood flow ranging from 120 to 150 ml/min . All patients received fentanyl and midazolam continuously and were on mechanical ventilation . PTX ( 300 mg ) was given as a loading dose , followed by continuous infusion of 1.2 mg/kg per h for the next 5 days . Measurements and results From arterial blood sample s , plasma levels of soluble adhesion molecules ( endothelial leukocyte adhesion molecules [ sELAM-1 ] , and intercellular adhesion molecule-1 [ sICAM-1 ] , vascular cell adhesion molecule-1 [ sVCAM-1 ] , and P-selectin granule membrane protein [ sGMP-140 ] were measured using enzyme-linked immuno-sorbent assays ( ELISA ) . Measurements were carried out before the start of CVVH to establish baseline values and continued during the next 5 days . Main results Eleven of the CVVH-PTX patients and 8 of the CVVH control patients survived during the investigation period . In the CVVH-PTX patients 2.4±0.3 g/day of PTX was given . At baseline , plasma levels of sELAM-1 , sICAM-1 , and sVCAM-1 were markedly higher than normal in both groups . In the CVVH control patients , all measured soluble adhesion molecules increased further during the study period ( sELAM-1 from 90±22 to 134±30 ng/ml ; sICAM-1 from 958±173 to 1460±209 ng/ml ; sVCAM-1 from 1100±188 to 1804 ng/ml ; sGM-140 from 499±102 to 688±121 ng/ml ) ( p<0.05 ) , whereas in the PTX-treated CVVH patients , plasma levels of all soluble adhesion molecules remained almost unchanged . The PaO2/FIO2 increased in the PTX-treated patients ( from 209±67 to 282±58 mmHg ) and remained almost unchanged in the CVVH control patients . Conclusion Leukocyte/endothelial interactions play an important role in the inflammatory process . Circulating adhesion molecules may serve as markers of the extent of inflammation . Continuous i.v . administration of PTX was successful in blunting the increase of soluble adhesion molecules in critically ill patients undergoing CVVH . Whether these effects result from improved circulation at the microcirculatory level or from ( direct or indirect ) beneficial effects on endothelial cells warrants further controlled studies Background The lack of early biomarkers for acute kidney injury ( AKI ) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner . We tested the hypothesis that insulin-like growth factor-binding protein 7 ( IGFBP7 ) and tissue inhibitor of metalloproteinases-2 ( TIMP-2 ) , both inducers of G1 cell cycle arrest , function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass ( CPB ) . Methods We prospect ively studied 51 children undergoing cardiac surgery with CPB . Serial urine sample s were analyzed for [TIMP-2]•[IGFBP7 ] . The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery . Results 12 children ( 24 % ) developed AKI within 1.67 ( SE 0.3 ) days after surgery . Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7 ] as early as 4 h after the procedure , compared to children who did not develop AKI ( mean of 1.93 ( (ng/ml)2/1000 ) ( SE 0.4 ) vs 0.47 ( (ng/ml)2/1000 ) ( SE 0.1 ) , respectively ; p<0.05 ) . Urinary [TIMP-2]•[IGFBP7 ] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85 . Sensitivity was 0.83 , and specificity was 0.77 for a cutoff value of 0.70 ( (ng/ml)2/1000 ) . Conclusions Urinary [TIMP-2]•[IGFBP7 ] represent sensitive , specific , and highly predictive early biomarkers for AKI after surgery for congenital heart disease . Trial Registration www.germanctr.de/ , Introduction Recombinant human erythropoietin ( EPO ) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties . The aim of this single-site , r and omized , case-controlled , and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury ( AKI ) in patients with risk factors for AKI undergoing complex valvular heart surgery . Methods We studied ninety-eight patients with preoperative risk factors for AKI . The patients were r and omly allocated to either the EPO group ( n = 49 ) or the control group ( n = 49 ) . The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction . The control group received an equivalent volume of normal saline . AKI was defined as an increase in serum creatinine > 0.3 mg/dl or > 50 % from baseline . Biomarkers of renal injury were serially measured until five days postoperatively . Results Patient characteristics and operative data , including the duration of cardiopulmonary bypass , were similar between the two groups . Incidence of postoperative AKI ( 32.7 % versus 34.7 % , P = 0.831 ) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups . The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups . None of the patients developed adverse complications related to EPO administration , including thromboembolic events , throughout the study period . Conclusions Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery . Trial registration Clinical Trial.gov , Introduction The aim of the study was to evaluate the effects of high-dose fenoldopam , a selective dopamine-1 receptor , on renal function and organ perfusion during cardiopulmonary bypass ( CPB ) in infants with congenital heart disease ( CHD ) . Methods A prospect i ve single-center r and omized double-blind controlled trial was conducted in a pediatric cardiac surgery department . We r and omized infants younger than 1 year with CHD and biventricular anatomy ( with exclusion of isolated ventricular and atrial septal defect ) to receive blindly a continuous infusion of fenoldopam at 1 μg/kg/min or placebo during CPB . Perioperative urinary and plasma levels of neutrophil gelatinase-associated lipocaline ( NGAL ) , cystatin C ( CysC ) , and creatinine were measured to assess renal injury after CPB . Results We enrolled 80 patients : 40 received fenoldopam ( group F ) during CPB , and 40 received placebo ( group P ) . A significant increase of urinary NGAL and CysC levels from baseline to intensive care unit ( ICU ) admission followed by restoration of normal values after 12 hours was observed in both groups . However , urinary NGAL and CysC values were significantly reduced at the end of surgery and 12 hours after ICU admission ( uNGAL only ) in group F compared with group P ( P = 0.025 and 0.039 , respectively ) . Plasma NGAL and CysC tended to increase from baseline to ICU admission in both groups , but they were not significantly different between the two groups . No differences were observed on urinary and plasma creatinine levels and on urine output between the two groups . Acute kidney injury ( AKI ) incidence in the postoperative period , as indicated by pRIFLE classification ( pediatric score indicating Risk , Injury , Failure , Loss of function , and End-stage kidney disease level of renal damage ) was 50 % in group F and 72 % in group P ( P = 0.08 ; odds ratio ( OR ) , 0.38 ; 95 % confidence interval ( CI ) , 0.14 to 1.02 ) . A significant reduction in diuretics ( furosemide ) and vasodilators ( phentolamine ) administration was observed in group F ( P = 0.0085 ; OR , 0.22 ; 95 % CI , 0.07 to 0.7 ) . Conclusions The treatment with high-dose fenoldopam during CPB in pediatric patients undergoing cardiac surgery for CHD with biventricular anatomy significantly decreased urinary levels of NGAL and CysC and reduced the use of diuretics and vasodilators during CPB.Trial registration Clinical Trial . Gov NCT00982527 Background : Acute kidney injury ( AKI ) is a common and life-threatening complication following coronary artery bypass graft ( CABG ) . Neutrophil gelatinase-associated lipocalin ( NGAL ) and Cystatin C have shown to be good predictive factors for AKI . Recently , there has been a growing interest in the use of hypertonic saline in cardiac operations . The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline ( Group A ) infusion versus normal saline ( Group B ) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients . Methods : This r and omized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center , Tehran , Iran . After applying exclusion criteria , the effects of preoperative hypertonic saline ( 294 meq Na ) versus normal saline ( 154 meq Na ) infusion on serum NGAL and Cystatin C levels were investigated in three intervals : before surgery and 24 and 48 hours postoperatively . The probable intraoperative or postoperative confounders , including pump time , cross-clamp time , heart rate , systolic and diastolic blood pressures , central venous pressure , arterial pH , partial pressure of arterial oxygen , fraction of inspired oxygen , blood sugar , Na , K , Mg , hemoglobins , white blood cells , hematocrits , and platelets , were recorded and compared between the two groups of study . Results : The study population comprised 40 patients , including 25 ( 62.5 % ) males , at a , mean age ± SD of 61.75 ± 8.13 years . There were no statistically significant differences between the patients ’ basic , intraoperative , and postoperative characteristics , including intraoperative and postoperative hemodynamic variables and supports such as inotropic use . Intra-aortic balloon pump use and mortality were not seen in our cases . Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml . Moreover , 10 patients in Group A and 17 patients in group B showed a rise in serum Cystatin C levels above 1.16 mg/dl . Patients with AKI had significantly elevated NGAL and Cystatin C levels ( p value < 0.001 ) , but there were no significant differences in the decrease in the NGAL level in the hypertonic saline group versus the normal saline group ( 230.91 ± 92.68 vs. 239.74 ± 116.58 ng/ml , respectively ; p value = 0.792 ) , or in the decrease in the Cystatin C level in the hypertonic saline group versus the normal saline group ( 1.05 ± 0.26 vs. 1.06 ± 0.31 , respectively ; p value = 0.874 ) . Conclusion : Pre-treatment of CABG patients with hypertonic saline had no significant effect on serum NGAL and Cystatin C levels compared to the normal saline-receiving group . Our present data , albeit promising , have yet to fully document outcome differences Background Extended criteria donor ( ECD ) and donation after circulatory death ( DCD ) kidneys are at increased risk of delayed graft function ( DGF ) . Experimental evidence suggests that erythropoietin ( EPO ) attenuates renal damage in acute kidney injury . This study piloted the administration of high dose recombinant human EPO-beta at implantation of ECD and DCD kidneys , and evaluated biomarkers of kidney injury post-transplant . Methods Forty patients were r and omly assigned to receive either rhEPO-b ( 100,000 iu ) ( n = 19 in the intervention group , as 1 patient was un-transplantable post r and omisation ) , or placebo ( n = 20 ) in this , double blind , placebo-controlled trial at Manchester Royal Infirmary from August 2007 to June 2009 . Participants received either an ECD ( n = 17 ) or DCD ( n = 22 ) kidney . Adverse events , renal function , haematopoietic markers , and rejections were recorded out to 90 days post-transplant . Biomarkers of kidney injury ( neutrophil gelatinase-associated lipocalin , Kidney Injury Molecule-1 and IL-18 ) were measured in blood and urine during the first post-operative week . Results The incidence of DGF ( 53 % vs 55 % ) ( RR = 1.0 ; CI = 0.5 - 1.6 ; p = 0.93 ) and slow graft function ( SGF ) ( 32 % vs 25 % ) ( RR = 1.1 ; CI = 0.5 - 1.9 ; p = 0.73 ) respectively , serum creatinine , eGFR , haemoglobin and haematocrit , blood pressure , and acute rejection were similar in the 2 study arms . High dose rhEPO-b had little effect on the temporal profiles of the biomarkers . Conclusions High dose rhEPO-b appears to be safe and well tolerated in the early post- transplant period in this study , but has little effect on delayed or slow graft function in recipients of kidneys from DCD and ECD donors . Comparing the profiles of biomarkers of kidney injury ( NGAL , IL-18 and KIM-1 ) showed little difference between the rhEPO-b treated and placebo groups . A meta- analysis of five trials yielded an overall estimate of the RR for DGF of 0.89 ( CI = 0.73 ; 1.07 ) , a modest effect favouring EPO but not a significant difference . A definitive trial based on this estimate would require 1000 - 2500 patients per arm for population s with base DGF rates of 50 - 30 % and 90 % power . Such a trial is clearly unfeasible . Trial registration EudraCT Number 2006 - 005373 - 22 IS RCT N IS RCT N85447324 registered 19/08/09 Background Gadolinium chelates ( GCs ) have been traditionally considered as non-nephrotoxic magnetic resonance imaging ( MRI ) contrast material s. However , it has been suggested in some recent articles that GCs may have a nephrotoxic potential , but most of these reports are retrospective . However , the evaluated contrast agents , their doses , and the tests used to determine the kidney function were not consistent across studies . We aim ed to investigate the effect of magnetic field and an MRI contrast agent , gadopentetate dimeglumine ( GD ) , on renal functions in patients at high risk for acute kidney injury ( AKI ) . Material / Methods We design ed a prospect i ve case-control study with 2 age- and sex-matched groups of patients at high-risk for AKI ( n=72 for each group ) . Patients in Group 1 received a fixed dose of ( 0.2 mmol/kg ) GD-enhanced non-vascular MRI and patients in Group 2 received MRI without GD . Before the MRI and at 6 , 24 , 72 , and 168 hours after the MRI , biochemical tests , estimated glomerular filtration rate ( eGFR ) , albumin/creatinine ratio in spot urine , and early AKI biomarkers ( cystatin C , N-Acetyl-Glucosaminidase [ NAG ] , Neutrophil gelatinase-associated lipocalin [ NGAL ] ) were measured . Results Serum creatinine , albumin/creatinine ratio , and eGFR were not different between Group 1 and 2 ( p>0.05 ) . There were no significant changes in renal function tests and AKI biomarkers ( Δserum creatinine , Δalbumin/creatinine ratio , ΔGFR , Δcystatin C , ΔNAG , and ΔNGAL ) for either groups 6 , 24 , 72 , and 168 hours after the procedures ( p>0.05 ) . Conclusions MRI without contrast agent and non-vascular contrast-enhanced ( GD , 0.2 mmol/kg ) MRI are not nephrotoxic procedures for patients at high risk for AKI Background Contrast-induced acute kidney injury ( CI-AKI ) particularly in high risk patients with chronic kidney disease ( CKD ) , increases morbidity and mortality . Neutrophil gelatinase-associated lipocalin ( NGAL ) is a protein excreted by the kidney during AKI . There are no urine ( u ) NGAL data as an early CI-AKI marker in CKD patients undergoing coronary procedures . Methods This prospect i ve study enrolled 130 patients with estimated glomerular filtration rate ( eGFR ) < 60 ml/min/1.73 m2 undergoing elective coronary procedures . Serial urine sample s , obtained at baseline and 3 , 6 , 12 , 18 , and 24 h post contrast administration were analyzed by NGAL ELISA kit . AKI was defined as an increase in serum creatinine ( SCr ) of ≥ 0.3 mg/dl or ≥ 1.5 times baseline SCr within 48 h per 2012 KDIGO guidelines . Receiver operator characteristic curve analyses identified optimal uNGAL and delta of uNGAL values for diagnosing CI-AKI . Results The uNGAL was significantly and inverse correlated with eGFR ( R = 0.25 , P < 0.005 ) . CI-AKI developed in 16/130 ( 12.31 % ) patients : 13 and 3 in CI-AKI stages I and II , respectively . uNGAL and delta of uNGAL were significantly higher in the CI-AKI group when compared with the No CI-AKI group ( P < 0.05 ) . The best uNGAL cut-off for optimal sensitivity 94 % , specificity 78 % , and area under the curve 0.84 for predicting CI-AKI was 117 ng/mL at 6 h , respectively . Corresponding values for predicting CI-AKI stage II were 100 % , 87 % and 0.9 when using an uNGAL of 264 ng/mL at 6 h. Conclusions Monitoring of uNGAL levels not only provide the early detecting CI-AKI but also predict the severity of CI-AKI in CKD patients undergoing elective coronary procedures BACKGROUND Probucol , a lipid-lowering drug with potent antioxidant properties , may reduce the risk of cystatin C (CyC)-based contrast-induced acute kidney injury ( CIAKI ) . The aim of this study was to observe the incidence of CyC-based CIAKI and assess the efficacy of probucol on prevention of CIAKI following primary or urgent coronary angioplasty . METHODS A total of 204 patients with acute coronary syndrome ( ACS ) were prospect ively r and omized to a control group ( 108 patients , 74 male , 65.4 ± 12.5 years ) or probucol group ( 96 patients , 67 male , 65.1 ± 10.5 years ) 1000 mg orally before primary or urgent angioplasty and 500 mg twice daily for 3 days following intervention . Serum CyC and serum creatinine ( Scr ) concentrations were measured before , and on day 1 , day 2 and day 3 after coronary intervention . RESULTS The clinical characteristics of the patients from the two groups were similar . Scr-based CIAKI was developed in 23 patients of the control group ( 21.3 % ) and in 4 patients of the probucol group ( 4.2 % ) ( P<0.001 ) . Furthermore , CyC-based CIAKI occurred in 56 patients of the control group ( 51.9 % ) and 28 patients of the probucol group ( 29.2 % ) ( P<0.001 ) . The CyC increase ≥ 10 % after exposure to contrast medium was the best increment cutoff value for the early identification of patients at risk of CIAKI . CONCLUSIONS Our study suggests that CyC is a reliable marker for early identification and ruling out the patients at the risk of CIAKI . Among the patients with ACS who are undergoing primary or urgent angioplasty , prophylactic treatment with probucol reduces the risk of both Scr and CyC-based CIAKI Abstract Background The aim of this study was to establish a composite pig model with sepsis and ischemic acute kidney injury ( AKI ) and to investigate the differences in serum neutrophil gelatinase-associated lipocalin ( NGAL ) and proinflammatory cytokines in septic and non-septic AKI . Methods Seventeen healthy hybridized pigs ( weighed 26.97 ± 2.26 kg ) were r and omly divided into two groups . Group A ( n = 12 ) served as the septic AKI model which received cecal ligation and puncture , result ing in abdominal infection plus clamping of renal artery ( CRA ) . Group B ( n = 5 ) received CRA only . Vital signs and the functions of the main organs were observed . Serum NGAL , TNF-α , and IL-6 were measured at 0 , 4 , 8 , 24 , and 48 h after surgical admissions . Results Septic AKI model was successfully induced , which manifested as multiple organ dysfunction syndrome , including AKI , liver dysfunction , progressive decline of cardiac function and abnormal pulmonary function . Apparent pathological changes were found in kidney , liver , lung and small intestine of group A. The proinflammatory cytokines in Group A were significantly higher than those in Group B at different time points ( P < 0.05 ) . In Group A , serum concentrations of TNF-α reached the peak at 8 h , while IL-6 levels dramatically increased at 24 h. There was a significant difference in serum NGAL between Group A and B at 8 h ( P < 0.05 ) . Conclusions Septic AKI animals have higher serum NGAL compared with non-septic AKI animals . Monitoring the activities of TNF-α , NGAL and IL-6 would make great contributions in discovering sepsis and evaluating the severity of sepsis Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury ( AKI ) . Both exercise-induced muscle damage and AKI are associated with the release of interleukin-6 , but whether muscle damage causes AKI in the heat is unknown . We hypothesized that muscle-damaging exercise , before exercise in the heat , would increase kidney stress . Ten healthy euhydrated men underwent a r and omized , crossover trial involving both a 60-min downhill muscle-damaging run ( exercise-induced muscle damage ; EIMD ) , and an exercise intensity-matched non-muscle-damaging flat run ( CON ) , in r and om order separated by 2 wk . Both treatments were followed by heat stress elicited by a 40-min run at 33 ° C . Urine and blood were sample d at baseline , after treatment , and after subjects ran in the heat . By design , EIMD induced higher plasma creatine kinase and interleukin-6 than CON . EIMD elevated kidney injury biomarkers ( e.g. , urinary neutrophil gelatinase-associated lipocalin ( NGAL ) after a run in the heat : EIMD-CON , mean difference [ 95 % CI ] : 12 [ 5 , 19 ] ng/ml ) and reduced kidney function ( e.g. , plasma creatinine after a run in the heat : EIMD-CON , mean difference [ 95 % CI ] : 0.2 [ 0.1 , 0.3 ] mg/dl ) , where CI is the confidence interval . Plasma interleukin-6 was positively correlated with plasma NGAL ( r = 0.9 , P = 0.001 ) . Moreover , following EIMD , 5 of 10 participants met AKIN criteria for AKI . Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise . Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments BACKGROUND Although intravenous hydration with isotonic saline is the st and ard therapy for the prevention of contrast-induced nephropathy ( CIN ) , there is still insufficient evidence concerning the optimal timing to initiate preprocedural intravenous hydration with isotonic saline . METHODS This study prospect ively compared the contrast-induced increases in serum creatinine and cystatin C between 5-hour preprocedural intravenous hydration with isotonic saline ( 5h-HS ) and 20-hour preprocedural intravenous hydration with isotonic saline ( 20 h-HS ) in 122 patients with renal insufficiency ( estimated glomerular filtration rate of 15 - 60 ml/min/1.73 m(2 ) ) undergoing an elective coronary procedure . The patients were r and omly assigned to receive either 5h-HS ( n=60 ) or 20 h-HS ( n=62 ) . Serum creatinine and cystatin C were measured at baseline , immediately before contrast exposure , and 24 hours and 48 hours after contrast exposure . The primary end points were the maximal absolute and percent changes in serum creatinine and cystatin C from the baseline up to 48 hours after contrast exposure . RESULTS The maximal absolute and percent changes in serum creatinine ( 0.01 ± 0.13 mg/dl vs. -0.03 ± 0.16 mg/dl , p=0.16 ; 0.87 ± 10.05 % vs. -1.50 ± 12.92 % , p=0.26 ; respectively ) and cystatin C ( -0.05 ± 0.17 mg/l vs. -0.06 ± 0.17 mg/l , p=0.59 ; -2.94 ± 9.29 % vs. -3.46 ± 9.21 % , p=0.75 ; respectively ) did not differ between the 2 regimens . CONCLUSIONS 20 h-HS is not superior to 5h-HS in the prevention of the contrast-induced increases in serum creatinine and cystatin C in patients with renal insufficiency undergoing an elective coronary procedure PURPOSE To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers ( NGALp , NGALu , KIM 1 and IL 18 ) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury . METHODS Thirty two Wistar rats were r and omly allocated to four groups : Sham ( S ) : laparotomy ; Control ( C ) : laparotomy and ischaemia-reperfusion in the left kidney ; Control Allopurinol ( CA ) : laparotomy and allopurinol at a dose of 100mg·kg 1·d 1 ; and Allopurinol ( A ) : laparotomy ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg·kg 1·d 1 . The NGALp , NGALu , KIM 1 , IL 18 and creatinine levels and the kidney histology were analysed . The significance level was established as p<0.05 . RESULTS Creatinine level increased in all the groups , with A ≈ C > S ≈ CA . The NGALp , NGALu and IL 18 levels exhibited similar behaviour in all the groups . KIM 1 was higher in group A than C and showed intermediate values in groups S and CA . Severity of injury in the left kidney was greater in groups C and A compared to S and CA . CONCLUSION Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury BACKGROUND High-dose statin loading is known to reduce periprocedural myocardial infa rct ion and contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention . However , the clinical role of high-dose statin loading in patients with acute heart failure ( AHF ) remains unknown . METHODS AND RESULTS In a prospect i ve , single-center , r and omized , controlled , open-label pilot study , patients hospitalized with AHF were r and omly assigned to receive oral high-dose atorvastatin loading ( 80 mg for 3 days , followed by 10 mg/day until discharge ) or no statin therapy , on top of optimal HF treatment . The primary outcome measures were changes to the level of biomarkers related to inflammation and renal injury from admission to hospital day 4 . No significant changes in the levels of NT-proBNP ( -2,627±4,956 vs. -2,981±6,951 pg/ml , P=0.845 ) , hsCRP ( -6.1±16.4 vs. -2.1±16.2 mg/L , P=0.105 ) , cystatin C ( 0.002±0.185 vs. 0.009±0.216 mg/L , P=0.904 ) , ACR ( -886.3±1,984.9 vs. -165.6±825.2 mg/day , P=0.124 ) were observed in either group . In-hospital mortality ( 4.3 % vs. 3.8 % , P>0.999 ) and all-cause mortality at 90 days ( 4.3 % vs. 3.8 % , P>0.999 ) were not significantly different between groups . CONCLUSIONS This pilot study showed that oral high-dose atorvastatin loading may be used safely in patients with AHF , but is not effective in reducing the levels of circulating biomarkers related to inflammation and renal injury during hospitalization BACKGROUND Acute kidney injury after cardiac surgery is common , has no effective treatments , and is associated with adverse outcomes . The aim of this study was to determine whether administration of the phosphodiesterase-5 inhibitor sildenafil citrate ( SDF ) would prevent the development of post-cardiopulmonary bypass ( CPB ) acute kidney injury in swine . METHODS Adult pigs ( n = 8 per group ) were r and omized to undergo sham procedure , CPB , or CPB plus administration of SDF , with recovery and re assessment at 24 hours . RESULTS Cardiopulmonary bypass result ed in a significant reduction in creatinine clearance relative to sham pigs ( mean difference CPB versus sham , -47.9 mL/min ; 95 % confidence interval [ CI ] : -93.7 to -2.2 ; p = 0.039 ) . This was prevented by the administration of SDF during CPB ( mean difference CPB+SDF versus CPB , + 55.6 mL/min ; 95 % CI : + 6.5 to + 104.7 ; p = 0.024 ) . Cardiopulmonary bypass also result ed in a significant rise in the urinary biomarker interleukin-18 compared with sham procedures ( mean difference 209.3 pg/mL ; 95 % CI : 120.6 to 298.1 ; p < 0.001 ) that was prevented by SDF administration . Post-CPB kidney injury was associated with vascular endothelial injury and dysfunction , reduced nitric oxide bioavailability , medullary hypoxia , cortical adenosine triphosphate depletion , inflammation , and evidence of proximal tubule epithelial cell stress manifest as phenotypic change . Administration of SDF to CPB pigs preserved nitric oxide bioavailability and prevented endothelial dysfunction , regional hypoxia , inflammation , and tubular changes . CONCLUSIONS In this model , phosphodiesterase-5 inhibition using SDF prevented post-CPB acute kidney injury by the preservation of nitric oxide bioavailability , and warrants evaluation as a renoprotective agent in clinical trials Background : Several recent studies have shown that neutrophil gelatinase-associated lipocalin ( NGAL ) may be a promising biomarker for the early detection of acute kidney injury ( AKI ) , but the role of NGAL in predicting adverse clinical outcomes has not been well addressed . The purpose of this study was to evaluate the usefulness of urine NGAL as outcome predictor in patients with AKI . Methods : This was a prospect i ve cohort study enrolling hospitalized AKI patients . Patients were divided into four groups according to initial urine NGAL excretion quartiles . The primary clinical outcome variables were in-hospital mortality and renal function at 4 weeks . Results : Initial urine NGAL was identified as an independent predictor of in-hospital mortality and persistent loss of renal function . In the analysis of predictive performance of urine NGAL , the AUC was 0.882 and a cutoff value of 298.28 ng/ml predicted loss of renal function with 88.2 % sensitivity and 81.0 % specificity . Conclusion : This study could suggest that urine NGAL , a new early biomarker might also be served as a reliable clinical outcome predictor in AKI patients Objective : Increased pneumoperitoneum pressure during laparoscopic surgery can result in acute kidney injury . We aim ed to clarify whether intraabdominal pressure tolerance is modified in various degrees of unilateral kidney hydronephrosis in rabbits . Methods : A total 90 rabbits were r and omly allocated to three groups ( group PN , PM and PS , i.e. rabbits with no , mild and severe hydronephrosis , respectively , subjected to intraabdominal pressures ) . Rabbits in group PM ( n = 30 ) and group PS ( n = 30 ) underwent a surgical procedure inducing a mild or severe left hydronephrosis . Rabbits in all groups were then allocated to 5 subgroups . Then , they were subjected to intraabdominal pressures of 0 , 6 , 9 , 12 , and 15 mm Hg , respectively . Acute kidney injury was assessed by measuring serum creatinine ( Scr ) , blood urea nitrogen ( BUN ) , tubular cell apoptosis , kidney injury molecule-1 ( KIM-1 ) and cysteine-rich 61 ( Cyr-61/CCN1 ) expression . Results : Acute kidney injury with increased tubular apoptosis and KIM-1 and Cyr-61 expression occurred when intraabdominal pressure reached 15 , 15 and 9 mm Hg in PN , PM and PS groups , respectively . The Scr and BUN levels were similar in all groups . Conclusions : In rabbits , kidneys with severe hydronephrosis were more likely to suffer acute injury when they were exposed to pneumoperitoneal pressure AIM The objective of this study was to determine the intraoperative ultrafiltration effect on postoperative AKI . METHODS In this prospect i ve r and omized clinical trail , 159 patients scheduled for elective cardiac surgery , were r and omly assigned to either hemofilter ( N.=87 ) or control group ( N.=72 ) . The primary and secondary outcomes were AKI ( defined as ≥50 % increase in the serum creatinine level ) and increased urinary neutrophil gelatinase-associated lipocalin ( NGAL ) in the postoperative period , respectively . RESULTS The two groups were similar with respect to comorbidities and also surgical procedure , except ultrafiltration . The incidence of AKI was equal in the both groups ( 11 % vs. 5 % , P=0.2 , respectively ) . Creatinine increased after surgery ( P=0.00 ) without significant differences between the both groups ( P=0.2 ) . Urinary NGAL also showed no significant difference between the groups . Age , euroscore , hyperlipidemia , pulmonary disease and urinary volume during operation correlated with the development of AKI . Postoperative blood loss was less in the hemofilter than control group ( 820±550 mL vs. 1100±630 mL , P=0.04 ) . There was no difference in the length of intubation and stay in intensive care unit . CONCLUSION Routine use of ultrafiltration during cardiac surgery offers no advantages in renal protection and reduction of AKI incidence RATIONALE Long-term outcomes after acute kidney injury ( AKI ) are poorly described . OBJECTIVES We hypothesized that one single episode of minimal ( stage 1 ) AKI is associated with reduced long-term survival compared with no AKI after recovery from critical illness . METHODS A prospect i ve cohort of 2,010 intensive care unit ( ICU ) patients admitted to the ICU between years 2000 and 2009 at a provincial tertiary care hospital . Development of AKI was determined according to the KDIGO classification and mortality up to 10 years after ICU admission was recorded . MEASUREMENTS AND MAIN RESULTS Of the 1,844 eligible patients , 18.4 % had AKI stage 1 , 12.1 % had stage 2 , 26.5 % had stage 3 , and 43.0 % had no AKI . The 28-day , 1-year , 5-year , and 10-year survival rates were 67.1 % , 51.8 % , 44.1 % , and 36.3 % in patients with mild AKI , which was significantly worse compared with the critically ill patients with no AKI at any time ( P < 0.01 ) . The unadjusted 10-year mortality hazard ratio was 1.53 ( 95 % confidence interval , 1.2 - 2.0 ) for 28-day survivors with stage 1 AKI compared with critically ill patients with no AKI . Adjusted 10-year mortality risk was 1.26 ( 1.0 - 1.6 ) . After propensity matching stage 1 AKI with no AKI patients , mild AKI was still significantly associated with decreased 10-year survival ( P = 0.036 ) . CONCLUSIONS Patients with one episode of mild AKI have significantly lower long-term survival rates than critically ill patients with no AKI . Close medical follow-up of these patients may be warranted and mechanistic research is required to underst and how AKI influences long-term events BACKGROUND Neutrophil gelatinase-associated lipocalin ( NGAL ) and cystatin C are biomarkers of kidney injury and function , respectively . This study assessed whether plasma NGAL and /or serum cystatin C predicted baseline estimated glomerular filtration rate ( eGFR ) and urinary protein excretion , rate of change of eGFR and urinary protein excretion and whether atorvastatin influenced changes in these biomarkers in patients with chronic kidney disease ( CKD ) . METHODS This is a post hoc analysis of the Lipid Lowering and Onset of Renal Disease trial , a r and omized double-blind , placebo-controlled trial where 88 patients with Stages 2 - 4 CKD received atorvastatin 10 mg/day ( 48 ) or placebo ( 40 ) . Stored blood sample s were analysed for NGAL and cystatin C at baseline and a mean of 1.5 and 2.9 years later . Serum creatinine and Modification of Diet in Renal Disease ( MDRD ) eGFR were obtained three monthly . RESULTS There were negative associations between NGAL and cystatin C and eGFR ( P = 0.025 and P < 0.001 , respectively ) at all time points . There were no associations between baseline NGAL and cystatin C and rate of change of eGFR ( P = 0.44 and P = 0.49 , respectively ) . Baseline NGAL but not cystatin C ( P = 0.043 and P = 0.35 , respectively ) predicted rate of change of urinary protein excretion . In atorvastatin-treated patients , NGAL decreased ( mean , -7.4 ng/mL/year ; SD 128.4 ) , whereas it increased in the placebo group [ mean , 4.6 ng/mL/year ; SD 56.6 ) , the difference being statistically significant ( P = 0.049 ) . CONCLUSIONS NGAL is a biomarker of existing CKD but did not predict CKD progression . Atorvastatin reduced plasma NGAL but the significance and mechanisms require further investigation . Atorvastatin had no significant effect on cystatin Background Cardiopulmonary bypass procedure is associated with an increased risk of renal impairment . To which extent structural damage causes functional decline is unknown . We evaluated perioperative kidney injury and function in patients treated with conventional extracorporeal circulation ( CECC ) , minimized extracorporeal circulation ( MECC ) , and off-pump coronary artery bypass grafting ( OPCAB ) . Methods Blood and urine sample s , collected at baseline and up to 72 hours after surgery from patients of the HEPCON trial ( DRKS00007580 , 120 patients r and omized for heparin management and for surgical technique ) , were analyzed for differences in renal injury and function . Neutrophil gelatinase-associated lipocalin , α glutathione S-transferase , liver fatty acid-binding protein , and kidney injury molecule-1 were measured as urinary protein markers of renal tubular injury . Serum creatinine , blood urea levels , and estimated glomerular filtration rate were determined to monitor renal function . Results Markers of tubular injury differed significantly between surgical technique groups early after surgery , indicating the most detrimental effect in CECC . Hemolysis and hemodilution correlated with these early changes . A late rise did not show intergroup differences . Time courses of renal function parameters , as well as the development of acute kidney injury in 15 patients ( 13.5 % ) , were irrespective of surgical technique . Heparin management did not influence renal parameters . Conclusion During coronary artery bypass grafting , CECC temporarily induces more tubular injury than MECC or OPCAB . However , late changes of renal function parameters occur irrespective of extracorporeal perfusion mode and even in off-pump surgery Introduction Acute kidney injury ( AKI ) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit . Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI , in which multiple etiologies exist . The objective of this study was to identify and vali date novel biomarkers of AKI . Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation . The top two markers from discovery were vali date d in a second study ( Sapphire ) and compared to a number of previously described biomarkers . In the discovery phase , we enrolled 522 adults in three distinct cohorts including patients with sepsis , shock , major surgery , and trauma and examined over 300 markers . In the Sapphire validation study , we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment ; the final analysis cohort was a heterogeneous sample of 728 critically ill patients . The primary endpoint was moderate to severe AKI ( KDIGO stage 2 to 3 ) within 12 hours of sample collection . Results Moderate to severe AKI occurred in 14 % of Sapphire subjects . The two top biomarkers from discovery were vali date d. Urine insulin-like growth factor-binding protein 7 ( IGFBP7 ) and tissue inhibitor of metalloproteinases-2 ( TIMP-2 ) , both inducers of G1 cell cycle arrest , a key mechanism implicated in AKI , together demonstrated an AUC of 0.80 ( 0.76 and 0.79 alone ) . Urine [TIMP-2]·[IGFBP7 ] was significantly superior to all previously described markers of AKI ( P < 0.002 ) , none of which achieved an AUC > 0.72 . Furthermore , [TIMP-2]·[IGFBP7 ] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model , generalized estimating equation , integrated discrimination improvement or net reclassification improvement . Finally , in sensitivity analyses [TIMP-2]·[IGFBP7 ] remained significant and superior to all other markers regardless of changes in reference creatinine method . Conclusions Two novel markers for AKI have been identified and vali date d in independent multicenter cohorts . Both markers are superior to existing markers , provide additional information over clinical variables and add mechanistic insight into AKI.Trial registration Clinical Trials.gov number NCT01209169 OBJECTIVE The purpose of this study was to assess the effect of i.v . administration of N-acetylcysteine ( NAC ) on serum levels of creatinine and cystatin C , two markers of renal function , in patients with renal insufficiency who undergo emergency contrast-enhanced CT . SUBJECTS AND METHODS Eighty-seven adult patients with renal insufficiency who underwent emergency CT were r and omized to two groups . In the first group , in addition to hydration , patients received a 900-mg injection of NAC 1 hour before and another immediately after injection of iodine contrast medium . Patients in the second group received hydration only . Serum levels of creatinine and cystatin C were measured at admission and on days 2 and 4 after CT . Nephrotoxicity was defined as a 25 % or greater increase in serum creatinine or cystatin C concentration from baseline value . RESULTS A 25 % or greater increase in serum creatinine concentration was found in nine ( 21 % ) of 43 patients in the control group and in two ( 5 % ) of 44 patients in the NAC group ( p = 0.026 ) . A 25 % or greater increase in serum cystatin C concentration was found in nine ( 22 % ) of 40 patients in the control group and in seven ( 17 % ) of 41 patients in the NAC group ( p = 0.59 ) . CONCLUSION On the basis of serum creatinine concentration only , i.v . administration of NAC appears protective against the nephrotoxicity of contrast medium . No effect is found when serum cystatin C concentration is used to assess renal function . The effect of NAC on serum creatinine level remains unclear and may not be related to a renoprotective action Purpose Serum uric acid ( SUA ) is a novel risk factor for acute kidney injury ( AKI ) , which adversely affects renal blood flow autoregulation , glomerular filtration rate ( GFR ) , and promotes inflammation and angiogenesis . This pilot study investigated the effect of lowering SUA therapy on AKI , by using traditional and non-traditional markers . Material s and methods In this prospect i ve , double-blind , placebo-controlled , r and omized pilot trial , 26 hyperuricemic patients undergoing cardiac surgery were r and omized to receive rasburicase or placebo in the preoperative period . Results Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo . Despite no difference in primary endpoint , the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin ( uNGAL ) concentrations , especially in subjects with higher SUA levels , more severe renal dysfunction ( baseline GFR ≤ 45 mL/min/1.73 m2 ) or heart failure ( left ventricular ejection fraction ≤45 % ) . Conclusions In this study , rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery . However , the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury Cisplatin-induced acute kidney injury ( AKI ) is a major concern among clinicians in prescribing cisplatin-based chemotherapy . This study evaluated and compared the ability of urinary biomarkers , including urinary neutrophil gelatinase-associated lipocalin ( NGAL ) , cystatin C , and the urinary albumin to creatinine ratio ( ACR ) to predict cisplatin-induced AKI . Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospect ively studied , including 10 ( 30 % ) who developed AKI ( the study group ) . Changes of urinary biomarkers were compared at 4 hours , 8 hours , and 12 hours , and 1 day , 2 days , 3 days , and 4 days after cisplatin intravenous infusions ( 75mg/m(2 ) ) versus the baseline . There was a significant increase in urinary NGAL levels from 12 hours to 4 days ( p<0.05 ) compared to baseline after cisplatin infusion in the AKI group . The magnitude of these changes over time differed significantly by group ( p<0.001 ) . The area under the receiver operating curve describing the relationship between urinary NGAL levels and AKI within 12 hours was 0.865 ( 95 % confidence interval=0.691 - 1.000 ) . Urinary NGAL levels independently predicted AKI 12 hours after cisplatin ( p=0.045 ) after adjustments for age , gender , body mass index , baseline serum creatinine , and urinary total protein . Urinary NGAL levels may be an early biomarker of AKI in patients receiving cisplatin-based treatment OBJECTIVE The objective of this study was to evaluate whether remote ischemic preconditioning can protect kidney function in children undergoing operation for complex congenital heart disease . METHODS Children ( n = 113 ) aged 0 to 15 years admitted for complex congenital heart disease were r and omly allocated according to age to remote ischemic preconditioning and control groups . After exclusion of 8 patients , we conducted the analysis on 105 patients ( remote ischemic preconditioning group , n = 54 ; control group , n = 51 ) . Before surgery , remote ischemic preconditioning was performed as 4 cycles of 5 minutes of ischemia by inflating a cuff around a leg to 40 mm Hg above the systolic pressure . End points were development of acute kidney injury , initiation of dialysis , plasma creatinine , estimated glomerular filtration rate , plasma cystatin C , plasma and urinary neutrophil gelatinase-associated lipocalin , and urinary output . Secondary end points included postoperative blood pressure , inotropic score , and mortality , as well as morbidity reflected by reoperation and stays in the intensive care unit and hospital . RESULTS Overall , 57 of the children ( 54 % ) had acute kidney injury develop , with 27 ( 50 % ) in the remote ischemic preconditioning group and 30 ( 59 % ) in the control group ( P > .2 ) . Remote ischemic preconditioning was not associated with improvement in either any of the renal biomarkers or any of the secondary end points . CONCLUSIONS We found no evidence that remote ischemic preconditioning provided protection of kidney function in children undergoing operation for complex congenital heart disease Abstract Purpose Interruption of renal blood flow is often necessary during nephron sparing surgery ( NSS ) and can induce renal injury . This study examines whether tadalafil , a phosphodiesterase-5 ( PDE-5 ) inhibitor and well-known vasodilator , exerts nephroprotective effects in patients undergoing NSS . Methods This non-r and omized study included 49 patients with enhancing solid renal mass . All patients were subjected to open NSS during which clamping the renal artery was performed . Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery . The other 27 patients underwent the same surgical procedure but did not receive tadalafil ( controls ) . Urine sample s were collected before surgery and following renal pedicle clamp removal . Urine levels of NGAL and KIM-1 , two novel biomarkers for acute kidney injury ( AKI ) , were determined . Results Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants . These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h , respectively . Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1 , but not of NGAL . Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects , the elevation in serum creatinine ( SCr ) was significantly attenuated in tadalafil-treated group as compared with NSS controls . Conclusions Tadalafil exerts nephroprotective effects in AKI following NSS , as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation . Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients Acute kidney injury ( AKI ) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality . N‐acetylcysteine ( NAC ) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical setting s. In the present study , we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients . A double‐blind r and omized placebo‐controlled trial was conducted , and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day −6 to day + 15 . AKI was determined on the basis of the Risk – Injury – Failure – Loss – End‐stage renal disease and AKI Network criteria as the primary outcome . We assessed urine neutrophil gelatinase‐associated lipocalin ( uNGAL ) on days −6 , −3 , + 3 , + 9 and + 15 as the secondary outcome . Moreover , transplant‐related outcomes and NAC adverse reactions were evaluated during the study period . Statistical analysis was performed using appropriate parametric and non‐parametric methods including Kaplan – Meier for AKI and generalized estimating equation for uNGAL . At the end of the trial , data from 72 patients were analysed ( NAC : 33 patients and placebo : 39 patients ) . Participants of each group were not different considering baseline characteristics . AKI was observed in 18 % of NAC recipients and 15 % of placebo group patients , and the occurrence pattern was not significantly different ( p = 0.73 ) . Moreover , no significant difference was observed between groups for uNGAL measures ( p = 0.10 ) . Transplant‐related outcomes were similar for both groups , and all patients had successful engraftment . Three patients did not tolerate NAC because of abdominal pain , shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation . However , the frequency of adverse reactions was not significantly different between groups . In conclusion , our findings could not show any clinical benefits from high‐dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients . Copyright © 2014 John Wiley & Sons , Objective The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine ( NAC ; antioxidant ) and furosemide ( diuretic ) on intrarenal oxygenation as evaluated by blood oxygen level – dependent ( BOLD ) magnetic resonance imaging ( MRI ) in combination with urinary neutrophil gelatinase – associated lipocalin ( NGAL ) measurements . Material s and Methods Rats received nitric oxide synthase inhibitor L-NAME ( 10 mg/kg ) and cyclooxygenase inhibitor indomethacin ( 10 mg/kg ) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions : NAC , furosemide , or placebo . One of the 3 iodinated contrast agents ( iohexol , ioxaglate , or iodixanol ) was then administered ( 1600-mg organic iodine per kilogram body weight ) . Fifty-four Sprague-Dawley rats were allocated in a r and om order into 9 groups on the basis of the intervention and the contrast agent received . Blood-oxygen-level – dependent MRI – weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline , after L-NAME , indomethacin , interventions or placebo , and iodinated contrast agents . Data acquisition and analysis were performed in a blind fashion . R2 * ( = 1/T2 * ) maps were generated inline on the scanner . A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data . Urinary NGAL , a marker of acute kidney injury , was measured at baseline , 2 and 4 hours after the contrast injection . Results Compared with the placebo-treated rats , those treated with furosemide showed a significantly lower rate of increase in R2 * ( P < 0.05 ) in the renal inner stripe of the outer medulla . The rats treated with NAC showed a lower rate of increase in R2 * compared with the controls , but the difference did not reach statistical significance . Urinary NGAL showed little to no increase in R2 * after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo ( P < 0.05 ) . Conclusions This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI . The rate of increase in R2 * after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL . Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media . Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury , the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans Background : Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes . This study was design ed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors . Methods : 20 adult kidney transplant recipients from living donors were included in a double-blind , r and omized , placebo-controlled clinical pilot study that compared spironolactone and placebo . Placebo or spironolactone ( 25 mg ) was administered 1 day before and 3 days posttransplantation . Renal function and urinary kidney injury molecule-1 , interleukin-18 , and heat shock protein 72 as well as urinary hydrogen peroxide ( H2O2 ) levels were quantified . Results : No significant differences were seen between the groups studied regarding age , gender , indication for kidney transplantation , residual renal function , renal replacement therapy , or warm and cold ischemia periods . In contrast , spironolactone administration significantly reduced the oxidative stress assessed by the urinary H2O2 excretion , in spite of no differences in renal function or reduction in tubular injury biomarkers . Conclusions : The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H2O2 as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon BACKGROUND Using either an angiotensin-converting enzyme inhibitor ( ACEi ) or an angiotensin receptor blocker ( ARB ) the morning of surgery may lead to ' functional ' postoperative acute kidney injury ( AKI ) , measured by an abrupt increase in serum creatinine . Whether the same is true for ' structural ' AKI , measured with new urinary biomarkers , is unknown . METHODS The TRIBE-AKI study was a prospect i ve cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010 . We classified the degree of exposure to ACEi/ARB into three categories : ' none ' ( no exposure prior to surgery ) , ' held ' ( on chronic ACEi/ARB but held on the morning of surgery ) or ' continued ' ( on chronic ACEi/ARB and taken the morning of surgery ) . The co- primary outcomes were ' functional ' AKI based upon changes in pre- to postoperative serum creatinine , and ' structural AKI ' , based upon peak postoperative levels of four urinary biomarkers of kidney injury . RESULTS Across the three levels ( none , held and continued ) of ACEi/ARB exposure there was a grade d increase in functional AKI , as defined by AKI stage 1 or worse ; ( 31 , 34 and 42 % , P for trend 0.03 ) and by percentage change in serum creatinine from pre- to postoperative ( 25 , 26 and 30 % , P for trend 0.03 ) . In contrast , there were no differences in structural AKI across the strata of ACEi/ARB exposure , as assessed by four structural AKI biomarkers ( neutrophil gelatinase-associated lipocalin , kidney injury molecule-1 , interleukin-18 or liver-fatty acid-binding protein ) . CONCLUSIONS Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury . As AKI from ACEi/ARB in this setting is unclear , interventional studies testing different strategies of perioperative ACEi/ARB use are warranted Objective : This study tests the hypothesis that methylprednisolone may influence eNOS activity in renal arterial and venous vascular beds and impede sub clinical renal injury . Summary Background Data : Acute renal failure is a major complication of cardiovascular surgery . Renal damage arises in part from excessive vasoconstriction mediated by an imbalance of vasoconstrictive ET-1 and vasodilatory NO produced by eNOS . While methylprednisolone may reduce sub clinical renal injury as measured by urinary N-acetyl-beta-D-glucosaminidase ( β-NAG ) , its effects upon eNOS activity in renal arterial and venous vascular beds , reflected by urinary nitrate levels , is unclear . Methods : A porcine model of normotensive , euvolemic infrarenal aortic ischaemia-reperfusion was used . Forty-two pigs underwent a 60-minute laparotomy followed by 150 minutes of infrarenal ischemia and 180 minutes of reperfusion . Animals were r and omized to receive methylprednisolone 30 mg/kg or placebo after induction of general anesthesia . Urinary β-NAG levels were assessed as an index of sub clinical renal injury , whereas urinary nitrate was assessed as an indicator of eNOS activity in renal arterial and venous vascular beds . Results : Methylprednisolone treatment did not influence mean arterial , central venous , or pulmonary artery wedge pressures but suppressed plasma IL-6 levels . After the ischemia-induced rise from preanaesthetic baseline levels , urinary β-NAG levels declined to significantly lower values in the MP group , indicative of MP renal protection ( P < 0.05 ) . Conversely , urinary nitrate levels indicative of vascular e-NOS activity remained significantly and persistently higher in MP-treated animals ( P < 0.05 ) . Conclusion : This study , in a porcine model of renal ischaemia-reperfusion injury , shows the benefits of methylprednisolone pretreatment in enhancing urinary nitrate levels indicative of vascular eNOS activity and the reduction of urinary β-NAG levels , which represent sub clinical renal injury Although contrast-induced acute kidney injury ( CI-AKI ) has a great impact on patients ’ prognosis , few data exist regarding predictors of CI-AKI in patients with severe renal dysfunction who have undergone contrast angiography . Therefore , we prospect ively studied 25 patients with renal dysfunction , which was defined as the estimated glomerular filtration rate ( eGFR ) level < 45 ml/min/1.73 m2 , undergoing coronary angiography ( CAG ) or percutaneous coronary intervention ( PCI ) . We performed hemodiafiltration with blood suction from the right atrium ( RA-HDF ) . The mean level of urinary liver-type fatty acid-binding protein ( L-FABP ) at baseline was significantly higher in the CI-AKI group than in the non-CI-AKI group ( 59.8 ± 45.6 vs 13.4 ± 11.9 μg/gCr , P = 0.0003 ) . Multivariate regression analysis demonstrated that baseline urinary L-FABP was an independent significant predictor of CI-AKI ( β = 0.741 , P = 0.013 ) . Receiver-operating characteristic analysis showed that baseline urinary L-FABP exhibited 100 % sensitivity and 81.8 % specificity for predicting CI-AKI when the cutoff value was defined as 19.0 μg/gCr . Interestingly , the incidence of CI-AKI after CAG or PCI was reduced in the RA-HDF group in a comparison with 41 control patients ( 12 % vs 27 % ) with eGFR level < 45 ml/min/1.73 m2 who underwent PCI before the introduction of RA-HDF . In conclusion , baseline L-FABP levels can be a predictor for occurrence of CI-AKI . We suggest that RA-HDF may prevent the development of CI-AKI in patients with severe renal dysfunction undergoing coronary procedures , although further large-scale prospect i ve study is necessary to confirm our conclusions RATIONALE Vitamin D and its metabolites have potent immunomodulatory effects in vitro , including up-regulation of cathelicidin , a critical antimicrobial protein . OBJECTIVES We investigated whether administration of 1,25-dihydroxyvitamin D ( calcitriol ) to critically ill patients with sepsis would have beneficial effects on markers of innate immunity , inflammation , and kidney injury . METHODS We performed a double-blind , r and omized , placebo-controlled , physiologic study among 67 critically ill patients with severe sepsis or septic shock . Patients were r and omized to receive a single dose of calcitriol ( 2 μg intravenously ) versus placebo . The primary outcome was plasma cathelicidin protein levels assessed 24 hours after study drug administration . Secondary outcomes included leukocyte cathelicidin mRNA expression , plasma cytokine levels ( IL-10 , IL-6 , tumor necrosis factor-α , IL-1β , and IL-2 ) , and urinary kidney injury markers . MEASUREMENTS AND MAIN RESULTS Patients r and omized to calcitriol ( n = 36 ) versus placebo ( n = 31 ) had similar plasma cathelicidin protein levels at 24 hours ( P = 0.16 ) . Calcitriol-treated patients had higher cathelicidin ( P = 0.04 ) and IL-10 ( P = 0.03 ) mRNA expression than placebo-treated patients 24 hours after study drug administration . Plasma cytokine levels ( IL-10 , IL-6 , tumor necrosis factor-α , IL-1β , and IL-2 ) and urinary kidney injury markers were similar in calcitriol- versus placebo-treated patients ( P > 0.05 for all comparisons ) . Calcitriol had no effect on clinical outcomes nor were any adverse effects observed . CONCLUSIONS Calcitriol administration did not increase plasma cathelicidin protein levels in critically ill patients with sepsis and had mixed effects on other immunomodulatory markers . Additional phase II trials investigating the dose and timing of calcitriol as a therapeutic agent in specific sepsis phenotypes may be warranted . Clinical trial registered with www . clinical trials.gov ( NCT 01689441 ) OBJECTIVE To study the prognostic value of neutrophil gelatinase-associated lipocalin ( NGAL ) in chronic heart failure ( HF ) of ischaemic aetiology . BACKGROUND Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF . We investigated whether serum NGAL levels could provide prognostic information in chronic HF . METHODS We assessed NGAL as a predictor of primary outcomes ( cardiovascular death , nonfatal stroke and nonfatal myocardial infa rct ion , n = 307 ) and all-cause mortality ( n = 321 ) , cardiovascular mortality ( n = 259 ) and hospitalization ( n = 647 ) as well as the number of hospitalizations during follow-up for all ( n = 1934 ) and CV causes ( n = 1204 ) in 1415 patients with chronic HF ( ≥60 years , New York Heart Association class II-IV , ischaemic systolic HF ) in the CORONA population , r and omly assigned to 10 mg rosuvastatin or placebo . Results . Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables , but was no longer significant when further adjusting for apolipoprotein A-1 ( ApoA-1 ) , glomerular filtration rate ( GFR ) , C-reactive protein ( CRP ) and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) . However , belonging to the highest NGAL tertile was associated with more frequent hospitalization , even after adjusting for clinical variables , GFR and ApoA-1 , but not after adjusting for CRP and NT-proBNP . There was no interaction between rosuvastatin treatment and NGAL . Conclusion . Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points PURPOSE S The purpose s of the study are to investigate the renal function in ventricular fibrillation ( VF ) and asphyxiation cardiac arrest in a swine model and to estimate the value of novel biomarkers in the acute kidney injury ( AKI ) after cardiac arrest . METHOD Thirty-two healthy inbred Wu-Zhi-Shan miniature piglets were r and omized into 2 groups ( n = 16 per group ) . Cardiac arrest was induced by programmed electric stimulation and clamping the endotracheal tube in the VF group and asphyxiation group , respectively . Cardiopulmonary resuscitation was done for return of spontaneous circulation ( ROSC ) . RESULTS One hundred percent ( 16/16 ) ROSC was observed in the VF group , and 50 % ( 8/16 ) in the asphyxiation group ( P < .01 ) . All AKI biomarkers elevated significantly after ROSC . The novel biomarkers changed much earlier than the creatinine . The concentration of novel biomarkers in the asphyxiation group was higher than the VF group . Live animals had an oliguria and developed AKI . Characteristic morphological injuries in renal tissues were observed under light microscope and transmission electron microscope and were more serious in the asphyxiation group . CONCLUSIONS Acute kidney injury at early stage of postresuscitation is common in different causes of cardiac arrest . Asphyxiation has more severe kidney injury and gets worse prognosis OBJECTIVES Acute kidney failure after coronary artery bypass grafting ( CABG ) is a serious complication that increases morbidity and mortality rates . Early detection and prevention of this complication are very important . A novel biomarker named neutrophil gelatinase-associated lipocalin ( NGAL ) can play an important role in early diagnosis of acute kidney injury . Recent studies on the favourable effects of Dexmedetomidine on cardiac surgery have been published . The aim of this study is to investigate whether there is a dose-dependent positive effect of Dexmedetomidine on neutrophil gelatinase-associated lipocalin levels and renal functions when used after CABG . METHODS Our r and omized , triple-blinded , placebo-controlled study was conducted among 295 patients scheduled for CABG surgery between August 2009 and March 2011 in a tertiary cardiac and vascular surgery clinic . A total of 90 consecutive patients who met inclusion criteria were r and omized and divided into three groups . The first group received a placebo . The second and the third groups received 4 and 8 µg/cc concentration of the Dexmedetomidine infusion , respectively . Infusion rates were regulated to obtain sedation with a Ramsey sedation score of 2 or 3 . Patients were regrouped according to the total Dexmedetomidine dose . Statistical analyses of variables including serum neutrophil gelatinase-associated lipocalin values and conventional renal function tests were made for all six possibilities before the blind was broken . RESULTS Results of conventional renal function tests were not significantly different . However , neutrophil gelatinase-associated lipocalin levels for the first postoperative day for placebo , low-dose and high-dose Dexmedetomidine groups were 176.8 ± 145.9 , 97.7 ± 63.4 and 67.3 ± 10.9 ng/ml , respectively . These values were significantly different among the groups ( P < 0.001 ) . CONCLUSIONS In our study , we found that Dexmedetomidine infusion for sedation after CABG under cardiopulmonary bypass can be useful in the prevention of kidney injury . Conventional renal function tests , including blood urea nitrogen , serum creatinine , urine output and creatinine clearance rate measurements typically may not detect the development of acute kidney dysfunction in the first 48-h postoperative period . Differences were detected in renal function in the early postoperative period and the development of acute kidney injury , as determined by measurements of blood NGAL levels , was significant and dose-dependent The effects of natural pigment betanin on oxidative stress and inflammation in kidney of paraquat-treated rat were investigated . Paraquat was injected intraperitoneally into rats to induce renal damage . The rats were r and omly divided into four groups : a control group , a paraquat group , and two paraquat groups that were treated with betanin at 25 and 100 mg/kg/d three days before and two days after paraquat administration . Treatment with betanin alleviated the paraquat-incurred acute kidney injury , evidence d by histological improvement , reduced serum and urine markers for kidney injury . Betanin antagonized the paraquat-induced inflammation , indicated by reduced expression of inducible nitric oxide synthase and cyclooxygenase , blunted activation of nuclear factor kappa B , and diminished lysosomal protease activities . Betanin also decreased oxidative stress elicited by paraquat . In conclusion , betanin may have a protective effect against paraquat-induced acute kidney damage . The mechanisms of the protection appear to be the inhibition of oxidative stress and inflammation Abstract Objective : Neutrophil gelatinase-associated lipocalin ( NGAL ) is produced in response to tubular injury . Contrast-induced acute kidney injury ( CI-AKI ) is associated with adverse outcomes in chronic kidney disease ( CKD ) patients . We sought to characterize blood NGAL level and the degree of kidney injury in CKD patients who underwent coronary angiography . Methods : This study was a prospect i ve , blinded assessment of blood sample s obtained from patients with estimated glomerular filtration rates ( eGFRs ) between 15 and 90 mL/min/1.73 m2 undergoing elective coronary angiography with iodinated contrast . Blood NGAL and serum creatinine were measured at baseline , 1 , 2 , 4 , 6 , 12 , 24 and 48 h after contrast administration . Results : A total of 63 subjects with a mean eGFR of 48.17 ± 16.45 mL/min/1.73 m2 were enrolled . There was a grade d increase in baseline NGAL levels across worsening stages of CKD ( p = 0.0001 ) . Post-procedure NGAL increased from baseline in each stage of CKD . Eight ( 12.7 % ) patients were diagnosed with CI-AKI by diagnostic criteria of 2012 KDIGO definition of CI-AKI , and seven ( 11.1 % ) patients developed sub clinical CI-AKI defined by a twofold or greater rise in NGAL . There was no relationship between baseline eGFR and diabetes on the composite outcome of sub clinical and clinical CI-AKI . Conclusions : Baseline and post-procedure NGAL are progressively elevated according to the baseline stage of CKD . Using a twofold rise in NGAL , 46.7 % of composite CI-AKI is detected and complements the 53.3 % of cases identified using KDIGO criteria . Traditional risk predictors were not independently associated with this composite outcome Objective : To compare the acute effects of 0.9 % saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis . Design : Controlled laboratory experiment . Setting : University laboratory . Subjects : Sixty adult , male Sprague-Dawley rats . Interventions : We induced sepsis by cecal ligation and puncture and r and omized animals to receive fluid resuscitation with either 0.9 % saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture ( 10 mL/kg in the first hour and 5 mL/kg in the next 3 hr ) . Blood and urine specimens were obtained from baseline , 18 hours after cecal ligation and puncture , immediately after 4 hours fluid resuscitation , and 24 hours later . We measured blood gas , plasma electrolytes , creatinine , interleukin-6 , cystatin C , and neutrophil gelatinase-associated lipocalin concentrations . We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin . We used Risk , Injury , Failure , Loss and End-stage criteria for creatinine to assess severity of acute kidney injury . We observed all animals for survival up to 1 day after resuscitation . Surviving animals were killed for kidney histology . Finally , we carried out an identical study in 12 healthy animals . Measurements and Main Results : Compared with Plasma-Lyte , 0.9 % saline resuscitation result ed in significantly greater blood chloride concentrations ( p < 0.05 ) and significantly decreased pH and base excess . Acute kidney injury severity measured by RIFLE criteria was increased with 0.9 % saline compared with Plasma-Lyte resuscitation ( p < 0.05 ) , and these results were consistent with kidney histology and biomarkers of acute kidney injury . Twenty-four-hour survival favored Plasma-Lyte resuscitation ( 76.6 % vs 53.3 % ; p = 0.03 ) . Finally , in healthy animals , we found no differences between fluids and no evidence of acute kidney injury . Conclusion : Volume resuscitation with Plasma-Lyte result ed in less acidosis and less kidney injury and improved short-term survival when compared with 0.9 % saline in this experimental animal model of sepsis Abstract This study aims to investigate the role of urinary biomarkers in the determination of the potential risks of renal parenchymal tubular damage in adult patients who underwent percutaneous nephrolithotomy ( PNL ) with the indication of renal stone . A r and omized and prospect i ve controlled study was performed between June and December 2013 . We enrolled 29 consecutive patients with renal calculi > 2 cm and who underwent PNL , as well as 47 healthy control subjects . Urine sample s , including 2 h before surgery , 2 and 24 h after surgery were collected from the patient group . Freshly voided urine sample s were collected from the control group . Kidney injury molecule-1 ( KIM-1 ) , neutrophil gelatinase-associated lipocalin ( NGAL ) , N-acetyl-glucosaminidase ( NAG ) , and liver-type fatty acid binding protein ( LFABP ) levels were measured from these urine sample s. The mean KIM-1/Cr value that measured 24 h after the operation was statistically significant , higher than its preoperative ( preop ) level ( p = 0.045 ) . A significant difference was detected between the mean preop and postoperative ( postop ) 24 h NAG/Cr values ( p < 0.001 ) . Also , postop 24 h NGAL/Cr levels were statistically significant , higher than its preop levels ( p = 0.013 ) . According to the comparison of preop and postop levels , an increase in LFABP/Cr values secondary to surgical intervention was observed without any statistically significant difference . Besides the LFABP/Cr levels do not change after percutaneous kidney surgery , KIM-1/Cr , NAG/Cr , and NGAL/Cr levels increase postop period , especially at 24 h. Further studies with a larger series and repeated measurements should be performed to clarify if they can be used to demonstrate renal damage after percutaneous surgery or not We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units . As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers , the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase . R and omization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3 , with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days . Of 529 patients , 162 were r and omized within an average of 3.5 h of a positive sample . There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups . The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury , dialysis , or death ; however , the marker elevations were transient . Early intervention with high-dose erythropoietin was safe but did not alter the outcome . Although these two urine biomarkers facilitated our early intervention , their transient increase compromised effective triaging . Further , our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury OBJECTIVE Acute kidney injury after cardiac surgery with cardiopulmonary bypass is closely related to systemic inflammatory reactions and oxidative stresses . Remote ischemic preconditioning is a systemic protective strategy whereby brief limb ischemia confers systemic protection against prolonged ischemia and inflammatory reactions in distant organs . This study investigated whether remote ischemic preconditioning provides systemic protective effect on kidneys that are not directly exposed to ischemia-reperfusion injury during complex valvular heart surgery . METHODS Seventy-six adult patients undergoing complex valvular heart surgery were r and omly assigned to either remote ischemic preconditioning group ( n = 38 ) or control group ( n = 38 ) . Remote ischemic preconditioning consisted of 3 10-minute cycles of lower limb ischemia and reperfusion with an automated cuff inflator . Primary end points were comparisons of biomarkers of renal injury including serum creatinine , cystatin C and neutrophil gelatinase-associated lipocalin , and incidence of acute kidney injury . Secondary end points were comparisons of myocardial enzyme release and pulmonary parameters . RESULTS There were no significant differences in serum levels of biomarkers of renal injury between groups throughout the study period . The incidence of acute kidney injury did not differ between groups . Creatine kinase isoenzyme MB at 24 hours after surgery was lower , and intensive care unit stay was shorter in the remote ischemic preconditioning group than in the control group . CONCLUSIONS In patients undergoing complex valvular heart surgery , remote ischemic preconditioning did not reduce degree of renal injury or incidence of acute kidney injury whereas it did reduce myocardial injury and intensive care unit stay Introduction To evaluate whether alkaline phosphatase ( AP ) treatment improves renal function in sepsis-induced acute kidney injury ( AKI ) , a prospect i ve , double-blind , r and omized , placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed . Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included . Dialysis intervention was st and ardized according to Acute Dialysis Quality Initiative consensus . Intravenous infusion of alkaline phosphatase ( bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours , or placebo ) starting within 48 hours of AKI onset and followed up to 28 days post-treatment . The primary outcome variable was progress in renal function variables ( endogenous creatinine clearance , requirement and duration of renal replacement therapy , RRT ) after 28 days . The secondary outcome variables included changes in circulating inflammatory mediators , urinary excretion of biomarkers of tubular injury , and safety . Results There was a significant ( P = 0.02 ) difference in favor of AP treatment relative to controls for the primary outcome variable . Individual renal parameters showed that endogenous creatinine clearance ( baseline to Day 28 ) was significantly higher in the treated group relative to placebo ( from 50 ± 27 to 108 ± 73 mL/minute ( mean ± SEM ) for the AP group ; and from 40 ± 37 to 65 ± 30 mL/minute for placebo ; P = 0.01 ) . Reductions in RRT requirement and duration did not reach significance . The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein , Interleukin-6 , LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo . The Drug Safety Monitoring Board did not raise any issues throughout the trial . Conclusions The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial Registration www . clinical trials.gov : |
13,080 | 20,406,229 | Most papers describe positive reactions , increased knowledge and skills , and improved behaviour after training .
Outcome is assessed less frequently , and positive effects are not always demonstrated .
Measures that can contribute to a positive effect of training programmes include h and s-on practise , team approaches and follow-up on training efforts .
AUTHOR 'S CONCLUSIONS Training programmes may improve quality of care , but strong evidence is lacking . | BACKGROUND Training of healthcare workers can play an important role in improving quality of care , and reducing maternal and perinatal mortality and morbidity .
OBJECTIVES To assess the effectiveness of training programmes aim ed at improving emergency obstetric care in low-re source environments .
Training programmes vary considerably in length , content and design .
The evaluation of effects is often hampered by inadequate study design and the use of non-vali date d measuring instruments . | Background Effective strategies for implementing best practice s in low and middle income countries are needed . RHL is an annually up date d electronic publication containing Cochrane systematic review s , commentaries and practical recommendations on how to implement evidence -based practice s. We are conducting a trial to evaluate the improvement in obstetric practice s using an active dissemination strategy to promote uptake of recommendations in The WHO Reproductive Health Library ( RHL ) . Methods A cluster r and omized trial to improve obstetric practice s in 40 hospitals in Mexico and Thail and is conducted . The trial uses a stratified r and om allocation based on country , size and type of hospitals . The core intervention consists of three interactive workshops delivered over a period of six months . The main outcome measures are changes in clinical practice s that are recommended in RHL measured approximately a year after the first workshop . Results The design and implementation of a complex intervention using a cluster r and omized trial design are presented . Conclusion Design ing the intervention , choosing outcome variables and implementing the protocol in two diverse setting s has been a time-consuming and challenging process . We hope that sharing this experience will help others planning similar projects and improve our ability to implement change OBJECTIVE : Changes in the ability of midwives to perform practical skills , after completion of the Maternal Care Manual of the Perinatal Education Program , were determined . STUDY DESIGN : A prospect i ve , controlled trial in a study town and two control towns . The practical skills of midwives caring for pregnant women in the towns were determined . Subsequently , the Maternal Care Manual was studied by midwives in the study town , and the skills of all midwives were subsequently evaluated . RESULTS : A total of 34 midwives in the study town and 39 midwives in the two control towns were studied . The marks showed a significant ( p ≤ 0.000 ) improvement in the study town when comparing the pre- and postintervention marks . The mean improvement in the study town was 36.6 % . DISCUSSION : The practical skills of midwives improved significantly . The Perinatal Education Program can be implemented with confidence as a distance learning program that is especially suited to the needs of health workers in remote regions OBJECTIVE : To assess the ability of midwives to interpret antenatal cards and partograms correctly following completion of the Maternal Care Manual of the Perinatal Education Programme . STUDY DESIGN : We conducted a prospect i ve , controlled trial in a study town and two control towns in the Eastern Cape Province of South Africa . All 93 midwives caring for pregnant women in the three towns were included in the study . Sample s were compared using the two-tailed Student ’s t-test . RESULTS : The marks achieved by the study group for questions from the antenatal card and the partogram improved by 33.0 % ( p < 0.001 ) and 17.5 % ( p = 0.001 ) , respectively . No changes were observed in the control group . CONCLUSION : Midwives that studied the Maternal Care Manual significantly improved their ability to interpret clinical information and apply knowledge . If this ability is applied in clinical practice , a reduction in maternal and perinatal deaths is possible OBJECTIVES To determine whether the Maternal Care manual of the Perinatal Education Programme ( PEP ) is effective in improving the cognitive knowledge of midwives . DESIGN A prospect i ve controlled trial in a region where PEP was not previously used . The midwifery knowledge of all midwives caring for pregnant women in the three towns was tested before the commencement of the study . The Maternal Care manual was then introduced to the midwives in he study town and they worked through the programme . Following the completion of the manual , all midwives were tested again with the same test . The time interval between the pre and post testing was 12 months . SETTING Three towns on the Eastern Cape Province of South Africa . PARTICIPANTS All Midwives caring for pregnant women in three towns . INTERVENTIONS The Maternal Care manual of PEP was studied by the midwives in the study town . MEASUREMENTS AND FINDINGS Changes in cognitive knowledge were tested with multiple choice questions . A significant improvement ( p < 0.0001 ) was achieved in the study town . The mean score ( maximum 70 ) improved by 22.4 ( 32 % ) marks , from 35.9 ( 51 % ) to 58.3 ( 83 % ) . KEY CONCLUSIONS The cognitive knowledge of midwives who completed the Maternal Care manual improved significantly . IMPLICATION S FOR PRACTICE These findings are to particular importance as the method by which the Maternal Care manual of PEP was applied conforms to the method suggested for the its national use OBJECTIVE In this study the changes in attitude of midwives towards their work following completion of the Maternal Care Manual of the Perinatal Education Programme ( PEP ) , were determined . METHOD A prospect i ve , controlled trial was performed in a study , and two control towns in a region where PEP had not previously been used . All midwives caring for pregnant women in the three towns were included in the study . First the attitude of these midwives was determined by means of a question naire . Subsequent to this , the Maternal Care Manual was introduced and studied by the midwives in the study town . Following the completion of the Manual after 12 months , the attitude of all midwives was again evaluated using the same question naire . RESULTS A total of 40 midwives in the study town and 53 in the two control towns were included in the study . There were no differences on comparing the ages of the midwives in the study town to those in the control towns . The attitude of the midwives in the study town improved significantly ( p < 0.001 ) . The mean result in the study town improved by 6.1 ( 24.4 % ) marks from 14.5 ( 58.0 % ) to 20.6 ( 82.4 % ) . A significant shift also occurred in the range of the marks from 0 - 25 to 13 - 25 . No changes were observed in the control towns . CONCLUSION Most studies that have evaluated educational programmes measured improvement in health services , and did not evaluate changes in attitude . This study found that the attitude of midwives improved significantly in the study town . This positive attitude of midwives towards their work and their ability to perform their daily tasks must be an important component of any programme to improve the quality of care rendered to women during pregnancy , labour and the puerperium The presence of a skilled birth attendant at delivery is important in averting maternal and neonatal mortality and morbidity . It has now shown that even trained traditional birth attendants ( TBAs ) can not , in most cases , save women 's lives effectively because they are unable to treat complications , and are often unable to refer . Qualified midwives and doctors are often not available in the rural areas and community setting s where most women in developing countries deliver . Defining the minimum competency level necessary to meet the definition of skilled birth attendant is important , particularly in countries such as Nepal with limited availability of facility-based emergency obstetric care . Maternal and child health workers are local women aged 18 - 35 who completed a 15-week course in maternal and child health . As the role of MCHWs has exp and ed to meet the country 's needs for skilled attendance , a 6-week " refresher " course in midwifery skills is offered . The results of this clinical skills assessment of 104 r and omly selected MCHWs from 15 districts across Nepal supports the premise that MCHWs with appropriate training have an acceptable level of knowledge and skill , demonstrated in a practice situation , to meet the definition of community level skilled birth attendants . Yet , competency alone will not necessarily improve the situation . To affect maternal mortality in Nepal , MCHWs must be widely available , they must be allowed to do what they are trained to do , and they must have logistical and policy support |
13,081 | 29,781,957 | Importantly , lower pressure pain threshold in patients with migraine was found in local areas but not in nonlocal areas .
This meta- analysis indicates that the alterations in nociceptive processing of patients with migraine may be modality , measure , and location specific . | Abstract Quantitative sensory testing ( QST ) is widely used to assess somatosensory function by application of controlled stimuli across a variety of modalities .
The aim of the present meta- analysis is to synthesize QST results across a wide array of studies of patients with migraine to identify the QST parameters that are reliably different between patients with migraine and healthy controls .
In addition , we aim ed to determine whether such differences vary according to stimulus location . | The aim of this case series was to investigate changes in pain and pressure pain sensitivity after manual treatment of active trigger points ( TrPs ) in the shoulder muscles in individuals with unilateral shoulder impingement . Twelve patients ( 7 men , 5 women , age : 25 ± 9 years ) diagnosed with unilateral shoulder impingement attended 4 sessions for 2 weeks ( 2 sessions/week ) . They received TrP pressure release and neuromuscular interventions over each active TrP that was found . The outcome measures were pain during arm elevation ( visual analogue scale , VAS ) and pressure pain thresholds ( PPT ) over levator scapulae , supraspinatus infraspinatus , pectoralis major , and tibialis anterior muscles . Pain was captured pre-intervention and at a 1-month follow-up , whereas PPT were assessed pre- and post-treatment , and at a 1-month follow-up . Patients experienced a significant ( P < 0.001 ) reduction in pain after treatment ( mean ± SD : 1.3 ± 0.5 ) with a large effect size ( d > 1 ) . In addition , patients also experienced a significant increase in PPT immediate after the treatment ( P < 0.05 ) and one month after discharge ( P < 0.01 ) , with effect sizes ranging from moderate ( d = 0.4 ) to large ( d > 1).A significant negative association ( r(s ) = -0.525 ; P = 0.049 ) between the increase in PPT over the supraspinatus muscle and the decrease in pain was found : the greater the decrease in pain , the greater the increase in PPT . This case series has shown that manual treatment of active muscle TrPs can help to reduce shoulder pain and pressure sensitivity in shoulder impingement . Current findings suggest that active TrPs in the shoulder musculature may contribute directly to shoulder complaint and sensitization in patients with shoulder impingement syndrome , although future r and omized controlled trials are required Background Lack of habituation during repetitive stimulation is the most consistent interictal abnormality of cortical information processing observed in migraine . Preventive migraine treatments might act by stabilizing cortical excitability level and thus the habituation to external stimuli . Methods We examined the effects of preventive treatment with topiramate on migraineur ’s habituation to nociceptive stimulation . Scalp potentials were evoked by Nd-YAP Laser stimulation of the h and dorsum and supraorbital region in 13 patients with migraine without aura ( MO ) and 15 healthy volunteers ( HV ) . The exam was repeated in MO before and after treatment . Results We observed a lack of habituation and lower initial amplitudes in MO compared to HV . These abnormalities reached statistical significance for N1 LEPs component , generated in the secondary somatosensory cortex ( SII ) , but not for N2/P2 complex , generated in the insula and anterior cingulated cortex ( ACC ) . Topiramate normalized the N1 habituation pattern in MO , with a significant correlation between clinical effects and normalization of neurophysiological responses . Conclusions Our results indicate a modulating action of topiramate on cortical processing of sensorial stimuli , mainly regarding the sensory-discriminative component of pain , elaborated by SII , without a significant effect on the affective dimension of pain , in which the ACC has an important role Visually induced analgesia has been correlated with the affective content of pleasant , neutral or unpleasant pictures . The aim of the present study was to assess the effect of affective images vision on laser evoked potentials and pain perception , in a cohort of healthy subjects and migraine patients . Twenty-two healthy subjects and 24 migraine without aura patients ( recorded during the inter-critical phase ) participated in the study . Eighty-four colour slides , arranged in two blocks , each consisting of 14 pleasant , 14 unpleasant and 14 neutral images , in r and om presentation , were chosen from the International Affective Picture System . The CO(2 ) laser stimuli were delivered on the dorsum of the right h and and supra-orbital zone at 7.5-watt intensity and 25-ms duration , in basal condition and during the viewing of affective pictures . Migraine patients expressed higher scores of valence and arousal for pleasant and unpleasant pictures , compared to controls . In both groups , a late positive potential in the 400 - 700 ms time range was clear for pleasant and unpleasant pictures , but its amplitude was significantly reduced in migraine patients . The pain rating and the N2 component were reduced in both groups during the visual task compared to basal condition . In migraineurs and controls the P2 wave was reduced during the vision of pleasant pictures , compared to basal condition . This indicates that stimulation by images with different affective content reduces subjective pain for a cognitive mechanism of attentive engagement , while a special inhibition of later LEPs is produced by a positive emotional impact . In migraine , affective images are able to modulate pain perception and LEPs , differently from other modalities of distraction , suggesting a possible emotive elaboration of painful stimuli Thirty-three migraineurs and 23 healthy controls were su bmi tted to pressure algometry before and after light-induced discomfort was elicited by progressive light stimulation in a monoblind fashion . Pressure algometries were performed on the emergence of the supraorbital , infraorbital , mental and greater occipital nerves , and over the temporal muscles , always throughout the same sequence and from right to left . Measurements were carried out before and immediately after light stimulation and after 10 min of the second algometry . The final result for each site measured at each time-point was the mean of the three measurements . Light stimulation was carried out progressively until light-induced discomfort was reported , to a maximum of 20 000 lux . A heat-blocking glass protected patients ' eyes . Migraineurs presented significant and persistent drops in pain perception thresholds after light stimulation , at all sites tested ( P = 0.002 to < 0.0001 ) . These drops were not seen in controls , in whom , conversely , a less significant increase was seen on right infraorbital and left temporal muscle sites . Our results indicate that in migraineurs , light may have a relevant role in trigeminal and cervical pain perception thresholds STUDY DESIGN R and omized clinical trial . OBJECTIVES To determine the effects of trigger point dry needling ( TrPDN ) on neck pain , widespread pressure pain sensitivity , and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle . BACKGROUND TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes . Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed . Methods Seventeen patients ( 53 % female ) were r and omly assigned to 1 of 2 groups : a single session of TrPDN or no intervention ( waiting list ) . Pressure pain thresholds over the C5 - 6 zygapophyseal joint , second metacarpal , and tibialis anterior muscle ; neck pain intensity ; and cervical spine range-of-motion data were collected at baseline ( pretreatment ) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient . Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable . RESULTS Patients treated with 1 session of TrPDN experienced greater decreases in neck pain , greater increases in pressure pain threshold , and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention ( P<.01 for all comparisons ) . Between-group effect sizes were medium to large immediately after the TrPDN session ( st and ardized mean score differences greater than 0.56 ) and large at the 1-week follow-up ( st and ardized mean score differences greater than 1.34 ) . CONCLUSION The results of the current r and omized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity , and also increase active cervical range of motion , in patients with acute mechanical neck pain . Changes in pain , pressure pain threshold , and cervical range of motion surpassed their respective minimal detectable change values , supporting clinical ly relevant treatment effects . Level of Evidence Therapy , level 1b- The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls ( DNICs ) in primary headaches . DNICs were examined in 24 migraineurs , 17 patients with chronic tension-type headache ( CTTH ) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test ( CPT ) as heterotopic noxious conditioning stimulation ( HNCS ) . The subjective pain thresholds ( Tp ) and the RIII reflex threshold ( Tr ) were significantly lower in CTTH vs. controls . In controls a significant inhibition of the RIII reflex was observed during the CPT ( -30± , P < 0.05 ) . Conversely , migraine and CTTH patients showed facilitation ( + 31± , P < 0.05 and + 40± , P < 0.01 , respectively ) of the RIII reflex during the HNCS . This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH . Impairment of endogenous supraspinal pain modulation systems may contribute to the development and /or maintenance of central sensitization in primary headaches Pain perception studies in migraine patients have shown trigeminal and peripheral pain facilitation during the migraine attack . We were interested in differences of trigeminal and peripheral pain perception between migraine patients during the migraine interval and healthy subjects . Perception of electrical pain stimulation was measured in 20 migraine subjects outside a migraine attack ( 10 migraine with aura and 10 migraine without aura ) and in 20 healthy subjects . We recorded sensory and pain thresholds , pain ratings after suprathreshold stimulation , and pain rating after two trains of repetitive stimulation ( i.e. , pain facilitation ) . Migraine subjects showed a significantly higher pain rating after suprathreshold stimulation in the trigeminal region as compared to healthy subjects ( 4.8 ± 1.6 versus 3.8 ± 2.2 , p < 0.04 after Bonferroni correction ) but not in the peripheral region . Furthermore , migraine subjects showed a pain facilitation after repetitive trigeminal stimulation whereas healthy subjects showed a pain habituation . We observed no significant differences between migraine subjects and healthy subjects for all parameters in the peripheral stimulation . Migraine patients with and without aura did not differ in any parameter . All subjects showed decreased sensory and pain thresholds after trigeminal as compared to peripheral stimulation . Migraine subjects show an increased pain perception after trigeminal but not after peripheral pain stimulation as compared to healthy subjects . This phenomenon is probably due to the observed pain facilitation after painful trigeminal stimulation Background The mechanisms associating sleep and migraine are unknown . No previous polysomnographic ( PSG ) or pain-threshold ( PT ) study has compared patients with sleep-related migraine attacks ( SM ) , non-sleep related migraine attacks ( NSM ) and healthy controls . Methods We have performed a blinded , prospect i ve exploratory study with case – control design . Thirty-four healthy controls , 15 patients with SM and 18 patients with NSM had interictal PSG heat- , cold- and pressure PT ( HPT , CPT , PPT ) recordings and completed diary- and question naire on sleep and headache related aspects . Results NSM patients had more slow-wave sleep ( SWS ) and more K-bursts than SM patients ( K-bursts : p = 0.023 and SWS : p = 0.030 ) and controls ( K-bursts : p = 0.009 and SWS : 0.041 ) . NSM patients also had lower HPT and CPT than controls ( p = 0.026 and p = 0.021 ) . In addition , SM patients had more awakenings and less D-bursts than controls ( p = 0.025 and p = 0.041 ) . ConclusionS M- and NSM patients differed in objective - , but not subjective sleep quality . NSM patients had PSG findings indicating foregoing sleep deprivation . As foregoing sleep times were normal , a relative sleep deficit might explain reduced PT among NSM patients . The SM patients had signs of slightly disturbed sleep UNLABELLED This study evaluated the contribution of myofascial trigger points ( TrPs ) to migraine pain . Seventy-eight migraine patients with cervical active TrPs whose referred areas ( RAs ) coincided with migraine sites ( frontal/temporal ) underwent electrical pain threshold measurement in skin , subcutis , and muscle in TrPs and RAs at baseline and after 3 , 10 , 30 , and 60 days ; migraine pain assessment ( number and intensity of attacks ) for 60 days before and 60 days after study start . Fifty-four patients ( group 1 ) underwent TrP anesthetic infiltration on the 3rd , 10th , 30th , and 60th day ( after threshold measurement ) ; 24 ( group 2 ) received no treatment . Twenty normal subjects underwent threshold measurements in the same sites and time points as patients . At baseline , all patients showed lower than normal thresholds in TrPs and RAs in all tissues ( P < .001 ) . During treatment in group 1 , all thresholds increased progressively in TrPs and RAs ( P < .0001 ) , with sensory normalization of skin/subcutis in RAs at the end of treatment ; migraine pain decreased ( P < .001 ) . Threshold increase in RAs and migraine reduction correlated linearly ( .0001 < P < .006 ) . In group 2 and normal subjects , no changes occurred . Cervical TrPs with referred areas in migraine sites thus contribute substantially to migraine symptoms , the peripheral nociceptive input from TrPs probably enhancing the sensitization level of central sensory neurons . PERSPECTIVE This article shows the beneficial effects of local therapy of active myofascial trigger points ( TrPs ) on migraine symptoms in patients in whom migraine sites coincide with the referred areas of the TrPs . These results suggest that migraine pain is often contributed to by myofascial inputs that enhance the level of central neuronal excitability The aim of this study was to compare the properties of the nociceptive system in eight migraine without aura patients in the pain-free phase with 10 healthy controls , by evaluating the topography and the source of the CO2 laser-evoked potentials ( LEPs ) obtained by the right supraorbital skin , during and after capsaicin topical application . In healthy subjects the acute cutaneous pain induced by capsaicin reduced the amplitude of the vertex LEPs and induced a posterior shifting of the P2 wave dipolar source within the anterior cingulate cortex . These functional changes seemed significantly reduced in migraine patients , for a disturbed pattern of pain modulation at the cortical level , which may subtend the onset and persistence of migraine & NA ; Tenderness and pain thresholds in pericranial muscles were studied in a r and om sample of 735 adults aged 25–64 years . This study was a part of a multifaceted , epidemiological study of different headache disorders . Manual palpation and pressure pain threshold were performed by observers blinded to the persons ' history of headache . The aim of the study was to evaluate the possible role of pericranial myofascial nociception in headache pathogenesis . Tenderness in migraineurs did not differ from non‐migraineurs . Subjects with episodic tension‐type headache and females with chronic tension‐type headache were more tender than the rest of the population , and males without any experience of headache were less tender than the rest of the male population . A strong positive correlation between tenderness and frequency of tension‐type headache was found ( males : P < 10−4 ; females : P < 10−5 ) , while no relation between tenderness and migraine frequency was seen ( P = 0.43 ) . In subjects having actual headache at the day of examination tenderness was 32 % increased compared to a matched group with identical usual frequency of headache , but without headache during the examination . A significant relation of tenderness to the recency of last episode of headache was detected in both sexes after control for usual frequency and actual headache ( males : P < 10−3 ; females : P < 10−4 ) . Pressure pain thresholds were largely normal indicating normal pain processing and contradicting the idea that tension‐type headache mainly is due to generally increased pain sensitivity . This study supports the pathogenetic importance of muscular factors in tension‐type headache , while muscular factors are of no primary importance in migraine OBJECTIVES Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine . The aim of this study was to investigate the blink reflex and its habituation in patients with " chronic migraine " . METHODS We studied 35 patients suffering from " chronic migraine " ( IHS classification criteria ) outside and during a spontaneous attack , and 35 control subjects . An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to r and omly repeat stimulations at different time intervals so as to induce habituation . RESULTS The R(1 ) and R(2 ) latencies , amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects , whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack . The percent changes in the R(2 ) areas from the baseline values , obtained when stimuli were delivered at time intervals of 10 , 5 , 4 , 3 , 2 and 1s , were statistically different ( p<0.01-p<0.001 ) from those of the same patients studied during a migraine attack and of those of control subjects . There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks . The stimulus intensities of the blink reflex ( multiples of the detection threshold intensities ) were significantly lower ( p<0.001 ) on the side affected , or more severely affected , by headache in patients studied during a migraine attack . CONCLUSIONS The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in " chronic migraine " , which normalizes during the attacks . The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks . Central sensitisation mechanisms ( allodynia ) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks . SIGNIFICANCE The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks Trigeminal and somatic nociceptive systems were studied in controls ( n = 15 ) , episodic migraine ( n = 16 ) , analgesics ( n = 14 ) and triptan-induced medication overuse headache ( MOH ) ( n = 15 ) before and after withdrawal . Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression . Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials ( PREP ) and nociceptive blink reflex ( nBR ) following nociceptive-specific electrical stimulation of the forehead . Somatic nociception was evaluated using PREP of upper limbs . We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH , which normalized after withdrawal . No differences were found comparing analgesics vs. triptan MOH . No differences were observed between controls and patients with episodic migraine and depression without headache . A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH , which was more pronounced on a supraspinal level OBJECTIVE Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine . The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects . METHODS An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides , and to r and omly repeat the stimulations at different time intervals in order to induce habituation . RESULTS Whereas the R1 and R2 latencies , amplitudes and areas in the basal assessment were similar in patients and control subjects , the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing ( group A ) . In these patients , the differences between the R2 areas , obtained when stimuli were delivered at subsequent time intervals ranging between 10 - 5 , 5 - 4 , 4 - 3 and 3 - 2 s , were statistically different ( P<0.001 ) from those of the patients who had a migraine attack after a longer time interval ( group B ) and control subjects . CONCLUSIONS Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks , probably through mechanisms that involve dopaminergic function Belief and expectation are part of placebo effect . Migraine patients are characterized by a dysfunctional modulation of pain processing , though a clear placebo effect emerges in clinical trials . The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls . Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls . The right h and and the right supraorbital zone were stimulated during a not conditioned and a conditioned task , where laser stimuli were delivered after a verbal and visual cues of decreased ( D ) , increased ( I ) or basal ( B ) intensity , which was left unmodified during the entire task . In control subjects pain rating changed , according to the announced intensity , while in migraine patients the basal hyper-algesia remained unmodified . The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls , while an opposite paradoxical increase in decreasing condition emerged in migraine . The P2 amplitude modulation was also reduced in migraine , differently from controls . The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine , disability and allodynia . In controls suggestion influenced cortical pain processing and subjective pain rating , while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia . This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization OBJECTIVE To investigate the efficacy and safety of the cutaneous application of menthol 10 % solution for the abortive treatment of migraine . BACKGROUND Peppermint and its active ingredient menthol have long been used for the treatment of various pain conditions including headache . METHODS This is a r and omised , triple-blind , placebo-controlled , crossed-over study conducted in the neurology Clinic of Nemazee Hospital , affiliated with Shiraz University of Medical Sciences , Shiraz , southern Iran , from March 2007 to March 2008 . The patients were recruited via local newspaper advertisements . Eligible patients were categorised into two groups and a 10 % ethanol solution of menthol ( as drug ) and 0.5 % ethanol solution of menthol ( as placebo ) were applied to the forehead and temporal area in a crossover design . Pain free , pain relief , sustained pain free and sustained pain relief end-points were measured by question naires using a visual analogue scale . RESULTS The intent-to-treat population consisted of 35 patients ( 80 % women , 20 % men , mean age : 29.6 + /- 6.2 ) with 118 migraine attacks . In the intent-to-treat population , the menthol solution was statistically superior to the placebo on 2-h pain free ( p = 0.001 ) , 2-h pain relief ( p = 0.000 ) , sustained pain free and sustained pain relief end-points ( p = 0.008 ) . The menthol solution was also more efficacious in the alleviation of nausea and /or vomiting and phonophobia and /or photophobia ( p = 0.02 ) . In the per- protocol population , there was significantly higher number of patients who experienced at least one pain free/pain relief after the application of menthol rather than the placebo ( p = 0.002 ) . No significant difference was seen between the adverse effects of the drug and the placebo groups ( p = 0.13 ) . CONCLUSION Menthol solution can be an efficacious , safe and tolerable therapeutic option for the abortive treatment of migraine BACKGROUND AND OBJECTIVE Migraine headache attacks have been shown to be accompanied by significant prolongation of somatosensory temporal discrimination threshold values , supporting signs of disrupted sensorial processing in migraine . Chronic migraine is one of the most debilitating and challenging headache disorders with no available biomarker . We aim ed to test the diagnostic value of somatosensory temporal discrimination for chronic migraine in this prospect i ve , controlled study . METHODS Fifteen chronic migraine patients and 15 healthy controls completed the study . Chronic migraine patients were evaluated twice , during a headache and headache-free period . Somatosensory temporal discrimination threshold values were evaluated in both h and s. Duration of migraine and chronic migraine , headache intensity , clinical features accompanying headache such as nausea , photophobia , phonophobia and osmophobia , and pressure pain thresholds were also recorded . RESULTS In the chronic migraine group , somatosensory temporal discrimination threshold values on the headache day ( 138.8 ± 21.8 ms for the right h and and 141.2 ± 17.4 ms for the left h and ) were significantly higher than somatosensory temporal discrimination threshold values on the headache free day ( 121.5 ± 13.8 ms for the right h and and 122.8 ± 12.6 ms for the left h and , P = .003 and P < .0001 , respectively ) and somatosensory temporal discrimination thresholds of healthy volunteers ( 35.4 ± 5.5 ms for the right h and and 36.4 ± 5.4 ms for the left h and , P < .0001 and P < .0001 , respectively ) . Somatosensory temporal discrimination threshold values of chronic migraine patients on the headache free day were significantly prolonged compared to somatosensory temporal discrimination threshold values of the control group ( 121.5 ± 13.8 ms vs 35.4 ± 5.5 ms for the right h and , P < .0001 and 122.8 ± 12.6 ms vs 36.4 ± 5.4 ms for the left h and , P < .0001 ) . Somatosensory temporal discrimination threshold values of the h and contralateral to the headache lateralization ( 153.3 ± 13.7 ms ) were significantly higher ( P < .0001 ) than the ipsilateral h and ( 118.2 ± 11.9 ms ) in chronic migraine patients when headache was lateralized . The headache intensity of chronic migraine patients rated with visual analog score was positively correlated with the contralateral somatosensory temporal discrimination threshold values . CONCLUSION Somatosensory temporal discrimination thresholds persist elevated during the headache-free intervals in patients with chronic migraine . By providing evidence for the first time for unremitting disruption of central sensory processing , somatosensory temporal discrimination test st and s out as a promising neurophysiological biomarker for chronic migraine Objectives Few studies have addressed central sensitization symptoms and pain processing in childhood migraine . Our aims were to examine pain sensitivity and responses , including habituation , evoked by CO2 laser stimuli ( laser-evoked potentials ( LEPs ) ) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization . Methods Thirty-five patients 8–15 years of age with migraines without aura were evaluated during the inter-critical phase and were compared to 17 controls . LEPs were analyzed , and their main features were correlated with clinical symptoms including allodynia and pericranial tenderness . Results The laser-evoked pain threshold was lower and the N2P2 vertex complex amplitude was higher in children with migraines . Furthermore , habituation of vertex waves of LEPs clearly showed a tendency toward progressive amplitude enhancement in the migraine group . Acute allodynia and inter-critical pericranial tenderness correlated with trigeminal LEP features , particularly with the abnormal habituation pattern . Discussion Abnormalities of pain processing and symptoms of central sensitization appear to be characteristics of children with migraine . Reduced habituation and progressive amplification of cortical responses to laser stimuli indicate an overactive nociceptive system at the onset of migraine , and this hyperactivity may subtend allodynia and pericranial tenderness . Future prospect i ve trials may aid in the early identification of clinical phenotypes that display a tendency to develop into the chronic form of migraine , warranting a timely therapeutic approach Abstract Central sensitization is thought to play an important role in the chronification of tension‐type headache and in the maintenance and exacerbation of the migraine attack . It has , however , almost exclusively been studied in highly selected patients from headache clinics . The aim of the present study was to evaluate pain perception in primary headaches in the general population . Stimulus – response functions for pressure versus pain , tenderness and pressure pain thresholds were studied in a r and om sample of 523 adults from the general population . All results were controlled for the effects of age and gender . The area under the stimulus – response function was increased in chronic‐ and frequent episodic tension‐type headache compared with subjects without headache ( p < 0.001 , p < 0.001 ) and in chronic tension‐type headache compared with migraine ( p = 0.01 ) . Increasing slope ( p < 0.0001 ) and displacement towards lower pressures was found in the following order : no headache , migraine , frequent episodic tension‐type headache , chronic tension‐type headache . The displacement of the stimulus – response function was closely associated with frequency of headache . Finally , the stimulus‐response function tended to be qualitatively altered in patients with frequent headache . The findings demonstrate , for the first time in a population ‐based study , a close relation between altered pain perception and chronification of headache , which most likely can be explained by central sensitization Background .—Lack of habituation , as reported in migraine patients between attacks for evoked cortical responses , was also recently found for the nociceptive blink reflex ( nBR ) mediated by brainstem neurons . It is not known if both brain stem and cortical habituation deficits are correlated in the same patient , which would favor a common underlying mechanism Background : Dilatation of pain-sensitized scalp vessels can cause pain in migraine headache , and extracranial vascular hyperreactivity to psychological stress and head pain could increase susceptibility to attacks . Objective : To determine whether changes in facial blood flow differed between migraine sufferers and control subjects during painful stimulation of a limb . Methods : To document changes in facial blood flow , pulse amplitude was monitored with photoelectric pulse transducers from the frontotemporal region of 23 migraine sufferers and 22 age- and sex-matched control subjects before , during , and after immersion of the nondominant h and in ice water at 2 ° C for 30 seconds . The h and was immersed three times at 4-minute intervals . Results : Migraine sufferers rated the pain of the ice-water immersion to be more intense and unpleasant than control subjects , and pain radiated further up the arm . Increases in pulse amplitude were greater ipsilateral than contralateral to painful stimulation ( 25.1 ± 2.9 vs 13.7 ± 4.4 % ; p < 0.01 ) . Pulse amplitude increased over repeated immersions ( p < 0.01 ) and peaked after the h and was removed from the ice water ( p < 0.001 ) , more so ipsilaterally than contralaterally ( p < 0.001 ) . Pulse amplitude increased 26.3 ± 4.3 % in migraine sufferers compared with 12.6 ± 4.4 % in control subjects ( p < 0.05 ) , and this group difference persisted 8 minutes after the final immersion . Conclusion : Limb pain triggers increases in facial blood flow and might exacerbate the vascular component of headache during attacks of migraine OBJECTIVE The primary aim was to investigate functional differences between medication overuse headache ( MOH ) patients and controls with the purpose of evaluating the presence of a global alteration in the processing of noxious stimuli throughout the pain matrix . The secondary aim was to investigate whether activations in MOH patients normalize after medication withdrawal , which would suggest a possible role of the pain matrix in headache chronification . DESIGN Functional magnetic resonance imaging was performed during painful mechanical stimulation in nine female patients with MOH immediately and at 6 months after beginning medication withdrawal , and in nine control participants . RESULTS Compared with controls , immediately after beginning withdrawal , the MOH patients showed reduced pain-related activity across the primary somatosensory cortex , inferior parietal lobule , and supramarginal gyrus , as well as in regions of the lateral pathway of the pain matrix . At 6 months , these differences were no longer detectable . CONCLUSION Our findings suggest that significant functional changes occur in the lateral pain pathway in MOH patients . These could result from different processes : 1 ) cortical down-regulation aim ed at reducing painful input to the cortex ; 2 ) activity-dependent plasticity induced by excessive painful input during migraine attacks ; and 3 ) direct effect of medication overuse . At 6 months after withdrawal , activity in these regions normalized , suggesting that no irreversible changes occur due to medication overuse Background and objective Somatosensory temporal discrimination was recently reported as prolonged during migraine attacks , which is consistent with disrupted sensorial perception in migraine . However , knowledge about central sensory processing in tension-type headache is still lacking . This prospect i ve , controlled study aim ed to investigate somatosensory temporal discrimination thresholds in tension-type headache . Methods The study included 10 tension-type headache patients , 10 migraine patients and 10 healthy volunteers without headache . Somatosensory temporal discrimination thresholds were evaluated during the headache attacks of tension-type headache and migraine patients . Results Somatosensory temporal discrimination thresholds of tension-type headache patients ( 39.0 ± 5.5 ms for the right h and and 40.6 ± 4.6 ms for the left h and ) were significantly lower than those of episodic migraine patients ( 137.1 ± 35.8 ms for the right h and and 118.4 ± 34.3 ms for the left h and , p < 0.0001 and p < 0.0001 respectively ) , and comparable to those of healthy volunteers ( 38.6 ± 5.3 ms for the right h and and 38.3 ± 7.2 ms for the left h and , p = 0.79 and p = 0.45 respectively ) . Conclusion Central sensory processing , as tested by somatosensory temporal discrimination , was remarkably disrupted during the headache attacks in migraineurs , whereas it remained intact in the tension-type headache patients Objective A prospect i ve clinical imaging study has been conducted to investigate pain processing functional pathways during trigeminal heat stimulation ( THS ) in patients with migraine without aura experiencing ictal cutaneous allodynia ( CA ) ( MwoA CA+ ) . Methods Using whole-brain BOLD-fMRI , functional response to THS at three different intensities ( 41 ° , 51 ° and 53 ℃ ) was investigated interictally in 20 adult MwoA CA+ patients compared with 20 MwoA patients without ictal CA ( MwoA CA− ) and 20 healthy controls ( HCs ) . Secondary analyses evaluated associations between BOLD signal change and clinical features of migraine . Results During moderate-noxious THS ( 51 ℃ ) , we observed a significantly greater activation in ( a ) the anterior cingulate cortex in MwoA CA+ patients compared to HCs and ( b ) the middle frontal gyrus in MwoA CA+ patients compared to both MwoA CA− patients and HCs . Furthermore , during high-noxious THS ( 53 ℃ ) a significantly decreased activation in the secondary somatosensory cortices was observed in ( a ) MwoA CA− patients compared to both MwoA CA+ patients and HCs and ( b ) MwoA CA+ patients compared to HCs . CA severity was positively correlated with the secondary somatosensory cortices activation . Conclusions Our findings suggest that CA may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients & NA ; Habituation deficits in various sensory modalities have been observed in migraine patients in several experimental design s. The underlying neuronal mechanisms are , however , still unknown . Past studies have used electrophysiological measures and focussed on habituation behaviour during one single session . We were interested in how repeated painful stimulation over several days is processed , perceived and modulated in migraineurs . Fifteen migraine patients and 15 healthy controls were stimulated daily with a 20 min trigeminal pain paradigm for eight consecutive days , using functional MRI performed on days one and eight and one follow‐up measurement three months later . The results demonstrate that migraine patients did not differ in behavioural pain ratings compared to the controls at any time . However , functional imaging data revealed a significant difference in several brain areas over time . The activity level in the prefrontal cortex ( PFC ) and the rostral anterior cingulate cortex ( rACC ) increased in healthy control subjects from day one to day eight , whereas it decreased in migraine patients . These data suggest that several brain areas known to be involved in endogenous pain control show a completely opposite behaviour in migraine patients compared to healthy controls . These brain networks seem not to be disrupted per se in migraine patients but changed activity over time responding to repetitive nociceptive input . The alteration of pain inhibitory circuits may be the underlying mechanism responsible for the dys‐functional neuronal filters of sensory input Background Which , medication , if any , to use to prevent the headache of pediatric migraine has not been established . Methods We conducted a r and omized , double‐blind , placebo‐controlled trial of amitriptyline ( 1 mg per kilogram of body weight per day ) , topiramate ( 2 mg per kilogram per day ) , and placebo in children and adolescents 8 to 17 years of age with migraine . Patients were r and omly assigned in a 2:2:1 ratio to receive one of the medications or placebo . The primary outcome was a relative reduction of 50 % or more in the number of headache days in the comparison of the 28‐day baseline period with the last 28 days of a 24‐week trial . Secondary outcomes were headache‐related disability , headache days , number of trial completers , and serious adverse events that emerged during treatment . Results A total of 361 patients underwent r and omization , and 328 were included in the primary efficacy analysis ( 132 in the amitriptyline group , 130 in the topiramate group , and 66 in the placebo group ) . The trial was concluded early for futility after a planned interim analysis . There were no significant between‐group differences in the primary outcome , which occurred in 52 % of the patients in the amitriptyline group , 55 % of those in the topiramate group , and 61 % of those in the placebo group ( amitriptyline vs. placebo , P=0.26 ; topiramate vs. placebo , P=0.48 ; amitriptyline vs. topiramate , P=0.49 ) . There were also no significant between‐group differences in headache‐related disability , headache days , or the percentage of patients who completed the 24‐week treatment period . Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo , including fatigue ( 30 % vs. 14 % ) and dry mouth ( 25 % vs. 12 % ) in the amitriptyline group and paresthesia ( 31 % vs. 8 % ) and weight loss ( 8 % vs. 0 % ) in the topiramate group . Three patients in the amitriptyline group had serious adverse events of altered mood , and one patient in the topiramate group had a suicide attempt . Conclusions There were no significant differences in reduction in headache frequency or headache‐related disability in childhood and adolescent migraine with amitriptyline , topiramate , or placebo over a period of 24 weeks . The active drugs were associated with higher rates of adverse events . ( Funded by the National Institutes of Health ; CHAMP Clinical Trials.gov number , NCT01581281 ) Migraine is characterized by an altered cortical excitability . Because transcranial direct current stimulation ( tDCS ) can change brain activity noninvasively , it is possible to hypothesize its efficacy in modulating pain in migraine . In this study , we compared the effects of tDCS of the left primary motor cortex ( M1 ) and left dorsolateral prefrontal cortex ( DLPFC ) both on subjective pain and on evoked responses induced by laser stimulation ( LEPs ) . Thirty-two patients and sixteen controls were r and omized to receive sham stimulation and real tDCS with the anode centered over M1 or DLPFC . Laser Evoked potentials were recorded in basal , sham and tDCS conditions . We did not find significant acute changes in LEPs parameters and pain perception among subjects who received tDCS of both M1 and DLPFC . After DLPFC tDCS , we observed a significant increase of N2-P2 component habituation in migraine patients while M1 stimulation reduced it . These findings may suggest a modulation of abnormal pain processing induced by DLPFC and M1 anodal tDCS and outline the need for future investigations exploring the possible neuronal plasticity changes supporting the clinical effect on migraine |
13,082 | 26,272,489 | The review found no evidence to support changing catheters every 72 to 96 hours .
Consequently , healthcare organisations may consider changing to a policy whereby catheters are changed only if clinical ly indicated .
This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications . | BACKGROUND US Centers for Disease Control guidelines recommend replacement of peripheral intravenous ( IV ) catheters no more frequently than every 72 to 96 hours .
Routine replacement is thought to reduce the risk of phlebitis and bloodstream infection .
Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation .
Costs associated with routine replacement may be considerable .
This is an up date of a review first published in 2010 .
OBJECTIVES To assess the effects of removing peripheral IV catheters when clinical ly indicated compared with removing and re-siting the catheter routinely . | Background Although intravenous therapy is one of the most commonly performed procedures in hospitalized patients , it remains susceptible to infectious and noninfectious complications . Previous studies investigated peripheral intravenous catheter ( PIVC ) complications mainly in pediatrics , but apparently none were investigated among Saudi adult population s. The aim of this study was to assess the pattern and complications of PIVCs at King Abdulaziz Medical City ( KAMC ) , Riyadh , Saudi Arabia . Methods An observational prospect i ve cohort study investigated PIVCs pattern and complications among adults with PIVCs , admitted to various wards at KAMC . PIVCs-related clinical outcomes ( pain , phlebitis , leaking , and others ) were recorded in 12-hour intervals , using the Visual Inspection Phlebitis scale . Density incidence ( DI ) and cumulative incidence ( CI ) of complications and their relative risks ( RRs ) were calculated . Regression analyses were applied and significance limits were set at P<0.05 . Results During the study period , 359 adults were included , mounting to 842 PIVCs and 2,505 catheter days . The majority of patients , 276 ( 76.9 % ) , had medical , chief admission complaints , whereas 83 ( 23.1 % ) were trauma/surgical and infectious cases . Complicated catheters were found in 141 ( 39.3 % ) patients , with 273 complications ( 32.4/100 catheters ) , in 190 complicated catheters ( CI = 22.56/100 catheters and DI = 75.84/1,000 catheter days ) . Phlebitis ranked first among complications , 148 ( CI = 17.6 % ) , followed by pain 64 ( CI = 7.6 % ) , leaking 33 ( CI = 3.9 % ) , dislodgement 20 ( CI = 2.4 % ) , and extravasations and occlusion 4 ( CI = 0.5 % each ) . Phlebitis was predicted with female sex ( P<0.001 ) , insertion in fore/upper arm ( P=0.024 ) , and infusion of medication ( P=0.02 ) . Removal time for PIVCs insertion was not a significant predictor of phlebitis ( RR = 1.46 , P=0.08 ) . Conclusion Incidence of complications in this study was significantly higher than rates in previous studies . Better insertion techniques may be sought to lower the incidences of PIVC complications , thus extending their onset beyond day 3 . Changing catheters is recommended when clinical ly indicated rather than routinely post-72 hours Background Peripheral intravenous device ( IVD ) complications were traditionally thought to be reduced by limiting dwell time . Current recommendations are to resite IVDs by 96 hours with the exception of children and patients with poor veins . Recent evidence suggests routine resite is unnecessary , at least if devices are inserted by a specialised IV team . The aim of this study was to compare the impact of peripheral IVD ' routine resite ' with ' removal on clinical indication ' on IVD complications in a general hospital without an IV team . Methods A r and omised , controlled trial was conducted in a regional teaching hospital . After ethics approval , 362 patients ( 603 IVDs ) were r and omised to have IVDs replaced on clinical indication ( 185 patients ) or routine change every 3 days ( 177 patients ) . IVDs were inserted and managed by the general hospital medical and nursing staff ; there was no IV team . The primary endpoint was a composite of IVD complications : phlebitis , infiltration , occlusion , accidental removal , local infection , and device-related bloodstream infection . Results IVD complication rates were 68 per 1,000 IVD days ( clinical ly indicated ) and 66 per 1,000 IVD days ( routine replacement ) ( P = 0.86 ; HR 1.03 ; 95 % CI , 0.74 - 1.43 ) . Time to first complication per patient did not differ between groups ( KM with log rank , P = 0.53 ) . There were no local infections or IVD-related bloodstream infections in either group . IV therapy duration did not differ between groups ( P = 0.22 ) , but more ( P = 0.004 ) IVDs were placed per patient in the routine replacement ( mean , 1.8 ) than the clinical indication group ( mean , 1.5 ) , with significantly higher hospital costs per patient ( P < 0.001 ) . Conclusions Resite on clinical indication would allow one in two patients to have a single cannula per course of IV treatment , as opposed to one in five patients managed with routine resite ; overall complication rates appear similar . Clinical ly indicated resite would achieve savings in equipment , staff time and patient discomfort . There is growing evidence to support the extended use of peripheral IVDs with removal only on clinical indication . Registration numberAustralian New Zeal and Clinical Trials Registry ( ANZCTR ) Number ACTRN12608000421336 Four techniques of administering peripheral parenteral nutrition ( PPN ) were examined prospect ively to investigate the role of mechanical trauma in the development of infusion phlebitis . Patients in group 1 ( n = 15 ) were fed via a st and ard 18-G Teflon cannula which was removed on completion of the infusion and was rotated to the contralateral arm every day . Group 2 patients ( n = 15 ) had a similar catheter sited in each forearm simultaneously , with rotation of the side of infusion each day . Patients in group 3 ( n = 17 ) had a 15-cm Silastic rubber catheter inserted into a forearm vein and a st and ard cannula sited in the contralateral forearm , with alternation of infusion each day . Those in group 4 ( n = 13 ) had a fine-bore 23-G silicone catheter sited in one arm only . Patients in groups 1 , 2 and 3 were fed over 12-h cycles and those in group 4 for a 24-h continuous cycle . A total of 408 patient-days of PPN were given . Mean duration of PPN in groups 1 - 4 was 7.5 , 9 , 5.5 and 5 days respectively . Infusion phlebitis was not recorded in patients who had a daily change of cannula ( group 1 ) , but occurred in four patients in group 2 , eight in group 3 and eight in group 4 . Phlebitis scores were 0 , 9 , 15 and 12 for groups 1 - 4 respectively . Severe phlebitis and line occlusion occurred more frequently in patients with a 15-cm catheter ( group 3 ) and in those fed continuously over 24 h ( group 4 ) . These results suggest that mechanical trauma is an important factor in the aetiology of infusion phlebitis . This can be minimized by reducing the time for which the vein wall is exposed to nutrient infusion and by reducing the amount of prosthetic material within the vein Summary A prospect i ve , r and omised , controlled clinical study was performed to compare the incidence and severity of postoperative peripheral venous thrombophlebitis associated with a single intravenous cannula used for both intra‐operative and postoperative purpose s , and two cannulae , one used intra‐operatively and the other postoperatively . Sixty American Society of Anaesthesiologists ( ASA ) physical status I or II patients aged 18–65 years undergoing elective surgery were studied . The technique of cannula insertion was st and ardised . After surgery , the cannulation sites were examined daily by a blinded investigator for the presence and severity of thrombophlebitis using the Baxter Scale . The two groups were similar in terms of age , gender , weight , type and duration of surgical procedures , and drugs and fluids administered both intra‐operatively and postoperatively . The proportion of patients that developed phlebitis was significantly less in the two cannulae group ( 26.1 % ) than in the single cannula group ( 63.3 % ) ( p < 0.0001 ) . The severity of phlebitis was greater in the single cannula group than in the two cannulae group . These results indicate that the use of a dedicated cannula for postoperative use decreases the incidence and severity of postoperative , peripheral , cannula‐related phlebitis INTRODUCTION Peripheral venous thrombophlebitis ( PVT ) represents a considerable source of iatrogenic morbidity , occurring in about 20 % of hospital in- patients . The aim of this prospect i ve r and omised study was to investigate the effect of elective change of intravenous cannulae on the incidence of PVT in hospital in- patients . PATIENTS AND METHODS General medical and surgical in patients requiring intravenous therapy were r and omised into control ( n = 26 ) or study ( n = 21 ) groups . Cannulae in the control group were only removed if the site became painful , the cannula dislodged , or there were signs of PVT . Cannulae in the study group were changed electively every 48 h. All patients were examined daily for signs of PVT . RESULTS Peripheral venous thrombophlebitis developed in 11/26 patients in the control group and 1/21 patients in the study group ( P = 0.003 ) . Elective change of cannulae did not significantly increase the total number of cannulae sited ( 41 cannulae in the control group versus 43 in the study group ) . CONCLUSIONS Elective change of cannulae result ed in a significant reduction in the incidence of infusion phlebitis . The authors recommend that elective re-siting of intravenous cannulae becomes st and ard practice for all patients requiring intravenous therapy Background Millions of peripheral intravenous catheters are used worldwide . The current guidelines recommend routine catheter replacement every 72–96 h. This practice requires increasing healthcare re source use . The clinical ly indicated catheter replacement strategy is proposed as an alternative . Objectives To assess the cost effectiveness of clinical ly indicated versus routine replacement of peripheral intravenous catheters . Methods A cost-effectiveness analysis from the perspective of Queensl and Health , Australia , was conducted alongside a r and omized controlled trial . Adult patients with an intravenous catheter of expected use for longer than 4 days were r and omly assigned to receive either clinical ly indicated replacement or third-day routine replacement . The primary outcome was phlebitis during catheterization or within 48 h after catheter removal . Re source use data were prospect ively collected and valued ( 2010 prices ) . The incremental net monetary benefit was calculated with uncertainty characterized using bootstrap simulations . Additionally , value of information ( VOI ) and value of implementation analyses were performed . Results The clinical ly indicated replacement strategy was associated with a cost saving per patient of AU$7.60 ( 95 % confidence interval [ CI ] 4.96–10.62 ) and a non-significant difference in the phlebitis rate of 0.41 % ( 95 % CI −1.33 to 2.15 ) . The incremental net monetary benefit was AU$7.60 ( 95 % CI 4.96–10.62 ) . The expected VOI was zero , whereas the expected value of perfect implementation of the clinical ly indicated replacement strategy was approximately AU$5 million over 5 years . Conclusion The clinical ly indicated catheter replacement strategy is cost saving compared with routine replacement . It is recommended that healthcare organizations consider changing to a policy whereby catheters are changed only if clinical ly indicated A peripheral intravenous catheter is often inserted as part of care during labour . The catheter is inserted into the back of the h and or lower forearm vein in usual practice . There is no trial data to guide the care provider on which is the better insertion site in any clinical setting . 307 women admitted to the labour ward who required insertion of intravenous catheter were r and omised to back of h and or lower forearm vein catheter insertion . Catheter insertion is by junior to mid- grade providers . We evaluated insertion success at the first attempt , pain during insertion and catheter replacement due to malfunction as main outcomes . After catheter removal , we recorded patient satisfaction with site , future site preference and insertion site swelling , bruising , tenderness , vein thrombosis and pain . Insertion of a catheter into back of h and vein is more likely to be successful at the first attempt . Insertion pain score , catheter replacement rate , patient satisfaction , patient fidelity to site in a future insertion and insertion site complications rate are not different between trial arms . In conclusion , both insertion sites are suitable ; the back of the h and vein maybe easier to cannulate and seems to be preferred by our frontline providers Objective To find a subset of patients with suspected central venous catheter (CVC)-related infection ( CRI ) in whom CVC removal is not needed . Design R and omized controlled trial . Setting Thirty-three-bed ICU . Patients and participants One hundred and forty four patients with suspected CRI in which a change of CVCs was planned were evaluated for inclusion . Interventions Hemodynamically stable patients without proven bacteremia , no insertion site infection , and no intravascular foreign body were r and omized to a st and ard-of-care group ( SOC , all CVCs were changed as planned ) or a watchful waiting group ( WW , CVCs changed when bacteremia was subsequently confirmed or hemodynamic instability occurred).Measurement and results Study groups were compared for incidence of CVC-related bloodstream infection ( CR-BSI ) , resolution of fever , C-reactive protein , SOFA score , duration of ICU stay , and mortality . Of 144 patients with suspected CRI , 80 patients met exclusion criteria . Sixty-four were r and omized . Forty-seven of 80 excluded patients were shown to be bacteremic , 20 ( 25 % ) of whom had a CR-BSI . Five of 64 ( 8 % ) included patients had a CR-BSI during their subsequent ICU stay ( two in SOC and three in WW group ) . All 38 CVCs were changed in the SOC group versus 16 of 42 in the WW group ( 62 % reduction , P<0.01 ) . Resolution of fever , C-reactive protein , SOFA score , duration of ICU stay , and ICU mortality did not differ between SOC and WW group ( P>0.1 for all ) . Conclusions The use of a simple clinical algorithm permits a substantial decrease in the number of unnecessarily removed CVCs without increased morbidity This r and omized , controlled trial involving 316 patients in the home setting found no difference in the rate of phlebitis and /or occlusion among patients for whom a peripheral intravenous catheter was routinely resited at 72 - 96 hours and those for whom it was replaced only on clinical indication ( 76.8 events per 1,000 device-days vs 87.3 events per 1,000 device-days ; P = .71 ) . There were no bloodstream infections OBJECTIVE To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters . DESIGN A r and omized trial of two catheter material s , with consideration of 21 potential risk factors . SETTING A university hospital . PATIENTS Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter . INTERVENTIONS House officers or ward nurses inserted the catheters , and each insertion was r and omized to a catheter made of tetrafluoroethylene-hexafluoropropylene ( FEP-Teflon ) or a novel polyetherurethane without leachable additives ( PEU-Vialon ) . MEASUREMENTS Research nurses scored insertion sites each day for inflammation and cultured catheters at removal . RESULTS The Kaplan-Meier risk for phlebitis exceeded 50 % by day 4 after catheterization . intravenous antibiotics ( relative risk , 2.00 ) , female sex ( relative risk , 1.88 ) , prolonged ( greater than 48 hours ) catheterization ( relative risk , 1.79 ) , and catheter material ( PEU-Vialon : FEP-Teflon ) ( relative risk , 0.73 ) strongly predicted phlebitis in a Cox proportional hazards model ( each , P less than 0.003 ) . The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection ( relative risk , 6.19 ) , phlebitis with a previous catheter ( relative risk , 1.54 ) , and anatomic site ( h and : forearm , relative risk , 0.71 ; wrist : forearm , relative risk , 0.60 ) . The low incidence of local catheter-related infection was comparable with the two catheter material s ( 5.4 % [ 95 % CI , 3.8 % to 7.6 % ] and 6.9 % [ CI , 4.9 % to 9.6 % ] ) ; none of the 1054 catheters prospect ively studied caused bacteremia . CONCLUSIONS Multiple factors , including the infusate and the duration of cannulation , contribute to the development of infusion-related phlebitis . The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon , and PEU-Vialon can permit longer cannulation with less risk for phlebitis . The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy Phlebitis is a major obstacle to successful and prolonged peripheral parenteral nutrition ( PPN ) . This study evaluated the effects of elective changes of the intravenous cannula and cyclic infusion of PPN on the incidence and the severity of phlebitis . 51 consecutive patients requiring PPN were r and omised into three groups . Group 1 received PPN continuously through a line which was changed only on evidence of phlebitis . In Group 2 intravenous lines were changed every 24h . Group 3 patients received PPN as a 12-h infusion after which the intravenous cannula was withdrawn . All patients received 1800 non-protein calories and 9.4 g nitrogen daily . Infusion sites were assessed daily for phlebitis and this was scored using a modified Maddox scale . The mean ( range ) duration of PPN was 7.5 ( 1 - 13 ) , 10.0 ( 2 - 42 ) and 8.2 ( 3 - 14 ) days in the three groups respectively . Severe phlebitis occurred more frequently ( p < 0.05 ) in Group 1 compared to Group 2 or Group 3 . The overall incidence of phlebitis assessed from the mean value of the Maddox scores for each group was highest in Group 1 and was significantly greater than that observed in either Group 2 ( p < 0.05 ) or Group 3 ( p < 0.001 ) . Group 3 patients who received cyclic PPN had the lowest incidence of phlebitis . The results of this study suggest that the incidence of infusion phlebitis is minimised during PPN by the cyclic infusion of nutrient solutions BACKGROUND There is currently no high grade evidence on which to base decisions about the frequency of intravenous cannula re-sites . OBJECTIVE To assess the safety of changing peripheral venous cannulas when clinical ly indicated . DESIGN R and omised controlled trial . SETTING A tertiary referral hospital in Brisbane , Australia . PARTICIPANTS Two hundred and six hospitalised patients from surgical , medical and orthopaedic wards . INTERVENTIONS Peripheral intravenous cannulas were re-sited only when complications occurred ( intervention group ) or every 3 days ( control group ) . MAIN OUTCOME MEASURES The primary endpoint was any unplanned cannula removal , the secondary outcome was cost . RESULTS Forty six patients had unplanned removals in the intervention group compared with 41 in the control group [ relative risk 1.12 , 95 % confidence interval 0.81 - 1.55 ( p=0.286 ) ] , a non-significant difference . Total duration of peripheral cannulation was similar in both groups ( mean 123.3h in the intervention group and 125.9h in the control group : P=0.82 ) but significantly more re-sites occurred in the control group ( 167 in intervention group , 202 in the control group : p=0.022 ) . Cost of cannula replacements in the intervention group was AUD$3,183.62 and in the control group AUD$3,837.56 ( p=0.006 ) . CONCLUSION Re-siting peripheral venous cannulas when clinical ly indicated compared with changing them routinely every 3 days does not lead to more complications and reduces costs STUDY OBJECTIVES To prospect ively assess the relative risk for phlebitis in a series of consecutive patients with pneumonia and to identify risk factors that predict an increased risk for phlebitis . SETTING Internal medicine department of a tertiary teaching hospital . PATIENTS Seven hundred sixty-six consecutive patients with acute pneumonia receiving IV therapy . INTERVENTIONS Only the first catheter was taken into account . There were 308 short lines ( a 51-mm , 18-gauge Teflon catheter ) ; 307 midsized lines ( a 28-cm , 16-gauge polyvinyl chloride catheter ) ; and 151 long lines ( 71-cm , 14-gauge plain polyurethane catheter ) . Eighteen variables were prospect ively evaluated in an open , nonr and omized study for their contribution to the occurrence of phlebitis . RESULTS The overall phlebitis rate was 39 % . Phlebitis developed in 53 % of patients with short lines , in 41 % of patients with midsized lines , and in 10 % of patients with long lines , and these catheters remained in place an average ( + /- SD ) of 3.0+/-2.4 days , 4.6+/-3.4 days , and 7.8+/-6.6 days , respectively . The variables that influenced the development of phlebitis , as determined by multivariate analysis , were the following : type of catheter ; blood hemoglobin levels ; and IV therapy with either corticosteroids or erythromycin . CONCLUSIONS According to our data , when the use of a catheter is expected to be required for < or = 36 h , a short line can be used . If a longer duration is expected , a longer line is warranted . Ours is the first study in which the relationship between blood hemoglobin levels and phlebitis has been reported . Because the use of intravascular devices is increasingly common , a more complete knowledge of the factors that influence their acceptance has become essential As part of a st and ardized , multi-hospital prospect i ve surveillance system for nosocomial infections in Rhode Isl and , an analysis was undertaken in March 1980-February 1982 to determine the interplay of factors that contribute to the risk of phlebitis in peripheral , non-steel , non-butterfly intravenous catheters . The authors studied 3094 patients with 5161 total episodes of peripheral intravenous catheters from day of admission until day of discharge . The overall rate of phlebitis was 2.3 % ( 118 episodes ) , and the rate of intravenous catheter-associated bacteremia was 0.08 % ( 1 definite episode , 3 possible episodes ) . Factors significantly associated with the occurrence of phlebitis were : underlying risk for any nosocomial infection , duration of the catheter episode , chronological order of the episode and an interaction between the latter two variables . Analysis of day-specific risk of phlebitis indicated that , for patients with low risk diagnoses , initial peripheral intravenous catheters might be left in place with relative safety for up to 96 hours . Over this time period , the day-specific risk for such patients ranged between 0.8 % and 1.4 % , exclusive of the first day . In all other circumstances , the current recommendation of 48 - 72 hours seems appropriate BACKGROUND Catheter-related phlebitis is a frequent problem in the clinical setting . Risk factors for catheter-related phlebitis were assessed at a single tertiary-care institution where no routine change policy for peripheral intravenous catheters is in place . METHODS In a nonr and omized , observational trial , peripheral intravenous Teflon catheters were inserted in patients with a diagnosis of leukemia , lymphoma , solid tumor , acquired immunodeficiency syndrome , other serious infection , or autoimmune disorder . Underlying disease , age , white blood cell count at the time of insertion , physician placing the catheter , catheter bore , duration of cannulation , reason for removal of the catheter , and visual inspection of the insertion site were recorded . RESULTS Four hundred twelve catheters were inserted in 175 patients . The number of catheterizations per episode varied between 1 and 7 . Three hundred sixty-four ( 88.3 % ) catheter placements were evaluable . The mean duration of cannulation was 4.2 days . The overall incidence of phlebitis was 12.9 % . Catheters in leukopenic patients showed a longer duration of cannulation compared with catheters in nonleukopenic patients , but no difference regarding the phlebitis rate . CONCLUSION Findings in this study partly contrast with data reported in the literature . In particular , leukopenia , female gender , prolonged duration of cannulation , antibiotics , and choice of insertion site could not be shown to be risk factors Temporary vascular access catheters ( VACs ) are important devices used in acute blood purification therapies . The aim of this study was to determine whether a catheterization duration of 2 weeks increased the risk of nosocomial complications when compared with a 1-week duration . Fifty-six patients with 90 double lumen VACs were r and omly chosen , and received either 1- or 2-week catheterizations from operators experienced in the placement of such catheters at three sites such as the internal jugular , subclavian , or femoral vein . The characteristics of the VACs , including the sites , procedures , and lengths , were similar in both groups . No significant difference in the rate of catheter colonization was observed between the groups ( 14.6 % vs 26.2 % , P = 0.1371 ) . No significant difference in the rate of catheter-related bloodstream infections was observed between the groups ( 2.1 % vs 4.8 % , P = 0.5967 ) . Two-week indwelling did not increase the risk of infection compared with 1-week indwelling at any of the sites in critically ill patients BACKGROUND The millions of peripheral intravenous catheters used each year are recommended for 72 - 96 h replacement in adults . This routine replacement increases health-care costs and staff workload and requires patients to undergo repeated invasive procedures . The effectiveness of the practice is not well established . Our hypothesis was that clinical ly indicated catheter replacement is of equal benefit to routine replacement . METHODS This multicentre , r and omised , non-blinded equivalence trial recruited adults ( ≥18 years ) with an intravenous catheter of expected use longer than 4 days from three hospitals in Queensl and , Australia , between May 20 , 2008 , and Sept 9 , 2009 . Computer-generated r and om assignment ( 1:1 ratio , no blocking , stratified by hospital , concealed before allocation ) was to clinical ly indicated replacement , or third daily routine replacement . Patients , clinical staff , and research nurses could not be masked after treatment allocation because of the nature of the intervention . The primary outcome was phlebitis during catheterisation or within 48 h after removal . The equivalence margin was set at 3 % . Primary analysis was by intention to treat . Secondary endpoints were catheter-related bloodstream and local infections , all bloodstream infections , catheter tip colonisation , infusion failure , catheter numbers used , therapy duration , mortality , and costs . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12608000445370 . FINDINGS All 3283 patients r and omised ( 5907 catheters ) were included in our analysis ( 1593 clinical ly indicated ; 1690 routine replacement ) . Mean dwell time for catheters in situ on day 3 was 99 h ( SD 54 ) when replaced as clinical ly indicated and 70 h ( 13 ) when routinely replaced . Phlebitis occurred in 114 of 1593 ( 7 % ) patients in the clinical ly indicated group and in 114 of 1690 ( 7 % ) patients in the routine replacement group , an absolute risk difference of 0·41 % ( 95 % CI -1·33 to 2·15 % ) , which was within the prespecified 3 % equivalence margin . No serious adverse events related to study interventions occurred . INTERPRETATION Peripheral intravenous catheters can be removed as clinical ly indicated ; this policy will avoid millions of catheter insertions , associated discomfort , and substantial costs in both equipment and staff workload . Ongoing close monitoring should continue with timely treatment cessation and prompt removal for complications . FUNDING Australian National Health and Medical Research Council OBJECTIVE To compare the rates of phlebitis of peripheral intravenous lines left in place for 72 hours versus rates of those left in place 96 hours . DESIGN A prospect i ve , nonr and omized study . SETTING A university teaching hospital with 375 beds . PATIENTS Consecutive adult patients who received peripheral intravenous lines and were admitted to the wards . MEASUREMENTS The phlebitis rates were monitored by the i.v . Team for 1 month according to a predetermined definition for phlebitis : palpable cord or at least two of the following : tenderness , warmth , erythema , and in duration . RESULTS A total of 2503 peripheral lines were evaluable . The overall phlebitis rate was 6.8 % . The phlebitis rates for lines left in for 72 and 96 hours were not significantly different ( 3.3 % vs 2.6 % , p = 1.000 ) by Fisher 's Exact Test and survival analysis . It was estimated that in 1 month approximately 300 intravenous lines potentially could be prolonged beyond 72 hours ; 215 lines were changed at 72 hours despite no signs of inflammation , 61 lines were kept till 96 hours , and 19 lines were kept beyond 96 hours . CONCLUSIONS Phlebitis rate for our peripheral intravenous catheters at 96 hours was not significantly different from that at 72 hours . If intravenous cannulas and lines were prolonged to 96 hours , a potential cost saving of $ 61,200 per year could be realized The incidence of thrombophlebitis following the use of two types of cannulae , a new generation polyurethane cannula Biovalve PUR and a polyurethane hybrid co‐polymer Vialon cannula , was compared in a r and omised trial . Seventy patients scheduled for elective cardiac surgery were r and omly assigned to have either a Biovalve cannula or a Vialon cannula inserted before induction of anaesthesia . Postoperatively , the cannulae were removed either as soon as signs of thrombophlebitis were observed or at the end of seven days , whichever was earlier . There was a significantly lower incidence of thrombophlebitis in the Biovalve PUR group ( 17 % ) compared to the Vialon group ( 60 % ) at the end of seven days ( p < 0.001 ) . None of the cannulae tip cultures result ed in the growth of micro‐organisms . There was also a lower incidence of the need for re‐siting with the Biovalve than with the Vialon cannulae BACKGROUND Peripheral venous thrombophlebitis ( PVT ) is a common complication of intravenous cannulation , occurring in about 30 % of patients . We evaluated the effect of elective re-siting of intravenous cannulae every 48 hours on the incidence and severity of PVT in patients receiving intravenous fluids/drugs . METHODS We r and omized 42 patients who were admitted for major abdominal surgery to either the control or study group ( n = 21 in either group ) . Informed consent was obtained from all of them . Cannulae in the control group were removed only if the site became painful , the cannula got dislodged or there were signs and symptoms suggestive of PVT , namely pain , erythema , swelling , excessive warmth or a palpable venous cord . Cannulae in the study group were changed and re-sited electively every 48 hours . All the patients were examined every 24 hours for signs and symptoms of PVT at the current and previous sites of infusion . RESULTS The incidence of PVT was 100 % ( 21/21 ) in the control group and only 9.5 % ( 2/21 ) in the study group ( p < 0.0001 ) . The severity of PVT was also less in the study group compared with that in the control group . Day-wise correlation of the incidence of PVT showed that 82.6 % of the episodes of PVT occurred on day 3 . CONCLUSION Elective re-siting of intravenous cannulae every 48 hours results in a significant reduction in the incidence and severity of PVT . We recommend that this should be adopted as st and ard practice in managing all patients who require prolonged intravenous therapy Methods which might be useful in preventing cephalothin-induced phlebitis following intravenous administration of the buffered drug were investigated . One hundred and twenty adult orthopedic patients were assigned r and omly to either a control group or one of five treatment groups . The treatment regimens studied were : addition of hydrocortisone phosphate 10 mg to each liter of intravenous fluid ; addition of heparin 1,000 units to each liter of intravenous fluid ; addition of heparin 500 units and hydrocortisone phosphate 1 mg to each liter of intravenous fluid ; addition of heparin 1,000 units and hydrocortisone phosphate 10 mg to each liter of intravenous fluid ; and filtration of intravenous solutions through a 0.22-mum inline filter . All patients in the study received intravenous buffered cephalothin at a dosage of 1 g every six hours for a minimum of 48 hours . Phlebitis was assessed every 12 hours according to predetermined criteria . Significant differences were found in the incidence of phlebitis at 48 hours between the control group and the last three study groups ( see above ) . It is concluded that postinfusion phlebitis following cephalothin administration can be reduced by the concomitant addition of heparin and hydrocortisone to the intravenous solution or by the use of an inline 0.22-mum final filter Objective To compare routine replacement of intravenous peripheral catheters with replacement only when clinical ly indicated . Design R and omised controlled trial . Setting Tertiary hospital in Australia . Participants 755 medical and surgical patients : 379 allocated to catheter replacement only when clinical ly indicated and 376 allocated to routine care of catheter ( control group ) . Main outcome measure A composite measure of catheter failure result ing from phlebitis or infiltration . Results Catheters were removed because of phlebitis or infiltration from 123 of 376 ( 33 % ) patients in the control group compared with 143 of 379 ( 38 % ) patients in the intervention group ; the difference was not significant ( relative risk 1.15 , 95 % confidence interval 0.95 to 1.40 ) . When the analysis was based on failure per 1000 device days ( number of failures divided by number of days catheterised , divided by 1000 ) , no difference could be detected between the groups ( relative risk 0.98 , 0.78 to 1.24 ) . Infusion related costs were higher in the control group ( mean $ A41.02 ; £ 19.71 ; € 24.80 ; $ 38.55 ) than intervention group ( $ A36.40 ) . The rate of phlebitis in both groups was low ( 4 % in intervention group , 3 % in control group ) . Conclusion Replacing peripheral intravenous catheters when clinical ly indicated has no effect on the incidence of failure , based on a composite measure of phlebitis or infiltration . Larger trials are needed to test this finding using phlebitis alone as a more clinical ly meaningful outcome . Registration number Australian New Zeal and Clinical Trials Registry ACTRN12605000147684 |
13,083 | 23,152,275 | There are still only a small number of studies assessing the use of hypnosis for labour and childbirth . | BACKGROUND This review is one in a series of Cochrane Review s investigating pain management for childbirth .
These review s all contribute to an overview of systematic review s of pain management for women in labour , and share a generic protocol .
We examined the current evidence regarding the use of hypnosis for pain management during labour and childbirth .
This review up date s the findings regarding hypnosis from an earlier review of complementary and alternative therapies for pain management in labour into a st and -alone review .
OBJECTIVES To examine the effectiveness and safety of hypnosis for pain management during labour and childbirth . | Background Although medical interventions play an important role in preserving lives and maternal comfort they have become increasingly routine in normal childbirth . This may increase the risk of associated complications and a less satisfactory birth experience . Antenatal hypnosis is associated with a reduced need for pharmacological interventions during childbirth . This trial seeks to determine the efficacy or otherwise of antenatal group hypnosis preparation for childbirth in late pregnancy . Methods / design A single centre , r and omised controlled trial using a 3 arm parallel group design in the largest tertiary maternity unit in South Australia . Group 1 participants receive antenatal hypnosis training in preparation for childbirth administered by a qualified hypnotherapist with the use of an audio compact disc on hypnosis for re-enforcement ; Group 2 consists of antenatal hypnosis training in preparation for childbirth using an audio compact disc on hypnosis administered by a nurse with no training in hypnotherapy ; Group 3 participants continue with their usual preparation for childbirth with no additional intervention . Women > 34 and < 39 weeks gestation , planning a vaginal birth , not in active labour , with a singleton , viable fetus of vertex presentation , are eligible to participate . Allocation concealment is achieved using telephone r and omisation . Participants assigned to hypnosis groups commence hypnosis training as near as possible to 37 weeks gestation . Treatment allocations are concealed from treating obstetricians , anaesthetists , midwives and those personnel collecting and analysing data . Our sample size of 135 women/group gives the study 80 % power to detect a clinical ly relevant fall of 20 % in the number of women requiring pharmacological analgesia – the primary endpoint . We estimate that approximately 5–10 % of women will deliver prior to receiving their allocated intervention . We plan to recruit 150 women/group and perform sequential interim analyses when 150 and 300 participants have been recruited . All participant data will be analysed , by a research er blinded to treatment allocation , according to the " Intention to treat " principle with comprehensive pre-planned cost- benefit and subgroup analyses . Discussion If effective , hypnosis would be a simple , inexpensive way to improve the childbirth experience , reduce complications associated with pharmacological interventions , yield cost savings in maternity care , and this trial will provide evidence to guide clinical practice BACKGROUND The use of negative words , such as ' sting ' and ' pain ' , can increase patient pain and anxiety . We aim ed to determine how pain scores compare with comfort scores and how the technique of pain assessment affects patient perceptions and experiences after operation . METHODS After Caesarean section , 300 women were r and omized before post-anaesthesia review . Group P women were asked to rate their pain on a 0 - 10-point verbal numerical rating scale ( VNRS ) , where ' 0 ' was ' no pain ' and ' 10 ' was ' worst pain imaginable ' . Group C women were asked to rate comfort on a 0 - 10-point VNRS , where ' 0 ' was ' no comfort ' and ' 10 ' was ' most comfortable ' . All women were asked whether the Caesarean wound was bothersome , unpleasant , associated with tissue damage , and whether additional analgesia was desired . RESULTS The median ( inter-quartile range ) VNRS pain scores was higher than inverted comfort scores at rest , 2 ( 1 , 4 ) vs 2 ( 0.5 , 3 ) , P=0.001 , and movement , 6 ( 4 , 7 ) vs 4 ( 3 , 5 ) , P<0.001 . Group P women were more likely to be bothered by their Caesarean section , had greater VNRS ' Bother ' scores , 4 ( 2 , 6 ) vs 1 ( 0 , 3 ) , P<0.001 , perceived postoperative sensations as ' unpleasant ' [ relative risk ( RR ) 3.05 , 95 % confidence interval ( CI ) 2.20 , 4.23 ] , P<0.001 , and related to tissue damage rather than healing and recovery ( RR 2.03 , 95 % CI 1.30 , 3.18 ) , P=0.001 . Group P women were also more likely to request additional analgesia ( RR 4.33 , 95 % CI 1.84 , 10.22 ) , P<0.001 . CONCLUSIONS Asking about pain and pain scores after Caesarean section adversely affects patient reports of their postoperative experiences British physician , Dr. Grantly Dick-Read , was the first to suggest the “ fear-tension-pain ” cycle in his work Natural Childbirth ( 1933 ) . As a result of his underst and ing of how this cycle affected birthing , he recommended women prepare for childbirth . Research studies from around the world have shown that the use of hypnosis for childbirth results in : ∗ shorter labors ∗ reduced use of pain medication ∗ higher Apgar scores ∗ reduced cesarean and forceps Background The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure . In this study , we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus . Methods The protocol used a factorial design with two factors : state ( hypnotic state , resting state , mental imagery ) and stimulation ( warm non-noxious vs. hot noxious stimuli applied to right thenar eminence ) . Two cerebral blood flow scans were obtained with the 15O-water technique during each condition . After each scan , the subject was asked to rate pain sensation and unpleasantness . Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions ( i.e. , brain areas that would be more or less activated in hypnosis than in control conditions , under noxious stimulation ) . Results Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli . Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices . The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex . The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations . Conclusions Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state . In addition , hypnotic modulation of pain is mediated by the anterior cingulate cortex Negative or harsh words such as ‘ pain ’ and ‘ sting ’ used to describe sensations prior to potentially painful procedures have been shown to increase pain . We aim ed to determine whether the reporting of pain and its severity is affected by the way it is assessed during anaesthesia follow-up after caesarean section . Following caesarean section , 232 women were r and omised prior to post-anaesthesia review . Group N participants were asked questions containing the negative word ‘ pain ’ , “ Do you have any pain ? ” and then asked to rate it on a 0 to 10 point Verbal Numerical Rating Scale . Group P participants were asked questions using more positive words , “ How are you feeling ? ” and “ Are you comfortable ? ” . Data are presented as median , interquartile range . In Group N , 63 participants ( 54.3 % ) reported pain compared with only 28 participants ( 24.1 % ) in Group P ( P < 0.001 ) . There were no significant differences between groups for Verbal Numerical Rating Scale at rest : Group N 2 ( 0 to 3 ) vs Group P 1 ( 0 to 4 ) ; P=0.97 , or Verbal Numerical Rating Scale with movement , Group N 5 ( 3 to 6 ) vs Group P 5 ( 3 to 6.3 ) ; P=0.90 . The assessment of pain after caesarean section , using more positive words , decreases its incidence but does not affect its severity when measured by pain scores . Words that focus the patient on pain during its assessment may lead some to interpret sensations as pain which they might not do otherwise . These findings may have important implication s when assessing and research ing postoperative pain The benefits of hypnotic analgesia as an adjunct to childbirth education were studied in 60 nulliparous women . Subjects were divided into high and low hypnotic susceptibility groups before receiving 6 sessions of childbirth education and skill mastery using an ischemic pain task . Half of the Ss in each group received a hypnotic induction at the beginning of each session ; the remaining control Ss received relaxation and breathing exercises typically used in childbirth education . Both hypnotic Ss and highly susceptible Ss reported reduced pain . Hypnotically prepared births had shorter Stage 1 labors , less medication , higher Apgar scores , and more frequent spontaneous deliveries than control Ss ' births . Highly susceptible , hypnotically treated women had lower depression scores after birth than women in the other 3 groups . We propose that repeated skill mastery facilitated the effectiveness of hypnosis in our study Comparaison de 29 primipares preparees avec un entrainement d'auto-hypnose et 36 preparees de facon traditionnelle . Les result ats indiquent que l'hypnose n'est pas significativement efficace en tant que method e d'analgesie , qu'elle donne cependant une amelioration de l'experience de l'accouchement , et qu'elle est peut-etre une cause de prolongement de la |
13,084 | 16,625,636 | AUTHORS ' CONCLUSIONS The short-term benefit of IA corticosteroids in treatment of knee OA is well established , and few side effects have been reported . | BACKGROUND Osteoarthritis ( OA ) is a common joint disorder .
In the knee , injections of corticosteroids into the joint ( intraarticular ( IA ) ) may relieve inflammation , and reduce pain and disability .
OBJECTIVES To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee . | OBJECTIVE --To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide ( THA ) in knee osteoarthritis ( OA ) and examine factors which may relate to treatment efficacy . METHODS --Eighty four patients with clinical and radiographic evidence of knee OA were recruited and r and omly allocated to receive either THA ( 20 mg in 1 ml ) or placebo ( 0.9 % normal saline , 1 ml ) . Follow up assessment s evaluated the following outcome variables : patient opinion of overall change in the treated knee , visual analogue pain score ( VAS ) , distance walked in one minute ( WD ) , and Health Assessment Question naire modified for lower limb function ( HAQ ) . RESULTS --Seventy eight percent of THA and 49 % of placebo treated patients reported overall improvement at week 1 ( p < 0.05 ) . At week 6 , improvement was reported in 57 % and 55 % of patient groups , respectively . VAS improved in both groups at week 1 ( THA , p < 0.001 ; placebo , p < 0.05 ) and week 6 ( both p < 0.01 ) . Improvement in VAS was significantly greater among THA treated patients at week 1 only ( p < 0.01 ) . Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion ( p < 0.05 ) , and those who had synovial fluid successfully aspirated at the time of injection ( p < 0.01 ) . WD improved in THA treated patients at week 1 ( p < 0.001 ) , and in both groups at week 6 ( THA , p < 0.001 ; placebo , p < 0.01 ) . Improvements in HAQ were seen in THA patients only at weeks 1 and 6 ( p < 0.05 ) . Regression analysis did not identify any additional clinical , radiographic , or synovial fluid characteristics which influenced the response . CONCLUSIONS --THA provided short term pain relief in knee OA . Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection We report the results of a double-blind three-centre study , employing a cross-over design , set up to compare the efficacy of intra-articular injections of Myc 2095 ( 20 mg ) , triamcinolone hexacetonide ( Lederspan ) ( 20 mg ) and placebo in 40 patients with synovitis of the knee joint . Each patient included in the study contributed data on 2 of the 3 treatment variables being compared . Seven clinical parameters were assessed every 6 weeks , while the doctor 's and the patient 's assessment s were scored . Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective . Placebo response was also very high . After the first Myc 2095 injection , improvement in " tenderness " , " pain under load " and " swelling and hydrops " was significantly superior to that following placebo treatment . The evaluation of the second injections indicated a marked carry-over effect from the first course . This was also evident from the doctor 's and patient 's assessment s. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials , emerged from this study Background : Since the good effect of intra‐articular injections of the 5‐HT3 receptor antagonist tropisetron in patients with arthritides and activated osteoarthritis has already been demonstrated in pilot studies , the effect of tropisetron is compared with that of methylprednisolone here . Objectives : In a double‐blind study , 34 patients with gonarthritides or activated osteoarthritis ( 18 patients with rheumatoid arthritis , 16 patients with osteoarthritis ) were treated with a single intra‐articular injection of 10 mg tropisetron ( 18 patients ) or 40 mg methylprednisolone ( 16 patients ) . Before treatment as well as one and three weeks later , the intensity of rest pain and pain following exercise was measured with the visual analog scale ( VAS ) for pain and the clinical findings in the knee joint were recorded . Results : By means of the intra‐articular tropisetron treatment , the inflammatory joint process with arthritides and activated arthroses could be influenced in a similar way as with corticosteroid treatment . No significant differences were detected . Conclusion : According to the results presented here , the intra‐articular treatment with the 5‐HT3 receptor antagonist tropisetron in patients with gonarthritides and activated arthroses was about equally effective as those for treatment with corticosteroids . Therefore , it can be used as an alternative in patients for whom concomitant diseases like diabetes and hypertension make it difficult to use corticosteroids . Whether increasing the tropisetron dose may further improve the results remains to be determined in future studies OBJECTIVES : To show whether intra-articular steroid injections are effective in osteoarthritis ; to determine factors that predict response ; and to determine whether injection has a beneficial effect on muscle strength . METHODS : Double blind , placebo controlled , crossover study in 59 patients with symptomatic osteoarthritis of the knee . Outcome measure- Primary outcome measure : change in visual analogue score for pain at three weeks . Predictors of response analysed using logistic regression with a 15 % decrease in pain score at three weeks defining response . RESULTS : Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline ( median change -2.0 mm , interquartile range -16.25 to 4.0 ) and placebo ( median 0.0 mm , interquartile range -9.0 to 6.25 ) . No clinical predictors of response could be identified . Muscle strength was not significantly improved in the short term by intra-articular injection . CONCLUSIONS : Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible . There may be a place for their more widespread use The natural course of primary osteoarthritis of the knee with or without treatment by intraarticular corticosteroid injections was investigated in 446 patients presenting from 1970 to 1973 . Sixty-one of these patients were able to be followed up in 1982 and were divided into two groups . One group included 53 patients ( 82 knees ) without corticosteroid injections . The other group had eight patients ( 14 knees ) who received intraarticular steroids ( mean number of injections : 25 ; range:4 - 78 ) . The st and ing femorotibial angle at followup in the male patients receiving injections ( p < 0.05 ) was four degrees of greater varus angulation . Radiographic degeneration was more advanced in 11 of the 24 steroid-treated knees ( 78.6 % ) , and in 43 of the 82 knees without steroid injections ( 52.4 % ) ( p < 0.01 ) BACKGROUND Osteoarthritis ( OA ) is the most common joint disease encountered throughout Europe . A task force for the EULAR St and ing Committee for Clinical Trials met in 1998 to determine the method ological and logistical approach required for the development of evidence based guidelines for treatment of knee OA . The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinical ly and /or radiographically affecting any compartment of the knee . METHODS The first stage was the selection of treatment modalities to be considered . The second stage comprised a search of the electronic data bases Medline and Embase using a combination of subject headings and keywords . All European language publications in the form of systematic review s , meta-analyses , r and omised controlled trials , controlled trials , and observational studies were included . During stage three all the relevant studies were quality scored . The summary statistics for vali date d outcome measures , when available , were recorded and , where practical , the numbers needed to treat and the effect size for each treatment were calculated . In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach . The final stage ranked these propositions according to the available evidence . A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach . RESULTS Over 2400 English language publications and 400 non-English language publications were identified . Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA . Quantitative analysis of treatment effect was possible in only 61 studies . Recommendations for the management of knee OA based on currently available data and expert opinion are presented . Proposals for a future research agenda are highlighted . CONCLUSIONS These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities . It is apparent that certain clinical propositions are supported by substantial research based evidence , while others are not . There is thus an urgent need for future well design ed trials to consider key clinical questions The index for hip disease ( ISH ) was established , vali date d and appraised as a new assessment test for the trial of new drugs as well as for long-term follow-up of patients , and to help with future indications for surgery . The ISH deals with pain , maximum walking distance , and some activities of daily living . Inter-observer reproducibility is good ( mean deviation 0.55 points ; p less than 0.05 ) . In a short-term , double-blind crossover trial , the ISH , judged according to its power to distinguish between the active drug period and the placebo period , appears as one of the best assessment tests . In the long term , total hip prosthesis is most often justified when the ISH score reaches 10 - 12 points . The index of severity for knee disease ( ISK ) was vali date d and appraised by the same statistical methods . Its value in non-steroidal anti-inflammatory drug ( NSAID ) or analgesic trials is lower than the value of the ISH . However , its use is still justified for that purpose , and for long-term follow-up of osteoarthritis of the knee OBJECTIVE The study was part of a r and omized open-label clinical trial design ed to evaluate the effects of intra-articular injections of hyaluronan ( Hyalgan ) ( HY ) in osteoarthritis ( OA ) of the human knee . Data were compared with those obtained after treatment with methylprednisolone acetate ( Depomedrol ) ( MP ) . METHODS Synovial membranes from patients with OA of the knee , primary or secondary to a traumatic event and classified according to the American College of Rheumatology criteria , were examined by arthroscopy and by light and electron microscopy before and 6 months after local injection of HY ( 2 ml of 500 - 730 000 MW hyaluronan , 10 mg/ml in saline , one injection per week for 5 weeks ) or MP ( 1 ml of methylprednisolone acetate , 40 mg/ml , one injection per week for 3 weeks ) . RESULTS Arthroscopy revealed a significant decrease in inflammatory score after both treatments . Histology showed that HY treatment was effective ( P < or = 0.05 ) in reducing the number and aggregation of lining synoviocytes , as well as the number and calibre of the vessels . MP treatment significantly reduced the number of mast cells in primary OA . Both treatments tended to decrease the number of hypertrophic and to increase the number of fibroblast-like lining cells , to decrease the numbers of macrophages , lymphocytes , mast cells and adipocytes , and to decrease oedema , especially in primary OA , and to increase the number of fibroblasts and the amount of collagen . These phenomena were evident throughout the thickness of the synovial tissue . CONCLUSION At least in the medium term , both HY and MP modified a number of structural variables of the synovial membrane of the osteoarthritic human knee towards the appearance of that of normal synovium . The effect was more evident in primary OA than in OA secondary to a traumatic event . This is the first evidence that local hyaluronan injections modify the structural organization of the human knee synovium in OA Osteoarthritic knee pain affects patient mobility . Relief of knee pain in osteoarthritis has been reported to increase loading of the knee during gait , but it is unknown whether such pain relief enhances knee loading during more dem and ing activities such as stair-stepping . The gait of 19 patients and stair-stepping of 14 patients with painful medial compartment osteoarthritis of the knee was assessed before and after pain-relieving intraarticular injection of the knee and compared with those of 21 healthy control subjects . There were significant increases in gait velocity , cadence , maximum external knee adduction moment ( indicating increased loading in the medial compartment of the knee ) , and maximum external hip adduction and ankle abduction moments immediately after the injection . With the exception of velocity and ankle abduction moment , these variables were returned to levels that were not statistically different from those of the control subjects . However , no significant differences were found during stair-stepping in the external adduction-abduction moments about the knee , hip , or ankle after injection . Furthermore , the postinjection magnitudes of these variables during stair-stepping were significantly less than those of the controls . Therefore , although the relief of knee pain is sufficient to enhance gait function in osteoarthritis of the knee , it is insufficient to enhance stair-stepping function The goal of this study was to assess the safety and efficacy of hyaluronan ( HA ) with/without corticosteroid in patients with knee osteoarthritis ( OA ) . In a 1-year , r and omized , single-blind trial , 24 patients were treated with HA weekly for 3 weeks , then three injections on the 6th month for a total of six injections . Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection . The treatment was repeated at the sixth month . The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and the visual analog pain scale ( VAS ) . After 1 year , progression of OA was evaluated with magnetic resonance imaging ( MRI ) . During the study , pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS ( p<0.05 ) . At the first year , no progression was observed in either treatment group . Although all patients had improvement for both pain and function , HA together with corticosteroid was superior to HA alone for early pain relief . The MRI findings showed that neither treatment showed a progression on the damage of the cartilage Background : Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis , little research involving a comparison of the two interventions has been done . We tested the hypothesis that there are no significant differences between Hylan G-F 20 ( Synvisc ) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate ( Celestone Soluspan ) in terms of pain relief or improvement in function , as determined by vali date d scoring instruments . Methods : One hundred patients with knee osteoarthritis were r and omized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid , and they were followed for six months . The patients treated with Hylan G-F 20 received one course of three weekly injections . The patients treated with the corticosteroid received one injection at the time of enrollment in the study , and they could request one more injection any time during the study . An independent , blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) , a modification of the Knee Society rating system , and the visual analog pain scale . Results : Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores ( a median decrease from 55 to 40 points and from 54 to 44 points , respectively ; p < 0.01 for both ) . The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid ( median , 58 to 70 points ; p = 0.06 ) or for those who received Hylan G-F 20 ( median , 58 to 68 points ; p = 0.15 ) . The scores on the visual analog scale improved for patients receiving Hylan G-F 20 ( median , 70 to 52 mm ; p < 0.01 ) but not for the patients who received the corticosteroid ( median , 64 to 52 mm ; p = 0.28 ) . However , no significant differences between the two treatment groups were found with respect to the WOMAC , Knee Society system , or visual analog scale results . Women demonstrated a significant improvement in only one of the six possible outcome -treatment combinations ( the WOMAC scale ) , whereas men demonstrated significant improvements in five of the six outcomes ( all measures except the Knee Society rating system ) . Conclusions : No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up . Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales . Such significant gender-related differences warrant further investigation . Level of Evidence : Therapeutic study , Level I-1b ( r and omized controlled trial [ no significant difference but narrow confidence intervals ] ) . See Instructions to Authors for a complete description of levels of evidence Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials OBJECTIVE To assess the efficacy of intra-articular steroid injections following arthroscopy and joint lavage in symptomatic OA of the knee . METHODS Seventy-seven patients with OA of the knee were r and omized to receive either 120 mg methylprednisolone acetate ( MPA ) or placebo following arthroscopy . Clinical assessment s included severity of pain on movement and at rest , stiffness , the presence of joint effusions , range of movement , WOMAC ( Western Ontario and McMaster Universities Osteoarthritis Index ) score and Lequesne functional assessment . The outcome measures were evaluated at baseline and 2 , 4 , 8 , 12 and 24 weeks . Further arthroscopies and synovial biopsies were performed at the time of clinical response and at relapse . RESULTS An intention-to-treat analysis was performed on 71 patients ( 38 MPA , 33 placebo ) . Using the OARSI ( Osteoarthritis Research Society International ) response criteria , 58 % of the steroid group vs 33 % of the placebo group ( adjusted relative risk = 2.38 ) ( P = 0.004 ) responded at 4 weeks . At other time points , there were no significant differences between the treatment groups . There were no significant differences between the two treatment groups for pain , stiffness or WOMAC or Lequesne assessment s at any time point . CONCLUSIONS The response to intra-articular corticosteroids following joint lavage is short-lived ( 2 - 4 weeks ) , achievement of an OARSI response criterion being the only difference between the two groups OBJECTIVE To evaluate the efficacy of joint lavage and intraarticular steroid injection , alone and in combination , in the treatment of patients with symptomatic knee osteoarthritis ( OA ) . METHODS Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospect i ve , r and omized , controlled , 2 x 2 factorial- design trial of 6 months ' duration . The 4 treatment groups consisted of 1 ) intraarticular placebo ( 1.5 ml of 0.9 % normal saline ) , 2 ) intraarticular corticosteroids ( 3.75 mg of cortivazol in 1.5 ml ) , 3 ) joint lavage and intraarticular placebo , and 4 ) joint lavage and intraarticular corticosteroid . Outcome measures evaluated at baseline , week 1 , week 4 , week 12 , and week 24 included severity of pain ( 100-mm visual analog scale [ VAS ] ) , global status ( 100-mm VAS ) , and Lequesne 's functional index . RESULTS No interaction between steroid injection and joint lavage was demonstrated . Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 ( P = 0.020 ) . In contrast , corticosteroid injection had no long-term effect ( P = 0.313 ) ; corticosteroid injection was associated with a decrease in pain only at week 1 ( P = 0.003 ) and week 4 ( P = 0.020 ) . After week 4 , Lequesne 's functional index was not significantly improved regardless of the assigned treatment . CONCLUSION Compared with placebo , both treatments significantly relieved pain but did not improve functional impairment . The effects of the 2 treatments were additive . Cortivazol provided short-term relief of pain ( up to week 4 ) . The effects of joint lavage persisted up to week 24 OBJECTIVE To evaluate the safety and efficacy of long-term intraarticular ( IA ) steroid injections for knee pain related to osteoarthritis ( OA ) . METHODS In a r and omized , double-blind trial , 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg ( 34 patients ) or saline ( 34 patients ) into the study knee every 3 months for up to 2 years . The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years . Measurements of minimum joint space width were performed by an automated computerized method on st and ardized fluoroscopically guided radiographs taken with the patient st and ing and with the knee in a semiflexed position . The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index ( WOMAC ) . Efficacy measures of secondary interest were the total score on the WOMAC , physician 's global assessment , patient 's global assessment , patient 's assessment of pain , range of motion ( ROM ) of the affected knee , and 50-foot walking time . Clinical symptoms were assessed just before each injection . RESULTS At the 1-year and 2-year followup evaluations , no difference was noted between the two treatment groups with respect to loss of joint space over time . The steroid-injected knees showed a trend toward greater symptom improvement , especially at 1 year , for the WOMAC pain subscale , night pain , and ROM values ( P = 0.05 ) compared with the saline-injected knees . Using area under the curve analyses , knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide , but not saline ( P < 0.05 ) . CONCLUSION Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA . No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted . Moreover , long-term treatment of knee OA with repeated steroid injections appears to be clinical ly effective for the relief of symptoms of the disease The aim of this study was to compare the effectiveness of triamcinolone hexacetonide ( THA ) and methylprednisolone acetate ( MPA ) , given via the intra-articular route at equipotent dosage to patients with symptomatic knee OA with effusion , in a double-blind r and omized comparative trial . Consecutive hospital-referred patients who fulfilled the American College of Rheumatology criteria for knee OA ( clinical and radiographic ) were r and omly allocated to receive either THA 20 mg ( 1 ml ) or MPA 40 mg ( 1 ml ) . All patients had synovial fluid aspirated from their knee joint at the time of injection . Assessment s were made at 0 , 3 and 8 weeks by a second operator , thus blinding both patient and assessor . Outcomes measured at each visit were : knee pain in the previous 48 h ( expressed on a 100 mm visual analog scale ; VAS ) , stair climb time ( SCT ) and Lequesne index score ( LEQ ) . Changes in VAS , SCT and LEQ were compared between the groups using a Student ’s paired t test . Fifty-seven patients were studied ( 44 female , 13 male ) with a mean age of 62.5 years . Both steroids gave significant pain relief ( VAS ) at week 3 ( p<0.01 ) but only MPA showed an effect on VAS and LEQ scores at week 8 compared to baseline ( p<0.05 ) . THA was more effective than MPA at pain reduction at week 3 ( p<0.01 ) ; this difference was lost at week 8 ( p=0.17 ) . There was no significant difference between the two drugs in functional endpoints ( SCT , LEQ ) at either 3 or 8 weeks . Both THA and MPA offer at least temporary symptomatic benefit in knee OA . THA is more effective than MPA at week 3 , but its effect is lost by week 8 . MPA still has an effect at week 8 Thirty-seven patients suffering from sustained gonitis with recurrent hydrops , not satisfactorily controlled by systemic treatment , participated in the study . Twenty-three patients had bilateral and fourteen patients had unilateral gonitis . Controls were obtained through the use of the contra-lateral knee joint in the twenty-three patients with bilateral gonitis . A total of 60 knees were r and omized into three groups of 20 knees and received either 30 mg triamcinolone hexacetonide ( TH ) , 60 mg methylprednisolone ( MP ) or 9 mg betamethasone ( BM ) . The clinical parameters evaluated were : recurrence of hydrops , pain , local tenderness , range of joint movement and joint circumference . The period of time elapsing between the injection and the need for a new injection or other treatment was used as the criterion for the duration of effect . Relief lasting for an average of 176 days was obtained in the 20 knees treated with local injections of TH , compared to 125 days for MP and 79 days for BM . No general or local adverse effects were noted in the patients studied . The observed long duration of effect and the absence of adverse effects justify the use of TH in cases of therapy-refractory gonitis SUMMARY Purpose : Joint lavage ( JL ) , involves the passage of cold sterile 0.9 % saline through the knee joint in order to have the fluid reach the inside of the joint capsule . This technique was evaluated as a local treatment for osteoarthritis ( OA ) of the knee alone ( JL ) and in combination with intra-articular infiltration with glucocorticoids ( JLC ) . Patients and methods : An overall 299 knees belonging to 205 patients ( 22 % males , 78 % females ) with a mean age of 67 ± 8 years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were r and omised in the ratio of 1:4 into two therapeutic groups , namely : JL ( n = 62 ) and JLC ( n = 237 ) . All patients received joint lavage on day 0 ; in those of the JLC group , joint lavage was followed by infiltration of 40 mg of triamcinolone acetonide . The efficacy of both treatments was assessed by recording the corresponding values for the following variables : pain strength as measured by a visual analogy scale ( VAS ) , effusion , crepitation , restricted motion , spontaneous pain , pain on pressure , pain on passive motion and pain on active motion ; all of these were recorded at the onset of the study , and after 1 and 3 months . Results : There were no significant differences in the values of the variables at the different follow-up times . Also , pain severity was similar in both treatment groups . Thus , VAS for pain was 7.3 ± 0.3 for the JL group and 7.1 ± 0.2 for the JLC group at the onset , and decreased to 3.0 ± 0.3 in the former and 2.8 ± 0.2 in the latter after 1 month ; the decrease was statistically significant in both cases . After 3 months , the JL and JLC groups had a VAS of 3.5 ± 0.3 and 3.8 ± 0.2 , respectively . Conclusions : The results of this work suggest the absence of significant differences between the two treatments , such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management of osteoarthritis of the knee Intra-articular steroid therapy for osteoarthritis of the knee has been reassessed by two placebo-controlled trials of 20 mg of triamcinalone hexacetonide in 48 joints . Steroid injections caused a significantly greater reduction in pain and tenderness than placebo , and were preferred by patients . However , the benefits were small and transient . Maximum pain reduction occurred one week after injection , and was accompanied by a fall in the thermographic index suggesting an anti-inflammatory mode of action . Synovial fluid was unafffected by injections , and there was no correlation between synovial fluid cell counts or the radiological grading , and the degree of pain reduction Intra-articular injection of micro-crystalline corticosteroid is used to treat symptomatic osteoarthritis ( OA ) of the knee , but its duration of effect and efficacy are uncertain . From the observation that pain in OA of the knee can often be blocked by infiltration of the soft tissues at the patella margin with local anaesthetic , this study investigated an injection technique in which corticosteroid was infiltrated around the patella . Thirty-eight patients with radiologically demonstrable and painful OA of the knee were treated either with peripatellar or intra-articular methylprednisolone in a r and omised double blind study . Assessment s of response to either injection were made at one week , one month and three months . Eleven of 15 measures improved significantly over time in both groups , but the differences between groups were not statistically significant . Analysis of individual responses showed that the majority of good outcomes were in the peripatellar group . Five patients receiving intra-articular injections but only one receiving a peripatellar injection withdrew because of treatment failure . Peripatellar injection is an alternative method of local administration of corticosteroid which is highly effective in a proportion of patients and merits further evaluation We review ed the result of treatment of knee osteoarthritis with intraarticular injection of betamethasone derivatives in 100 patients over a 5 year period . Knee involvement was bilateral in 34 of these patients . 1 ml of a mixture of betamethasone dipropionate and betamethasone phosphate was injected intraarticularly in each patient and repeated if needed at 3 week intervals . A total of 496 injections ( mean 3.7 per knee , minimum 1 and maximum 18 ) were performed . Clinical and radiological evaluation before and midway through therapy revealed no side effects . The clinical response in terms of pain , mobility and functional capacity was good . We conclude that the therapy described results in good clinical and functional results over long periods of time in patients with knee osteoarthritis The aim of this study was to determine the comparative efficacy and safety of intra-articular ( i/a ) triamcinolone . hexacetonide ( TH ) and i/a hyaluronic acid ( HA ) in inflammatory knee osteoarthritis . A r and omized double-blind comparative trail was carried out in a rheumatology outpatient department . There were 63 patients ( 24 male , 39 female , mean age 70.5 years ) with bilateral symptomatic knee osteoarthritis with effusion . Each was given five HA injections at weekly intervals ; or 20 mg TH followed by four placebo ( saline ) injections . Patients were examined weekly during the treatment period and then at monthly intervals for a further 6 months . Assessment included recording of : visual analog scores ( VAS ) for pain ; duration of stiffness ; range of movement ; joint effusion ; local heat ; synovial thickening ; joint-line and periarticular tenderness . The principal outcome measure was pain on a self-selected activity assessed by Vas . The two groups were comparable at entry and no significant differences between the groups developed at any time during the treatment period . However , there was a high drop-out rate and intention to treat analysis failed to demonstrate statistically significant differences between the groups . In patients remaining in the study , significantly less pain was experienced by the HA group during the 6 month follow-up period . Other parameters showed a similar trend in favor of experienced by the HA group during the 6 month follow-up period . Other parameters showed a similar trend in favor of HA . We could not , however , demonstrate significant differences between the placebo and active treatments . HA may therefore be a useful additional therapy for symptomatic knee osteoarthritis and may have a long duration of action OBJECTIVE To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration , the expression of the chemokines monocyte chemoattractant protein 1 ( MCP-1 ) and macrophage inflammatory protein 1alpha ( MIP-1alpha ) , and the expression of matrix metalloproteinases 1 and 3 ( MMPs 1 and 3 ) and their inhibitors , the tissue inhibitors of metalloproteinases 1 and 2 ( TIMPs 1 and 2 ) , in osteoarthritis ( OA ) synovial membranes . METHODS Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids . Twenty-one patients received 120 mg of methylprednisolone acetate ( Depo-Medrol ; Upjohn , Kalamazoo , MI ) , and 20 patients received placebo ( 1 patient received placebo in 1 knee and methylprednisolone acetate in the other ) . Immunoperoxidase staining for the expression of CD68 , MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 was performed , and the immunostaining was quantified by color video image analysis . RESULTS CD68 , MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 immunostaining was observed in all synovial membranes . Intraarticular glucocorticoid treatment was associated with a small ( 30 % ) but statistically significant ( P = 0.048 ) reduction in CD68 + macrophage staining in the synovial lining layer , but there was no change in the CD68 expression in the synovial sublining layer . No significant differences were observed for MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 immunostaining in the synovial lining or sublining layers . CONCLUSION Intraarticular glucocorticoids may reduce CD68 + macrophage infiltration into the synovial lining layer , but not the expression of MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 in the synovial membrane , in patients with OA |
13,085 | 30,730,250 | Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function .
Conclusions : Our meta- analysis revealed no significant effect of NMDA-enhancing agents on overall cognition .
However , subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia , and NAC may have an effect on working memory . | Background : Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia .
However , the results of studies have been conflicting .
This up date d meta- analysis explored the effect of NMDA-receptor-enhancing agents on cognitive function . | BACKGROUND Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia . One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses . Animal and human data suggest NMDA antagonists worsen executive cognitive controls -- e.g . increase perseverative responses and impair set-shifting . We conducted a preliminary study to test the hypothesis that L-carnosine , an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction , a cognitive domain associated with glutamate . METHODS Seventy-five symptomatically stable adults with chronic schizophrenia were r and omly assigned to L-carnosine as adjunctive treatment ( 2 g/day ) or a matched placebo in a double-blind manner for 3 months . Cognitive domains ( executive dysfunction , memory , attention and motor speed ) were assessed using a computerized battery at baseline , 4 and 12 weeks , along with psychopathology ratings and safety parameters . RESULTS The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments . On the strategic target detection test , the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo . Other cognitive tests showed no significant differences between treatments . Psychopathology scores remained stable . The carnosine group reported more adverse events ( 30 % ) compared with the placebo group ( 14 % ) . Laboratory indices remained within acceptable ranges . CONCLUSIONS These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia Abstract Biomarker-guided treatments are needed in psychiatry , and previous data suggest oxidative stress may be a target in schizophrenia . A previous add-on trial with the antioxidant N-acetylcysteine ( NAC ) led to negative symptom reductions in chronic patients . We aim to study NAC ’s impact on symptoms and neurocognition in early psychosis ( EP ) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment . In a double-blind , r and omized , placebo-controlled trial in 63 EP patients , we assessed the effect of NAC supplementation ( 2700 mg/day , 6 months ) on PANSS , neurocognition , and redox markers ( brain GSH [ GSHmPFC ] , blood cells GSH levels [ GSHBC ] , GSH peroxidase activity [ GPxBC ] ) . No changes in negative or positive symptoms or functional outcome were observed with NAC , but significant improvements were found in favor of NAC on neurocognition ( processing speed ) . NAC also led to increases of GSHmPFC by 23 % ( P = .005 ) and GSHBC by 19 % ( P = .05 ) . In patients with high-baseline GPxBC compared to low-baseline GPxBC , subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC . In conclusion , NAC supplementation in a limited sample of EP patients did not improve negative symptoms , which were at modest baseline levels . However , NAC led to some neurocognitive improvements and an increase in brain GSH levels , indicating good target engagement . Blood GPx activity , a redox peripheral index associated with brain GSH levels , could help identify a subgroup of patients who improve their positive symptoms with NAC . Thus , future trials with antioxidants in EP should consider biomarker-guided treatment Abstract Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology , particularly cognitive impairment , of schizophrenia . Sarcosine , a glycine transporter I ( GlyT-1 ) inhibitor , and sodium benzoate , a d-amino acid oxidase ( DAAO ) inhibitor , can both enhance NMDA receptor-mediated neurotransmission . We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients . Methods This study compared add-on sarcosine ( 2 g/day ) plus benzoate ( 1 g/day ) vs. sarcosine ( 2 g/day ) for the clinical symptoms , as well as the cognitive and global functioning , of chronic schizophrenia patients in a 12-week , double-blind , r and omised , placebo-controlled trial . Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks . Seven cognitive domains , recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee , were measured at weeks 0 and 12 . Results Adjunctive sarcosine plus benzoate , but not sarcosine alone , improved the cognitive and global functioning of patients with schizophrenia , even when their clinical symptoms had not improved . Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia , further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms BACKGROUND It is difficult to improve negative symptoms and cognitive impairments in schizophrenia . A previous pilot study has shown that minocycline , a semi-synthetic second-generation tetracycline , is effective in treating for negative and /or cognitive symptoms in schizophrenia . OBJECTIVES The present study was design ed to examine the efficacy and safety of minocycline for the treatment of negative symptoms and cognitive impairments in patients with schizophrenia . METHODS Ninety-two patients with early stage schizophrenia treated with risperidone entered this 16-week , double blind , r and omized , placebo-controlled clinical trial . Subjects were r and omly assigned to receive minocycline ( 200 mg per day ) or the placebo . The primary outcome was evaluated using the Scale for the Assessment of Negative Symptoms ( SANS ) . Secondary outcomes included the response rate of SANS , the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression Scale ( CGI ) , and cognitive tests . RESULTS Subjects receiving minocycline had greater improvements on SANS total scores and PANSS negative subscale scores ( P<0.001 ) when compared with those receiving the placebo . Rates of treatment response ( 43.6 % ) in the minocycline group were significantly higher than those in the placebo group ( 10.0 % ) after 16weeks of treatment . There was no significant difference between the seven cognitive domains ( P>0.05 ) , except for the attention domain ( P=0.044 ) . CONCLUSIONS The addition of minocycline to atypical antipsychotic drugs in early schizophrenia had significant efficacy on negative symptoms but had a slight effect on the attention domains of patients with schizophrenia . It may be considered as a new adjunct treatment for negative symptoms of schizophrenia . Clinical trials.gov identifier : NCT01493622 BACKGROUND Hypofunction of N-methyl-D-aspartate ( NMDA ) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia . D-serine is a full agonist of the glycine site of NMDA receptor , an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor . Supplementation of D-serine may improve the symptoms of schizophrenia . METHODS Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind , placebo-controlled trial of D-serine ( 30 mg/kg/day ) , which was added to their stable antipsychotic regimens . Of these , 28 completed the trial . Measures of clinical efficacy , side effects , and serum levels of amino acids and D-serine were determined every other week . Wisconsin Card Sorting Test ( WCST ) was performed at the beginning and end of the trial . RESULTS Patients who received D-serine treatment revealed significant improvements in their positive , negative , and cognitive symptoms as well as some performance in WCST . D-serine levels at week 4 and 6 significantly predicted the improvements . D-serine was well tolerated and no significant side effects were noted . CONCLUSIONS The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia . Given the effects of D-serine on positive symptoms , a trial of D-serine alone in schizophrenia should be considered The combination of pharmacotherapy and cognitive retraining ( CRT ) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone , but this has not yet been tested . This study evaluated the feasibility , safety , tolerability , and efficacy of 12 weeks of D-serine , combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel , in India and the United States . In a r and omized , partial double-blind , placebo-controlled , parallel-group design , 104 schizophrenia subjects ( US site=22 , Indian site=82 ) were r and omized to : ( 1 ) D-serine ( 30 mg/kg)+CRT ( 5 h/week ) , ( 2 ) D-serine+control CRT , ( 3 ) CRT+placebo D-serine , and ( 4 ) placebo+control CRT . Completion rates were 84 and 100 % in the Indian and US sample s , respectively . On various outcome measures of safety and tolerability , the interventions were well tolerated . D-Serine and CRT did not show any significant effect on the Global Cognitive Index , although both interventions showed differential site effects on individual test performance . CRT result ed in a significant improvement in Verbal Working Memory , and a trend toward improvement in Attention/Vigilance . This is the first study to demonstrating the feasibility , safety , and tolerability of combination pharmacotherapy and CRT in a multicenter international clinical trial . These preliminary findings provide support for future studies using higher doses of D-serine that have been shown to be efficacious or other pharmacotherapies , along with the newer cognitive remediation strategies that are individualized and that target basic information processing Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia , yet many patients only partially respond . Accumulating pre clinical and clinical data suggest benefits with minocycline . We tested adjunct minocycline to clozapine in a 10-week , double-blind , placebo-controlled trial . Primary outcomes tested were positive , and cognitive symptoms , while avolition , anxiety/depression , and negative symptoms were secondary outcomes . Methods Schizophrenia and schizoaffective participants ( n = 52 ) with persistent positive symptoms were r and omized to receive adjunct minocycline ( 100 mg oral capsule twice daily ; n = 29 ) or placebo ( n = 23 ) . Results Brief Psychiatric Rating Scale ( BPRS ) psychosis factor ( P = 0.098 ; effect size [ ES ] , 0.39 ) and BPRS total score ( P = 0.075 ; ES , 0.55 ) were not significant . A change in total BPRS symptoms of more than or equal to 30 % was observed in 7 ( 25 % ) of 28 among minocycline and 1 ( 4 % ) of 23 among placebo participants , respectively ( P = 0.044 ) . Global cognitive function ( MATRICS Consensus Cognitive Battery ) did not differ , although there was a significant variation in size of treatment effects among cognitive domains ( P = 0.03 ) , with significant improvement in working memory favoring minocycline ( P = 0.023 ; ES , 0.41 ) . The Scale for the Assessment of Negative Symptoms total score did not differ , but significant improvement in avolition with minocycline was noted ( P = 0.012 ; ES , 0.34 ) . Significant improvement in the BPRS anxiety/depression factor was observed with minocycline ( P = 0.028 ; ES , 0.49 ) . Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo . Conclusions Minocycline 's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant . Significant improvements with minocycline were seen in working memory , avolition , and anxiety/depressive symptoms in a chronic population with persistent symptoms . Larger studies are needed to vali date these findings OBJECTIVE Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known . Agents that act at the glycine site of the N-methyl-D-aspartic acid ( NMDA ) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments . METHOD The Cognitive and Negative Symptoms in Schizophrenia Trial ( CONSIST ) was a 16-week double-blind , double-dummy , parallel group , r and omized clinical trial of adjunctive glycine , D-cycloserine , or placebo conducted at four sites in the United States and one site in Israel . The participants were 157 in patients and out patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospect i ve criteria for moderate to severe negative symptoms without marked positive , depressive , or extrapyramidal symptoms . The primary outcome measures were the average " rate of change " of Scale for the Assessment of Negative Symptoms ( SANS ) total scores and change in the average cognitive domain z scores . RESULTS There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects . A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests . One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo . A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients . There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score . CONCLUSIONS The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia : negative symptoms and cognitive deficits . Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders . Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia . These findings may be linked to the effect of minocycline on the glutamatergic system , through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity . Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation . OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia . METHOD A longitudinal double-blind , r and omized , placebo-controlled design was used , and patients were followed for 6 months from August 2003 to March 2007 . Seventy early-phase schizophrenia patients ( according to DSM-IV ) were recruited and 54 were r and omly allocated in a 2:1 ratio to minocycline 200 mg/d . All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry ( risperidone , olanzapine , quetiapine , or clozapine ; 200 - 600 mg/d chlorpromazine-equivalent doses ) . Clinical , cognitive , and functional assessment s were conducted , with the Scale for the Assessment of Negative Symptoms ( SANS ) as the primary outcome measure . RESULTS Minocycline was well tolerated , with few adverse events . It showed a beneficial effect on negative symptoms and general outcome ( evident in SANS , Clinical Global Impressions scale ) . A similar pattern was found for cognitive functioning , mainly in executive functions ( working memory , cognitive shifting , and cognitive planning ) . CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning , both related to frontal-lobe activity . Overall , the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00733057 IMPORTANCE In addition to dopaminergic hyperactivity , hypofunction of the N-methyl-d-aspartate receptor ( NMDAR ) has an important role in the pathophysiology of schizophrenia . Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach . To date , several trials on adjuvant NMDA-enhancing agents have revealed beneficial , but limited , efficacy for positive and negative symptoms and cognition . Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism . Sodium benzoate is a d-amino acid oxidase inhibitor . OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer . INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo . MAIN OUTCOMES AND MEASURES The primary outcome measure was the Positive and Negative Syndrome Scale ( PANSS ) total score . Clinical efficacy and adverse effects were assessed biweekly . Cognitive functions were measured before and after the add-on treatment . RESULTS Benzoate produced a 21 % improvement in PANSS total score and large effect sizes ( range , 1.16 - 1.69 ) in the PANSS total and subscales , Scales for the Assessment of Negative Symptoms-20 items , Global Assessment of Function , Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health 's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative , including the domains of processing speed and visual learning . Benzoate was well tolerated without significant adverse effects . CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia . The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia BACKGROUND In a preliminary dose-finding study , D-cycloserine , a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate ( NMDA ) receptor , improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d . METHODS Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were r and omized to D-cycloserine , 50 mg/d ( n=23 ) or placebo ( n=24 ) added to their conventional neuroleptic for an 8-week , double-blind trial . Clinical assessment s were performed at baseline and at weeks 1 , 2 , 4 , 6 , and 8 . Serum concentrations of D-cycloserine , relevant amino acids , and homovanillic acid were assayed at baseline and at weeks 4 and 8 . A cognitive battery was performed at baseline and at week 8 . RESULTS Thirty-nine patients completed the 8-week trial . Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group . The mean reduction in negative symptoms with D-cycloserine ( 23 % ) was significantly greater than with placebo ( 7 % ) as calculated by slopes representing Scale for the Assessment of Negative Symptoms ( SANS ) total scores . Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score . No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure . Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8 . CONCLUSION These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms Rationale Pre clinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia . Pregnenolone is neuroprotective and enhances learning and memory , myelination , and microtubule polymerization . Treatment with pregnenolone elevates allopregnanolone ( a neurosteroid that enhances GABAA receptor responses ) and pregnenolone sulfate ( a positive NMDA receptor modulator ) . Pregnenolone could thus potentially mitigate GABA dysregulation and /or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids . Objective The objective of this study is to conduct a r and omized controlled trial of adjunctive pregnenolone in schizophrenia . Methods Following a placebo lead-in , 120 participants were r and omized to pregnenolone or placebo for 8 weeks ( Institute for Mental Health , Singapore ) . Primary endpoints were changes in MATRICS Consensus Cognitive Battery ( MCCB ) composite scores ( cognitive symptoms ) , UCSD Performance-based Skills Assessment —Brief ( UPSA-B ) composite scores ( functional capacity ) , and Scale for Assessment of Negative Symptoms ( SANS ) total scores ( negative symptoms ) . A modified intent-to-treat analysis approach was utilized . Results No significant changes compared to placebo were demonstrated in composite MCCB scores . In contrast , participants r and omized to pregnenolone ( n = 56 ) demonstrated greater improvements in functional capacity ( UPSA-B composite changes ) compared to placebo ( n = 55 ) , p = 0.03 . Pregnenolone was also superior to placebo in the communication subscale of the UPSA-B ( p < 0.001 ) . Serum pregnenolone changes post-treatment were correlated with UPSA-B composite score changes in females ( rs = 0.497 , p < 0.042 , n = 17 ) but not in males . Mean total SANS scores were very low at baseline and did not improve further post-treatment . Pregnenolone was well-tolerated . Conclusions Pregnenolone improved functional capacity in participants with schizophrenia , but did not improve cognitive symptoms over an 8-week treatment period . Neurosteroid changes correlated with functional improvements in female participants . Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents . Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia . Furthermore , clozapine increases pregnenolone in rodent hippocampus , possibly contributing to its superior efficacy . We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot r and omized , placebo-controlled , double-blind trial . Following a 2-week single-blind placebo lead-in , patients were r and omized to pregnenolone ( fixed escalating doses to 500 mg/day ) or placebo , for 8 weeks . Primary end points were changes in BACS and MCCB composite and total SANS scores . Of 21 patients r and omized , 18 completed at least 4 weeks of treatment ( n=9/group ) . Pregnenolone was well tolerated . Patients receiving pregnenolone demonstrated significantly greater improvements in SANS scores ( mean change=10.38 ) compared with patients receiving placebo ( mean change=2.33 ) , p=0.048 . Mean composite changes in BACS and MCCB scores were not significantly different in patients r and omized to pregnenolone compared with placebo . However , serum pregnenolone increases predicted BACS composite scores at 8 weeks in the pregnenolone group ( rs=0.81 , p=0.022 ) . Increases in allopregnanolone , a GABAergic pregnenolone metabolite , also predicted BACS composite scores ( rs=0.74 , p=0.046 ) . In addition , baseline pregnenolone ( rs=−0.76 , p=0.037 ) , pregnenolone sulfate ( rs=−0.83 , p=0.015 ) , and allopregnanolone levels ( rs=−0.83 , p=0.015 ) were inversely correlated with improvements in MCCB composite scores , further supporting a possible role for neurosteroids in cognition . Mean BACS and MCCB composite scores were correlated ( rs=0.74 , p<0.0001 ) . Pregnenolone may be a promising therapeutic agent for negative symptoms and merits further investigation for cognitive symptoms in schizophrenia BACKGROUND N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory . Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease ( AD ) , particularly in the early phase . Enhancing NMDAR activation might be a novel treatment approach . One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism . This study examined the efficacy and safety of sodium benzoate , a D-amino acid oxidase inhibitor , for the treatment of amnestic mild cognitive impairment and mild AD . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in four major medical centers in Taiwan . Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250 - 750 mg/day of sodium benzoate or placebo for 24 weeks . Alzheimer 's Disease Assessment Scale-cognitive subscale ( the primary outcome ) and global function ( assessed by Clinician Interview Based Impression of Change plus Caregiver Input ) were measured every 8 weeks . Additional cognition composite was measured at baseline and endpoint . RESULTS Sodium benzoate produced a better improvement than placebo in Alzheimer 's Disease Assessment Scale-cognitive subscale ( p = .0021 , .0116 , and .0031 at week 16 , week 24 , and endpoint , respectively ) , additional cognition composite ( p = .007 at endpoint ) and Clinician Interview Based Impression of Change plus Caregiver Input ( p = .015 , .016 , and .012 at week 16 , week 24 , and endpoint , respectively ) . Sodium benzoate was well-tolerated without evident side-effects . CONCLUSIONS Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD . The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes PURPOSE This study aim ed to examine the effect of add-on treatment with the neurosteroid pregnenolone ( PREG ) on neurocognitive dysfunctions of patients with recent-onset schizophrenia ( SZ ) and schizoaffective disorder ( SA ) . METHOD Sixty out- and in patients that met DSM-IV criteria for SZ/SA were r and omized to an 8-week , double-blind , r and omized , placebo-controlled , 2-center trial . Participants received either pregnenolone ( 50 mg/d ) or placebo added on to antipsychotic medications . Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment . ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time . RESULTS Compared to placebo , adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task ( p=0.002 ) , with moderate effect sizes ( d=0.42 ) . In addition , a significant improvement was observed from baseline to end-of- study with respect to the visual ( p=0.008 ) and sustained attention ( Rapid Visual Information Processing , p=0.038 ) deficits , and executive functions ( Stockings of Cambridge , p=0.049 ; Spatial Working Memory , p<0.001 ) among patients receiving PREG but not among those receiving placebo ( all p's>0.05 ) . This beneficial effect of PREG was independent of the type of antipsychotic agents , gender , age , education , and illness duration . CONCLUSIONS Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA . Long-term , large-scale studies are required to obtain greater statistical significance and more confident clinical generalization The N-methyl-d-aspartate ( NMDA ) receptor has been implicated in the pathophysiology of schizophrenia . We administered subanesthetic doses of the NMDA receptor antagonist ketamine in a double-blind , placebo – controlled design to 13 neuroleptic-free schizophrenic patients to investigate if schizophrenics will experience an exacerbation of psychotic symptoms and cognitive impairments with ketamine . We also examined whether schizophrenics experienced quantitative or qualitative differences in ketamine response in comparison to normal controls . Schizophrenics experienced a brief ketamine-induced exacerbation of positive and negative symptoms with further decrements in recall and recognition memory . They also displayed greater ketamine-induced impairments in free recall than normals . Qualitative differences included auditory hallucinations and paranoia in patients but not in normals . These data indicate that ketamine is associated with exacerbation of core psychotic and cognitive symptoms in schizophrenia . Moreover , ketamine may differentially affect cognition in schizophrenics in comparison to normal controls OBJECTIVE D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate ( NMDA ) receptor . Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive , negative , and cognitive symptoms , whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients . To study the difference between full and partial agonists at the NMDA receptor glycine site , the clinical effects of adding D-serine to clozapine were assessed . METHOD In a 6-week double-blind trial , 20 schizophrenic patients received placebo or D-serine ( 30 mg/kg per day ) in addition to clozapine . Clinical efficacy , side effects , and serum levels of D-serine were determined every other week . RESULTS The patients exhibited no improvement with D-serine , nor did their symptoms worsen , as previously reported with D-cycloserine . CONCLUSIONS The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine BACKGROUND Clozapine is the last-line antipsychotic agent for refractory schizophrenia . To date , there is no convincing evidence for augmentation on clozapine . Activation of N-methyl-D-aspartate receptors , including inhibition of D-amino acid oxidase that may metabolize D-amino acids , has been reported to be beneficial for patients receiving antipsychotics other than clozapine . This study aim ed to examine the efficacy and safety of a D-amino acid oxidase inhibitor , sodium benzoate , for schizophrenia patients who had poor response to clozapine . METHODS We conducted a r and omized , double-blind , placebo-controlled trial . Sixty schizophrenia in patients that had been stabilized with clozapine were allocated into three groups for 6 weeks ' add-on treatment of 1 g/day sodium benzoate , 2 g/day sodium benzoate , or placebo . The primary outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total score , Scale for the Assessment of Negative Symptoms , Quality of Life Scale , and Global Assessment of Functioning . Side effects and cognitive functions were also measured . RESULTS Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms . The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score , PANSS-positive score , and Quality of Life Scale . Sodium benzoate was well tolerated without evident side effects . The changes of catalase , an antioxidant , were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group . CONCLUSIONS Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia . Further studies are warranted to eluci date the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia AMPA-receptor-positive modulators ( Ampakines ) facilitate learning and memory in animal models and in preliminary trials in human subjects . CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia . Stable schizophrenia patients treated with clozapine ( n=52 ) , olanzapine ( n=40 ) , or risperidone ( n=13 ) were r and omly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks . Subjects were assessed with a cognitive battery at baseline , week 4 , and at 4-week follow-up . Clinical scales and safety monitoring were also performed . The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample . Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone . A total of 105 patients were r and omized and 95 ( 90 % ) completed the 4-week trial . Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score , or on any cognitive test at weeks 4 or 8 . The between groups effect size at week 4 for the cognitive composite score was −0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone . The placebo group improved more on the PANSS total score than the CX516 group ; no other clinical rating differed between treatment groups . CX516 was associated with fatigue , insomnia and epigastric discomfort compared to placebo , but was generally well tolerated . CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine , olanzapine , or risperidone d-Cycloserine ( DCS ) has been shown to enhance memory and , in a previous trial , once-weekly DCS improved negative symptoms in schizophrenia subjects . We hypothesized that DCS combined with a cognitive remediation ( CR ) program would improve memory of a practice d auditory discrimination task and that gains would generalize to performance on un practice d cognitive tasks . Stable , medicated adult schizophrenia out patients participated in the Brain Fitness CR program 3 - 5 times per week for 8weeks . Subjects were r and omly assigned to once-weekly adjunctive treatment with DCS ( 50 mg ) or placebo administered before the first session each week . Primary outcomes were performance on an auditory discrimination task , the MATRICS cognitive battery composite score and the Scale for the Assessment of Negative Symptoms ( SANS ) total score . 36 subjects received study drug and 32 completed the trial ( average number of CR sessions=26.1 ) . Performance on the practice d auditory discrimination task significantly improved in the DCS group compared to the placebo group . DCS was also associated with significantly greater negative symptom improvement for subjects symptomatic at baseline ( SANS score ≥20 ) . However , improvement on the MATRICS battery was observed only in the placebo group . Considered with previous results , these findings suggest that DCS augments CR and alleviates negative symptoms in schizophrenia patients . However , further work is needed to evaluate whether CR gains achieved with DCS can generalize to other un practice d cognitive tasks CX516 , a positive modulator of the glutamatergic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor , improves performance in tasks requiring learning and memory in animals . CX516 was added to clozapine in 4-week , placebo-controlled , dose-finding ( N = 6 ) and fixed-dose ( N = 13 ) trials . CX516 was tolerated well and was associated with moderate to large , between-group effect sizes compared with placebo , representing improvement in measures of attention and memory . These preliminary results suggest that CX516 and other “ ampakines ” hold promise for the treatment of schizophrenia Cognitive deficits in schizophrenia have been hypothesized to reflect N-methyl-D-aspartate receptor ( NMDAR ) dysfunction . However , the mechanisms through which the NMDAR contributes to individual cognitive functions differ . To explore how NMDAR signaling relates to specific cognitive deficits in schizophrenia , we tested the effects of enhancing NMDAR signaling on working memory and experience-dependent plasticity using d-cycloserine ( DCS ) . Plasticity was assessed using an EEG paradigm that utilizes high-frequency visual stimulation ( HFvS ) to induce neural potentiation , and 2 learning tasks , the information integration ( IIT ) and weather prediction ( WPT ) tasks . Working memory was assessed using an N-back task . Forty-five schizophrenia patients were r and omized to receive a single 100 mg DCS dose ( SZ-DCS ; n = 24 ) or placebo ( SZ-PLC ; n = 21 ) in a double-blind , between-groups design . Testing occurred on a single day after placebo or DCS administration ; baseline values were not obtained . DCS did not affect plasticity , as indicated by similar neural potentiation , and similar IIT and WPT learning between groups . However , among patients who successfully engaged in the working memory task ( ie , performed above chance ) , SZ-DCS ( n = 17 ) showed superior 2-back performance compared to SZ-PLC ( n = 16 ) . Interestingly , SZ-DCS also showed larger pre-HFvS neural responses during the LTP task . Notably , this pattern of DCS effects is the opposite of those found in our prior study of healthy adults . Results are consistent with target engagement of the NMDAR by DCS , but suggest that NMDAR signaling was not translated into synaptic plasticity changes in schizophrenia . Results highlight the importance of considering how distinct NMDAR-associated processes contribute to individual cognitive deficits in schizophrenia BACKGROUND Observations that antagonists of the N-methyl-d-aspartate ( NMDA ) receptor of glutamatergic neurons can mimic symptoms of schizophrenia have raised the hope that NMDA agonists can improve symptoms . On the basis of encouraging results of trials in which NMDA agonists were added to antipsychotics , we conducted an adequately powered r and omized controlled trial adding d-serine , an NMDA modulator , to antipsychotics . METHOD This study was a 195-patient , multicenter , double-blind , r and omized , placebo-controlled , 16-week trial of d-serine 2 g/d as an add-on treatment to antipsychotics . Subjects had DSM-IV schizophrenia or schizoaffective disorder and were in patients or out patients stabilized on antipsychotics , with persistent negative symptoms . The primary outcome measures were changes in negative symptoms and cognition as measured by the Scale for the Assessment of Negative Symptoms ( SANS ) and the Measurement and Treatment Research to Improve Cognition in Schizophrenia ( MATRICS ) battery , respectively . The study was performed between 2003 and 2007 . RESULTS Mean total Positive and Negative Syndrome Scale scores at baseline were 75.5 . Subjects receiving d-serine and placebo improved in scores on the SANS and MATRICS , but no significant differences were observed between groups : improvement on SANS was 11.4 % for d-serine vs 14.8 % for placebo , F1,147=1.18 , P=.32 ; and improvement on MATRICS was 6.8 % for d-serine vs 6.1 % for placebo , F1,125=0.96 , P=.39 , respectively . d-Serine was well tolerated . DISCUSSION This study did not find a significant difference between drug and placebo . However , the results are limited by a relatively large placebo response and somewhat lower-achieved doses than in prior studies . Future studies will administer higher doses and will attempt to affect the NMDA receptor using other mechanisms , such as agonists of the presynaptic metabotropic glutamate 2/3 receptor or glycine reuptake inhibitors . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00138775 BACKGROUND To characterize further behavioral , cognitive , neuroendocrine , and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects . Ketamine , a phencyclidine hydrochloride derivative , is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor . METHODS Nineteen healthy subjects recruited by advertisements from the community participated in this r and omized , double-blind , placebo-controlled study . Subjects completed three test days involving the 40-minute intravenous administration of placebo , ketamine hydrochloride ( 0.1 mg/kg ) , or ketamine hydrochloride ( 0.5 mg/kg ) . Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale . Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale . Cognitive function was assessed by using the ( 1 ) Mini-Mental State Examination ; ( 2 ) tests sensitive to frontal cortical dysfunction , including a continuous performance vigilance task , a verbal fluency task , and the Wisconsin Card Sorting Test ; and ( 3 ) tests of immediate and delayed recall . Plasma levels of cortisol , prolactin , homovanillic acid , and 3-methoxy-4-hydroxyphenethyleneglycol were measured . RESULTS Ketamine ( 1 ) produced behaviors similar to the positive and negative symptoms of schizophrenia ; ( 2 ) elicited alterations in perception ; ( 3 ) impaired performance on tests of vigilance , verbal fluency , and the Wisconsin Card Sorting Test ; ( 4 ) evoked symptoms similar to dissociative states ; and ( 5 ) preferentially disrupted delayed word recall , sparing immediate recall and postdistraction recall . Ketamine had no significant effect on the Mini-Mental State Examination at the doses studied . Ketamine also had no effect on plasma 3-methoxy-4-hydroxyphenethyleneglycol levels , although it blunted a test day decline in plasma homovanillic acid levels at the higher dose . It also dose dependently increased plasma cortisol and prolactin levels . Ketamine produced small dose-dependent increases in blood pressure . CONCLUSIONS These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms , behaviors , and cognitive deficits that resemble aspects of endogenous psychoses , particularly schizophrenia and dissociative states Abstract Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic ( SGA ) was hypothesized to ameliorate negative and /or cognitive symptoms in subjects with schizophrenia . Subjects with predominant persistent negative symptoms ( previously stabilized ≥3 months on an SGA ) were enrolled in a r and omized , placebo-controlled trial to investigate adjunctive treatment with Org 25935 , a selective inhibitor of type 1 glycine transporter , over 12 weeks in a flexible dose design . Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo . Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score . Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores , depressive symptoms ( Calgary Depression Scale for Schizophrenia ) , global functioning ( Global Assessment of Functioning scale ) , and cognitive measures using a computerized battery ( Central Nervous System Vital Signs ) . Responder rates were assessed post hoc . A total of 215 subjects were r and omized , of which 187 ( 87 % ) completed the trial . Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms , Positive and Negative Syndrome Scale ( total or subscale scores ) , Global Assessment of Functioning , or the majority of tested cognitive domains . Org 25935 was generally well tolerated within the tested dose range , with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects . Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA . In our study population , Org 25935 appeared to be well tolerated in the tested dose ranges BACKGROUND Cognitive deficits are predictors of functional outcome in patients with psychosis . While conventional antipsychotics are relatively effective on positive symptoms , their impact on negative and cognitive symptoms is limited . Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis . N-acetylcysteine ( NAC ) , a glutathione precursor with glutamatergic properties , has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder , respectively . However , there are few evidence -based approaches for managing cognitive impairment in psychosis . The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder . METHOD A sample of 58 participants were r and omized in a double fashion to receive 2 g/day of NAC ( n = 27 ) or placebo ( n = 31 ) for 24 weeks . Attention , working memory and executive function domains were assessed . Differences between cognitive performance at baseline and end point were examined using Wilcoxon 's test . The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point . RESULTS Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo ( U = 98.5 , p = 0.027 ) . CONCLUSIONS NAC may have an impact on cognitive performance in psychosis , as a significant improvement in working memory was observed in the NAC-treated group compared with placebo ; however , these preliminary data require replication . Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis Background : Schizophrenia is one of the most disabling psychiatric syndromes with the prevalence of 1 % in the general population . Despite availability of various antipsychotics , negative symptoms and cognitive impairment are difficult to treat . In addition antipsychotic monotherapy is not effective in most of these patients . Current evidence indicates the roles of glutamatergic system in this disorder . N‐acetyl cysteine ( NAC ) also increases extracellular glutamate . This study was conducted to evaluate the clinical effects of oral NAC as an add‐on to maintenance medication for the treatment of chronic schizophrenia . Material s and methods : This 12‐week , double‐blind , r and omized , placebo‐controlled , clinical trial was performed to determine the effectiveness of 1200 mg N‐acetyl cysteine as an adjunctive treatment with conventional antipsychotic medications in 84 patients with chronic schizophrenia . The subjects were evaluated with the Positive and Negative Syndrome Scale ( PANSS ) , Mini‐Mental State Examination ( MMSE ) , and a st and ard neuropsychological screening test . Data were analyzed with SPSS‐16 software . Results : NAC‐treated patients showed significantly improvement in the positive ( F = 5.47 , P = 0.02 ) and negative ( F = 0.20 , df = 1 ) PANSS subscale . Also the general and total PANSS score of NAC group declined over times whilst it was increased for placebo group . Regarding cognitive functions , improvement was observed in some explored areas , such as attention , short‐term and working memory , executive functioning and speed of processing . There was no significant difference between the 2 groups in the frequency of adverse effects . Conclusion : The present study detected improvement in positive , negative , general and total psychopathology symptoms as well as cognitive performance with NAC treatment . It is also well‐tolerated , safe and easy‐to‐use agent as an effective therapeutic strategy to improve outcome in schizophrenia treatment . Highlights Evidence indicates roles for glutamatergic systems in schizophrenia . This study has evaluated the effects of NAC in chronic schizophrenia . We detected improvement in psychotic and cognitive symptom with NAC treatment A rapidly growing body of pre clinical data has implicated the glutamatergic N-methyl-d-aspartate ( NMDA ) receptor in memory and other cognitive processes . There is comparatively less information about this receptor system in human cognition . We examined the effects of subanesthetic doses of ketamine , a noncompetitive NMDA receptor antagonist , on two forms of memory , free recall and recognition , as well as attention and behavior in a double-blind , placebo-controlled , 1-hour infusion in 15 healthy volunteers . Ketamine produced decrements in free recall , recognition memory , and attention . In addition , ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation . Ketamine-induced memory impairments were not accounted for by changes in subject 's attention and were not significantly related to psychosis ratings . These data suggest that the NMDA receptor plays a direct role in two types of explicit memory . The implication s of these data for the pathophysiology of schizophremia are discussed |
13,086 | 18,794,560 | Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture .
Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures .
In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures .
Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) .
Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . | The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture .
Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization .
Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected .
Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older .
Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis .
Osteoporosis can be diagnosed by the occurrence of fragility fracture .
In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .
Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .
Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures .
How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ?
What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ?
Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . | Osteoporosis is a well-recognized adverse effect of corticosteroid therapy . This study aim ed to investigate the effect of etidronate , intermittent cyclical therapy , in the prevention of corticosteroid-induced bone loss . Patients with various medical conditions starting high-dose corticosteroid therapy were enrolled in the study . The treatment had to be expected to continue for at least 12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of prednisone , with subsequent treatment of at least 2.5 mg/day . One hundred seventeen patients were r and omly assigned oral etidronate 400 mg/day , or placebo , for 14 days , followed by 76 days of oral calcium carbonate ( 500 mg elemental calcium ) , cycled over 12 months . The primary outcome measure was the difference in percent change from baseline in bone mineral density of the lumbar spine between the groups at the end of year 1 . Secondary measures included changes in femur bone density and in biochemical markers of bone remodeling . The mean ( + /- SEM ) lumbar spine bone density changed 0.30 + /- 0.61 % and -2.79 + /- 0.63 % in the etidronate and placebo groups , respectively . The mean difference between groups after 1 yr was 3.0 + /- 0.84 % ( P = 0.004 ) . The changes in the femoral neck and great trochanter were not different between the groups . There was a decrease in pyridinium crosslinks , significant from baseline at both 6 and 12 months , in the etidronate group . Osteocalcin increased in the placebo group , and difference between groups was -25.07 + /- 14.89 % ( P = 0.032 ) and -34.68 + /- 19.77 % ( P = 0.051 ) , at 6 and 12 months respectively . There was no significant difference between the groups in number of adverse experiences , including gastrointestinal disorders . Etidronate intermittent cyclical therapy prevents lumbar vertebral bone loss in patients starting high-dose corticosteroid therapy UNLABELLED Oral daily ( 2.5 mg ) and intermittent ib and ronate ( between-dose interval of > 2 months ) , delivering a similar cumulative exposure , were evaluated in 2946 osteoporotic women with prevalent vertebral fracture . Significant reduction in incident vertebral fracture risk by 62 % and 50 % , respectively , was shown after 3 years . This is the first study to prospect ively show antifracture efficacy for the intermittent administration of a bisphosphonate . INTRODUCTION Bisphosphonates are important therapeutics in postmenopausal osteoporosis . However , they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy . Less frequent , intermittent administration may help to overcome these deficiencies . This study assessed the efficacy and safety of oral ib and ronate administered either daily or intermittently with a dose-free interval of > 2 months . MATERIAL S AND METHODS This r and omized , double-blind , placebo-controlled , parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra ( L1-L4 ) and one to four prevalent vertebral fractures ( T4-L4 ) . Patients received placebo or oral ib and ronate administered either daily ( 2.5 mg ) or intermittently ( 20 mg every other day for 12 doses every 3 months ) . RESULTS AND CONCLUSIONS After 3 years , the rate of new vertebral fractures was significantly reduced in patients receiving oral daily ( 4.7 % ) and intermittent ib and ronate ( 4.9 % ) , relative to placebo ( 9.6 % ) . Thus , daily and intermittent oral ib and ronate significantly reduced the risk of new morphometric vertebral fractures by 62 % ( p = 0.0001 ) and 50 % ( p = 0.0006 ) , respectively , versus placebo . Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures ( 49 % and 48 % for daily and intermittent ib and ronate , respectively ) . Significant and progressive increases in lumbar spine ( 6.5 % , 5.7 % , and 1.3 % for daily ib and ronate , intermittent ib and ronate , and placebo , respectively , at 3 years ) and hip BMD , normalization of bone turnover , and significantly less height loss than in the placebo group were also observed for both ib and ronate regimens . The overall population was at low risk for osteoporotic fractures . Consequently , the incidence of nonvertebral fractures was similar between the ib and ronate and placebo groups after 3 years ( 9.1 % , 8.9 % , and 8.2 % in the daily , intermittent , and placebo groups , respectively ; difference between arms not significant ) . However , findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures ( 69 % ; p = 0.012 ) in a higher-risk subgroup ( femoral neck BMD T score < -3.0 ) . In addition , oral ib and ronate was well tolerated . Oral ib and ronate , whether administered daily or intermittently with an extended between-dose interval of > 2 months , is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women . This is the first time that significant fracture efficacy has been prospect ively shown with an intermittently administered bisphosphonate in the overall study population of a r and omized , controlled clinical trial . Thus , oral ib and ronate holds promise as an effective and convenient alternative to current bisphosphonate therapies Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems . We conducted a 1-year prospect i ve , r and omized , double-blind trial in 143 postmenopausal osteoporotic women ( mean + /- SD age , 68.4+/-5.0 years ) with at least one prevalent vertebral fractures and low bone mineral density ( BMD ) , comparing groups receiving raloxifene at 60 mg/day ( RLX60 ) or 120 mg/day ( RLX120 ) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding , thrombophlebitis , breast abnormalities , or increased endometrial thickness ( assessed by ultrasonography ) . As compared with controls , the changes in values over 1 year for RLX60 and RLX120 , respectively , were significant for serum bone alkaline phosphatase ( -14.9 % , -8.87 % ) , serum osteocalcin ( -20.7 % , -17.0 % ) , and urinary C-telopeptide fragment of type I collagen/creatinine ( -24.9 % , -30.8 % ) , markers of bone turnover ; for serum total cholesterol ( -7.0 % for RLX60 ) and low density lipoprotein cholesterol ( LDL ) ( -11.4 % for RLX60 ) and for the LDL/HDL cholesterol ratio ( -13.2 % , -8.3 % ) . BMD increased significantly in the total hip ( 1.66 % for RLX60 ) and ultradistal radius ( 2.92 % , 2.50 % ) . There were nonsignificant trends toward increases over controls in BMD for lumbar spine , total body , and total hip ( for RLX120 ) . Using a > 15 % cutoff definition , raloxifene had no effect on incident fractures , but using a > 30 % cutoff , there was a dose-related reduction ( p = 0.047 ) . We conclude that raloxifene therapy is well tolerated , reduces serum lipids , and does not stimulate the uterus or breasts . It has beneficial effects on bone , although , under the conditions of this study , these appear to be of a smaller magnitude than have been reported with estrogen therapy Patients with inflammatory bowel disease ( IBD ) have frequently a bone mineral density ( BMD ) significantly lower than age-matched healthy subjects . The low BMD observed in IBD patients is related also to a higher incidence of bone fractures . In this prospect i ve r and omized study we evaluated the effect of 1-year risedronate administration on bone mass and turnover , and on vertebral fractures in osteoporotic postmenopausal women with IBD in remission . Ninety osteoporotic postmenopausal women were r and omized to receive oral risedronate 35 mg/week ( risedronate group ) or placebo tablets ( placebo group ; one tab/week ) . The duration of treatment was 12 months . At entry and after treatment , lumbar spine and hip BMD , and serum osteocalcin ( OC ) and urinary deoxypyridinoline/creatinine ratio ( DPD-Cr ) levels were evaluated . Vertebral fractures were assessed from thoracic and lumbar lateral and anterior-posterior spinal radiographs taken at baseline , and from lateral spinal radiographs taken at the end of the study . At study entry , no difference between groups was also detected in BMD and in bone turnover markers . At the end of the study , lumbar spine , trochanter and femoral neck BMD was significantly ( p < 0.05 ) higher in comparison with baseline in the risedronate group , whereas a significant ( p < 0.05 ) decrease was observed in the placebo group . For the same visit , a significant ( p < 0.05 ) difference in lumbar spine , trochanter and femoral neck BMD was detected between groups . After 12-month follow-up , serum OC and urinary DPD-Cr levels were significantly ( p < 0.05 ) lower and higher in comparison with basal values in risedronate and placebo group , respectively . At the same time , a significant ( p < 0.05 ) difference in serum OC and urinary DPD-Cr levels was observed between groups . Throughout the study , the incidence of vertebral fractures was significantly ( p < 0.05 ) lower in the risedronate group than in the placebo group ( 12.5 % vs 34.1 % ) . The relative risk ( RR ) to develop a new vertebral fracture after 1 year of risedronate administration was of 0.36 ( 95 % confidence interval , 0.14–0.85 ) . In conclusion , risedronate administration is an effective anti-osteoporotic treatment in osteoporotic postmenopausal women with IBD in remission To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of involutional osteoporosis , the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate . A total of 547 patients with one to four vertebral fractures were r and omized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment ( treatment of 2 weeks and off period of 10 weeks ) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion . All patients received 200 mg calcium supplement daily . Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24 , 48 , 72 , and 96 weeks . Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3 % for risedronate and 14.2 % for etidronate , and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate . The incidence rates of fracture during the initial 24-week period were 8.8 % for risedronate and 6.0 % for etidronate , but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group ( 3.9 % ) as compared to the etidronate group ( 8.7 % ) . Height loss was significantly less in the risedronate group ( −0.28 cm ) than in the etidronate group ( −0.70 cm ) after 96 weeks . Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period . An improvement of patient QOL was observed in both groups . No significant difference in the incidence of adverse events was observed between the two treatments . Daily oral risedronate ( 2.5 mg ) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability OBJECTIVES Hip fracture is among the most common causes of acute immobilization in elderly patients leading to increased bone resorption , and elderly patients with hip fracture are at high risk for a subsequent hip fracture . DESIGN In this double-blind , r and omized , prospect i ve study , 80 female patients who were immobilized because of a hip fracture were divided into two groups . The etidronate group received oral administration of 200 mg/day etidronate for 2 wks starting 1 day after the surgery . Then , after a 9-wk intermission , etidronate administration was resumed for 2 wks . The placebo group received placebo in a similar manner . RESULTS At baseline , both groups had high serum concentrations of ionized calcium , high urinary deoxypyridinoline ( D-Pyr ) concentrations , and decreased calcitriol concentrations , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of calcitriol . After treatment , serum calcitriol concentrations increased in the etidronate and placebo groups . The etidronate group had significant decreases in serum ionized calcium and urinary D-Pyr , and the placebo group had higher serum calcium and urinary D-Pyr concentrations . CONCLUSIONS Etidronate therapy inhibits bone resorption and improves calcium balance , and such therapy may prevent bone loss and reduce the risk of subsequent hip fracture CONTEXT The Women 's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens ( CEE ) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease . Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis . OBJECTIVE To determine the effects of CEE on breast cancers and mammographic findings . DESIGN , SETTING , AND PARTICIPANTS Following breast cancer risk assessment , 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were r and omized to CEE or placebo at 40 US clinical centers from 1993 through 1998 . Mammography screenings and clinical breast examinations were performed at baseline and annually . All breast cancers diagnosed through February 29 , 2004 , are included . INTERVENTION A dose of 0.625 mg/d of CEE or an identical-appearing placebo . MAIN OUTCOME MEASURES Breast cancer incidence , tumor characteristics , and mammogram findings . RESULTS After a mean ( SD ) follow-up of 7.1 ( 1.6 ) years , the invasive breast cancer hazard ratio ( HR ) for women assigned to CEE vs placebo was 0.80 ( 95 % confidence interval [ CI ] , 0.62 - 1.04 ; P = .09 ) with annualized rates of 0.28 % ( 104 cases in the CEE group ) and 0.34 % ( 133 cases in the placebo group ) . In exploratory analyses , ductal carcinomas ( HR , 0.71 ; 95 % CI , 0.52 - 0.99 ) were reduced in the CEE group vs placebo group ; however , the test for interaction by tumor type was not significant ( P = .054 ) . At 1 year , 9.2 % of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5 % in the placebo group ( P<.001 ) , a pattern that continued through the trial to reach a cumulative percentage of 36.2 % vs 28.1 % , respectively ( P<.001 ) ; however , this difference was primarily in assessment s requiring short interval follow-up . CONCLUSIONS Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy . However , treatment with CEE increases the frequency of mammography screening requiring short interval follow-up . Initiation of CEE should be based on consideration of the individual woman 's potential risks and benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care Incidence of a fracture , particularly in the hip joint , is high in elderly women with Parkinson 's disease ( PD ) , and this is due to the immobilization-induced bone resorption and vitamin D deficiency with reduced bone mineral density ( BMD ) . The objective of this study was to address the possibility that treatment with alendronate and vitamin D2 may reduce the incidence of hip fractures in elderly women with PD . PD patients were r and omly assigned to daily treatment with 5 mg alendronate ( n = 144 ) or a placebo combined with 1,000 IU of vitamin D2 ( n = 144 ) and followed for 2 years . Incidence of hip fractures in the two patient groups during the 2-year follow-up period was studied . At baseline , both groups of patients had low BMD with high levels of serum-ionized calcium and urinary deoxypyridinoline ( D-Pyr ) . Hip fractures occurred in 14 patients in the placebo group and 4 in the alendronate group . The relative risk for hip fractures in the alendronate group as compared with the placebo group was 0.29 ( 95 % CI , 0.10 - 0.85 ) . The number of hip fracture per 1,000 patient-years was 14 and 49 for the alendronate and placebo groups , respectively . In the alendronate group , serum calcium and urinary D-Pyr levels decreased significantly during the follow-up period , while the levels in the placebo group were increased . BMD increased by 3.1 % in the alendronate group and decreased by 2.8 % in the placebo group ( P < 0.01 ) . Treatment with alendronate and vitamin D2 increases BMD in elderly women with PD and leads to the prevention of hip fractures OBJECTIVE The aim of this study was to compare bone mineral density ( BMD ) and biochemical markers of bone turnover in patients receiving long-term alendronate therapy who continued alendronate , were switched to raloxifene , or discontinued antiresorptive therapy . DESIGN , PATIENTS , AND INTERVENTIONS Ninety-nine ambulatory women who were diagnosed with postmenopausal osteoporosis and treated with alendronate ( 10 mg/d ) for a mean period of 43 months were r and omized to double-blind raloxifene ( 60 mg/d ; n = 33 ) , placebo ( n = 33 ) , or continuation of open-label alendronate ( n = 33 ) for 12 months . Patients continued their assigned treatment in a subsequent 12-month , open-label extension phase . All patients received supplemental calcium ( 500 mg/d ) and vitamin D ( 800 IU/d ) . MAIN OUTCOME MEASURES BMD ( lumbar spine , total femur , femoral neck , distal forearm , and total body ) and biochemical markers ( serum intact amino-terminal propeptide of type I procollagen , type 1 collagen cross-linked C-telopeptide , and osteocalcin ) were measured at baseline and follow-up visits . RESULTS Discontinuation of alendronate therapy result ed in a decrease in lumbar spine BMD at 12 months ( -2.66 % ; P < 0.05 ) , but did not change total femur BMD ( + 0.35 % ; nonsignificant ) . Raloxifene and alendronate , compared with discontinuation , prevented lumbar spine BMD loss ( -0.75 % and -0.54 % at 12 months , respectively ; P < 0.05 ) . Raloxifene and alendronate caused a similar increase in total femur BMD at 12 months ( 1.45 % and 1.56 % ; both P < 0.05 vs. baseline ; nonsignificant vs. discontinuation ) . Patients , who discontinued alendronate therapy experienced an increase in bone turnover . Bone turnover increases were less pronounced in patients taking raloxifene and were absent in those who continued alendronate . Of the three groups , mean bone turnover in raloxifene patients was the closest to premenopausal mean values . CONCLUSIONS BMD preservation and increase were most pronounced in patients continuing alendronate . Raloxifene treatment , compared with placebo , demonstrated beneficial effects on BMD and bone turnover after discontinuation of long-term alendronate therapy The prevention and treatment of glucocorticoid-induced osteoporosis is a major concern for rheumatologists since inflammatory joint disease is among the most common reasons for long-term glucocorticoid therapy . We used a r and omized placebo-controlled design to evaluate the efficacy of one-year cyclical etidronate therapy in preventing bone loss in 83 glucocorticoid-treated patients with rheumatoid arthritis , polymyalgia rheumatica , or giant cell arteritis . Glucocorticoid treatment duration was shorter than three months , and the starting dose was greater than 7.5 mg of prednisone-equivalent per day . Etidronate was given according to the st and ard cyclical schedule , i.e. 400 mg/d for periods of 14 days separated by 76-day intervals during which patients took 500 mg of supplemental calcium per day . The primary evaluation criterion was the change in lumbar spine bone mineral density after one year of etidronate therapy . Bone mineral density decreased by 1.94 + /- 0.61 % in the placebo group and increased by 0.86 + /- 0.6 % in the etidronate group , yielding a between-group difference of 2.8 + /- 0.86 % ( P = 0.002 ) . The difference was largest in postmenopausal women ( 3.38 + /- 1.11 % ; P = 0.004 ) . At the femoral neck , there was a smaller bone mineral density decrease in the etidronate than in the placebo group , but the difference ( 1.11 + /- 1.13 % ) was not statistically significant . The most common side effects were gastrointestinal symptoms and showed no difference between the two groups . Four fractures ( including one vertebral fracture ) occurred in the placebo group versus two ( including one vertebral ) in the etidronate group . Etidronate prevents glucocorticoid-induced lumbar spine bone loss in patients with rheumatoid arthritis , polymyalgia rheumatica , or giant cell arteritis BACKGROUND There is a high incidence of hip fractures in patients after hemiplegic stroke . Bone mineral density is decreased on the hemiplegic side in patients after stroke , correlating with the immobilization-induced bone resorption , the degree of paralysis , and hypovitaminosis D. The purpose of this study is to evaluate the effectiveness of risedronate sodium , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in men 65 years or older after stroke . METHODS We conducted an 18-month r and omized double-blind trial . Of 280 male patients 65 years or older who were poststroke , 140 received a daily dose of 2.5 mg risedronate sodium and the other 140 received placebo . Incidence of hip fractures in the 2 groups was compared . RESULTS Ten patients sustained hip fractures in the placebo group , and 2 hip fractures occurred in the risedronate group . The relative risk of a hip fracture was 0.19 ( 95 % confidence interval , 0.04 - 0.89 ) . The number of patients needing the treatment was 16 ( 95 % confidence interval , 9 - 32 ) . Bone mineral density increased by 2.5 % in the risedronate group and decreased by 3.5 % in the placebo group ( P<.001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 58.7 % in the risedronate group and by 37.2 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density and reduces hip fractures in elderly men who are poststroke Abstract : Raloxifene , a selective estrogen receptor modulator ( SERM ) , has been shown to improved bone mineral density ( BMD ) and serum lipid profiles in healthy postmenopausal women . The objective of this study was to examine the effects of raloxifene on BMD , biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis . This Phase II , multicenter , 24-month , double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women ( mean age ± SD : 60.2 ± 6.7 years ) with osteoporosis or low bone density ( baseline mean lumbar spine BMD T-score : −2.8 ) . Women were r and omly assigned to one of three treatment groups : placebo , 60 mg/day raloxifene-HCl ( RLX 60 ) or 150 mg/day raloxifene-HCl ( RLX 150 ) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3 . At 24 months , BMD was significantly increased in the lumbar spine ( + 3.2 % ) , femoral neck ( + 2.1 % ) , trochanter ( + 2.7 % ) and total hip ( + 1.6 % ) in the RLX 60 group compared with the placebo group ( p<0.05 ) . The RLX 150 group had increases in BMD similar to those observed with RLX 60 . A greater percentage of raloxifene-treated patients , compared with those receiving placebo , had increased BMD ( p<0.05 ) . Serum bone-specific alkaline phosphatase activity , serum osteocalcin , and urinary type I collagen : creatinine ratio were significantly decreased in the RLX-treated groups , compared with the placebo group ( p<0.01 ) . RLX 60 treatment significantly decreased serum levels of triglycerides , and total- and LDL-cholesterol levels ( p<0.01 ) . The rates of patient discontinuation and adverse events were not significantly different among groups . In this study , raloxifene increased bone density , decreased bone turnover , and improved the serum lipid profile with minimal adverse events , and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density SUMMARY Objective : To compare the effects of alendronate ( ALN ) 70 mg once weekly ( OW ) and risedronate ( RIS ) 5 mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density ( BMD ) in postmenopausal women with osteoporosis . Research design and methods : This was a 3-month , r and omised , double-blind , placebo-controlled study with a double-blind extension to 12 months . The study enrolled 549 postmenopausal women ( ALN 219 , RIS 222 and placebo ( PBO ) 108 ) who were > 60 years of age at outpatient centres . Main outcome measures : The primary endpoint was reduction in urine N-telopeptides of type 1 collagen ( NTx ) corrected for creatinine level at 3 months . Secondary parameters included change in BMD at the spine and hip at 6 and 12 months , NTx at 1,6 and 12 months , and serum bone-specific alkaline phosphatase ( BSAP ) at 1 , 3 , 6 and 12 months . Adverse experiences ( AEs ) were recorded throughout the study for an assessment of treatment safety profiles and tolerability . Results : Over 3 months , ALN produced a significantly greater mean reduction in urine NTx than did RIS ( −52 % vs −32 % , p < 0.001 ) , which was maintained at 12 months . ALN produced a significantly greater mean BMD increase than did RIS at 6 months , and it was maintained at 12 months at the lumbar spine ( 4.8 % vs 2.8 % , p < 0.001 ) and total hip ( 2.7 % vs 0.9 % , p < 0.001 ) , as well as at the trochanter and femoral neck . Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment . Study size did not allow for meaningful assessment of differences in fracture rates . Tolerability was generally similar between ALN , RIS and PBO , and the incidence of upper GIAEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups . Conclusion : In this study , ALN 70 mg OW produced a 50 % greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily . The treatments had similar safety profiles and were generally well-tolerated . Additional studies are needed comparing OW ALN with OW RIS , which became available after the commencement of the present study Objective : To compare the efficacy and tolerability of once-weekly ( OW ) alendronate ( ALN ) 70 mg and raloxifene ( RLX ) 60 mg daily in the treatment of postmenopausal osteoporosis . Design : This 12-month , r and omized , double-blind study enrolled 456 postmenopausal women with osteoporosis ( 223 ALN , 233 RLX ) at 52 sites in the United States . Efficacy measurements included lumbar spine ( LS ) , total hip , and trochanter bone mineral density ( BMD ) at 6 and 12 months , biochemical markers of bone turnover , and percent of women who maintained or gained BMD in response to treatment . The primary endpoint was percent change from baseline in LS BMD at 12 months . Adverse experiences were recorded to assess treatment safety and tolerability . Results : Over 12 months , OW ALN produced a significantly greater increase in LS BMD ( 4.4 % , P < 0.001 ) than RLX ( 1.9 % ) . The percentage of women with ≥ 0 % increase in LS BMD ( ALN , 94 % ; RLX , 75 % ; P < 0.001 ) and ≥ 3 % increase in LS BMD ( ALN , 66 % ; RLX , 38 % ; P < 0.001 ) were significantly greater with ALN than RLX . Total hip and trochanter BMD increases were also significantly greater ( P ≤0.001 ) with ALN . Greater ( P < 0.001 ) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months . No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen . Conclusion : ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months . A greater percentage of women maintained or gained BMD on ALN than RLX . Both medications had similar safety and tolerability profiles Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience . Ib and ronate is a highly potent nitrogen-containing bisphosphonate , proven to significantly increase vertebral and nonvertebral bone mineral density ( BMD ) when administered as a convenient intravenous injection . A recent double-blind , placebo-controlled , r and omized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ib and ronate injections , given once every 3 months , in 2862 women ( 55 - 76 years ) with postmenopausal osteoporosis [ one to four prevalent vertebral fractures and lumbar spine ( L1-L4 ) BMD T score of less than -2.0 and greater than -5.0 in > or=1 vertebra ] . All participants received daily vitamin D ( 400 IU ) and calcium ( 500 mg ) supplementation . The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years . However , although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo ( 9.2 % vs. 8.7 % vs. 10.7 % in the 1 mg , 0.5 mg and placebo groups , respectively ) , as well as in the incidence of nonvertebral and hip fractures , the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance . At the studied doses , intravenous ib and ronate injections also produced dose-dependent , but comparatively small , increases in lumbar spine BMD ( 4.0 % and 2.9 % , respectively ) and decreases in biochemical markers of bone resorption and formation , relative to placebo . Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover . In light of the clear dose-response relationship observed in this and other studies , this is likely to be achieved with higher intravenous doses of ib and ronate . The results of a recent phase II/III study ( Intermittent Regimen Intravenous Ib and ronate Study : the IRIS study ) provide support for this hypothesis The identification of risk factors for osteoporosis has been an essential step towards the underst and ing of the onset of the disease as well as of the osteoporosis-related fractures due to bone fragility . The present study has been aim ed at assessing whether a correlation may exist between the increment in bone mass , consequent to an antiresorption therapy , and the reduction in the incidence of fractures . Moreover , the possibility that such a reduction might result from the action of other factors , such as the changes in bone microstructure , has been investigated . A total of 2,000 osteoporotic women ( mean age : 68 + /- 9 years ) were enrolled in the study and divided at r and om into 4 treatment groups . Each group received one of the following treatments : Alendronate 10 mg/daily ( 1,000 patients ) , Clodronate 100 mg/weekly i.m . ( 800 patients ) , Risedronate 5 mg/dailt ( 100 patients ) , and Raloxifene 60 mg/daily ( 100 patients ) . Clinical evaluation was based on bone mineral density ( BMD ) assay on lumbar vertebrae ( L1-L4 ) by means of a DEXA ( Lunar DPX ) mineralometer , as well as on the incidence of fractures following both 12- and 24-month treatment periods . The results showed an overlapping pattern in patients treated with Alendronate or Risedronate , namely a significant increment in BMD after a 24-month treatment period , whereas such an increment in BMD was less evident in patients receiving either Clodronate or Risedronate after a 24-month treatment period . In addition , a total of 18 osteoporosis-related fractures were observed during the entire study period ; 10 out of 18 fractures occurred in the Alendronate treated group , whereas the remaining 8 fractures were observed in the Clodronate treated group . Fourteen fractures were detected in patients over 80-year old , whereas the remaining 4 occurred in patients aged from 70 to 79 years and appeared to be independent of both the T-score assigned and the BMD increment obtained as a result of the therapy . Such findings suggest that the plain monitoring of BMD appears not to be adequate to anticipate clearly the danger of the probable onset of additional fractures , while the higher incidence of fractures in patients over 80-year old evidence s that " old age " has to be considered the most serious risk factor for osteoporosis , since it is also the real responsible factor for changes taking place in bone microstructure Long-term use of high-dose corticosteroids often results in bone loss , which may lead to osteoporosis-related fractures . This was a multicenter , double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy ( prednisone > or = 7.5 mg/day or equivalent ) for 6 or more months were r and omized to receive placebo , risedronate 2.5 mg/day , or risedronate 5 mg/day for 12 months . All patients received calcium 1 g and vitamin D 400 IU daily . The primary endpoint was lumbar spine bone mineral density ( BMD ) at month 12 . Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures . Overall , there were statistically significant treatment effects on BMD at 12 months at the lumbar spine ( p < 0.001 ) , femoral neck ( p = 0.004 ) , and trochanter ( p = 0.010 ) . Risedronate 5 mg increased BMD at 12 months by a mean ( SEM ) of 2.9 % ( 0.49 % ) at the lumbar spine , 1.8 % ( 0.46 % ) at the femoral neck , and 2.4 % ( 0.54 % ) at the trochanter , whereas BMD was maintained only in the control group . Although not powered to show fracture efficacy , we observed a reduction in the incidence of vertebral fractures of 70 % in the combined risedronate treatment groups , relative to placebo ( p = 0.042 ) . Risedronate was well tolerated , had a good safety profile , and was not associated with gastrointestinal adverse events . We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis Estrogen replacement therapy ( ERT ) decreases total serum calcium by about 0.5 mg/dl in postmenopausal women with primary hyperparathyroidism ( PHPT ) . We investigated the ability of raloxifene , which has skeletal antiresorptive properties similar to those of ERT , to decrease serum calcium concentrations and markers of bone turnover in PHPT . Eighteen postmenopausal women with asymptomatic PHPT were r and omized to 8 wk of raloxifene ( 60 mg/d ) or placebo , followed by a 4-wk washout . At baseline , the groups were well matched . The calcium concentration decreased significantly by 8 wk of raloxifene administration ( 10.8 + /- 0.2 to 10.4 + /- 0.2 mg/dl ; P < 0.05 ) , as did markers of bone resorption and formation [ osteocalcin , 11.4 + /- 1.6 to 9.9 + /- 1.6 nmol/liter ( P < 0.05 ) ; serum N-telopeptide , 21.2 + /- 3.4 to 17.3 + /- 2.8 nmol bone collagen equivalents/liter ( P < 0.05 ) ] . Four weeks after raloxifene was discontinued , indices were indistinguishable from baseline . Raloxifene administration did not affect serum PTH , 1,25-dihydroxyvitamin D , total alkaline phosphatase , or urinary calcium excretion . Calcium and bone marker changes were therefore similar to those observed with ERT in PHPT . This short-term study suggests that raloxifene may be a useful approach to the treatment of postmenopausal women with mild PHPT Cyclical etidronate is well established in the treatment of postmenopausal osteoporosis , but there are less data on its effects on bone loss in the early menopause . The aim of this study was to investigate the effects of cyclical etidronate therapy on bone loss in the lumbar spine and proximal femur in early menopausal women . Seventy-seven women aged over 40 yr who had ceased menstruating 6 - 36 mo prior to enrollment into the study were recruited into an open , r and omized controlled study of cyclical etidronate therapy . Bone mineral density in the lumbar spine and proximal femur was assessed by dual-energy X-ray absorptiometry using a Lunar DPX bone densitometer . Fifty-five women completed the study . At the end of the 104-wk study period , significant treatment effects were observed in both the lumbar spine and the proximal femur . The estimated mean treatment effect in the lumbar spine was 2.79 % ( 95 % confidence interval 0.47 , 5.10 ; p = 0.019 ) . Corresponding figures for the femoral neck and greater trochanter were 3.23 % ( 0.63 , 5.82 ; p = 0 . 016 ) and 3.77 % ( 1.09 , 6.45 ; p = 0.007 ) . No significant differences between the groups were demonstrated at Ward 's triangle . These results demonstrate that cyclical etidronate therapy prevents bone loss in the spine and proximal femur in early postmenopausal women and provides a safe and effective alternative for women who are unwilling or unable to tolerate hormone replacement therapy Severe osteoporosis frequently is observed after organ transplantation . In kidney transplantation , it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established . Eighty kidney recipients were included in a r and omized controlled prospect i ve intervention trial . Treated patients ( n = 40 ) received an injection of ib and ronate , a bisphosphonate , immediately before and at 3 , 6 , and 9 mo after transplantation . The primary outcome measured was the change in bone mineral density . Secondary measures included graft outcome , spinal deformities , fracture rate , body height , and hormonal and metabolic data . Loss of spongy and cortical bone after transplantation was prevented by ib and ronate . Changes of bone mineral density ( ib and ronate versus controls ) were as follows : lumbar spine , -0.9 + /- 6.1 % versus -6.5 + /- 5.4 % ( P < 0.0001 ) ; femoral neck , + 0.5 + /- 5.2 % versus -7.7 + /- 6.5 % ( P < 0.0001 ) ; and midfemoral shaft , + 2.7 + /- 12.2 % versus -4.0 + /- 10.9 % ( P = 0.024 ) . Fewer spinal deformities developed with ib and ronate ( 7 patients with 7 deformities versus 12 patients with 23 deformities ; P = 0.047 ) . Loss of body height was 0.5 + /- 1.0 cm versus 1.1 + /- 1.0 cm in control subjects ( P = 0.040 ) . Two bone fractures occurred in each group . There were fewer acute rejection episodes with ib and ronate ( 11 versus 22 ; P = 0.009 ) . Graft function after 1 yr was comparable . Bone loss , spinal deformation , and loss of body height during the first year after kidney transplantation are prevented by injection of ib and ronate at intervals of 3 mo . The smaller number of rejection episodes of the ib and ronate-treated group should be confirmed and its mechanism should be explored in additional studies Abstract . Cardiac transplantation is associated with severe bone loss caused by glucocorticoids , immunosuppressive treatment , and other factors . Treatment protocol s for the prevention of bone loss is being studied . Forty patients who underwent cardiac transplantation were r and omly given calcitonin ( n= 13 ; 100 UI/d , nasal route ) , etidronate ( n= 14 ; cyclical treatment 400 mg p.o./d/2 weeks/3 months ) , or calcidiol ( n= 13 ; 32,000 IU/weekly ) therapy for at least 18 months . Serum parameters ( Ca , P , alkaline phosphatase , osteocalcin , intact PTH ) , urinary calcium , and vertebral mineral density ( VMD ; L2–L4 , DXA Hologic QDR 1000 ) were measured immediately before treatment and after 6 , 12 , and 18 months of therapy after cardiac transplantation . Patients with cardiac transplantation had a VMD significantly lower than age and sex-matched Spanish controls . Prevalence of osteoporosis ( Z-score below −2 SD ) was 30 % . Osteocalcin levels increased at 6 , 12 , and 18 months of treatment in the three groups . After 18 months of treatment , VMD increased significantly in the calcidiol 4.9 % , vs. −1.19 % and −0.19 % in the calcitonin and etidronate groups , respectively . A lower incidence of fracture was found in patients treated with calcidiol during the study . In summary , we have found in this open r and omized study that calcidiol was the most effective drug in the prevention and treatment of bone loss in patients after cardiac transplantation OBJECTIVE Risedronate , a new pyridinyl bisphosphonate , is a potent antiresorptive bone agent . This study examines the safety and efficacy of daily , oral risedronate therapy for the prevention of corticosteroid-induced bone loss . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study was conducted in 224 men and women who were initiating long-term corticosteroid treatment . Patients received either risedronate ( 2.5 mg or 5 mg ) or placebo daily for 12 months . Each patient also received 500 mg of elemental calcium daily . The primary outcome measure was the percentage of change in lumbar spine bone mineral density ( BMD ) . Secondary measures included proximal femur BMD and incidence of vertebral fractures . RESULTS After 12 months , the lumbar spine BMD ( mean + /- SEM ) did not change significantly compared with baseline in the 5-mg ( 0.6 + /- 0.5 % ) or the 2.5-mg ( -0.1 + /- 0.7 % ) risedronate groups , while it decreased in the placebo group ( -2.8 + /- 0.5 % ; P < 0.05 ) . The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 + /- 0.8 % at the lumbar spine ( P < 0.001 ) , 4.1 + /- 1.0 % at the femoral neck ( P < 0.001 ) , and 4.6 + /- 0.8 % at the femoral trochanter ( P < 0.001 ) . A trend toward a decrease in the incidence of vertebral fracture was observed in the 5-mg risedronate group compared with the placebo group ( 5.7 % versus 17.3 % ; P = 0.072 ) . Risedronate was well tolerated , and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups . CONCLUSION Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment BACKGROUND The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention . To test this hypothesis , the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial ( P-1 ) in 1992 . METHODS Women ( N=13388 ) at increased risk for breast cancer because they 1 ) were 60 years of age or older , 2 ) were 35 - 59 years of age with a 5-year predicted risk for breast cancer of at least 1.66 % , or 3 ) had a history of lobular carcinoma in situ were r and omly assigned to receive placebo ( n=6707 ) or 20 mg/day tamoxifen ( n=6681 ) for 5 years . Gail 's algorithm , based on a multivariate logistic regression model using combinations of risk factors , was used to estimate the probability ( risk ) of occurrence of breast cancer over time . RESULTS Tamoxifen reduced the risk of invasive breast cancer by 49 % ( two-sided P<.00001 ) , with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups , respectively . The decreased risk occurred in women aged 49 years or younger ( 44 % ) , 50 - 59 years ( 51 % ) , and 60 years or older ( 55 % ) ; risk was also reduced in women with a history of lobular carcinoma in situ ( 56 % ) or atypical hyperplasia ( 86 % ) and in those with any category of predicted 5-year risk . Tamoxifen reduced the risk of noninvasive breast cancer by 50 % ( two-sided P<.002 ) . Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69 % , but no difference in the occurrence of estrogen receptor-negative tumors was seen . Tamoxifen administration did not alter the average annual rate of ischemic heart disease ; however , a reduction in hip , radius ( Colles ' ) , and spine fractures was observed . The rate of endometrial cancer was increased in the tamoxifen group ( risk ratio = 2.53 ; 95 % confidence interval = 1.35 - 4.97 ) ; this increased risk occurred predominantly in women aged 50 years or older . All endometrial cancers in the tamoxifen group were stage I ( localized disease ) ; no endometrial cancer deaths have occurred in this group . No liver cancers or increase in colon , rectal , ovarian , or other tumors was observed in the tamoxifen group . The rates of stroke , pulmonary embolism , and deep-vein thrombosis were elevated in the tamoxifen group ; these events occurred more frequently in women aged 50 years or older . CONCLUSIONS Tamoxifen decreases the incidence of invasive and noninvasive breast cancer . Despite side effects result ing from administration of tamoxifen , its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease The efficacy and safety of treatment with oral alendronate ( ALN ) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind , r and omized , multicenter study of Japanese patients with involutional osteoporosis . The primary efficacy end point was the percent change from baseline in the lumbar spine ( L1–L4 ) bone mineral density ( BMD ) after 52 weeks of treatment . In this study , 328 patients were r and omized to ALN 5 mg once daily ( 160 patients ) or ALN 35 mg once weekly ( 168 patients ) . The adjusted mean percent change from baseline in lumbar spine ( L1–L4 ) BMD after 52 weeks of treatment was 5.8 % and 6.4 % in the once-daily group and the once-weekly group , respectively ( both P < 0.001 ) . The 95 % confidence interval for the difference in spine BMD change between the two treatment groups was −0.31 % to 1.48 % , indicating that the two regimens were therapeutically equivalent , since the confidence interval fell entirely within the predefined equivalence criterion ( ±1.5 % ) . The time course of the spine BMD increase was also similar for both regimens . Regarding total hip BMD , mean changes from baseline at 52 weeks were 2.8 % and 3.0 % in the once-daily group and the once-weekly group , respectively . In addition , the bone markers ( urinary deoxypyridinoline , urinary type-I collagen N-telopeptides , and serum bone-specific alkaline phosphatase ) were reduced to a similar level by either treatment throughout the treatment period . The tolerability and safety profiles were also similar between the treatment groups . Taken together , we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) . Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin CONTEXT Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis , but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown . OBJECTIVE To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe , and how they compare with monotherapy in community-dwelling elderly women . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING AND PARTICIPANTS Five hundred seventy-three community-dwelling women age 65 years or older were screened : 485 completed screening and 373 ( aged 65 to 90 years ) were r and omized following a 3-month , open-label , run-in phase with hormone replacement and alendronate placebo . The trial was conducted at a single academic US medical center from January 1996 to May 2001 . INTERVENTIONS Participants were r and omly assigned in a 2 x 2 factorial design to receive hormone replacement ( conjugated equine estrogen , 0.625 mg/d , with or without medroxyprogesterone , 2.5 mg/d ) and alendronate , 10 mg daily , both agents , or neither . All participants received calcium and vitamin D supplements . MAIN OUTCOME MEASURES Annualized change in bone mineral density of the hip and spine and occurrence of adverse events . RESULTS Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy , with mean ( SD ) increases of 5.9 % ( 3.8 ) at the total hip , 10.4 % ( 5.4 ) at the posteroanterior lumbar spine , and 11.8 % ( 6.8 ) at the lateral lumbar spine . Mean ( SD ) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone ( 4.2 % [ 3.8 ] vs 3.0 % [ 4.9 ] ; P<.05 , respectively ) , and alendronate result ed in more responders to therapy . All therapies were well tolerated and participant retention was 90 % at 3 years . CONCLUSIONS Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort . Alendronate was superior to hormone replacement , and combination therapy was superior to either therapy alone . Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy Ovarian failure after allogeneic stem cell transplant ( allo-SCT ) is an important risk factor for development of osteoporosis . We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT . A total of 60 women with osteoporosis or osteopenia were divided r and omly into four groups of 15 women each . Group 1 was treated with calcium and vitamin D alone , group 2 received the same treatment in combination with hormone replacement therapy ( HRT ) , group 3 received risedronate ( 35 mg weekly , orally for 1 year ) and group 4 zoledronic acid ( 3 monthly doses of 4 mg ( intravenous ) ) . All groups were similar for age , body mass index , underlying disease and time elapsed from transplant . Lumbar and femoral bone mineral density ( BMD ) were measured at baseline and after 12 months , together with serum osteocalcin and urinary hydroxyproline . At 12 months , a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2 . Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck . Zoledronic acid increased significantly both lumbar and femoral BMD . In groups 3 and 4 the hydroxyproline excretion was significantly reduced , while osteocalcin mildly increased only in group 4 . In conclusion , bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT OBJECTIVES To determine the efficacy of alendronate treatment on risk of vertebral fracture in a subgroup of women from the Fracture Intervention Trial who had bone mineral density T scores between -1.6 and -2.5 at the femoral neck and to describe how soon after initiation of therapy alendronate becomes effective and whether it is consistent in women with and without existing radiographic vertebral fracture . PATIENTS AND METHODS From May 1992 to March 1997 , postmenopausal women aged 55 to 80 years were r and omized to receive alendronate at 5 mg/d for 2 years and 10 mg/d thereafter or placebo for up to 4.5 years ( mean , 3.8 years ) in a controlled , double-blind , multicenter study . RESULTS A total of 3737 postmenopausal women were included in the study , 1878 in the alendronate group and 1859 in the placebo group . Risk of vertebral fracture was significantly reduced by alendronate compared with placebo for clinical ( relative risk [ RR ] , 0.40 ; 95 % confidence interval [ CI ] , 0.19 - 0.76 ; P=.005 ) and radiographic ( RR , 0.57 ; 95 % CI , 0.41 - 0.81 ; P=-.002 ) fracture . The reductions in vertebral fracture risk were consistent in women with and without an existing radiographic vertebral fracture for clinical ( RR , 0.34 ; 95 % CI , 0.12 - 0.84 ; and RR , 0.46 ; 95 % CI , 0.16 - 1.17 ; respectively ) and radiographic ( RR , 0.53 ; 95 % CI , 0.34 - 0.82 ; and RR , 0.64 ; 95 % CI , 0.38 - 1.10 ; respectively ) fractures . In both groups , the effect of alendronate on clinical vertebral fracture was noted soon after therapy was initiated . The absolute risk of vertebral fracture was low in women without a baseline radiographic fracture . CONCLUSIONS In women with low bone mass who do not meet the bone mineral density criterion for osteoporosis , alendronate is effective in reducing the risk of vertebral fractures . The absolute benefit of this therapy in women with a T score between -1.6 and -2.5 is greater in women with an existing vertebral fracture and /or with other risk factors . The effect of alendronate occurs early CONTEXT Raloxifene hydrochloride , a selective estrogen receptor modulator , prevents bone loss in postmenopausal women , but whether it reduces fracture risk in these women is not known . OBJECTIVE To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures . DESIGN The Multiple Outcomes of Raloxifene Evaluation ( MORE ) study , a multicenter , r and omized , blinded , placebo-controlled trial . SETTING AND PARTICIPANTS A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis . The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events . INTERVENTIONS Participants were r and omized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills ; in addition , all women received supplemental calcium and cholecalciferol . MAIN OUTCOME MEASURES Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits . Nonvertebral fracture was ascertained by interview at 6-month-interim visits . Bone mineral density was determined annually by dual-energy x-ray absorptiometry . RESULTS At 36 months of the evaluable radiographs in 6828 women , 503 ( 7.4 % ) had at least 1 new vertebral fracture , including 10.1 % of women receiving placebo , 6.6 % of those receiving 60 mg/d of raloxifene , and 5.4 % of those receiving 120 mg/d of raloxifene . Risk of vertebral fracture was reduced in both study groups receiving raloxifene ( for 60-mg/d group : relative risk [ RR ] , 0.7 ; 95 % confidence interval [ CI ] , 0.5 - 0.8 ; for 120-mg/d group : RR , 0.5 ; 95 % CI , 0.4 - 0.7 ) . Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture . Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly ( RR , 0.9 ; 95 % CI , 0.8 - 1.1 for both raloxifene groups combined ) . Compared with placebo , raloxifene increased bone mineral density in the femoral neck by 2.1 % ( 60 mg ) and 2.4 % ( 120 mg ) and in the spine by 2.6 % ( 60 mg ) and 2.7 % ( 120 mg ) P<0.001 for all comparisons ) . Women receiving raloxifene had increased risk of venous thromboembolus vs placebo ( RR , 3.1 ; 95 % CI , 1.5 - 6.2 ) . Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer . CONCLUSIONS In postmenopausal women with osteoporosis , raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture Background : Glucocorticoids are associated with a reduction in bone density and an increased risk of fracture . Concurrent treatment with bisphosphonates reduces bone loss and may prevent fractures . A r and omised study was performed to determine whether treatment with cyclical etidronate and /or calcium for 5 years prevents fractures or reverses/reduces bone loss in patients receiving glucocorticoid treatment for asthma . Methods : A multicentre , r and omised , parallel group comparison of etidronate alone , calcium alone , etidronate + calcium , and no treatment , with stratification according to level of glucocorticoid exposure was carried out in 39 chest clinics in the UK . Three hundred and forty nine postmenopausal female and male out patients with asthma aged 50–70 years were r and omised . The main outcome measures were fractures and changes in bone mineral density ( BMD ) . Results : Overall , 8 % of the patients experienced symptomatic fractures and 17.5 % developed either a symptomatic fracture and /or a semiquantitative vertebral fracture by the end of 5 years There were no significant differences between the four treatment groups . Comparing etidronate with no etidronate , the rates of new fractures were not significantly different for symptomatic fractures ( OR 1.07 ( 95 % CI 0.46 to 2.47 ) ) or for any fractures ( OR 0.82 ( 95 % CI 0.45 to 1.47 ) ) . For the comparison of calcium with no calcium the corresponding ORs were 1.43 ( 95 % CI 0.62 to 3.33 ) and 0.91 ( 95 % CI 0.50 to 1.63 ) . In post hoc analysis the effect of etidronate was greater in women than in men ( interaction p value 0.02 ) with the fracture incidence roughly halved ( OR 0.39 , 95 % CI 0.14 to 0.99 ) . Etidronate increased BMD at the lumbar spine by 4.1 % ( p = 0.001 ) while calcium had no significant effect . At the proximal femur the effects of treatment were not significant ( relative increases etidronate 1.6 % ; calcium 1.1 % ) . The rate of new fractures in patients with fractures at entry ( 23.7 % ) was higher than in those without fractures at entry ( 14.3 % ) : OR 1.87 ( 95 % CI 1.06 to 3.07 ) . No association was found between change in BMD and new fractures . Conclusions : In patients receiving glucocorticoids for asthma etidronate significantly increased BMD over 5 years at the lumbar spine but not at the hip and had little if any protective effect against fractures , except possibly in postmenopausal women . The effects of calcium were not significant . Combination treatment had no advantage but increased unwanted effects The efficacy and safety of oral pamidronate was examined in a double-blind , placebo-controlled trial in women and men with established osteoporosis . Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were r and omized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years . In addition , all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium . Pamidronate increased significantly bone mineral density of the lumbar spine ( LS-BMD ) and of the femoral neck ( FN-BMD ) . The total increase in BMD of the spine after 5 years of treatment was 14.3 % . Lateral spine radiographs were obtained at baseline and after 3 years of treatment . Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo ( 33.3 % ) and in 5 of 46 patients treated with pamidronate ( 11 % ) . The relative risk was 0.33 ( 95 % CI , 0.14 - 0.77 ) . Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients . One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis Abstract : To demonstrate the clinical benefit of 2.5 mg daily risedronate in the treatment of involutional osteoporosis , the effect of risedronate on bone mineral density ( BMD ) of the lumbar spine was compared with that of etidronate , selected as a representative of the bisphosphonates currently marketed in Japan . In this multicenter , r and omized , double-masked , active ( etidronate ) controlled comparative study , a total of 235 Japanese patients with involutional osteoporosis were r and omized to receive either treatment with 2.5 mg/day of risedronate for 48 weeks or intermittent treatment with etidronate ( 4 cycles of 2 weeks of treatment with 200 mg/day followed by 10-week medication-free periods ) . All patients received 200 mg of calcium supplement daily in the form of the calcium lactate . Bone mineral density of the lumbar spine ( L2–L4 BMD ) was determined at 12 , 24 , 36 and 48 weeks by dual-energy X-ray absorptiometry . The primary endpoint was the percent change in L2–L4 BMD from baseline to the time of final evaluation . Changes in biochemical markers of bone turnover and safety profiles were also compared . A significant increase in L2–L4 BMD was observed at 12 weeks after initiation of therapy in both the risedronate ( 2.8 % ) and etidronate ( 1.8 % ) groups . The increase in L2–L4 BMD at the time of final evaluation in the risedronate group ( 4.9 % ) was significantly greater ( p = 0.002 ) than that in the etidronate group ( 3.1 % ) . The changes in bone resorption markers ( urinary total deoxypyridinoline and N-terminal telopeptide of type I collagen ) from baseline to 48 weeks were −37.6 % and −41.3 % for risedronate and −22.5 % and −26.6 % for etidronate , respectively . New vertebral fractures or deterioration of existing fractures were observed in 2.8 % ( 3/106 ) of the patients in the etidronate group , while no such cases ( 0/101 ) were observed in the risedronate group . No significant difference in the incidence of adverse events was found between two treatments . Daily oral risedronate ( 2.5 mg ) exhibited efficacy superior to that of intermittent cyclical etidronate ( 200 mg ) in increasing L2–L4 BMD , and was well tolerated by Japanese patients with involutional osteoporosis BACKGROUND A double blind , placebo controlled study was undertaken to determine the effects of 104 weeks of intermittent cyclical etidronate therapy on bone mineral density ( BMD ) in patients undergoing long term oral corticosteroid therapy . METHODS Forty nine patients of mean age 59 years on long term ( > 6 months ) corticosteroid treatment were r and omised to receive either 400 mg/day etidronate or placebo for 14 days followed in both groups by calcium ( equivalent to 97 mg elemental Ca/day ) with vitamin D ( 400 IU ) for 76 days . The cycle was repeated a total of eight times over a period of two years . Dual energy x ray absorptiometry ( DEXA ) measurements of the lumbar spine and hip BMD and biochemical bone marker analyses were performed at baseline and every six months . RESULTS Twenty six patients ( 10 men ) received cyclical etidronate and 23 ( nine men ) received placebo . The mean ( SD ) dose of corticosteroid ( prednisone or equivalent ) at baseline in the etidronate group was 8 ( 4 ) mg/day and in the placebo group was 7 ( 4 ) mg/day . Most of the patients ( 43 % ) suffered from asthma . Forty one patients completed the study ( 22 in the etidronate group and 19 in the placebo group ) . All had a low BMD at entry and with treatment a significant difference was observed between groups in the mean ( SE ) percentage change from baseline in lumbar spine BMD at week 104 of 4.5 (1.65)% ( p = 0.007 ) with a 95 % confidence interval ( CI ) of 1.12 to 7.87 % . No clinical ly or statistically significant treatment differences were observed at the hip or with bone markers . The incidence of adverse events was similar in the two groups . CONCLUSIONS The results show that intermittent cyclical etidronate therapy with calcium and vitamin D supplementation significantly increases lumbar spine BMD in patients with osteoporosis result ing from long term treatment with corticosteroids Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( < 58 kg ) , smoker , family history of hip fracture , or fair or poor self reported health . Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry BACKGROUND Results of observational studies suggest that hormone replacement therapy ( HRT ) could reduce the risk of coronary heart disease ( CHD ) , but those of r and omised trials do not indicate a lower risk in women who use oestrogen plus progestagen . The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infa rct ion . METHODS The study was a r and omised , blinded , placebo controlled , secondary prevention trial of postmenopausal women , age 50 - 69 years ( n=1017 ) who had survived a first myocardial infa rct ion . Individuals were recruited from 35 hospitals in Engl and and Wales . Women received either one tablet of oestradiol valerate ( 2 mg ; n=513 ) or placebo ( n=504 ) , daily for 2 years . Primary outcomes were reinfa rct ion or cardiac death , and all-cause mortality . Analyses were by intention-to-treat . Secondary outcomes were uterine bleeding , endometrial cancer , stroke or other embolic events , and fractures . FINDINGS Frequency of reinfa rct ion or cardiac death did not differ between treatment groups at 24 months ( rate ratio 0.99 , 95 % CI 0.70 - 1.41 , p=0.97 ) . Similarly , the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant ( 0.79 , 0.50 - 1.27 , p=0.34 ) . The relative risk of any death ( 0.56 , 0.23 - 1.33 ) and cardiac death ( 0.33 , 0.11 - 1.01 ) was lowest at 3 months post-recruitment . INTERPRETATION Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infa rct ion Both raloxifene ( RLX ) and alendronate ( ALN ) can treat and prevent new vertebral fractures , increase bone mineral density ( BMD ) , and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis . This phase 3 , r and omized , double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis ( femoral neck BMD T-score , less than -2 ) . Women ( aged < or = 75 yr ; > or = 2 yr since their last menstrual period ) received placebo , RLX 60 mg/d , ALN 10 mg/d , or RLX 60 mg/d and ALN 10 mg/d combined . At baseline , 6 and 12 months , BMD was measured by dual x-ray absorptiometry . The bone turnover markers serum osteocalcin , bone-specific alkaline phosphatase , and urinary N- and C-telopeptide corrected for creatinine were measured . The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant ( P > 0.10 ) in a two-way ANOVA model . All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups , and between the RLX and RLX+ALN groups ( P < 0.05 ) . On average , lumbar spine BMD increased by 2.1 , 4.3 , and 5.3 % from baseline with RLX , ALN , and RLX+ALN , respectively . The increase in femoral neck BMD in the RLX+ALN group ( 3.7 % ) was greater than the 2.7 and 1.7 % increases in the ALN ( P = 0.02 ) and RLX ( P < 0.001 ) groups , respectively . The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0 % with placebo , -23.8 to -46.5 % with RLX , -42.3 to -74.2 % with ALN , and -54.1 to -81.0 % in the RLX+ALN group . RLX and ALN increased lumbar spine and femoral neck BMD , and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner , because the interaction effects were not significant . Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group , it is not known how well these changes correlate to the clinical outcome of fracture . RLX+ALN reduced bone turnover more than either drug alone , result ing in greater BMD increment , but whether this difference reflects better fracture risk reduction was not assessed in this study BACKGROUND Receptor activator of nuclear factor-kappaB lig and ( RANKL ) is essential for osteoclast differentiation , activation , and survival . The fully human monoclonal antibody denosumab ( formerly known as AMG 162 ) binds RANKL with high affinity and specificity and inhibits RANKL action . METHODS The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density ( T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur ) . Subjects were r and omly assigned to receive denosumab either every three months ( at a dose of 6 , 14 , or 30 mg ) or every six months ( at a dose of 14 , 60 , 100 , or 210 mg ) , open-label oral alendronate once weekly ( at a dose of 70 mg ) , or placebo . The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months . Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase . RESULTS Denosumab treatment for 12 months result ed in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent ( as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo ) , at the total hip of 1.9 to 3.6 percent ( as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo ) , and at the distal third of the radius of 0.4 to 1.3 percent ( as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo ) . Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab . The duration of the suppression of bone turnover appeared to be dose-dependent . CONCLUSIONS In postmenopausal women with low bone mass , denosumab increased bone mineral density and decreased bone resorption . These preliminary data suggest that denosumab might be an effective treatment for osteoporosis . ( Clinical Trials.gov number , NCT00043186 . ) OBJECTIVE : To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen . METHODS : The Multiple Outcomes of Raloxifene Evaluation , a multicenter , r and omized , double-blind trial , enrolled 7,705 postmenopausal women with osteoporosis . Women were r and omly assigned to raloxifene 60 mg/d or 120 mg/d or placebo . Outcomes included venous thromboembolism , cataracts , gallbladder disease , and endometrial hyperplasia or cancer . RESULTS : During a mean follow-up of 3.3 years , raloxifene was associated with an increased risk for venous thromboembolism ( relative risk [ RR ] 2.1 ; 95 % confidence interval [ CI ] 1.2–3.8 ) . The excess event rate was 1.8 per 1,000 woman-years ( 95 % CI −0.5–4.1 ) , and the number needed to treat to cause 1 event was 170 ( 95 % CI 100–582 ) over 3.3 years . Risk in the raloxifene group was higher than in the placebo group for the first 2 years , but decreased to about the same rate as in the placebo group thereafter . Raloxifene did not increase risk for cataracts ( RR 0.9 ; 95 % CI 0.8–1.1 ) , gallbladder disease ( RR 1.0 ; 95 % CI 0.7–1.3 ) , endometrial hyperplasia ( RR 1.3 ; 95 % CI 0.4–5.1 ) , or endometrial cancer ( RR 0.9 ; 95 % CI 0.3–2.7 ) . CONCLUSION : Raloxifene was associated with an increased risk for venous thromboembolism , but there was no increased risk for cataracts , gallbladder disease , endometrial hyperplasia , or endometrial cancer . LEVEL OF EVIDENCE : Abstract . The aim of this study was to assess whether early intermittent I.V. administration of disodium pamidronate can effectively achieve primary prevention of glucocorticoid-induced osteoporosis ( GIOP ) . A total of 27 in- or out patients who required first-time , long-term corticosteroid therapy at a daily dose of at least 10 mg prednisolone were studied . Patients were r and omly selected to receive either pamidronate and calcium or calcium alone . Patients allocated to pamidronate treatment ( pamidronate group ) received a first intravenous infusion of 90 mg pamidronate simultaneously with the initiation of their steroid treatment . Subsequently , they received 30 mg pamidronate , intravenously , every 3 months , for as long as steroid therapy was continued . As with the control patients ( calcium group ) , they were put on a daily 800-mg elemental calcium supplement given as calcium carbonate . Lumbar spine and hip ( total and subregions ) bone mineral densities ( BMDs ) were measured at the start and every 3-months by dual-energy X-ray absorptiometry ( Hologic ® QDR-2000 ) . Over 1 year , the pamidronate group showed a significant BMD increase in the lumbar spine ( 3.6 % ) , and at all sites of the hip ( 2.2 % at the femoral neck ) . In the calcium group , a significant BMD reduction was registered at the lumbar spine ( −5.3 % ) and at the femoral neck ( −5.3 % ) . Differences between the groups were significant at all sites measured . Intermittent intravenous pamidronate effectively achieves primary prevention of GIOP , as assessed by BMD measurements over 1 year BACKGROUND High doses of corticosteroids , and the use of alkylating agents like cyclophosphamide with subsequent hypogonadism , have been implicated in the pathogenesis of chemotherapy-induced osteoporosis . In this study , we evaluated whether intravenous pamidronate can prevent bone loss and reduce vertebral fractures in patients with malignant lymphoma who were receiving chemotherapy . METHODS We enrolled 50 patients who had newly diagnosed stage III or IV malignant lymphoma . All patients were assigned r and omly to receive either intravenous pamidronate or placebo . Pamidronate ( 30 mg per treatment ) or placebo was given at 3-month intervals for 12 months . Five patients in the control group dropped out during the trial . The main outcomes were the incidence of vertebral fractures and changes in bone mineral density of the lumbar spine and proximal femur . RESULTS During the 12-month study , 6 ( 30 % ) of the 20 patients in the control group and 1 ( 4 % ) of the 25 patients in the pamidronate group developed new vertebral fractures ( P = 0.01 ) . In the control group , the mean percentage changes in bone mineral density were -11.2 % in the lumbar spine and -4.5 % in the femoral neck . In contrast , pamidronate treatment led to minor losses of bone mineral density at both sites ( -2.7 % at the lumbar spine ; -2.3 % at the femoral neck ) . The difference between the groups was significant at the lumbar spine ( P = 0.005 ) . CONCLUSION Pamidronate reduces trabecular bone loss and the risk of new vertebral fractures in patients with malignant lymphoma receiving chemotherapy 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 The purpose of the present study was to compare the effects of treatment with etidronate and alendronate on bone resorption , back pain , and activities of daily living ( ADL ) in elderly women with vertebral fractures . Fifty elderly women , 63 - 84 years of age , with back pain due to osteoporotic vertebral fractures were r and omly divided into two groups with 25 patients in each group : the cyclical etidronate treatment group ( 200 mg/day for 2 weeks per 3 months ) and the alendronate treatment group ( 5 mg/day ) . The level of urinary cross-linked N-terminal telopeptides of type I collagen ( NTx ) measured by an enzyme-linked immunosorbent assay , back pain evaluated with the face scale score , and the ADL score ( disability ) determined with a question naire were assessed before and 3 and 6 months after the start of treatment . No significant differences in these parameters were found between the two groups before the treatment . The urinary NTx level , the face scale score , and the ADL score decreased significantly in both groups . Although the reduction in the urinary NTx level was significantly greater in the alendronate group than in the etidronate group , the reduction in the face scale score was transiently significantly greater in the etidronate group than in the alendronate group . However , changes in the ADL score did not significantly differ between the two groups . The present study showed that although back pain was reduced and ADL was improved in both treatment groups of elderly women with vertebral fractures , the mechanism for the reduction in back pain differs to some extent between the two treatment groups . A double-blind placebo-controlled study is needed to confirm the therapeutic effects of these agents on back pain and deterioration of ADL Significant decreases in bone mineral density ( BMD ) occur on the hemiplegic side in chronic stroke patients , which correlate with the degree of paralysis and hypovitaminosis D. In this double-blind , r and omized , and prospect i ve study of 98 patients with hemiplegia involving both an upper and lower extremity ( 55 males and 53 females ; mean age , 71.4 + /- 0.6 years ) after an acute stroke , 49 were given etidronate for 56 weeks and 49 received a placebo . The BMD was measured by computed X-ray densitometry ( CXD ) of the second metacarpal bone bilaterally . Forty age-matched control subjects were followed for 56 weeks . At baseline , both groups had 25-hydroxyvitamin D [ 25(OH)D ] insufficiency , increased serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen ( ICTP ) , and low serum concentrations of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1,25(OH)2D . The BMD on the hemiplegic side decreased by 2.3 % and 4.8 % in the etidronate and placebo groups , respectively ( p = 0.0003 ) . After treatment , the serum 1,25(OH)2D concentration increased by 62.2 % in the etidronate group and decreased by 12.4 % in the placebo group . The etidronate group had significant decreases in the serum ionized calcium and ICTP and increases in PTH and bone Gla protein ( BGP ) , whereas the placebo group had higher serum calcium and ICTP concentrations but stable PTH . These results suggest that etidronate can prevent decreases in the BMD in hemiplegic stroke patients because it decreases the serum calcium through inhibition of bone resorption and causes a subsequent increase in the serum 1,25(OH)2D concentration UNLABELLED To determine if alendronate had differential effects on BMD and fracture by renal function , we performed a secondary data analysis of women participating in the FIT . Alendronate increased BMD and decreased fractures to a similar degree among women with and without reduced renal function . There was no increase in adverse events among women with impaired renal function treated with alendronate . Alendronate is safe and effective among this group of women with reduced renal function . INTRODUCTION Alendronate is cleared by the kidney and may have sustained effects on bone in subjects with impaired renal function . We hypothesized that , with decreasing renal function , alendronate treatment would result in greater increases in BMD and greater decreases in fractures and that the frequency of adverse events would be increased . MATERIAL S AND METHODS We studied women participating in the Fracture Intervention Trial ( FIT ) , a r and omized controlled trial of alendronate or placebo ( n = 6458 ) . We estimated baseline creatinine clearance ( eGFR ) using the Cockcroft Gault Formula . RESULTS Five hundred eighty-one ( 9.9 % ) participants had a severely reduced eGFR ( < 45 ml/minute ) . Alendronate increased BMD regardless of eGFR , but women with reduced eGFR had a 5.6 % ( 95 % CI : 4.8 - 6.5 ) increase in total hip BMD compared with 4.8 % ( 95 % CI : 4.6 - 5.0 ) among women with normal to moderate renal dysfunction ( interaction : p = 0.04 ) . Compared with placebo , alendronate increased spine BMD by 6.6 + /- 5.8 % , but there was no significant interaction for the increase in spine BMD ( interaction : p = 0.75 ) . Treatment with alendronate reduced the risk of clinical fractures to a similar degree in those with ( OR : 0.78 ; 95 % CI : 0.51 - 1.21 ) and without reduced renal function ( OR : 0.80 ; 95 % CI ; 0.70 - 0.93 ; p for interaction = 0.89 ) . Treatment with alendronate reduced the risk of spine fractures to a similar degree in those with ( OR : 0.72 ; 95 % CI : 0.31 - 1.7 ) and without reduced renal function ( OR : 0.50 ; 95 % CI : 0.32 - 0.76 ; p for interaction = 0.44 ) . There were no differences in adverse events by renal function . CONCLUSIONS Alendronate is safe and effective at increasing BMD and decreasing fractures among this group of women with reduced renal function BACKGROUND Hormone replacement therapy ( HRT ) , the mainstay of osteoporosis prevention , is limited because of dose-related risks , side effects , and patient acceptance . The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women . OBJECTIVE To determine the bone-sparing effect of continuous low-dose HRT in elderly women . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING University osteoporosis research and clinical center . PATIENTS 128 healthy white women ( age > 65 years ) with low bone mass recruited by word of mouth and by local advertisement . The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less . INTERVENTION Continuous therapy with conjugated equine estrogen , 0.3 mg/d , and medroxyprogesterone , 2.5 mg/d , or matching placebo . Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups ; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups . MEASUREMENTS Bone mineral density of the spine , hip , total body , and forearm ; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals ; and 24-hour urine creatinine and hydroxyproline excretion at baseline , 12 months , and 42 months . RESULTS During 3.5 years of observation , spinal bone mineral density increased by 3.5 % ( P < 0.001 ) in an intention-to-treat analysis and by 5.2 % among patients with greater than 90 % adherence to therapy . Significant increases were seen in total-body and forearm bone density ( P < 0.01 ) . Symptoms related to HRT ( breast tenderness , spotting , pelvic discomfort , and mood changes ) were mild and short-lived . CONCLUSIONS Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other , higher-dose HRT regimens in elderly women . This combination is well tolerated by most patients We have performed a 2-year prospect i ve double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen . One hundred and twenty-one such women ( mean ± SD age 57.6±3.4 years ; mean ± SD time since menopause 7.5±3.5 years ) were r and omized to receive either oral pamidronate ( 300 mg/day ) for 4 weeks every 4 months ( group A ) , oral pamidronate ( 150 mg/day ) for 4 weeks every 2 months ( group B ) or identical placebo capsules ( group C ) . Bone mineral density ( BMD ) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry . BMD at the lumbar spine ( L2–4 ) increased significantly in groups A and B after 2 years of treatment ( mean ± SD 2.8±2.1 % and 3.0±2.9 % respectively , bothp<0.001 ) but decreased in the placebo group ( −1.6±3.1%,p<0.01 ) . Identical results were seen for BMD at the femoral neck , which increased significantly in groups A and B after 2 years of treatment ( 1.2±2.3 % and 1.3±2.9 % respectively , bothp<0.05 ) but decreased in the placebo group ( −1.9±3.9%,p<0.05 ) . There were significant differences over 2 years between the groups at all anatomical sites ( lumbar spine , femoral neck and trochanteric region , allp<0.001 ; Ward 's triangle , p<0.01 ) . However , there were no significant differences between groups A and B , suggesting that the two treatment regimens were equally effective in conserving BMD . There were , however , marked differences in tolerability between the two treatment regimens : 13 women ( 34 % ) in group A withdrew from the study because of side-effects , but only 5 women ( 12 % ) in group B , which was comparable with placebo . These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women , and that the more frequent but lower dose regimen is well tolerated Objectives To assess the efficacy and tolerability of risedronate , a pyridinyl bisphosphonate , in preventing loss of bone mineral density ( BMD ) of the lumbar spine and proximal femur in early postmenopausal women . Methods A total of 383 patients were r and omly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months . All patients received 1 g elemental calcium daily . BMD was measured by dual X-ray absorptiometry at baseline and at 3 , 6 , 12 , 18 , and 24 months . Results Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women . Significant results were observed as early as 3 months . In the control calcium-supplemented group , BMD decreased steadily at each site throughout the study . The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site . At 24 months , the differences were 4.5 ± 0.45 % at the lumbar spine , 3.3 ± 0.49 % at the femoral neck , and 4.3 ± 0.67 % at the femoral trochanter . Risedronate 2.5 mg maintained BMD at each site , although the effect was less pronounced than that of risedronate 5 mg . Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events . Conclusions Risedronate 5 mg prevents bone loss in early postmenopausal women , is well tolerated , and represents an effective choice to maintain bone mass and prevent osteoporosis Teriparatide [ rhPTH(1 - 34 ) ] increases bone mineral density and reduces the risk of vertebral fracture in women . We r and omized 437 men with spine or hip bone mineral density more than 2 SD below the young adult male mean to daily injections of placebo , teriparatide 20 microg , or teriparatide 40 microg . All subjects also received supplemental calcium and vitamin D. The study was stopped after a median duration of 11 months because of a finding of osteosarcomas in rats in routine toxicology studies . Biochemical markers of bone formation increased early in the course of therapy and were followed by increases in indices of osteoclastic activity . Spine bone mineral density was greater than in placebo subjects after 3 months of teriparatide therapy , and by the end of therapy it was increased by 5.9 % ( 20 microg ) and 9.0 % ( 40 microg ) above baseline ( p < 0.001 vs. placebo for both comparisons ) . Femoral neck bone mineral density increased 1.5 % ( 20 microg ; p = 0.029 ) and 2.9 % ( 40 microg ; p < 0.001 ) , and whole body bone mineral content increased 0.6 % ( 20 microg ; p = 0.021 ) and 0.9 % ( 40 microg;p = 0.005 ) above baseline in the teriparatide subjects . There was no change in radial bone mineral density in the teriparatide groups . Bone mineral density responses to teriparatide were similar regardless of gonadal status , age , baseline bone mineral density , body mass index , smoking , or alcohol intake . Subjects experienced expected changes in mineral metabolism . Adverse events were similar in the placebo and 20-microg groups , but more frequent in the 40-microg group . This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss . The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early post-menopausal women . One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year , r and omised , placebo-controlled , double-blind trial . Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline . Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years . Urinary collagen cross-links ( deoxypyridinoline and pyridinoline ) were measured at the same time points . Seventy-seven women completed the study . At the end of the treatment period , the mean bone mineral density change from baseline in the treated group was + 0.14 % and −0.06 % in the lumbar spine and femoral neck , respectively , compared to −1.49 and −2.22 in the control group . Overall , there was a significant difference between the two groups at both these sites ( p=0.01 and 0.001 , respectively ) . No significant differences between the groups were demonstrated at the greater trochanter or Ward ’s triangle . The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women . It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy BACKGROUND There is a high incidence of hip fractures in patients with hemiplegic stroke . Bone mineral density ( BMD ) is decreased in the hemiplegic side in patients after stroke , correlating with the degree of paralysis and of hypovitaminosis D. OBJECTIVE To evaluate the efficacy of risedronate in reducing the severity of osteoporosis and in decreasing the risk of hip fractures in elderly women following an acute stroke . METHODS This was a 12-month , r and omized , double blind , placebo-controlled trial . In a prospect i ve study of stroke patients , 187 patients received a daily dose of 2.5 mg risedronate for 12 months , and the remaining 187 received placebo . Incidence of hip fracture was compared between the two groups at the endpoint of the study . RESULTS Seven patients sustained hip fractures on the hemiplegic side in the placebo group , and one hip fracture occurred in the risedronate group ( p = 0.0360 ; OR = 7.0 ) . BMD increased by 1.5 % and decreased by 4.9 % in the risedronate group and placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 53.4 % in the risedronate group and increased by 35.8 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density in elderly women following an acute stroke and prevents hip fractures UNLABELLED Oral daily ib and ronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis ( n = 653 ) . BMD at the lumbar spine and hip were significantly increased ( 3.1 % and 1.8 % , respectively ; p < or = 0.0001 versus placebo ) with 2.5 mg ib and ronate after 24 months . Oral ib and ronate is a promising option for the prevention of postmenopausal bone loss . INTRODUCTION Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required . The objectives of this multicenter , double-blind , r and omized , placebo-controlled study were to examine the efficacy , tolerability , and optimal dose of oral daily ib and ronate in the prevention of bone loss in postmenopausal women . MATERIAL S AND METHODS In total , 653 women ( mean bone mineral density [ BMD ] T-score > -2.5 at the lumbar spine ) , who had been postmenopausal for at least 1 year , were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD . Women were r and omized to receive calcium ( 500 mg daily ) plus either placebo ( n = 162 ) or ib and ronate 0.5 mg ( n = 162 ) , 1 mg ( n = 166 ) , or 2.5 mg ( n = 163 ) as once-daily oral treatment for 2 years . The primary endpoint was the mean percent change in lumbar spine BMD with ib and ronate versus placebo . RESULTS AND CONCLUSIONS After 2 years , oral daily ib and ronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip ( total hip , femoral neck , trochanter ) , together with a dose-related reduction in the rate of bone turnover . The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose , which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip ( 3.1 % and 1.8 % increase in lumbar spine and total hip BMD , respectively , versus placebo ; p < or = 0.0001 after 24 months ) . Oral daily ib and ronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo . No safety concerns were identified . In summary , oral daily ib and ronate 2.5 mg decreases bone turnover , preserves or increases BMD in the spine and proximal femur , and is well tolerated . Oral ib and ronate provides a promising option for the prevention of bone loss in postmenopausal women The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density ( BMD ) in idiopathic male osteoporosis without vertebral fractures . We conducted a r and omized , open label , controlled trial in 71 male patients ( mean age 59 + /- 6 years ) suffering from idiopathic osteoporosis ( femoral neck T-score < -2.5 ) without vertebral deformity . Patients in the control group ( n = 31 ) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group ( n = 40 ) received 400 IU Vitamin D , 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months . The study period was 18 months . Compared to controls , nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine ( + 3.5 + /- ( -4.3 % ) vs. + 0.83 + /- 6.4 % , P = 0.04 ) and the femoral neck ( + 3.2 + /- 3.9 % vs. + 0.68 + /- 5.7 % , P = 0.004 ) . No significant difference was observed at the radius between the treatment groups ( + 1.4 + /- 8.8 % vs. + 1.4 + /- 10.9 % , P = 0.98 ) . Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group . We conclude that 200 IU salmon calcitonin nasal spray used daily , intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis BACKGROUND A high incidence of fractures , particularly of the hip , represents an important problem in patients with Alzheimer disease ( AD ) , who are prone to falls and have osteoporosis . We previously found that deficiency of 25-hydroxyvitamin D and compensatory hyperparathyroidism cause reduced bone mineral density in female patients with AD . We address the possibility that treatment with risedronate sodium and ergocalciferol plus calcium supplementation may reduce the incidence of nonvertebral fractures in elderly women with AD . METHODS A total of 500 elderly women with AD were r and omly assigned to daily treatment with 2.5 mg of risedronate sodium or a placebo , combined with 1000 IU of ergocalciferol and 1200 mg of elementary calcium , and followed up for 18 months . RESULTS At baseline , patients of both groups showed 25-hydroxyvitamin D deficiency with compensatory hyperparathyroidism . During the study period , bone mineral density in the risedronate group increased by 4.1 % and decreased by 0.9 % in the control group . Vertebral fractures occurred in 29 patients ( 24 hip fractures ) in the control group and 8 patients ( 5 hip fractures ) in the risedronate group . The relative risk in the risedronate group compared with the control group was 0.28 ( 95 % confidence interval , 0.13 - 0.59 ) . CONCLUSIONS Elderly patients with AD hypovitaminosis D are at increased risk for hip fracture . Treatment with risedronate and ergocalciferol may be safe and effective in reducing the risk of a fracture in elderly patients with AD The objective of the study was to evaluate the effects of cyclical therapy with etidronate and calcium on spinal and femoral bone loss in the early post menopausal period . Fifty-four women , 53 + /- 2.8 yr old ( mean + /- SD ) and 2.3 + /- 1.3 yr post menopause received oral doses of either 400 mg/day etidronate for 2 weeks followed by 500 mg/day elemental calcium for 11 weeks , or placebo for 14 days followed by calcium for 11 weeks , repeated over a total of 24 months . A statistically significant increase in spinal bone mineral density ( BMD ) was observed after 6 months in the etidronate group . At 2 yr , the mean treatment differences in spinal and femoral neck BMD were + 2.93 % ( P < 0.02 ) and 2.02 % ( P < 0.03 ) , respectively . Serum osteocalcin and urinary crossLaps/creatinine excretion were decreased significantly by etidronate . Etidronate was well tolerated with a safety profile similar to that of placebo . Thirty-seven women participated in a 1-yr open-label follow-up study . Twelve months after treatment withdrawal , spinal BMD in the former etidronate group decreased by 1.43 % and serum osteocalcin and urinary crossLaps returned to pretreatment values . In conclusion , cyclical etidronate is an effective therapy for the prevention of both trabecular and cortical bone loss in the early menopause and has a good safety profile Teriparatide ( rDNA origin ) injection [ recombinant human PTH ( 1 - 34 ) ] stimulates bone formation , increases bone mineral density ( BMD ) , and restores bone architecture and integrity . In contrast , bisphosphonates reduce bone resorption and increase BMD . We compared the effects of teriparatide and alendronate sodium on BMD , nonvertebral fracture incidence , and bone turnover in 146 postmenopausal women with osteoporosis . Women were r and omized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo ( n = 73 ) or oral alendronate 10 mg plus placebo injection ( n = 73 ) . Median duration of treatment was 14 months . At 3 months , teriparatide increased lumbar spine BMD significantly more than did alendronate ( P < 0.001 ) . Lumbar spine-BMD increased by 12.2 % in the teriparatide group and 5.6 % in the alendronate group ( P < 0.001 teriparatide vs. alendronate ) . Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate , but BMD at the one third distal radius decreased , compared with alendronate ( P < or = 0.05 ) . Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group ( P < 0.05 ) . Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment . In conclusion , teriparatide , a bone formation agent , increased BMD at most sites and decreased nonvertebral fractures more than alendronate OBJECTIVE A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density ( BMD ) , bone turnover , and upper gastrointestinal tolerability over 2 yr of treatment . DESIGN This was a r and omized , double-blind extension conducted at 72 U.S. sites . PATIENTS AND METHODS Of the 1053 women who completed yr 1 , 833 postmenopausal women with low BMD entered the extension , continuing their same treatment allocation [ once-weekly ( OW ) alendronate 70 mg or OW risedronate 35 mg ] . Changes in BMD at the hip trochanter , total hip , femoral neck , and lumbar spine and in markers of bone turnover were compared at 24 months . Tolerability was assessed by adverse experience reporting . RESULTS Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter ( alendronate , 4.6 % ; risedronate , 2.5 % , P < 0.001 ) as well as at all other BMD sites . Significantly more alendronate than risedronate patients had measured BMD increases of 0 % or more and 3 % or more at all BMD sites ( P < 0.001 ) , and fewer alendronate patients had measured decreases of 3 % or more at all BMD sites . Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate , compared with risedronate . No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences . CONCLUSIONS Patients receiving 70 mg OW alendronate had greater gains in BMD , were more likely to maintain or gain BMD , and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months , with no differences in upper gastrointestinal tolerability When subjected to strains or strain rates higher than usual , the bone remodels to repair microdamage and to strengthen itself . During the initial resorption phase of remodeling , the bone is transitorily weakened and microdamage can accumulate leading to stress fracture . To determine whether short-term suppression of bone turnover using bisphosphonates can prevent the initial loss of bone during the remodeling response to high bone strain and strain rates and potentially prevent stress fracture , we conducted a r and omized , double-blind , placebo-controlled trial of 324 new infantry recruits known to be at high risk for stress fracture . Recruits were given a loading dose of 30 mg of risedronate or placebo daily for 10 doses during the first 2 weeks of basic training and then a once a week maintenance dose for the following 12 weeks . Recruits were monitored by biweekly orthopedic examinations during 15 weeks of basic training for stress fractures . Bone scans for suspected tibial and femoral stress fractures and radiographs for suspected metatarsal stress fractures were used to verify stress fracture occurrence . By the intention-to-treat analysis and per- protocol analysis , there was no statistically significant difference in the tibial , femoral , metatarsal , or total stress fracture incidence between the treatment group and the placebo . We conclude that prophylactic treatment with risedronate in a training population at high risk for stress fracture using a maintenance dosage for the treatment of osteoporosis does not lower stress fracture risk BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) BACKGROUND Few data are available on the safety and efficacy of once-weekly oral bisphosphonate therapy in breast cancer survivors . OBJECTIVE Our objective was to determine whether risedronate , 35 mg weekly , is efficacious and safe in preventing bone loss associated with chemotherapy-induced menopause . DESIGN The study was a r and omized , double-blind , placebo-controlled clinical trial over 12 months . SETTING AND PARTICIPANTS Participants included 87 newly postmenopausal women with status post chemotherapy , recruited from a breast cancer clinic in an academic medical center . INTERVENTION Participants were r and omly assigned to receive risedronate 35 mg/wk or placebo . MAIN OUTCOME MEASURES The primary outcomes were the 12-month changes in spine and hip bone mineral density . Secondary outcomes included changes in markers of bone resorption ( urine N-telopeptide cross-linked collagen type I ) and formation ( osteocalcin , N-terminal propeptide of type I procollagen , and bone-specific alkaline phosphatase ) . RESULTS After 12 months , bone mineral density increased by 1.2 % at the spine and 1.3 % at the hip in women on risedronate vs. significant decreases for women in the placebo group of 0.9 % at the spine and 0.8 % at the hip ( P < 0.01 , difference between groups ) . N-telopeptide cross-linked collagen type I , a marker of bone resorption , decreased by 19.3 % , and N-terminal propeptide of type I procollagen , a marker of bone formation , decreased by 26.6 % in participants on active therapy compared with increases in the control group . Risedronate was well tolerated , and the retention rate was 95 % at 1 yr . CONCLUSIONS Risedronate once weekly prevented bone loss and reduced bone turnover in women with breast cancer treated with chemotherapy . Early measures to prevent bone loss should be considered in this cohort of breast cancer survivors In healthy Caucasian postmenopausal women , raloxifene increases bone mineral density ( BMD ) , decreases biochemical markers of bone turnover , and lowers low-density lipoprotein ( LDL ) cholesterol , without effects on high-density lipoprotein ( HDL ) cholesterol and triglycerides . This r and omized , double-blind study examines the effects of raloxifene 60 mg/d ( n = 483 ) or placebo ( n = 485 ) in healthy postmenopausal Asian women ( mean age 57 yr ) from Australia , Hong Kong , India , Indonesia , Malaysia , Pakistan , Philippines , Singapore , Taiwan , and Thail and . Serum osteocalcin , serum N-telopeptide , total cholesterol , HDL cholesterol , LDL cholesterol , and triglycerides were assessed at baseline and 6 months . Lumbar spine BMD was measured at baseline and 1 yr in 309 women from 4 countries . Clinical adverse events were recorded at each interim visit . At 6 months , raloxifene 60 mg/d significantly decreased osteocalcin , N-telopeptide , total cholesterol , and LDL cholesterol by medians of 15.9 % , 14.6 % , 5.3 % , and 7.7 % , respectively , from placebo . Changes in HDL cholesterol and triglycerides were similar between raloxifene and placebo . Raloxifene 60 mg/d increased mean lumbar spine BMD ( 1.9 % ) from placebo at 1 yr ( P = 0.0003 ) . The incidences of hot flashes ( placebo 3.5 % , raloxifene 5.6 % , P = 0.12 ) , and leg cramps ( placebo 2.7 % , raloxifene 4.3 % , P = 0.16 ) were not different between groups . No case of venous thromboembolism was reported . The effects of raloxifene 60 mg/d on bone turnover , BMD , and serum lipids in healthy postmenopausal Asian women were similar to that previously reported in Caucasian women UNLABELLED The double-blind , r and omized raloxifene alendronate comparison trial was the first study design ed to compare two osteoporosis therapies head-to-head for fracture risk reduction . The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day ( ALN ) or raloxifene 60 mg/day ( RLX ) for 5 years , and to recruit women ( 50 - 80 years old ) with a femoral neck bone mineral density ( BMD ) T-score between -2.5 and -4.0 , inclusive , no prevalent vertebral fractures , and no prior bone-active agent use . The trial was stopped early , due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline , result ing in insufficient power to show non-inferiority between therapies in the primary endpoint ( number of women with > or=1 new osteoporotic vertebral or nonvertebral fracture ) . Except for vertebral fractures , fracture analyses were based upon 1412 of the 1423 women r and omized ( mean age of 66 years ) . After 312+/-254 days ( mean+/-SD ) , 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures . Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures , a pre-specified endpoint ( P=0.04 ) . Lumbar spine , femoral neck , and total hip BMD were increased from baseline at 2 years in each group ( P<0.001 ) , with greater increases in the ALN group ( each P<0.05 ) . Similar numbers of women in each group had > or=1 adverse event and discontinued due to an adverse event . The only adverse events with an incidence that differed between groups were colonoscopy , diarrhea , and nausea ; each was more common with ALN treatment ( each P<0.05 ) . One woman in each group had a venous thromboembolic event . One case of breast cancer occurred in each group . In summary , as this trial was terminated early , there was insufficient power to compare the fracture risks between alendronate and raloxifene . Safety profiles were as expected from clinical trial and post-marketing reports . TRIAL REGISTRATION Clinical Trials.gov Identifier NCT00035971 Abstract : The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55–75 years with established vertebral osteoporosis . Patients on active therapy received disodium pamidronate 300 mg/day ( group A ) for 4 weeks every 16 weeks , 150 mg/day ( group B ) for 4 weeks every 8 weeks or placebo ( group C ) . All patients additionally received 500 mg of calcium and 400 IU vitamin D daily . Dual-energy X-ray absorptiometry measurements of the spine , hip , forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites . Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months . The percentage change ( SEM ) in spine bone mineral density ( BMD ) at 2 years based on intention-to-treat analysis was 4.64 ( 1.01 ) in group A , 6.10 ( 0.87 ) in group B and 1.13 ( 1.32 ) in group C. Analysis of variance showed significant increases in group A and B compared with placebo ( p<0.01 ) . There were also significant rises in femoral neck BMD for group A ( p = 0.005 ) , trochanter BMD for groups A and B ( p<0.01 ) and total-body BMD for groups A and B ( p<0.001 ) . There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B ( p<0.01 ) . There was an excess of gastrointestinal side-effects in the treated groups , particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis , although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage Bone loss is a well‐recognized complication of primary biliary cirrhosis ( PBC ) . Although it has been suggested that alendronate might improve bone mineral density ( BMD ) in PBC , no r and omized placebo‐controlled trial has been conducted . The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC‐associated bone loss . We conducted a double‐blinded , r and omized , placebo‐controlled trial . Patients with a PBC and BMD t score of less than −1.5 were r and omized to receive 70 mg per week of alendronate or placebo over 1 year . BMD of the lumbar spine and proximal femur were measured at entry and at 1 year . Changes from baseline in BMD and biochemical measurements of bone turnover were assessed . Thirty‐four patients were enrolled . Seventeen patients were r and omized to each arm . After 1 year , a significantly larger improvement ( P = .005 ) in spine BMD was observed in the alendronate group ( 0.09 ± 0.03 g/cm2 SD from baseline ) compared with the placebo group ( −0.003 ± 0.02 g/cm2 SD from baseline ) . A larger improvement ( P = .046 ) was also observed in the femoral BMD of alendronate patients versus placebo . BMD changes were independent of concomitant estrogen therapy . The rate of adverse effects was similar in both groups . In conclusion , in patients with PBC‐related bone loss , alendronate significantly improves BMD compared with placebo . Although in this study oral alendronate appears to be well tolerated in patients with PBC , larger studies are needed to formally evaluate safety . ( HEPATOLOGY 2005;42:762–771 . OBJECTIVE A 3 year prospect i ve r and omized study was conducted to clarify the efficacy of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis . METHODS A group of 102 Japanese patients were enrolled , each taking > 7.5 mg of prednisolone daily for at least 90 days . Patients were r and omly divided into 2 treatment groups : Group E ( etidronate ) took 200 mg etidronate disodium per day for 2 weeks with 3.0 g calcium lactate and 0.75 microg alphacalcidol daily ; Group C ( control ) took 3.0 g calcium lactate and 0.75 microg alphacalcidol daily . Outcome measurements included changes from baseline in bone mineral density ( BMD ) of the lumbar spine and the rate of new vertebral fractures at 48 and 144 weeks . RESULTS The mean ( + /- SD ) lumbar spine BMD increased 3.7 + /- 5.6 % ( p < 0.01 ) and 1.5 + /- 4.1 % ( NS ) from baseline at 48 weeks and 4.8 + /- 6.9 % ( p < 0.005 ) and 0.4 + /- 5.0 % ( NS ) from baseline at 144 weeks in Group E and Group C , respectively . The improvement of BMD in Group E was significantly greater than in Group C at 144 weeks ( p < 0.01 ) . In 3 subgroups , men and premenopausal and postmenopausal women , the postmenopausal women showed the greatest improvement . Mean percentage change in this subgroup was 10.1 + /- 8.0 % and 1.35 + /- 6.4 % in Group E and Group C , respectively . We noted that 2 patients in Group C had new vertebral fractures , whereas no fractures were observed in Group E. CONCLUSION These results indicate that intermittent cyclical etidronate therapy is effective for the prevention and treatment of corticosteroid induced osteoporosis in patients with connective tissue diseases Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae , fractures and kyphosis , in patients with lung disease , many of whom already suffer from severe osteoporosis . Patients with cystic fibrosis ( CF ) are one of the most severely affected groups . We conducted a controlled , r and omized , nonblinded trial of pamidronate ( 30 mg intravenously every 3 mo ) with vitamin D ( 800 IU/d ) and calcium ( 1 g/d ) ( n = 16 ) compared with vitamin D and calcium alone ( n = 18 , the control subjects ) for 2 yr in 34 patients after lung transplant to improve bone mineral density ( BMD ) . The treatment groups were similar in age , sex , baseline T-scores , renal function , hospitalization rates , immunosuppressant levels , change in lung function , and body mass index ( BMI ) over the study period . The patients treated with pamidronate gained 8.8 + /- 2.5 % and 8.2 + /- 3.8 % in spine and femur BMD after 2 yr in comparison to control subjects , who gained , on average ( + /- SD ) , 2.6 + /- 3.2 and 0.3 + /- 2.2 % , respectively ( p < /= 0.015 for both ) . Seven and six fractures occurred in the control and pamidronate groups , respectively ( p > 0.2 ) . Measures of bone resorption were highest immediately after lung transplant and improved with both pamidronate and time . Measures of bone formation were very poor after lung transplant , but recovered in the first post-lung transplant year irrespective of therapy . We conclude that pamidronate was more effective than control in improving bone mineral density after lung transplantation in patients with CF and appears to be one of the most promising agents studied to date for posttransplant osteoporosis BACKGROUND Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations , there are few direct comparative data . METHODS R and omized placebo-controlled trial for 3 years , intention-to-treat analysis . Six hundred nineteen postmenopausal women with prior hysterectomy ( mean age , 53.0 years ) were studied in 38 centers in Europe , North America , Australasia , and South Africa . They were r and omized to 60 mg/d or 150 mg/d of raloxifene , 0.625 mg/d of conjugated equine estrogen ( CEE ) , or placebo . Bone density of the lumbar spine and proximal femur , biochemical markers of bone turnover , and fasting serum lipid concentrations were assessed for 3 years . RESULTS Compared with baseline , bone density in the lumbar spine progressively declined by 2.0 % in the placebo group ( P < .05 ) , was stable in the 2 raloxifene groups , and increased 4.6 % in the subjects receiving CEE ( P < .001 ) . Effects in both raloxifene groups were different from those observed in the CEE and placebo groups ( P < .001 ) . Bone density in the total hip showed similar results . Conjugated equine estrogen produced significantly greater depression of serum osteocalcin , bone-specific alkaline phosphatase , and urine C-telopeptide , compared with raloxifene . Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels ( P < .001 at most time points ) . Raloxifene did not affect high-density lipoprotein cholesterol , whereas CEE increased it by 13.4 % compared with placebo at 3 years ( P < .001 ) . Triglyceride concentrations increased 24.6 % in the CEE group at 3 years ( P < .003 ) , a significantly greater change than in the raloxifene groups , which were 4.9 % and 8.0 % above baseline ( P < or = .002 ) but not different from placebo . Urinary incontinence was reported in 11 women receiving CEE , but in only 1 or 2 in each of the other groups ( P < or = .01 compared with the other groups ) . Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE ( P = .03 vs placebo ) . CONCLUSIONS Raloxifene and CEE have beneficial effects on bone density and bone turnover , although effects of CEE are more marked . Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles Teriparatide ( rhPTH[1 - 34 ] ) , a bone-forming agent for the treatment of osteoporosis , increases bone mineral density in men and women , and reduces the risk of fractures in women with osteoporosis . However , fracture efficacy has not yet been confirmed in men . Further , there is limited information on the effect of withdrawal of teriparatide . The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period , from the baseline of the previously reported treatment study in men [ 1 ] through 30 months of posttreatment follow-up . Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 µg of teriparatide participated in the follow-up study . Bone mineral density gradually decreased following discontinuation of teriparatide therapy . However , the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up ( p≤0.001 ) . Antiresorptive treatment prevented the decline and tended to further increase bone mineral density . Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men . Of these men , 11.7 % assigned to placebo , 5.4 % treated with teriparatide 20 µg , and 6.0 % treated with teriparatide 40 µg had an incident vertebral fracture . In the combined teriparatide treated groups vs placebo , the risk of vertebral fracture was reduced 51 % ( nonsignificant , p=0.07 ) . The incidence of moderate or severe fractures was significantly reduced by 83 % ( p=0.01 ) . In conclusion , men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer . Raloxifene increases bone mineral density in postmenopausal women , but its efficacy in hypogonadal men is not known . In a 12-month open-label study , men with nonmetastatic prostate cancer ( n = 48 ) who were receiving a GnRH agonist were assigned r and omly to raloxifene ( 60 mg/d ) or no raloxifene . Bone mineral densities of the posteroanterior lumbar spine and proximal femur were measured by dual energy x-ray absorptiometry . Mean ( + /-se ) bone mineral density of the posteroanterior lumbar spine increased by 1.0 + /- 0.9 % in men treated with raloxifene and decreased by 1.0 + /- 0.6 % in men who did not receive raloxifene ( P = 0.07 ) . Bone mineral density of the total hip increased by 1.1 + /- 0.4 % in men treated with raloxifene and decreased by 2.6 + /- 0.7 % in men who did not receive raloxifene ( P < 0.001 ) . Similar between-group differences were observed in the femoral neck ( P = 0.06 ) and trochanter ( P < 0.001 ) . In men receiving a GnRH agonist , raloxifene significantly increases bone mineral density of the hip and tends to increase bone mineral density of the spine BACKGROUND AND METHODS Osteoporosis is a recognized complication of corticosteroid therapy . Whether it can be prevented is not known . We conducted a 12-month , r and omized , placebo-controlled study of intermittent etidronate ( 400 mg per day for 14 days ) followed by calcium ( 500 mg per day for 76 days ) , given for four cycles , in 141 men and women ( age , 19 to 87 years ) who had recently begun high-dose corticosteroid therapy . The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52 . Secondary measures included changes in the bone density of the femoral neck , trochanter , and radius and the rate of new vertebral fractures . RESULTS The mean ( + /-SE ) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61 + /- 0.54 and 1.46 + /- 0.67 percent , respectively , as compared with decreases of 3.23 + /- 0.60 and 2.74 + /- 0.66 percent , respectively , in the placebo group . The mean differences between the groups after one year were 3.72 + /- 0.88 percentage points for the lumbar spine ( P = 0.02 ) and 4.14 + /- 0.94 percentage points for the trochanter ( P = 0.02 ) . The changes in the femoral neck and the radius were not significantly different between the groups . There was an 85 percent reduction in the proportion of postmenopausal woman with new vertebral fractures in the etidronate group as compared with the placebo group ( 1 of 31 patients vs. 7 of 32 patients , P = 0.05 ) , and the etidronate-treated postmenopausal women also had significantly fewer vertebral fractures per patient ( P = 0.04 ) . CONCLUSIONS Intermittent etidronate therapy prevents the loss of vertebral and trochanteric bone in corticosteroid-treated patients BACKGROUND / AIMS Increased rates of bone loss and fracture have been reported after liver transplantation . The aim of this study was to investigate the effects of a pre-transplant infusion of pamidronate on fracture incidence and bone loss during the first year after transplantation . METHODS Ninety-nine adults awaiting orthotopic liver transplantation ( OLT ) were r and omised to pamidronate or no treatment . Spinal X-rays were obtained at baseline and after 12 months . Bone mineral density ( BMD ) was measured at the lumbar spine ( L1 - 4 ) and femoral neck at baseline , and 3 , 6 , and 12 months after OLT . RESULTS The incidence of fractures in the first year after OLT was 8 % , four patients within the pamidronate treated group and two in the untreated group developing fractures ( P=0.40 ) . No significant spinal bone loss occurred in either group during the first year . However , significant and sustained bone loss occurred at the femoral neck in both groups . No significant differences were seen between pamidronate treated or untreated groups at either site . CONCLUSIONS Pamidronate in the regimen used had no significant effect on fracture rate or BMD post-transplant . The low incidence of fracture and absence of spinal bone loss indicate that bone disease after liver transplantation may be less common than previously reported Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures . These are related to underlying renal osteodystrophy , hypophosphatemia , and immunosuppressive treatment regimen . Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation , it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease . A r and omized , prospect i ve , controlled , clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants . Treatment subjects ( PAM ) received pamidronate with vitamin D and calcium at baseline and at months 1 , 2 , 3 , and 6 . Control ( CON ) subjects received vitamin D and calcium only . During months 6 to 12 , the subjects were observed without pamidronate treatment . Biochemical parameters of bone turnover were obtained monthly and , bone mineral density ( BMD ) was obtained at baseline and months 6 and 12 . Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation . PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry . CON had decreased vertebral BMD at 6 and 12 mo ( 4.8 + /- 0.08 and 6.1 + /- 0.09 % , respectively ) . Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo . Bone histology revealed low turnover bone disease in 50 % of the patients at baseline . At 6 mo , all of PAM had adynamic bone disease , whereas 50 % of CON continued to have or developed decreased bone turnover . Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment . Pamidronate treatment was associated with development of adynamic bone histology . Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study Abstract . Men and women ( n = 518 ) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocol s and r and omly assigned to receive either placebo or risedronate ( 2.5 or 5 mg ) for 1 year . All patients received daily calcium supplementation ( 500–1000 mg ) , and most also received supplemental vitamin D ( 400 IU ) . The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density ( BMD ) at 1 year ; changes in BMD at other sites , biochemical markers of bone turnover , and the incidence of vertebral fractures were also assessed . In the overall population , the mean ( SE ) lumbar spine BMD increased 1.9 ± 0.38 % from baseline in the risedronate 5 mg group ( P < 0.001 ) and decreased 1.0 ± 0.4 % in the placebo group ( P= 0.005 ) . BMD at the femoral neck , trochanter , and distal radius increased or was maintained with risedronate 5 mg treatment , but decreased in the placebo group . Midshaft radius BMD did not change significantly in either treatment group . The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites ( P < 0.05 ) except the midshaft radius at 1 year . The 2.5 mg dose also had a positive effect on BMD , although of a lesser magnitude than that seen with risedronate 5 mg . A significant reduction of 70 % in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group ( P= 0.01 ) . Risedronate was efficacious in both men and women , irrespective of underlying disease and duration of corticosteroid therapy , and had a favorable safety profile , with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups . Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy BACKGROUND Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption , but the balance between its long-term risks and benefits remains unclear . Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear . METHODS We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age . An additional 435 women who were prepared to receive a combination of estrogen and progestin were r and omly assigned to one of the above treatments or open-label estrogen-progestin . The main outcome measure was the change in bone mineral density of the lumbar spine , hip , distal forearm , and total body measured annually for two years by dual-energy x-ray absorptiometry . RESULTS The women who received placebo lost bone mineral density at all measured sites , whereas the women treated with 5 mg of alendronate daily had a mean ( + /-SE ) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine , 1.9+/-0.1 percent at the hip , and 0.7+/-0.1 percent for the total body ( all P<0.001 ) . Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density . Alendronate did not increase bone mineral density of the forearm , but it slowed the loss . The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate . Alendronate was well tolerated , with a safety profile similar to that of placebo or estrogen-progestin . CONCLUSIONS Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin BACKGROUND Mortality is increased after a hip fracture , and strategies that improve outcomes are needed . METHODS In this r and omized , double-blind , placebo-controlled trial , 1065 patients were assigned to receive yearly intravenous zoledronic acid ( at a dose of 5 mg ) , and 1062 patients were assigned to receive placebo . The infusions were first administered within 90 days after surgical repair of a hip fracture . All patients ( mean age , 74.5 years ) received supplemental vitamin D and calcium . The median follow-up was 1.9 years . The primary end point was a new clinical fracture . RESULTS The rates of any new clinical fracture were 8.6 % in the zoledronic acid group and 13.9 % in the placebo group , a 35 % risk reduction with zoledronic acid ( P=0.001 ) ; the respective rates of a new clinical vertebral fracture were 1.7 % and 3.8 % ( P=0.02 ) , and the respective rates of new nonvertebral fractures were 7.6 % and 10.7 % ( P=0.03 ) . In the safety analysis , 101 of 1054 patients in the zoledronic acid group ( 9.6 % ) and 141 of 1057 patients in the placebo group ( 13.3 % ) died , a reduction of 28 % in deaths from any cause in the zoledronic acid group ( P=0.01 ) . The most frequent adverse events in patients receiving zoledronic acid were pyrexia , myalgia , and bone and musculoskeletal pain . No cases of osteonecrosis of the jaw were reported , and no adverse effects on the healing of fractures were noted . The rates of renal and cardiovascular adverse events , including atrial fibrillation and stroke , were similar in the two groups . CONCLUSIONS An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival . ( Clinical Trials.gov number , NCT00046254 [ Clinical Trials.gov ] . ) This r and omized , double-blind , placebo-controlled , multicenter , 8-week study evaluated short-term effects of raloxifene on bone turnover , serum lipids , and endometrium in healthy , postmenopausal women . A total of 251 women received either placebo , raloxifene HCl 200 or 600 mg/day , or conjugated estrogens ( Premarin , 0.625 mg/day ) . Bone turnover ( serum alkaline phosphatase , serum osteocalcin , urinary pyridinoline cross-links , urinary calcium excretion , urinary hydroxyproline ) and serum lipids ( total serum cholesterol , high- and low-density lipoprotein cholesterol [ HDL-C and LDL-C ] ) were evaluated at weeks 0 , 2 , 4 , and 8 . Endometrial biopsies were performed at weeks 0 and 8 . Treatment groups were compared for each parameter for baseline-to-endpoint changes . The estrogen and raloxifene groups experienced similar decreases in serum alkaline phosphatase ( range 10 - 11 % ) , serum osteocalcin ( range 21 - 26 % ) , urinary pyridinoline cross-links ( range 20 - 26 % ) , and urinary calcium excretion ( range 45 - 72 % ) . These decreases differed significantly compared with placebo-treated subjects for all markers except serum osteocalcin , the raloxifene HCl 200 mg group . LDL-C decreased significantly in the estrogen and both raloxifene groups ( range 5 - 9 % ) compared with placebo-treated subjects . HDL-C increased significantly in the estrogen group ( 16 % ) but was unchanged in the raloxifene groups . HDL-C : LDL-C ratios increased significantly in the estrogen and raloxifene groups ( range 9 - 29 % ) . Serum cholesterol decreased significantly in both raloxifene groups ( range 4 - 8 % ) but was unchanged in the estrogen group . Uterine biopsies of raloxifene-treated subjects showed no change in the endometrium during this short-term treatment . Biopsies of the estrogen group showed significant endometrial stimulation . The only adverse event possibly related to raloxifene was vasodilatation ( hot flashes ) which was most common in the raloxifene HCl 600 mg group . Study results indicate that raloxifene may provide beneficial effects to bone and serum lipids in humans without uterine stimulatory effects BACKGROUND A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis . We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period . METHODS In this double-blind , placebo-controlled trial , 3889 patients ( mean age , 73 years ) were r and omly assigned to receive a single 15-minute infusion of zoledronic acid ( 5 mg ) and 3876 were assigned to receive placebo at baseline , at 12 months , and at 24 months ; the patients were followed until 36 months . Primary end points were new vertebral fracture ( in patients not taking concomitant osteoporosis medications ) and hip fracture ( in all patients ) . Secondary end points included bone mineral density , bone turnover markers , and safety outcomes . RESULTS Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70 % during a 3-year period , as compared with placebo ( 3.3 % in the zoledronic-acid group vs. 10.9 % in the placebo group ; relative risk , 0.30 ; 95 % confidence interval [ CI ] , 0.24 to 0.38 ) and reduced the risk of hip fracture by 41 % ( 1.4 % in the zoledronic-acid group vs. 2.5 % in the placebo group ; hazard ratio , 0.59 ; 95 % CI , 0.42 to 0.83 ) . Nonvertebral fractures , clinical fractures , and clinical vertebral fractures were reduced by 25 % , 33 % , and 77 % , respectively ( P<0.001 for all comparisons ) . Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers . Adverse events , including change in renal function , were similar in the two study groups . However , serious atrial fibrillation occurred more frequently in the zoledronic acid group ( in 50 vs. 20 patients , P<0.001 ) . CONCLUSIONS A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral , hip , and other fractures . ( Clinical Trials.gov number , NCT00049829 . Objective Raloxifene hydrochloride ( 60 mg/day ) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis . Raloxifene treatment for 3 years increases bone mineral density ( BMD ) and , unlike tamoxifen ( a triphenylethylene selective estrogen receptor modulator ) , does not stimulate the endometrium in healthy postmenopausal women . The effect of longer duration of treatment with raloxifene is not known . Therefore , the main objectives of these analyses are ( 1 ) to compare the effect of 5 years of treatment with raloxifene ( 60 mg/day ) with placebo in terms of the likelihood of developing osteoporosis and ( 2 ) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding . Design The current analyses include integrated data from two identically design ed , prospect i ve , double-blinded trials including postmenopausal women ( mean age , 55 years ) r and omly assigned to either placebo ( n = 143 ) or raloxifene ( 60 mg/day ; n = 185 ) . Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria , using the manufacturer 's data base for the lumbar spine and the National Health and Nutrition Examination Survey 's 1998 reference base for the hip . Endometrial thickness was determined using transvaginal ultrasonography . Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports . Results Compared with the case of placebo , raloxifene treatment for 5 years reduced bone turnover markers ( osteocalcin : −10.9 % , P < 0.001 ; bone-specific alkaline phosphatase : −7.2 % , P = 0.042 ; urinary C-telopeptide : −11.1 % , P = 0.034 ) and was associated with increased BMD in the lumbar spine ( 2.8 % ; P < 0.001 ) and total hip BMD ( 2.6 % ; P < 0.001 ) . Women taking raloxifene were less likely to develop osteoporosis ( relative risk [ RR ] for raloxifene v placebo : 0.13 ; 95 % CI : 0.00 , 0.37 ; P = 0.001 ) or osteopenia ( RR : 0.23 ; 95 % CI : 0.00 , 0.81 ; P = 0.038 ) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine ( RR : 4.01 ; 95 % CI : 1.34 , 11.23 ; P = 0.043 ) and total hip ( RR : 3.92 ; 95 % CI : 1.12,14.27 ; P = 0.011 ) at 5 years , compared with the case of placebo . Raloxifene also significantly reduced total cholesterol ( −5.5 % ; P < 0.001 ) and low-density lipoprotein cholesterol ( −8.7 % ; P < 0.001 ) , compared with the case of placebo . No significant changes in high-density lipoprotein cholesterol ( P = 0.257 ) or triglycerides ( P = 0.620 ) were detected . Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [ raloxifene , 47 ( 28.8 % ) ; placebo , 21 ( 16.8 % ) ; P = 0.017 ] . Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding ( P = 0.999 ) or of mean endometrial thickness of more than 5 mm at baseline and at each visit , up to the 5-year endpoint ( P ≥ 0.349 ) . No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group . Conclusions Five years of raloxifene treatment in healthy postmenopausal women preserves BMD , significantly reduces the likelihood of development of osteoporosis , and was not associated with an increased rate of vaginal bleeding , endometrial hyperplasia , or endometrial carcinoma , compared with the case of placebo OBJECTIVE To study the effect of cyclic etidronate in secondary prevention of corticosteroid induced osteoporosis . METHODS A double blind , r and omised placebo controlled study comparing cyclic etidronate and placebo during two years in 37 postmenopausal women receiving long term corticosteroid treatment , mainly for polymyalgia rheumatica ( 40 % of the patients ) and rheumatoid arthritis ( 30 % ) . Bone density was measured in the lumbar spine , femoral neck , and femoral trochanter . RESULTS After two years of treatment there was a significant difference between the groups in mean per cent change from baseline in bone density in the spine in favour of etidronate ( p=0.003 ) . The estimated treatment difference ( mean ( SD ) ) was 9.3 (2.1)% . Etidronate increased bone density in the spine ( 4.9 (2.1)% , p<0.05 ) whereas the placebo group lost bone ( −2.4 (1.6)% ) . At the femoral neck there was an estimated difference of 5.3 (2.6)% between the groups ( etidronate : 3.6 (1.4)% , p<0.05 , placebo : −2.4 (2.1)% ) . The estimated difference at the trochanter was 8.2 ( 3.0 ) ( etidronate : 9.0 (1.5)% , p<0.0001 , placebo : 0.5 (2.3)% ) . No significant bone loss occurred in the hip in placebo treated patients . CONCLUSIONS Cyclic etidronate is an effective treatment for postmenopausal women receiving corticosteroid treatment and is well tolerated PURPOSE To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss . PATIENTS AND METHOD This was a 2-year outpatient , r and omized , double-blind , placebo-controlled clinical trial . The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density ( BMD ) between 0 and -2 SD of normal values for a 50 year old woman . The women were stratified according to years since the menopause ( 1 to 3 years : n = 43 ; 4 to 6 years : n = 53 ; 7 to 10 years : n = 56 ) . Measurements of lumbar spine , proximal femur and total body BMD were performed at baseline , 12 and 24 months by dual x-ray absorptiometry . Biochemical markers of bone resorption and bone formation were measured on the same visits . RESULTS One hundred thirty-five subjects completed the study . Mean percentage change in lumbar spine BMD ( and SEM ) at 2 years was + 2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group . Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were : 1 to 3 years : + 1.73 (0.84)% and -3.30 (0.70)% ; 4 to 6 years : + 1.37 (0.88)% and -1.80 (0.61)% ; 7 to 10 years : + 3.42 (0.61)% and -0.38 (0.70)% . The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD . Treatment group , but not stratum , was significant for BMD in the proximal femur . Markers of bone resorption and bone formation were significantly decreased by etidronate therapy . CONCLUSIONS Cyclical etidronate prevents bone loss in the total skeleton and at the clinical ly relevant sites ( spine and proximal femur ) even in the early postmenopausal years . Hence , it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P<.001 ) . Within the overall null effect , there was a statistically significant time trend , with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo . The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant CONTEXT In controlled studies , bisphosphonates have been used to prevent bone loss after solid organ transplantations but not in conjunction with stem cell transplantation ( SCT ) . OBJECTIVE The objective of the study was to test whether additional iv pamidronate would prevent bone loss associated with SCT more effectively than the combination of calcium , vitamin D , and sex steroid replacement therapy alone . SETTING The study was carried out at the Helsinki University Central Hospital . PATIENTS , DESIGN , INTERVENTION : Ninety-nine adult recipients of allogeneic SCT were r and omized by age and gender into two groups . In one group , the patients received 1000 mg calcium carbonate and 800 IU vitamin D daily , and females received estrogen and males received testosterone replacement therapy . In another group , the patients received the same treatments plus six iv infusions of 60 mg pamidronate before and 1 , 2 , 3 , 6 , and 9 months after SCT . MAIN OUTCOME MEASURES Bone mineral density ( BMD ) of the lumbar spine and the upper femur , measured by dual-energy x-ray absorptiometry , and bone turnover markers were followed for 12 months . RESULTS In the pamidronate group , lumbar spine BMD remained stable but decreased in the other group by 2.9 % at 12 months ( P = 0.0084 between the groups over time ) . Total hip BMD reduced 5.1 % in the pamidronate group and 7.8 % in the other group by 12 months ( P = 0.0015 ) , and femoral neck BMD reduced 4.2 and 6.2 % , respectively ( P = 0.074 ) . In the pamidronate group , serum type I procollagen amino-terminal propeptide ( P = 0.032 between the groups over time ) and urinary type I collagen amino-terminal telopeptide ( P = 0.035 ) decreased 79 and 68 % during the first 3 months , and remained lowered thereafter , but did not change in the other group . CONCLUSIONS The recipients of allogeneic SCT receiving additional pamidronate sustain less bone loss than those treated with calcium , vitamin D , and sex steroid replacement alone . Despite all the efforts , however , bone loss is not totally abolished at the hip There is a need for effective and acceptable therapies for postmenopausal osteoporosis . The bisphosphonates show promise in this role , but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported . We performed a 2-yr , r and omized , double blind , placebo-controlled trial of pamidronate ( 150 mg/day ) in 48 postmenopausal osteoporotic women . Bone mineral density of the total body , lumbar spine , and proximal femur was measured every 6 months by dual energy x-ray absorptiometry . Bone mineral density increased progressively in the total body ( 1.9 + /- 0.7 % ; P < 0.01 ) , lumbar spine ( 7.0 + /- 1.0 % ; P < 0.0001 ) , and femoral trochanter ( 5.4 + /- 1.3 % ; P < 0.001 ) in subjects receiving pamidronate , but did not change significantly in those receiving placebo . There were significant decreases in bone density at both the femoral neck ( P < 0.02 ) and Ward 's triangle ( P < 0.01 ) in subjects taking placebo , which did not occur in the pamidronate group . The differences between the treatment groups were significant at all sites ( 0.0001 < P < 0.05 ) except Ward 's triangle . Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo ( P = 0.07 ) , and there was a nonsignificant trend toward height loss being less in those receiving pamidronate ( P = 0.16 ) . It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis There is no well-established treatment for osteoporosis in male patients with leprosy , because no clinical trials have examined the efficacy of treatment on bone mineral density ( BMD ) or fracture incidence in such patients . The purpose of the present study was to evaluate the therapeutic effect on oral administration of risedronate in male osteoporotic patients with leprosy . Twenty-three male patients with leprosy , 63 - 87 years of age , were r and omly divided into two administration groups : R group ( risedronate , 2.5 mg/day , daily ) and P group ( placebo , daily ) . The BMD of the lumbar spine ( L2-L4 ) was measured by dual-energy X-ray absorptiometry , and urinary cross linked N-telopeptides of type I collagen ( NTX ) were assessed at baseline , 6 months , and 12 months after treatment . There were no significant differences in age , body mass index , BMD , or urinary NTX levels at baseline between the two groups . In the present study , oral administration of risedronate apparently prevented vertebral fractures by increasing lumbar BMD and caused a significant reduction in urinary NTX levels , while oral administration of placebo did not increase the lumbar BMD and prevent vertebral fractures due to osteoporosis . The above findings suggested that oral administration of risedronate contributed to the prevention of vertebral fractures by suppressing bone resorption and increasing in lumbar BMD in the elderly male patients with leprosy BACKGROUND Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment . METHODS We carried out two 48-week , r and omized , placebo-controlled studies of two doses of alendronate in 477 men and women , 17 to 83 years of age , who were receiving glucocorticoid therapy . The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups . Secondary outcomes included changes in bone density of the hip , biochemical markers of bone turnover , and the incidence of new vertebral fractures . RESULTS The mean ( + /-SE ) bone density of the lumbar spine increased by 2.1+/-0.3 percent and 2.9+/-0.3 percent , respectively , in the groups that received 5 and 10 mg of alendronate per day ( P<0.001 ) and decreased by 0.4+/-0.3 percent in the placebo group . The femoral-neck bone density increased by 1.2+/-0.4 percent and 1.0+/-0.4 percent in the respective alendronate groups ( P<0.01 ) and decreased by 1.2+/-0.4 percent in the placebo group ( P<0.01 ) . The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate . There were proportionally fewer new vertebral fractures in the alendronate groups ( overall incidence , 2.3 percent ) than in the placebo group ( 3.7 percent ) ( relative risk , 0.6 ; 95 percent confidence interval , 0.1 to 4.4 ) . Markers of bone turnover decreased significantly in the alendronate groups ( P<0.001 ) . There were no differences in serious adverse effects among the three groups , but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate . CONCLUSIONS Alendronate increases bone density in patients receiving glucocorticoid therapy BACKGROUND / AIMS Accelerated bone loss occurs early after liver transplantation ( OLT ) and , in cholestatic patients with pre-existing osteopenia , causes spontaneous fracturing . This study aim ed to investigate the efficacy of calcitonin , a powerful inhibitor of bone resorption , in preventing or reducing the accelerated rate of bone loss and fracturing which occurs in patients with primary biliary cirrhosis and primary sclerosing cholangitis early after OLT . METHODS Sixty-three patients undergoing OLT for primary biliary cirrhosis ( n = 26 ) and primary sclerosing cholarigitis ( n = 37 ) were r and omized to receive : ( a ) , 100 IU/day of salmon calcitonin subcutaneously for the first 6 months posttransplant ; or ( b ) , no therapy . At pretransplant , and at 4 and 12 months after OLT , patients were investigated clinical ly , biochemically , by bone mineral density of the lumbar spine , and by radiographs of the thoracolumbar spine , chest and site of any bone pain . RESULTS The bone mineral density of the lumbar spine fell equally at 4 months in both groups , from 0.85 to 0.81 g/cm2 in calcitonin-treated patients ( n = 29 ) and from 0.88 to 0.82 g/cm2 in controls ( n = 34 ) ; at 12 months , both groups had stabilized to 0.83 g/cm2 . Fracturing was the same in both groups . CONCLUSIONS Calcitonin therapy for the first 6 months after OLT is unable to prevent or reduce accelerated bone loss or spontaneous fractures which occur in the first posttransplant year The relationship between prior fractures and risk of new fractures was evaluated in 931 postmenopausal women with prevalent vertebral fractures r and omized to daily placebo or teriparatide ( 20 mug ) in the Fracture Prevention Trial . The median observation time was 21 months . Among placebo patients with one , two , or three or more prevalent vertebral fractures , 7 % , 16 % , and 23 % , respectively , developed vertebral fractures ( by Cochran-Armitage trend test , P < 0.001 ) , and 3 % , 9 % , and 17 % developed moderate or severe vertebral fractures ( P < 0.001 ) . Among placebo patients with mild , moderate , or severe prevalent vertebral fractures , 10 % , 13 % , and 28 % , respectively , developed vertebral fractures ( P < 0.001 ) , and 4 % , 8 % , and 23 % developed moderate or severe vertebral fractures ( P < 0.001 ) . Among placebo patients with zero , one , or two or more prior nonvertebral fragility fractures , 4 % , 8 % , and 18 % , respectively , developed nonvertebral fragility fractures ( P < 0.001 ) . In the teriparatide-treated group , there was no significant increase in vertebral or nonvertebral fracture risk in these subgroups . In summary , the number and severity of prevalent vertebral fractures independently predicted the risk for new vertebral fractures , and the number of prior nonvertebral fractures predicted the risk for new nonvertebral fractures in placebo patients . However , in teriparatide-treated patients , the increased fracture risk associated with prior number and severity of fracture was not observed PURPOSE Hormone replacement therapy ( HRT ) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density ( BMD ) in postmenopausal women . This 4-year prospect i ve r and omized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis . PATIENTS AND METHODS Seventy-two postmenopausal women ( mean age 64.9+/-0.5 years ) attending metabolic bone disease outpatient clinics with established osteoporosis were r and omly allocated into one of four treatment groups and monitored for 4 years . All patients enrolled in this study including the control group ( n=18 ) received 1.0 g elemental calcium and 400 units vitamin D per day . The HRT group ( n=18 ) received cyclical estrogen and progesterone ; the etidronate group ( n=17 ) received intermittent cyclical etidronate ; and the combined therapy group ( n=19 ) received both HRT and etidronate . BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment . Changes in height were recorded , and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation . In 40 patients ( 10 patients per group ) , analysis of bone histomorphometry was carried out after 4 years of treatment . RESULTS In patients who received the combined therapy , BMD increased in the lumbar spine by 10.4 % ( P < 0.001 ) and in the hip by 7.0 % ( P < 0.001 ) at 4 years . For patients treated with ICE , these increases were 7.3 % ( P < 0.001 ) and 0.9 % ( P < 0.05 ) , and with HRT , the increases were 7.0 % ( P < 0.001 ) and 4.8 % ( P < 0.01 ) in the vertebrae and femora , respectively . The group treated with calcium and vitamin D lost 2.5 % ( P < 0.05 ) and 4.4 % ( P < 0.01 ) of BMD in the vertebrae and femora , respectively , after 4 years . Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora ( P < 0.05 ) in comparison with patients who were treated with HRT or etidronate alone after 4 years . In comparison with patients in the control group , there was a trend toward a lower rate of new vertebral fractures in the treatment groups . Height loss was significantly less in all three active treatment groups ( HRT [ P < 0.001 ] , etidronate [ P < 0.02 ] , and combined therapy group [ P < 0.0001 ] ) , in comparison with the control group . The combined therapy group did not have a significant height loss , in comparison with the HRT ( P < 0.02 ) and the etidronate ( P < 0.001 ) groups . None of the patients had histomorphometric evidence of osteomalacia . CONCLUSION This 4-year r and omized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures . DESIGN Double-blind , r and omized , placebo-controlled clinical trial lasting 1 year . SETTING Referral-based outpatient clinic . PATIENTS Seventy-five postmenopausal women , 47 to 75 years of age , with one or more vertebral fractures due to osteoporosis . INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle . Another 39 women received placebo . MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry ; bone loss assessed by serial measurement of bone density ; and vertebral fracture rate . RESULTS Compared with the placebo group , the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine ( 5.3 compared with 0.2 ; P = 0.007 ) , femoral trochanter ( 7.6 compared with 2.1 ; P = 0.03 ) , and midradius ( 1.0 compared with -2.6 , P less than 0.001 ) but showed no significant difference at the femoral neck ( 2.6 compared with 1.4 ; P = 0.17 ) . Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration ( median change , -0.35 compared with 0.02 nmol/L ; P less than 0.001 ) . Histomorphometric evaluation of iliac biopsy sample s confirmed the effect of estrogen on bone formation rate per bone volume ( median change , -12.9 compared with -6.2 % per year ; P = 0.004 ) . Also , 8 new fractures occurred in 7 women in the estrogen group , whereas 20 occurred in 12 women in the placebo group , yielding a lower vertebral fracture rate in the estrogen group ( relative risk , 0.39 ; 95 % CI , 0.16 to 0.95 ) . CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis OBJECTIVES : Osteopenia increases the morbidity of primary biliary cirrhosis ( PBC ) . In this study , we have compared two bisphosphonates , alendronate and cyclical etidronate , that inhibit osteoclast-mediated bone resorption and have examined their effects on bone mass in patients with this disease . METHODS : A total of 32 women with PBC were r and omly assigned to receive alendronate ( 10 mg/day ) or etidronate ( 400 mg/day ) for 14 days every 3 months . Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months . Bone fractures and markers of bone mineral metabolism were also evaluated . RESULTS : Sixteen patients were allocated to each group , which were comparable with respect to the severity of PBC and osteopenia . Thirteen patients in each group completed the 2-yr trial . Both treatments increased bone mineral density after 2 yr , although the increase at the lumbar spine and at the proximal femur was significantly higher in patients receiving alendronate than in patients on etidronate . This higher effect of alendronate paralleled with changes in the biochemical markers of bone turnover . No patient developed new vertebral fractures , but new peripheral fractures were detected in two patients on alendronate and in one on etidronate . There were no serious adverse effects . Neither treatment impaired liver function or cholestasis . CONCLUSIONS : Alendronate effectively increases bone mass and has greater antiresorptive power than etidronate in patients with primary biliary cirrhosis , and is associated with minor or no side effects OBJECTIVES To study the fracture reducing potential of hormonal replacement therapy ( HRT ) in recent postmenopausal women in a primary preventive scenario . METHODS Prospect i ve controlled comprehensive cohort trial : 2016 healthy women aged 45 - 58 years , from three to 24 months past last menstrual bleeding were recruited from a r and om sample of the background population . Mean age was 50 . 8+/-2.8 years , and the number of person years followed was 9335.3 . There were two main study arms : a r and omised arm ( r and omised to HRT ; n=502 , or not ; n=504 ) and a non-r and omised arm ( on HRT ; n=221 , or not ; n=789 by own choice ) . First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women . RESULTS After five years , a total of 156 fractures were sustained by 140 women . There were 51 forearm fractures in 51 women . By intention-to-treat analysis ( n=2016 ) , overall fracture risk was borderline statistically significantly reduced ( RR=0.73 , 95 % CI : 0.50 - 1.05 ) , and forearm fracture risk was significantly reduced ( RR=0.45 , 95 % CI : 0.22 - 0.90 ) with HRT . Restricting the analysis to women who had adhered to their initial allocation of either HRT ( n=395 ) or no HRT ( n=977 ) showed a significant reduction in both the overall fracture risk ( RR=0.61 , 95 % CI : 0.39 - 0.97 ) and the risk of forearm fractures ( RR=0.24 , 95 % CI : 0.09 - 0.69 ) . Compliance with HRT was 65 % after five years . CONCLUSIONS It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women Objective To determine the lowest effective dose of an estradiol ( E2 ) matrix-type transdermal delivery system ( EMTDS ; Alora ) for preventing bone loss in postmenopausal women . Design This double-blind , double-dummy , r and omized , placebo-controlled , multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier . Participants were r and omly assigned to one of three doses of the EMTDS ( 0.025 , 0.05 , or 0.075 mg/day ) or placebo administered twice weekly . Lumbar bone mineral density ( LBMD ) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment . Safety was assessed at regularly scheduled visits . Results EMTDS provided statistically significant and clinical ly meaningful changes in LBMD relative to placebo . At 2 years , LBMD declined from baseline by 0.59 % in the placebo group , but it increased from baseline by 1.65 % ( p = 0.0065 ) , 4.08 % ( p = 0.0001 ) , and 4.82 % ( p = 0.0001 ) in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . The corresponding responder rates ( defined as no change or increase in LBMD at endpoint ) were 39.7 % for placebo , 59.6 % , 79.3 % , and 83.9 % in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . Mean serum E2 concentrations were proportional to the dose of the E2 transdermal system and did not accumulate over the course of the study . Adverse events were generally comparable across treatment groups , with the majority being mild or moderate in severity and unrelated to study medication . Mammogram findings and other safety assessment s were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E2 treatment . Conclusions The EMTDS ( Alora ) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women , with the benefit of treatment evident by 1 year . The lowest effective dose is 0.025 mg/day We have performed a study of the safety and efficacy of cyclic sequential oral phosphate , diphosphonate and calcium carbonate . Forty-two postmenopausal women with osteoporosis diagnosed by dual-photon absorptiometry were treated with a sequential cyclic regimen of oral phosphate for 3 days , etidronate for 2 wk , and then a calcium salt for 12 wk . This was repeated cyclically for 3 yr . They were rescanned after every two 101-day cycles . A control group of 20 patient receiving only the calcium salt was matched for age , time since menopause , race and sex . The group treated with cyclic phosphate , etidronate , and calcium regimen had 80 % fewer fractures than the control group over 3 yr of follow-up . Significant response in halting bone mineral loss and increasing bone mineral density was seen in none of the controls but in 90 % of treated patients ' lumbar spine and 70%-80 % of the three regions of the femoral neck examined UNLABELLED Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis . These two agents were compared in a 12-month head-to-head trial . Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability . INTRODUCTION The nitrogen-containing bisphosphonates , alendronate and risedronate , are available in once-weekly ( OW ) formulations for the treatment of postmenopausal osteoporosis . A 12-month , head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD . MATERIAL S AND METHODS A total of 1053 patients from 78 U.S. sites were r and omized to OW alendronate 70 mg ( N = 520 ) or risedronate 35 mg ( N = 533 ) , taken in the morning after fasting . Endpoints included BMD changes over 6 and 12 months at the hip trochanter , total hip , femoral neck , and lumbar spine ( LS ) ; percent of patients with predefined levels of change in trochanter and LS BMD at 12 months ; and change in biochemical markers of bone turnover at 3 , 6 , and 12 months . Tolerability was evaluated by adverse experience ( AE ) reporting . RESULTS Significantly greater increases in hip trochanter BMD were seen with alendronate ( 3.4 % ) than risedronate ( 2.1 % ) at 12 months ( treatment difference , 1.4 % ; p < 0.001 ) as well as 6 months ( treatment difference , 1.3 % ; p < 0.001 ) . Significantly greater gains in BMD were seen with alendronate at all BMD sites measured ( 12-month difference : total hip , 1.0 % ; femoral neck , 0.7 % ; LS , 1.2 % ) . Significant differences were seen as early as 6 months at all sites . A greater percentage of patients had > or = 0 % ( p < 0.001 ) and > or =3 % ( p < 0.01 ) gain in trochanter and spine BMD at 12 months with alendronate than risedronate . Significantly greater ( p < 0.001 ) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months . No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation . CONCLUSIONS In this 12-month , head-to-head trial of alendronate and risedronate , given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women , alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate . The greater antiresorptive effect of alendronate was seen as early as 3 months , and the tolerability profiles were similar CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P<.001 ) . The HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people OBJECTIVE To evaluate the continued efficacy and safety of alendronate ( ALN ) for up to 2 years in patients receiving glucocorticoids . METHODS This is a 12-month extension of a previously completed 1-year trial of daily ALN , performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily . All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density ( BMD ) from baseline to 24 months . Other outcomes included changes in hip and total body BMD , biochemical markers of bone turnover , radiographic joint damage of the h and s , and vertebral fracture incidence . RESULTS The mean ( + /-SEM ) lumbar spine BMD increased by 2.8 + /- 0.6 % , 3.9 + /- 0.7 % , and 3.7 + /- 0.6 % , respectively , in the groups that received 5 mg , 10 mg , and 2.5/10 mg of ALN daily ( P < or = 0.001 ) and decreased by -0.8 + /- 0.6 % in the placebo group ( P not significant ) over 24 months . In patients receiving any dose of ALN , BMD was increased at the trochanter ( P < or = 0.05 ) and maintained at the femoral neck . Total body BMD was increased in patients receiving 5 or 10 mg ALN ( P < or = 0.01 ) . These 2 dose levels of ALN were more effective than placebo at all sites ( P < or = 0.05 ) . Bone turnover markers ( N-telopeptides of type I collagen and bone-specific alkaline phosphatase ) decreased 60 % and 25 % , respectively , during treatment with ALN ( P < or = 0.05 ) . There were fewer patients with new vertebral fractures in the ALN group versus the placebo group ( 0.7 % versus 6.8 % ; P = 0.026 ) . The safety profile was similar between treatment groups . CONCLUSION Alendronate is an effective , well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis , with sustained treatment advantages for up to 2 years PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women . Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness |
13,087 | 28,475,100 | Reflexive threshold was lower in people with clinical pain than it was in pain-free controls , but reflex size , latency , and duration were unaffected .
The pattern of difference was not consistent with sensitisation of nociceptive neurones , as these changes were not isolated to the affected body part but was more consistent with top-down cognitive control reflective of heightened protection of body tissue .
The pattern of modulation is dependent on potentially complex evaluative mechanisms .
We offer recommendations for future investigations and suggest that defensive reflex threshold may reflect a biomarker of a broader psychological construct related to bodily protection , rather than sensitisation of primary nociceptors , spinal nociceptors , or pain | Abstract Upregulation of defensive reflexes such as the nociceptive flexion reflex ( NFR ) has been attributed to sensitisation of peripheral and spinal nociceptors and is often considered biomarkers of pain .
Experimental modulation of defensive reflexes raises the possibility that they might be better conceptualised as markers of descending cognitive control .
Despite strongly held views on both sides and several narrative review s , there has been no attempt to evaluate the evidence in a systematic manner . | Objective To investigate trigeminal sensory processing in patients with migraine using a novel “ nociception-specific ” blink reflex . Methods Seventeen patients with unilateral migraine headache were studied within 6 hours of onset . Blink reflexes were elicited with a st and ard stimulating electrode ( st and ard blink reflex ) and concentric stimulating electrode ( nociception-specific blink reflex ) during the acute migraine attack , after treatment with IV lysine acetylsalicylate ( 1,000 mg ) or oral zolmitriptan ( 5 mg ) and interictally . Results After st and ard stimulation , no differences were detected for the R1 and R2 onset latencies and areas under the curve ( AUC ) between the different time points and the headache and nonheadache side . Nociception-specific stimulation revealed a shortening of R2 onset latencies ( 44.3 ± 5.4 ms for headache side vs 48.9 ± 5.8 ms for nonheadache side ) during the acute migraine attack compared with the headache-free interval ( 49.8 ± 5.3 vs 49.8 ± 4.5 ms ) . The AUC of the R2 increased on the headache side by 680 % and on the nonheadache side by 230 % compared with the headache-free interval . Drug treatment parallel to pain relief increased the onset latencies ( zolmitriptan : 48.0 ± 8.2 ms for headache side vs 52.3 ± 7.6 ms for nonheadache side ; lysine acetylsalicylate : 48.0 ± 5.0 ms for headache side vs 51.2 ± 5.6 ms for nonheadache side ) and reduced the AUC of R2 ( zolmitriptan by 45 % and lysine acetylsalicylate by 48 % ) . Conclusion The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls ( DNICs ) in primary headaches . DNICs were examined in 24 migraineurs , 17 patients with chronic tension-type headache ( CTTH ) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test ( CPT ) as heterotopic noxious conditioning stimulation ( HNCS ) . The subjective pain thresholds ( Tp ) and the RIII reflex threshold ( Tr ) were significantly lower in CTTH vs. controls . In controls a significant inhibition of the RIII reflex was observed during the CPT ( -30± , P < 0.05 ) . Conversely , migraine and CTTH patients showed facilitation ( + 31± , P < 0.05 and + 40± , P < 0.01 , respectively ) of the RIII reflex during the HNCS . This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH . Impairment of endogenous supraspinal pain modulation systems may contribute to the development and /or maintenance of central sensitization in primary headaches OBJECTIVE This study aims to determine if cervical medial branch radiofrequency neurotomy reduces psychophysical indicators of augmented central pain processing and improves motor function in individuals with chronic whiplash symptoms . DESIGN Prospect i ve observational study of consecutive patients with healthy control comparison . SETTING Tertiary spinal intervention centre in Calgary , Alberta , Canada . SUBJECTS Fifty-three individuals with chronic whiplash associated disorder symptoms ( Grade 2 ) ; 30 healthy controls . METHODS Measures were made at four time points : two prior to radiofrequency neurotomy , and 1- and 3-months post-radiofrequency neurotomy . Measures included : comprehensive quantitative sensory testing ( including brachial plexus provocation test ) , nociceptive flexion reflex , and motor function ( cervical range of movement , superficial neck flexor activity during the craniocervical flexion test ) . Self-report pain and disability measures were also collected . One-way repeated measures analysis of variance and Friedman 's tests were performed to investigate the effect of time on the earlier measures . Differences between the whiplash and healthy control groups were investigated with two-tailed independent sample s t-test or Mann-Whitney tests . RESULTS Following cervical radiofrequency neurotomy , there were significant early ( within 1 month ) and sustained ( 3 months ) improvements in pain , disability , local and widespread hyperalgesia to pressure and thermal stimuli , nociceptive flexor reflex threshold , and brachial plexus provocation test responses as well as increased neck range of motion ( all P < 0.0001 ) . A nonsignificant trend for reduced muscle activity with the craniocervical flexion test ( P > 0.13 ) was measured . CONCLUSIONS Attenuation of psychophysical measures of augmented central pain processing and improved cervical movement imply that these processes are maintained by peripheral nociceptive input OBJECTIVES Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine . The aim of this study was to investigate the blink reflex and its habituation in patients with " chronic migraine " . METHODS We studied 35 patients suffering from " chronic migraine " ( IHS classification criteria ) outside and during a spontaneous attack , and 35 control subjects . An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to r and omly repeat stimulations at different time intervals so as to induce habituation . RESULTS The R(1 ) and R(2 ) latencies , amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects , whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack . The percent changes in the R(2 ) areas from the baseline values , obtained when stimuli were delivered at time intervals of 10 , 5 , 4 , 3 , 2 and 1s , were statistically different ( p<0.01-p<0.001 ) from those of the same patients studied during a migraine attack and of those of control subjects . There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks . The stimulus intensities of the blink reflex ( multiples of the detection threshold intensities ) were significantly lower ( p<0.001 ) on the side affected , or more severely affected , by headache in patients studied during a migraine attack . CONCLUSIONS The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in " chronic migraine " , which normalizes during the attacks . The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks . Central sensitisation mechanisms ( allodynia ) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks . SIGNIFICANCE The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks Trigeminal and somatic nociceptive systems were studied in controls ( n = 15 ) , episodic migraine ( n = 16 ) , analgesics ( n = 14 ) and triptan-induced medication overuse headache ( MOH ) ( n = 15 ) before and after withdrawal . Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression . Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials ( PREP ) and nociceptive blink reflex ( nBR ) following nociceptive-specific electrical stimulation of the forehead . Somatic nociception was evaluated using PREP of upper limbs . We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH , which normalized after withdrawal . No differences were found comparing analgesics vs. triptan MOH . No differences were observed between controls and patients with episodic migraine and depression without headache . A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH , which was more pronounced on a supraspinal level OBJECTIVE To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia ( FM ) as compared with controls , by using quantitative sensory testing ( QST ) and a neurophysiologic paradigm independent from subjective reports . METHODS A total of 164 out patients with FM who were attending a self-management program were invited to participate in the study . Data for 85 patients were available and were compared with those for 40 non-FM controls matched for age and sex . QST was performed using thermal , mechanical , and electrical stimuli at locations of nonspontaneous pain . Pain assessment was 2-fold and included use of subjective scales and the spinal nociceptive flexion reflex ( NFR ) , a specific physiologic correlate for the objective evaluation of central nociceptive pathways . Question naires regarding quality of life and the impact of FM were available . RESULTS Participants were mainly middle-aged women , with a mean disease duration of 8 years . Between-group differences were significant for neurophysiologic , clinical , and quality of life measures . In patients with FM , peripheral QST showed significantly altered cold and heat pain thresholds , and tolerance to cold pain was radically reduced . The median NFR threshold in patients with FM ( 22.7 mA [ range 17.5 - 31.7 ] ) was significantly decreased compared with that in controls ( 33 mA [ range 28.1 - 41 ] ) . A cutoff value of < 27.6 mA for NFR provided sensitivity of 73 % and specificity of 80 % for detecting central allodynia in the setting of FM . CONCLUSION Our results strongly , although indirectly , point to a state of central hyperexcitability of the nociceptive system in patients with FM . The NFR can be used to assess central allodynia in FM . It may also help discriminate patients who may benefit from use of central ly acting analgesics Background : Visceral hypersensitivity has been evidence d in patients with irritable bowel syndrome ( IBS ) but its mechanisms remain poorly eluci date d. We investigated the spinal transmission of nociceptive signals in IBS patients by analysing the effects of rectal distensions on electromyographic recordings of the somatic nociceptive flexion ( RIII ) reflex , an objective index of spinal nociceptive processes . Methods : Fourteen IBS and 10 healthy volunteers were included in the study . Slow ramp ( 40 ml/min ) and rapid phasic ( 900 ml/min , 10 , 20 , 30 , and 40 mm Hg ) rectal distensions were r and omly performed while the RIII reflex evoked by electrical stimulation of the sural nerve at the ankle was continuously recorded from the ipsilateral biceps femoris . Results : In healthy volunteers , significant progressive inhibition of the RIII reflex was observed during slow ramp distension ( 61 (13)% of control values ) while biphasic effects ( facilitation and inhibition ) were observed during rapid distensions . In contrast , in IBS patients , the RIII reflex was significantly facilitated during slow ramp distension ( 139 (15)% of control values ) and inhibitions induced by rapid distensions were significantly reduced . Volumes of distension and rectal compliance were similar in both groups . Conclusions : Our results provide direct evidence that a hyperexcitability of spinal nociceptive processes is present in a large subgroup of IBS patients & NA ; The processing of pain‐related , body‐related and neutral words was assessed in chronic pain patients and matched healthy controls . During and after word presentation at perception threshold , electromyographic activity ( EMG ) , heart rate , skin conductance level and electroencephalographic ( EEG ) data from 11 electrode sites were recorded . Startle responses were measured to suprathreshold word stimuli . Although the patients did not recognize more pain‐related words , they produced an enhanced left‐hemispheric N100 and N200 to pain‐related as compared to neutral words . In addition , the patients did not show a distinct P300 but a continuous positive shift to all words extending into the 800‐ms range . Skin conductance levels to the pain‐related words were also enhanced in patients only . These data partially support the notion of pain‐related implicit memory structures in the brain of chronic pain patients that may selectively draw attention to pain‐related stimuli and may thus enhance pain perception The aim of this study was to investigate central anti-nociceptive mechanisms of i.v . acetylsalicylic acid ( ASA ) and oral zolmitriptan ( ZOL ) in migraine patients and healthy subjects using the ‘ nociceptive ’ blink reflex ( nBR ) . Twenty-eight migraine patients received ASA ( n = 14 , 1000 mg i.v ) or ZOL ( n = 14 , 5 mg p.o ) during the acute migraine attack and interictally . Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design . nBR was recorded in all patients and subjects before , 60 and 90 min after treatment . ASA and ZOL did not inhibit nBR responses in healthy subjects . Both ASA and ZOL suppressed nBR responses ( ASA by 68 % , ZOL by 78 % ) only during the acute attack but not interictally . The data suggest , that the anti-nociceptive effects of migraine drugs on the trigeminal nociceptive processing are different during and outside an acute migraine attack |
13,088 | 29,025,004 | Conclusions Better diet quality is associated with reduced risk of pancreatic cancer .
The associations between dietary patterns and pancreatic cancer were stronger in case-control studies than in cohort studies and were stronger among men than among women | Context Pancreatic cancer has the highest case fatality rate of all major cancers .
Objective A systematic review using PRISMA guidelines was conducted to summarize the associations between dietary patterns and risk of pancreatic cancer . | BACKGROUND The Mediterranean diet has been suggested to play a beneficial role for health and longevity . However , to our knowledge , no prospect i ve US study has investigated the Mediterranean dietary pattern in relation to mortality . METHODS Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP ( formerly known as the American Association of Retired Persons ) Diet and Health Study . During follow-up for all-cause mortality ( 1995 - 2005 ) , 27,799 deaths were documented . In the first 5 years of follow-up , 5,985 cancer deaths and 3,451 cardiovascular disease ( CVD ) deaths were reported . We used a 9-point score to assess conformity with the Mediterranean dietary pattern ( components included vegetables , legumes , fruits , nuts , whole grains , fish , monounsaturated fat-saturated fat ratio , alcohol , and meat ) . We calculated hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) using age- and multivariate-adjusted Cox models . RESULTS The Mediterranean diet was associated with reduced all-cause and cause-specific mortality . In men , the multivariate HRs comparing high to low conformity for all-cause , CVD , and cancer mortality were 0.79 ( 95 % CI , 0.76 - 0.83 ) , 0.78 ( 95 % CI , 0.69 - 0.87 ) , and 0.83 ( 95 % CI , 0.76 - 0.91 ) , respectively . In women , an inverse association was seen with high conformity with this pattern : decreased risks that ranged from 12 % for cancer mortality to 20 % for all-cause mortality ( P = .04 and P < .001 , respectively , for the trend ) . When we restricted our analyses to never smokers , associations were virtually unchanged . CONCLUSION These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes , including deaths due to CVD and cancer , in a US population The Healthy Eating Index-2005 ( HEI-2005 ) measures adherence to the 2005 Dietary Guidelines for Americans , but the association between the HEI-2005 and risk of chronic disease is not known . The Alternative Healthy Eating Index ( AHEI ) , which is based on foods and nutrients predictive of chronic disease risk , was associated inversely with chronic disease risk previously . We up date d the AHEI , including additional dietary factors involved in the development of chronic disease , and assessed the associations between the AHEI-2010 and the HEI-2005 and risk of major chronic disease prospect ively among 71,495 women from the Nurses ' Health Study and 41,029 men from the Health Professionals Follow-Up Study who were free of chronic disease at baseline . During ≥24 y of follow-up , we documented 26,759 and 15,558 incident chronic diseases ( cardiovascular disease , diabetes , cancer , or nontrauma death ) among women and men , respectively . The RR ( 95 % CI ) of chronic disease comparing the highest with the lowest quintile was 0.84 ( 0.81 , 0.87 ) for the HEI-2005 and 0.81 ( 0.77 , 0.85 ) for the AHEI-2010 . The AHEI-2010 and HEI-2005 were most strongly associated with coronary heart disease ( CHD ) and diabetes , and for both outcomes the AHEI-2010 was more strongly associated with risk than the HEI-2005 ( P-difference = 0.002 and < 0.001 , respectively ) . The 2 indices were similarly associated with risk of stroke and cancer . These findings suggest that closer adherence to the 2005 Dietary Guidelines may lower risk of major chronic disease . However , the AHEI-2010 , which included additional dietary information , was more strongly associated with chronic disease risk , particularly CHD and diabetes BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation , which implies the contribution of diet and lifestyle in its etiology . We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis . Until 2008 , 865 nonendocrine pancreatic cancer cases have been observed . Calibrated relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were computed using multivariable-adjusted Cox hazard regression models . The consumption of red meat ( RR per 50 g increase per day = 1.03 , 95 % CI = 0.93 - 1.14 ) and processed meat ( RR per 50 g increase per day = 0.93 , 95 % CI = 0.71 - 1.23 ) were not associated with an increased pancreatic cancer risk . Poultry consumption tended to be associated with an increased pancreatic cancer risk ( RR per 50 g increase per day = 1.72 , 95 % CI = 1.04 - 2.84 ) ; however , there was no association with fish consumption ( RR per 50 g increase per day = 1.22 , 95 % CI = 0.92 - 1.62 ) . Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer . The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings BACKGROUND Advanced glycation end products ( AGEs ) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures . AGEs have been associated with insulin resistance , oxidative stress , and chronic inflammation in patients with diabetes . Dietary AGEs are an important contributor to the AGE pool in the body . N(ϵ)-(carboxymethyl)lysine ( CML ) AGE is one of the major biologically and chemically well-characterized AGE markers . The consumption of red meat , which is CML-AGE rich , has been positively associated with pancreatic cancer in men . OBJECTIVES With the use of a published food CML-AGE data base , we estimated the consumption of CML AGE in the prospect i ve NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer . DESIGN Multivariate Cox proportional hazard regression models were used to estimate HRs and 95 % CIs for pancreatic cancer . RESULTS During an average of 10.5 y of follow-up , we identified 2193 pancreatic cancer cases ( 1407 men and 786 women ) from 528,251 subjects . With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption , we observed increased pancreatic cancer risk in men ( HR : 1.43 ; 95 % CI : 1.06 , 1.93 , P-trend = 0.003 ) but not women ( HR : 1.14 ; 95 % CI : 0.76 , 1.72 , P-trend = 0.42 ) . Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer ( HR : 1.35 ; 95 % CI : 1.07 , 1.70 ) , which attenuated after adjustment for CML-AGE consumption ( HR : 1.20 ; 95 % CI : 0.95 , 1.53 ) . CONCLUSION Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer BACKGROUND & AIMS Diet could affect risk for esophageal and gastric cancers , but associations have been inconsistent . The diet is complex , so studies of dietary patterns , rather than studies of individual foods , might be more likely to identify cancer risk factors . There is limited research on index-based dietary patterns and esophageal and gastric cancers . We prospect ively evaluated associations between the Healthy Eating Index-2005 ( HEI-2005 ) and alternate Mediterranean Diet ( aMED ) scores and risk of esophageal and gastric cancers . METHODS We analyzed data from 494,968 participants in the National Institutes of Health-AARP Diet and Health study , in which AARP members ( age , 51 - 70 y ) completed a self-administered baseline food frequency question naire between 1995 and 1996 . Their answers were used to estimate scores for each index . RESULTS During the follow-up period ( 1995 - 2006 ) , participants developed 215 esophageal squamous cell carcinomas ( ESCCs ) , 633 esophageal adenocarcinomas ( EACs ) , 453 gastric cardia adenocarcinomas , and 501 gastric noncardia adenocarcinomas . Higher scores from the HEI-2005 were associated with a reduced risk of ESCC ( comparing the highest quintile with the lowest quintile : hazard ratio , 0.51 ; 95 % confidence interval , 0.31 - 0.86 ; Ptrend = .001 ) and EAC ( hazard ratio , 0.75 ; 95 % confidence interval , 0.57 - 0.98 ; Ptrend = .01 ) . We observed an inverse association between ESCC , but not EAC , and a higher aMED score ( meaning a higher- quality diet ) . HEI-2005 and aMED scores were not associated significantly with gastric cardia or noncardia adenocarcinomas . CONCLUSIONS By using data collected from 1995 through 2006 from the National Institutes of Health-AARP Diet and Health Study , HEI-2005 and aMED scores were associated inversely with risk for esophageal cancers , particularly ESCC . Adherence to dietary recommendations might help prevent esophageal cancers Epidemiological data investigating the relation between fruit and vegetable consumption and pancreatic cancer risk have shown inconsistent results so far . Most case-control studies observed an inverse association with total fruit and vegetable consumption , whereas results from most cohort studies have largely been null . We examined prospect ively the relation between pancreatic cancer risk and intake of vegetables , fruits , carotenoids and vitamins C and E. The Netherl and s Cohort Study consisted of 120,852 men and women who completed a question naire at baseline in 1986 , including a vali date d 150-item food-frequency question naire . After 16.3 years of follow-up , 423 cases were available for analysis . Total vegetable and total fruit consumption were not associated with pancreatic cancer risk ( highest vs. lowest quintile , multivariable-adjusted hazard rate ratio = 1.23 , 95 % confidence interval : 0.86 - 1.75 and multivariable-adjusted hazard rate ratio = 0.90 , 95 % confidence interval : 0.66 - 1.24 , respectively ) . Also , for cooked vegetables , raw vegetables and vegetables and fruits classified into subgroups , no associations were observed . Dietary carotenoids , vitamin C and E intake and supplements containing vitamin C or E were not associated with pancreatic cancer risk . The results were not modified by sex , smoking status and body mass index . In conclusion , we observed no association between a high consumption of vegetables and fruits and pancreatic cancer risk in this large cohort study , which is in agreement with previous prospect i ve studies . Furthermore , we observed no association between the intake of carotenoids , vitamins and vitamin supplements and pancreatic cancer risk BACKGROUND Head and neck cancer ( HNC ) is the seventh most common cancer worldwide . Although diet has been proposed to play an important role in HNC , few associations with diet have been convincing other than alcohol intake . Studies of dietary patterns that examine overall diets may provide broader insight than studies of individual foods . Little is known about the association between dietary patterns and risk of HNC . OBJECTIVE We prospect ively evaluated the association between 2 index-based dietary patterns [ ie , the Healthy Eating Index-2005 ( HEI-2005 ) and alternate Mediterranean Diet Score ( aMED ) ] and risk of head and neck squamous cell carcinoma . DESIGN We included 494,967 participants from the NIH-AARP Diet and Health study ( 1995 - 2006 ) . HRs ( 95 % CIs ) were estimated by using Cox regression . Scores for the HEI-2005 and aMED were calculated on the basis of diet assessed by using a baseline food-frequency question naire . Higher scores reflected adherence to dietary recommendations for healthy eating . Our main outcome was the incidence of HNC , including cancer of the larynx , oral cavity , and orohypopharynx . RESULTS A total of 1868 HNC cases were identified during follow-up . Higher HEI-2005 scores were associated with reduced risk of HNC in men [ HR : 0.74 ( 95 % CI : 0.61 , 0.89 ) for highest compared with lowest quintiles ; P-trend = 0.0008 ] and women [ HR : 0.48 ; 95 % CI : 0.33 , 0.70 ; P-trend < 0.0001 ] . High aMED scores were also associated with lower HNC risk in men ( HR : 0.80 ; 95 % CI : 0.64 , 1.01 ; P-trend = 0.002 ) and women ( HR : 0.42 ; 95 % CI : 0.24 , 0.74 ; P-trend < 0.0001 ) . Associations were similar among subsites . We did not find significant interactions between smoking and alcohol intake and each index on HNC risk . CONCLUSIONS HEI-2005 and aMED scores were associated inversely with risk of HNC . Large interventional studies are required to assess the causality before conveying definite public health messages BACKGROUND Smoking , alcohol use , diet , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , and physical activity have been studied independently in relation to pancreatic cancer . We generated a healthy lifestyle score to investigate their joint effect on risk of pancreatic cancer . METHODS In the prospect i ve National Institutes of Health-AARP Diet and Health Study , a total of 450 416 participants aged 50 to 71 years completed the baseline food frequency question naire ( 1995 - 1996 ) eliciting diet and lifestyle information and were followed up through December 31 , 2003 . We identified 1057 eligible incident pancreatic cancer cases . Participants were scored on 5 modifiable lifestyle factors as unhealthy ( 0 points ) or healthy ( 1 point ) on the basis of current epidemiologic evidence . Participants received 1 point for each respective lifestyle factor : nonsmoking , limited alcohol use , adherence to the Mediterranean dietary pattern , body mass index ( > or = 18 and < 25 ) , or regular physical activity . A combined score ( 0 - 5 points ) was calculated by summing the scores of the 5 factors . Cox proportional hazards regression models were used to estimate relative risk ( 95 % confidence interval ) for pancreatic cancer . RESULTS Compared with the lowest combined score ( 0 points ) , the highest score ( 5 points ) was associated with a 58 % reduction in risk of developing pancreatic cancer in all participants ( relative risk , 0.42 ; 95 % confidence interval , 0.26 - 0.66 ; P(trend ) < .001 ) . Scores of less than 5 points were associated with 27 % of pancreatic cancer cases in our population . CONCLUSION Findings from this large study suggest that having a high score , as opposed to a low score , on an index combining 5 modifiable lifestyle factors substantially reduces the risk of developing pancreatic cancer BACKGROUND Previous research relating dietary fat , a modifiable risk factor , to pancreatic cancer has been inconclusive . METHODS We prospect ively analyzed the association between intakes of fat , fat subtypes , and fat food sources and exocrine pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study , a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency question naire in 1995 - 1996 . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were calculated using Cox proportional hazards regression models , with adjustment for energy intake , smoking history , body mass index , and diabetes . Statistical tests were two-sided . RESULTS Over an average follow-up of 6.3 years , 865 men and 472 women were diagnosed with exocrine pancreatic cancer ( 45.0 and 34.5 cases per 100 000 person-years , respectively ) . After multivariable adjustment and combination of data for men and women , pancreatic cancer risk was directly related to the intakes of total fat ( highest vs lowest quintile , 46.8 vs 33.2 cases per 100 000 person-years , HR = 1.23 , 95 % CI = 1.03 to 1.46 ; P(trend ) = .03 ) , saturated fat ( 51.5 vs 33.1 cases per 100 000 person-years , HR = 1.36 , 95 % CI = 1.14 to 1.62 ; P(trend ) < .001 ) , and monounsaturated fat ( 46.2 vs 32.9 cases per 100 000 person-years , HR = 1.22 , 95 % CI = 1.02 to 1.46 ; P(trend ) = .05 ) but not polyunsaturated fat . The associations were strongest for saturated fat from animal food sources ( 52.0 vs 32.2 cases per 100 000 person-years , HR = 1.43 , 95 % CI = 1.20 to 1.70 ; P(trend ) < .001 ) ; specifically , intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk ( HR = 1.27 and 1.19 , respectively ) . CONCLUSION In this large prospect i ve cohort with a wide range of intakes , dietary fat of animal origin was associated with increased pancreatic cancer risk Summary . Background : A prospect i ve cohort study with university level participants was initiated to study the effect of Mediterranean diet on health . Aims : The objective of this study was to identify possible lifestyle and socioeconomic variables associated with the consumption of a Mediterranean dietary pattern ( MDP ) . Method : This analysis includes 1587 males and 2260 females . MDP was defined “ a priori ” by summing the st and ardized residuals of nutrients and foods after adjusting a regression model using total energy intake as the independent variable . Multiple regression and non-parametric locally weighted regression models were adjusted with the relative adherence to the MDP as the dependent variable in males and females . Results : Women were more compliant than men with the MDP ( Coefficient regression ( b ) = 4.1 ; Confidence Interval ( CI ) 95 % = 3.2 to 4.9 ) . The compliance with the MDP was significantly poorer among younger participants both in men and women ( p < 0.001 in men and in women ) . Participants who were more physically active were more likely to fulfill the traditional MDP ( p = 0.01 in men and p < 0.001 in women ) . Conclusions : Our findings provide evidence supporting the progressive departure from the traditional MDP in younger and highly educated subjects of the Mediterranean area . A more active life-style is associated with a better compliance with the MDP Background Few epidemiologic studies have examined the role of nutrient intake in the development of pancreatic cancer in Japan . We addressed this association in a population -based case-control study . Methods The cases were 109 patients who were newly diagnosed with pancreatic cancer between January 2000 and March 2002 , and controls were selected by a r and om procedure from the general population . Data on dietary intake were collected by in-person interview , with the use of a food-frequency question naire . The risk of pancreatic cancer associated with nutrient intake was estimated by using the odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) derived from a conditional logistic model . Results A statistically positive trend in risk was observed with increasing cholesterol intake , with subjects in the highest tertile experiencing a two fold increased risk ( OR , 2.06 ; 95 % CI , 1.11–3.85 ; Ptrend = 0.02 ) . Vitamin C intake was negatively associated with risk of pancreatic cancer . The OR was 0.45 ( 95 % CI , 0.22–0.94 ) for subjects in the highest tertile compared to the lowest tertile ( Ptrend = 0.04 ) . Conclusions Our study indicates that high cholesterol intake is significantly associated with an increased risk of pancreatic cancer and that high vitamin C intake decreases the risk of pancreatic cancer Although mounting evidence suggests that insulin resistance is involved in pancreatic carcinogenesis , few epidemiologic studies have comprehensively investigated the role of lifestyle factors influencing this metabolic disorder in the etiology of pancreatic cancer . We sought to examine this problem in a case-control study conducted in 1994–1998 in Minnesota . Cases ( n = 186 ) , aged 20 yr or older , were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic ; from the latter , only cases residing in the Upper Midwest of the United States were recruited . Controls ( n = 554 ) were r and omly selected from the general population and frequency matched to cases by age ( within 5 yr ) and sex . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were estimated using unconditional logistic regression . After adjustment for confounders , physical activity was associated with a reduced risk , but this protective effect was confined to light activity and moderate activity only ( OR = 0.55 , 95 % CI = 0.30–0.97 , P trend = 0.038 and OR = 0.51 , 95 % CI = 0.28–0.93 , P trend = 0.07 , for highest vs. lowest quartile , respectively ) . An increased risk was found for dietary intakes of energy and fat but was statistically significant for saturated and polyunsaturated fat only . Of note , no appreciable difference in the magnitude of the associations existed between saturated , monounsaturated , and polyunsaturated fat . Compared with individuals in the lowest quartile of fiber intake , the risk was approximately halved for those in the third ( OR = 0.49 , 95 % CI = 0.26–0.94 ) and the highest quartile ( OR = 0.52 , 95 % CI = 0.21–1.30 ) . Our study lends support to the hypothesis that dietary and other lifestyle factors influencing insulin resistance modulate pancreatic cancer risk The Mediterranean diet has been widely promoted and may be associated with chronic disease prevention and a better overall health status . The aim of this study was to evaluate whether the Mediterranean diet score inversely predicted total or cause-specific mortality in a prospect i ve population study in Northern Sweden ( Västerbotten Intervention Program ) . The analyses were performed in 77,151 participants ( whose diet was measured by means of a vali date d FFQ ) by Cox proportional hazard models adjusted for several potential confounders . The Mediterranean diet score was inversely associated with all-cause mortality in men [ HR = 0.96 ( 95 % CI = 0.93 , 0.99 ) ] and women [ HR = 0.95 ( 95 % CI = 0.91 , 0.99 ) ] , although not in obese men . In men , but not in women , the score was inversely associated with total cancer mortality [ HR = 0.92 ( 95 % CI = 0.87 , 0.98 ) ] , particularly for pancreas cancer [ HR = 0.82 ( 95 % CI = 0.68 , 0.99 ) ] . Cardiovascular mortality was inversely associated with diet only in women [ HR = 0.90 ( 95 % CI = 0.82 , 0.99 ) ] . Except for alcohol [ HR = 0.83 ( 95 % CI = 0.76 , 0.90 ) ] and fruit intake [ HR = 0.90 ( 95 % CI = 0.83 , 0.98 ) ] , no food item of the Mediterranean diet score independently predicted mortality . Higher scores were associated with increasing age , education , and physical activity . Moreover , healthful dietary and lifestyle-related factors additively decreased the mortality likelihood . Even in a suba rct ic region , increasing Mediterranean diet scores were associated with a longer life , although the protective effect of diet was of small magnitude compared with other healthful dietary and lifestyle-related factors examined BACKGROUND In the Multiethnic Cohort ( MEC ) study , we showed inverse associations between flavonols and pancreatic cancer risk . OBJECTIVE We aim ed to define a food pattern associated with intakes of quercetin , kaempferol , and myricetin ; to examine the association of that pattern with pancreatic cancer risk ; and to investigate the associations in an independent study . DESIGN Reduced rank regression was applied to dietary data for 183,513 participants in the MEC . A food group pattern was extracted and simplified and applied to dietary data of 424,978 participants in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Dietary intake in both studies was assessed by using specially developed question naires . Multivariate Cox proportional hazards models were used to estimate relative risks for pancreatic cancer in the MEC ( 610 cases ) and the EPIC ( 517 cases ) studies . RESULTS The food group pattern consisted mainly of tea , fruit , cabbage , and wine . In the MEC , inverse associations with pancreatic cancer in smokers were observed for the food group pattern [ relative risk : 0.59 ( 95 % CI : 0.31 , 1.12 ) when extreme quintiles were compared ; P for trend = 0.03 ] . In the EPIC study , the simplified pattern was not associated with pancreatic cancer risk ( P for trend = 0.78 ) . CONCLUSIONS A food pattern associated with the intake of quercetin , kaempferol , and myricetin was associated with lower pancreatic cancer risk in smokers in a US-based population . However , failure to replicate the associations in an independent study weakens the conclusions and raises questions about the utility of food patterns for flavonols across population The authors investigated the association of adherence to Mediterranean diet with colorectal cancer ( CRC ) risk in the European Prospect i ve Investigation into Cancer and nutrition study . Adherence to Mediterranean diet was expressed through two 10-unit scales , the Modified Mediterranean diet score ( MMDS ) and the Centre-Specific MMDS ( CSMMDS ) . Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales . Adjusted hazard ratios ( HR ) for the associations of these scales with CRC incidence were estimated . After 5,296,617 person-years of follow-up , 4,355 incident CRC cases were identified . A decreased risk of CRC , of 8 and 11 % was estimated when comparing the highest ( scores 6–9 ) with the lowest ( scores 0–3 ) adherence to CSMMDS and MMDS respectively . For MMDS the HR was 0.89 ( 95 % confidence interval ( CI ) : 0.80 , 0.99 ) . A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk ( HR for MMDS : 0.96 ; 95 % CI : 0.92 , 1.00 ) . These associations were somewhat more evident , among women , were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS . These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk Introduction : Identifying modifiable risk factors for pancreatic cancer is important because of its poor prognosis . Previous findings on diet are inconsistent . Methods : Associations between intake of nutrients , food groups , dietary patterns , and pancreatic cancer risk were examined among 34,642 postmenopausal women in the Iowa Women 's Health Study ( IWHS ) . Results : No significant associations were observed between intake of nutrients and food groups or dietary patterns and pancreatic cancer . Conclusion : Our findings do not support the hypothesis that fruits , vegetables , and red meat are associated with risk of pancreatic cancer . Impact : Dietary intake , assessed in multiple aspects in a large prospect i ve cohort study , was not associated with pancreatic cancer . Cancer Epidemiol Biomarkers Prev ; 20(4 ) ; 711–4 . © 2011 AACR Case-control studies of pancreatic cancer were conducted in 5 population s with moderate to high rates and differing dietary practice s , using a common protocol and question naire . Comprehensive diet histories were completed for a total of 802 cases and 1669 controls identified in Adelaide ( Australia ) , Montreal and Toronto ( Canada ) , Utrecht ( The Netherl and s ) and Opole ( Pol and ) . Positive associations were observed with intake of carbohydrates and cholesterol , and inverse associations with dietary fiber and vitamin C. These relationships were generally consistent among the 5 studies , and showed statistically significant and generally monotonic dose-response relationships . The relative risks for highest vs. lowest quintile of intake were estimated for carbohydrates to be 2.57 ( 95 % confidence interval 1.64 - 4.03 ) , cholesterol 2.68 ( 1.72 - 4.17 ) , dietary fiber 0.45 ( 0.30 - 0.63 ) , and vitamin C 0.53 ( 0.38 - 0.76 ) . The consistency , strength , and specificity of these associations provides evidence for the hypothesis that some or all of these dietary factors may alter the risk of pancreatic cancer BACKGROUND Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China . Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis . The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China . MATERIAL S AND METHODS Cases ( n=323 ) were ascertained from four provincial cancer hospitals . Controls ( n=323 ) were r and omly selected from the family members of patients without pancreatic cancer in the same hospitals , 1:1 matched to cases by gender , age and study center . Data were collected with a question naire by personal interview . Odds ratios ( OR ) and 95 % confidence intervals ( 95%CI ) were estimated using conditional logistic regression . RESULTS Tea intake ( OR = 0.49 ; 95%CI : 0.30 - 0.80 ) was associated with a half reduction in risk of pancreatic cancer . Reduced vegetable consumption ( P trend : 0.04 ) was significant related to pancreatic cancer . Although no significant association was found for meat and fruit , ORs were all above or below the reference group . A protective effect was found for fruit ( OR=1.73 for consumption of 1 - 2 times/week vs more than 3 times/week ; 95%CI : 1.05 - 2.86 ) . A high intake of meat was associated to a higher risk of pancreatic cancer ( OR=0.59 for consumption of 1 - 2 times /week vs. more than 3 times /week ; 95%CI : 0.35 - 0.97 ) . CONCLUSIONS The present study supports fruit consumption to reduce pancreatic cancer risk and indicates that high consumption of meat is related to an elevated risk . Direct inverse relations with tea and vegetable intake were also confirmed Observational studies have reported inconsistent results on the association between fruit and vegetable intake and the risk of pancreatic cancer . We carried out a meta- analysis of epidemiological studies to summarize available evidence . We search ed PubMed , Scopus , and ISI Web of Science data bases for relevant studies published until the end of January 2015 . Fixed-effects and r and om-effects models were used to estimate the summary relative risks ( RRs ) and 95 % confidence intervals ( CIs ) for the associations between fruit and vegetable intake and the risk of pancreatic cancer . A total of 15 case – control studies , eight prospect i ve studies , and one pooled analysis fulfilled the inclusion criteria . The summary RR for the highest versus the lowest intake was 0.73 ( 95 % CI=0.53–1.00 ) for fruit and vegetables , 0.73 ( 95 % CI=0.63–0.84 ) for fruit , and 0.76 ( 95 % CI=0.69–0.83 ) for vegetables , with significant heterogeneities ( I2=70.5 , 55.7 , and 43.0 % , respectively ) . Inverse associations were observed in the stratified analysis by study design , although the results of prospect i ve studies showed borderline significance , with corresponding RR=0.90 ( 95 % CI=0.77–1.05 ) for fruit and vegetable intake , 0.93 ( 95 % CI=0.83–1.03 ) for fruit intake , and 0.89 ( 95 % CI=0.80–1.00 ) for vegetable intake . Besides , significant inverse associations were observed in the majority of other subgroup analyses by study quality , geographic location , exposure assessment method , and adjustment for potential confounders . Findings from the present meta- analysis support that fruit and vegetable intake is associated inversely with the risk of pancreatic cancer . However , study design may play a key role in the observed magnitude of the aforementioned association . Future well- design ed prospect i ve studies are warranted to confirm these findings |
13,089 | 28,638,496 | We did not find a difference in effectiveness between studies using a 7-day versus a 30-day follow-up .
Based on low- and very low- quality evidence , follow-up within 7 days and within 30 days of discharge from hospitalization for heart failure or COPD -compared with usual care or no follow-up-were both associated with a reduced risk of all-cause readmission , emergency department visits , and mortality .
Overall , there is a lack of large , method ologically robust studies specifically focusing on the effectiveness of 7-day follow-up after discharge in improving patient outcomes | BACKGROUND Transitions in care can increase patients ' vulnerability to adverse events .
In particular , patients admitted for heart failure or chronic obstructive pulmonary disorder ( COPD ) have high rates of readmission and return emergency department visits .
Heart failure patients have the highest 30-day readmission rates in Canada , and COPD patients comprise the highest volume of readmissions .
Combined , these two conditions account for the largest number of emergency department returns .
Prompt follow-up of discharged patients has been linked with reduced rates of readmission , emergency department use , and death .
This systematic review evaluated the clinical effectiveness of early follow-up , within either 7 days or 30 days after hospital discharge , compared with usual care or a different time to follow-up , in reducing readmissions , emergency department visits , and mortality in patients with heart failure or COPD . | Importance The transition from hospital to home can expose patients to adverse events during the post discharge period . Post discharge care including phone calls may provide support for patients returning home but the impact on care transitions is unknown . Objective To examine the effect of a 72-hour post discharge phone call on the patient 's transition of care experience . Design Cluster-r and omized control trial . Setting Urban , academic medical center . Participants General medical patients age 18 and older discharged home after hospitalization . Main Outcomes and Measures Primary outcome measure was the Care Transition Measure ( CTM-3 ) score , a vali date d measure of the quality of care transitions . Secondary measures included self-reported adherence to medication and follow up plans , and 30-day composite of emergency department ( ED ) visits and hospital readmission . Results 328 patients were included in the study over an 6-month period . 114 ( 69 % ) received a post discharge phone call , and 214 of all patients in the study completed the follow outcome survey ( 65 % response rate ) . A small difference in CTM-3 scores was observed between the intervention and control groups ( 1.87 points , 95 % CI 0.47–3.27 , p = 0.01 ) . Self-reported adherence to treatment plans , ED visits , and emergency readmission rates were similar between the two groups ( odds ratio 0.57 , 95 % CI 0.13–2.45 , 1.20 , 95 % CI 0.61–2.37 , and 1.18 , 95 % CI 0.53–2.61 , respectively ) . Conclusions and Relevance A single post discharge phone call had a small impact on the quality of care transitions and no effect on hospital utilization . Higher intensity post discharge support may be required to improve the patient experience upon returning home . Trial Registration Clinical Trials.gov OBJECTIVES To determine if a community pharmacy-based transition of care ( TOC ) program that included the full scope of medication therapy management ( MTM ) services ( TransitionRx ) decreased hospital readmissions , resolved medication-related problems , and increased patient satisfaction . DESIGN Prospect i ve , quasi-experimental study . SETTING Nine Kroger Pharmacies located in Western Cincinnati . PATIENTS Patients older than 18 years of age and discharged from two local hospitals with a diagnosis of congestive heart failure , chronic obstructive pulmonary disease , or pneumonia . Patients were recruited from two local hospitals and referred to the community pharmacy for MTM services with the pharmacist within 1 week of discharge . MAIN OUTCOME MEASURES Pharmacists reconciled the patients ' medications , identified drug therapy problems , recommended changes to therapy , and provided self-management education . At 30 days after discharge , research personnel conducted telephone surveys , using a previously vali date d survey instrument , to assess hospital readmissions and patient satisfaction . Pharmacist interventions and medication-related problems were documented . RESULTS A total of 90 patients completed the study . Of these , 20 % of patients in the usual care group were admitted to the hospital within 30 days compared with 6.9 % of patients in the intervention group ( P = 0.019 ) . In the 30 patients who received MTM services from the pharmacist , 210 interventions were made . The overall mean patient satisfaction with the TOC process was not significantly different between patients who were seen by the pharmacist and those who were not seen by the pharmacist . CONCLUSION Community pharmacies successfully collaborated with hospitals to develop a referral process for TOC interventions . Patients who received MTM services from the pharmacist experienced significantly fewer readmissions than patients who received usual care ABSTRACT BACKGROUND Rehospitalizations within 30 days of discharge are responsible for a large portion of healthcare spending . One approach to preventing rehospitalizations is early follow-up , usually defined as an office visit with a primary care physician within 7 days of discharge — an approach that is being incentivized by health plans . However , evidence regarding its effectiveness is limited . OBJECTIVE We aim ed to determine whether an office visit with a primary care physician within 7 days after discharge is associated with 30-day rehospitalization . DESIGN This was an observational study set within a r and omized trial . PARTICIPANTS The study included patients age 65 and older receiving care from a multi-specialty group practice and discharged from hospital to home between 26 August 2010 and 25 August 2011 . To control for confounding , we identified characteristics of patients and hospital stays that are predictive of rehospitalization , and also developed high-dimensional propensity scores . Analyses used Cox proportional hazards models and took into account varying amounts of opportunity time for office visits . MAIN MEASURES We looked at 30-day rehospitalizations at any hospital . KEY RESULTS Of 3,661 patients discharged to home during the study year , 707 ( 19.3 % ) were rehospitalized within 30 days . Patients receiving an office visit within 7 days numbered 1,808 ( 49.4 % ) , and of these , 1,000 ( 27.3 % ) were with a primary care physician . In models predicting rehospitalization , stratified on deciles of propensity score and controlling for additional confounders , the hazard ratios associated with office visits with a primary care physician within 7 days were 0.98 ( 95 % CI 0.80 , 1.21 ) ; for visits with any physician , the hazard ratio was HR 1.04 , ( 95 % CI 0.87 , 1.25 ) . CONCLUSIONS We found no protective effect for office visits within 7 days . Such visits may need to be specifically focused on a range of issues related to the specific reasons why patients are rehospitalized . It is likely that outpatient visits will need to be set within comprehensive transition programs 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 AIM This paper reports a study to determine whether a nurse-initiated telephone follow-up programme could increase patients ' self-efficacy in managing dyspnoea and decrease health care service use . BACKGROUND Chronic obstructive pulmonary disease is a worldwide health problem and has been labelled a burdensome disease . Because of the fear of activity-induced dyspnoea , patients with chronic obstructive pulmonary disease lack the confidence to perform daily activities . Studies of cardiac and diabetic patients have shown that telephone follow-up care is an effective approach to increasing self-efficacy . However , little such research has been done with patients with chronic obstructive pulmonary disease . METHODS This was a r and omized controlled study . A total of 60 participants ( 30 telephone follow-up , 30 control ) with chronic obstructive pulmonary disease were recruited from an acute care hospital in Hong Kong . The Chinese Self-Efficacy Scale was used to assess self-efficacy . Measures of health care use were numbers of visits to an accident and emergency department , hospitalizations , and unscheduled visits by physicians . FINDINGS The self-efficacy scores ( U = 272.5 , P = 0.009 ) of patients who were followed up by telephone improved significantly compared with those of patients in the control group . Multiple regression analyses showed that telephone follow-up ( Beta = 0.33 , CI : 0.19 - 0.48 , P = 0.001 ) , the pulmonary rehabilitation programme ( Beta = 0.44 , CI : 0.16 - 0.72 , P = 0.003 ) , smoking ( Beta = 0.34 , CI : 0.09 - 0.57 , P = 0.009 ) , and health care use ( Beta = -0.27 , CI : -0.47-(-0.07 ) , P = 0.008 ) were significant factors in predicting patient self-efficacy . CONCLUSIONS Nurse-initiated telephone follow-up care was effective in increasing self-efficacy in managing dyspnoea . The study needs to be replicated in other setting to strengthen its external validity BACKGROUND Chronic obstructive pulmonary disease ( COPD ) exacerbation increases mortality and re sources used associated with hospitalization . We studied whether early home monitoring reduces the rate of readmission and if there are any predictor variables . PATIENTS AND METHODS We performed a prospect i ve , controlled , parallel-group study in patients who were hospitalized for COPD . Patients whose residence was within less than 15 km from the hospital were assigned to an interventional group ( home visits by nurses about 48 - 72hours after discharge ) , the remainder were assigned to a conventional care group . The rate of rehospitalization within the first month was compared between the two groups , as well as those variables that showed a predictive capability . RESULTS Seventy one patients were included : 35 in the conventional care group and 36 in the interventional group . In the latter , the treatment was modified in 13 patients ( 36 % ) . The hospital readmission rate was 17 % , which was similar in both groups ( P=.50 ) . For every 5-year increase in age , the risk for readmission was 2.54 ( 95%CI , 1.06 - 5.07 ) and for each increase of 10mmHg in PaCO(2 ) , the risk of readmission was 8.34 ( 95%CI , 2.43 - 18.55 ) . CONCLUSIONS Early home monitoring did not decrease the readmission rate during the first month . Older age and high PaCO(2 ) are factors that identify the group with a high risk for rehospitalization |
13,090 | 26,945,986 | Temsirolimus increases progression-free survival and overall survival compared to IFN-alpha .
Discussion Experts tend to prefer sunitinib as first-line therapy even in poor-prognosis mRCC .
In light of the systematic review , no targeted therapy appears to be more effective than another . | Background and Objectives No head-to-head clinical trials are available to help physicians in the decision-making process of first-line therapy in poor-prognosis metastatic renal cell carcinoma ( RCC ) .
The objectives of our study were to identify experts ’ prescribing practice s and to review available clinical data in first-line therapies for poor-prognosis metastatic RCC ( mRCC ) . | PURPOSE To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma ( RCC ) treated with interferon-alfa as initial systemic therapy . The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy . PATIENTS AND METHODS Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospect i ve clinical trials were the subjects of this retrospective analysis . Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model . RESULTS The median overall survival time was 13 months . The median time to progression was 4.7 months . Five variables were used as risk factors for short survival : low Karnofsky performance status , high lactate dehydrogenase , low serum hemoglobin , high corrected serum calcium , and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year . Each patient was assigned to one of three risk groups : those with zero risk factors ( favorable risk ) , those with one or two ( intermediate risk ) , and those with three or more ( poor risk ) . The median time to death of patients deemed favorable risk was 30 months . Median survival time in the intermediate-risk group was 14 months . In contrast , the poor-risk group had a median survival time of 5 months . CONCLUSION Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations . The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma ( nccRCC ) . PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes . Patients were treated with 50 mg/day oral sunitinib for 4 weeks , followed by 2 weeks of rest . The primary end point was overall response rate ( RR ) . RESULTS Thirty-one eligible patients were enrolled . Twenty-four patients ( 77 % ) had prior nephrectomy . By Memorial Sloan-Kettering Cancer Center criteria , 8 patients ( 26 % ) had poor risk and 14 ( 45 % ) had intermediate risk . Twenty-two patients had papillary renal cell carcinoma ( RCC ) , and three had chromophobe RCC . Eleven patients had partial response with a RR of 36 % ( 95 % confidence interval ( CI ) 19 % to 52 % ) and an additional 17 patients ( 55 % ) had stable disease . Median duration of response was 12.7 months ( 95 % CI 6.3 - 19.1 months ) , and median progression-free survival was 6.4 months ( 95 % CI 4.2 - 8.6 months ) . At a median follow-up duration of 18.7 months ( 95 % CI 13.7 - 23.7 months ) , 13 patients ( 42 % ) had died , result ing in an estimated median survival of 25.6 months ( 95 % CI 8.4 - 42.9 months ) . Toxicity profiles were commensurate with prior reports . CONCLUSIONS Sunitinib has promising activity in patients with nccRCC ( NCT01219751 ) BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) STUDY OBJECTIVE To quantify the influence of a high-fat meal on the oral bioavailability of the immunosuppressant everolimus in a single-dose study in healthy subjects and to confirm the results in a small food-effect screening assessment in patients with renal transplants who were receiving multiple-dose everolimus . DESIGN R and omized , open-label , crossover , single-dose study and confirmatory screening . SETTING Phase 1 unit for the single-dose study and two German hospitals for the patient screening . SUBJECTS Twenty-four healthy male volunteers ; six clinical ly stable patients with renal transplants who were originally part of a phase I dose-escalation study . INTERVENTION The 24 healthy men received everolimus 2 mg orally under fasting conditions and after a high-fat meal . The six patients received everolimus 2.5 mg/day orally , in addition to cyclosporine and prednisone . On two occasions , a pharmacokinetic profile was obtained over the dosing interval after drug administration under fasting conditions and after a high-fat meal in a r and omized sequence . MEASUREMENTS AND MAIN RESULTS In the single-dose study in healthy subjects , a high-fat meal delayed everolimus time to maximum concentration ( Tmax ) by a median 1.25 hours , reduced peak blood concentration ( Cmax ) by 60 % , and reduced area under the concentration-time curve ( AUC ) by 16 % . In the multiple-dose screening in patients with renal transplants , a high-fat meal delayed Tmax by a median 1.75 hours and reduced Cmax by 53 % and AUC by 21 % . Everolimus trough levels showed no food effect , whereas the peak-trough fluctuation was dampened by 52 % . CONCLUSIONS A high-fat meal modestly reduced everolimus AUC . To minimize longitudinal variability in exposure , everolimus should be administered consistently either with food or without food To assess the response rate and safety of sorafenib in different sub population s of patients with advanced renal cell carcinoma ( RCC ) BACKGROUND Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies . PATIENTS AND METHODS PREDICT ( Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib ) was a prospect i ve , noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries . Patient characteristics , therapy duration , tumor status , and tolerability were assessed at baseline and during routine follow-up . RESULTS Overall , 2599 patients were evaluable for safety and 2311 for efficacy . The diverse population included patients with brain metastases ( 5 % ) , non-clear-cell histologies ( 17 % ) , high Memorial Sloan-Kettering Cancer Center risk score ( 11 % ) , poor Eastern Cooperative Oncology Group performance status ( PS ≥ 2 , 29 % ) , and patients with no previous nephrectomy ( 16 % ) or no previous systemic therapy ( 37 % ) . The median duration of sorafenib therapy was 7.3 months and was similar in clinical ly relevant subgroups ( eg , patients with PS 2 , brain metastases , or concomitant hypertension or diabetes [ range , 6.7 - 7.0 months ] ) . The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies ( 4.6 and 4.8 months , respectively ) . The most common drug-related adverse events were h and -foot skin reaction ( 20 % ) , diarrhea ( 17 % ) , and rash ( 8 % ) . CONCLUSION Sorafenib was generally well tolerated and provided clinical benefit in a large , diverse population of patients with advanced RCC treated in routine clinical practice OBJECTIVE Temsirolimus , an inhibitor of the mammalian target of rapamycin , is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe . Temsirolimus was not yet evaluated in East Asian patients . METHODS This non-r and omized Phase II study enrolled 82 patients with advanced renal cell carcinoma [ 20 ( 24 % ) Japanese , 30 ( 37 % ) Korean and 32 ( 39 % ) Chinese patients ; median age ( range ) : 55 ( 26 - 83 ) years ] . Most ( 71 % ) received prior systemic therapy for metastatic disease ; two-thirds were intermediate risk . Six Japanese patients received intravenous temsirolimus 20 mg/m(2 ) weekly for tolerability assessment ( Group A ) ; the remaining 76 received a 25 mg flat dose weekly ( Group B ) . Temsirolimus was dosed once weekly . Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population . RESULTS In the entire population , regardless of treatment group , the clinical benefit rate was 48 % ( 95 % confidence interval : 36 , 59 ) . Objective response rate was 11 % ( 95 % confidence interval : 5 , 20 ) , median progression-free survival was 7.3 months ( 95 % confidence interval : 4.0 , 9.2 ) and median time to treatment failure was 5.4 months ( 95 % confidence interval : 3.5 , 7.4 ) . No patient in Group A demonstrated dose-limiting toxicity . The most frequent Grade 3 or 4 drug-related adverse events were anemia , hyperglycemia , hypophosphatemia and stomatitis ( 5 % each ) . Serious adverse events reported in ≥ 5 % of patients were pneumonia ( 9 % ) and interstitial lung disease ( 7 % ) . Temsirolimus and its major metabolite , sirolimus , were long-lived throughout the dosage interval , with no evidence of accumulation . CONCLUSION Temsirolimus was well tolerated and showed promising activity in Japanese , Korean and Chinese patients with advanced renal cell carcinoma PURPOSE Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma ( RCC ) treatment , when given by the st and ard intermittent schedule as well as a continuous daily dosing ( CDD ) schedule . A trial was conducted to compare the schedules . PATIENTS AND METHODS Patients with treatment-naive , clear cell advanced RCC were r and omly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment ( schedule 4/2 ; n = 146 ) or 37.5 mg/d on the CDD schedule ( n = 146 ) for up to 2 years . The primary end point was time to tumor progression . RESULTS Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule ( hazard ratio , 0.77 ; 95 % CI , 0.57 to 1.04 ; P = .090 ) . No significant difference was observed in overall survival ( 23.1 v 23.5 months ; P = .615 ) , commonly reported adverse events , or patient-reported kidney cancer symptoms . Schedule 4/2 was statistically superior to CDD in time to deterioration , a composite end point of death , progression , and disease-related symptoms ( P = .034 ) . CONCLUSION ; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2 . Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2 , adherence to this dose and schedule remains the treatment goal for patients with advanced RCC PURPOSE The combination of interferon alfa-2a ( IFNalpha2a ) plus vinblastine ( VLB ) induces objective tumor responses in patients with advanced renal cell cancer . However , no prospect i ve r and omized trial has shown that this treatment prolongs overall survival . We compared overall survival after treatment with IFNalpha2a plus VLB versus VLB alone in patients with advanced renal cell cancer . PATIENTS AND METHODS We prospect ively r and omized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNalpha2a plus VLB for 12 months or until progression of disease . In both groups , VLB was administered intravenously at 0.1 mg/kg every 3 weeks , and in the combination group IFNalpha2a was administered subcutaneously at 3 million units three times a week for 1 week , and 18 million units three times a week thereafter for the second and subsequent weeks . For patients unable totolerate IFNalpha2a at 18 million units per injection , the dose was reduced to 9 million units . RESULTS Median survival was 67.6 weeks for the 79 patients receiving IFNalpha2a plus VLB and 37.8 weeks for the 81 patients treated with VLB ( P = .0049 ) . Overall response rates were 16 . 5 % for patients treated with IFNalpha2a plus VLB and 2.5 % for patients treated with VLB alone ( P = .0025 ) . Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters , but no toxic deaths were reported . CONCLUSION The combination of IFNalpha2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma . This is the first study to demonstrate that survival can be prolonged by using IFNalpha2a for these patients PURPOSE Everolimus is a selective mammalian target of rapamycin ( mTOR ) inhibitor with promising anticancer activity . In order to identify a rationally based dose and schedule for cancer treatment , we have conducted a tumor pharmacodynamic phase I study in patients with advanced solid tumors . PATIENTS AND METHODS Fifty-five patients were treated with everolimus in cohorts of 20 , 50 , and 70 mg weekly or 5 and 10 mg daily . Dose escalation depended on dose limiting toxicity ( DLT ) rate during the first 4-week period . Pre- and on-treatment steady-state tumor and skin biopsies were evaluated for total and phosphorylated ( p ) protein S6 kinase 1 , eukaryotic initiation factor 4E ( elF-4E ) binding protein 1 ( 4E-BP1 ) , eukaryotic initiation factor 4 G ( eIF-4 G ) , AKT , and Ki-67 expression . Plasma trough levels of everolimus were determined on a weekly basis before dosing during the first 4 weeks . RESULTS We observed a dose- and schedule-dependent inhibition of the mTOR pathway with a near complete inhibition of pS6 and peIF-4 G at 10 mg/d and > or= 50 mg/wk . In addition , pAKT was upregulated in 50 % of the treated tumors . In the daily schedule , there was a correlation between everolimus plasma trough concentrations and inhibition of peIF4 G and p4E-BP1 . There was good concordance of mTOR pathway inhibition between skin and tumor . Clinical benefit was observed in four patients including one patient with advanced colorectal cancer achieving a partial response . DLTs occurred in five patients : one patient at 10 mg/d ( grade 3 stomatitis ) and four patients at 70 mg/wk ( two with grade 3 stomatitis , one with grade 3 neutropenia , and one with grade 3 hyperglycemia ) . CONCLUSION Everolimus achieved mTOR signaling inhibition at doses below the DLT . A dosage of 10 mg/d or 50 mg/wk is recommended for further development |
13,091 | 25,027,980 | Conclusion The finding raises the possibility that drains are not required to assist in recovery following TKA | Purpose The purpose of this systematic review and meta- analysis of r and omised controlled trials is to assess the effectiveness of no drainage when compared to drainage in total knee arthroplasty , in terms of recovery of knee flexion , reduction in swelling , length of hospital stay and haemoglobin levels following TKA . | OBJECTIVE To determine the value of using a closed-suction drain in cemented knee arthroplasty . METHODS One hundred patients were prospect ively r and omized into two groups , one group underwent cemented total knee replacement with a single deep closed-suction drain , and the other group ( n = 50 ) no drain . RESULTS The total blood loss was significantly greater in those with a drain although those without lost more blood into the dressings . There was no statistical difference in the postoperative swelling or pain score , ecchymosis , deep vein thromboses ( DVT ) , time at which flexion was regained or the incidence of infection at a minimum of two years after surgery in the two groups . CONCLUSION There is no evidence to support the use of a closed-suction drain in cemented knee arthroplasty OBJECTIVE To compare the impact of rehabilitative process of placing drainage versus no drainage during total knee arthroplasty ( TKA ) . METHOD A prospect i ve study was performed in 30 osteoarthritic patients who underwent one-stage bilateral TKA between October 2007 and December 2008 . For every patient , drainage was r and omly placed intra-operatively only on one knee side . Pain VAS scores , extremity swelling , incision healing , recovery of knee joint flexion and extension function and early postoperative complications were compared statistically as a self-control study . RESULTS All patients were followed up for at least one month . Comparing drainage side with non-drainage side , the mean pain VAS scores at Day 3 post-operation were 4.7 + /- 1.8 and 4 . 9 + /- 1.9 respectively ; the mean extremity swelling differences of supra patellar ( infra patellar ) perimeter at Day 6 post-operation were 1.8 + /- 1.7 ( 0.7 + /- 1.0 ) cm and 1.7 + /- 1.3 ( 1.0 + /- 1.0 ) cm respectively ; the mean flexion ( extension ) differences at Day 30 post-operation were 12.5 + /- 21.6 ( 4.4 + /- 6.9 ) degrees and 11.7 + /- 23.9 ( 4.2 + /- 6.4 ) degrees respectively . There was no obvious statistical difference between placing drainage and no drainage in all the above aspects ( paired t-test , P > 0.05 ) . There was also no statistical difference of early postoperative complications between two groups ( exact Fisher test , P > 0.05 ) . CONCLUSION For unsophisticated TKA , placing drainage had no effect upon reducing the pain , extremity swelling and incision exudation . It also had no effect upon reducing the incidence of hematoma to prevent early infections and promoting rehabilitation . Comparing with no drainage , placing drainage had no obvious advantage . On the contrary , it might complicate the surgical steps and increase the chances of post-operative hemorrhage and retro grade infections . Thus no drainage is recommended in such a kind of operation In a prospect i ve study we analyzed the volume of drainage , the contamination of the drain track , and drain tip in 81 primary total hip arthroplasties in 78 patients . The drain was removed when the drainage from midnight to the following morning was 20 mL or less . The drainage in the first 12 h and in total was reduced in cases with a drain period of 24 h , compared to cases with a drain period of 48 and 72 h. 4 cases had a positive culture from the wound before closure . 5 cases had a positive culture from the tip of the drain , and 6 from the drain track . The most frequently isolated microorganism was coagulase-negative Staphylococcus . The positive cultures from the drain track and tip were not correlated to the duration of drainage . 68 drains were removed within 48 h with no risk of developing wound complications We prospect ively r and omised 78 patients into two groups , ' drains ' or ' no drains ' to assess the effectiveness of suction drains in reducing haematoma and effusion in the joint and its effect on wound healing after total knee replacement . Ultrasound was used to measure the formation of haematoma and effusion on the fourth post-operative day . This was a semi-quantitative assessment of volume estimation . There was no difference in the mean effusion between the groups ( 5.91 mm in the drain group versus 6.08 mm in the no-drain , p = 0.82 ) . The mean amount of haematoma in the no-drain group was greater ( 11.07 mm versus 8.41 mm , p = 0.03 ) . However , this was not clinical ly significant judged by the lack of difference in the mean reduction in the post-operative haemoglobin between the groups ( drain group 3.4 g/dl ; no-drain group 3.0 g/dl , p = 0.38 ) . There were no cases of wound infection or problems with wound healing at six weeks in any patient . Our findings indicate that drains do not reduce joint effusion but do reduce haematoma formation . They have no effect on wound healing We studied the management of postoperative drainage after total knee replacement ( TKR ) . 90 primary total knee joint arthroplasties were prospect ively r and omized into 3 groups : a ) no drain , b ) an autotransfusion system , c ) a st and ard disposable closed suction drainage system . We monitored hemoglobin and hematocrit values , drainage volume and transfusions ( homologous and autologous ) , range of knee motion , knee swelling and hospital stay . Parameters were recorded preoperatively , days 0 - 8 and 4 months postoperatively . No significant differences were seen between the groups in any of the parameters measured . The results show no benefit from using postoperative drainage systems in knee arthroplasties . Savings of SEK 400 ( USD 55 ) per patient would have result ed if drains had not been used at all Abstract . Sixty patients were operated on for primary gonarthrosis by means of a cemented , posterior cruciate preserving total knee and were r and omly allocated to postoperative drainage or nondrainage . The primary criterion was duration of hospital stay . Secondary criteria included serial evaluation of knee pain , knee flexion , knee circumference , calculated blood loss after 7 days , complications , reoperations , and the need for blood transfusions . There was no difference between the two groups in any of the criteria during the entire follow-up . There was a nonsignificant trend to a decreased calculated blood loss in the nondrained group and significantly less transfused blood units in the nondrained group . Lack of drainage does not increase complication risk after total knee prosthesis implantation . We therefore recommend using no routine drainage after this procedure OBJECTIVE To prospect ively compare of no drain or with drain after unilateral total knee arthroplasty ( TKA ) . METHODS A r and omized prospect i ve study was conducted between February 2006 and February 2007 . The study included 100 patients who were divided into 2 groups : group A ( n = 50 ) , which included patients without drain release , and group B ( n = 50 ) , which included patients who had a drain release . The true total blood loss was calculated depending on the height , body mass and pre- and post-operative Hct , and hidden blood loss was gotten by subtracting the visible blood loss from total loss . The recovery after surgery , the correlative complications and transfusion amounts were compared and analyzed . RESULTS All 100 patients undergoing TKA were involved in the result analysis . In patients without a drain , the total blood loss was ( 535 + /- 295 ) ml and the hidden blood loss was ( 513 + /- 290 ) ml , in patients with a drain , the total blood loss was ( 853 + /- 331 ) ml and the hidden blood loss ( 689 + /- 324 ) ml . The total and hidden blood loss , blood transfusion amount between drain-group and without drain-group was significantly different ( P < 0.05 ) . The difference in the incidence of infection and post-op recovery and correlative complications did not reach statistical significance . CONCLUSIONS In patients having primary TKA , using a drain , compared with no use of a drain , does not show us a clear advantage that make us accept it . Without a drain release could present an effective and economic method for reducing blood loss and preventing blood transfusion in patients undergoing unilateral TKA We prospect ively r and omised 100 patients undergoing cemented total knee replacement to receive either a single deep closed-suction drain or no drain . The total blood loss was significantly greater in those with a drain ( 568 ml versus 119 ml , p < 0.01 ; 95 % CI 360 to 520 ) although those without lost more blood into the dressings ( 55 ml versus 119 ml , p < 0.01 ; 95 % CI -70 to 10 ) . There was no statistical difference in the postoperative swelling or pain score , or in the incidence of pyrexia , ecchymosis , time at which flexion was regained or the need for manipulation , or in the incidence of infection at a minimum of five years after surgery in the two groups . We have been unable to provide evidence to support the use of a closed-suction drain in cemented knee arthroplasty . It merely interferes with mobilisation and complicates nursing . Reinfusion drains may , however , prove to be beneficial A prospect i ve investigation was design ed to determine the volume and the evolution of bleeding after closure of the surgical wound following knee arthroplasty , as well as the incidence of infection and bacterial contamination in relation with the time that the suction drain was left in place . The drain was removed either 12 , 24 or 48 hours after the operation . The presence of any signs of clinical infection was recorded . The tip of the drain , 1 cm of its subcutaneous portion and a sample from the collecting bottle were studied for bacterial contamination . In the 12-hr group , no microorganisms were isolated in cultures either from the tip , the subcutaneous portion or the bottle of the drain . In the 24-hr group , 87 % of the total postoperative bleeding was collected during the first 12 hours . In two cases , the sample s obtained from the tip and the subcutaneous portion of the drain were positive for Staphylococcus epidermidis . In the 48-hr group , 91 % and 97 % of the total bleeding volume was collected during the first 12 and 24 hours , respectively . In two cases , St. epidermidis was isolated in cultures from the subcutaneous portion of the drain . The clinical evaluation of wound healing was comparable in all three groups OBJECTIVE To identify risk factors associated with the development of surgical-site infection ( SSI ) following total knee arthroplasty ( TKA ) . DESIGN A case-control study . SETTING A 1,100-bed , university-affiliated , tertiary-care teaching hospital . METHODS Case- patients with SSI occurring up to 1 year following primary TKA performed between January 1999 and December 2001 were identified prospect ively by infection control practitioners using National Nosocomial Infections Surveillance ( NNIS ) System methods . Three control- patients were selected for each case-patient , matched by date of surgery . Stepwise logistic regression analysis was used to determine the relation of potential risk factors to the development of infection . RESULTS Twenty-two patients with infections ( 6 superficial and 16 deep ) were identified . Infection rates per year were 0.95 % , 1.07 % , and 1.19 % in 1999 , 2000 , and 2001 , respectively . Logistic regression analysis identified two variables independently associated with the development of infection : the use of closed suction drainage ( odds ratio [ OR ] , 7.0 ; 95 % confidence interval [ CI95 ] , 2.1 - 25.0 ; P = .0015 ) and increased international normalized ratio ( INR ) ( OR , 2.4 ; CI95 , 1.1 - 5.7 ; P = .035 ) . Factors not statistically associated with the development of infection included age , NNIS System risk index score , presence of various comorbidities , surgeon , duration of procedure or tourniquet time , type of bone cement or prosthesis used , or receipt of blood product transfusions . CONCLUSIONS The use of closed suction drainage and a high postoperative INR were associated with the development of SSI following TKA . Avoiding the use of surgical drains and careful monitoring of anticoagulant prophylaxis in patients undergoing TKA should reduce the risk of infection A prospect i ve study of 69 patients ( 138 knees ) who had a primary simultaneous bilateral total knee replacement was conducted to assess the effect of postoperative suction drainage on wound healing and infection . A suction drain was placed by r and omization of side for the drained versus nondrained side . The same operative technique was used in all wounds of total knee arthroplasty . The knees that had no drains had a higher incidence of drainage from the wound , had soaked dressings requiring dressing reinforcements , and had more ecchymosis and erythema around the wound . However , the final results regarding quadriceps strength , range of motion , and wound complications were not affected significantly by nonuse of closed suction drainage . Although the incidence of infection in the two groups is not statistically different , the development of infection in two knees in which drains were not used suggests that suction drainage may reduce deep infection One hundred thirty-six primary total knee arthroplasty patients were r and omized for the use of closed-suction , nonreinfusable wound drains . Blood loss was identical in the drained and undrained groups . Forty percent of undrained wounds compared with 0 % of drained wounds required dressing reinforcement . Sixty-nine percent of undrained wounds compared with 39 % of drained wounds developed ecchymosis , measuring 92 cm2 in the undrained group and 28 cm2 in the drained group . This study concludes that a simple wound drain effectively minimizes the undesirable accumulation of blood in the surrounding soft tissues and the postoperative wound dressing after total knee arthroplasty There is no firm published evidence to support the use of closed suction drains . Over 20 years ago , large studies by the Public Health Laboratory Service and the National Research Council found that drains were risk factors for wound infection . A prospect i ve r and omised study of the use of closed suction drains after surgery for fractured neck of femur in 70 patients failed to show that drains improved wound healing . Drained cases had more complications PROBLEM In a prospect i ve r and omised clinical study , we investigated the impact of drain-suction on the post-operative blood loss and on both clinical and laboratory parameters after knee replacement operations . PATIENTS AND METHOD In this study , 116 patients with unilateral implantation of knee replacements were evaluated . The patients ' average age was 71.2 years . The operation was carried out mostly without tourniquet application . All patients received two wound drains , 57 with and 59 without suction . The postoperative blood loss as well as clinical and laboratory parameters were assessed . RESULTS The average peri-operative blood loss amounted to 338 ml . The post-operative blood loss in the group without drain suction was 436 ml and 528 ml in the group with suction . No significant differences could be found concerning the hemoglobin values pre-operatively and on the first and seventh post-operative day , the drainage quantity 12 , 24 , 36 , and 48 hours post-operatively , the wound healing and the CRP . Six patients in the group without and five patients in the group with drain-suction had to receive blood transfusions . DISCUSSION The application of suction on the drainage system had no significant impact on the post-operative blood loss and the postoperative course . In nine out of ten cases no homologous blood was needed |
13,092 | 29,708,310 | When they are included , the CAARMS scores differ between some minorities and the native-born majority group .
This selection bias may result in lower validity for the CAARMS among these population s and thus in inadequate intervention programmes . | AIM Over the past 20 years , early management of psychosis has become both a research and policy priority .
In Western countries , psychotic disorders appear more prevalent in migrant and minority ethnic groups than in native or dominant groups .
Moreover , disparities exist in health conditions and access to care among immigrants and minority ethnic groups , compared with native-born and majority groups .
Appropriate early detection tools are necessary for the different groups .
METHODS This systematic review provides a synthesis of the assessment and discussion of transcultural issues in ultra-high-risk ( UHR ) cohorts . | BACKGROUND Previously , we demonstrated that cognitive behavior therapy for ultra-high risk ( called CBTuhr ) halved the incidence of psychosis over an 18-month period . Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline . METHOD The Dutch Early Detection and Intervention Evaluation study was a r and omized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual ( TAU ) for comorbid disorders with TAU only . Of the original 196 patients , 113 consented to a 4-year follow-up ( 57.7 % ; CBTuhr = 56 vs TAU = 57 ) . Over the study period , psychosis incidence , remission from UHR status , and the effects of transition to psychosis were evaluated . RESULTS The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group ( n = 22 ) ; this still represents a clinical ly important ( incidence rate ratio [ IRR ] = 12/22 = 0.55 ) and significant effect ( F(1,5 ) = 8.09 , P = .03 ) , favoring CBTuhr . The odds ratio of CBTuhr compared to TAU was 0.44 ( 95 % CI : 0.24 - 0.82 ) and the number needed to treat was 8 . Moreover , significantly more patients remitted from their UHR status in the CBTuhr group ( 76.3 % ) compared with the TAU group ( 58.7 % ) [ t(120 ) = 2.08 , P = .04 ] . Importantly , transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up . CONCLUSIONS CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up . Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases . TRIAL REGISTRATION The trial is registered at Current Controlled Trials as trial number IS RCT N21353122 ( http://controlled-trials.com/IS RCT N21353122/gaag ) Objective : Impaired social functioning is one of the defining features of patients with schizophrenia and subjects at ultra-high risk ( UHR ) for psychosis . This prospect i ve study aim ed to investigate the course of social dysfunction in UHR subjects and to examine its relationship with later conversion to psychosis . The effect of pharmacotherapy on the course of social dysfunction was also examined . Method : A total of 57 UHR subjects and 58 healthy controls participated in this study . The Social Functioning Scale ( SFS ) was used to assess social functioning of UHR subjects at baseline and at the 1 year follow up . The changes in social functioning of UHR subjects have been examined to compare the social functioning of those who later converted to psychosis ( ‘ converters ’ ) with those who did not ( ‘ non-converters ’ ) . The effect of pharmacotherapy on longitudinal change in social functioning was also evaluated . Results : Subjects at UHR for psychosis showed more impaired social functioning at baseline than did healthy controls . Moreover , the course of social dysfunction of the converter and non-converter groups differed during the 1 year follow up period . The converters showed decreases in SFS average ( F ( 1,32 ) = 7.85 , p = 0.009 ) and interpersonal behaviour ( F ( 1,32 ) = 10.43 , p = 0.003 ) scores over time , whereas the non-converters showed increased scores . Additionally , we found that pharmacological treatment was associated with increased prosocial activities score ( F ( 1,32 ) = 4.66 , p = 0.038 ) . Conclusions : We found that the social functioning of converters was impaired before the onset of the psychosis and further declined during the at-risk phase . A series of social functioning indices in the longitudinal course may be helpful in predicting conversion to psychosis in subjects at UHR . Appropriate pharmacotherapy can offer clinical benefits by improving social functioning in UHR individuals AIM Recent research has indicated that preventative intervention is likely to benefit patients ' at-risk ' for psychosis , both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder . The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids ( PUFAs ) , coupled with the falling transition rate in ultra high-risk ( UHR ) sample s , mean that further study of such benign , potentially neuroprotective interventions is clinical ly and ethically required . Employing a multicentre approach , enabling a large sample size , this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group . METHODS This trial is a 6-month , double-blind , r and omized placebo-controlled trial of 1.4 g day-1 omega-3 PUFAs in UHR patients aged between 13 and 40 years . The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management ( CBCM ) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM . Secondary outcomes will examine symptomatic and functional changes , as well as examine if c and i date risk factors predict response to omega-3 PUFA treatment in the UHR group . CONCLUSION This is the protocol of the NeuraproE study . Utilizing a large sample , results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders , which may be the strongest avenue for reducing the burden , stigmatization , disability and economic consequences of these disorders Despite increased efforts over the last decade to prospect ively identify individuals at ultra-high risk of developing a psychotic illness , limited attention has been specifically directed towards adolescent population s ( < 18 years ) . In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State ( ARMS ) present and fare over time , we conducted an observational study . Participants ( N = 30 ) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance , mainly in the form of auditory hallucinations . Seventy percent ( 21/30 ) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder , with mood ( affective ; 13/30 ) disorders being most prevalent . Overall transition rates to psychosis were low at 24 months follow-up ( 2/28 ; 7.1 % ) whilst many participants demonstrated a significant reduction in psychotic-like symptoms . The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample BACKGROUND Although there is evidence for the effectiveness of interventions for psychosis among ultra-high-risk ( UHR ) groups , health economic evaluations are lacking . This study aim ed to determine the cost effectiveness and cost-utility of cognitive-behavioural therapy ( CBT ) to prevent first-episode psychosis . METHOD The Dutch Early Detection and Intervention Evaluation study was a r and omized controlled trial of 196 UHR patients with an 18-month follow-up . All participants were treated with routine care ( RC ) for non-psychotic disorders . The experimental group ( n = 95 ) received add-on CBT to prevent first-episode psychosis . We report the intervention , medical and travel costs , as well as costs arising from loss of productivity . Treatment response was defined as psychosis-free survival and quality -adjusted life years ( QALYs ) gained . RESULTS In the cost-effectiveness analysis , the proportion of averted psychoses was significantly higher in the CBT condition ( 89.5 % v. 76.2 % ) . CBT showed a 63.7 % probability of being more cost effective , because it was less costly than RC by US$ 844 ( £ 551 ) per prevented psychosis . In the cost-utility analysis , QALY health gains were slightly higher for CBT than for RC ( 0.60 v. 0.57 ) and the CBT intervention had a 52.3 % probability of being the superior treatment because , for equal or better QALY gains , the costs of CBT were lower than those of RC . CONCLUSIONS Add-on preventive CBT for UHR result ed in a significant reduction in the incidence of first psychosis . QALY gains show little difference between the two conditions . The CBT intervention proved to be cost saving BACKGROUND Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear . The objective of this study was to assess prospect ively the influence of cannabis use on transition to psychosis in people at ultra-high risk ( UHR ) for the disorder . METHOD Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people ( 104 male , 78 female ) at UHR for psychosis . Individuals were then followed clinical ly for 2 years to determine their clinical outcomes . RESULTS Lifetime cannabis use was reported by 134 individuals ( 73.6 % ) . However , most of these individuals had stopped using cannabis before clinical presentation ( n=98 , 73.1 % ) , usually because of adverse effects . Among lifetime users , frequent use , early-onset use and continued use after presentation were all associated with an increase in transition to psychosis . Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently ( frequent early-onset use : 25 % ; infrequent or late-onset use : 5 % ; χ(2)1=10.971 , p=0.001 ) . However , within the whole sample , cannabis users were no more likely to develop psychosis than those who had never used cannabis ( cannabis use : 12.7 % ; no use : 18.8 % ; χ(2)1=1.061 , p=0.303 ) . CONCLUSIONS In people at UHR for psychosis , lifetime cannabis use was common but not related to outcome . Among cannabis users , frequent use , early-onset use and continued use after clinical presentation were associated with transition to psychosis Social amotivation and diminished expression have been reported to underlie negative symptomatology in schizophrenia . In the current study we sought to establish and vali date these negative symptom domains in a large cohort of schizophrenia subjects ( n=887 ) and individuals who are deemed to be Ultra-High Risk ( UHR ) for psychosis . Confirmatory factor analysis conducted on PANSS item domains demonstrate that the dual negative symptom domains exist in schizophrenia and UHR subjects . We further sought to examine if these negative symptom domains were associated with functioning in UHR subjects . Linear regression analyses confirmed that social amotivation predicted functioning in UHR subjects prospect ively at 1 year follow up . Results suggest that the association between social amotivation and functioning is generalisable beyond schizophrenia population s to those who are at-risk of developing psychosis . Social amotivation may be an important dimensional clinical construct to be studied across a range of psychiatric conditions Background Psychotic disorders are a serious mental health problem . Intervention before the onset of psychosis might result in delaying the onset , reducing the impact or even preventing the first episode of psychosis . This study explores the effectiveness of cognitive behavioural therapy ( CBT ) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra-high risk for developing psychosis . A single blind r and omised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis . Method / design All help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherl and s are pre-screened with the Prodromal Question naire during a period of two years . Patients with a score of 18 or more on the sub- clinical positive symptoms items ( 45 items in total ) will be assessed with the Comprehensive Assessment of At Risk Mental State ( CAARMS ) . In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS . The primary outcome is the transition rate to psychosis according to the CAARMS- criteria . Group differences will be analysed with chi-square tests and survival analyses . Discussion CBT is a highly tolerated treatment . The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State ( ARMS ) are distressed by odd disturbing experiences . Giving explanations for and normalising these experiences may reduce the arousal ( distress ) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis . Screening the entire help-seeking population referred to community mental health services with a two-stage strategy , as compared with traditional referral to a specialist clinical psychosis centre , might detect more ultra-high-risk ( UHR ) patients . This type of screening could be implemented in mental health care as routine screening . The trial is registered at Current Controlled trials as trial number IS RCT N21353122 AIM Based on previous reports of second-generation antipsychotic agents having a beneficial effect on prodromal symptoms , we investigated the effectiveness and tolerability of atypical antipsychotic therapies in individuals at high risk for developing psychosis . METHODS We examined prodromal symptoms and functioning in individuals at ultra-high-risk for psychosis using an uncontrolled prospect i ve design with pre- and post-treatment measures . RESULTS Of the 27 subjects taking antipsychotics during the study period , 15 took part in at least one follow-up assessment . Overall Comprehensive Assessment of At-Risk Mental States scores significantly improved at the last evaluation point , with a medium-size effect of Cohen 's d = 0.54 ( 95 % confidence interval , -0.02 to 1.08 ) ( mean follow-up period = 8.8 ; SD = 8.3 months ) . Depression and anxiety symptoms were markedly reduced , and global and social functioning also significantly improved . Of the 27 subjects , two ( 7.4 % ) converted to psychosis and 16 ( 59.3 % ) experienced at least one treatment-emergent adverse event , but no subjects exhibited serious adverse events . CONCLUSIONS The results of this study support treating high-risk individuals with antipsychotics to reduce prodromal symptoms with adequate safety Objective Recent studies suggest that psychotic-like experiences may also act as markers for non-psychotic psychiatric disorders , which may indicate that the focus of research in individuals at high risk ( HR ) for psychosis needs updating . In this study we thoroughly examined the clinical and functional characteristics of a consecutive cohort of young people at HR for psychosis and compared them to a matched sample of healthy volunteers . Method Between February 2010 and September 2012 60 help-seeking HR individuals , aged 16–35 , were recruited from CAMEO Early Intervention in Psychosis Service , Cambridgeshire , UK . Forty-five age- and gender-matched healthy volunteers were r and omly recruited from the same geographical area . Sociodemographic , psychiatric morbidity , functioning and quality of life measures were compared between both groups . Results HR individuals suffered a wide range of DSM-IV psychiatric disorders , mainly within the affective and anxiety diagnostic spectra . In comparison to healthy volunteers , young people at HR reported more suicidal ideation/intention , depressive and anxiety symptoms and presented with remarkably poor functioning and quality of life . Conclusion The presence of co-morbid moderate or severe depressive and anxiety symptoms was common in our sample of young people at enhanced risk for psychosis . A HR mental state may be associated not only with an increased risk for psychosis , but also other psychiatric disorders . Our findings may have implication s for the future implementation of therapeutic interventions that this population could benefit from Background Cognitive deficits are a distinct feature among people at ultra-high risk ( UHR ) for psychosis and pose a barrier to functional recovery . Insufficient evidence exists on how to ameliorate these cognitive deficits in patients at UHR for psychosis and hence improve daily living and quality of life . The aim of the trial is to investigate whether cognitive remediation can improve cognitive and psychosocial function in patients at UHR for psychosis . Methods The FOCUS trial ( Function and Overall Cognition in Ultra-high risk States ) is a r and omised , parallel group , observer-blinded clinical trial enrolling 126 patients meeting the st and ardised criteria of being at UHR for psychosis . Patients are recruited from psychiatric in- and outpatient facilities in the Copenhagen catchment area . Patients are r and omised to one of the two treatment arms : cognitive remediation plus st and ard treatment versus st and ard treatment . The cognitive remediation consists of 24 weekly group-based and manualised sessions targeting neurocognition and social cognition . In addition to the group sessions , the patients will be offered 12 individual sessions aim ing at maximising the transfer of the effects of the cognitive training to their everyday lives . Follow-up assessment s will be conducted at 6 and 12 months after r and omisation . The primary outcome is the composite score on the Brief Assessment of Cognition in Schizophrenia at cessation of treatment after 6 months . Secondary outcomes are social and daily functioning , psychosis-like symptoms , negative symptomatology , and depressive symptomatology as measured with the Personal and Social Performance Scale , Brief Psychiatric Rating Scale-Exp and ed Version , Scale for the Assessment of Negative Symptoms , and the Montgomery-Åsberg Depression Rating Scale . Discussion This is the first trial to evaluate the effects of neurocognitive and social cognitive remediation in UHR patients . The FOCUS trial results will provide evidence on the effect of targeted and comprehensive cognitive rehabilitation on cognition , daily living , and symptomatology as well as long-term outcome in preventing transition to psychosis in UHR patients .Trial registration Clinical Trials.gov NCT 02098408 . Date of registration 18 March 2014 Background : Brief Limited Intermittent Psychotic Symptoms ( BLIPS ) are key inclusion criteria to define individuals at ultra high risk for psychosis ( UHR ) . Their diagnostic and prognostic significance is unclear . Objectives : To address the baseline diagnostic relationship between BLIPS and the ICD-10 categories and examine the longitudinal prognostic impact of clinical and sociodemographic factors . Methods : Prospect i ve long-term study in UHR individuals meeting BLIPS criteria . Sociodemographic and clinical data , including ICD-10 diagnoses , were automatically drawn from electronic health records and analyzed using Kaplan – Meier failure function ( 1-survival ) , Cox regression models , bootstrapping methods , and Receiver Operating Characteristics ( ROC ) curve . Results : Eighty BLIPS were included . At baseline , two-thirds ( 68 % ) of BLIPS met the diagnostic criteria for ICD-10 Acute and Transient Psychotic Disorder ( ATPD ) , most featuring schizophrenic symptoms . The remaining individuals met ICD-10 diagnostic criteria for unspecified nonorganic psychosis ( 15 % ) , mental and behavioral disorders due to use of cannabinoids ( 11 % ) , and mania with psychotic symptoms ( 6 % ) . The overall 5-year risk of psychosis was 0.54 . Recurrent episodes of BLIPS were relatively rare ( 11 % ) but associated with a higher risk of psychosis ( hazard ratio [ HR ] 3.98 ) than mono-episodic BLIPS at the univariate analysis . Multivariate analysis revealed that seriously disorganizing or dangerous features increased greatly ( HR = 4.39 ) the risk of psychosis ( 0.89 at 5-year ) . Bootstrapping confirmed the robustness of this predictor ( area under the ROC = 0.74 ) . Conclusions : BLIPS are most likely to fulfill the ATPD criteria , mainly acute schizophrenic subtypes . About half of BLIPS cases develops a psychotic disorder during follow-up . Recurrent BLIPS are relatively rare but tend to develop into psychosis . BLIPS with seriously disorganizing or dangerous features have an extreme high risk of psychosis OBJECTIVES The identification of individuals at high risk of becoming psychotic within the near future creates opportunities for early intervention before the onset of psychosis . This study sets out to identify a group of symptomatic young people in a Chinese population with the high likelihood of transition to psychosis within a follow-up period of 6 months , and to determine the rate of transition to psychosis in this group . METHOD Symptomatic individuals with a family history of psychotic disorder , sub-threshold psychotic symptoms or brief transient psychotic symptoms were identified using the operationalized criteria of an ' At Risk Mental State ' . The individuals were prospect ively assessed monthly on a measure of psychopathology for 6 months . RESULTS Eighteen out of 62 individuals ( 29 % ) made the transition to frank psychosis within a 6 month follow-up period , with the majority occurring within 3 months . In addition , significant differences were found in the intake Positive and Negative Syndrome Scale , Comprehensive Assessment of ' At Risk Mental State ' and Global Assessment of Functioning scores between the group that ultimately became psychotic and the group that did not . CONCLUSION The period of the highest risk of transition to psychosis was within the 3 months after the study began . Thus , distressed youths in our outpatient clinic , who meet the high-risk criteria should be monitored most closely in the initial 3 months , particularly those individuals with high levels of psychopathology and functional decline OBJECTIVE The ultra-high risk clinical phenotype is associated with substantial distress and functional impairment and confers a greatly enhanced risk for transition to full-threshold psychosis . A range of interventions aim ed at relieving current symptoms and functional impairment and reducing the risk of transition to psychosis has shown promising results , but the optimal type and sequence of intervention remain to be established . The aim of this study was to determine which intervention was most effective at preventing transition to psychosis : cognitive therapy plus low-dose risperidone , cognitive therapy plus placebo , or supportive therapy plus placebo . METHOD A double-blind , r and omized , placebo-controlled 12-month trial of low-dose risperidone , cognitive therapy , or supportive therapy was conducted in a cohort of 115 clients of the Personal Assessment and Crisis Evaluation Clinic , a specialized service for young people at ultra-high risk of psychosis located in Melbourne , Australia . Recruitment commenced in August 2000 and ended in May 2006 . The primary outcome measure was transition to full-threshold psychosis , defined a priori as frank psychotic symptoms occurring at least daily for 1 week or more and assessed using the Comprehensive Assessment of At-Risk Mental States . Secondary outcome measures were psychiatric symptoms , psychosocial functioning , and quality of life . RESULTS The estimated 12-month transition rates were as follows : cognitive therapy + risperidone , 10.7 % ; cognitive therapy + placebo , 9.6 % ; and supportive therapy + placebo , 21.8 % . While there were no statistically significant differences between the 3 groups in transition rates ( log-rank test P = .60 ) , all 3 groups improved substantially during the trial , particularly in terms of negative symptoms and overall functioning . CONCLUSIONS The lower than expected , essentially equivalent transition rates in all 3 groups fail to provide support for the first-line use of antipsychotic medications in patients at ultra-high risk of psychosis , and an initial approach with supportive therapy is likely to be effective and carries fewer risks Objective : Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder , or at least of reducing the impact of such a disorder if it does develop . The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk ( UHR ) of psychosis . Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder . Method : The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were r and omized to one of three treatment groups : cognitive therapy plus risperidone ( CogTher + Risp : n = 43 ) ; cognitive therapy plus placebo ( CogTher + Placebo : n = 44 ) ; and supportive counselling + placebo ( Supp + Placebo ; n = 28 ) . A fourth group of young people who did not agree to r and omization were also followed up ( monitoring : n = 78 ) . Baseline characteristics of participants are provided . Results and conclusion : The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared . Issues associated with recruitment and r and omization are discussed BACKGROUND Intervention trials for young people at ultra high risk ( UHR ) for psychosis have shown cognitive behaviour therapy ( CBT ) to have promising effects on treating psychotic symptoms but have not focused on functional outcomes . We hypothesized that compared to an active control , CBT would : ( i ) reduce the likelihood of , and /or delay , transition to psychosis ; ( ii ) reduce symptom severity while improving social functioning and quality of life , whether or not transition occurred . METHOD This was a single-blind r and omised controlled trial for young people at UHR for psychosis comparing CBT to an active control condition , Non Directive Reflective Listening ( NDRL ) , both in addition to st and ard care , with a 6month treatment phase and 12months of follow-up . Statistical analysis is based on intention-to-treat and used r and om effect models to estimate treatment effects common to all time-points . RESULTS Fifty-seven young people ( mean age=16.5years ) were r and omised to CBT ( n=30 ) or NDRL ( n=27 ) . Rate of transition to psychosis was 5 % ; the 3 transitions occurred in the CBT condition ( baseline , 2months , 5months respectively ) . The NDRL condition result ed in a significantly greater reduction in distress associated with psychotic symptoms compared to CBT ( treatment effect=36.71 , st and ard error=16.84 , p=0.029 ) . There were no significant treatment effects on frequency and intensity of psychotic symptoms , global , social or role functioning . CONCLUSION Our sample was higher functioning , younger and experiencing lower levels of psychotic like experiences than other trials . The significantly better treatment effect of NDRL on distress associated with psychotic symptoms supports the recommendations for a stepped-care model of service delivery . This treatment approach would accommo date the younger UHR population and facilitate timely intervention . TRIAL REGISTRATION ANZCTR 12606000101583 OBJECTIVE Cognitive therapy and /or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness . However , it is unclear which of these treatments are most effective , how long treatment should be given , and whether effects will be sustained over a prolonged period . METHOD In order to examine these issues , we conducted a r and omized controlled trial of cognitive therapy + risperidone ; cognitive therapy + placebo ; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder ( that is , putatively prodromal ) . The main outcome was transition to psychotic disorder , with level of symptoms and functioning the secondary outcomes . This article reports the interim 6-month follow-up results . The study was conducted from August 2000 to May 2007 . RESULTS Of a possible 464 eligible ultra high risk individuals , 115 were recruited to the r and omized controlled trial ( cognitive therapy + risperidone , n = 43 ; cognitive therapy + placebo , n = 44 ; and supportive therapy + placebo , n = 28 ) . An additional 78 individuals agreed to follow-up assessment s but not to r and omization ( " monitoring group , " n = 78 ) . At 6 months , 8 of the 115 participants ( 7.0 % ) and 4 of the monitoring group ( 5.1 % ) had developed psychotic disorder . There were no significant differences between the 3 r and omized groups ( log rank test , P = .92 ) or between all 4 groups ( log rank test , P = .93 ) . There was also no difference between the 4 groups in secondary measures , with all groups showing a reduction in symptoms and increased functioning . CONCLUSIONS Rates of transition to psychosis were lower than expected , particularly in the control supportive therapy + placebo group . This may have accounted for the negative finding , as the sample was therefore underpowered to find any difference between groups . Alternatively , it may be that all treatments were equally effective or equally ineffective at 6 months . TRIAL REGISTRATION http://www.anzctr.org.au Identifier : ACTRN012605000247673 The onset of psychosis typically occurs during adolescence or early adulthood and can have a detrimental impact on social and cognitive development . Cognitive behavioural therapy ( CBT ) shows promise in reducing the risk of psychosis . Teaching families to apply CBT with their offspring may bolster therapeutic gains made in time‐limited treatment . We developed a comprehensive group‐ and ‐family‐based CBT ( GF‐CBT ) program that aims to facilitate psychosocial recovery , decrease symptoms and prevent transition to psychosis in youth at risk . GF‐CBT is grounded in ecological systems and cognitive theories , resilience models and research on information processing in delusions . The theoretical rationale and description of GF‐CBT are presented together with a pilot study that evaluated the program 's feasibility and explored participants ' outcomes Aims : Much research has begun to focus on the identification of people who are at high risk of developing psychosis , and clinical services have been initiated for this population . However , only a small number of studies have reported on the efficacy of interventions for preventing or delaying the onset of psychosis . The results of prior work suggest that cognitive therapy ( CT ) may be an effective , well‐tolerated treatment . We report on the rationale and design for a large‐scale , multi‐site r and omized , controlled trial of CT for people who are assessed to be at high risk of psychosis because of either state or state‐plus‐trait risk factors Biases in cognition such as Jumping to Conclusions ( JTC ) and Verbal Self-Monitoring ( VSM ) are thought to underlie the formation of psychotic symptoms . This prospect i ve study in people with an At Risk Mental State ( ARMS ) for psychosis examined how these cognitive biases changed over time , and predicted clinical and functional outcomes . Twenty-three participants were assessed at clinical presentation and a mean of 31 months later . Performance on a JTC and VSM tasks were measured at both time points . Relationships to symptom severity , level of function and the incidence of psychotic disorder were then examined . The levels of symptoms , function and VSM all improved over time , while JTC was stable . Five participants ( 22 % ) developed a psychotic disorder during the follow-up period , but the risk of transition was not related to performance on either task at baseline , or to longitudinal changes in task performance . JTC performance correlated with symptom severity at baseline and follow-up . Similarly , performance on the two tasks was not related to the level of functioning at follow-up . Thus , while the ARMS is associated with both VSM and JTC biases , neither predict the onset of psychosis or the overall functional outcome |
13,093 | 24,762,010 | Conclusions Diagnostic modalities such as acoustic rhinometry , rhinomanometry and nasal spectral sound analysis may be useful in identifying NSD in anterior region of the nasal cavity , but these tests in isolation are of limited utility .
Compared to anterior rhinoscopy , nasal endoscopy , and imaging the above mentioned index tests lack sensitivity and specificity in identifying the presence , location , and severity of NSD | Objective To perform a systematic review of measurement tools utilized for the diagnosis of nasal septal deviation ( NSD ) . | Authors report an experiment performed in a r and omized group of newborns to evaluate the frequency of post-partum septal deviations . A number of 423 subjects out of 1142 have been examined in a 17-month period . Newborns have been examined with an otoscope and two different kinds of nasal lesions have been considered : ( 1 ) pyramid deformation with septum dislocation and columella deviation ; ( 2 ) deviation and subluxation of the septum . A number of 315 newborns were naturally delivered and 108 by cesarean section . In the former group , 10 pyramid deformations and 12 septal deviations have been found ; in the latter , only septal deviations have been revealed ( 5 infants ) . Pyramid deformations may be related to delivery(labor)trauma while for septal deviations a developmental defect may be postulated Objective . The sphenoidal process of the septal cartilage ( SP ) is a small strip of cartilage between the perpendicular plate of ethmoid bone and vomer . The present study was performed to evaluate the clinical significance of the SP in the development of nasal septal deviation . Study Design . Prospect i ve , controlled . Setting . Academic rhinologic practice . Subjects and Methods . The authors examined 136 patients with nasal septal deviation . The length of SP was measured during septal surgery , and values were compared with the deviation angle . The distance between the anterior nasal spine ( ANS ) and the breakpoint of the suture line between the septal cartilage and the perpendicular plate of the ethmoid bone ( ANS-PPE ) and that from the ANS to the point where the choana meets the sphenoid sinus ( ANS-CS ) were determined and compared according to the age . Results . The mean length of SP in patients with a deviated nasal septum was 25.90 ± 7.82 mm and decreased with age . The average deviation angles at the level of the ostiomeatal unit and nasal valve area were 8.28 ° ± 3.50 ° and 10.37 ° ± 4.38 ° , respectively . These angles increased with the length of SP ( P < .01 ) . The mean length of ANS-PPE showed a significant negative correlation with age . The mean length of ANS-CS had no correlation with age . Conclusion . SP was longer with increasing deviation angle in patients with nasal septal deviation . A long SP , a remnant cartilaginous tail of the nasal septum result ing from delayed ossification of the nasal septum , contributes to the exacerbation of septal deviation OBJECTIVE A high incidence of septal deviation with significant inter-rater variability has been reported . An explanation could be the presence of physiological septal deviation besides pathological ones . We differentiated an unselected cohort by their nasal resistance into groups with physiological normal and pathologically increased resistance to detect differences and analogies in comparison to healthy subjects and a pathological cohort . STUDY DESIGN Prospect i ve cohort study . SETTING A total of 356 patients were assessed using rhinoresistometry , acoustic rhinometry , endoscopy and visual analogue scales . After definition of a benchmark between physiological and pathological nasal resistance , group differences were calculated and correlations analysed . RESULTS The normal one-sided inspiratory nasal resistance was defined as less or equal to 0.35 sPa/cm^3 at a flow-velocity of 250 cm^3/s ( R250 ) . Using this benchmark , the unselected group of non-rhinological patients was differentiated into 114 subjects with physiological nasal resistance and 44 with pathological septal deviation . Nasal resistance after decongestion was significantly lower for normal or patients with a physiological septal deviation in comparison to the rhinological one on both nasal sides . Healthy subjects and patients with physiological septal deviation showed similarities in objective rhinological parameters as well as rhinological patients and patients with pathological septal deviation derived from the unselected group of non-rhinological patients . Furthermore , this benchmark of nasal resistance shows significant correlations with subjective assessment of nasal breathing . CONCLUSION Inspiratory nasal resistance obtained at a flow-velocity of 250 cm^3/s using rhinoresistometry may be useful to distinguish patients with physiological and pathological septal deviation . Correlation with subjective assessment and endoscopic findings is improved OBJECTIVES /HYPOTHESIS Septoplasty is a frequently performed surgical procedure with the most common indication being nasal airway obstruction . Almost universally , health insurance companies m and ate a trial of medical therapy consisting of intranasal corticosteroids prior to performance of septoplasty regardless of clinical assessment . Evidence for this requirement is lacking . We sought to evaluate the initial clinical assessment as a predictor of response to this m and ated trial of medical treatment . STUDY DESIGN Retrospective review of prospect ively collected data on 137 consecutive patients who presented with symptoms of nasal obstruction and a deviated nasal septum on physical examination . METHODS Patients were placed into one of three cohorts based on prediction of 1 ) failure of medical therapy with subsequent septoplasty , 2 ) success of medical therapy without subsequent septoplasty , or 3 ) unable to make a prediction . Patients from each cohort were assessed for subsequent response to medical therapy and ultimate need for septoplasty . RESULTS Overall clinical assessment had a sensitivity of 86.9 % , specificity of 91.8 % , positive predictive value of 93.6 % , and negative predictive value of 96.4 % for detecting/predicting need for septoplasty . The accuracy of the overall clinical assessment is considerably better than severe deviation at any one septal anatomical site . Of patients whose response to medical therapy could not be predicted , 61.3 % failed medical therapy and needed surgery ; this is statistically equivalent to a 50/50 distribution between either needing septoplasty or not . CONCLUSIONS Clinical assessment at initial presentation of patients with nasal obstruction and deviated septum is highly accurate in predicting which patients will need septoplasty The aim of the present study was to assess the clinical utility of acoustic rhinometry ( AR ) compared with active anterior rhinomanometry ( AAR ) in the evaluation of nasal patency in subjects with nasal septal deviation . Fifty patients were divided into three groups based upon the part of the nasal cavity where the septal deviation was situated ( anterior : up to 2.5 cm ; middle : between 2.5 and 4.5 cm ; posterior : between 4.5 and 8 cm measured from the columella ) . The control group consisted of 15 subjects with no nasal complaints and no history of nasal disease . Inspiratory and expiratory nasal airway resistance ( NAR ) at 75 Pa and at 150 Pa before and after decongestion were measured by AAR . Minimal Cross-sectional Area ( MCA ) , distance of MCA , and nasal volume ( Vol ) were measured before and after decongestion by AR ( Rhino 2000 ) . Subjective nasal patency was assessed by Visual Analogue Score ( VAS ) . In the statistical analysis the deviated unilateral nasal cavities were compared with the r and omly chosen unilateral nasal cavities of normal subjects . Both techniques AR and AAR were sufficiently sensitive to reveal severe deviations in the anterior nasal cavity ( MCA , Volant , NAR75 , NAR150 , p < 0.05 ) . The techniques were less sensitive in cases of middle and posterior deviations ( MCA , Volmid , Volpost , MCAmid , MCApost , NAR75 , p > 0.05 ) . The nondecongested inspiratory and expiratory NAR at 150 Pa were the only parameter that differed from normal in cases of posterior deviations . The VAS correlated better with NAR than with MCA . MCA correlated more frequently with expiratory than with inspiratory NAR BACKGROUND A subjective feeling of nasal airflow obstruction is a common symptom . An objective method for quantitative measurement of nasal airflow has long been desired . Rhinomanometry and acoustic rhinometry have been developed for anatomical and physiological evaluation of nasal obstruction . This study was design ed to determine the usefulness of a portable spirometer in assessing upper airway obstruction . METHODS One hundred and ninety-six patients were assessed with nasal inspiratory spirometry to determine nasal airflow . All patients also underwent paranasal sinus computed tomography to determine anatomical abnormalities . Spirometry was performed on each nostril separately . RESULTS Sensitivity and specificity levels were high . This portable and easy to use device may be useful in respiratory assessment . Correlation between anatomical obstructions and subjects ' complaints was statistically significant ( p < 0.001 ) , but no definite correlation between septal deviation severity and spirometric values was found . CONCLUSION Portable spirometry is an objective and useful method of evaluating nasal obstruction , but needs more investigation to establish a st and ardised test OBJECTIVE The aim in this study was to evaluate the efficiency of Nasal Obstruction Symptom Evaluation ( NOSE ) scale for septoplasty ( without turbinate reduction ) in comparison with other examination methods . METHODS Prospect i ve observational study was undertaken in otolaryngology department of university hospital . NOSE scale for quality of life assessment , visual analog scale for examination findings , acoustic rhinometry and coronal computed tomography were performed before and after septoplasty . The efficiency of NOSE scale to assess for septoplasty results and the correlation between NOSE scores and other techniques was analyzed . RESULTS Twenty-seven patients underwent septoplasty ; there was a very significant improvement in mean NOSE scores of patients ( 60.2 versus 11.28 , p<0.01 ) . There was no correlation between NOSE scores and acoustic rhinometry . Correlation was found between NOSE scores and examination and computed tomography findings ( p<0.05 ) . CONCLUSION NOSE scale that is well correlated with examination findings and computed tomography , is very useful tool to evaluate the effectiveness of pure septoplasty Two auxiliary methods of diagnosing nasopharyngeal airway obstruction were compared . Cephalometric radiography and nasopharyngeal videoendoscopy were evaluated for efficacy in terms of reproducibility and validity . Thirty orthodontic patients ( 7 to 12 years of age ) seeking otorhinolaryngologic treatment for mouth breathing , or mouth and nose breathing , had nasopharyngeal endoscopy and radiographic examinations performed on the same day . Two otorhinolaryngologists analyzed the results . Nasopharyngeal endoscopy was more reliable in identifying all the obstructive nasopharyngeal processes . Endoscopy obtained kappa index scores of almost perfect agreement for diagnosis of posterior nasal septum deviation , of substantial agreement for anterior nasal septum deviation and lower turbinate hypertrophy , and of moderate agreement for middle turbinate hypertrophy . Lateral cephalometric radiography obtained scores of perfect agreement for imaging hypertrophy of the middle turbinate , of almost perfect agreement for imaging hypertrophy of the posterior portion of the inferior turbinate , and of substantial agreement for imaging hypertrophy of the inferior turbinate . Radiographic diagnoses of hypertrophy of the middle and lower turbinates exhibited high sensitivity and low specificity when compared with diagnoses by nasopharyngeal endoscopy |
13,094 | 20,375,494 | When analyzed separately , dopamine and N-acetylcysteine did not reduce the risk for AKI .
The results advocate large , good- quality , multicenter studies to determine whether promising interventions reliably reduce rates of acute renal replacement therapy and mortality in the cardiac surgery setting | Background : Acute kidney injury ( AKI ) is common in patients undergoing cardiac surgery and is associated with a high rate of death , long-term sequelae and healthcare costs .
We conducted a systematic review of r and omized controlled trials for strategies to prevent or treat AKI in cardiac surgery . | OBJECTIVES Cardiopulmonary bypass ( CPB ) is widely regarded as an important contributor to renal failure , a well recognized complication following coronary artery surgery ( coronary artery bypass grafting ( CABG ) ) . Anecdotally off-pump coronary surgery ( OPCAB ) is considered renoprotective . We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass ( ONCAB ) . METHODS Forty low-risk patients with normal preoperative cardiac and renal functions awaiting elective CABG were prospect ively r and omized into those undergoing OPCAB ( n=20 ) and ONCAB ( n=20 ) . Glomerular and tubular injury were measured respectively by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum Cr and blood urea were also monitored . RESULTS No mortality or renal complication were observed . Both groups had similar demographic makeup , Parsonnet score , functional status and extent of coronary revascularization ( 2.1+/-1.0 vs. 2.5+/-0.7 grafts ; P=0.08 ) . Serum Cr and blood urea remained normal in both groups throughout the study . A significant and similar rise in urinary RBP : Cr occurred in both groups peaking on day 1 ( 3183+/-2534 vs. 4035+/-4079 ; P=0.43 ) before reapproximating baseline levels . These trends were also observed with urinary microalbumin : Cr ( 5.05+/-2.66 vs. 6.77+/-5.76 ; P=0.22 ) . Group B patients had a significantly more negative fluid balance on postoperative day 2 ( -183+/-1118 vs. 637+/-847 ml ; P=0.03 ) . CONCLUSIONS Although renal complication or serum markers of kidney dysfunction were absent , sensitive indicators revealed significant and similar injury to renal tubules and glomeruli following either OPCAB or ONCAB . These results suggest that avoidance of CPB does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG OBJECTIVES We aim ed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction . The latter included older patients or those with pre-existing renal disease , elevated preoperative serum creatinine ( Cr ) , poor ventricular function , hypertension , diabetes mellitus and unstable angina requiring intravenous therapy . METHODS Fifty patients undergoing cardiopulmonary bypass ( CPB ) who fulfilled the entry criteria were prospect ively r and omized into two groups : Group 1 received a ' renal-dose ' ( 3 microg kg(-1 ) min(-1 ) ) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2 . The anaesthetic and CPB regimes were st and ardized . Urinary excretion of retinol binding protein ( RBP ) indexed to Cr , an accurate and sensitive marker of early renal tubular damage , was assessed daily for 6 days . Additional outcome measures included daily fluid balance , blood urea and serum Cr . Statistical comparisons were made using ANOVA and Mann-Whitney U-test . RESULTS No significant difference was found between the groups in their age , gender , preoperative NYHA class , ejection fraction , baseline serum Cr and duration of CPB and aortic cross-clamping . Renal replacement therapy was not required in any instance . Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period . Dopamine-treated patients achieved more negative average fluid balance than those on placebo ( 5 vs. 229 ml , P<0.05 ) . CONCLUSIONS Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics . The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure , and undergoing coronary artery bypass . No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo . Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group ; during cardiopulmonary bypass , urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo . These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery ; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure Between August 2004 and May 2006 , 124 patients undergoing coronary artery bypass grafting with ejection fractions ≤ 35 % were r and omly assigned to off-pump or conventional procedures . Preoperative characteristics were the same in both groups , except for age and degree of mitral regurgitation . Off-pump coronary artery grafting was carried out using a tissue stabilizer and a single-suture technique ; conventional coronary bypass employed cardiopulmonary bypass , moderate hypothermia , and ante grade -retro grade cold blood cardioplegic arrest . There were significantly fewer vessels grafted ( 3.09 ± 0.41 ) in the off-pump group than in those who had a conventional procedure ( 3.42 ± 0.86 ) . The rates of mortality , morbidity , balloon pump support , inotropic usage , gastrointestinal bleeding , renal dysfunction , reintubation , as well as intensive care and hospital stay , were significantly lower in the off-pump group . The incidence of perioperative myocardial infa rct ion did not differ significantly between groups . The results of this study indicate that beating-heart coronary bypass is safe and effective in patients with left ventricular dysfunction AIM Renal function is one of the most important prognostic factors following cardiac surgery . Whether aspirin affects cardiopulmonary bypass related renal injury is investigated in this study . METHODS Ninety-four patients with impaired renal function ( creatinine = or > 1.5 mg/dl ) undergoing coronary artery bypass grafting ( CABG ) were categorized into 2 groups according to aspirin administration before surgery . Serum creatinine , urinary output and creatinine clearance along with other perioperative factors were compared between the 2 groups prior to surgery , 24 hours and 48 hours following cardiopulmonary bypass . RESULTS Creatinine levels increased significantly in the second postoperative day only in the non-aspirin ( control ) group ( 3.7+/-1.6 vs 2.9+/-1.7 mg/dl , p=0.03 ) . Aspirin ( study ) group had lower creatinine levels in day 1 ( p=0.03 ) and day 2 ( p=0.001 ) . Furthermore , in the study group creatinine clearance was higher in day 1 ( 34.3+/-14.3 vs 30.9+/-13.1 ml/min , p=0.01 ) and in day 2 ( 32.6+/-13.8 vs 26.4+/-9.8 ml , p<0.0001 ) . Creatinine levels at discharge were elevated compared to the preoperative levels in the control group ( p=0.01 ) . However , the study group had lower creatinine levels at discharge ( 2.6+/-1.4 vs 3.8+/-1.6 mg/dl , p<0.0001 ) . Urinary output was higher in the study group in the first postoperative day compared to the control group ( p=0.01 ) . Postoperative bleeding was slightly increased in the study group compared to the control group ( 760+/-230 ml vs 530+/-210 ml , p=0.01 ) . CONCLUSIONS Continuation of aspirin administration until the day of surgery may have a protective effect against renal injury result ing from cardiopulmonary bypass , with only a negligible increase in bleeding . Possible explanations for this effect are antiplatelet activity of aspirin during cardiopulmonary bypass causing inhibition of vasoconstrictive agents like thromboxane , and improvement of renal perfusion by reducing blood viscosity Mannitol is often added to the cardiopulmonary bypass pump prime to reduce the incidence of renal dysfunction , but studies so far have been inconclusive . Urinary excretion of microalbumin and retinol binding protein are more sensitive than routine biochemical tests of renal function after cardiac surgery . We performed a double‐blind , r and omised , controlled trial in cardiac surgical patients with pre‐operative plasma creatinine < 130 μmol.l−1 . Twenty patients received 0.5 g.kg−1 of mannitol in the pump prime , whereas 20 control patients received an equivalent volume of Hartmann ’s solution . Blood and urine sample s were taken on the day before surgery and daily for 5 days postoperatively for measurement of plasma urea and creatinine , urinary creatinine , retinol binding protein and microalbumin . We found no differences between the mannitol and control patients for any measured variable , and conclude that mannitol has little impact on renal function in patients with normal pre‐operative plasma creatinine concentrations Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine ( D ) and dopamine-nitroprusside ( DN ) on renal function during cardiopulmonary bypass ( CPB ) . No differences from the control group ( C ) were found in creatinine clearance , fractional sodium excretion , osmolarity and free-water clearance . Sodium output/intake ratio during CPB was higher in group D than in groups C and DN ( P less than 0.05 ) ; water output/intake ratio was higher in group D than in group C ( P less than 0.05 ) . Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups , suggesting ischemic tubular cell damage . No patients showed acute postoperative renal failure or a worsening of their renal dysfunction . The data suggest an increased water and sodium excretion during CPB with a dopamine infusion , possibly result ing from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation , respectively . We hypothesised that fenoldopam , a selective dopamine receptor agonist , would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects , and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation . We examined the effects of fenoldopam on haemodynamic parameters , creatinine clearance , fractional excretion of sodium , urine output , free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation . Patients were r and omly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 ( n = 16 ) or placebo ( n = 15 ) . Renal parameters were measured : during a 24‐h period before hospital admission , during cardiopulmonary bypass , from completion of cardiopulmonary bypass until 4 h later , from 4 to 8 h after cardiopulmonary bypass , and from 8 to 14 h after cardiopulmonary bypass . Gastric intramucosal pH was measured using a gastric tonometer before , during and after cardiopulmonary bypass . In the placebo group , but not the fenoldopam group , mean ( SD ) creatinine clearance decreased after separation from cardiopulmonary bypass , from 107 ( 36 ) to 71 ( 22 ) ml.min−1 ( p < 0.01 ) and from 107 ( 36 ) to 79 ( 26 ) ml.min−1 ( p < 0.01 ) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass , respectively . Changes in intramucosal pH were similar in both groups . The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass OBJECTIVES The purpose of this study was to determine the role nesiritide might play in patients with left ventricular dysfunction undergoing coronary artery bypass grafting ( CABG ) using cardiopulmonary bypass ( CPB ) . BACKGROUND Given the hemodynamic , neurohormonal , and renal effects of natriuretic peptides , nesiritide might be useful in the management of patients undergoing cardiac surgery . METHODS This prospect i ve , double-blind , exploratory evaluation r and omly assigned patients with ejection fraction < /=40 % who were undergoing CABG with anticipated use of CPB to receive either nesiritide or placebo , in addition to usual care , for 24 to 96 h after induction of anesthesia . Postoperative renal function , hemodynamics , and drug use ( primary end points ) were assessed in patients who underwent CABG using CPB ; mortality and safety ( secondary end points ) were assessed in all patients who received the study drug . RESULTS Of 303 r and omized patients , 279 received the study drug and 272 underwent CABG using CPB . Compared with placebo , nesiritide was associated with a significantly attenuated peak increase in serum creatinine ( 0.15 + /- 0.29 mg/dl vs. 0.34 + /- 0.48 mg/dl ; p < 0.001 ) and a smaller fall in glomerular filtration rate ( -10.8 + /- 19.3 ml/min/1.73 m(2 ) vs. -17.2 + /- 21.9 ml/min/1.73 m(2 ) ; p = 0.001 ) during hospital stay or by study day 14 , and a greater urine output ( 2,926 + /- 1,179 ml vs. 2,350 + /- 1,066 ml ; p < 0.001 ) during the initial 24 h after surgery . In addition , nesiritide-treated patients had a shorter hospital stay ( p = 0.043 ) and lower 180-day mortality ( p = 0.046 ) . CONCLUSIONS Nesiritide in the setting of CABG with CPB is associated with improved postoperative renal function and possibly enhanced survival . ( The NAPA Trial ; ; ) OBJECTIVE To evaluate the influence of the alpha2-adrenergic receptor agonist clonidine on creatinine clearance as a measure of renal function . DESIGN Prospect i ve , double-blind , r and omized , placebo-controlled clinical trial . SETTING University hospital . PATIENTS Patients undergoing coronary artery bypass graft surgery ( n = 48 ) with normal risk . INTERVENTIONS Administration of clonidine ( 4 micrograms/kg iv ) ) or placebo 1 hr before induction of anesthesia . MEASUREMENTS AND MAIN RESULTS Induction and maintenance of anesthesia ( etomi date , midazolam , and fentanyl ) and cardiopulmonary bypass technique ( nonpulsatile , normothermic , intermittent cold blood cardioplegia ) were st and ardized in all patients . The night before surgery and the first and third night after surgery , creatinine clearance was calculated from a 12-hr urine collection period . Venous blood sample s for determination of plasma antidiuretic hormone ( ADH ) concentrations were taken the evening before surgery , immediately before induction of anesthesia and the evening after surgery ( n = 16 ) . Arterial catecholamine plasma concentrations were determined ( high-performance liquid chromatography ) before induction , 15 mins after induction of anesthesia , immediately after sternotomy , before initiation of cardiopulmonary bypass , as well as 5 , 15 , and 30 mins after initiation of cardiopulmonary bypass ( n = 16 ) . The total amount of anesthetics , infusions , transfusions , diuresis , and blood loss was not different between the groups . Creatinine clearance decreased over the first postoperative night from 98 + /- 18 ( preoperatively ) to 68 + /- 19 mL/min ( p < .05 ) in placebo-treated patients . Creatinine clearance remained unchanged in clonidine-treated patients ( 90 + /- 19 [ preoperatively ] to 92 + /- 17 mL/min ) . There was a significant difference in creatinine clearance between the groups during the first postoperative night ( p < .05 ; Mann-Whitney U test ) . In the third postoperative night , mean creatinine clearance of both groups was not different ( 75 + /- 31 vs. 86 + /- 28 mL/min ) . ADH concentrations were not different between the groups at any time , while plasma catecholamine concentrations were always significantly lower in clonidine-treated patients . CONCLUSIONS Preoperative treatment with clonidine ( 4 microgram/kilogram ) prevents the deterioration of renal function after cardiac surgery . This effect might be due to clonidine-induced reduction in the sympathetic nervous system response to coronary artery bypass graft surgery BACKGROUND We evaluated the effects of human atrial natriuretic peptide ( hANP ) during cardiopulmonary bypass ( CPB ) . METHODS Forty patients undergoing coronary artery bypass grafting were investigated . A group of patients given hANP for 24 hours from the start of CPB ( hANP group ) was compared with a non-hANP group . Parameters examined were hemodynamics , urine volume , dosage of furosemide , respiratory index , pleural effusion , ANP , cyclic guanosine monophosphate , renin activity ( renin ) , angiotensin-II , aldosterone , and glomerular filtration rate . RESULTS Central venous pressure , systemic vascular resistance index , and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group . The hANP group showed significantly higher levels of ANP , cyclic guanosine monophosphate , glomerular filtration rate , and respiratory index , and significantly lower levels of renin , angiotensin-II , aldosterone , and pleural effusion , as compared with the non-hANP group . The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group . CONCLUSIONS hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance , suppressing the renin-angiotensin-aldosterone system , and exerting a strong diuretic effect BACKGROUND In cardiac surgery with cardiopulmonary bypass ( CPB ) , corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response . The effects of corticosteroids on CPB-associated renal damage have not been documented . The purpose of this study was to evaluate the effects of dexamethasone on perioperative renal dysfunction in patients undergoing cardiac surgery with CPB . METHODS Renal damage was prospect ively studied in 20 patients without concomitant morbidity undergoing coronary artery surgery with CPB . Patients were r and omized in a double-blind fashion to receive dexamethasone or placebo . Markers of glomerular function ( creatinine clearance ) and damage ( microalbuminuria ) , and markers of tubular function ( fractional excretion of sodium and free water clearance ) and damage ( N-acetyl-beta-D glucosaminidase ( NAG ) ) were evaluated in addition to plasma and urinary glucose levels . Plasma and urinary specimens were obtained at the following time periods : ( 1 ) baseline , during the 12 h before surgery ; ( 2 ) skin incision before heparinization ; ( 3 ) from heparinization until the end of CPB ; ( 4 ) during the 2 h following weaning from CPB ; ( 5 ) in the intensive care unit from 2 to 6 h after weaning of CBP ; ( 6 ) and from 36 to 60 h after weaning of CPB . RESULTS CPB was associated with an increase in markers in the placebo group , which returned to baseline during the second postoperative day , demonstrating a transient impairment of glomerular and tubular renal function . Similar patterns were observed in patients treated with dexamethasone . While postoperative glycosuria was significantly higher in the dexamethasone-treated group , no other differences between groups were observed . CONCLUSION Dexamethasone administration before CPB has no protective effect on perioperative renal dysfunction in low-risk cardiac surgical patients OBJECTIVE The purpose of this study was to evaluate the renoprotective effects of fenoldopam in patients at high risk of postoperative acute kidney injury undergoing elective cardiac surgery requiring cardiopulmonary bypass . DESIGN A double-blind r and omized clinical trial . SETTING Hospital . PARTICIPANTS One hundred ninety-three patients . INTERVENTIONS Patients undergoing cardiac surgery were r and omly assigned to receive a continuous infusion of fenoldopam , 0.1 microg/kg/min ( 95 patients ) , or placebo ( 98 patients ) for 24 hours . Patients were included if at least 1 of the following risk factors was present : preoperative serum creatinine > or = 1.5 mg/dL , age > 70 years , diabetes mellitus , or prior cardiac surgery . Serum creatinine and urinary output were measured at baseline ( T1 ) , 24 hours ( T2 ) , and 48 hours after surgery ( T3 ) . Acute kidney injury was defined as a postoperative serum creatinine level of > or = 2 mg/dL with an increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to maximum postoperative values . MEASUREMENTS AND MAIN RESULTS Acute kidney injury developed in 12 of 95 ( 12.6 % ) patients receiving fenoldopam and in 27 of 98 ( 27.6 % ) patients receiving placebo ( p = 0.02 ) , whereas renal replacement therapy was started in 0 of 95 and 8 of 98 ( 8.2 % ) patients , respectively ( p = 0.004 ) . Serum creatinine was similar at baseline ( 1.8 + /- 0.4 mg/dL v 1.9 + /- 0.3 mg/dL ) in the fenoldopam and placebo groups but differed significantly ( p < 0.001 and p < 0.001 ) 24 hours ( 1.6 + /- 0.2 mg/dL v 2.5 + /- 0.6 mg/dL ) and 48 hours ( 1.5 + /- 0.3 mg/dL v 2.8 + /- 0.4 mg/dL ) after the operation . CONCLUSIONS A 24-hour infusion of 0.1 mug/kg/min of fenoldopam prevented acute kidney injury in a high-risk population undergoing cardiac surgery OBJECTIVE Preoperative renal insufficiency is a predictor of acute renal failure in patients undergoing coronary artery revascularization with cardiopulmonary bypass . Off-pump coronary artery bypass grafting has been shown to be less deleterious than on-pump bypass in patients with normal renal function , but the effect of this technique in patients with non-dialysis dependent renal insufficiency in a r and omized study is unknown . METHODS From August 2004 through October 2005 , 116 consecutive patients with preoperative non-dialysis-dependent renal insufficiency ( glomerular filtration rate measured using the Modification of Diet in Renal Disease equation [ MDRD GFR ] < or = 60 mL x min(-1 ) x 1.73 m(-2 ) ) undergoing primary coronary artery bypass grafting were r and omized to on-pump ( n = 60 ) and off-pump ( n = 56 ) groups . MDRD GFR and serum creatinine levels were measured preoperatively and postoperatively at days 1 and 5 . The changes in renal function and clinical outcomes were compared between the two groups . RESULTS Preoperative characteristics were comparable between the two groups . The repeated- measures analysis of variance was performed on the data that showed worsening of renal function in the on-pump group compared with the off-pump group ( serum creatinine , P < .000 ; glomerular filtration rate , P < .000 ) . Further analysis of subgroups of patients with diabetes alone , hypertension alone , and combined hypertension and diabetes also showed significant deterioration renal function in the on-pump group compared with the off-pump group . In covariate analysis , diabetes has emerged as a significant covariate by serum creatinine criteria while compromised left ventricular function has emerged as a significant covariate by glomerular filtration rate criteria . These analyses showed that the use of cardiopulmonary bypass is significantly associated with adverse renal outcome ( P < .000 ) . Three patents required hemodialysis in the on-pump group and none in the off-pump group . The mean number of grafts per patient was 3.85 + /- 0.86 and 3.11 + /- 0.89 in the on-pump and off-pump groups , respectively ( P < .001 ) , but the indices of completeness of revascularization , 1.00 + /- 0.08 for off-pump coronary bypass and 1.01 + /- 0.08 for on-pump coronary bypass , were similar ( P = .60 ) . CONCLUSIONS This study suggests that on-pump as compared with off-pump coronary artery bypass grafting is more deleterious to renal function in diabetic patients with non-dialysis dependent renal insufficiency . MDRD GFR is a more sensitive investigation than serum creatinine levels to assess renal insufficiency in patients undergoing coronary bypass We prospect ively studied the effects of renal protection intervention in 17 patients with preoperative abnormal renal function ( plasma creatinine > 1.5 mg/dL ) scheduled for elective coronary surgery . Patients were r and omized to either dopamine 2.0 micro g [ center dot ] kg-1 [ center dot ] min-1 ( Group 1 , n = 10 ) or perfusion pressure > 70 mm Hg during cardiopulmonary bypass ( CPB ) ( Group 2 , n = 7 ) . Glomerular filtration rate and effective renal plasma flow were measured with inulin and 125 I-hippuran clearances before the induction of anesthesia , after sternotomy and before CPB , during hypo- and normothermic CPB , after sternal closure , and 1 h postoperatively . Plasma and urine electrolytes were measured , and free water , osmolar , and creatinine clearances , as well as fractional excretion of sodium and potassium , were calculated before and after surgery . Significant differences between groups were found before CPB for glomerular filtration rate ( higher in Group 1 ) , urine output ( 2.0 vs 0.29 mL/min in Group 1 versus Group 2 ) , urinary creatinine ( 66 vs 175 mg/dL ) , urinary osmolarity ( 370 vs 627 mOsm/L ) , osmolar clearance ( 2.1 vs 0.7 mL/min ) , and urinary potassium ( 33 vs 71 mEq/L ) . There were no differences between groups during hypo- and normothermic CPB . After CPB , the only difference was a slightly higher urinary creatinine in Group 2 . Renal plasma flow was lower than normal in all patients before the induction of anesthesia . A nonsignificant trend toward increased flow was seen during hypothermic CPB . Filtration fraction was high before CPB , which suggests efferent arteriolar vasoconstriction , descending toward normal during and after CPB . The same pattern of changes was present in both groups . In conclusion , there were no clinical ly relevant differences between the two treatment modalities during and after CPB . However , significant differences were observed before CPB , when dopamine seemed to partially revert renal vasoconstriction . Implication s : Two protective interventions were compared in patients undergoing heart surgery to prevent deterioration of renal function ; these were dopamine infusion throughout the operation and phenylephrine infusion during cardiopulmonary bypass . We found clinical ly relevant differences only during surgery before cardiopulmonary bypass Objective : To assess the preventive effect of the antioxidant N-acetylcysteine on postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery . Design : R and omized , placebo-controlled , prospect i ve study . Setting : University cardiology center . Patients : Two hundred fifty-four consecutive patients with chronic renal insufficiency ( estimated creatinine clearance ≤60 mL/min ) undergoing elective cardiac surgery . Interventions : Patients were r and omized to receive N-acetylcysteine ( n = 129 ) or placebo ( n = 125 ) . Patients of the N-acetylcysteine group received four boluses of intravenous N-acetylcysteine ( 1200 mg every 12 hrs , starting immediately before cardiac surgery ) . Measurements and Main Results : The incidence of postoperative acute renal failure ( > 25 % increase in serum creatinine from baseline ) and the in-hospital clinical course were evaluated . Acute renal failure occurred in 46 % of patients and was associated with increased in-hospital mortality ( 7 % vs. 0.7 % ; p = .024 ) . It occurred in 52 % of control patients and 40 % of N-acetylcysteine-treated patients ( p = .06 ) . In-hospital mortality and need for renal replacement therapy were not affected by N-acetylcysteine , but a lower percentage of N-acetylcysteine-treated patients required mechanical ventilation prolonged for > 48 hrs ( 3 % vs. 18 % ; p < .001 ) and had an intensive care unit stay > 4 days ( 13 % vs. 33 % ; p < .001 ) . Conclusions : Intravenous administration of N-acetylcysteine does not clearly prevent postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery BACKGROUND In order to evaluate the effect of the combined use of dopamine and diltiazem on renal function in patients undergoing coronary artery bypass grafting ( CABG ) , we conducted a prospect i ve r and omized study . MATERIAL / METHODS Sixty patients ( 8F , 52 M ) with normal preoperative renal function undergoing CABG were divided r and omly into four groups , including control ( n=15 ) , use of dopamine-only ( n=15 ) , use of diltiazem-only ( n=15 ) , and combined use of dopamine and diltiazem ( n=15 ) . The patients ranged in age from 38 to 74 years ( mean 59.3 ) . Drug administration ( diltiazem : intravenous infusion of 2 microg x kg(-1 ) x min(-1 ) , dopamine : 2 microg x kg(-1 ) x min(-1 ) ) was initiated 24 hours before surgery and was continued for 72 hours . RESULTS Creatinine and osmotic clearances were found to be significantly higher in the combined group compared with the other groups 24 hours after surgery ( p<0.05 ) . There was no significant difference in respect to creatinine clearance , osmotic clearance , and free water clearance in the dopamine-only and diltiazem-only groups compared to the control group . The free water clearance at 24 and 72 hours after surgery were significantly higher in the combined group compared with the other groups ( p<0.05 ) . In the control group , dopamine-only , and diltiazem-only groups beta(2)-microglobulin was statistically higher 72 hours postoperative than preoperatively ( p<0.05 ) . There were no significant changes in beta(2)-microglobulin levels in the combined group . CONCLUSIONS The combined use of dopamine and diltiazem may provide a positive contribution and sufficient protection for early postoperative renal function in patients undergoing CABG Acute renal failure increases risk of death after cardiac surgery . However , it is not known whether more subtle changes in renal function might have an impact on outcome . Thus , the association between small serum creatinine changes after surgery and mortality , independent of other established perioperative risk indicators , was analyzed . In a prospect i ve cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery , the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed . Cox regression was used to correct for various established demographic preoperative risk indicators , intraoperative parameters , and postoperative complications . In the 2441 patients in whom serum creatinine decreased , early mortality was 2.6 % in contrast to 8.9 % in patients with increased postoperative serum creatinine values . Patients with large decreases ( DeltaCrea < -0.3 mg/dl ) showed a progressively increasing 30-d mortality ( 16 of 199 [ 8 % ] ) . Mortality was lowest ( 47 of 2195 [ 2.1 % ] ) in patients in whom serum creatinine decreased to a maximum of -0.3 mg/dl ; mortality increased to 6 % in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl . Mortality ( 65 of 200 [ 32.5 % ] ) was highest in patients in whom creatinine increased > or = 0.5 mg/dl . For all groups , increases in mortality remained significant in multivariate analyses , including postoperative renal replacement therapy . After cardiac and thoracic aortic surgery , 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine . Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival Background — Aprotinin is frequently used in high-risk cardiac surgery patients to decrease bleeding complications and transfusions of packed red blood cells ( PRBC ) . Transfusions of PRBC are known to directly increase the risk of new onset postoperative renal failure ( ARF ) in cardiac surgery patients . A recent highly publicized report implicated aprotinin as an independent causal factor for postoperative renal failure , but ignored the potential confounding affect of numerical PRBC data on ARF . We sought to investigate that cl aim with an analysis that included all perioperative risk factors for renal failure , including PRBC transfusion data . Methods and Results — Prospect ively collected patient data from 12 centers contributing to the Merged Cardiac Registry , an international multicenter cardiac surgery data base , operated on between January 2000 and February 2006 were retrospectively analyzed . A previously published risk model for ARF incorporating 12 variables was used to calculate a baseline ARF risk score for each patient in whom those variables were available ( n=15 174 ) . After adding transfused PRBC data 11 198 patients remained for risk-adjusted assessment of ARF in relation to aprotinin use . Risk-adjusted multivariable analyses were carried out with , and without , consideration of transfused PRBC . Aprotinin was used in 24.6 % ( 2757/11 198 ) . The overall incidence of ARF was 1.6 % ( 180/11 198 ) and was higher in the aprotinin subset ( 2.6 % , 72/2757 versus 1.3 % , 108/8441 ; P<0.001 ) . The incidence of ARF directly and significantly increased with increasing transfusions of PRBC ( P<0.001 ) . Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF ( P=0.008 ; OR=1.5 ) . However , further risk adjustment with the addition of the highly significant transfused PRBC variable ( P<0.0001 ; OR=1.23/transfused PRBC ) to the model attenuates the purported independent affect of aprotinin ( P=0.231 ) on ARF . Conclusions — The increase in renal failure seen in patients who were administered aprotinin was directly related to increased number of transfusions in that high-risk patient population . Aprotinin use does not independently increase the risk of renal failure in cardiac surgery patients CONTEXT Renal dysfunction is a complication of coronary artery bypass graft ( CABG ) surgery performed with cardiopulmonary bypass ( CPB ) that is associated with increased morbidity and mortality . N-acetylcysteine , an antioxidant and vasodilator , counteracts renal ischemia and hypoxia . OBJECTIVE To determine whether perioperative intravenous ( IV ) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo . DESIGN , SETTING , AND PATIENTS R and omized , quadruple blind , placebo-controlled trial ( October 2003-September 2004 ) in operating rooms and general intensive care units ( ICUs ) of 2 Ontario tertiary care centers . The 295 patients required elective or urgent CABG and had at least 1 of the following : preexisting renal dysfunction , at least 70 years old , diabetes mellitus , impaired left ventricular function , or undergoing concomitant valve or redo surgery . INTERVENTIONS Patients received 4 ( 2 intraoperative and 2 postoperative ) doses of IV N-acetylcysteine ( 600 mg ) ( n = 148 ) or placebo ( n = 147 ) over 24 hours . MAIN OUTCOME MEASURES The primary outcome was the proportion of patients developing postoperative renal dysfunction , defined by an increase in serum creatinine level greater than 0.5 mg/dL ( 44 micromol/L ) or a 25 % increase from baseline within the first 5 postoperative days . Secondary outcomes included postoperative interventions and complications , the requirement for renal replacement therapy ( RRT ) , adverse events , hospital mortality , and ICU and hospital length of stay . RESULTS There was no difference in the proportion of patients with postoperative renal dysfunction ( 29.7 % vs 29.0 % , P = .89 ; relative risk [ RR ] , 1.03 [ 95 % confidence interval { CI } , 0.72 - 1.46 ] ) in the N-acetylcysteine and placebo groups , respectively . We noted nonsignificant differences in postoperative interventions and complications , the need for RRT ( 0.7 % vs 2.1 % ; P = .37 ) , total ( 6.1 % vs 9.6 % ; P = .26 ) and serious adverse events , hospital mortality ( 3.4 % vs 2.7 % ; P>.99 ) , and ICU and hospital length of stay between the N-acetylcysteine and placebo groups . A post hoc subgroup analysis of patients ( baseline creatinine level > 1.4 mg/dL [ 120 micromol/L ] ) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group ( 25.0 % vs 37.1 % ; P = .29 ) . CONCLUSIONS N-acetylcysteine did not prevent postoperative renal dysfunction , interventions , complications , or mortality in high-risk patients undergoing CABG surgery with CPB . Further research is required to identify CABG patients at risk for postoperative renal events , valid markers of renal dysfunction , and to establish renal thresholds associated with important clinical outcomes Background — Renal insufficiency is associated with increased morbidity and mortality after cardiopulmonary bypass cardiac surgery . B-type natriuretic peptide is a cardiac hormone that enhances glomerular filtration rate and inhibits aldosterone . Cystatin has been shown to be a better endogenous marker of renal function than creatinine . Methods and Results — We performed a double-blinded placebo-controlled proof of concept pilot study in patients ( n=40 ) with renal insufficiency preoperatively ( defined as an estimated creatinine clearance of < 60 mL/min determined by the Cockroft-Gault formula ) , undergoing cardiopulmonary bypass cardiac surgery . Patients were r and omized to placebo ( n=20 ) or IV low dose nesiritide ( n=20 ; 0.005 & mgr;g/Kg/min ) for 24 hours started after the induction of anesthesia and before cardiopulmonary bypass . Patients in the nesiritide group had an increase of plasma B-type natriuretic peptide and its second messenger cGMP with a decrease in plasma cystatin levels at the end of the 24-hour infusion . These changes were not observed in the placebo group . There was a significant activation of aldosterone in the placebo group at the end of the 24-hour infusion , but not in the nesiritide group . At 48 and 72 hours , there was a decrease in estimated creatinine clearance and an increase in plasma cystatin as compared with end of the 24-hour infusion in the placebo group . In contrast , renal function was preserved in the nesiritide group with no significant change in estimated creatinine clearance and a trend for plasma cystatin to increase as compared with end of the 24-hour infusion . Conclusion — This proof of concept pilot study supports the conclusion that perioperative administration of low dose nesiritide is biologically active and decreases plasma cystatin in patients with renal insufficiency undergoing cardiopulmonary bypass cardiac surgery . Further studies are warranted to determine whether these physiological observations can be translated into improved clinical outcomes BACKGROUND Pre-existing chronic renal failure is a significant risk factor for acute renal failure ( ARF ) after cardiac surgery . N-acetylcysteine ( NAC ) has been shown to prevent contrast media-induced ARF . Our objective was to evaluate whether i.v . NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery . METHODS In this prospect i ve , r and omized , double-blind study , 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited . All received either i.v . NAC ( n=38 ) or placebo ( n=39 ) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase ( NAG ) and urine creatinine ratio , plasma creatinine , and serum cystatin C levels indicated renal function . RESULTS Levels of urinary NAG/creatinine ratio , plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days . Urine NAG/creatinine ratio increased over 30 % in 100 % of patients in the NAC group vs 92.3 % in the placebo group ( P=0.081 ) . Plasma creatinine increased by 25 % from baseline or over 44 mumol litre(-1 ) in 42.1 % in NAC group vs 48.7 % in placebo group ( P=0.560 ) . Serum cystatin C exceeded 1.4 mg litre(-1 ) in 78.9 % in NAC group vs 61.5 % in placebo group ( P=0.096 ) . CONCLUSIONS Prophylactic treatment with i.v . N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery BACKGROUND Coronary artery disease is the major cause of death in patients with chronic renal failure . We studied the early and long-term outcome of patients with mild chronic renal impairment , preoperative regular diuresis , and normal potassium levels having undergone pump myocardial revascularization . METHODS From January 1992 to December 2000 , 67 patients with serum creatinine level higher than 1.7 mg/dl and less than 2.5 mg/dl underwent on-pump myocardial revascularization . The patients were divided into 2 groups and treated with renal doses of dopamine in the postoperative or preoperative period , respectively . A homogeneous group of 100 patients was selected as control . RESULTS There were no statistically significant differences in mortality and morbidity between the two groups A , while there was a significant difference in cardiac and respiratory complications , ICU stay and LOS between the A and B group in the early and long-term follow-up . Survival at 12-year follow-up is significantly higher in the B group . CONCLUSIONS Patients with relatively mild renal insufficiency should be evaluated carefully for open cardiac surgery due to the significant increase in early and long-term morbidity and mortality BACKGROUND The incidence of acute renal failure ( ARF ) after cardiac surgery remains high , despite improvements in surgical techniques and perioperative care , and is associated with an unacceptably high mortality . The adenosine receptor antagonist theophylline has been shown to confer some benefit in experimental and clinical ARF due to ischaemia , contrast media and various nephrotoxic agents . METHODS In a double-blind , r and omized , placebo-controlled trial , the effectiveness of theophylline for prevention of renal impairment after elective coronary artery bypass grafting ( CABG ) was evaluated . Fifty-six patients with normal renal function received a bolus of 4 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h theophylline ( n=28 ) or isotonic saline ( n=28 ) for up to 96 h. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery , and the glomerular filtration rate ( GFR ) ( [(51)Cr]EDTA-clearance ) was determined preoperatively , and at days 1 , 3 and 5 after surgery . RESULTS Serum creatinine and GFR were the same in both groups . The number of patients with increases of serum creatinine > or = 0.4 mg/dl were five in the theophylline group and four in the placebo group . Volumes of infused fluid and urine volumes were not different between groups , both ranging from approximately 7.5 to 8 l during the first 24 h after surgery . The number of patients with termination of study medication due to presumed side effects was not different between placebo and theophylline groups . CONCLUSIONS Theophylline administration for renal protection after CABG appears to be ineffective in a pilot study in well-hydrated patients . However , the statistical power of our study was not sufficient to exclude a possible protective effect of theophylline . The present study demonstrated the feasability of a larger trial with theophylline or one of the new specific adenosine A1 receptor antagonists in the setting of ARF after cardiac surgery BACKGROUND Renal dysfunction and acute renal failure are serious complications of open heart operations . Previous reports have suggested beneficial effects of exogenous glutathione for preservation of renal function after ischemic renal injury . We prospect ively studied the effect of perioperative administration of glutathione on renal function in patients who underwent coronary artery bypass operation . STUDY DESIGN Two hundred mg per kg of glutathione was administered to the treated group ( n = 10 ) before cardiopulmonary bypass , and on the first and second postoperative days . The control group was administered placebo in the same volume . Hemodynamics , renal function , and plasma hormone levels were measured consecutively . RESULTS In the glutathione group , the mean arterial pressure and systemic vascular resistance index were lower than in the control group . Urine volume , creatinine clearance , and renal excretory index were well preserved in the group treated with glutathione . Moreover , the fractional excretion of sodium was lower and urine and plasma osmolarity was higher in the group treated with glutathione . No differences in plasma renin activity , angiotensin II , or aldosterone concentrations between the two groups were observed . CONCLUSIONS Perioperative glutathione treatment has a salutary effect on perioperative renal function through effects on both renal hemodynamics and tubular mechanism BACKGROUND Because patients with low albumin levels may benefit from human albumin ( HA ) administration , we studied correction of hypovolemia with HA in hypoalbuminic elderly cardiac surgery patients . METHODS In a prospect i ve , r and omized study , 50 patients aged > 80 yr undergoing cardiac surgery using cardiopulmonary bypass with a preoperative serum albumin concentration of < 3.5 mg/dL , received either 5 % HA ( n = 25 ) or hydroxyethyl starch ( 6 % HES 130/0.4 ) ( n = 25 ) . Volume was added to the priming ( 500 mL ) and given until the morning of the second postoperative day to keep pulmonary capillary wedge pressure or central venous pressure between 12 and 14 mm Hg . RESULTS Inflammatory response ( interleukins-6 , -10 ) , endothelial activation ( intercellular adhesion molecule-1 ) , and kidney function ( including glutathione transferase-alpha and neutrophil gelatinase-associated lipocalin ) were measured after induction of anesthesia , 5 h after surgery , and the first and second postoperative day . A follow-up , approximately 60 days after discharge from the hospital , was done . Two thous and nine hundred eighty + /- 430 mL of HA and 3060 + /- 680 mL of HES 130/0.4 were given . Serum albumin concentration was significantly increased by HA ( to 4.5 + /- 0.3 mg/dL ) . Serum creatinine , glomerular filtration rate , and urinary levels of alpha-glutathione transferase and neutrophil gelatinase-associated lipocalin were not different in the HA-compared to the HES-treated patients . The inflammatory response was similar in both groups , whereas endothelial activation was less in the HES group . None of the patients developed renal failure requiring renal replacement therapy . CONCLUSION Use of HA in hypoalbuminemic cardiac surgery patients aged > 80 yr was without benefit with regard to inflammatory response , endothelial activation , and renal function compared to 6 % HES 130/0.4 BACKGROUND This prospect i ve , r and omized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting . METHODS Two groups of patients with normal preoperative renal function were r and omly divided into a dopamine group ( n=11 ) , who received dopamine in a dose of 2 mg/kg x min , and a control group ( n=11 ) , who received no treatment . Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively . Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st , 3rd , and 7th postoperative days . Urinary excretion of b2-Microglobulin ( b2-M ) , considered a sensitive means for diagnosing proximal tubular damage , was measured during the early ( day 3 ) and late ( day 7 ) postoperative period . RESULTS There were no significant differences respect to the clearances of creatinine , osmotic , and free-water in the dopamine group compared with the control group ( p>0.05 ) . Urine microalbumin levels significantly increased on postoperative day 3 in both groups . During the early postoperative period , excretion of urine b2-M was significantly greater in the dopamine group than in the control group ( p<0.05 ) . CONCLUSIONS Consequently , in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting , renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period Background and objectives : Postoperative acute renal failure predicts morbidity and mortality . We investigated the effect of nifedipine infusion on glomerular filtration rate in patients with impaired renal function undergoing cardiopulmonary bypass surgery . Methods : Twenty patients accepted for coronary bypass and /or heart valve surgery were enrolled prospect ively and r and omized to nifedipine infusion or no treatment . Males and females with creatinine ⩾150 & mgr;mol L−1 and ⩾130 & mgr;mol L−1 , respectively , were included . Patients with unstable angina pectoris , ejection fraction ⩽35 % and those on dialysis were excluded . Glomerular filtration rate was measured preoperatively and 48 h postoperatively . Creatinine clearance was measured preoperatively and 0‐4 , 20‐24 and 44‐48 h postoperatively . There were no statistically significant differences in patient characteristics . Biochemical markers in plasma and urine were measured before and 48 h after surgery . Results : The mean ± SD preoperative glomerular filtration rates were 32.2 ± 11.5 and 31.4 ± 17.0 mL min−1 per 1.73 m2 in the nifedipine and control groups ( P = 0.90 ) , respectively . There was no statistically significant change in the glomerular filtration rate or in creatinine clearance over time within or between groups . A linear mixed model showed no effect of nifedipine ( P = 0.44 ) , time ( P = 0.97 ) or interaction of nifedipine and time ( P = 0.99 ) on creatinine clearance . Perioperative arterial pressure was kept within predefined targets . Three patients received dialysis postoperatively , all in the control group ( P = 0.21 ) . There were no statistically significant differences between groups in changes of urinary or plasma biochemistry . Conclusions : Renal function was well preserved after cardiopulmonary bypass surgery in patients with impaired renal function when maintaining thorough intensive care surveillance . Nifedipine did not influence early postoperative renal function BACKGROUND Despite the widespread availability of dialytic and intensive care unit technology , the probability of early mortality in critically ill persons with acute renal failure is distressingly high . Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria . Additionally , data obtained decades ago may not apply today owing to changes in case mix . METHODS The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded review er . RESULTS The overall in-hospital mortality rate was 70 % . Twelve readily available historical , clinical , and laboratory variables were significantly associated with in-hospital mortality . Multivariate logistic regression analysis showed that mechanical ventilation , malignancy , and nonrespiratory organ system failure were independently associated with in-hospital mortality . Using a 95 % positivity criterion , this model identified 24 % of high-risk patients who died , without misclassification of any survivors . Of those who survived to hospital discharge , 33 % were dialysis dependent and 28 % were institutionalized long-term . CONCLUSIONS Among critically ill patients , acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality . This risk appears to depend largely on comorbid conditions , such as the need for mechanical ventilation and underlying malignancy . While this prognostic model requires prospect i ve validation , it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit OBJECTIVE Acute renal failure remains a common and serious complication of cardiac surgery . In this r and omized trial , we aim ed to assess whether sodium nitroprusside ( SNP ) infusion during cardiopulmonary bypass ( CPB ) could prevent renal dysfunction after coronary artery bypass grafting ( CABG ) surgery . METHODS Between October 2004 and May 2006 , 240 consecutive patients with stable angina undergoing elective CABG for multi-vessel coronary artery disease were prospect ively r and omized into control ( n=116 , 72 men , mean age 61.3+/-9.7 years ) or SNP groups ( n=124 , 81 men , 60.8+/-10.8 years ) . SNP group received SNP after initiation of rewarming period during CPB at a dose of 0.1mg/kg/h and the infusion was concluded by weaning from CPB . The anesthetic and CPB regimes were st and ardized . Blood urea nitrogen ( BUN ) , serum creatinine ( SCr ) , estimated glomerular filtration rate ( eGFR ) , creatinine clearance ( C(Cr ) ) , urine output , serum cardiac specific troponin I ( cTnI ) , creatine kinase cardiac isoenzyme ( CKMB ) , and CPK were measured preoperatively and daily until day 5 after surgery . RESULTS There were no differences in baseline levels of BUN , SCr , eGFR , C(Cr ) , cTnI , CKMB , CPK levels and EuroSCORES between the groups . Although the duration s of cross clamp , CPB times , and postoperative cardiac enzymes were similar in both groups ; in the control group , there was a significantly lower urine excretion during CPB ( p=0.002 ) and the operation ( p=0.041 ) . Peak postoperative SCr levels were significantly ( p=0.001 ) lower in the SNP group than in the control group ( 1.29+/-0.28 vs 1.42+/-0.34mg/dl ) . The incidence of > or=50%DeltaSCr was significantly higher in the control group when compared with the SNP group ( 35.3 vs 13.7 % , p<0.001 ) . Development of new C(Cr ) less than 50ml/min postoperatively was significantly higher in the control group compared with the SNP group ( 14 vs 38 % , p<0.001 ) . CONCLUSION SNP administration during rewarming period of non-pulsatile CPB in patients undergoing CABG surgery is associated with improved renal function compared with conventional medical treatment providing adequate preload and mean arterial pressures BACKGROUND We aim ed to show the impact of leukodepletion on renal function in patients undergoing on-pump coronary revascularization . PATIENTS AND METHODS Fifty patients awaiting elective on-pump coronary revascularization with normal preoperative cardiac functions and with plasma creatinine levels ranging between 1.5 and 2.0 mg/dL were prospect ively r and omized into two groups : on-pump CABG with ( group A : n = 25 ) and without leukodepletion ( group B , n = 25 ) . Renal glomerular and tubular injury were assessed by urinary alpha glutathione s-transferase ( GST ) , plasma creatinine , and blood urea nitrogen ( BUN ) levels . RESULTS The patients consisted of 14 females and 36 males with a mean age of 57.6 + /- 5.3 years . In the leukodepletion group , the mean levels of creatinine , BUN and urinary GST were found to be decreased on the first , third and fifth postoperative days compared with the control group . There was no mortality . Three patients in the control group needed postoperative dialysis . CONCLUSION Patients with renal dysfunction undergoing on-pump CABG surgery seem to benefit from leukodepletion as a measure to prevent tubular damage and renal impairment compared with a control group BACKGROUND Acute renal failure occurring in the postoperative period , requiring dialysis after cardiac surgery is an important risk factor for an early mortality , and the overall mortality of this complication is as high as 40 % to 60 % . Dialysis in the early postoperative period is often complicated by acute hemodynamic , metabolic , and hematologic effects that adversely affect cardiopulmonary function in patients stabilizing from recent surgery . The purpose of this study was to avoid the need for dialysis by infusion of the solution of mannitol , furosemide , and dopamine in the early postoperative period in oliguric renal failure . METHODS One hundred patients with postoperative oliguric or anuric renal failure despite adequate postoperative cardiac output and hemodynamic function were r and omized . Forty patients ( group A ) were given intermittent doses of diuretics ( furosemide , bumetadine , and ethracrynic acid ) and fluids . Sixty patients ( group B ) were given continuous infusion of the solution of mannitol , furosemide , and dopamine ; the infusion was started within 6 hours ( mean 3.5 hours ) in subgroup B1 ( n = 30 ) , and later than 6 hours ( mean 7.5 hours ) in subgroup B2 ( n = 30 ) after the onset of renal failure . RESULTS Diuresis occurred in 93.3 % of group B ( n = 56 ) versus 10 % in group A ( n = 4 ; patients with preop normal renal function ) . Ninety percent of group A ( n = 36 ) required dialysis versus only 6.7 % of group B ( n = 4 ; patients with preexisting renal disease of subgroup B2 ) . Renal function returned to preoperative normal ( serum creatinine 0.9 + /- 0.05 , p < 0.0001 ) or baseline value ( serum creatinine 2.5 + /- 0.01 , p < 0.0001 ) after first postoperative week in subgroup B1 and third postoperative week in subgroup B2 . CONCLUSIONS Infusion of solution of mannitol , furosemide , and dopamine promoted diuresis in patients with acute postoperative renal failure with adequate postoperative cardiac output and had decreased the need for dialysis in the majority of patients . Early administration of this solution in acute renal failure caused early restoration of renal function to normal or baseline status . It remains to be determined whether routine administration of this solution in the early postoperative period for oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis Purpose N-acetylcysteine may prevent acute kidney injury after cardiac surgery . To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial , we evaluated its effects on a surrogate outcome , estimated glomerular filtration rate ( eGFR ) , in a r and omized trial . Methods One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency ( eGFR ≤ 60 mL.min-1 ) were recruited in a blinded ( patients , clinicians , data -collectors ) placebo-controlled r and omized trial . Eighty-nine were r and omized to N-acetylcysteine ( 100 mg·kg-1 iv bolus , 20 mg·kg-1hr·-1 infusion until four hours after cardiopulmonary bypass ) , and 88 to placebo . The primary outcome was the percent change in eGFR during the first 72 postoperative hours . Secondary outcomes included renal replacement therapy , mortality , atrial fibrillation , vasoactive medications , and adverse effects . A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better ( small benefit ) , and with an upper 95 % confidence interval including 9.5 ( moderate benefit ) . Results The median percent change in eGFR was 5.2 % better ( absolute difference ) in the N-acetylcysteine arm ( 95 % confidence interval 2.4 % worse to 12.1 % better ; P = 0.22 ) . With regard to secondary outcomes , all-cause mortality was lower in the N-acetylcysteine arm ( 0 % vs 8 % ; P = 0.007 ) . Conclusion N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study . Nonetheless , its treatment effect was consistent with a plausible small-to-moderate benefit . Given this finding , N-acetylcysteine should be definitively evaluated in a large r and omized trial . RésuméObjectifLa N-acétylcystéine pourrait empêcher une atteinte rénale aiguë après une chirurgie cardiaque . Afin de déterminer si la N-acétylcystéine mérite une évaluation définitive menée par une étude multi-centrique étendue , nous avons évalué ses effets sur un pronostic de remplacement , le taux de filtration glomérulaire estimé ( eGFR ) , dans une étude r and omisée . MéthodeCent soixante-dix-sept patients de chirurgie cardiaque souffrant d’insuffisance rénale modérée préexistante ( eGFR ≤ 60 mL·min-1 ) ont été recrutés dans le cadre d’une étude en aveugle ( patients , cliniciens , collecteurs de données ) , r and omisée et contrôlée par placebo . Quatre-vingt-neuf patients ont été r and omisés à recevoir de la N-acétylcystéine ( bolus 100 mg·kg-1 iv , perfusion 20 mg·kg-1 · h-1 jusqu’à quatre heures après la circulation extracor-porelle ) , et 88 ont reçu un placebo . Le changement en pourcentage du eGFR durant les premières 72 h postopératoires a constitué le résultat primaire . Les résultats secondaires comptaient la dialyse , la mortalité , la fibrillation atriale , les médicaments vasomoteurs administrés , ainsi que les effets secondaires . Une étude multi-centrique ultérieure a été considérée nécessaire si la N-acétylcystéine était associée à une modification en pourcentage du eGFR qui était meilleure de 3,8 ( bénéfice modeste ) , avec un intervalle de confiance de 95 % supérieur comprenant 9,5 ( bénéfice modéré).RésultatsLe changement en pourcentage moyen du eGFR était meilleur de 5,2 % ( différence absolue ) dans le groupe N-acétylcystéine ( intervalle de confiance 95 % 2,4 % moins bon à 12,1 % meilleur ; P = 0,22 ) . En ce qui concerne les résultats secondaires , la mortalité — toutes causes — était plus basse dans le groupe N-acétylcystéine ( 0 % vs 8 % ; P = 0,007 ) . Conclusion La N-acétylcystéine n’a pas causé d’amélioration statistiquement significative dans l’eGFR postopératoire dans cette étude uni-centrique . Néanmoins , son effet thérapeutique pouvait correspondre à un bénéfice plausible modeste à modéré . Au vu de cette découverte , la N-acétylcystéine devrait être évaluée de manière définitive dans une étude r and omisée étendue BACKGROUND Cardiopulmonary bypass ( CPB ) is an important contributor to renal failure , which is a well-recognized complication after coronary artery bypass grafting ( CABG ) . Leukodepletion reduces CPB-associated inflammation and result ant end-organ injuries . However , its effectiveness in renal protection has not been evaluated in a prospect i ve r and omized clinical setting . METHODS Forty low-risk patients awaiting elective CABG with normal preoperative cardiac and renal function were prospect ively r and omized into those undergoing nonpulsatile CPB without ( group A : n = 20 ) and with leukodepletion ( group B : n = 20 ) . Renal glomerular and tubular injury were assessed by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) , respectively . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum creatinine , and blood urea were also monitored . RESULTS No mortality or renal complication occurred . Both groups had similar demographic makeups , Parsonnet scores , extents of coronary revascularization and , duration s of CPB and aortic cross-clamping . Daily fluid balance , serum creatinine , and blood urea remained comparable in both groups throughout the study period . From equal preoperative values , a significantly higher release of urinary RBP : Cr ( 7,807 + /- 2,227 vs 3,942 + /- 2,528 ; p < 0.001 ) and urinary microalbumin : Cr ( 59.4 + /- 38.0 vs 4.7 + /- 6.7 ; p < 0.0001 ) occurred in group A , peaking on day 1 before returning to approximate baseline levels . CONCLUSIONS Although clinical ly overt renal complications were absent , sensitive indicators revealed significantly more injury to both renal tubules and glomeruli after nonpulsatile CPB without leukodepletion . These data suggest that leukocytes play an important role in post-CPB renal dysfunction , and leukodepletion may offer some renal protection in low-risk patients during CABG Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass ( CPB ) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses . We examined the effects of dopexamine on hemodynamic parameters , creatinine clearance , systemic and splanchnic oxygenation , gastric mucosal pH ( pHi ) , and mixed and hepatic venous plasma levels of endotoxin , interleukin-6 ( IL-6 ) , serum amyloid A ( SAA ) , and C-reactive protein ( CRP ) in 44 patients scheduled for coronary artery bypass grafting . Patients were r and omized to receive continuous infusions of 0.5 , 1.0 , or 2 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( n = 10 per group ) or placebo ( n = 14 ) prior to surgery , intraoperatively , and postoperatively . Dopexamine infusion increased systemic oxygen delivery ( P < or = to 0.01 ) . Hepatic venous oxygen saturation did not change , and pHi decreased during and after CPB in all patients ( P < or = to 0.01 ) . Postoperative increases in IL-6 were smallest in patients who received 2.0 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( P < or = to 0.02 ) . SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study . Creatinine clearance was elevated in all dopexamine groups ( P < or = to 0.025 ) . This elevation was higher with lower dopexamine doses ( P < or = to 0.025 ) . We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation . ( Anesth Analg 1997;84:950 - 7 BACKGROUND Off-pump coronary artery bypass surgery is becoming increasingly popular despite the lack of sufficient evidence from r and omized trials . The aim of our prospect i ve , r and omized , single-center study was to examine the role of off-pump revascularization among nonselected patients . METHODS A total of 400 consecutive nonselected patients ( mean age 63 years ) scheduled for isolated coronary revascularization were r and omized by a cardiologist into two groups : A ( on-pump ) and B ( off-pump ) . The cardiac surgeon was allowed to change the operative technique at any time after r and omization . The only exclusion criterion was an emergency procedure . The primary end point was any of the following within 30 days : death , myocardial infa rct ion , stroke , or new renal failure requiring hemodialysis . The study was analyzed on the intention-to-treat principle . RESULTS The primary end point occurred in 4.9 % of patients in group A versus 2.9 % in group B ( not significant ) . Mortality was 1.1 % in group A versus 2.0 % in group B ( not significant ) . Preoperative crossover occurred in 5.4 % of patients in each group ( not significant ) . Intraoperative conversion was necessary in 9.8 % of patients in group B versus 1.1 % of patients in group A ( p < 0.001 ) . Group B patients had fewer distal anastomoses ( 2.3 versus 2.7 in group A ; p < 0.001 ) , less blood loss ( 560 versus 680 mL ; p < 0.001 ) , lower postoperative creatine kinase MB levels ( 0.15 versus 0.56 microkat/L ; p < 0.001 ) and lower total hospital costs ( 3,451 versus 4,387 ; p < 0.001 ) . CONCLUSIONS In our study off-pump technique was applicable in 85 % of nonselected patients and is at least as clinical ly safe and effective as on-pump surgery BACKGROUND The use of dopamine to protect the kidneys against hypoperfusion injury remains controversial with little clinical evidence of benefit and increasing concerns regarding safety . In this double-blind , prospect i ve , r and omised study , we investigated the effect of dopamine infusion ( 2.5 microg/kg/min ) on glomerular filtration rate ( GFR ) and tubular injury in patients undergoing routine cardiopulmonary bypass ( CPB ) . METHODS Forty eight patients were r and omly assigned to receive intravenous dopamine or saline from induction of anaesthesia until 48 hours post-operatively . There were no differences in mean age , bypass time or pre-op creatinine in the 36 patients ( 33 men ) who completed the study . 51Cr-EDTA GFR ( ml/min/1.73 m2 ) was measured pre-operatively and on day 5 only . Urinary markers of tubular injury ( albumin , N-acetyl glucosaminidase , NAG ; retinol binding protein , RBP ) were measured pre-operatively , and on days 1 , 2 and 5 . RESULTS GFR was preserved equally in both groups . All patients demonstrated significant tubular injury but urinary levels of NAG and RBP were lower in the dopamine group ( 41 % , p=0.057 and 41 % , p=0.007 , respectively ) on the first post-operative day . CONCLUSION We conclude that low dose dopamine infusion may reduce renal tubular injury following CPB in patients with normal or near normal baseline renal function Forty-five patients who underwent open heart surgery were divided into a short-perfusion group ( SPG , 21 patients ) with a perfusion time shorter than 60 minutes and a long-perfusion group ( LPG , 24 patients ) with a perfusion time longer than 60 minutes . Nine patients in the SPG and 13 in the LPG received furosemide prophylactically prior to the perfusion . The furosemide dose was 20 - 60 mg . During the perfusion and postoperatively all patients were given furosemide when necessary , i.e. when the volume for diuresis per hour declined below 40 ml/h . The patients who received prophylactic furosemide in the LPG subsequently had clearly less need for furosemide ( 3.9 mg/h ) than the control subjects ( 7.9 mg/h/3 day ) . The patients with furosemide prophylaxis in the LPG had significantly ( less than 0.05 ) higher creatinine clearance and lower serum creatinine values during the postoperative night period and on the 3rd day . In perfusions lasting less than 60 minutes the patients with furosemide prophylaxis had significantly higher urine flow ( p less than 0.001 ) , sodium excretion ( p less than 0.001 ) and potassium excretio-n ( p less than 0.01 ) during bypass surgery and postoperatively compared with that of controls . According to our findings , the prophylactic use of furosemide had a beneficial effect on glomerular filtration rate ( endogenous creatinine clearance ) and postoperative serum creatinine level in LPG . In perfusion shorter than 60 minutes furosemide prophylaxis may be harmful owing to the increased excretion of water , sodium and potassium OBJECTIVE To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blind , clinical study . SETTING Cardiothoracic anesthesia department at a university hospital . PARTICIPANTS Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass , with a preoperatively elevated serum creatinine level ( n = 24 ) . INTERVENTIONS R and omized infusions of diltiazem ( bolus 0.25 mg/kg followed by a continuous infusion of 1.7 microg/kg/min ) ( DTZ , n = 12 ) or placebo ( C , n = 12 ) were started 30 minutes before induction of anesthesia and continued for 24 hours . MEASUREMENTS AND MAIN RESULTS Median plasma concentrations of diltiazem ( DTZ group ) were 79 microg/L before cardiopulmonary bypass , 67 microg/L at the end of cardiopulmonary bypass , and 164 microg/L at 24 hours postoperatively . Serum creatinine levels ; on postoperative days 1 , 3 , and 5 ; and 3 weeks postoperatively were similar between groups . Iohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery ( median , 51 v 40 mL/min/1.73 m(2 ) ; p < 0.05 ) . Urinary N-acetyl-beta-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively . CONCLUSION Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass . Within the limits of this study , the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage result ing from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery Because development of acute renal failure is one of the most potent predictors of outcome in cardiac surgery patients , the prevention of renal dysfunction is of utmost importance in perioperative care . In a double-blind r and omized controlled trial , the effectiveness of dopamine or furosemide in prevention of renal impairment after cardiac surgery was evaluated . A total of 126 patients with preoperatively normal renal function undergoing elective cardiac surgery received a continuous infusion of either " renal-dose " dopamine ( 2 microg/kg per min ) ( group D ) , furosemide ( 0.5 microg/kg per min ) ( group F ) , or isotonic sodium chloride as placebo ( group P ) , starting at the beginning of surgery and continuing for 48 h or until discharge from the intensive care unit , whichever came first . Renal function parameters and the maximal increase of serum creatinine above baseline value within 48 h ( deltaCrea(max ) ) were determined . The increase in plasma creatinine was twice as high in group F as in groups D and P ( P < 0.01 ) . Acute renal injury ( defined as deltaCreamax ) > 0.5 mg/dl ) occurred more frequently in group F ( six of 41 patients ) than in group D ( one of 42 ) and group P ( zero of 40 ) ( P < 0.01 ) . ( The difference between group D and group P was not significant . ) Creatinine clearance was lower in group F ( P < 0.05 ) . Two patients in group F required renal replacement therapy . The mean volume of infused fluids , blood urea nitrogen , serum sodium , serum potassium , and osmolar- and free-water clearance was similar in all groups . It was shown that continuous infusion of dopamine for renal protection was ineffective and was not superior to placebo in preventing postoperative dysfunction after cardiac surgery . In contrast , continuous infusion of furosemide was associated with the highest rate of renal impairment . Thus , renaldose dopamine is ineffective and furosemide is even detrimental in the protection of renal dysfunction after cardiac surgery Introduction : The objective of this study was to evaluate the effects of dopexamine on renal function in 4 groups of patients either with or without renal dysfunction . Transient renal dysfunction is often not clinical ly relevant in patients with normal renal function , but it is an important clinical factor in patients with pre-existing renal failure . Dopexamine ( DX ) is a commonly used catecholamine which probably exerts a selective effect at the splanchnic bed . Material and Methods : 24 patients with normal renal function and 24 patients with impaired renal function ( creatinine in serum ≥ 1.5 mg/dL ) were each r and omly allocated to 2 groups . Group 1 ( control ) without renal dysfunction and group 3 ( control/dysfunction ) with renal dysfunction were considered as control groups , while the patients in DX and DX/dysfunction groups received 1 μg/kg/min dopexamine until the end of surgery . Kidney function was investigated using st and ard parameters and by investigating specific proteins and enzymes . Results : All patients showed pathologic excretions of the investigated parameters during cardiopulmonary bypass ( CPB ) with no differences between the study groups . The distal tubule , the lysosomal regions , Henle 's loop and the glomerular tuft were all damaged . Heart rate and cardiac index increased significantly in the DX-groups , first until the end of surgery , second until the start of ECC . Conclusion : Dopexamine at a dose of 1 μg/kg/min had no influence on renal function and protein excretion and can not be regarded as a kidney function protecting substance BACKGROUND Biological activity of endogenous atrial natriuretic peptide ( ANP ) may decrease during cardiopulmonary bypass . To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass , we conducted a prospect i ve r and omized study . METHODS Eighteen patients undergoing mitral valve surgery were r and omized to receive either ANP treatment ( ANP group ; n = 9 ) or no ANP treatment ( control group ; n = 9 ) . Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours ( 0.05 microg x kg(-1 ) x min(-1 ) ) . Plasma ANP , brain natriuretic peptide and cyclic guanosine monophosphate ( cGMP ) levels , hemodynamic variables and renal function were assessed perioperatively . RESULTS Administration of ANP increased plasma cyclic guanosine monophosphate levels , urine output and fractional sodium excretion , and decreased preload , afterload and plasma brain natriuretic peptide levels significantly ( p < 0.05 ) . Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels ( r = 0.95 , p = 0.0001 ) , correlated with fractional sodium excretion ( r = 0.53 , p = 0.02 ) , and correlated inversely with systemic vascular resistance ( r = -0.54 , p = 0.02 ) . CONCLUSIONS Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels . The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass OBJECTIVE The subset of patients most likely to benefit from off-pump coronary artery bypass grafting ( CABG ) remains a controversial issue , but the technique has been proposed to decrease postoperative mortality and morbidity . Th e objective of this study was to compare off-pump to onpump CABG in patients with known risk factors for mortality and morbidity . METHODS Between October 2001 and September 2002 , 65 high-risk patients were prospect ively r and omized to undergo off-pump or o n-pump CABG . Recruited patients had at least 3 of the following criteria : age greater than 65 years , high blood pressure , diabetes , serum creatinine greater than 133 mol/L , left ventricular ejection fraction lower than 45 % , chronic pulmonary diseas e , unstable angina , congestive heart failure , repeat CABG , anemia , and carotid atherosclerosis . Hospital mortality and morbidity were the primary end-points of the study . RESULTS Six patients ( 9 % ) crossed over from the original r and omized group . Twenty-eight patients averaging 70 + /- 8 years of age underwent 3 + /- 1 grafts off pump , and 37 patients averaging 70 + /- 6 years of age underwent 3.4 + /- 1 grafts on pump . Revascularization was considered complete in 21 ( 7 5 % ) of off-pump patients compared to 33 ( 89 % ) of onpump patients ( P = .1 ) . There were no hospital deaths in off-pump patients , and 2 patients ( 5 % ) undergoing onpump CABG died early following surgery ( P = .2 ) . Two offpump ( 7 % ) compared to 11 on-pump ( 30 % ) of patients presented composite end-points including death , neurological injury , renal failure , respiratory failure , and operative myocardial infa rct ion after CABG ( P = .02 ) . CONCLUSION The present study suggests that off-pump CABG , when technically feasible , significantly reduces morbidity following surgery in a group of high-risk patients UNLABELLED Whilst elevated urinary transforming growth factor beta-1 ( TGFbeta ) is associated with chronic renal dysfunction its role in acute peri-operative renal dysfunction is unknown . In contrast , peri-operative increases in urinary IL-1 receptor antagonist ( IL-1ra ) and TNF soluble receptor-2 ( TNFsr-2 ) mirror pro-inflammatory activity in the nephron and correlate with renal complications . Steroids modulate some plasma cytokines ( decreasing TNFalpha , IL-8 , IL-6 and increasing IL-10 ) , whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri-operative renal injury is unknown . Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass ( CPB ) were r and omised to receive methylprednisolone ( n = 18 ) or placebo ( n = 17 ) before induction of anaesthesia . Plasma and urinary pro- and anti-inflammatory cytokine balance was determined along with sub clinical proximal tubular injury and dysfunction , measured by urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1-microglobulin/creatinine ratios , respectively . In the control group compared with baseline , plasma IL-8 , TNFalpha , IL-10 , IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra , TNFsr-2 and TGFbeta1 . Urinary NAG/creatinine and alpha-1-microglobulin/creatinine ratios rose from completion of revascularisation until 6 h with recovery at 24 h with a further rise in NAG/creatinine ratio at 48 h. Compared to placebo , the methylprednisolone group showed significantly reduced plasma IL-8 , TNFalpha , IL-1ra and TNFsr-2 whereas plasma IL-10 increased . Compared to placebo , the methylprednisolone group demonstrated significantly reduced urinary NAG/creatinine ratio , TNFsr-2 and TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios increased . CONCLUSIONS Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra , urinary TGFbeta1 and sub clinical renal injury but not dysfunction A total of 775 consecutive patients who survived the first 24 hours after cardiac operation were prospect ively studied to assess the prevalence , mortality rate , and main risk factors for development of new acute renal failure . Normal renal function before operation ( serum creatinine level less than 1.5 mg/dl ) was registered in 734 ( 94.7 % ) patients . Of these , 111 ( 15.1 % ) showed a postoperative renal complication including 84 ( 11.4 % ) classified as renal dysfunction ( serum creatinine level between 1.5 and 2.5 mg/dl ) and 27 ( 3.7 % ) as acute renal failure ( serum creatinine level higher than 2.5 mg/dl ) . The mortality rate was 0.8 % in normal patients , 9.5 % in patients with renal dysfunction , and 44.4 % when acute renal failure developed ( p < 0.0001 ) . Indeed , the renal impairment proved to be an independent predictor of mortality ( p < 0.001 ) , along with the infective ( p < 0.001 ) , gastrointestinal ( p < 0.001 ) , and cardiovascular ( p < 0.05 ) complications . Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment : use of intraaortic balloon pump ( p < 0.0001 ) , need for deep hypothermic circulatory arrest ( p < 0.005 ) , low-output syndrome ( p < 0.005 ) , advanced age ( p < 0.005 ) , need for emergency operation ( p < 0.025 ) , and low urinary output during cardiopulmonary bypass ( p < 0.05 ) . The 41 patients ( 5.3 % ) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation . We conclude that in patients undergoing cardiac operation without preexisting renal dysfunction the likelihood of severe renal complications is reasonably low , but the associated mortality remains high . A prominent role in the development of postoperative acute renal failure must be recognized for preoperative , intraoperative , and postoperative hemodynamic factors , whereas cardiopulmonary bypass seems to be of lesser importance in this respect Objective Renal failure after bypass is still a threatening problem prolonging hospital care and reducing overall survival . The following pilot study was aim ed to analyze whether perioperative low-dose prostacyclin infusion is able to preserve renal function in a selected group of patients who according to a poor cardiac function were stratified as high risk for the development of renal failure after bypass . Design Prospect i ve r and omized study . Setting Tertiary care university medical center . Patients Thirty-four patients scheduled for primary cardiac bypass surgery were included in the study ( prostacyclin n = 17 , control n = 17 ) . Inclusion criteria were normal renal function before surgery and a cardiac ejection fraction < 40 % . Interventions Low-dose prostacyclin ( 2 ng/kg/min ) was added to the st and ard anesthetic protocol . Infusion was started immediately before surgery and was continued for a maximum of 48 hrs . Measurements and Main Results Significant differences in the endogenous creatinine clearance were found between the prostacyclin and the control group . Whereas there was a significant drop in the creatinine clearance at 6 hrs after surgery in the control group with a prolonged recovery period , values in the prostacyclin group remained stable . Creatinine clearance before intervention was 100 ± 22 mL/min in the control group and 91 ± 22 mL/min in the prostacyclin group , values at 24 hr were 68 ± 34 mL/min vs. 103 ± 37 mL/min , respectively ( p < .01 ) . Significant findings in favor for the prostacyclin group were also found for urine output and the fractional excretion rate of sodium . Conclusion This first pilot study indicates that low-dose prostacyclin may be of substantial value for preserving renal function in high-risk patients after coronary bypass surgery Summary We have evaluated the effect of prostagl and in E1(PGE1 ) on renal function after cardiac surgery with cardiopulmonary bypass in 20 patients , ten of whom received 0.02 μg·kg−1·min−1 of PGE1 by infusion into the oxygenator during bypass ; ten patients served as controls . Serum β2-microglobulin fell significantly and urine β2-microglobulin increased significantly after surgery in both groups . Urine N-acetyl-β-D-glucosaminidase was high after surgery in both groups , but it was significantly lower in the PGE1 group . Free water clearance fell significantly on the 1st , 3rd , and 5th postoperative days compared with preoperative values in the control but not in the PGE1 group . These results suggest that PGE1 may prevent renal dysfunction after cardiopulmonary bypass BACKGROUND Acute kidney injury ( AKI ) after heart surgery is associated with increased mortality . We sought to determine whether prophylactic perioperative administration of N-acetylcysteine ( NAC ) prevents postoperative AKI in patients with chronic kidney disease undergoing cardiac surgery ( clinical trials.gov identifier NCT00211653 ) . METHODS In this prospect i ve , r and omized , placebo-controlled , double-blinded clinical trial , 102 patients with chronic kidney disease who underwent heart surgery at the Minneapolis Veterans Affairs Medical Center were r and omized to either NAC ( n = 50 ) 600 mg PO twice daily or placebo ( n = 52 ) for a total of 14 doses ( 3 preoperative ) . The primary outcome was maximum change in creatinine from baseline within 7 days after surgery . Secondary outcome was AKI ( ie , > 0.5 mg/dL or > or=25 % increase in creatinine from baseline ) . RESULTS Creatinine increased in both groups ( 0.45 + /- 0.7 mg/dL in NAC vs 0.55 + /- 0.9 mg/dL in placebo , P = .53 ) and peaked on postoperative day 5 . Acute kidney injury occurred in 41 patients ( 22 NAC vs 19 placebo , P = .44 ) by postoperative day 5 , but persisted in only 14 ( 7 NAC vs 7 placebo , P = .94 ) by day 30 . In multivariable analysis , perioperative NAC was unassociated with AKI ( relative risk 1.2 , 95 % CI , 0.8 - 1.9 , P = .34 ) . Five patients ( 3 NAC vs 2 placebo , P = .68 ) underwent hemodialysis , and 5 ( 2 NAC vs 3 placebo , P = 1.0 ) died perioperatively . There was no difference in lengths of stay in the intensive care unit ( 4.9 + /- 7 days in NAC vs 6.5 + /- 9 days in placebo , P = .06 ) and the hospital ( 13.2 + /- 13 days in NAC vs 16.7 + /- 17 days in placebo , P = .12 ) . CONCLUSION Prophylactic perioperative NAC administration does not prevent AKI after cardiac surgery Objective : Acute renal failure is associated with significant morbidity and mortality rates . Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery . Human atrial natriuretic peptide ( h-ANP ) is a potent endogenous natriuretic and diuretic substance . Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure . We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure . Design : A prospect i ve , double-blind , r and omized , placebo-controlled study . Setting : Cardiothoracic intensive care units of two tertiary care centers . Patients : Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support . Interventions : The patients were r and omized to receive a continuous infusion of either recombinant h-ANP ( 50 ng·kg−1·min−1 ) or placebo when serum creatinine increased by > 50 % from baseline . The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis . Measurements and Main Results : The primary outcome variable was dialysis on or before day 21 after the start of treatment . Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance . Twenty-nine patients were assigned h-ANP and 30 placebo . Six ( 21 % ) patients in the h-ANP group compared with 14 ( 47 % ) in the placebo group needed dialysis before or at day 21 ( hazard ratio , 0.28 ; 95 % confidence interval , 0.10–0.73 ; p = .009 ) . Eight ( 28 % ) patients in the h-ANP group compared with 17 ( 57 % ) in the placebo group suffered from the combined end point dialysis or death before or at day 21 ( hazard ratio , 0.35 ; 95 % confidence interval , 0.14–0.82 ; p = .017 ) . h-ANP improved creatinine clearance in contrast to placebo ( p = .040 ) . Conclusions : Infusion of h-ANP at a rate of 50 ng·kg−1·min−1 enhances renal excretory function , decreases the probability of dialysis , and improves dialysis-free survival in early , ischemic acute renal dysfunction after complicated cardiac surgery Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role . Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft ( CABG ) surgery were allocated to a treatment group [ enalaprilat for 2 days ; ACEI ( angiotensin-converting enzyme inhibitor ) group , n=7 ] or a control group ( n=7 ) . The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass ( CPB ) ( P<0.05 ) and on postoperative day 2 ( P<0.05 ) . The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB ( P<0.05 ) . Renal plasma flow , measured as [131I]orthoiodohippuran clearance ( ClH ) , was higher in the ACEI group than in the control group before CPB , as was endogenous creatinine clearance after CPB ( P<0.05 ) . On post-operative day 7 , ClH was significantly higher in the ACEI group than in the control group ( P<0.05 ) . Plasma renin activity and vasopressin concentration increased in both groups during CPB ( P<0.05 ) . The study demonstrates that administration of an i.v . ACEI , enalaprilat , improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction . Moreover , renal perfusion was better maintained during surgery , and this effect was sustained up to post-operative day 7 Patients with chronic kidney disease ( CKD ) are at risk to develop acute renal failure ( ARF ) after open heart surgery . This complication is associated with high morbidity , mortality , and cost . Because the ability to concentrate urine is lost early in the progression of CKD , renal patients kept on fluid restriction prior to surgery may develop severe dehydration , a situation consistently found to be one of the most critical risk factors for postoperative ARF . Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD . This is a prospect i ve study in a tertiary cardiac surgery center . Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD , as evidence d by a quantified glomerular filtration rate less than 45 mL/min , were assigned using a 2/1 r and omization process , to either receive an intravenous infusion of half-isotonic saline ( 1 mL/kg/h ) for 12 h before the operation ( hydration group , n = 30 , 29 men , 64 + 1.7 years old ) , or to be simply kept on fluid restriction ( control group , n = 15 , 14 men , 64.2 + 2.8 years old ) . Groups were not different in clinical and intraoperative variables associated with postoperative renal injury . ARF developed in 8 of 15 ( 53 % ) patients in the control group , but in only 9 of the 30 ( 30 % ) patients in the hydration group . Four patients in the control group ( 27 % ) , but no one in the hydration group , required dialysis after the operation ( P < 0.01 ) . Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group . Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery The effects of pulsatile perfusion on microcirculation and renal function in high-risk patients were evaluated in this study . Pulsatile roller pumps with a pulsatile control module and membrane oxygenator were used in a clinical setting . 40 patients undergoing elective cardiac surgery with a high risk of either having chronically obstructive pulmonary disease or chronic renal failure were r and omly included in the study to be perfused using pulsatile or continuous flows . Blood sample s were collected at induction of anesthesia , at the time of aortic clamping and declamping and 1 and 24 h following cessation of the bypass . Urea and creatinine concentrations in blood were measured and systemic vascular resistance was calculated . Urine output , crystalloid and colloid infusions were recorded . We observed that pulsatile roller pump perfusion and the extracorporeal circuit used in the clinical study improved microcirculation and renal function in high-risk patients undergoing cardiopulmonary bypass BACKGROUND Preoperative creatinine values higher than 2.5 mg/dL are associated with markedly increased risk for both mortality and morbidity in patients undergoing coronary artery bypass surgery . We aim ed to determine the effects of prophylactic perioperative hemodialysis on operative outcome in patients with nondialysis-dependent moderate renal dysfunction . METHODS Forty-four adult patients with creatinine levels greater than 2.5 mg/dL but not requiring dialysis underwent coronary artery bypass surgery with cardiopulmonary bypass . The patients were r and omly divided into two groups . In group 1 ( dialysis group , 21 patients ) , perioperative prophylactic hemodialysis was performed in all patients . Group 2 ( 23 patients ) was taken as a control group and hemodialysis was performed only if postoperative acute renal failure was diagnosed . RESULTS The hospital mortality was 4.8 % ( 1 patient ) in the dialysis group , and 30.4 % ( 7 patients ) in the control group ( p = 0.048 ) . Postoperative acute renal failure requiring hemodialysis was seen in 1 patient ( 4.8 % ) in the dialysis group and in 8 patients ( 34.8 % ) in the control group ( p = 0.023 ) . Thirty-three postoperative complications were observed in the control group for an early morbidity of 52.2 % ( 12 patients ) and 13 complications occurred in 8 patients in the dialysis group ( 38.1 % ) . The average length of the intensive care unit and postoperative hospital stay were shorter in the dialysis group than in the control group ( p = 0.005 and p = 0.023 , respectively ) . CONCLUSIONS Preoperative creatinine levels higher than 2.5 mg/dL , increase the risk of mortality and the development of acute renal failure and prolong the length of hospital stay after on-pump coronary artery bypass surgery . Perioperative prophylactic hemodialysis decreases both operative mortality and morbidity in these high-risk patients Objective : To determine whether fenoldopam and N-acetylcysteine prevent renal deterioration and improve hospital outcome for patients with chronic renal insufficiency undergoing cardiac surgery . Design : Prospect i ve , r and omized , double-blinded , placebo-controlled trial . Setting : A community hospital that is a cardiac referral center . Patients : Seventy-nine adult patients with chronic renal insufficiency ( creatinine clearance ≤40 mL/min ) who underwent cardiac surgery . Interventions : Group 1 received intravenous fenoldopam 0.1 & mgr;g/kg/min started at surgical induction and continued for 48 hrs . Group 2 received N-acetylcysteine 600 mg orally twice a day , from preoperative day 1 to postoperative day 1 . Group 3 received both fenoldopam and N-acetylcysteine , and group 4 patients served as controls . Measurements and Main Results : Using multiple comparisons ( analysis of variance ) with change scores , and statistically adjusting for group differences in aortic cross-clamp time , use of intraoperative aprotinin , and preoperative use of statin , we found that the change in creatinine clearance from preoperative to postoperative day 3 was statistically less for group 1 ( −1.47 mL/min ± 2.06 se , p = .0286 ) and for group 2 ( −0.67 mL/min ± 2.11 se , p = .0198 ) and less but not quite significant for group 3 ( −3.08 mL/min ± 1.95 se , p = .0891 ) compared with controls ( −8.15 mL/min ± 2.18 se ) . Furthermore , the adjusted weight gain on postoperative day 3 was 5.55 kg ± 1.00 se ( p = .0988 ) for group 1 , 5.06 kg ± 1.06 se ( p = .0631 ) for group 2 , and 5.14 kg ± .91 se ( p = .0445 ) for group 3 compared with 8.03 kg ± 1.07 se for group 4 . However , there was no decrease in length of critical care or hospital stay or hospital costs . Finally , fenoldopam contributed to perioperative hypotension . Conclusions : Perioperative fenoldopam and N-acetylcysteine abrogate the early postoperative decline in renal function of patients who have chronic renal insufficiency , although these agents do not affect other parameters of cardiac surgical outcome OBJECTIVE To evaluate the possible protective effects of fenoldopam on renal function in patients undergoing cardiopulmonary bypass . DESIGN Prospect i ve , r and omized trial . SETTING University teaching hospital . PARTICIPANTS One hundred sixty consecutive patients with serum creatinine > 1.5 mg/dL who underwent uncomplicated moderate hypothermic cardiopulmonary bypass for cardiac surgery . INTERVENTIONS A r and om group of 80 patients was managed conventionally ( group A ) , whereas another r and om group of 80 patients received continuous intravenous administration of low-dose fenoldopam ( 0.1 - 0.3 microg/kg/min ) during cardiopulmonary bypass and in the early postoperative period ( group B ) . MEASUREMENTS AND MAIN RESULTS An improvement of postoperative renal parameters were observed only in group B : preoperative serum creatinine 1.82 + /- 0.2 versus 1.43 + /- 0.73 postoperatively ( p < 0.001 ) , preoperative creatinine clearance 51.34 + /- 22.26 versus 67.14 + /- 18.55 postoperatively ( p < 0.001 ) . CONCLUSIONS In this study , fenoldopam was an effective agent in the prevention of renal dysfunction after cardiopulmonary bypass BACKGROUND Coronary revascularization with cardiopulmonary bypass has the potential risk of renal dysfunction related to the nonphysiologic nature of cardiopulmonary bypass . Recently , there has been a revival of interest in performing myocardial revascularization on the beating heart and we investigated whether this prevents renal compromise . METHODS A prospect i ve , r and omized , controlled trial was performed in 50 patients ( 45 males , mean age 61+/-3.7 years ) undergoing elective coronary artery bypass grafting . Patients were r and omly assigned to conventional revascularization with cardiopulmonary bypass ( on pump ) or beating heart revascularization ( off pump ) . Glomerular and tubular function were assessed up to 48 hours postoperatively . RESULTS There were no deaths , myocardial infa rct ions or acute renal failure in either group . Glomerular filtration as assessed by creatinine clearance and the urinary microalbumin/creatinine ratio was significantly worse in the on pump group ( p < 0.0004 and 0.0083 , respectively ) . Renal tubular function was also impaired in the on pump group as assessed by increased N-acetyl glucosaminidase activity ( p < 0.0272 ) . CONCLUSIONS These results suggest that off pump coronary revascularization offers a superior renal protection when compared with conventional coronary revascularization with cardiopulmonary bypass and cardioplegic arrest in first time coronary bypass patients BACKGROUND Nonpulsatile perfusion during cardiopulmonary bypass can induce renal damage . We evaluated whether pulsatile perfusion using an intra-aortic balloon pump preserves renal function in patients undergoing myocardial revascularization . STUDY DESIGN R and omized controlled trial , nonmasked parallel-group design . SETTING & PARTICIPANTS 100 patients undergoing preoperative perfusion using an intra-aortic balloon pump ; 64 with baseline estimated glomerular filtration rate ( eGFR ) of 60 mL/min/1.73 m(2 ) or greater ( > or=1 mL/s/1.73 m(2 ) ; stage 1 or 2 ) and 36 with eGFR of 30 to 59 mL/min/1.73 m(2 ) ( 0.5 to 0.98 mL/s/1.73 m(2 ) ; stage 3 ) . INTERVENTION Patients were r and omly assigned to nonpulsatile perfusion during cardiopulmonary bypass ( group A ) or automatic intra-aortic balloon pump-induced pulsatile perfusion during cardiopulmonary bypass ( group B ) . OUTCOMES & MEASUREMENTS Renal function , daily diuresis , complications , serum lactate levels , and other biochemical indices at 24 and 48 hours . RESULTS GFR , adjusted for baseline eGFR , was 16 mL/min/1.73 m(2 ) [ 0.27 mL/s/1.73 m(2 ) ] less in group A ( 58.1 mL/min/1.73 m(2 ) ; 95 % confidence interval [ CI ] , 56.1 to 60.1 mL/min/1.73 m(2 ) [ 0.97 mL/s/1.73 m(2 ) ; 95 % CI , 0.94 to 1.0 mL/s/1.73 m(2 ) ] ) than in group B ( 74.0 mL/min/1.73 m(2 ) ; 95 % CI , 72.0 to 76.1 mL/min/1.73 m(2 ) [ 1.23 mL/s/1.73 m(2 ) ; 95 % CI , 1.20 to 1.27 mL/s/1.73 m(2 ) ] ; P < 0.001 ) . Plasma lactate levels were + 3.9 mg/dL ( + 0.43 mmol/L ) higher in group A ( 19.5 mg/dL ; 95 % CI , 18.4 to 20.5 mg/dL [ 2.16 mmol/L ; 95 % CI , 2.04 to 2.28 mmol/L ] ) than in group B ( 16.7 mg/dL ; 95 % CI , 14.4 to 16.7 mg/dL [ 1.73 mmol/L ; 95 % CI , 1.60 to 1.85 mmol/L ] ; P < 0.001 ) . No significant difference between the 2 groups was observed for 24-hour diuresis . Patients with eGFR stage 3 had a greater decrease in GFR and daily diuresis and greater increase in lactate levels than those with eGFR stages 1 to 2 . LIMITATIONS Short-term change in kidney function as a surrogate outcome for " hard " clinical outcomes of mortality , morbidity , and length of hospitalization . Other limitations are short-term follow-up and absence of measurement of hemodynamic parameters or inflammatory mediators . CONCLUSIONS Use of automatic pulsatile intra-aortic balloon pumps during cardiopulmonary bypass is associated with better renal function during myocardial reperfusion . More studies are needed to verify the effects of pulsatile intra-aortic balloon pumps OBJECTIVE Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction , diabetes and impaired left-ventricular function , and following complicated procedures involving prolonged cardiopulmonary bypass ( CPB ) . The aim of this prospect ively r and omised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group . METHODS Patients with preoperative serum creatinine > 130 micromol/l ( 1.4 mg/dl ) , left-ventricular ejection fraction < 50 % , congestive heart failure , diabetes , or procedures involving prolonged CPB were r and omised to receive either saline at 2 ml/h ( n=21 ) , or furosemide at 4 mg/h ( n=21 ) . Infusion was commenced after induction of anaesthesia and continued for 12h postoperatively . Renal dysfunction was defined as > 50 % increase in serum creatinine postoperatively , or > 130 micromol/l ( 1.4 mg/dl ) , or requirement for haemodialysis , or all of these . In patients with preoperative serum creatinine > 130 micromol/l , > 50 % increase over preoperative levels was used to define postoperative renal dysfunction . RESULTS Following cardiac surgery , patients receiving furosemide had a higher urine output ( 3.4+/-1.2 ml/kg/h in furosemide group and 1.2+/-0.5 ml/kg/h in placebo group ; p<0.001 ) , higher postoperative fluid requirement ( 4631+/-1359 ml in furosemide group and 3714+/-807 ml in placebo group , p=0.011 ) , and lower urinary-creatinine ( 2+/-1.3 micromol/l in furosemide group and 5.9+/-2.5 micromol/l in placebo group p<0.001 ) . Both groups had significant increase in retinol binding protein/creatinine ratio ( 7.2+/-6 to 3152+/-1411 in furosemide group ; 4.9+/-2.1 to 2809+/-1125 in placebo group ; p<0.001 ) and peak serum creatinine ( 98+/-33 to 177+/-123 micromol/l in furosemide group ; 96+/-20 to 143+/-87 micromol/l in placebo group ; p<0.001 ) , and a significant decrease in peak creatinine-clearance ( 64.3+/-29.4 to 39.1+/-16.6 ml/min in furosemide group ; 65.5+/-38.6 to 41.8+/-17.8 ml/min in placebo group ; p<0.001 ) following cardiac surgery , implying significant renal injury following cardiac surgery . Peak creatinine levels ( 177+/-123 micromol/l in furosemide group and 143+/-87 micromol/l in placebo group ; p=0.35 ) and peak creatinine-clearance ( 39.1+/-16.6 ml/min in furosemide group and 41.8+/-17.8 ml/min in placebo group ; p=0.61 ) were similar in the two groups . Importantly , there was no difference in incidence of renal dysfunction between the furosemide group ( 9/21 ) and the control group ( 8/21 ) ( relative risk 1.1 , 95 % confidence interval 0.6 - 2.2 ; p=0.99 ) . CONCLUSIONS Our r and omised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients . Although urinary output increased with furosemide , there was no decrease in renal injury , and no decrease in incidence of renal dysfunction OBJECTIVE A prospect i ve double-blind r and omized study undertaken to assess the effect of postoperative prophylactic " renal-dose " dopamine on post-coronary artery bypass grafting surgery 's clinical outcome . METHODS Eighty-five consecutive patients undergoing CABG operation were r and omized to receive either 3 - 5 microg/kg/min dopamine ( group D , n = 41 ) or saline as placebo ( group P , n = 45 ) for 48 postoperative hours . Clinical outcome parameters were collected for four postoperative days . RESULTS Preoperative and operative parameters were similar in both groups . Four patients from group P and none from group D reached an end-point of the study ( oliguria , renal dysfunction ) and received dopamine . Two patients from group P and none from group D needed an additional inotropic support . Mean arterial pressure values were similar during the first 24 hours after operation , but left atrial pressure values tended to be higher in group P ( 10 + /- 4 vs 7 + /- 3 mmH2O , p = 0.18 ) . The mean pH was higher in group D at 8 hours after operation ( 7.38 + /- 0.2 vs 7.36 + /- 0.3 , p = NS ) , due to higher bicarbonate levels ( 23 + /- 2 mmol/l vs 21 + /- 2 , p = 0.49 ) . The incidence of lung congestion in chest X-rays and CT scans was significantly higher in group P ( 50 % vs 29 % , p = 0.073 at 48 hours postoperatively ) . Room air blood O2 saturation and maximal expiratory volume tended to be higher in group D ( at 72 hours after operation- 92 + /- 4 vs 90%+/- 5 , p = 0.29 and 646 + /- 276 vs 485 ml + /- 206 , p = 0.16 , respectively ) . There was no statistical difference in urine output but the amount of furosemide given to patients in group P was significantly higher ( during the first 8 hours 2.5 + /- 0.5 vs. 0.3 mg + /- 1.6 , p = 0.07 ) . Plasma creatinine levels were significantly lower in group D ( at 24 hours 0.93 + /- 0.02 vs 1.05 mg/dL + /- 0.02 , p = 0.02 ) . Mobilization after surgery was faster in group D. CONCLUSIONS Prophylactic dopamine administration after coronary artery bypass grafting surgery improves patient hemodynamic and renal status , reduces the need for additional medical support ( inotropes and furosemide ) and thus , provides stable postoperative course In this prospect i ve , r and omized , placebo-controlled , double-blinded study , we determined the effects of two commonly used adjuncts , mannitol and dopamine , on & bgr;2-microglobulin ( & bgr;2 M ) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass ( CPB ) . & bgr;2 M excretion rate has been described as a sensitive marker of proximal renal tubular function . One-hundred patients with a preoperative serum creatinine level ≤1.5 mg/dL were prospect ively r and omized into 4 groups : 1 ) placebo , 2 ) mannitol 1 g/kg added to the CPB prime , 3 ) dopamine 2 & mgr;g · kg−1 · min−1 from the induction of anesthesia to 1 h post-CPB , or 4 ) mannitol plus dopamine . The primary outcome measure was & bgr;2 M excretion rate at 1 h post-CPB . Secondary outcome measures included & bgr;2 M excretion rate at 6 and 24 h post-CPB ; urinary flow rate and creatinine clearance at 1 , 6 , and 24 h post-CPB ; and the highest postoperative serum creatinine level . Length of intensive care stay and hospitalization , as well as adverse events , were also considered secondary outcomes . Dopamine significantly increased & bgr;2 M excretion rate at 1 h post-CPB ( 2.48 ± 3.61 & mgr;g/min ) compared with placebo ( 0.59 ± 1.04 & mgr;g/min ; P = 0.001 ) . This effect was not ameliorated by the addition of mannitol ( & bgr;2 M excretion rate , 2.05 ± 2.77 & mgr;g/min ; P = 0.007 compared with placebo ) . & bgr;2 M excretion rate was similar in patients given placebo or mannitol alone ( P = 0.831 ) . Rather than being a protective drug in the setting of CPB , dopamine alone or in combination with mannitol increases & bgr;2 M excretion rate , which may be a measure of renal tubular dysfunction . The clinical implication s of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation Background . Coronary artery bypass grafting ( CABG ) with cardiopulmonary bypass ( CPB ) has the risk of renal dysfunction . The cause of renal dysfunction after CPB is multifactorial , such as nonpulsatile flow , renal hypoperfusion , hypothermia , and duration of CPB . This study compared off-pump technique with on-pump technique on renal function in patients who underwent CABG . Methods . Sixty patients with normal preoperative renal functions undergoing CABG were r and omly assigned to conventional revascularization with CPB ( on-pump ) or beating heart revascularization ( off-pump ) . Renal functions were assessed up to 10 days postoperatively . Results . Creatinine clearance was found to be significantly higher in the off-pump group than in the on-pump group ( p < .05 ) . The off-pump group had significantly less increase in creatinine levels when compared with the on-pump group ( p < .05 ) . The free water clearance values decreased similarly in both groups ; however , the recovery was more prompt in the off-pump group ( p < .05 ) . No significant differences were found in the prevalence of postoperative hemodialysis . Conclusion . The off-pump technique may provide a positive contribution and sufficient protection on postoperative renal functions in patients undergoing CABG STUDY OBJECTIVE Acute renal failure , which is a serious complication following open heart surgery , has a high mortality rate . Previous reports have shown that the calcium antagonist diltiazem is beneficial either as an adjunct to cardioplegic solution or perioperative treatment for preservation of postoperative cardiovascular function . We studied the effects of diltiazem on renal function , plasma atrial natriuretic peptide levels , and the renin-angiotensin-aldosterone system in patients who had undergone coronary artery bypass grafting . PATIENTS AND MEASUREMENTS Diltiazem was administered , 0.1 mg/kg , in a bolus injection followed by continuous infusion at a rate of 2 micrograms/kg/min during surgery , and 30 mg through a nasogastric tube at every 8 h. Hemodynamics , renal function , and plasma hormone levels were measured in the diltiazem-treated group ( n = 13 ) and the nontreated group ( n = 10 ) . RESULTS Heart rate , mean arterial pressure , and systemic vascular resistance index in the diltiazem-treated group were significantly lower than those in the nontreated group following cardiopulmonary bypass . Urine volume , creatinine clearance , and free water clearance were well preserved in the diltiazem-treated group . However , plasma renin activity and aldosterone levels were significantly higher in the diltiazem-treated group with the same changes in plasma atrial natriuretic peptide levels . CONCLUSION Perioperative treatment with diltiazem has a beneficial effect on postoperative renal function , and reflex sympathetic activation induced by peripheral vasodilation activated the renin-angiotensin-aldosterone system OBJECTIVE Acute renal failure complicating open heart surgery is not uncommon . Dopamine infusion ( 2.5 - 4.0 microg/kg per min ) has often been advocated for prophylactic ' renal protection ' in this setting despite little objective evidence of real benefit . We aim ed to investigate whether dopamine offers any ' renal protection ' in patients with normal heart and kidney functions undergoing routine coronary artery bypass grafting ( CABG ) . Urinary excretion of retinol-binding protein ( RBP ) , previously vali date d as a sensitive and accurate marker of early renal tubular injury , was used to assess the renal effects of dopamine during the first postoperative week . METHODS Forty consecutive patients from the elective waiting list were prospect ively r and omized into two equal groups : those in Group A received dopamine infusion at ' renal dose ' ( 2.5 - 4.0 microg/kg per min ) starting from induction of anaesthesia for 48 h , whereas those in Group B served as untreated controls . Daily measurements were made of weight-adjusted urine output ( ml/kg ) , fluid balance ( input/output ) , serum creatinine , blood urea and urinary RBP . Statistical comparisons were made using Mann-Whitney U-test . RESULTS The two groups matched in terms of age , time and temperature on cardiopulmonary bypass , number of grafts performed and perioperative haemodynamic status . No differences were detected in the weight-adjusted urine output , fluid balance , serum creatinine and blood urea between the groups . Control subjects ( Group B ) showed an increase in urinary RBP during the first and second postoperative days ( 323+/-4 microg/ mmolCr and 50+/-3 microg/mmolCr ; mean+/-SD ) . However , patients treated with dopamine ( Group A ) demonstrated much greater urinary excretion of RBP over the same period ( 1257+/-15 microg/mmolCr and 449+/-21 microg/mmolCr ; P = 0.0006 and 0.03 ) than those in Group B. CONCLUSIONS Dopamine given at ' renal-dose ' appears to offer no renal protection in patients with normal heart and kidney functions undergoing elective coronary surgery . On the contrary , it exacerbates the severity of renal tubular injury during the early postoperative period . Based on these findings we do not recommend the use of dopamine for routine renal prophylaxis in this group of patients The usefulness of mannitol in the priming fluid for cardiopulmonary bypass is uncertain in patients with normal renal function , and has not been studied in patients with established renal dysfunction . We studied 50 patients with serum creatinine between 130 and 250 μmol.l−1 having cardiac surgery . Patients were r and omised to receive mannitol 0.5 g.kg−1 , or an equivalent volume of Hartmann ’s solution , in the bypass prime . There were no differences between the groups in plasma creatinine or change in creatinine from baseline , urine output , or fluid balance over the first three postoperative days . We conclude that mannitol has no effect on routine measures of renal function during cardiac surgery in patients with established renal dysfunction |
13,095 | 24,129,770 | Aerobic exercise may be effective at improving NTproBNP and the VE/VCO2 slope in systolic HF patients , but these effects are limited to a specific HF population meeting specific inclusion criterion in a limited number of studies . | Abstract From previous systematic review s and meta-analyses , there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure ( HF ) ; however , the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production ( VE/VCO2 ) slope has not been evaluated .
The primary aim of the proposed study is to determine the effect of aerobic exercise training ( AEX ) on the VE/VCO2 slope and NTproBNP . | Background Heart rate recovery ( HRR1 ) immediately after exercise reflects parasympathetic activity , which is markedly attenuated in chronic heart failure ( CHF ) patients . The aim of our study was to examine both continuous and interval exercise training effects on HRR1 in these patients . Design The population study consisted of 29 stable CHF patients that participated at a rehabilitation program of 36 sessions , three times per week . Of the 29 patients , 24 completed the program . Patients were r and omly assigned to interval { n = 10 [ 100 % peak work rate ( WRp ) for 30 s , alternating with rest for 30 s ] } and to continuous training [ n = 14 ( 50%WRp ) ] . Methods All patients performed a symptom-limited cardiopulmonary exercise test on a cycle ergometer before and after the completion of the program . Measurements included peak oxygen uptake ( VO2p ) , anaerobic threshold ( AT ) , WRp , first degree slope of VO2 during the first minute of recovery ( VO2/t-slope ) , chronotropic response [ % chronotropic reserve ( CR ) = ( peak HR - resting HR ) × 100/(220 - age - resting HR ) ] , HRR1 ( HR difference from peak exercise to one minute after ) . Results After the completion of the rehabilitation program there was a significant increase of WRp , VO2p , AT and VO2/t-slope ( by 30 % , P=0.01 ; 6 % , P=0.01 ; 10 % , P=0.02 ; and 27 % , P=0.03 respectively for continuous training and by 21 % , P≤0.05 ; 8 % , P=0.01 ; 6 % , P = NS ; and 48 % , P=0.02 respectively for interval training ) . However , only patients exercised under the continuous training regime had a significant increase in HRR1 ( 15.0±9.0 to 24.0±12bpm ; P=0.02 ) and CR ( 57±19 to 72±21 % , P=0.02 ) , in contrast with those assigned to interval training ( HRR1 : 21 ± 11 to 21 ± 8 bpm ; P = NS and CR : 57 ± 18 to 59 ± 21 % , P = NS ) . Conclusions Both continuous and interval exercise training program improves exercise capacity in CHF patients . However , continuous rather than interval exercise training improves early HRR1 , a marker of parasympathetic activity , suggesting a greater contribution to the autonomic nervous system AIMS Diastolic dysfunction ( DD ) was identified as a predictor of adverse prognosis in heart failure with reduced ejection fraction ( HFREF ) . It is , however , unknown if DD is improved by exercise training , which is known to induce reverse remodelling , and if the training effect is attenuated in elderly HFREF patients . We therefore assessed DD in a cohort of referent controls ( RCs ) and HFREF patients and studied the response of DD to endurance exercise in two age groups ( ≤55 years and ≥65 years ) . METHODS AND RESULTS Sixty RC ( 30 ≤ 55 years , mean age 50 ± 5 years ; 30 ≥ 65 years , 72 ± 4 years ) and 60 HFREF patients ( 30 ≤ 55 years , 46 ± 5 years ; 30 ≥ 65 years , 72 ± 5 years , EF 28 ± 5 % ) were r and omized to 4 weeks of supervised endurance training or to a control group . Exercise training was effective in reducing LV isovolumetric relaxation time by 29 % in young and by 26 % in old HFREF patients ( P < 0.05 for both ) . As assessed by tissue Doppler , septal E ' increased by 37 % in young and by 39 % among old HFREF patients ( P < 0.005 for both ) result ing in a significant decrease in the E/E ' ratio from 13 ± 1 to 10 ± 1 in young and 14 ± 1 to 11 ± 1 in old HFREF patients ( P < 0.05 for both ) . Serum levels of N-terminal pro brain natriuretic peptide were significantly reduced after endurance training in HFREF patients of all ages . CONCLUSION In HFREF , diastolic function is significantly impaired in all age groups . Endurance training is highly effective in improving left ventricular diastolic function in HFREF patients regardless of age . This study is registered at Clinical Trials.gov ( number : NCT00176319 ) Background Optimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult . To determine whether measurement of peak oxygen consumption ( Vo2 ) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred , we prospect ively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989 . Methods and Results Patients were assigned into one of three groups on the basis of exercise data : Group 1 ( n = 35 ) comprised patients accepted for transplant ( Vo2<14 ml/kg/min ) ; group 2 ( n = 52 ) comprised patients considered too well for transplant ( Vo2 > 14 ml/kg/min ) ; and group 3 ( n = 27 ) comprised patients with low Vo2 rejected for transplant due to noncardiac problems . All three groups were comparable in New York Heart Association functional class , ejection fraction , and cardiac index ( p = NS ) . Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 ( p<0.05 ) , although there was wide overlap . Patients with preserved exercise capacity ( group 2 ) had cumulative 1- and 2-year survival rates of 94 % and 84 % , which are equal to survival levels after transplantation . In contrast , patients rejected for transplant ( group 3 ) had survival rates of only 47 % at 1 year and 32 % at 2 years , whereas patients awaiting transplantation ( group 1 ) had a survival rate of 790 % at 1 year ( both ( p < 0.005 versus patients with Vo2 > 14 ml/kg/min ) . All deaths in group 2 were sudden . By univariate and multivariate analyses , peak Vo2 was the best predictor of survival , with only pulmonary capillary wedge pressure providing additional prognostic information . Conclusions .These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise Vo2 of more than 14 ml/min/kg . ( Circulation 1991;83:778–786 BACKGROUND Exercise testing with ventilatory expired gas analysis has proven to be a valuable tool for assessing patients with heart failure ( HF ) . Peak oxygen consumption ( peak VO2 ) continues to be considered the gold st and ard for assessing prognosis in HF . The minute ventilation -- carbon dioxide production relationship ( VE/VCO2 slope ) has recently demonstrated prognostic significance in patients with HF , and in some studies , it has outperformed peak VO2 . METHODS Two hundred thirteen subjects , in whom HF was diagnosed , underwent exercise testing between April 1 , 1993 , and October 19 , 2001 . The ability of peak VO2 and VE/VCO2 slope to predict cardiac-related mortality and hospitalization was examined . RESULTS Peak VO2 and VE/VCO2 slope were demonstrated with univariate Cox regression analysis both to be significant predictors of cardiac-related mortality and hospitalization ( P < .01 ) . Multivariate analysis revealed that peak VO2 added additional value to the VE/VCO(2 ) slope in predicting cardiac-related hospitalization , but not cardiac mortality . The VE/VCO2 slope was demonstrated with receiver operating characteristic curve analysis to be significantly better than peak VO2 in predicting cardiac-related mortality ( P < .05 ) . Although area under the receiver operating characteristic curve for the VE/VCO2 slope was greater than peak VO2 in predicting cardiac-related hospitalization ( 0.77 vs 0.73 ) , the difference was not statistically significant ( P = .14 ) . CONCLUSIONS These results add to the present body of knowledge supporting the use of cardiopulmonary exercise testing in HF . Consideration should be given to revising clinical guidelines to reflect the prognostic importance of the VE/VCO2 slope in addition to peak VO2 Background : Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device ( VAD ) implantation . The benefits of exercise training in patients with VAD are unknown . Design and methods : Fifteen patients , aged 38.3 ± 15.9 years , bridged to heart transplantation with left ventricular assist device or biventricular assist device were r and omized at a ratio of 2 : 1 to a training group ( TG , n = 10 ) or a control group ( n = 5 ) , 6.3 ± 4 months after implantation . Both the groups were advised to walk 30–45 min/day . TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min , three to five times a week , combined with high-intensity inspiratory muscle training using a computer- design ed software to respiratory exhaustion , two to three times a week for 10 weeks . The patients were tested using cardiopulmonary exercise testing , 6-min walk test , spirometry and electronic pressure manometer for inspiratory muscle strength ( Pimax ) and endurance ( sustained Pimax ) measurement . Quality of life was assessed with the Minnesota Living with Heart Failure question naire . Results : TG improved peak oxygen consumption ( 19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min , P = 0.008 ) and VO2 at ventilatory threshold ( 15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min , P = 0.01 ) , whereas the ventilation/carbon dioxide slope decreased ( 35.9 ± 5.6 vs. 40 ± 6.5 , P = 0.009 ) . The 6-min walk test distance increased ( 527 ± 76 vs. 462 ± 88 m , P = 0.005 ) and quality of life was improved ( 38.2 ± 11.6 vs. 48.9 ± 12.8 , P = 0.005 ) , as well as Pimax ( 131.8 ± 33 vs. 95.5 ± 28cmH2O , P = 0.005 ) , sustained Pimax ( 484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005 ) , and inspiratoty lung capacity ( 2.4 ± 0.9 vs. 1.7 ± 0.7 L , P = 0.008 ) were improved . No significant changes were noted in the control group . Conclusion : Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus , may have additional importance in cases of destination therapy AIMS This study was design ed to evaluate the effects of combined endurance/resistance training on NT-proBNP levels in patients with chronic heart failure ( CHF ) . The safety of resistive weight training for patients with CHF is question ed . Possible detrimental effects include an increase in ventricular diastolic pressure and secondary unfavourable remodelling . Circulating levels of the N-terminal fragment of brain natriuretic peptide ( NT-proBNP ) reflect left ventricular diastolic wall stress and are strongly related to mortality and treatment success in CHF . METHODS AND RESULTS In this study , 27 consecutive patients with stable CHF and left ventricular ejection fraction ( LVEF ) < 35 % were enrolled in a 4 months non-r and omized combined endurance/resistance training programme . Blood sampling for measurement of NT-proBNP , functional assessment , cardiopulmonary exercise testing , echocardiography and radionuclide angiography were performed at entry and after 4 months . After 4 months , exercise training caused a significant reduction in circulating concentrations of NT-proBNP ( 2124+/-397 pg/ml before , 1635+/-304 pg/ml after training , p=0.046 , interaction ) , whereas no changes were observed in an untrained heart failure control group . NYHA functional class ( p=0.02 , interaction ) , maximal ( peak VO2 : p=0.035 , interaction ; maximal workload : p<0.00001 , interaction ) and submaximal ( workload at anaerobic threshold : p=0.001 , interaction ; rate-pressure product at anaerobic threshold : p=0.001 , interaction ) exercise parameters as well as work efficiency ( Wattmax/VO2peak : p=0.0001 , interaction ) were significantly improved . In addition , a decrease in left ventricular end-systolic diameter was observed in the trained heart failure group ( p=0.016 ) . CONCLUSION Four months of combined endurance/resistance training significantly reduced circulating levels of NT-proBNP in patients with CHF , without evidence of adverse remodelling . Exercise training might offer additional non-pharmacological modulation of the activated neurohormonal pathways in the setting of CHF OBJECTIVES The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide ( BNP ) levels . BACKGROUND The prognosis of chronic heart failure ( CHF ) remains poor , even among patients treated in specialized departments . METHODS A total of 220 New York Heart Association functional class II to III patients considered optimally treated with angiotensin-converting enzyme inhibitors ( ACEIs ) , beta-blockers , and diuretics by CHF specialists were r and omized to medical treatment according to either current guidelines ( clinical group ) or a goal of decreasing BNP plasma levels < 100 pg/ml ( BNP group ) . Outpatient visits were scheduled every month for 3 months , then every 3 months . The primary combined end point was CHF-related death or hospital stay for CHF . RESULTS Both groups were similar for baseline clinical and biological characteristics . Left ventricular ejection fraction was slightly lower in the BNP group than in the clinical group ( 29.9 + /- 7.7 % vs. 31.8 + /- 8.4 % , p = 0.05 ) . At the end of the first 3 months , all types of drugs were changed more frequently in the BNP group . Mean dosages of ACEIs and beta-blockers were significantly higher in the BNP group ( p < 0.05 ) , whereas the mean increase in furosemide dosage was similar in both groups . During follow-up ( median 15 months ) , significantly fewer patients reached the combined end point in the BNP group ( 24 % vs. 52 % , p < 0.001 ) . CONCLUSIONS In optimally treated CHF patients , a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF . The result was mainly obtained through an increase in ACEI and beta-blocker dosages Background — We aim ed to develop a multivariable statistical model for risk stratification in patients with chronic heart failure with systolic dysfunction , using patient data that are routinely collected and easily obtained at the time of initial presentation . Methods and Results — In a cohort of 2331 patients enrolled in the HF-ACTION ( Heart Failure : A Controlled Trial Investigating Outcomes of Exercise TraiNing ) study ( New York Heart Association class II – IV , left ventricular ejection fraction ⩽0.35 , r and omized to exercise training and usual care versus usual care alone , median follow-up of 2.5 years ) , we performed risk modeling using Cox proportional hazards models and analyzed the relationship between baseline clinical factors and the primary composite end point of death or all-cause hospitalization and the secondary end point of all-cause death alone . Prognostic relationships for continuous variables were examined using restricted cubic spline functions , and key predictors were identified using a backward variable selection process and bootstrapping methods . For ease of use in clinical practice , point-based risk scores were developed from the risk models . Exercise duration on the baseline cardiopulmonary exercise test was the most important predictor of both the primary end point and all-cause death . Additional important predictors for the primary end point risk model ( in descending strength ) were Kansas City Cardiomyopathy Question naire symptom stability score , higher serum urea nitrogen , and male sex ( all P<0.0001 ) . Important additional predictors for the mortality risk model were higher serum urea nitrogen , male sex , and lower body mass index ( all P<0.0001 ) . Conclusions — Risk models using simple , readily obtainable clinical characteristics can provide important prognostic information in ambulatory patients with chronic heart failure with systolic dysfunction . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00047437 OBJECTIVE To investigate the influence of rehabilitation on left ventricular remodeling and systolic function in acute myocardial infa rct ion patients . METHODS Patients meeting the inclusion criteria with uneventful clinical course after a first myocardial infa rct ion were r and omly assigned to a 3-month exercise training period ( exercise group , n = 35 ) or a control group ( n = 29 ) . Before r and omization , all patients underwent NT-proBNP test , 2-dimensional echocardiography , and submaximal exercise test . RESULTS ( 1 ) At baseline , there were no significant differences in NT-proBNP , left ventricular end-diastolic diameter ( LVDd ) and left ventricular ejection fraction ( LVEF ) between the exercise and control groups . After 3 months , a significant decrease in NT-proBNP was observed only in the exercise group [ from ( 845.29 + /- 93.48 ) ng/L to ( 335.64 + /- 246.14 ) ng/L , P < 0.05 ] , but not in the control group [ from ( 1091.62 + /- 101.78 ) ng/L to ( 1099.83 + /- 168.75 ) ng/L , P > 0.05 ) and there was significant difference in NT-proBNP level between the two groups after 3 months ( P < 0.01 ) . The LVDd increased in the control group [ from ( 50.9 + /- 5.8 ) to ( 52.6 + /- 5.4 ) mm , P < 0.05 ] but not in the exercise group [ from ( 50.7 + /- 4.5 ) to ( 50.3 + /- 3.9 ) mm , P > 0.05 ] and there was significant difference in LVDd between the two groupsafter 3 months ( P < 0.05 ) . Conversely , LVEF improved in the exercise group [ from ( 55.0 + /- 8.6)% to ( 60.0 + /- 8.0)% , P < 0.05 ] but not in the control group ( P > 0.05 ) and there was significant difference in LVEF between the two groups after 3 months ( P < 0.05 ) . ( 2 ) NT-proBNP was inversely correlated with LVEF . CONCLUSIONS Rehabilitation exercise training under instructions based on family condition in the early and recovery stage of AMI can lower the NT-proBNP level , improve ejection fraction , and prevent the increase of left ventricular end-diastolic diameter . Therefore , it may reduce unfavorable remodeling response and improve cardiac systolic function hereafter Background We aim ed to compare the effects of three different training advices , after 1 year , following a 6 months supervised cardiac rehabilitation period in patients with chronic heart failure ( CHF ) . Methods Sixty-nine CHF patients were r and omized , at the end of their rehabilitation period , either to usual care ( UC ) or to UC and controlled home training ( HT ) , prolonged supervised training ( ST ) or preferred training ( PT ) . Treadmill cardiopulmonary exercise testing was performed before rehabilitation , postrehabilitation and thereafter at 3-month intervals during the 1-year follow-up . submaximal exercise capacity [ Oxygen consumption and workload at the respiratory compensation point ( VO2RCP , WattRCP ) and submaximal workload ( SMW ) efficiency ( SMW/HR ) at 70 % of the initial maximal workload ] was chosen as a primary endpoint , because health status in CHF patients depends largely on their ability to perform activities at a submaximal level . Results After 6 months of rehabilitation , the four groups ( UC , HT , ST and PT ) were comparable with regard to cardiac rehabilitation-derived benefit , both at the submaximal and maximal level . Although exercise capacity during follow-up declined in both UC and HT patients , ST and especially PT patients maintained and even improved VO2peak and VO2RCP . However , only PT patients managed to maintain or even increase submaximal ( WattRCP and SMW/HR ratio ) workload ( P= 0.045 and < 0.0001 for interaction , respectively ) . Ventilatory-derived prognostic markers during treadmill cardio pulmonary exercise testing evolved similarly in the four subgroups . Conclusion This study suggests that engagement in physical training of their own choice ( PT ) , might be the optimal training modality for maintaining physical capacity in CHF patients Background Quality of life ( QoL ) decreases as heart failure worsens , which is one of the greatest worries of these patients . Physical exercise has been shown to be safe for people with heart failure . Previous studies have tested heterogeneous exercise programs using different QoL instruments and reported inconsistent effects on QoL. The aim of this study is to evaluate the effectiveness of a new exercise program for people with heart failure ( EFICAR ) , additional to the recommended optimal treatment in primary care , to improve QoL , functional capacity and control of cardiovascular risk factors . Methods / Design Multicenter clinical trial in which 600 patients with heart failure in NYHA class II-IV will be r and omized to two parallel groups : EFICAR and control . After being recruited , through the reference cardiology services , in six health centres from the Spanish Primary Care Prevention and Health Promotion Research Network ( redIAPP ) , patients are followed for 1 year after the beginning of the intervention . Both groups receive the optimized treatment according to the European Society of Cardiology guidelines . In addition , the EFICAR group performs a 3 month supervised progressive exercise program with an aerobic ( high-intensity intervals ) and a strength component ; and the programme continues linked with community re sources for 9 months . The main outcome measure is the change in health-related QoL measured by the SF-36 and the Minnesota Living with Heart Failure Question naires at baseline , 3 , 6 and 12 months . Secondary outcomes considered are changes in functional capacity measured by the 6-Minute Walking Test , cardiac structure ( B-type natriuretic peptides ) , muscle strength and body composition . Both groups will be compared on an intention to treat basis , using multi-level longitudinal mixed models . Sex , age , social class , co-morbidity and cardiovascular risk factors will be considered as potential confounding and predictor variables . Discussion A key challenges of this study is to guarantee the safety of the patients ; however , the current scientific evidence supports the notion of there being no increase in the risk of decompensation , cardiac events , hospitalizations and deaths associated with exercise , but rather the opposite . Safety assurance will be based on an optimized st and ardised pharmacological therapy and health education for all the participants .Trial Registration Clinical Trials.gov Identifier : Background —In chronic heart failure ( CHF ) , overactivation of ergoreceptors ( afferents sensitive to the metabolic effects of muscular work ) may be a link between peripheral changes , sympathetic overactivation , and increased hemodynamic and ventilatory responses to exercise . The relationship between ergoreceptors , autonomic changes , and the progression of the syndrome has not yet been studied . Methods and Results —Thirty-eight stable CHF patients ( age , 57±1 years ; ejection fraction , 26±2 % ) were compared with 12 age-matched normal control subjects . The ergoreflex contribution to the ventilatory and hemodynamic responses to exercise , together with peripheral and central chemoreceptor sensitivity , arterial baroreflex sensitivity , plasma norepinephrine , epinephrine , and heart rate variability , were measured . Enhanced ergoreflex effects on ventilation ( 78±2 % versus 50±8 % ) , peripheral chemosensitivity ( 0.6±0.4 versus 0.2±0.1 L/min per percent Sao2 ) , and central chemosensitivity ( 2.9±0.2 versus 2.0±0.2 L · min−1 · mm Hg−1 ) and an impaired baroreflex function ( 4.1±0.6 versus 9.1±5.6 ms/mm Hg ) were confirmed in CHF compared with control subjects ( P < 0.01 in all comparisons ) . Ergoreceptor overactivity was associated with a worse symptomatic state ( NYHA class , P < 0.05 ) , lower exercise tolerance ( peak Vo2 , P < 0.05 ) , and pronounced exercise hyperventilation ( & OV0312;e/Vco2 , P < 0.01 ) . It was also a strong predictor of increased central chemosensitivity ( independently of clinical parameters ) , baroreflex impairment , and sympathetic activation ( plasma catecholamines and heart rate variability indexes ; all P < 0.05 ) . In multivariate analysis , among all reflexes studied , the ventilatory component of the ergoreflex was the only independent predictor of peak Vo2 and & OV0312;e/Vco2 . Conclusions —In CHF , overactivation of the ergoreflex is associated with abnormal cardiorespiratory reflex control , independently of clinical severity . Among impaired reflexes , overactivation of the ergoreflex is an important determinant of exercise hyperventilation and reduced exercise tolerance OBJECTIVE To assess whether exercise training in adult patients with a systemic right ventricle ( RV ) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide ( NT-proBNP ) levels . DESIGN Multi-centre parallel r and omized controlled trial . PARTICIPANTS Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries . METHODS Fifty-four adult patients with a systemic RV , were r and omized using unmarked opaque envelopes to an intervention group ( n = 28 ) with three training sessions per week for 10 consecutive weeks , and a control group ( n = 26 ) . R and omization was stratified by participating centre . At baseline , and follow-up , we determined maximal exercise capacity ( V'O(2peak ) ) , serum NT-proBNP levels , and quality of life by means of the SF-36 , and the TAAQOL Congenital Heart Disease question naires . The final analysis was performed by linear regression , taking into account the stratified r and omization . RESULTS Forty-six patients were analysed ( male 50 % , age 32 ± 11 years , intervention group n = 24 , control group n = 22 ) . Analysis at 10 weeks showed a significant difference in V'O(2peak ) ( 3.4 mL/kg/min , 95 % CI : 0.2 to 6.7 ; P = 0.04 ) and resting systolic blood pressure ( -7.6 mmHg , 95 % CI : -14.0 to -1.3 ; P = 0.03 ) in favour of the exercise group . No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups . None of the patients in the intervention group had to discontinue the training programme due to adverse events . CONCLUSION In adult patients with a systemic RV exercise training improve exercise capacity . We recommend to revise restrictive guidelines , and to encourage patients to become physically active . ( TRIAL REGISTRATION The study was registered at http://trialregister.nl . Identifier : NTR1909 . ) BACKGROUND Physical training improves exercise capacity in patients with chronic heart failure . It decreases plasma noradrenaline at rest , which may be prognostically favourable . The effect on atrial natriuretic peptide , another prognostic factor , and on catabolic and anabolic hormones remains unknown . Furthermore , to our knowledge , the contribution of exertional hormonal responses to the improved exercise capacity has not been evaluated . METHODS 27 patients with stable chronic heart failure ( New York Heart Association class II-III ) were r and omized to training ( n=12 ) and control ( n=15 ) groups . The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months . The load corresponded to 50 - 60 % of their peak oxygen consumption . For the next 3 months they exercised at home according to personal instructions . The control group did not change its physical activities . The levels of hormones regulating the cardiovascular system and metabolism were determined at rest and after grade d maximal exercise and during exercise with constant submaximal workload . RESULTS Submaximal exercise capacity increased significantly and peak oxygen consumption tended to improve by 12 % in the training group . The plasma noradrenaline at rest tended to decrease by 19 % . The plasma level of N-terminal pro atrial natriuretic peptide did not change . Serum cortisol , a catabolic hormone , was normal at baseline and remained unchanged . The serum levels of anabolic hormones , growth hormone and insulin , as well as dehydroepi and rosteronesulfate and free testosterone were within a normal range at baseline . They were not altered by training . The dehydroepi and rosteronesulfate/cortisol , and the free testosterone/cortisol ratios , reflecting anabolic/catabolic balance , did not change , either . Training result ed in a higher peak noradrenaline response during grade d maximal exercise . The rise in serum cortisol during exercise tended to attenuate . CONCLUSION Physical training , which improves exercise capacity , does not have an unfavourable effect on anabolic/catabolic balance or neurohumoral activation in patients with congestive heart failure . It decreases plasma noradrenaline at rest . Minor changes in hormonal responses during exercise emerged after physical training which unlikely contribute to the improved exercise capacity BACKGROUND regional or global impairment of left ventricular ( LV ) systolic or diastolic function leading to increased LV wall stress results in increased circulating levels of N-terminal pro-brain natriuretic peptide ( NT-pro-BNP ) . OBJECTIVE this study aims at evaluating the effect of exercise training ( ET ) on NT-pro-BNP plasma levels in older patients recovering from acute myocardial infa rct ion ( AMI ) . DESIGN prospect i ve r and omised study . SETTING Academic Medical Centre . SUBJECTS forty older patients ( 33 males and 7 females ) who experienced AMI . METHODS patients were r and omised into two groups , each composed of 20 patients : Group A were enrolled in a 3-month exercise-based cardiac rehabilitation ( CR ) programme and Group B were discharged home with generic instructions to continue physical activity . NT-pro-BNP , cardiopulmonary and Doppler-echocardiographic parameters were measured at baseline and at 3-month follow-up . RESULTS in Group A , ET reduced NT-pro-BNP levels ( from 1446 + /- 475 to 435 + /- 251 pg/ml , P<0.001 ) and increased maximal exercise parameters ; there was also an inverse correlation between changes in NT-pro-BNP levels and in VO(2peak ) ( r = -0.67 , P<0.01 ) , E-wave ( r = -0.42 , P<0.01 ) and E/A ratio ( r = -0.60 , P<0.01 ) . In Group B , after 3 months , no changes were observed in NT-pro-BNP levels , exercise and echocardiographic parameters . LV volumes and left ventricular ejection fraction ( LVEF ) were unchanged after 3 months in both groups . CONCLUSIONS three months ET in older patients after AMI was associated with a reduction in NT-pro-BNP levels and an overall improvement of exercise capacity , without negative LV remodelling and with improvement in early LV filling . Further investigation is required to evaluate whether in these patients the reduction of NT-pro-BNP levels at 3 months could be useful as a surrogate marker of favourable LV remodelling at a later follow-up OBJECTIVES This study investigated the effect of a very long-term exercise training program is not known in chronic heart failure ( CHF ) patients . BACKGROUND We previously showed that long-term moderate exercise training ( ET ) improves functional capacity and quality of life in New York Heart Association class II and III CHF patients . METHODS We studied 123 patients with CHF whose condition was stable over the previous 3 months . After r and omization , a trained group ( T group , n = 63 ) underwent a supervised ET at 60 % of peak oxygen consumption ( Vo(2 ) ) , 2 times weekly for 10 years , whereas a nontrained group ( NT group , n = 60 ) did not exercise formally . The ET program was supervised and performed mostly at a coronary club with periodic control sessions twice yearly at the hospital 's gym . RESULTS In the T group , peak Vo(2 ) was more than 60 % of age- and gender-predicted maximum Vo(2 ) each year during the 10-year study ( p < 0.05 vs. the NT group ) . In NT patients , peak Vo(2 ) decreased progressively with an average of 52 ± 8 % of maximum Vo(2 ) predicted . Ventilation relative to carbon dioxide output ( VE/Vco(2 ) ) slope was significantly lower ( 35 ± 9 ) in T patients versus NT patients ( 42 ± 11 , p < 0.01 ) . Quality -of-life score was significantly better in the T group versus the NT group ( 43 ± 12 vs. 58 ± 14 , p < 0.05 ) . During the 10-year study , T patients had a significant lower rate of hospital readmission ( hazard ratio : 0.64 , p < 0.001 ) and cardiac mortality ( hazard ratio : 0.68 , p < 0.001 ) than controls . Multivariate analysis selected peak Vo(2 ) and resting heart rate as independent predictors of events . CONCLUSIONS Moderate supervised ET performed twice weekly for 10 years maintains functional capacity of more than 60 % of maximum Vo(2 ) and confers a sustained improvement in quality of life compared with NT patients . These sustained improvements are associated with reduction in major cardiovascular events , including hospitalizations for CHF and cardiac mortality OBJECTIVES To assess the effects of a home-based aerobic and resistance training program on the physical function of adults with New York Heart Association ( NYHA ) class II and III patients and systolic heart failure ( HF ) . DESIGN R and omized controlled trial . SETTING Home based . PARTICIPANTS Stable patients ( N=24 ; mean age , 60 ± 10 y ; left ventricular ejection fraction , 25 % ± 9 % ; 50 % white ; 50 % women ) with New York Heart Association ( NYHA ) classes II and III ( NYHA class III , 58 % ) systolic heart failure ( HF ) . INTERVENTION A 12-week progressive home-based program of moderate-intensity aerobic and resistance exercise . Attention control wait list participants performed light stretching and flexibility exercises . MAIN OUTCOME MEASURES A 10-item performance-based physical function measure , the Continuous Scale Physical Functional Performance test ( CS-PFP10 ) , was the major outcome variable and included specific physical activities measured in time to complete a task , weight carried during a task , and distance walked . Other measures included muscle strength , HRQOL ( Minnesota Living With Heart Failure Question naire , Epworth Sleepiness Scale ) , functional capacity ( Duke Activity Status Index ) , and disease severity ( brain natriuretic peptide ) levels . RESULTS After the exercise intervention , 9 of 10 specific task activities were performed more rapidly , with increased weight carried by exercise participants compared with the attention control wait list group . Exercise participants also showed significant improvements in CS-PFP10 total score ( P<.025 ) , upper and lower muscle strength , and HRQOL ( P<.001 ) compared with the attention control wait list group . Adherence rates were 83 % and 99 % for the aerobic and resistance training , respectively . CONCLUSIONS Patients with stable HF who participate in a moderate-intensity combined aerobic and resistance exercise program may improve performance of routine physical activities of daily living by using a home-based exercise approach . Performance-based measures such as the CS-PFP10 may provide additional insights into physical function in patients with HF that more commonly used exercise tests may not identify . Early detection of subtle changes that may signal declining physical function that are amenable to intervention potentially may slow further loss of function in this patient population BACKGROUND B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes . METHODS We conducted a prospect i ve , r and omized , controlled study of 452 patients who presented to the emergency department with acute dyspnea : 225 patients were r and omly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay , and 227 were assessed in a st and ard manner . The time to discharge and the total cost of treatment were the primary end points . RESULTS Base-line demographic and clinical characteristics were well matched between the two groups . The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care ; 75 percent of patients in the B-type natriuretic peptide group were hospitalized , as compared with 85 percent of patients in the control group ( P=0.008 ) , and 15 percent of those in the B-type natriuretic peptide group required intensive care , as compared with 24 percent of those in the control group ( P=0.01 ) . The median time to discharge was 8.0 days in the B-type natriuretic peptide group and 11.0 days in the control group ( P=0.001 ) . The mean total cost of treatment was 5,410 dollars ( 95 percent confidence interval , 4,516 dollars to 6,304 dollars ) in the B-type natriuretic peptide group , as compared with 7,264 dollars ( 95 percent confidence interval , 6,301 dollars to 8,227 dollars ) in the control group ( P=0.006 ) . The respective 30-day mortality rates were 10 percent and 12 percent ( P=0.45 ) . CONCLUSIONS Used in conjunction with other clinical information , rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment 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 BACKGROUND Exercise training increases exercise capacity in patients with reduced ventricular function in part through improved skeletal muscle metabolism , but the effect training might have on abnormal ventilatory and gas exchange responses to exercise has not been clearly defined . METHODS Twenty-five male patients with reduced ventricular function after a myocardial infa rct ion were r and omized to either a 2-month high-intensity residential exercise training program or to a control group . Before and after the study period , upright exercise testing was performed with measurements of ventilatory gas exchange , lactate , arterial blood gases , cardiac output , and pulmonary artery and wedge pressures . RESULTS In the exercise group , peak VO2 and VO2 at the lactate threshold increased 29 and 39 % , respectively , whereas no increases were observed among controls . Maximal cardiac output increased only in the exercise group ( 1.7 L x min(-1 ) , P < 0.05 ) , and no changes in rest or peak exercise pulmonary pressures were observed in either group . At baseline , modest inverse relationships were observed between pulmonary wedge pressure and peak VO2 both at rest ( r = -0.56 , P < 0.05 ) and peak exercise ( r = -0.43 , P < 0.05 ) . Maximal VE/VCO2 was inversely related to maximal cardiac output ( r = -0.72 , P < 0.001 ) . Training did not have a significant effect on these relationships . Training lowered VE/VO2 , heart rate , and blood lactate levels at matched work rates throughout exercise and tended to lower maximal Vd/Vt . The slope of the relationship between VE and VCO2 was reduced after training in the exercise group ( 0.33 pre vs 0.27 post , P < 0.01 ) , whereas control patients did not differ . CONCLUSIONS Exercise training among patients with reduced left ventricular function results in a systematic improvement in the ventilatory response to exercise . Training increased maximal cardiac output , tended to lower Vd/Vt , and markedly improved the efficiency of ventilation . Peak VO2 and ventilatory responses to exercise were only modestly related to pulmonary vascular pressures , and training had no effect on the relationships between exercise capacity , ventilatory responses , and pulmonary pressures BACKGROUND : Measures of ventilatory inefficiency , such as the slope of the relation between ventilation and carbon dioxide production ( slope ) and the oxygen uptake efficiency slope ( OUES ) have recently been shown to be strong prognostic markers in patients with heart failure . Little is known regarding the effects of exercise training on these indices . METHODS : Fifty heart failure patients ( mean age = 55 ± 6 years , ejection fraction = 33 ± 6 % ) referred to a residential cardiac rehabilitation program were r and omized to a 2-month high — intensity training program ( n = 24 ) or to a control group ( n = 26 ) . Before and after the study period , maximal cardiopulmonary exercise testing was performed , and markers of ventilatory inefficiency were determined . RESULTS : Training increased peak oxygen uptake ( ; 23 % ) , exercise time ( 29 % ) , and peak workload ( 28 % ) , whereas no changes were observed in controls ( all P < .05 between groups ) . No differences were observed in the slope in either group . However , the ventilatory equivalent for oxygen ( ratio ) was reduced at matched work rates throughout exercise ( P < .01 ) . The OUES increased by 12 % in the exercise groups ( P = .003 ) and 4 % in controls . At baseline , trained patients had an OUES that was 69 % of the age-predicted value and this improved to 78 % after training ( P = .004 ) . The change in OUES was significantly related to the change in peak with training ( r = 0.63 , P = .001 ) . CONCLUSION : High-intensity training result ed in marked improvements in exercise capacity in patients with heart failure . Training improved the OUES and reduced the ratio , but the slope was unchanged . Among measures of ventilatory inefficiency , the OUES may be more sensitive to training than the slope BACKGROUND It remains unclear whether patients with chronic heart failure ( CHF ) and advanced left ventricular ( LV ) dysfunction on β-blocker therapy benefit from exercise training ( ET ) . METHODS AND RESULTS We studied 45 CHF patients with advanced LV dysfunction [ ejection fraction ( LVEF ) < 25 % ] and impaired exercise tolerance [ normalized peak oxygen uptake ( PVO₂ ) < 70 % ] receiving a β-blocker : 33 patients participated in a cardiac rehabilitation program with ET ( ET group ) and 12 did not ( inactive control group ) . Exercise capacity , LV dimension and plasma B-type natriuretic peptide ( BNP ) were assessed before and after a 3-month study period . At baseline , both groups had markedly reduced LVEF ( ET group 18 ± 4 % vs. Control group 18 ± 5 % , NS ) and impaired exercise capacity ( normalized PVO₂ 51 ± 10 % vs. 55 ± 9 % , NS ) . Although one patient in the ET group withdrew from the program due to worsening CHF , no serious cardiac events occurred during the ET sessions . After 3 months , the ET group ( n = 24 ) had significantly improved PVO₂ by 16 ± 15 % ( 1,005 ± 295 to 1,167 ± 397ml/min , P < 0.001 ) , while the PVO₂ of the control group was unchanged . LV end-diastolic dimension decreased in both groups to a similar extent , but plasma BNP was significantly decreased only in the ET group ( 432 to 214 pg/ml , P < 0.05 ) . CONCLUSIONS The data indicate that in CHF patients with advanced LV dysfunction on β-blocker therapy , ET successfully improves exercise capacity and BNP without adversely affecting LV remodeling or causing serious cardiac complications OBJECTIVES We sought to evaluate the effect of physical training on neurohormonal activation in patients with heart failure ( HF ) . BACKGROUND Patients with HF benefit from physical training . Chronic neurohormonal activation has detrimental effects on ventricular remodeling and prognosis of patients with HF . METHODS A total of 95 patients with HF were assigned r and omly into two groups : 47 patients ( group T ) underwent a nine-month training program at 60 % of the maximal oxygen uptake ( VO2 ) , whereas 48 patients did not ( group C ) . The exercise load was adjusted during follow-up to achieve a progressive training effect . Plasma assay of B-type natriuretic peptide ( BNP ) , amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , norepinephrine , plasma renin activity , and aldosterone ; quality -of-life question naire ; echocardiogram ; and cardiopulmonary stress test were performed upon enrollment and at the third and ninth month . RESULTS A total of 85 patients completed the protocol ( 44 in group T , left ventricular ejection fraction [ EF ] 35 + /- 2 % , mean + /- SEM ; and 41 in group C , EF 32 + /- 2 % , p = NS ) . At the ninth month , patients who underwent training showed an improvement in workload ( + 14 % , p < 0.001 ) , peak VO2 ( + 13 % , p < 0.001 ) , systolic function ( EF + 9 % , p < 0.01 ) , and quality of life . We noted that BNP , NT-proBNP , and norepinephrine values decreased after training ( -34 % , p < 0.01 ; -32 % , p < 0.05 ; -26 % , p < 0.01 , respectively ) . Increase in peak VO2 with training correlated significantly with the decrease in both BNP/NT-proBNP level ( p < 0.001 and p < 0.01 , respectively ) . Patients who did not undergo training showed no changes . CONCLUSIONS Clinical benefits after physical training in patients with HF are associated with blunting of adrenergic overactivity and of natriuretic peptide overexpression Background and aim The oxygen uptake efficiency slope ( OUES ) is a novel measure of cardiopulmonary reserve . OUES is measured during an exercise test , but it is independent of the maximally achieved exercise intensity . It has a higher prognostic value in chronic heart failure ( CHF ) than other exercise test-derived variables such as V . O 2 peak or V . E / V . CO 2 slope . Exercise training improves V . O 2 peak and V . E / V . CO 2 in CHF patients . We hypothesized that exercise training also improves OUES . Methods and results We studied 34 New York Heart Association ( NYHA ) class II – III CHF patients who constituted an exercise training group T ( N = 20 ; 19 men/1 woman ; age 60 ± 9 years ; left ventricular ejection fraction 34 ± 5 % ) and a control group C ( N = 14 ; 13 men/one woman ; age 63 ± 10 years ; left ventricular ejection fraction 34 ± 7 % ) . A symptom-limited exercise test was performed at baseline and repeated after 4 weeks ( C ) or after completion of the training program ( T ) . Exercise training increased NYHA class from 2.6 to 2.0 ( P [ 0.05 ) , V . O 2 peak by 14 % [ P(TvsC)[0.01 ] , and OUES by 19 % [ P(TvsC ) [ 0.01 ] . Exercise training decreased V . E / V . CO 2 by 14 % [ P(TvsC ) [ 0.05 ] . Conclusion Exercise training improved NYHA class , V . O 2 peak , V . E / V . CO 2 and also OUES . This finding is of great potential interest as OUES is insensitive for peak load . Follow-up studies are needed to demonstrate whether OUES improvements induced by exercise training are associated with improved prognosis Introduction N-terminal-pro-brain ( B-type ) natriuretic peptide ( NT-pro-BNP ) is a peptide hormone released from ventricles in response to myocyte stretch . The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infa rct ion patients undergoing an exercise training programme . Methods Forty-four patients after myocardial infa rct ion were enrolled into a cardiac rehabilitation programme , and were r and omized in two groups of 22 patients each . Group A patients followed a 3-month exercise training programme , while group B patients received only routine recommendations . All patients underwent NT-pro-BNP assay , and cardiopulmonary exercise test before hospital discharge and after 3 months . Results In Group A , exercise training reduced NT-pro-BNP levels ( from 1498 ± 438 to 470 ± 375 pg/ml , P = 0.0026 ) , increased maximal ( V O2peak + 4.3 ± 2.9 ml/kg per min , P<0.001 ; Powermax + 38 ± 7 , P<0.001 ) exercise parameters and work efficiency ( Powermax/V O2peak + 1.3 ± 0.4 Power/ml per kg per min , P<0.001 ) ; there was also an inverse correlation between changes in NT-pro-BNP levels and in V O2peak ( r = −0.72 , P<0.001 ) , E-wave ( r = −0.51 , P<0.001 ) and E/A ratio ( r = 0.59 , P<0.001 ) . In group B , at 3 months , no changes were observed in NT-pro-BNP levels , exercise and echocardiographic parameters . Conclusion Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infa rct ion induced a reduction in NT-pro-BNP levels , an improvement of exercise capacity and early left ventricular diastolic filling , without negative left ventricular remodelling . Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored The authors compared the effects of continuous ( CON ) and intermittent ( INT ) exercise training programs on functional capacity , quality of life ( QOL ) , and cardiac function in 23 congestive heart failure patients . Patients were r and omized to CON exercise training ( n=13 ; aged 66±7 years ; peak oxygen consumption [ VO(2 ) ] , 12.4±2.5 mL/kg/min ; weight , 83±12 kg ; left ventricular ejection fraction [ LVEF ] , 29.5%±7.2 % ) or INT exercise training ( n=10 ; aged 59±11 years ; VO(2 ) , 12.2±6.5 mL/kg/min ; weight , 87±24 kg ; LVEF 27%±7.9 % ) . These groups completed 16 weeks of stationary cycling at 70 % VO(2 ) thrice weekly for 30 minutes continuously or 60 minutes ( 60 seconds work:60 seconds rest ) intermittently ; both groups completed the same absolute volume of work . Three QOL question naire responses , VO(2 ) , LVEF , and regional tissue Doppler were quantified . After exercise training , VO(2 ) increased by 13 % in the CON group ( P=.12 ) and significantly by 21 % in the INT group ( P=.03 ) , although not significantly between the groups ( P=.72 ) . In the CON group , Minnesota Living With Heart Failure score improved at 16 weeks ( P=.02 ) , while in the INT group , Hare-Davis scores improved ( P=.02 ) . Cardiac volumes , resting and peak LVEF , contractile reserve , and tissue velocities were all unchanged from baseline . Intermittent exercise may improve functional capacity to a greater extent than continuous exercise . QOL changes were variable between groups BACKGROUND Exercise training is beneficial in ischemic and congestive heart disease . However , the effect on atrial fibrillation ( AF ) is unknown . METHODS Forty-nine patients with permanent AF ( age [ mean ± SD ] , 70.2 ± 7.8 years ; male-to-female ratio , 0.75 ; body mass index [ mean ± SD ] , 29.7 ± 4.3 kg/m(2 ) ) were r and omized to 12-week aerobic exercise training or a control group . Exercise capacity , 6-minute walk test ( 6MWT ) , cardiac output , quality of life , and natriuretic peptides were measured . Cardiac output was measured at rest and during ergometer testing , and atrial natriuretic peptide and N-terminal pro-B-type natriuretic peptide were measured before and after the training period . Quality of life was evaluated using the Short-Form 36 and Minnesota Living With Heart Failure ( MLHF-Q ) question naires . RESULTS Improved exercise capacity and 6MWT were observed in the active patients ( P < .001 ) , and at study end , there was a significant difference between the active patients and the controls ( P = .002 ) . Resting pulse decreased in the active patients ( 94.8 ± 22.4 to 86.3 ± 22.5 beats/min , P = .049 ) but remained unchanged in the controls . Cardiac output was unchanged from baseline to end-of- study period . The MLHF-Q score improved in the active group ( 21.1 ± 18.0 vs 15.4 ± 17.5 , P = .03 ) . Active patients showed progress in 3 of the 8 Short-Form 36 subscales : physical functioning ( P = .02 ) , general health perceptions ( P = .001 ) , and vitality ( P = .02 ) . Natriuretic peptides were unchanged . CONCLUSION Twelve weeks of exercise training increased exercise capacity and 6MWT and decreased resting pulse rate significantly in patients with AF . Overall quality of life increased significantly as measured by the cardiology-related MLHF-Q. Cardiac output and natriuretic peptides were unchanged in both groups BACKGROUND Although there are limited clinical data to support the use of exercise training as a means to reduce mortality and morbidity in patients with heart failure , current guidelines state that exercise is beneficial . TRIAL DESIGN The objective of this trial is to determine whether exercise training reduces all-cause mortality or all-cause hospitalization for patients with left ventricular systolic dysfunction and heart failure symptoms . After undergoing baseline assessment s to determine whether they can safely exercise , patients are r and omized to either usual care or exercise training . Patients in the exercise training arm attend 36 supervised facility-based exercise training sessions . Exercise modalities are cycling or walking . After completing 18 sessions , patients initiate home-based exercise and then transition to solely home-based exercise after completing all 36 sessions . Patients return for facility-based training every 3 months to reinforce their exercise training program . Patients are followed for up to 4 years . Physiologic , quality -of-life , and economic end points that characterize the effect of exercise training in this patient population will be measured at baseline and at intervals throughout the trial . Blood sample s will be collected to examine biomarkers such as brain natriuretic peptide , tumor necrosis factor , and C-reactive protein . CONCLUSIONS Because of its relatively low cost , high availability , and ease of use , exercise training is an intervention that could be accessible to most patients with heart failure . The HF-ACTION trial is design ed to definitively assess the effect of exercise training on the clinical ly relevant end points of mortality , hospitalization , and quality of life in patients with heart failure BACKGROUND Supervised cardiac rehabilitation programs have been offered to patients following myocardial infa rct ( MI ) , coronary artery bypass graft surgery ( CABG ) and percutaneous coronary intervention ( PCI ) for many years . However , limited information is available on the usefulness of rehabilitation programs in chronic heart failure ( CHF ) . The aim of our study was to evaluate the outcome of supervised physical training on CHF patients by measuring both central and peripheral factors . METHODS This was a prospect i ve r and omized study , including 43 patients with CHF , New York Heart Association ( NYHA ) class II or III , mean age 68 years . After initial measurements of VO2 peak , 6 min walk distance , muscle strength , plasma levels of atrial natriuretic peptide ( ANP ) and brain natriuretic peptide ( BNP ) , echocardiogram , measurements of pulmonary function and quality of life question naire , patients were r and omized to either a training group ( n = 21 ) or a control group ( n = 22 ) . The training group had supervised aerobic and resistance training program twice a week for five months . After the training program was completed , all measurements were repeated in both groups . RESULTS No training related adverse events were reported . Significant improvement was found between groups in the six minute walk test ( + 37.1 m vs. + 5.3 m , p = 0.01 ) , work load on the bicycle exercise test ( + 6.1 W vs. + 2.1 W , p = 0.03 ) , time on the bicycle exercise test ( + 41 s vs. + 0 s , p = 0.02 ) and quadriceps muscle strength test ( + 2.8 kg . vs. + 0.2 kg . , p = 0.003 ) . Quality of life factors that reflect exercise tolerance and general health , improved significantly in the training group compared to the control group . No other significant changes were found between the two groups . CONCLUSION Supervised physical training as used in this study appears safe for CHF patients in NYHA class II or III . The improvement in functional capacity observed in the training group seems to be related to peripheral factors rather than in central cardiovascular performance BACKGROUND Echocardiography and B-type natriuretic peptide ( BNP ) are diagnostic tests for congestive heart failure ( CHF ) , but an emergency diagnosis can be difficult . OBJECTIVE To assess the diagnostic performance of BNP testing and echocardiographic assessment of left ventricular systolic function , separately and combined , for the identification of CHF in patients with acute dyspnea . DESIGN Prospect i ve , multinational , multicenter study . SETTING Patients presenting to emergency departments in seven hospitals between June 1999 and December 2000 . PATIENTS A total of 1,586 patients with acute dyspnea . MAIN OUTCOME MEASURES Echocardiographic determination of ejection fraction ( EF ) and point-of care BNP measurement for the diagnosis of CHF . RESULTS Seven hundred nine of the 1,586 patients underwent echocardiography ; 492 patients ( 69.4 % ) had a final diagnosis of CHF . Patients with CHF were older ( 68.5 years vs 61.6 years , p < 0.0001 ) , had a lower EF ( 39.5 % vs 56.1 % , p < 0.0001 ) , and a higher BNP ( 683 pg/mL vs 129 pg/mL , p < 0.0001 ) than patients without CHF . Area under the receiver operating characteristic ( ROC ) curve for the diagnosis of CHF was significantly higher for BNP ( 0.89 ) than for EF ( 0.78 ; area under the ROC curve difference , 0.12 ; p < 0.0001 ) . The sensitivity of BNP > or = 100 pg/mL for the diagnosis of CHF was 89 % , and specificity was 73 % . Values for EF < or = 50 % had a sensitivity of 70 % and a specificity of 77 % . Multivariate logistic regression analysis showed that , in combination with clinical , ECG , and chest radiograph data , BNP > or = 100 pg/mL and EF < or = 50 % remained independent predictors of CHF ( odds ratios , 32.1 and 6.2 , respectively ) . The proportions of patients who were correctly classified were 67 % for BNP alone , 55 % for EF alone , 82 % for the two variables together , and 97.3 % when clinical , ECG , and chest radiograph data were added . CONCLUSION BNP measurement was superior to two-dimensional echocardiographic determination of EF in identifying CHF , regardless of the threshold value . The two methods combined have marked additive diagnostic value Background The aim of the present study was to determine whether regular exercise training ( ET ) is effective at promoting the mobilization of CPCs and improving their functional activity in patients with recently acquired myocardial infa rct ion(STEMI ) . Regular physical training has been shown to improve myocardial perfusion and cardiovascular function . This mayberelatedin part to a mobilization of bonemarrow-derived circulating progenitor cells ( CPCs ) as well as an enhanced vascularisation . Methods 37 patients with STEMI were r and omly assigned to an ET group or a non-ET group(controls ) . Two weeks after STEMI , three weeks after regular ET and three months after ET , BNP levels , exercise echocardiography and exercise spiroergometry were evaluated . The number of CD34+/CD45 + and CD133+/CD45+CPCs was measured by flow cytometry analysis . The migration capacity of the CPCs was determined with a boyden chamber and the clonogenic capacity by CFU-assay . Results In the ET-group the number and migration capacity of CPCs increased significantly after regular exercise training . The BNP level decreased significantly from 121 ± 94 to 75 ± 47 pg/ml ( p < 0.001 ) after the ET period , the left ventricular rejection fraction raised in parallel at peak exercise , and the cardiorespiratory condition improved as demonstrated by an increase of VO2max ( from 1641 ± 522 to 1842 ± 724 ml/min , p < 0.02 ) . These three effects persist till three months after the ET period . Conclusions Regular physical activity appears to predispose the mobilization and enhanced functional activity of CPCs , a phenomenon which might lead to an improved cardiac function in patients with recently acquired acute myocardial infa rct ion Objective To study the effects of aerobic exercise on exercise tolerance in patients with chronic heart failure ( CHF ) . Methods Total of 50 CHF patients were enrolled in the study , left ventricular ejection fraction ( LVEF ) < 0.49 by Doppler echocardiography and were r and omly divided into aerobic exercise group ( T group ) 25 cases and non-aerobic exercise group ( non-T group ) 25 cases , cardiopulmonary exercise testing ( CPET ) were performed . The patients of T group executed the aerobic exercise prescription which exercise intensity is decided by anaerobic threshold ( AT ) before 10W ( 1 min before ) of the oxygen consumption , non-T group required daily activities . After six sessions under supervised aerobic exercise training , the home-based aerobic exercise training began . CPET were review ed 3 months later respectively . Results The VO2 AT , VO2 peak , peak VO2/HR , load AT and load peak in patients of T group were increased compared with baseline , the differences of ▱ VO2 AT , ▱ VO2 peak , ▱ peak VO2/HR , ▱ load AT and ▱ load between two groups were statistically significant ( p<0.01 or 0.05 ) ; the slope of VE/VCO2 in patients of T group was decreased compared with baseline , but the slope of VE/VCO2 in non-T group was increased over baseline , the difference of ▱ VE/VCO2 slope between two groups was not statistically significant ( p>0.05 ) . Conclusion After 3 months of aerobic exercise , exercise capacity can be improved in patients with CHF Background Decreased exercise capacity is the main factor restricting the daily life of patients with chronic heart failure . N-terminal pro-brain natriuretic peptide ( NT pro-BNP ) is strongly related to the severity of and is an independent predictor of outcome in chronic heart failure . Design The study aim ed to evaluate the effect of exercise training on functional capacity and on changes in NT pro-BNP levels and to assess the effect of exercise training on quality of life . Material s and methods Sixty patients ( 45 men/15 women , mean age 52.7 years ; ±5.3 SD ) , with stable heart failure ( 45 ischaemic/hypertensive and 15 idiopathic patients ) , in New York Heart Association ( NYHA ) functional class II ( n = 35 ) to III ( n = 25 ) , with an ejection fraction less than 40 % , were r and omly assigned to a training ( n = 30 ) and a control group ( n = 30 ) . The training group ( 30 patients ) performed 3 months of supervised physical training programme using a bicycle ergometer for 30 min three times a week at a load corresponding to 60–70 % of their oxygen consumption ( Vo2 ) peak . The control group did not change their previous physical activity . A grade d maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85 % of the peak oxygen load at the baseline and after 3 months were performed , and at the same times NT pro-BNP levels were measured . Results The exercise capacity increased from 15.8 ( ±2.3 SD ) to 29.9 ( ±2.1 SD ) min ( P<0.0001 ) and the peak Vo2 tended to improve from 14.5 ( ±1.4 SD ) to 17.7 ( ±2.6 SD ) ml/kg per min ( P<0.0001 ) during the supervised training period . Vo2 at the anaerobic threshold increased from 12.9 ( ±1.0 SD ) to 15.5 ( ±1.7 SD ) ml/kg per min ( P<0.0001 ) . NT pro-BNP levels decreased from 3376 ( ±3133 SD ) to 1434 ( ±1673 SD ) pg/ml ( P=0.043 ) . The positive training effects were associated with an improvement in the NYHA functional class . Conclusion Physical training of moderate intensity significantly improves the exercise capacity and neurohormonal modulation in patients with chronic heart failure . This is associated with an alleviation of symptoms and improvement in quality of life Background Both endurance training ( ET ) and cardiac resynchronization therapy ( CRT ) improve quality of life ( QOL ) and exercise tolerance in patients with advanced chronic heart failure ( CHF ) . Design A r and omized intervention trial to study the effect on exercise capacity of ET in addition to CRT in patients with CHF and dyssynchrony . Methods Seventeen patients ( eight men , aged 59 ± 9 years ) with CHF and dyssynchrony were r and omized to CRT with ( n = 8) or without ( n = 9 ) ET and compared with two matched control CHF groups ( st and ard care with ET : n = 9 , st and ard care only : n = 10 ) . At baseline and after 5 months , exercise tolerance , left ventricular ( LV ) remodelling , QOL and NT-pro brain natriuretic peptide ( NT-proBNP ) levels were assessed . Results Peak oxygen consumption ( VO2peak ) , maximal workload ( Wattmax ) , circulatory power , LV ejection fraction , dyssynchrony and QOL improved in both CRT groups . However , the increase in VO2peak ( + 40 % versus + 16 % , P = 0.005 ) , Wattmax ( + 43 % versus + 13 % , P = 0.0005 ) , and circulatory power ( + 74 % versus + 32 % , P = 0.01 ) , was significantly greater in the trained versus the untrained CRT patients . Comparison of the four patient groups confirmed the cumulative effects of CRT plus ET . Conclusions ET in resynchronized CHF patients is feasible and further enhances exercise tolerance . Patients with severe CHF should be prescribed an exercise training programme after implantation in order to maximize the expected benefit . Eur J Cardiovasc Prev Rehabil 14 : 99 - 106 © 2007 The European Society of Objectives and Design . This study describes the long-term outcome of 163 patients with stable mild to moderate heart failure ( NYHA II-III ) , who already were enrolled in a heart failure clinic and now were r and omized to continued follow-up in the heart failure ( HF ) clinic or else to usual care ( UC ) . The primary outcome was unplanned hospitalisations and death , the secondary endpoints were pharmacological therapy , NYHA class , six-minute-walking distances and NT-pro BNP level . Results . At the end of follow-up we found no significant differences in total number of hospitalisation ( p = 0.2 ) or mortality ( 16 % vs. 16 % ) between the two groups . Patients in the HF clinic cohort achieved a significantly better NYHA score ( p < 0.01 ) , significantly longer walking-distances ( p = 0.04 ) and received a significantly higher dose of angiotensin-converting enzyme inhibitors ( p < 0.001 ) and beta-blockers ( p < 0.001 ) . No significant difference was found on the level of NT-pro BNP ( p = 0.4 ) . Conclusions . Patients with mild to moderate HF may benefit from long-term follow-up in a HF clinic in terms of pharmacological therapy and functional status , but we found no significant impact on unplanned hospitalisations or death Objective : To evaluate the effects of home-based exercise for patients with chronic heart failure and sleep apnoea and to compare two different training programmes . Design : A r and omized , prospect i ve controlled trial . Setting : Department of Cardiology , University Hospital , Brazil . Subjects : Fifty chronic heart failure patients with sleep apnoea were r and omized in three groups : Group 1 ( aerobic training , n = 18 ) , Group 2 ( aerobic with strength training , n = 18 ) , and Group 3 ( untrained , n = 14 ) . Interventions : The training programme for Groups 1 and 2 began with three supervised exercise sessions , after they underwent three months of home-based exercise . Patients were followed by weekly telephone call and were review ed monthly . Group 3 had the status of physical activity evaluated weekly by interview to make sure they remained untrained . Main outcome measures : At baseline and after three months : cardiopulmonary exercise testing , isokinetic strength and endurance , Minnesota living with heart failure question naire and polysomnography . Adherence was evaluated weekly . Results : Of the 50 patients enrolled in the study , 45 completed the programme . Clinical events : Group 1 ( one death ) , Group 2 ( one myocardial infa rct ion ) , Group 3 ( one death and two strokes ) . None were training related . Training groups showed improvement in all outcomes evaluated and the adherence was an important factor ( Group 1 = 98.5 % and Group 2 = 100.2 % , P = 0.743 ) . Untrained Group 3 demonstrated significant decrease or no change on measurements after three months without training . Conclusion : Home-based exercise training is an important therapeutic strategy in chronic heart failure patients with sleep apnoea , and strength training result ed in a higher increase in muscle strength and endurance Background : We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease . Methods and results : A r and omized , controlled trial was conducted to determine the effects of an 8-week exercise training programme ( n = 32 ) vs. controls ( n = 32 ) on brachial flow-mediated dilation ( FMD ) in patients with stable CAD . After 8 weeks , patients received exercise training had significant improvements in FMD ( 1.84 % , p = 0.002 ) and exercise capacity ( 2.04 metabolic equivalents , p < 0.001 ) compared with controls . The change in FMD correlated inversely with baseline FMD ( r = −0.41 , p = 0.001 ) and positively with the increase in exercise capacity ( r = 0.35 , p = 0.005 ) . After adjusting for confounders , every 1 metabolic equivalent increase in exercise capacity was associated with 0.55 % increase in FMD . Furthermore , patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls . However , exercise training did not alter high-sensitivity C-reactive protein , oxidative stress measured as superoxide dismutase and 8-isoprostane , and CD34/KDR + endothelial progenitor cell count . Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity ( < median value of 7.65 metabolic equivalents , p = 0.004 ) but not in those with normal exercise capacity . Conclusion : Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation , oxidative stress , or endothelial progenitor cells . The beneficial effects of exercise training on FMD and exercise capacity are inter-related , and more pronounced in those with baseline impaired exercise capacity Abstract Objectives . Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure ( CHF ) . N-terminal pro-B-type natriuretic peptide ( NT pro-BNP ) , is associated with the severity of the disease , and has been reported to be an independent predictor of outcome in CHF . We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF . We have previously reported improved functional capacity in 80 patients after exercise in this exercise program . Methods . Seventy-eight patients with stable CHF ( 21 % women ; 70±8 years ; left ventricular ejection fraction 30±8.6 % ) on optimal medical treatment were r and omized either to interval training ( n=39 ) , or to a control group ( n=39 ) . Circulating levels of NT pro-BNP , a six minute walk test ( 6MWT ) and cycle ergometer test were evaluated at baseline , post exercise , and further after 12 months . Results . There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups . Inverse correlations were observed between NT pro-BNP and 6MWT ( r=−0.24 , p=0.035 ) and cycle exercise time ( r=−0.48 , p<0.001 ) at baseline . But no significant correlations were observed between change in NT pro-BNP and change in functional capacity ( 6MWT ; r=0.12 , p=0.33 , cycle exercise time ; r=0.04 , p=0.72 ) . Conclusion . No significant changes in NT pro-BNP levels were observed after interval training , despite significant improvement of functional capacity |
13,096 | 29,368,662 | The reporting of this protocol follows the PRISMA -P. Discussion We expect that this review will help determine whether patients that were initially exposed to opioids through a prescription differ in OST treatment outcomes in comparison to people who used opioids through illicit means . | Background In North America , opioid use has become a public health crisis with policy makers declaring it a state of emergency .
Opioid substitution therapy ( OST ) is a harm-reduction method used in treating opioid use disorder .
While OST has shown to be successful in improving treatment outcomes , there is still a great degree of variability among patients .
This cohort of patients has shifted from young males using heroin to a greater number of older people and women using prescription opioids .
The primary objective of this review is to examine the literature on the association between the first exposure to opioids through prescription versus illicit use and OST treatment outcomes . | 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 Summary An intricate relationship between chronic pain , opioid use and addictive behaviors was demonstrated , and certain addictive behaviors seem to predict or be associated with opioid use in chronic non‐cancer pain . Abstract The growing body of research showing increased opioid use in patients with chronic pain coupled with concerns regarding addiction encouraged the development of this population ‐based study . The goal of the study was to investigate the co‐occurrence of indicators of addictive behaviors in patients with chronic non‐cancer pain in long‐term opioid treatment . The study combined data from the individual‐based Danish Health Survey in 2010 and the official Danish health and socio‐economic , individual‐based registers . From a simple r and om sample of 25,000 adults ( 16 years or older ) living in Denmark , 13,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain ( lasting ≥6 months ) , opioid use , health behavior , and body mass index . Six potential addictive behaviors were identified : daily smoking ; high alcohol intake ; illicit drug use in the past year ; obesity ; long‐term use of benzodiazepines ; and long‐term use of benzodiazepine‐related drugs . At least 2 of the 6 addictive behaviors were observed in 22.6 % of the long‐term opioid users with chronic pain compared with 11.5 % of the non‐opioid users with chronic pain and 8.9 % of the individuals without chronic pain . Thus , a strong association was demonstrated between long‐term opioid use and the clustering of addictive behaviors . An intricate relationship between chronic pain , opioid use , and addictive behaviors was observed in this study , which deserves both clinical attention and further research AIMS To test ( 1 ) whether abstinence and reduction in illicit psychoactive drug use were associated with changes in health outcomes in primary care patients and ( 2 ) whether these associations varied by drug type . DESIGN Secondary analysis of data from a r and omized controlled trial that tested a brief intervention for drug use in primary care patients ( 589 enrolled , 574 completed a 6-month assessment ) . Analyses were conducted overall and stratified by the most commonly self-identified main drugs ( marijuana , cocaine and opioids ) . SETTING AND PARTICIPANTS Patients who screened positive for illicit drug use at an urban primary care clinic in Boston , Massachusetts , USA . MEASUREMENTS Differences in past-month main drug use at baseline and 6-month outcome were categorized as continued or increased use , decreased use without abstinence and abstinence . Primary outcomes were 6-month changes in drug use consequences [ Short Inventory of Problems scores ( range 0 - 45 ) ] , depressive symptoms and health-related quality of life ( HRQol ) . FINDINGS Abstinence was associated with a greater decrease in adverse drug use consequences than continued or increased use among the full sample and cocaine and opioids subgroups ( adjusted means , full sample : -8.11 versus -0.05 , P < 0.001 ; cocaine : -13.33 versus + 1.09 , P < 0.001 , opioids ; -16.84 versus -2.10 , P < 0.001 ) . Differences were not significant between those who decreased use compared with those who continued or increased use . There were no significant associations between drug use and depressive symptoms or HRQol . Neither abstinence nor decreased use was associated significantly with consequences in the marijuana subgroup . CONCLUSIONS Among primary care patients in the United States who use illicit psychoactive drugs , abstinence but not reduction in use without abstinence appears to be associated with decreased adverse drug use consequences |
13,097 | 22,376,192 | Inclusion criteria were met by 59 controlled trials , 7 meta-analyses and 8 review s. The studies included in this review indicate that bone-related variables can be increased , or at least the common decline in bone mass during ageing attenuated , through following specific training programmes .
Walking provides a modest increase in the loads on the skeleton above gravity and , therefore , this type of exercise has proved to be less effective in osteoporosis prevention .
Strength exercise seems to be a powerful stimulus to improve and maintain bone mass during the ageing process .
Some novelties are that WBV training is a promising alternative to prevent bone fractures and osteoporosis .
Because this type of exercise under prescription is potentially safe , it may be considered as a low impact alternative to current methods combating bone deterioration .
In other respects , the ability of peripheral quantitative computed tomography ( pQCT ) to assess bone strength and geometric properties may prove advantageous in evaluating the effects of training on bone health .
As a result of changes in bone mass becoming evident by pQCT even when dual energy X-ray absortiometry ( DXA ) measurements were unremarkable , pQCT may provide new knowledge about the effects of exercise on bone that could not be eluci date d by DXA . | It is widely recognized that the risk of fractures is closely related to the typical decline in bone mass during the ageing process in both women and men .
Exercise has been reported as one of the best non-pharmacological ways to improve bone mass throughout life .
However , not all exercise regimens have the same positive effects on bone mass , and the studies that have evaluated the role of exercise programmes on bone-related variables in elderly people have obtained inconclusive results .
This systematic review aims to summarize and up date present knowledge about the effects of different types of training programmes on bone mass in older adults and elderly people as a starting point for developing future interventions that maintain a healthy bone mass and higher quality of life in people throughout their lifetime .
Multi-component exercise programmes of strength , aerobic , high impact and / or weight-bearing training , as well as whole-body vibration ( WBV ) alone or in combination with exercise , may help to increase or at least prevent decline in bone mass with ageing , especially in postmenopausal women .
This review provides , therefore , an overview of intervention studies involving training and bone measurements among older adults , especially postmenopausal women . | Background Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents . Low-volume exercise interventions with similar training effects might be an alternative . The aim of this r and omised controlled trial was to investigate the feasibility of Whole Body Vibration ( WBV ) in institutionalised elderly , and its impact on functional capacity and muscle performance . Methods Twenty-four nursing home residents ( 15 female , 9 male ; mean age 77.5 ± 11.0 years ) were r and omised ( stratification for age , gender and ADL-category ) to 6 weeks static WBV exercise ( WBV+ , N = 13 ) or control ( only static exercise ; N = 11 ) . Outcome measures were exercise compliance , timed up- and -go , Tinetti-test , back scratch , chair sit- and -reach , h and grip strength and linear isokinetic leg extension . Results At baseline , WBV+ and control groups were similar for all outcome variables . Twenty-one participants completed the program and attended respectively 96 % and 86 % of the exercise sessions for the WBV+ and control groups . Training-induced changes in timed up- and -go and Tinetti-test were better for WBV+ compared to control ( p = 0.029 for timed up- and -go , p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively ) . In an alternative analysis ( Worst Rank Score & Last Observation Carried Forward ) the differences in change remained significant on the Tinetti body balance and total score . No other significant differences in change between both groups were observed . Conclusion In nursing home residents with limited functional dependency , six weeks static WBV exercise is feasible , and is beneficial for balance and mobility . The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further OBJECTIVE To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults . DESIGN A r and omized controlled trial with subjects assigned either to high-intensity resistance training 1 ( EX1 ) , 2 ( EX2 ) , or 3 ( EX3 ) days per week for 24 weeks or to a control group ( CO ) . SETTING An exercise facility at an academic medical center . SUBJECTS Forty-six community-dwelling healthy men ( n = 29 ) and women ( n = 17 ) aged 65 to 79 years . INTERVENTION Progressive resistance training consisting of three sets of eight exercises targeting major muscle groups of the upper and lower body , at 80 % of one-repetition maximum ( 1-RM ) for eight repetitions , either 1 , 2 , or 3 days per week . MEASURES Dynamic muscle strength ( 1-RM ) using isotonic equipment every 4 weeks , bone mineral density and body composition by dual energy X-ray absorptiometry ( DXA ) , and neuromuscular performance by timed chair rise and 6-meter backward t and em walk . RESULTS For each of the eight exercises , muscle strength increased in the exercise groups relative to CO ( P < .01 ) , with no difference among EX1 , EX2 and EX3 groups at any measurement interval . Percent change averaged 3.9 + /- 2.4 ( CO ) , 37.0 + /- 15.2 ( EX1 ) , 41.9 + /- 18.2 ( EX2 ) , and 39.7 + /- 9.8 ( EX3 ) . The time to rise successfully from the chair 5 times decreased significantly ( P < .01 ) at 24 weeks , whereas improvement in the 6-meter backward t and em walk approached significance ( P = .10 ) in the three exercise groups compared with CO . Changes in chair rise ability were correlated to percent changes in quadriceps strength ( r = -0.40 , P < .01 ) and lean mass ( r = -0.40 , P < .01 ) . CONCLUSIONS A program of once or twice weekly resistance exercise achieves muscle strength gains similar to 3 days per week training in older adults and is associated with improved neuromuscular performance . Such improvement could potentially reduce the risk of falls and fracture in older adults Increased fat mass , particularly abdominal fat mass , is associated with poor metabolic profiles and an increase in cardiovascular risk factors . The purpose of this study was to evaluate the effect of a 1-year combined aerobic and strength training regimen , compared to aerobic training only , on body composition in patients with coronary artery disease ( CAD ) . Thirty-six males with CAD were assigned to 3 groups : 13 to weight training plus aerobic training ( combined training group [ CT ] ) , 13 to aerobic training only ( aerobic training group [ AT ] ) , and 10 to a control group ( no exercise [ CG ] ) . Body composition was determined by dual-energy x-ray absorptiometry ( DEXA ) . Differences were observed between groups at the end of the study , controlling for prevalues . The total and trunk percent fat mass ( % FM ) were lower in CT compared with AT and CG ( P<.05 ) . The total % FM in AT was significantly ( P<.05 ) lower than in CG , but the % FM of the trunk did not differ between the 2 groups . Fat-free mass ( FFM ) was significantly higher in CT than in AT and CG ( P<.05 ) . The results suggest that a long-term CT program is more effective than an AT program alone in producing changes in body composition . The percentage changes in total and trunk fat mass were higher in CT ( -11 % and -12 % , respectively ) than in AT ( -2.4 % and -0.7 % , respectively ) . Future studies need to investigate the specific health effects of trunkal fat mass loss in patients with CAD Aim . To analyse the effect of a specific program of weight training exercise with closed kinetic chain in bone mineral density in postmenopausal women with osteopenia or osteoporosis . Methods . A total of 59 postmenopausal women with osteoporosis or osteopenia were included in this prospect i ve study . Subjects were divided into two groups : the study group ( SG , n = 30 ; 57.5 ± 5.1 years ) and the control group ( CG , n = 29 ; 56.6 ± 4.6 years ) . In the study group was applied a weight exercise protocol ( longitudinal forces in closed kinetic chain ) during 12 months , whereas in the control group no weight exercise protocol was applied . Bone mineral density at the lumbar spine and hip was assessed at baseline and at the end of follow-up by dual energy X-ray absorptiometry . Results . Although no significant intragroup differences were found , patients in SG showed a 1.17 % increase in the lumbar spine whereas in CG a 2.26 % decrease in bone density was detected . Conclusion . This protocol of weight training exercise did not significantly improve bone mineral density in postmenopausal women with osteopenia or osteoporosis , but in comparison to the control group , the results showed the importance of practising the specific exercise program for maintenance of bone health in postmenopausal women OBJECTIVE To test whether training on a high-frequency ( 28Hz ) vibrating platform improves muscle power and bone characteristics in postmenopausal women . DESIGN R and omized controlled trial with 6-month follow-up . SETTING Outpatient clinic in a general hospital in Italy . PARTICIPANTS Twenty-nine postmenopausal women ( intervention group , n=14 ; matched controls , n=15 ) . INTERVENTION Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session , twice weekly for 6 months . The controls did not receive any training . Both groups were evaluated at baseline and after 6 months . MAIN OUTCOME MEASURES Muscle power , calculated from ground reaction forces produced by l and ing after jumping as high as possible on a forceplate , cortical bone density , and biomarkers of bone turnover . RESULTS Over 6 months , muscle power improved by about 5 % in women who received the intervention , and it remained unchanged in controls ( P=.004 ) . Muscle force remained stable in both the intervention and control groups . No significant changes were observed in bone characteristics . CONCLUSION Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women PURPOSE The purpose of this study was to determine the effects of 6 months of whole-body resistive training ( RT ) on total and regional bone mineral density ( BMD ) and bone mineral content ( BMC ) by age and gender in young and older men and women . METHODS Younger men ( n=10 ) and women ( n=7 ) aged 20 - 29 years ( 25+/-1 years ) and older men ( n=10 ) and women ( n=10 ) aged 65 - 74 years ( 69+/-1 years ) participated in 6 months of progressive whole-body RT . Upper- and lower-body strength was assessed by the one repetition maximum ( 1RM ) test , and total body fat , lean tissue mass , femoral neck BMD , Ward 's triangle BMD , greater trochanter BMD , total-body BMD , and L2-L4 spine BMD were determined by dual-energy X-ray absorptiometry before and after 6 months of RT . RESULTS Percent body fat decreased only in the young men ( P<0.05 ) . Lean tissue mass increased after training in young men and women and older men ( P<0.05 ) but did not change significantly in older women . Upper- and lower-body 1RM strength increased in all groups ( P<0.01 ) . Overall , there was a significant increase in BMD at the femoral neck , ward 's triangle and greater trochanter BMD , as well as total body BMC and leg BMC ( P<0.05 ) . Total-body BMD and L2-L4 spine BMD did not change with RT . There were no gender differences in the training response between men and women for any of the BMD regions and no age differences in the training response , except for a trend between young and older subjects for femoral neck ( P<0.08 ) . CONCLUSION A 6-month RT program increases muscle mass and improves BMD of the femoral region in young and healthy older men and women as a group , with a trend for this to be greater in young subjects Background Whole-body vibration ( WBV ) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people . There are two currently marketed vibrating plates : a ) the whole plate oscillates up and down ; b ) reciprocating vertical displacements on the left and right side of a fulcrum , increasing the lateral accelerations . A few studies have shown recently the effectiveness of the up- and -down plate for increasing Bone Mineral Density ( BMD ) and balance ; but the effectiveness of the reciprocating plate technique remains mainly unknown . The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women . Methods Twenty-eight physically untrained post-menopausal women were assigned at r and om to a WBV group or a Walking group . Both experimental programmes consisted of 3 sessions per week for 8 months . Each vibratory session included 6 bouts of 1 min ( 12.6 Hz in frequency and 3 cm in amplitude with 60 ° of knee flexion ) with 1 min rest between bouts . Each walking session was 55 minutes of walking and 5 minutes of stretching . Hip and lumbar BMD ( g·cm-2 ) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test . ANOVA for repeated measurements was adjusted by baseline data , weight and age . Results After 8 months , BMD at the femoral neck in the WBV group was increased by 4.3 % ( P = 0.011 ) compared to the Walking group . In contrast , the BMD at the lumbar spine was unaltered in both groups . Balance was improved in the WBV group ( 29 % ) but not in the Walking group . Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures : hip BMD and balance This study examines the effects of weight loss by caloric restriction ( WL ) and aerobic exercise plus weight loss ( AEx+WL ) on total and regional bone mineral density ( BMD ) in older women . Healthy , postmenopausal women [ age 63 + /- 1 ( SE ) yr ] not on hormone-replacement therapy underwent 6 mo of WL ( n = 15 ) consisting of dietary counseling one time per week with a caloric deficit ( 250 - 350 kcal/day ) or AEx+WL ( n = 15 ) consisting of treadmill exercise three times per week in addition to the weight loss . Maximal aerobic capacity increased only in the AEx+WL group ( P < 0 . 001 ) . Body weight , percent fat , and fat mass decreased similarly in both groups ( P < 0.005 ) , with no changes in fat-free mass . Total body BMD ( by dual-energy X-ray absorptiometry ) decreased in both groups ( P < 0.05 ) . Femoral neck , Ward 's triangle , and greater trochanter BMD decreased in the WL group ( P < /= 0.05 ) but were not significantly different after AEx+WL . L2-L4 BMD did not significantly change in either group . Thus WL and AEx+WL both result in losses of total body BMD ; however , AEx+WL appears to prevent the loss in regional BMD seen with WL alone in healthy , older women . This suggests that the addition of exercise to weight-loss programs may reduce the risk for bone loss Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility STUDY OBJECTIVE To assess the effect of weight-bearing exercise training and subsequent detraining on lumbar bone mineral content in postmenopausal women . DESIGN Non-r and omized , controlled , short-term ( 9 months ) trial and long-term ( 22 months ) exercise training and detraining ( 13 months ) . SETTING Section of applied physiology at a university school of medicine . PATIENTS Thirty-five healthy , sedentary postmenopausal women , 55 to 70 years old . All women completed the study . There was 90 % compliance with exercise training . INTERVENTIONS All women were given calcium , 1500 mg daily . The exercise group did weight-bearing exercise ( walking , jogging , stair climbing ) at 70 % to 90 % of maximal oxygen uptake capacity for 50 to 60 min , 3 times weekly . MEASUREMENTS AND MAIN RESULTS Bone mineral content increased 5.2 % ( 95 % confidence interval [ CI ] , 2.0 % to 8.4 % ; P = 0.0037 ) above baseline after short-term training whereas there was no change ( -1.4 % ) in the control group . After 22 months of exercise , bone mineral content was 6.1 % ( 95 % CI , 3.9 % to 8.3 % above baseline ; P = 0.0001 ) in the long-term training group . After 13 months of decreased activity , bone mass was 1.1 % above baseline in the detraining group . CONCLUSIONS Weight-bearing exercise led to significant increases above baseline in bone mineral content which were maintained with continued training in older , postmenopausal women . With reduced weight-bearing exercise , bone mass reverted to baseline levels . Further studies are needed to determine the threshold exercise prescription that will produce significant increases in bone mass Abstract . There is evidence that high intensity resistance training promotes bone maintenance in older women , however , the effect of high intensity free weight training has not been investigated in older men or women . Furthermore , little is known about the chronic effect of weight training on serum insulin growth factor-I ( IGF-I ) in this population . We compared the effects of a moderate intensity seated resistance-training program with a high intensity st and ing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women . Twenty-eight men ( 54.6 ± 3.2 years ) and 26 nonestrogen-replaced women ( 52.8 ± 3.3 years ) served as their own controls for 12 weeks , then were r and omly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks . Prior to and after the control period and at the end of training , bone mass and body composition were assessed by dual energy X-ray absorptiometry ( DXA ) , muscle strength by isokinetic dynamometry , muscular power by Wingate Anaerobic Power Test , and IGF-I by radioimmunoassay ( RIA ) . A repeated measures analysis of covariance ( ANCOVA ) revealed that high intensity training result ed in a gain in spine BMD in men ( 1.9 % ) , P < 0.05 , but not in women , whereas moderate intensity training produced no changes in either gender at this site . Increases were observed at the greater trochanter , P < 0.03 , in men regardless of training intensity , but not in women at any hip site . However , when compared with zero , both men and women in the high intensity group demonstrated significant increases in trochanteric BMD ( 1.3 % and 2.0 % , respectively ) and a decrease in femoral BMD ( −1.8 % ) . Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen , but both training programs result ed in improvements in total body strength ( 37.62 % ) and lean mass ( males 4.1 % , females 3.1 % ) . We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults , a higher magnitude is necessary to stimulate osteogenesis at the spine . However , at the spine , intensity was not sufficient to offset low levels of estrogen in early postmenopausal women . Furthermore , bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3 The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program ( RT+WLoss ) could maintain bone mineral density ( BMD ) and lean mass compared to moderate weight loss ( WLoss ) alone in older overweight adults with type 2 diabetes . We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program . This was a 12-month trial in which 36 sedentary , overweight adults aged 60 to 80 years with type 2 diabetes were r and omized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months ( phase 1 ) . Thereafter , all participants completed an additional 6-month home-based training without further dietary modification ( phase 2 ) . Total body and regional BMD and bone mineral content ( BMC ) , fat mass ( FM ) and lean mass ( LM ) were assessed by DXA every 6 months . Diet , muscle strength ( 1-RM ) and serum total testosterone , estradiol , SHBG , insulin and IGF-1 were measured every 3 months . No between group differences were detected for changes in any of the hormonal parameters at any measurement point . In phase 1 , after 6 months of gymnasium-based training , weight and FM decreased similarly in both groups ( P<0.01 ) , but LM tended to increase in the RT+WLoss ( n=16 ) relative to the WLoss ( n=13 ) group [ net difference ( 95 % CI ) , 1.8 % ( 0.2 , 3.5 ) , P<0.05 ] . Total body BMD and BMC remained unchanged in the RT+WLoss group , but decreased by 0.9 and 1.5 % , respectively , in the WLoss group ( interaction , P<0.05 ) . Similar , though non-significant , changes were detected at the femoral neck and lumbar spine ( L2-L4 ) . In phase 2 , after a further 6 months of home-based training , weight and FM increased significantly in both the RT+WLoss ( n=14 ) and WLoss ( n=12 ) group , but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months . These results indicate that in older , overweight adults with type 2 diabetes , dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health 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 and aims : Exercise may enhance the effect of alendronate on bone mineral density ( BMD ) and reduce chronic back pain in elderly women with osteoporosis . The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover , and reduce chronic back pain in post-menopausal women with osteoporosis . Methods : Fifty post-menopausal women with osteoporosis , 55–88 years of age , were r and omly divided into two groups of 25 patients each : one taking alendronate ( 5 mg daily , ALN ) and one taking alendronate plus exercise ( ALN+EX ) . Exercise consisted of whole-body vibration using a Galileo machine ( Novotec , Pforzheim , Germany ) , at an intensity of 20 Hz , frequency once a week , and duration of exercise 4 minutes . The study lasted 12 months . Lumbar BMD was measured by dual energy X-ray absorptiometry ( Hologic QDR 1500W ) . Urinary cross-linked N-terminal telopeptides of type I collagen ( NTX ) and serum alkaline phos-phatase ( ALP ) levels were measured by enzyme-linked immunosorbent assay and st and ard laboratory techniques , respectively . Chronic back pain was evaluated by face scale score at baseline and every 6 months . Results : There were no significant differences in baseline characteristics , including age , body mass index , years since menopause , lumbar BMD , urinary NTX and serum ALP levels , or face scale score between the two groups . The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups . However , the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group . Conclusions : The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain , probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate BACKGROUND Weight loss typically reduces bone mineral density ( BMD ) . Exercise may preserve or increase BMD even while reducing fatness . We examined the relationships among exercise-induced changes in fitness and fatness with BMD . DESIGN R and omized controlled trial conducted between July 1999 and November 2003 . PARTICIPANTS Men and women ( n = 115 ) aged 55 to 75 years . INTERVENTION Six months of exercise training . MAIN OUTCOME MEASURES Fitness measured as peak oxygen uptake and muscle strength , body composition by anthropometry , dual-energy x-ray absorptiometry , and magnetic resonance imaging . RESULTS A total of 51 men and 53 women completed the trial . Exercise increased aerobic and strength fitness and lean body mass , and reduced general and abdominal obesity . BMD did not change among men in either group . Among women exercisers , there were reductions in total skeleton BMD ( p = 0.02 ) and greater trochanter BMD ( p = 0.02 ) . By bivariate correlation , among women , increased femoral neck BMD was associated with increased aerobic fitness ( p = 0.01 ) and with reduced body weight ( p = 0.02 ) and BMI ( p = 0.02 ) . In the final regression model , 13 % of the change in femoral neck BMD was explained by the change in aerobic fitness ( p < 0.01 ) . Among the men , increased total hip BMD and femoral shaft BMD were associated with increased lean mass and lower-body strength . In the final regression models , the change in lean mass explained 9 % of the variance in total hip BMD ( p = 0.04 ) . The change in lean mass explained 20 % of the change in femoral shaft BMD ( p < 0.01 ) , and the change in lower-body strength explained an additional 6 % ( p < 0.04 ) . CONCLUSIONS When examined by group assignment , 6 months of exercise had no effect on BMD among men , and reduced BMD among women . When examined by change in fitness and fatness , women who had the greatest increases in aerobic capacity and men who had the greatest increases in strength and lean mass were more likely to increase their BMD . Exercise-induced reductions in fatness did not lead to bone loss Summary The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold ( AT ) . Thirty-three postmenopausal women were r and omized to control ( group C : n=12 ) or two exercise groups ( group H and group M ) . All women performed a treadmill exercise test , and the AT was measured by expired gas analysis . The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT ( group H : n=12 ) or below the AT ( group M : n=9 ) . Exercise was performed for 30 minutes , three times a week for 7 months . The bone mineral density ( BMD ) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry . The BMD level in group C decreased by 1.7±2.7 % , but there was a significant increase of 1.1±2.9 % in group H. In group M there was a decrease of 1.0±3.1 % which did not differ from group C. In group C , serum osteocalcin and urinary hydroxyproline excretion were significantly increased , but no changes were seen in either of the exercise groups . Urinary calcium significantly decreased in the exercise groups . We conclude that short-term ( 7 months ) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss Introduction Longitudinal studies on the age-related bone loss in men concerns the decrease in areal bone mineral density ( aBMD ) , which can be qualified as “ apparent bone loss ” because it does not reflect the change in bone mineral content ( BMC ) . Loss of BMC can be referred to as “ net bone loss ” because it does not take into account the morphological basis of the bone loss ( decreased periosteal apposition ; endosteal bone loss , i.e. bone loss on the trabecular , endocortical and intracortical surfaces ) . The aim of this study was to assess age-related apparent net and endosteal bone loss as well as their morphological basis and age-related changes during a prospect i ve follow-up in a large cohort of elderly men . Methods This analysis was performed in 725 men aged 51–85 at baseline who were followed up for 90 months . Results Bone densitometry was carried out at the lumbar spine , hip and whole body by using the HOLOGIC QDR1500 device and at the distal forearm by using the Osteometer DTX100 device . Sixty-five men who ab and oned the study after the first examination were older and had lower a BMC at most sites of measurement . Apparent bone loss was significant at the hip , distal forearm and whole body . Net bone loss was also significant at these sites , except for the femoral neck . Periosteal expansion was significant at all sites of measurement . Apparent and net bone loss accelerated with age , whereas the rate of periosteal expansion remained stable . At the distal radius and ulna , endosteal bone loss accelerated with age , whereas the rate of periosteal apposition remained stable . Conclusion In a large cohort of elderly men , age-related apparent bone loss ( aBMD ) at the hip , distal forearm and whole body was determined by the net bone loss ( BMC ) , except for the femoral neck . Apparent and net bone loss accelerated with age , whereas the periosteal expansion rate ( bone widening ) remained constant . At the distal forearm , age-related acceleration of the apparent bone loss was determined by the higher endosteal bone loss , whereas the periosteal apposition rate ( estimated mass of deposited bone ) remained constant BACKGROUND Physical exercise affects many risk factors and diseases and therefore can play a vital role in general disease prevention and treatment of elderly individuals and may reduce costs . We sought to determine whether a single exercise program affects fracture risk ( bone mineral density [ BMD ] and falls ) , coronary heart disease ( CHD ) risk factors , and health care costs in community-dwelling elderly women . METHODS We conducted a r and omized , single-blinded , controlled trial from May 1 , 2005 , through July 31 , 2008 , recruiting women 65 years or older who were living independently in the area of Erlangen-Nuremberg , Germany . In all , 246 women were r and omly assigned to an 18-month exercise program ( exercise group ) or a wellness program ( control group ) . The exercise group ( n = 123 ) performed a multi purpose exercise program with special emphasis on exercise intensity ; the controls ( n = 123 ) focused on well-being with a low-intensity , low-frequency program . The main outcome measures were BMD , the number of falls , the Framingham-based 10-year CHD risk , and direct health care costs . RESULTS For the 227 women who completed the 18-month study , significant exercise effects were observed for BMD of the lumbar spine ( mean [ 95 % confidence interval ( CI ) ] percentage of change in BMD [ baseline to follow-up ] for the exercise group : 1.77 % [ 1.26 % to 2.28 % ] vs controls : 0.33 % [ -0.24 % to 0.91 % ] ; P < .001 ) , femoral neck ( exercise group : 1.01 % [ 0.37 % to 1.65 % ] vs controls : -1.05 % [ -1.70 % to -0.40 % ] ; P < .001 ) , and fall rate per person during 18 months ( exercise group : 1.00 [ 0.76 to 1.24 ] vs controls : 1.66 [ 1.33 to 1.99 ] ; P = .002 ) . The 10-year CHD risk was significantly affected in both subgroups ( absolute change for the exercise group : -1.96 % [ 95 % CI , -2.69 % to -1.23 % ] vs controls : -1.15 % [ -1.69 % to -0.62 % ] ; P = .22 ) , with no significant difference between the groups . The direct health care costs per participant during the 18-month intervention showed nonsignificant differences between the groups ( exercise group : 2255 euros[95 % CI , 1791 euros-2718 euros ] vs controls : 2780 euros [ 2187 euros-3372 euros ] ; P = .20 ) . CONCLUSION Compared with a general wellness program , our 18-month exercise program significantly improved BMD and fall risk , but not predicted CHD risk , in elderly women . This benefit occurred at no increase in direct costs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00267839 OBJECTIVE to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture . DESIGN r and omized placebo-controlled trial . Assessment s of bone mineral density were made before and at 1 and 2 years after intervention . St and ardized and vali date d measures of physical capacity , self-rated health status and falls were used . SETTING district general hospital outpatient department . SUBJECTS 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years . Women were r and omly allocated to intervention ( self-paced brisk walking ) or placebo ( upper limb exercises ) groups . INTERVENTION both groups were seen at 3-monthly intervals to assess progress , measure physical capacity and maintain enthusiasm . The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them . The upper limb exercise placebo group were asked to carry out a series of exercises design ed to improve flexibility and fine h and movements , appropriate for a past history of upper limb fracture . RESULTS drop-outs from both intervention and placebo groups were substantial ( 41 % ) , although there were no significant differences in bone mineral density , physical capacity or health status between drop-outs and participants . At 2 years , among those completing the trial , bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [ mean net difference between intervention and placebo groups 0.019 g/cm2 , 95 % confidence interval ( CI ) -0.0026 to + 0.041 g/cm2 , P = 0.056 ] . Lumbar spine bone mineral density had increased to a similar extent ( + 0.017 g/cm2 ) in both groups . The cumulative risk of falls was higher in the brisk-walking group ( excess risk of 15 per 100 person-years , 95 % CI 1.4 - 29 per 100 person-years , P < 0.05 ) . There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups . CONCLUSION the promotion of exercise through brisk-walking advice given by nursing staff may have a small , but clinical ly important , impact on bone mineral density but is associated with an increased risk of falls . Self-paced brisk walking is difficult to evaluate in r and omized controlled trials because of drop-outs , placebo group exercise , limited compliance and lack of st and ardization of the duration and intensity of walking . Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups , such as older women and those at high risk of fractures Physical exercise is advised as a preventive and therapeutic strategy against aging-induced bone weakness . In this study we examined the effects of 8-month multicomponent training with weight-bearing exercises on different risk factors of falling , including muscle strength , balance , agility , and bone mineral density ( BMD ) in older women . Participants were r and omly assigned to either an exercise-training group ( ET , n = 30 ) or a control group ( CON , n = 30 ) . Twenty-seven subjects in the ET group and 22 in the CON group completed the study . Training was performed twice a week and was design ed to load bones with intermittent and multidirectional compressive forces and to improve physical function . Outcome measures included lumbar spine and proximal femoral BMD ( by dual X-ray absorptiometry ) , muscle strength , balance , h and grip strength , walking performance , fat mass , and anthropometric data . Potential confounding variables included dietary intake , accelerometer-based physical activity , and molecularly defined lactase nonpersistence . After 8 months , the ET group decreased percent fat mass and improved h and grip strength , postural sway , strength on knee flexion at 180 ° /s , and BMD at the femoral neck ( + 2.8 % ) . Both groups decreased waist circumference and improved dynamic balance , chair st and performance , strength on knee extension for the right leg at 180 ° /s , and knee flexion for both legs at 60 ° /s . No associations were found between lactase nonpersistence and BMD changes . Data suggest that 8 months of moderate-impact weight-bearing and multicomponent exercises reduces the potential risk factors for falls and related fractures in older women OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to < .001 ) . CONCLUSIONS High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women Summary A 1-year r and omized controlled trial of resistance training compared with a control group was undertaken in 143 men aged 55–80 years . Although hip bone mineral density , lean body mass , and function increased in both groups , lean body mass and function but not bone density increased more in the resistance group . Introduction Previous studies have demonstrated a positive effect of resistance training on bone mineral density ( BMD ) in postmenopausal women , but the effect in men is unclear . The aim was to examine the effect of a 1-year resistance training program on bone and lean body mass in 143 men aged 55–80 years , r and omized to either resistance training or active control . Methods Resistance exercises were selected to provide loading at the hips . Measurements were taken at 0 , 6 , and 12 months for BMD ( whole body , hip , and spine ) , lean body mass , strength , and functional fitness . Results The intervention showed a significant increase in total hip BMD for both groups at 12 months ( active control , 1,014–1,050 mg/cm2 ; resistance , 1,045–1,054 mg/cm2 , p < 0.05 ) with no increased effect of resistance training compared to active control . However , compared to the active control group , the resistance group increased their lean body mass ( active control , 0.1 ± 2.1 % ; resistance , 1.5 ± 2.7 % , p < 0.05 ) , fitness ( active control , 4.6 ± 11.1 % ; resistance , 13.0 ± 13.4 % , p < 0.05 ) , and lower limb muscle strength ( active control , 14.3 ± 16.8 % ; resistance , 39.4 ± 30.87 % , p < 0.05 ) . Conclusions In contrast to previous findings in older women , in older men , a resistance training program does not increase hip bone mass more than walking 30 min three times a week Summary We examined the independent and combined effects of a multi-component exercise program and calcium – vitamin-D3-fortified milk on bone mineral density ( BMD ) in older men . Exercise result ed in a 1.8 % net gain in femoral neck BMD , but additional calcium – vitamin D3 did not enhance the response in this group of older well-nourished men . Introduction This 12-month r and omised controlled trial assessed whether calcium – vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men . Methods Men ( n = 180 ) aged 50–79 years were r and omised into : ( 1 ) exercise + fortified milk ; ( 2 ) exercise ; ( 3 ) fortified milk ; or ( 4 ) controls . Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise . Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3 . Femoral neck ( FN ) , total hip , lumbar spine and trochanter BMD and body composition ( DXA ) , muscle strength 25-hydroxyvitamin D and parathyroid hormone ( PTH ) were assessed . Results There were no exercise-by-fortified milk interactions at any skeletal site . Exercise result ed in a 1.8 % net gain in FN BMD relative to no-exercise ( p < 0.001 ) ; lean mass ( 0.6 kg , p < 0.05 ) and muscle strength ( 20–52 % , p < 0.001 ) also increased in response to exercise . For lumbar spine BMD , there was a net 1.4–1.5 % increase in all treatment groups relative to controls ( all p < 0.01 ) . There were no main effects of fortified milk at any skeletal site . Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men , but additional calcium – vitamin D3 did not enhance the osteogenic response Abstract . Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women . The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density ( BMD ) in osteopenic postmenopausal women . Forty-three postmenopausal women aged 48–65 years participated in this study . The BMD of the spine ( L2–L4 ) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women , as examined by dual X-ray absorptiometry . The assignment of subjects into exercise or control group was not r and omized but based on each subject 's anticipated compliance to the 6-month long exercise program . Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group . Exercise programs included treadmill walking at an intensity above 70 % of maximal oxygen consumption ( VO2max ) for 30 minutes , followed by 10 minutes of stepping exercise using a 20-cm-high bench . The program was conducted three times per week for 24 weeks . Physical fitness measurements included testing of flexibility , muscular strength and endurance , body composition , and cardiopulmonary fitness . The results showed that the quadriceps strength , muscular endurance , and VO2max in the exercise group had significant improvements , whereas no improvement was found in any of the physical fitness parameters in the control group . The BMD of the L2–L4 and the femoral neck in the exercise group increased 2.0 % ( P > 0.05 ) and 6.8 % ( P < 0.05 ) and those in the control group decreased 2.3 % ( P < 0.05 ) and 1.5 % ( P > 0.05 ) , respectively . In conclusion , aerobics combined with high-impact exercise at a moderate intensity was effective in off setting the decline in BMD in osteopenic postmenopausal women UNLABELLED High-frequency mechanical strain seems to stimulate bone strength in animals . In this r and omized controlled trial , hip BMD was measured in postmenopausal women after a 24-week whole body vibration ( WBV ) training program . Vibration training significantly increased BMD of the hip . These findings suggest that WBV training might be useful in the prevention of osteoporosis . INTRODUCTION High-frequency mechanical strain has been shown to stimulate bone strength in different animal models . However , the effects of vibration exercise on the human skeleton have rarely been studied . Particularly in postmenopausal women-who are most at risk of developing osteoporosis-r and omized controlled data on the safety and efficacy of vibration loading are lacking . The aim of this r and omized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration ( WBV ) in postmenopausal women . MATERIAL S AND METHODS Seventy volunteers ( age , 58 - 74 years ) were r and omly assigned to a whole body vibration training group ( WBV , n = 25 ) , a resistance training group ( RES , n = 22 ) , or a control group ( CON , n = 23 ) . The WBV group and the RES group trained three times weekly for 24 weeks . The WBV group performed static and dynamic knee-extensor exercises on a vibration platform ( 35 - 40 Hz , 2.28 - 5.09 g ) , which mechanically loaded the bone and evoked reflexive muscle contractions . The RES group trained knee extensors by dynamic leg press and leg extension exercises , increasing from low ( 20 RM ) to high ( 8 RM ) resistance . The CON group did not participate in any training . Hip bone density was measured using DXA at baseline and after the 6-month intervention . Isometric and dynamic strength were measured by means of a motor-driven dynamometer . Data were analyzed by means of repeated measures ANOVA . RESULTS No vibration-related side effects were observed . Vibration training improved isometric and dynamic muscle strength ( + 15 % and + 16 % , respectively ; p < 0.01 ) and also significantly increased BMD of the hip ( + 0.93 % , p < 0.05 ) . No changes in hip BMD were observed in women participating in resistance training or age-matched controls ( -0.60 % and -0.62 % , respectively ; not significant ) . Serum markers of bone turnover did not change in any of the groups . CONCLUSION These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies OBJECTIVES To determine whether exercise training added to ongoing hormone replacement therapy ( HRT ) increases bone mineral density ( BMD ) in physically frail elderly women . DESIGN Prospect i ve controlled trial . SETTING University-based research center . PARTICIPANTS Twenty-eight women on HRT , aged 75 and older with physical frailty . INTERVENTIONS Participants were assigned to 9 months of supervised ( EXER ) or home ( HOME ) exercise . The EXER program started with physical therapy and gradually incorporated resistance and endurance training . The HOME program consisted of flexibility exercises . MEASUREMENTS Changes in BMD and body composition . RESULTS There were larger increases in lumbar spine BMD in response to EXER than with HOME ( 3.5 % vs 1.5 % , P = .048 ) , with a trend for larger increases in total body BMD ( 1.5 % vs 0.2 % , P = .058 ) . There were no significant between-group differences in hip BMD . The EXER group had decreases in weight ( -2.2 + /- 0.3 kg , P = .010 ) and fat mass ( -2.7 + /- 0.4 kg , P = .018 ) and increases in muscle strength ( 9 - 30 % , P < .05 ) . CONCLUSION In physically frail elderly women on HRT , relatively vigorous exercise training significantly increased lumbar spine BMD . The improved BMD and strength in response to exercise could reduce fracture risk in frail women already on HRT Sarcopenia and osteoporosis represent a growing public health problem . We studied the potential benefit of whole-body vibration ( WBV ) training given a conventional or a high dose of daily vitamin D supplementation in improving strength , muscle mass , and bone density in postmenopausal women . In a 2 × 2 factorial- design trial , 113 institutionalized elderly females aged over 70 years ( mean age 79.6 years ) were r and omly assigned either to a WBV or a no-training group , receiving either a conventional dose ( 880 IU/day ) or a high dose ( 1600 IU/day ) of vitamin D(3 ) . The primary aim was to determine the effects of 6 months of WBV and /or vitamin D supplementation on isometric and dynamic strength , leg muscle mass , and hip bone mineral density ( BMD ) . Additionally , the increase in 25-hydroxyvitamin D [ 25(OH)D ] levels between conventional and high-dose supplementation was compared . After 6 months of treatment , dynamic muscle strength , hip BMD , and vitamin D serum levels improved significantly in all groups , whereas isometric strength and muscle mass did not change . When compared with no training , the WBV program did not result in additional improvements . When compared with 880 IU , a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements . In institutionalized women older than 70 years , the WBV training protocol tested is not more efficient in enhancing muscle mass , strength , and hip BMD compared with vitamin D supplementation . A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses Increased inflammation and weight loss are associated with a reduction in bone mineral density ( BMD ) . Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines . We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers , thus mediating changes in BMD . This was a nonr and omized controlled trial . Eighty-six overweight and obese postmenopausal women ( 50–70 years of age ; BMI , 25–40 kg/m2 ) participated in a weight loss ( WL ; n = 40 ) or weight loss plus walking ( WL + AEX ; n = 46 ) program . Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry , interleukin-6 , tumor necrosis factor-α , soluble receptors of IL-6 , and TNF-α ( sTNFR1 and sTNFR2 ; receptors in a subset of the population ) , VO2 max , fat mass , and lean mass . Weight decreased in the WL ( p < 0.001 ) and WL + AEX ( p < 0.001 ) groups . VO2 max increased ( p < 0.001 ) after WL + AEX . There was a 2 % increase in femoral neck BMD in the WL + AEX group ( p = 0.001 ) , which was significantly different from the WL group . The change in sTNFR1 was significantly associated with the change in femoral neck BMD ( p < 0.05 ) . The change in VO2 max was an independent predictor of the change in femoral neck BMD . Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women , and no population -based , long-term interventions have been performed . The purpose of this population -based , r and omized , controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density ( BMD ) at the radius and hip . Participants ( n = 160 ) were r and omly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention . The primary outcome measures were femoral neck , trochanter and total hip BMD , and the secondary outcomes were bone density measures at the radius and calcaneum . Outcomes were assessed at baseline , 12 months and 30 months using blinded operators . The analyses were performed on an intention-to-treat analysis . Mean femoral neck and trochanter BMD decreased in the control group [ −1.1 % , 95 % confidence interval ( CI ) −0.1 % to −2.1 % and −1.6 % , 95 % CI −0.4 % to −2.7 % ] , while no change occurred in the exercise group . Mean trochanter BMC decreased more in the control group ( −7.7 % , 95 % CI −9.7 % to −5.6 % vs. −2.9 % , 95 % CI −5.3 to −0.9 ) . There were six falls that result ed in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P = 0.019 ) . A significant bone loss occurred in both groups at the radius and calcaneum . In multivariate analysis , weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups . In conclusion , impact exercise had no effect on BMD , while there was a positive effect on BMC at the trochanter . Exercise may prevent fall-related fractures in elderly women with low bone mass OBJECTIVES To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults . DESIGN R and omized controlled trial with subjects assigned to either an aerobic exercise condition , non-aerobic yoga , or a wait list non-exercise control group for 4 months . Aerobic fitness and bone density were evaluated in all subjects at baseline ( Time 1 ) and after 4 months ( Time 2 ) . A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise , followed by another evaluation ( Time 3 ) . All subjects were then given the option of 6 additional months of aerobic exercise , after which they had a fourth evaluation ( Time 4 ) . SETTING An outpatient exercise rehabilitation facility at a large , major medical center . SUBJECTS One-hundred-one healthy men ( n = 50 ) and women ( n = 51 ) over age 60 ( Mean age = 67.0 ) , recruited from the community . INTERVENTION The exercise program included stretching , cycle ergometry , and walking three times per week for 60 minutes throughout the course of the study . OUTCOME MEASURES Aerobic fitness ( VO2max ) as assessed by cycle ergometry , and bone density ( bone mineral content ) measured by single photon absorptiometry . RESULTS Subjects achieved a 10%-15 % increase in VO2max after 4 months of exercise training , and 1%-6 % further improvement with additional training . Aerobic fitness was associated with significant increases in bone density in men , but not women , who maintained aerobic exercise for 14 months The effects of a vertical jumping exercise regime on bone mineral density ( BMD ) have been assessed using r and omized controlled trials in both pre- and postmenopausal women , the latter stratified for hormone replacement therapy ( HRT ) . Women were screened for contraindications or medication likely to influence bone . The premenopausal women were at least 12 months postpartum and not lactating ; the postmenopausal women had been stable on , or off , HRT for the previous 12 months and throughout the study . BMD was measured blind using dual-energy X-ray absorptiometry at the spine ( L2-L4 ) and the proximal femur . The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm , which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women . In the premenopausal women , the exercise result ed in a significant increase of 2.8 % in femoral BMD after 5 months ( p < 0.001 , n = 31 ) . This change was significantly greater ( p < 0.05 ) than that found in the control group ( n = 26 ) . In the postmenopausal women , there was no significant difference between the exercise and control groups after 12 months ( total n = 123 ) nor after 18 months ( total n = 38 ) . HRT status did not affect this outcome , at least up to 12 months . It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not Objective : The study was design ed to evaluate the effects of strength training ( ST ) on the bone mineral density ( BMD ) of postmenopausal women without hormone replacement therapy . Method : Subjects were r and omized into untrained ( UN ) or trained ( TR ) groups . The TR group exercised three ST sessions per week for 24 weeks , and body composition , muscular strength , and BMD of the lumbar spine and femur neck were evaluated . Results : Body weight , mass index , and fat percentage were lower after 24 weeks only in the TR group ( p < .05 ) . SR also improved the one repetition maximum test in 46 % and 39 % of upper and lower limbs , respectively . The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck ( p < .05 ) . Discussion : Results indicated that 24 weeks of ST improved body composition parameters , increased muscular strength , and preserved BMD in postmenopausal women OBJECTIVES This study determined the effect of enriched foods and all-around physical exercise on bone and body composition in frail elderly persons . METHODS A 17-week r and omized , controlled intervention trial , following a 2 x 2 factorial design --(1 ) enriched foods , ( 2 ) exercise , ( 3 ) both , or ( 4 ) neither -- was performed in 143 frail elderly persons ( aged 78.6 + /- 5.6 years ) . Foods were enriched with multiple micronutrients ; exercises focused on skill training , including strength , endurance , coordination , and flexibility . Main outcome parameters were bone and body composition . RESULTS Exercise preserved lean mass ( mean difference between exercisers and non-exercisers : 0.5 kg + /- 1.2 kg ; P < .02 ) . Groups receiving enriched food had slightly increased bone mineral density ( + 0.4 % ) , bone mass ( + 0.6 % ) , and bone calcium ( + 0.6 % ) compared with groups receiving non-enriched foods , in whom small decreases of 0.1 % , 0.2 % , and 0.4 % , respectively , were found . These groups differed in bone mineral density ( 0.006 + /- 0.020 g/cm2 ; P = .08 ) , total bone mass ( 19 + /- g ; P = .04 ) , and bone calcium ( 8 + /- 21 g ; P = .03 ) . CONCLUSIONS Foods containing a physiologic dose of micronutrients slightly increased bone density , mass , and calcium , whereas moderately intense exercise preserved lean body mass in frail elderly persons A r and omized , controlled , single-blinded 25-wk prospect i ve study was conducted to compare the effects of group-based resistance and agility training on bone , as measured by both dual-energy X-ray absorptiometry ( DXA ) and peripheral quantitative computed tomography ( pQCT ) , in older women with low bone mass . Ninety-eight community-dwelling women aged 75 - 85 yr were r and omized to one of three experimental groups : resistance training ( n = 32 ) , agility training ( n = 34 ) , or stretching ( sham exercise ) ( n = 32 ) . Total hip , femoral neck , and trochanteric bone mineral density ( BMD ) were measured by DXA . Peripheral QCT measurements were performed at the tibia and radius . The pQCT outcome measures at the shaft regions were cortical bone content , cortical bone cross-sectional area , cortical bone density , and density-weighted polar section modulus ( SSI ) . The pQCT outcome measures at the distal sites were total bone content , total bone cross-sectional area , and total bone density . At trial completion , the agility training group significantly increased cortical bone density by 0.5 + /- 0.2 % ( SE ) at the tibial shaft compared with a 0.4 + /- 0.3 % loss in the stretching group . The resistance training group significantly increased cortical bone density ( 1.4 + /- 0.6 % ) at the radial shaft compared , with a 0.4 + /- 0.5 % loss in the agility training group . No significant between-group differences were observed in the other bone outcome measures ( by DXA or pQCT ) . Future research is needed to determine the mechanism(s ) responsible for the observed adaptation of the cortical bone to mechanical loading 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 UNLABELLED Age-related changes in body composition are well-documented with a decrease in lean body mass and a redistribution of body fat generally observed . Resistance training alone has been shown to have positive effects on body composition , however , these benefits may be enhanced by the addition of a vibration stimulus . OBJECTIVE The purpose of this study was to determine the effects of 8 months of resistance training with and without whole-body vibration ( WBV ) on body composition in sedentary postmenopausal women . METHODS Fifty-five women were assigned to resistance only ( RG , n=22 ) , vibration plus resistance ( VR , n=21 ) or non-exercising control ( CG , n=12 ) groups . Resistance training ( 3 sets 10 repetitions 80 % strength ) was performed using isotonic weight training equipment and whole-body vibration was done with the use of the power plate ( Northbrooke , IL ) vibration platform for three times per week for 8 months . Total and regional body composition was assessed from the total body DXA scans at baseline ( pre ) and after 8 months ( post ) of training . RESULTS In the VR group , total % body fat decreased from pre- to post-time points ( p<0.05 ) , whereas , the CG group had a significant increase in total % body fat ( p<0.05 ) . Both training groups exhibited significant increases in bone free lean tissue mass for the total body , arm and trunk regions from pre to post ( p<0.05 ) . CG did not show any changes in lean tissue . CONCLUSION In older women , resistance training alone and with whole-body vibration result ed in positive body composition changes by increasing lean tissue . However , only the combination of resistance training and whole-body vibration was effective for decreasing percent body fat Summary We determined whether the effect of exercise on bone mineral density ( BMD ) and falls can be enhanced by whole body vibration ( WBV ) . In summary , the multi- purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect . However , falls were lowest in the exercise program combined with WBV . Introduction WBV is a new approach to reduce the risk of osteoporotic fractures . In the “ Erlangen Longitudinal Vibration Study ” ( ELVIS ) , we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls . Methods One hundred fifty-one postmenopausal women ( 68.5 ± 3.1 years ) were r and omly assigned to a : ( 1 ) conventional training group ( TG ) ; ( 2 ) conventional training group including vibration ( TGV ) ; and ( 3 ) wellness control group ( CG ) . TG conducted an exercise program consisting of 20 min dancing aerobics , 5 min balance training , 20 min functional gymnastics , and 15 min dynamic leg-strength training on vibration plates ( without vibration ) twice a week . TGV performed an identical exercise regimen with vibration ( 25–35 Hz ) during the leg-strengthening sequence . CG performed a low-intensity wellness program . BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method . Falls were recorded daily via the calendar method . Results After 18 months , an increase in BMD at the lumbar spine was observed in both training groups ( TGV : + 1.5 % vs. TG : + 2.1 % ) . The difference between the TG and the CG ( 1.7 % ) was significant . At the hip no changes were determined in either group . The fall frequency was significantly lower in TGV ( 0.7 falls/person ) compared with CG ( 1.5 ) , whereas the difference between TG ( 0.96 ) and CG was not significant . Conclusions A multifunctional training program had a positive impact on lumbar BMD . The application of vibration did not enhance these effects . However , only the training including WBV affected the number of falls significantly Given the negative effects of a breast cancer diagnosis and its treatments on body weight and bone mass , we investigated the effects of a 6-month r and omized controlled aerobic exercise intervention vs. usual care on body composition in breast cancer survivors . Secondary aims were to examine the effects stratified by important prognostic and physiologic variables . Seventy-five physically inactive postmenopausal breast cancer survivors were recruited through the Yale-New Haven Hospital Tumor Registry and r and omly assigned to an exercise ( n = 37 ) or usual care ( n = 38 ) group . The exercise group participated in 150 min/week of supervised gym- and home-based moderate-intensity aerobic exercise . The usual care group was instructed to maintain their current physical activity level . Body composition was assessed at baseline and 6-months through dual-energy X-ray absorptiometry ( DXA ) by one radiologist blinded to the intervention group of the participants . On an average , exercisers increased moderate-intensity aerobic exercise by 129 min/week over and above baseline levels compared with 45 min/week among usual care participants ( P < 0.001 ) . Exercisers experienced decreases in percent body fat ( P = 0.0022 ) and increases in lean mass ( P = 0.047 ) compared with increases in body fat and decreases in lean mass in usual care participants . Bone mineral density ( BMD ) was also maintained among exercisers compared with a loss among usual care participants ( P = 0.043 ) . In summary , moderate-intensity aerobic exercise , such as brisk walking , produces favorable changes in body composition that may improve breast cancer prognosis Underst and ing the stress/strain relationship between exercise and bone is critical to underst and ing the potential benefit of exercise in preventing postmenopausal bone loss . This study examined the effect of a 2-year exercise intervention and calcium supplementation ( 600 mg ) on bone mineral density ( BMD ) in 126 postmenopausal women ( mean age , 60 + /- 5 years ) . Assignment was by block r and omization to one of three groups : strength ( S ) , fitness ( F ) , or nonexercise control ( C ) . The two exercise groups completed three sets of the same nine exercises , three times a week . The S group increased the loading , while the F group had additional stationary bicycle riding with minimal increase in loading . Retention at 2 years was 71 % ( 59 % in the S group , 69 % in the F group , and 83 % in the C group ) , while the exercise compliance did not differ between the exercise groups ( S group , 74 + /- 13 % ; F group , 77 + /- 14 % ) . BMD was measured at the hip , lumbar spine , and forearm sites every 6 months using a Hologic 4500 . Whole body BMD also was measured every 6 months on a Hologic 2000 . There was no difference between the groups at the forearm , lumbar spine , or whole body sites . There was a significant effect of the strength program at the total ( 0.9 + /- 2.6 % ; p < 0.05 ) and intertrochanter hip site ( 1.1 + /- 3.0 % ; p < 0.01 ) . There was a significant time and group interaction ( p < 0.05 ) at the intertrochanter site by repeated measures . This study shows the effectiveness of a progressive strength program in increasing bone density at the clinical ly important hip site . We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies It is considered that skeletal mass in humans may respond to loading or the number of loading cycles . The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women . Assignment was by block r and omization to one of two resistance training groups : a strength trained group ( 3 x 8 repetition maximum ) or an endurance group ( 3 x 20 repetition maximum ) . The resistance exercises were selected to stress the ipsilateral forearm and hip region . The exercising side was r and omly assigned with one side exercised while the alternate side acted as the nonexercise control . Bone mineral density ( BMD ) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer . A linear regression function was fitted for each individual 's bone density results , and the slope was compared for the exercise and control side using paired t-tests . The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site ( control -0.6 + /- 2.2 % , exercise 1.7 + /- 4.1 % , p < 0.01 ) , at the intertrochanteric hip site ( control -0.1 + /- 2.1 % , exercise 1.5 + /- 3.0 % , p < 0.05 ) , Ward 's triangle ( control 0.8 + /- 5.2 % , exercise 2.3 + /- 4.0 % , p < 0.05 ) , and at the ultradistal radial site ( control -1.4 + /- 2.3 % , exercise 2.4 + /- 4.3 % , p < 0.01 ) . There was no significant increase in BMD with the endurance regimen except at the radius midsite ( control -1.0 + /- 2.3 % , exercise 0.1 + /- 1.4 % , p < 0.01 ) . In both the endurance and the strength group , muscle strength , tested by a one-repetition maximum ( 1RM ) test , increased significantly for all 10 exercises ( p < 0.01 ) and to a similar degree in the two groups . In the strength group but not the endurance group there were significant correlations between the slope of the change in BMD and the percentage increase in strength as follows : trochanter with leg press ; intertrochanter with leg press ( p < 0.05 ) ; and Ward 's triangle with hip extension and hip adduction ( p < 0.05 ) . Thus these results support the notion of a site-specific response of bone to maximal loading from resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken , there was no effect on the femoral neck value . Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions . We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women UNLABELLED A 1-year prospect i ve , r and omized , double-blind , and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods ( < 20 minutes ) of a low-level ( 0.2 g , 30 Hz ) vibration applied during quiet st and ing can effectively inhibit bone loss in the spine and femur , with efficacy increasing significantly with greater compliance , particularly in those subjects with lower body mass . INTRODUCTION Indicative of the anabolic potential of mechanical stimuli , animal models have demonstrated that short periods ( < 30 minutes ) of low-magnitude vibration ( < 0.3 g ) , applied at a relatively high frequency ( 20 - 90 Hz ) , will increase the number and width of trabeculae , as well as enhance stiffness and strength of cancellous bone . Here , a 1-year prospect i ve , r and omized , double-blind , and placebo-controlled clinical trial in 70 women , 3 - 8 years past the menopause , examined the ability of such high-frequency , low-magnitude mechanical signals to inhibit bone loss in the human . MATERIAL S AND METHODS Each day , one-half of the subjects were exposed to short- duration ( two 10-minute treatments/day ) , low-magnitude ( 2.0 m/s2 peak to peak ) , 30-Hz vertical accelerations ( vibration ) , whereas the other half stood for the same duration on placebo devices . DXA was used to measure BMD at the spine , hip , and distal radius at baseline , and 3 , 6 , and 12 months . Fifty-six women completed the 1-year treatment . RESULTS AND CONCLUSIONS The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group . Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention , particularly at the lumbar spine ( p = 0.004 ) . Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality . Evaluating those in the highest quartile of compliance ( 86 % compliant ) , placebo subjects lost 2.13 % in the femoral neck over 1 year , whereas treatment was associated with a gain of 0.04 % , reflecting a 2.17 % relative benefit of treatment ( p = 0.06 ) . In the spine , the 1.6 % decrease observed over 1 year in the placebo group was reduced to a 0.10 % loss in the active group , indicating a 1.5 % relative benefit of treatment ( p = 0.09 ) . Considering the interdependence of weight , the spine of lighter women ( < 65 kg ) , who were in the highest quartile of compliance , exhibited a relative benefit of active treatment of 3.35 % greater BMD over 1 year ( p = 0.009 ) ; for the mean compliance group , a 2.73 % relative benefit in BMD was found ( p = 0.02 ) . These preliminary results indicate the potential for a noninvasive , mechanically mediated intervention for osteoporosis . This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause , perhaps most effectively in the spine of lighter women who are in the greatest need of intervention The effects of a supervised 1-y walking program and increased dietary calcium ( milk supplement , 831 mg/d , vs placebo drink , 41 mg/d ) on bones were examined in 36 postmenopausal women ( 60.2 + /- 6.5 y ) . Trabecular bone-mineral density ( BMD ) of the lumbar spine ( L1-L3 ) , measured by computed tomography , increased by 0.5 % in exercising women ( n = 18 ) and decreased by 7.0 % in sedentary women ( n = 18 ; P = 0.02 ) . Femoral-neck BMD measured by dual-photon absorptiometry ( DPA ) increased by 2.0 % in women consuming high dietary calcium ( n = 18 ) and decreased by 1.1 % in those on moderate calcium intake ( n = 18 ; P = 0.001 ) . Neither exercise nor dietary calcium had an effect on lumbar spine ( L2-L4 ) measured by DPA , distal radius measured by single-photon absorptiometry , or total body calcium measured by in vivo neutron activation . The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial . Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry . We studied 250 postmenopausal women , aged 52 - 72 years , willing to participate in a 6-month exercise program . The first 125 started the program immediately and the remaining 125 served as controls . The training program included exercises design ed to maximize the stress on the wrist . One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later . Bone mineral density ( BMD ) of the femoral neck , lumbar spine , ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry ( DXA ) both before and at the end of the exercise program . The forearm was also evaluated by peripheral quantitative computed tomography , which measures the area , bone mineral content ( BMC ) , and volumetric density for both the cortical and the trabecular component . The results showed that the DXA measurements at the femoral neck , lumbar spine , ultradistal and proximal radius were similar between the two groups . No significant difference was detected after the exercise program at the proximal radius . At the ultradistal radius , the cross-sectional area of cortical bone rose by 2.8 + /- 15.0 % ( SD , p < 0.05 ) , apparently for both periosteal apposition and corticalization of the trabecular tissue . The volumetric density of cortical bone rose by 2 . 2 + /- 15.8 % ( p < 0.1 ) , and that of trabecular bone decreased by 2.6 + /- 10.7 % ( p < 0.01 ) . The combined changes in both bone volume and density in the exercise group were associated with marked increase in cortical BMC ( 3.1 + /- 10.7 % , p < 0.01 ) and decrease in trabecular BMC ( -3.4 + /- 14.2 % , p < 0.05 ) , which were statistically different from those observed in the control group ( p < 0.05 ) . In conclusion , these results confirm that site-specific moderate physical exercises have very little effect on bone mass . However , it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component . These structural changes are theoretically associated with increases in the bending strength Abstract We examined the effect of exercise training and detraining on bone mineral density ( BMD ) in postmenopausal women with osteoporosis . Thirty-five postmenopausal women with osteoporosis , aged 53–77 years , were r and omly assigned to three groups : a control group ( n = 20 ) , a 2-year exercise training group ( n = 8) , and an 1-year exercise training plus 1-year detraining group ( n = 7 ) . Exercise training consisted of daily brisk walking and gymnastic training . Calcium lactate , 2.0 g , and 1α-hydroxyvitamin D3 , 1 μg were supplied daily to all subjects . No significant differences in initial lumbar BMD , measured by dual-energy X-ray absorptiometry ( DXA ) were found among the three groups . The mean percent change in BMD compared with the baseline was significantly higher at 1 and 2 years in the exercise training group and at 1 year in the detraining group than in the control group , and did not differ significantly at 2 years between the detraining and control groups . These findings indicate that our exercise training program led to a significant increase in lumbar BMD in postmenopausal women with osteoporosis compared with the control , but that the BMD reverted toward a level that was not significantly different from the control with detraining . Continued exercise training is needed to maintain the bone mass gained through exercise training |
13,098 | 29,297,029 | An EpiPen Jr kept 4 years after expiration would probably not deliver an adequate dose to a child on the upper end of the indicated weight range | TO THE EDITOR : Cantrell and colleagues ' ( 1 ) brief research report discussing the degradation of epinephrine in EpiPens and EpiPen Jrs ( Mylan ) is welcome information .
However , we have concerns about the remaining concentrations of epinephrine in EpiPen Jrs that they have listed .
Parish and associates ' systematic review of epinephrine degradation discusses the findings of 1 study in which lower concentrations of epinephrine de grade more quickly than higher concentrations ( 2 ) .
If we apply this information to Cantrell and colleagues ' report , the epinephrine in EpiPen Jrs may de grade more quickly than that in adult EpiPens . | Background and Purpose — Retrospective studies have found that patients receiving general anesthesia for endovascular treatment in acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation . In this prospect i ve r and omized single-center study , we investigated the impact of anesthesia technique on neurological outcome in acute ischemic stroke patients . Methods — Ninety patients receiving endovascular treatment for acute ischemic stroke in 2013 to 2016 were included and r and omized to general anesthesia or conscious sedation . Difference in neurological outcome at 3 months , measured as modified Rankin Scale score , was analyzed ( primary outcome ) and early neurological improvement of National Institutes of Health Stroke Scale and cerebral infa rct ion volume . Age , sex , comorbidities , admission National Institutes of Health Stroke Scale score , intraprocedural blood pressure , blood glucose , Paco2 and Pco2 modified Thrombolysis in Cerebral Ischemia score , and relevant time intervals were recorded . Results — In the general anesthesia group 19 of 45 patients ( 42.2 % ) and in the conscious sedation group 18 of 45 patients ( 40.0 % ) achieved a modified Rankin Scale score ⩽2 ( P=1.00 ) at 3 months , with no differences in intraoperative blood pressure decline from baseline ( P=0.57 ) ; blood glucose ( P=0.94 ) ; PaCO2 ( P=0.68 ) ; time intervals ( P=0.78 ) ; degree of successful recanalization , 91.1 % versus 88.9 % ( P=1.00 ) ; National Institutes of Health Stroke Scale score at 24 hours 8 ( 3–5 ) versus 9 ( 2–15 ; P=0.60 ) ; infa rct ion volume , 20 ( 10–100 ) versus 20(10–54 ) mL ( P=0.53 ) ; and hospital mortality ( 13.3 % in both groups ; P=1.00 ) . Conclusions — In endovascular treatment for acute ischemic stroke , no difference was found between general anesthesia and conscious sedation in neurological outcome 3 months after stroke . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01872884 Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from r and omized trials . Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy . Design , Setting , and Participants SIESTA ( Sedation vs Intubation for Endovascular Stroke Treatment ) , a single-center , r and omized , parallel-group , open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany ( April 2014-February 2016 ) included 150 patients with acute ischemic stroke in the anterior circulation , higher National Institutes of Health Stroke Scale ( NIHSS ) score ( > 10 ) , and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery . Intervention Patients were r and omly assigned to an intubated general anesthesia group ( n = 73 ) or a nonintubated conscious sedation group ( n = 77 ) during stroke thrombectomy . Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours ( 0 - 42 [ none to most severe neurological deficits ; a 4-point difference considered clinical ly relevant ] ) . Secondary outcomes were functional outcome by modified Rankin Scale ( mRS ) after 3 months ( 0 - 6 [ symptom free to dead ] ) , mortality , and peri-interventional parameters of feasibility and safety . Results Among 150 patients ( 60 women [ 40 % ] ; mean age , 71.5 years ; median NIHSS score , 17 ) , primary outcome was not significantly different between the general anesthesia group ( mean NIHSS score , 16.8 at admission vs 13.6 after 24 hours ; difference , -3.2 points [ 95 % CI , -5.6 to -0.8 ] ) vs the conscious sedation group ( mean NIHSS score , 17.2 at admission vs 13.6 after 24 hour ; difference , -3.6 points [ 95 % CI , -5.5 to -1.7 ] ) ; mean difference between groups , -0.4 ( 95 % CI , -3.4 to 2.7 ; P = .82 ) . Of 47 prespecified secondary outcomes analyzed , 41 showed no significant differences . In the general anesthesia vs the conscious sedation group , substantial patient movement was less frequent ( 0 % vs 9.1 % ; difference , 9.1 % ; P = .008 ) , but postinterventional complications were more frequent for hypothermia ( 32.9 % vs 9.1 % ; P < .001 ) , delayed extubation ( 49.3 % vs 6.5 % ; P < .001 ) , and pneumonia ( 13.7 % vs 3.9 % ; P = .03 ) . More patients were functionally independent ( unadjusted mRS score , 0 to 2 after 3 months [ 37.0 % in the general anesthesia group vs 18.2 % in the conscious sedation group P = .01 ] ) . There were no differences in mortality at 3 months ( 24.7 % in both groups ) . Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy , conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours . The study findings do not support an advantage for the use of conscious sedation . Trial Registration clinical trials.gov Identifier : NCT02126085 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 BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion , intraarterial treatment is highly effective for emergency revascularization . However , proof of a beneficial effect on functional outcome is lacking . METHODS We r and omly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone . Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset . The primary outcome was the modified Rankin scale score at 90 days ; this categorical scale measures functional outcome , with scores ranging from 0 ( no symptoms ) to 6 ( death ) . The treatment effect was estimated with ordinal logistic regression as a common odds ratio , adjusted for prespecified prognostic factors . The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores , as compared with usual care alone ( shift analysis ) . RESULTS We enrolled 500 patients at 16 medical centers in The Netherl and s ( 233 assigned to intraarterial treatment and 267 to usual care alone ) . The mean age was 65 years ( range , 23 to 96 ) , and 445 patients ( 89.0 % ) were treated with intravenous alteplase before r and omization . Retrievable stents were used in 190 of the 233 patients ( 81.5 % ) assigned to intraarterial treatment . The adjusted common odds ratio was 1.67 ( 95 % confidence interval [ CI ] , 1.21 to 2.30 ) . There was an absolute difference of 13.5 percentage points ( 95 % CI , 5.9 to 21.2 ) in the rate of functional independence ( modified Rankin score , 0 to 2 ) in favor of the intervention ( 32.6 % vs. 19.1 % ) . There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation , intraarterial treatment administered within 6 hours after stroke onset was effective and safe . ( Funded by the Dutch Heart Foundation and others ; MR CLEAN Netherl and s Trial Registry number , NTR1804 , and Current Controlled Trials number , IS RCT N10888758 . ) BACKGROUND EpiPen and EpiPen Jr autoinjectors are often recommended for prehospital treatment of anaphylaxis . When these units become out date d , there may be a delay in replacing them . OBJECTIVES Our purpose was to evaluate unused , out date d EpiPen and EpiPen Jr autoinjectors , obtained from patients at risk for anaphylaxis , for epinephrine bioavailability and epinephrine content . METHODS We conducted a prospect i ve , r and omized , cross-over study of epinephrine bioavailability after injection from out date d autoinjectors in rabbits ; controls included EpiPen and EpiPen Jr autoinjectors that had not expired ( " in- date " autoinjectors ) and intramuscular injection of 0.9 % saline solution . In addition , the epinephrine content of the out date d EpiPen and EpiPen Jr autoinjectors was measured by a spectrophotometric method and an HPLC-UV method . RESULTS Twenty-eight EpiPen and 6EpiPen Jr autoinjectors were studied 1 to 90 months after the stated expiration date . Most were not discolored and did not contain precipitates . Epinephrine bioavailability from the out date d EpiPen autoinjectors was significantly reduced ( P < .05 ) compared with epinephrine bioavailability from the in- date autoinjectors . The inverse correlation between the decreased epinephrine content of the out date d autoinjectors , assessed with an HPLC-UV method , and the number of months past the expiration date was 0.63 . CONCLUSIONS For prehospital treatment of anaphylaxis , we recommend the use of EpiPen and EpiPen Jr autoinjectors that are not out date d. If , however , the only autoinjector available is an out date d one , it could be used as long as no discoloration or precipitates are apparent because the potential benefit of using it is greater than the potential risk of a suboptimal epinephrine dose or of no epinephrine treatment at all Injectable formulations of L-adrenaline are commonly used in emergency medicine . Despite numerous studies , the comparative contribution and kinetics of the L-adrenaline inactivation pathways during storage have not been conclusively evaluated . We examined the kinetics of L-adrenaline degradation in a prospect i ve study and determined the extent of drug inactivation by different pathways during and beyond the stipulated product shelf-life in 42 batches of adrenaline ampules stored under controlled conditions . The content of L-adrenaline and degradation products was determined with a chiral high-performance liquid chromatography ( HPLC ) assay , and the degradation products were identified by mass spectrometric detection as D-adrenaline and L- and D-adrenaline sulfonate . The kinetics of the content change with storage was analyzed simultaneously for L-adrenaline and the degradation products using kinetic modeling . The lower acceptable level of adrenaline content in the formulation stated by US Pharmacopoeia ( 90 % as a sum of L- and D-isomers ) was attained after 2.0 years of storage , at which time the content of the therapeutically active L-isomer amounted to as low as 85 % . The modeling revealed significant differences in the degradation kinetics in the formulations produced before and after 1997 , whose cause remained unidentified in this study Background : The aim of the current study was to assess the influence of anesthetic management on the effect of treatment in the Multicenter R and omized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherl and s ( MR CLEAN ) . Methods : MR CLEAN was a multicenter , r and omized , open-label trial of intra-arterial therapy ( IAT ) vs no IAT . The intended anesthetic management at the start of the procedure was used for this post hoc analysis . The primary effect parameter was the adjusted common odds ratio ( acOR ) for a shift in direction of a better outcome on the modified Rankin Scale ( mRS ) at 90 days , estimated with multivariable ordinal logistic regression analysis , which included a term for general anesthesia ( GA ) . Results : GA was associated with significant ( p = 0.011 ) effect modification , result ing in estimated decrease of 51 % ( 95 % confidence interval [ CI ] 31%–86 % ) in treatment effect compared to non-GA . We found a shift in the distribution on the mRS in favor of non-GA compared to control group ( acOR 2.18 [ 95 % CI 1.49–3.20 ] ) . The shift in distribution between GA and control group was in a similar direction ( acOR 1.12 [ 95 % CI 0.71–1.78 ] ) with loss of statistical significance . Conclusions : In this post hoc analysis , we found that the type of anesthetic management influences outcome following IAT . Only treatment without general anesthesia was associated with a significant treatment benefit in MR CLEAN . Classification of evidence : This study provides Class II evidence that for patients with acute ischemic stroke undergoing IAT , mRS scores at 90 days improve only in patients treated without GA IMPORTANCE Intra-arterial treatment ( IAT ) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset . The influence of treatment delay on treatment effect is not yet known . OBJECTIVE To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT . DESIGN , SETTING , AND PARTICIPANTS The Multicenter R and omized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherl and s ( MR CLEAN ) was a multicenter , r and omized clinical open-label trial of IAT vs no IAT in 500 patients . The time to the start of treatment was defined as the time from onset of symptoms to groin puncture ( TOG ) . The time from onset of treatment to reperfusion ( TOR ) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved . Data were collected from December 3 , 2010 , to June 3 , 2014 , and analyzed ( intention to treat ) from July 1 , 2014 , to September 19 , 2015 . MAIN OUTCOMES AND MEASURES Main outcome was the modified Rankin Scale ( mRS ) score for functional outcome ( range , 0 [ no symptoms ] to 6 [ death ] ) . Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to r and omization , TOG , and TOR with treatment . The effect of treatment as a risk difference on reaching independence ( mRS score , 0 - 2 ) was computed as a function of TOG and TOR . Calculations were adjusted for age , National Institutes of Health Stroke Scale score , previous stroke , atrial fibrillation , diabetes mellitus , and intracranial arterial terminus occlusion . RESULTS Among 500 patients ( 58 % male ; median age , 67 years ) , the median TOG was 260 ( interquartile range [ IQR ] , 210 - 311 ) minutes ; median TOR , 340 ( IQR , 274 - 395 ) minutes . An interaction between TOR and treatment ( P = .04 ) existed , but not between TOG and treatment ( P = .26 ) . The adjusted risk difference ( 95 % CI ) was 25.9 % ( 8.3%-44.4 % ) when reperfusion was reached at 3 hours , 18.8 % ( 6.6%-32.6 % ) at 4 hours , and 6.7 % ( 0.4%-14.5 % ) at 6 hours . CONCLUSION AND RELEVANCE For every hour of reperfusion delay , the initially large benefit of IAT decreases ; the absolute risk difference for a good outcome is reduced by 6 % per hour of delay . Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion . TRIAL REGISTRATION trialregister.nl Identifier : NTR1804 Background The presence of extracranial carotid disease ( ECD ) is associated with less favorable clinical outcomes in patients with acute ischemic stroke caused by intracranial proximal occlusion . Acute intra-arterial treatment ( IAT ) in the setting of extracranial and intracranial lesions is considered challenging , and whether it yields improved outcomes remains uncertain . Objective To examine whether the presence of ECD modified the effect of IAT for intracranial proximal anterior circulation occlusion . Design Prespecified subgroup analysis of a r and omized clinical trial of endovascular treatment for acute ischemic stroke in the Netherl and s. ( Trial registration s : NTR1804 [ Netherl and s Trial Register ] and IS RCT N10888758 ) . Setting 16 hospitals in the Netherl and s. Patients Acute ischemic stroke caused by proximal intracranial arterial occlusion of the anterior circulation . Extracranial carotid disease was defined as cervical internal carotid artery stenosis ( > 50 % ) or occlusion . Intervention IAT treatment versus no IAT . Measurements The primary outcome was functional outcome , as measured by the modified Rankin Scale at 90 days and reported as adjusted common odds ratio ( acOR ) for a shift in direction of a better outcome . Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by ECD . Results The overall acOR was 1.67 ( 95 % CI , 1.21 to 2.30 ) in favor of the intervention . The acOR was 3.1 ( CI , 1.7 to 5.8 ) in the prespecified subgroup of patients with ECD versus 1.3 ( CI , 0.9 to 1.9 ) in patients presenting without ECD . Both acORs are in favor of the intervention ( P for interaction = 0.07 ) . Limitation The study was not powered for subgroup analysis . Conclusion Intra-arterial treatment may be at least as effective in patients with ECD as in those without ECD , and it should not be withheld in these complex patients with acute ischemic stroke . Primary Funding Source Dutch Heart Foundation , AngioCare BV , Medtronic/Covidien/EV3 , MEDAC Gmbh/LAMEPRO , Penumbra , Stryker , and Top Medical/Concentric |
13,099 | 31,262,972 | These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM | Patients with type 2 diabetes mellitus ( T2DM ) have a very high risk of cardiovascular related events , and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs .
Previous studies have shown that the dipeptidyl peptidase-4 ( DPP-4 ) inhibitors ( DPP4i ) , such as sitagliptin , might reduce the incidence of major cardiovascular events ( MACEs ) .
However , the safety and efficacy of sitagliptin remains controversial , especially the safety for cardiovascular related events .
Here , a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients . | Background In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes , treatment with sitagliptin , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , was shown to be generally well tolerated compared with treatment with control agents . As clinical development of sitagliptin continues , additional studies have been completed , and more patients have been exposed to sitagliptin . The purpose of the present analysis is to up date the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies . Methods The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day ( N = 5,429 ; sitagliptin group ) or a comparator agent ( placebo or an active comparator ) ( N = 4,817 ; non-exposed group ) . The 19 studies from which this pooled population was drawn represent the double-blind , r and omized studies that included patients treated with the usual clinical dose of sitagliptin ( 100 mg/day ) for between 12 weeks and 2 years and for which results were available as of July 2009 . These 19 studies assessed sitagliptin taken as monotherapy , initial combination therapy with metformin or pioglitazone , or as add-on combination therapy with other antihyperglycemic agents ( metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin ) . Patients in the non-exposed group were taking placebo , metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin . The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events . Results Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups , except for an increased incidence of drug-related adverse events in the non-exposed group . Incidence rates of specific adverse events were also generally similar between the two groups , except for increased incidence rates of hypoglycemia , related to the greater use of a sulfonylurea , and diarrhea , related to the greater use of metformin , in the non-exposed group and constipation in the sitagliptin group . Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events . Conclusions In this up date d pooled safety analysis of data from 10,246 patients with type 2 diabetes , sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration AIM The efficacy and safety of sitagliptin ( SITA ) monotherapy and SITA/metformin ( MET ) vs. pioglitazone ( PIO ) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia ( A1C = 7.5 - 12.0 % ) . METHODS In an initial 12-week phase ( Phase A ) , 492 patients were r and omised 1 : 1 in a double-blind fashion to SITA ( 100 mg qd ) or PIO ( 15 mg qd , up-titrated to 30 mg after 6 weeks ) . In Phase B ( 28 additional weeks ) , the SITA group was switched to SITA/MET ( up-titrated to 50/1000 mg bid over 4 weeks ) and the PIO group was up-titrated to 45 mg qd RESULTS At the end of Phase A , mean changes from baseline were -1.0 % and -0.9 % for A1C ; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose ; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO , respectively . At the end of Phase B , improvements in glycaemic parameters were greater with SITA/MET vs. PIO : -1.7 % vs. -1.4 % for A1C ( p = 0.002 ) ; -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose ( p = 0.03 ) ; -90.3 mg/dl vs. -69.1 mg/dl for 2-h postmeal glucose ( p = 0.001 ) ; and 55.0 % vs. 40.5 % for patients with A1C < 7 % ( p = 0.004 ) . A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO . The incidence of hypoglycaemia was similarly low in both groups . Body weight decreased with SITA/MET and increased with PIO ( -1.1 kg vs. 3.4 kg ; p < 0.001 ) . CONCLUSION Improvements in glycaemic control were greater with SITA/MET vs. PIO , with weight loss vs. weight gain . Both treatments were generally well tolerated AIMS This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes . METHODS This double-blind study ( 18-week Phase A and 26-week Phase B ) r and omized 1250 drug-naÏve patients with type 2 diabetes [ mean baseline haemoglobin A1c ( HbA1c ) 9.9 % ] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid ( uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid ) . Results of the primary efficacy endpoint ( mean HbA1c reductions from baseline at the end of Phase A ) are reported herein . RESULTS At week 18 , mean change from baseline HbA1c was -2.4 % for sitagliptin/metformin FDC and -1.8 % for metformin monotherapy ( p < 0.001 ) ; more patients treated with sitagliptin/metformin FDC had an HbA1c value < 7 % ( p < 0.001 ) versus metformin monotherapy . Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC ( -3.8 mmol/l ) versus metformin monotherapy ( -3.0 mmol/l ; p < 0.001 ) . Homeostasis model assessment of β-cell function ( HOMA-β ) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy . Baseline body weight was reduced by 1.6 kg in each group . Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia . Abdominal pain ( 1.1 and 3.9 % ; p = 0.002 ) and diarrhoea ( 12.0 and 16.6 % ; p = 0.021 ) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy ; the incidence of nausea and vomiting was similar in both groups . CONCLUSION Compared with metformin monotherapy , initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea Abstract Introduction We evaluated the tolerability and efficacy of the addition of sitagliptin in Chinese patients with type 2 diabetes mellitus receiving stable insulin therapy alone or in combination with metformin . Material s and Methods A total of 467 patients with inadequate glycemic control on insulin ( glycated hemoglobin [ HbA1c ] ≥7.5 % and ≤11 % ) were r and omized 1:1 to receive sitagliptin 100 mg once daily or a matching placebo for 24 weeks . R and omization was stratified based on metformin use ( on or not on metformin ) and type of insulin ( pre‐mixed vs intermediate‐/long‐acting ) at screening . The primary end‐point was the change from baseline at week 24 in HbA1c . Results The addition of sitagliptin led to a significantly ( P < 0.001 ) greater week 24 HbA1c reduction ( 0.7 % ) compared with the reduction ( 0.3 % ) with placebo . A significantly ( P = 0.013 ) greater proportion of patients taking sitagliptin ( 16 % ) had an HbA1c of < 7.0 % at week 24 compared with placebo ( 8 % ) . The addition of sitagliptin significantly ( P < 0.001 ) reduced 2‐h post‐meal glucose by 26.5 mg/dL ( 1.5 mmol/L ) relative to placebo . Reductions from baseline in fasting plasma glucose were observed in both the sitagliptin ( 14.4 mg/dL reduction ) and placebo ( 10.7 mg/dL reduction ) groups ; the between‐group difference was not significant . A total of 64 ( 27.4 % ) patients taking sitagliptin and 51 ( 21.9 % ) taking placebo experienced adverse events of hypoglycemia ( symptomatic or asymptomatic ) . Neither group had a significant change from baseline in bodyweight . Conclusions After 24 weeks , sitagliptin added to stable insulin therapy ( ±metformin ) was generally well tolerated and improved glycemic control in Chinese patients with type 2 diabetes mellitus BACKGROUND Type 2 diabetes mellitus ( T2DM ) is a significant burden in China , where approximately 114 million patients have been diagnosed with diabetes . Chinese patients present with prominent β-cell failure , with result ing deficiency in insulin secretion , particularly early phase insulin secretion leading to postpr and ial hyperglycemia . Sitagliptin , a selective once-daily oral dipeptidyl peptidase-4 inhibitor , has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents , including sulfonylureas and metformin . METHODS This was a multicenter r and omized double-blind placebo-controlled study conducted in China . The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c , fasting plasma glucose ( FPG ) and 2-h post-meal glucose ( PMG ) . Patients were aged 18 - 79 years , had T2DM with inadequate glycemic control , and were taking a sulfonylurea , with or without metformin . RESULTS After 24 weeks , sitagliptin reduced HbA1c , FPG , and 2-h PMG significantly more than placebo ( between-treatment differences : -0.61 % , -16.8 mg/dL , and -32.9 mg/dL , respectively ; P < 0.001 for all ) . The addition of sitagliptin was generally well tolerated , with a comparable incidence of adverse events and drug-related adverse events in both treatment groups . The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group ( 25/248 [ 10.1 % ] vs 13/249 [ 5.2 % ] , respectively ; P = 0.042 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea , with or without metformin therapy . The addition of sitagliptin was generally well tolerated . ( clinical trials.gov : NCT01590771 ) OBJECTIVE To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes . METHODS After a 2 week placebo run-in period , eligible patients inadequately controlled on long-acting , intermediate-acting or premixed insulin ( HbA1c > or = 7.5 % and < or = 11 % ) , were r and omised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period . The study capped the proportion of r and omised patients on insulin plus metformin at 75 % . Further , the study capped the proportion of r and omised patients on premixed insulin at 25 % . The metformin dose and the insulin dose were to remain stable throughout the study . The primary endpoint was HbA1c change from baseline at week 24 . RESULTS Mean baseline characteristics were similar between the sitagliptin ( n = 322 ) and placebo ( n = 319 ) groups , including HbA1c ( 8.7 vs. 8.6 % ) , diabetes duration ( 13 vs. 12 years ) , body mass index ( 31.4 vs. 31.4 kg/m(2 ) ) , and total daily insulin dose ( 51 vs. 52 IU ) , respectively . At 24 weeks , the addition of sitagliptin significantly ( p < 0.001 ) reduced HbA1c by 0.6 % compared with placebo ( 0.0 % ) . A greater proportion of patients achieved an HbA1c level < 7 % while r and omised to sitagliptin as compared with placebo ( 13 vs. 5 % respectively ; p < 0.001 ) . Similar HbA1c reductions were observed in the patient strata defined by insulin type ( long-acting and intermediate-acting insulins or premixed insulins ) and by baseline metformin treatment . The addition of sitagliptin significantly ( p < 0.001 ) reduced fasting plasma glucose by 15.0 mg/dl ( 0.8 mmol/l ) and 2-h postmeal glucose by 36.1 mg/dl ( 2.0 mmol/l ) relative to placebo . A higher incidence of adverse experiences was reported with sitagliptin ( 52 % ) compared with placebo ( 43 % ) , due mainly to the increased incidence of hypoglycaemia ( sitagliptin , 16 % vs. placebo , 8 % ) . The number of hypoglycaemic events meeting the protocol -specified criteria for severity was low with sitagliptin ( n = 2 ) and placebo ( n = 1 ) . No significant change from baseline in body weight was observed in either group . CONCLUSION In this 24-week study , the addition of sitagliptin to ongoing , stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes 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 AIM To assess the 54-week efficacy of initial combination therapy with sitagliptin and pioglitazone , compared with pioglitazone monotherapy , and to assess safety in these groups during the 30 weeks after the dosage of pioglitazone was increased from 30 to 45 mg/day , in drug-naÏve patients with type 2 diabetes mellitus and inadequate glycaemic control [ haemoglobin A1c ( HbA1c ) 8 - 12 % ] . METHODS Following a 24-week , r and omized , double-blind , parallel-group study ( Sitagliptin Protocol 064 , Clinical trials.gov : NCT00397631 ; Yoon KH , Shockey GR , Teng R et al. Effect of initial combination therapy with sitagliptin , a dipeptidyl peptidase-4 inhibitor , and pioglitazone on glycaemic control and measures of beta-cell function in patients with type 2 diabetes . Int J Clin Pract 2011 ; 65 : 154 - 164 ) in which patients were treated with the combination of sitagliptin 100 mg/day and pioglitazone 30 mg/day or monotherapy with pioglitazone 30 mg/day , patients entered a 30-week extension study . In the extension study , the pioglitazone dose was increased from 30 to 45 mg/day in both groups . Depending upon treatment allocation , patients took one tablet of sitagliptin 100 mg or matching placebo daily . Pioglitazone was administered in an open-label fashion as a single 45-mg tablet taken once daily . Patients not meeting specific glycaemic goals in the extension study were rescued with metformin therapy . Efficacy and safety results for the extension study excluded data after initiation of rescue therapy . RESULTS Of the 520 patients initially r and omized , 446 completed the base study and , of these , 317 entered the extension . In this extension study cohort , the mean reductions from baseline in HbA1c and fasting plasma glucose ( FPG ) at the end of the base study ( week 24 ) were -2.5 % and -62.1 mg/dl with the combination of sitagliptin 100 mg and pioglitazone 30 mg versus -1.9 % and -48.7 mg/dl with pioglitazone monotherapy . At the end of the extension study ( week 54 ) , the mean reduction in haemoglobin A1c ( HbA1c ) was -2.4 % with the combination of sitagliptin 100 mg and pioglitazone 45 mg versus -1.9 % with pioglitazone monotherapy [ between-group difference ( 95 % CI ) = -0.5 % ( -0.8 , -0.3 ) ] and the mean reduction in FPG was -61.3 mg/dl versus -52.8 mg/dl , respectively [ between-group difference ( 95 % CI ) = -8.5 mg/dl ( -16.3 , -0.7 ) ] . Safety and tolerability of initial treatment with the combination of sitagliptin and pioglitazone and pioglitazone monotherapy were similar . As expected , increases in body weight from baseline were observed in both treatment groups at week 54 : 4.8 and 4.1 kg in the combination and monotherapy groups , respectively [ between-group difference ( 95 % CI ) = 0.7 kg ( -0.7 , 2.1 ) ] . CONCLUSION In this study , initial combination therapy with sitagliptin 100 mg and pioglitazone 30 mg increased to 45 mg after 24 weeks led to a substantial and durable incremental improvement in glycaemic control compared with initial treatment with pioglitazone monotherapy during a 54-week treatment period . Both initial combination therapy with sitagliptin and pioglitazone and pioglitazone monotherapy were generally well tolerated ( Clinical trials.gov : NCT01028391 ) AIM To assess the efficacy and safety of a 24-week treatment with sitagliptin , a highly selective once-daily oral dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in patients with type 2 diabetes who had inadequate glycaemic control [ glycosylated haemoglobin ( HbA(1c ) ) > or=7.5 % and < or=10.5 % ] while on glimepiride alone or in combination with metformin . METHODS After a screening , diet/exercise run-in and drug wash-off period , a glimepiride + /- metformin dose titration/stabilization period and a 2-week , single-blind placebo run-in , 441 patients ( of ages 18 - 75 years ) were r and omized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks . Of these patients , 212 were on glimepiride ( > or=4 mg/day ) monotherapy and 229 were on glimepiride ( > or=4 mg/day ) plus metformin ( > or=1,500 mg/day ) combination therapy . Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy ( pioglitazone ) until study end . The primary efficacy analysis evaluated the change in HbA(1c ) from baseline to Week 24 . Secondary efficacy endpoints included fasting plasma glucose ( FPG ) , 2-h post-meal glucose and lipid measurements . RESULTS Mean baseline HbA(1c ) was 8.34 % in the sitagliptin and placebo groups . After 24 weeks , sitagliptin reduced HbA(1c ) by 0.74 % ( p < 0.001 ) relative to placebo . In the subset of patients on glimepiride plus metformin , sitagliptin reduced HbA(1c ) by 0.89 % relative to placebo , compared with a reduction of 0.57 % in the subset of patients on glimepiride alone . The addition of sitagliptin reduced FPG by 20.1 mg/dl ( p < 0.001 ) and increased homeostasis model assessment -beta , a marker of beta-cell function , by 12 % ( p < 0.05 ) relative to placebo . In patients who underwent a meal tolerance test ( n = 134 ) , sitagliptin decreased 2-h post-pr and ial glucose ( PPG ) by 36.1 mg/dl ( p < 0.001 ) relative to placebo . The addition of sitagliptin was generally well tolerated , although there was a higher incidence of overall ( 60 vs. 47 % ) and drug-related adverse experiences ( AEs ) ( 15 vs. 7 % ) in the sitagliptin group than in the placebo group . This was largely because of a higher incidence of hypoglycaemia AEs ( 12 vs. 2 % , respectively ) in the sitagliptin group compared with the placebo group . Body weight modestly increased with sitagliptin relative to placebo ( + 0.8 vs. -0.4 kg ; p < 0.001 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy . The addition of sitagliptin was generally well tolerated , with a modest increase in hypoglycaemia and body weight , consistent with glimepiride therapy and the observed degree of glycaemic improvement OBJECTIVE The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control ( glycosylated hemoglobin [ HbA(1c ) ] > or = 7 % and < or = 10 % ) while receiving a stable dose of pioglitazone . METHODS This was a 24-week , multicenter , r and omized , double-blind , placebo-controlled , parallel group study in patients aged > or = 18 years ( Clinical Trials . gov NCT00086502 ) . At screening , all patients began a diet/exercise program that continued throughout the study period . Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period . Patients with an HbA(1c ) > or = 7 % and < or = 10 % at the end of this period entered a 2-week , single-blind , placebo run-in period ( total duration of run-in period , up to 21 weeks ) . Patients who had been receiving pioglitazone monotherapy ( 30 or 45 mg/d ) and had an HbA(1c ) > or = 7 % and < or = 10 % entered the 2-week , single-blind , placebo run-in period directly . Thus , at the time of r and omization , all patients were receiving ongoing pioglitazone ( 30 or 45 mg/d ) . Patients were r and omized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks . The primary efficacy end point was the change from baseline in HbA(1c ) at week 24 . Secondary efficacy end points included the change from baseline in fasting plasma glucose ( FPG ) , insulin , and proinsulin ; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes ; the proinsulin/ insulin ratio ; the Quantitative Insulin Sensitivity Check Index ; the percent changes from baseline in selected lipid parameters ; the proportion of patients meeting the American Diabetes Association HbA(1c ) , goal of < 7.0 % ; the proportion of patients requiring metformin rescue therapy ; and the time to the initiation of rescue therapy . RESULTS One hundred seventy-five patients were r and omized to receive sitagliptin , and 178 were r and omized to receive placebo . The mean ( SD ) baseline HbAlc value was 8.1 % ( 0.8 ) in the sitagliptin group and 8.0 % ( 0.8 ) in the placebo group . After 24 weeks , sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c ) ( between-treatment difference in least squares [ LS ] mean change from baseline . -0.70 % ; 95 % CI , -0.85 to -0.54 ; P < 0.001 ) and FPG ( -17.7 mg/dL ; 95 % CI , -24.3 to -11.0 ; P < 0.001 ) . Mean HbA(1c ) values at end point were 7.2 % ( 0.9 ) and 7.8 % ( 1.1 ) in the respective treatment groups , and the proportions of patients reaching a target HbA(1c ) of < 7.0 % were 45.4 % and 23.0 % ( P < 0.001 ) . Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo ( both , P < 0.01 ) . Sitagliptin was generally well tolerated , with no increased risk of hypoglycemia compared with placebo ( 2 vs 0 patients , respectively ) AIM to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy . METHODS patients with type 2 diabetes and an HbA(1c ) of 6.5 - 9.0 % while on a stable dose of metformin ( ≥ 1500 mg/day ) combined with diet and exercise for at least 12 weeks were r and omized in a double-blind manner to receive either sitagliptin 100 mg daily ( N = 516 ) or glimepiride ( starting dose 1 mg/day and up-titrated , based upon patient 's self-monitoring of blood glucose results , to a maximum dose of up to 6 mg/day ) ( N = 519 ) for 30 weeks . The primary analysis assessed whether sitagliptin is non-inferior to glimepiride in reducing HbA(1c ) at week 30 ( based on the criterion of having an upper bound of the 95 % CI less than the prespecified non-inferiority bound of 0.4 % ) . RESULTS the mean baseline HbA(1c ) was 7.5 % in both the sitagliptin group ( n = 443 ) and the glimepiride group ( n = 436 ) . After 30 weeks , the least squares ( LS ) mean change in HbA(1c ) from baseline was -0.47 % with sitagliptin and -0.54 % with glimepiride , with a between-group difference ( 95 % CI ) of 0.07 % ( -0.03 , 0.16 ) . This result met the prespecified criterion for declaring non-inferiority . The percentages of patients with an HbA(1c ) < 7.0 % at week 30 were 52 and 60 % in the sitagliptin and glimepiride groups , respectively . The LS mean change in fasting plasma glucose from baseline ( 95 % CI ) was -0.8 mmol/l ( -1.0 , -0.6 ) with sitagliptin and -1.0 mmol/l ( -1.2 , -0.8 ) with glimepiride , for a between-group difference ( 95 % CI ) of 0.2 mmol/l ( -0.1 , 0.4 ) . The percentages of patients for whom hypoglycaemia was reported were 7 % in the sitagliptin group and 22 % in the glimepiride group ( percentage-point difference = -15 , p < 0.001 ) . Relative to baseline , sitagliptin was associated with a mean weight loss ( -0.8 kg ) , whereas glimepiride was associated with a mean weight gain ( 1.2 kg ) , yielding a between-group difference of -2.0 kg ( p < 0.001 ) . CONCLUSIONS in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy , the addition of sitagliptin or glimepiride led to similar improvement in glycaemic control after 30 weeks . Sitagliptin was generally well tolerated . Compared to treatment with glimepiride , treatment with sitagliptin was associated with a lower risk of hypoglycaemia and with weight loss versus weight gain ( Clinical Trials.gov : NCT00701090 ) The mechanisms underlying the weight-loss effect of GLP-1 receptor agonists need further elucidation . The present study was performed to explore the effects of liraglutide and saxagliptin on the composition of the gut microbiota . Mice were r and omly treated with saxagliptin or liraglutide for eight weeks . Their metabolic profiles were assessed , and 454 pyrosequencing of 16s rRNA of faeces was performed . Liraglutide induced a smaller body weight gain in mice . The pyrosequencing showed that liraglutide , but not saxagliptin , substantially changed the overall structure of the gut microbiota as well as the relative abundance of weight-relevant phylotypes . Subsequent ridge regression analyses indicated that , in addition to food intake ( β = −0.182 , p = 0.043 in phylotypes inversely correlated with body weight ) and blood glucose level ( β = −0.240 , p = 0.039 in phylotypes positively correlated with body weight ) , the administration of liraglutide was another independent factor associated with the abundance of weight-relevant phylotypes ( β = 0.389 , p = 6.24e-5 in inversely correlated ones ; β = −0.508 , p = 2.25e-5 in positively correlated ones ) . These results evidence d that GLP-1 receptor agonist liraglutide could modulate the composition of the gut microbiota , leading to a more lean-related profile that was consistent with its weight-losing effect Abstract Introduction The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here . Material s and Methods This was a multicenter , r and omized , double‐blind , placebo‐controlled , parallel group , 24‐week clinical trial carried out in China . Patients ( n = 744 ) with type 2 diabetes and inadequate glycemic control ( glycated hemoglobin ≥7.5 and ≤11.0 % ) who were either drug‐naïve or washed out of previous therapy were r and omized in equal ratios to sitagliptin 100 mg once daily ( q.d . ; S100 ) , metformin 500 mg twice daily ( b.i.d . ; M1000 ) , metformin 850 mg b.i.d . ( M1700 ) , sitagliptin 50 mg b.i.d . plus metformin 500 mg b.i.d . ( S100/M1000 ) , sitagliptin 50 mg b.i.d . plus metformin 850 mg b.i.d . ( S100/M1700 ) , or placebo . Results The mean baseline glycated hemoglobin in r and omized patients was 8.7 % . Least squares mean changes from baseline in glycated hemoglobin were −0.59 % ( placebo ) , −0.99 % ( S100 ) , −1.29 % ( M1000 ) , −1.56 % ( M1700 ) , −1.67 % ( S100/M1000 ) and −1.83 % ( S100/M1700 ) ( P < 0.05 for each active group vs placebo , for S100/M1700 and S100/M1000 vs S100 , and for S100/M1000 vs M1000 ) . All treatments were generally well‐tolerated . The overall incidence of hypoglycemia ( symptomatic or asymptomatic ) was higher in the two co‐administration groups ( S100/M1700 and S100/M1000 ) compared with the placebo . The incidence of symptomatic hypoglycemia was low , and similar , across all treatment groups . The incidences of gastrointestinal adverse events were generally higher in high‐dose metformin groups than in the placebo group . Conclusions In Chinese patients with type 2 diabetes , initial combination therapy with sitagliptin and metformin was generally well‐tolerated , and provided improvement in glycemic control OBJECTIVE Patients with type 2 diabetes mellitus ( T2DM ) and chronic kidney disease have an increased risk of micro- and macrovascular disease , but limited options for antihyperglycemic therapy . We compared the efficacy and safety of sitagliptin with glipizide in patients with T2DM and moderate-to-severe chronic renal insufficiency and inadequate glycemic control . RESEARCH DESIGN AND METHODS Patients ( n = 426 ) were r and omized 1:1 to sitagliptin ( 50 mg every day [ q.d . ] for moderate renal insufficiency and 25 mg q.d . for severe renal insufficiency ) or glipizide ( 2.5 mg q.d . , adjusted based on glycemic control to a 10-mg twice a day maximum dose ) . R and omization was stratified by : 1 ) renal status ( moderate or severe renal insufficiency ) ; 2 ) history of cardiovascular disease ; and 3 ) history of heart failure . RESULTS At week 54 , treatment with sitagliptin was noninferior to treatment with glipizide in A1C change from baseline ( −0.8 vs. −0.6 % ; between-group difference −0.11 % ; 95 % CI −0.29 to 0.06 ) because the upper bound of the 95 % CI was less than the prespecified noninferiority margin of 0.4 % . There was a lower incidence of symptomatic hypoglycemia adverse events ( AEs ) with sitagliptin versus glipizide ( 6.2 and 17.0 % , respectively ; P = 0.001 ) and a decrease in body weight with sitagliptin ( −0.6 kg ) versus an increase ( 1.2 kg ) with glipizide ( difference , −1.8 kg ; P < 0.001 ) . The incidence of gastrointestinal AEs was low with both treatments . CONCLUSIONS In patients with T2DM and chronic renal insufficiency , sitagliptin and glipizide provided similar A1C-lowering efficacy . Sitagliptin was generally well-tolerated , with a lower risk of hypoglycemia and weight loss versus weight gain , relative to glipizide We tested the feasibility of setting individualized glycemic goals and factors influencing targets set in a clinical trial in elderly patients with type 2 diabetes . A 24-week , r and omized , double-blind , placebo-controlled study was conducted in 45 outpatient centers in seven European countries . 278 drug-naïve or inadequately controlled ( mean HbA1c 7.9 % ) patients with type 2 diabetes aged ≥70 years with HbA1c levels ≥7.0 % and ≤10.0 % were enrolled . Investigator-defined individualized HbA1c targets and the impact of baseline characteristics on individualized treatment targets was evaluated . The average individualized HbA1c target was set at 7.0 % . HbA1c at baseline predicted a target setting such that higher the HbA1c , more aggressive was the target ( P<0.001 ) . Men were more likely to be set aggressive targets than women ( P=0.026 ) . Frailty status of patients showed a trend towards significance ( P=0.068 ) , whereas diabetes duration , age , or polypharmacy did not . There was heterogeneity between countries regarding how baseline factors were viewed . Despite training and guidance to individualize HbA1c goals , targets were still set in line with conventional values . A strong influence of country-specific guidelines on target setting was observed ; confirming the importance of further education to implement new international guidelines in older adults Aims /hypothesisThe aim of this study was to assess the efficacy and safety of sitagliptin ( MK-0431 ) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control ( HbA1c ≥7 % and ≤10 % ) on exercise and diet . Methods A total of 521 patients aged 27–76 years with a mean baseline HbA1c of 8.1 % were r and omised in a 1:2:2 ratio to treatment with placebo , sitagliptin 100 mg once daily , or sitagliptin 200 mg once daily , for 18 weeks . The efficacy analysis was based on an all- patients -treated population using an analysis of covariance , excluding data obtained after glycaemic rescue . Results After 18 weeks , HbA1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo ( placebo-subtracted HbA1c reduction : −0.60 % and −0.48 % , respectively ) . Sitagliptin also significantly decreased fasting plasma glucose relative to placebo . Patients with higher baseline HbA1c ( ≥9 % ) experienced greater placebo-subtracted HbA1c reductions with sitagliptin ( −1.20 % for 100 mg and −1.04 % for 200 mg ) than those with HbA1c < 8 % ( −0.44 % and −0.33 % , respectively ) or ≥8 % to 8.9 % ( −0.61 % and −0.39 % , respectively ) . Homeostasis model assessment beta cell function index and fasting proinsulin : insulin ratio , markers of insulin secretion and beta cell function , were significantly improved with sitagliptin . The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo . Sitagliptin had a neutral effect on body weight . Conclusions /interpretationSitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet OBJECTIVE To assess the safety of sitagliptin in patients with type 2 diabetes and moderate [ creatinine clearance ( CrCl ) > or = 30 to < 50 ml/min ] or severe renal insufficiency [ CrCl < 30 ml/min including patients with end-stage renal disease ( ESRD ) on dialysis ] . The efficacy of sitagliptin in this patient population was also assessed . METHODS In a 54-week , r and omized , double-blind , parallel-group study , patients with baseline glycosylated haemoglobin A(1c ) ( HbA(1c ) ) values of 6.5 - 10 % were allocated ( 2:1 ) to sitagliptin ( for 54 weeks ) or the sequence of placebo ( for 12 weeks ) followed by active treatment with glipizide ( for 42 weeks ) . To achieve plasma concentrations similar to those observed in patients with normal renal function treated with 100 mg sitagliptin once daily , patients with moderate renal insufficiency were allocated to receive sitagliptin 50 mg once daily and patients with severe renal insufficiency to receive 25 mg once daily . Glipizide treatment was initiated at 2.5 or 5 mg/day and uptitrated to a maximum of 20 mg/day . RESULTS Patients ( N = 91 ) with a mean baseline HbA(1c ) value of 7.7 % ( range : 6.2 - 10.3 % ) were r and omized to sitagliptin ( n = 65 ) or placebo ( n = 26 ) . After 12 weeks , the mean change [ 95 % confidence interval ( CI ) ] from baseline in HbA(1c ) was -0.6 % ( -0.8 , -0.4 ) in the sitagliptin group compared with -0.2 % ( -0.4 , 0.1 ) in the placebo group [ between-group difference ( 95 % CI ) = -0.4 % ( -0.7 , -0.1 ) ] . At 54 weeks , patients continuously treated with sitagliptin had a mean change ( 95 % CI ) from baseline in HbA(1c ) of -0.7 % ( -0.9 , -0.4 ) . The overall incidence of adverse experiences was generally similar between groups . Between-group differences in incidences of specific clinical adverse experiences were generally small ; however , the proportion of patients for whom hypoglycaemia was reported was lower in the sitagliptin group ( 4.6 % ) compared with the placebo/glipizide group ( 23.1 % ) . Consistent with the high mortality risk in this patient population , there were six deaths during this 54-week study [ 5 of 65 patients ( 7.7 % ) in the sitagliptin group and 1 of 26 patients ( 3.8 % ) in the placebo/glipizide group ] ; no death was considered by the investigator to be drug related . The overall incidences of drug-related and serious adverse experiences and discontinuations because of adverse experiences were generally similar between groups . CONCLUSIONS In this study , sitagliptin was generally well tolerated and provided effective glycaemic control in patients with type 2 diabetes and moderate to severe renal insufficiency , including patients with ESRD on dialysis AIM To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes . METHODS Patients with A1c ≥7.5 and ≤11.0 % were r and omized among seven arms that received , once daily , 100 mg sitagliptin alone ; 15 , 30 or 45 mg pioglitazone alone , or 100 mg sitagliptin plus 15 , 30 or 45 mg pioglitazone for 54 weeks . The primary endpoint was change from baseline in A1c at week 24 . Protocol -specified analyses compared combination therapies with monotherapies at respective dose-strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy . Post-hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses . RESULTS Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c ( 0.4 - 0.7 % differences ) and other glycaemic endpoints than either monotherapy at the same doses . Combining sitagliptin with low-dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy ( 0.3 - 0.4 % differences in A1c ) . Combination therapy was generally well tolerated ; adverse events ( AEs ) of hypoglycaemia were reported with similar incidence ( 7.8 - 11.1 % ) in all treatment groups over the 54 weeks of study ; oedema was reported in 0.5 % of patients in the sitagliptin monotherapy group and 2.7 - 5.3 % among pioglitazone-treated groups . Significant weight gain was observed in all combination-treated groups compared with the sitagliptin monotherapy group . CONCLUSIONS Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated Abstract Objective : Type 2 diabetes in the elderly is an important and insufficiently studied public health problem . This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥65 years . Research design and methods : This was a r and omized , double-blind , placebo-controlled , parallel-group study conducted at 52 sites in the United States . Patients were treated with once-daily sitagliptin ( 100 or 50 mg , depending on renal function ) or placebo for 24 weeks . Key endpoints included change from baseline in glycated hemoglobin ( HbA1c ) , 2-hour post-meal glucose ( 2-h PMG ) and fasting plasma glucose ( FPG ) at week 24 , and average blood glucose on treatment days 3 and 7 . Clinical trial registration : NCT00305604 . Results : Among r and omized patients ( N = 206 ) , mean age was 72 years and mean baseline HbA1c was 7.8 % . At week 24 , HbA1c decreased by 0.7 % , 2-h PMG by 61 mg/dL , and FPG by 27 mg/dL in sitagliptin-treated patients compared with placebo ( all p < 0.001 ) . On day 3 of treatment , mean average blood glucose was decreased from baseline by 20.4 mg/dL in sitagliptin-treated patients compared with placebo ( p < 0.001 ) . In subgroups defined by baseline HbA1c < 8.0 % ( n = 132 ) , ≥8.0 % to < 9.0 % ( n = 42 ) , and ≥9.0 % ( n = 18 ) , the placebo-adjusted reductions in HbA1c with sitagliptin treatment were 0.5 % , 0.9 % , and 1.6 % , respectively . Patients in the sitagliptin and placebo groups had similar rates of adverse events overall ( 46.1 % and 52.9 % , respectively ) ; serious adverse events were reported in 6.9 % and 13.5 % , respectively . No adverse events of hypoglycemia were reported . Potential study limitations include a relatively small number of patients with more severe hyperglycemia ( HbA1c ≥9.0 % ) and the exclusion of patients with severe renal insufficiency . Conclusion : In this study , sitagliptin treatment significantly and rapidly improved glycemic measures and was well tolerated in patients aged ≥65 years with type 2 diabetes AIMS To assess efficacy and safety of sitagliptin , a dipeptidyl peptidase-4 inhibitor , in combination therapy with metformin ( ≥1500 mg/day ) and pioglitazone ( ≥30 mg/day ) in patients with type 2 diabetes ( T2DM ) with inadequate glycemic control ( hemoglobin A1c [ HbA1c ] ≥7.5 % and ≤11 % ) . METHODS This placebo-controlled , double-blind study included 313 patients , mean baseline HbA1c=8.7 % , who were r and omized to receive sitagliptin 100 mg/day or placebo for 26 weeks . RESULTS The addition of sitagliptin led to significant ( P<.001 ) mean changes from baseline relative to placebo in HbA1c ( -0.7 % ) , fasting plasma glucose ( -1.0 mmol/L ) , and 2-h post-meal glucose ( -2.2 mmol/L ) . In patients with baseline HbA1c ≥9.0 % , mean changes from baseline in HbA1c were -1.6 % and -0.8 % for the sitagliptin and placebo groups , respectively ( between-group difference -0.8 % ; P<.001 ) . The incidences of reported adverse events were generally similar between the treatment groups . Incidences of symptomatic hypoglycemia were 7/157 [ 4.5 % ] and 6/156 [ 3.8 % ] in the sitagliptin and placebo groups , respectively ( P=.786 ) . Two patients , both in the placebo group , experienced an episode of hypoglycemia that required non-medical assistance . CONCLUSIONS In this 26-week study , addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated AIM /HYPOTHESIS To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naïve patients with type 2 diabetes . METHODS A total of 520 patients were r and omised to initial combination therapy with sitagliptin 100 mg q.d . and pioglitazone 30 mg q.d . or pioglitazone 30 mg q.d . monotherapy for 24 weeks . RESULTS Initial combination therapy with sitagliptin and pioglitazone led to a mean reduction from baseline in A1C of -2.4 % compared with -1.5 % for pioglitazone monotherapy ( p<0.001 ) . Mean reductions from baseline were greater in patients with a baseline A1C≥10 % ( -3.0 % with combination therapy vs. -2.1 % with pioglitazone monotherapy ) compared with patients with a baseline A1C<10 % ( -2.0 % with combination therapy vs. -1.1 % with pioglitazone monotherapy ) . Sixty percent of patients in the combination therapy group vs. 28 % in the pioglitazone monotherapy group had an A1C of < 7 % at week 24 ( p<0.001 ) . Fasting plasma glucose decreased by -63.0 mg/dl ( -3.5 mmol/l ) in the combination therapy group compared with -40.2 mg/dl ( -2.2 mmol/l ) for pioglitazone monotherapy ( p<0.001 ) , and 2-h post meal glucose decreased by -113.6 mg/dl ( -6.3 mmol/l ) with combination therapy compared with -68.9 mg/dl ( -3.8 mmol/l ) for pioglitazone monotherapy ( p<0.001 ) . Measures related to β-cell function also improved significantly with combination therapy compared with pioglitazone monotherapy . Combination therapy was generally well-tolerated compared with pioglitazone monotherapy , with similar incidences of hypoglycemia ( 1.1 % and 0.8 % , respectively ) , gastrointestinal adverse events ( 5.7 % and 6.9 % , respectively ) , and oedema ( 2.7 % and 3.5 % , respectively ) . CONCLUSION /INTERPRETATION Initial combination therapy with sitagliptin and pioglitazone substantially improved glycemic control and was generally well-tolerated compared with pioglitazone monotherapy AIM To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with type 2 diabetes . METHODS In a double-blind study , 1050 treatment-naïve patients ( i.e. not taking an antihyperglycaemic agent for > or = 16 weeks prior to study entry ) with type 2 diabetes and an HbA(1c ) 6.5 - 9 % were r and omized ( 1:1 ) to treatment with once-daily sitagliptin 100 mg ( N = 528 ) or twice-daily metformin 1000 mg ( N = 522 ) for 24 weeks . Metformin was up-titrated from 500 to 2000 mg per day ( or maximum tolerated daily dose > or = 1000 mg ) over a period of 5 weeks . The primary analysis used a per- protocol ( PP ) approach to assess whether sitagliptin was non-inferior to metformin based on HbA(1c ) change from baseline at week 24 . Non-inferiority was to be declared if the upper boundary of the 95 % confidence interval ( CI ) for the between-group difference in this endpoint was < 0.40 % . RESULTS From a mean baseline HbA(1c ) of 7.2 % in the PP population , HbA(1c ) change from baseline was -0.43 % with sitagliptin ( n = 455 ) and -0.57 % with metformin ( n = 439 ) . The between-group difference ( 95 % CI ) was 0.14 % ( 0.06 , 0.21 ) , thus confirming non-inferiority . Baseline HbA(1c ) influenced treatment response , with larger reductions in HbA(1c ) observed in patients with baseline HbA(1c ) > or = 8 % in the sitagliptin ( -1.13 % ; n = 74 ) and metformin ( -1.24 % ; n = 73 ) groups . The proportions of patients at week 24 with HbA(1c ) values at the goals of < 7 or < 6.5 % were 69 and 34 % with sitagliptin and 76 and 39 % with metformin , respectively . Fasting plasma glucose changes from baseline were -11.5 mg/dL ( -0.6 mmol/l ) and -19.4 mg/dl ( -1.1 mmol/l ) with sitagliptin and metformin , respectively ( difference in LS mean change from baseline [ 95 % CI ] = 8.0 mg /dl [ 4.5,11.4 ] ) . Both treatments led to similar improvements from baseline in measures of homeostasis model assessment -beta cell function ( HOMA-beta ) and insulin resistance ( HOMA-IR ) . The incidence of hypoglycaemia was 1.7 % with sitagliptin and 3.3 % with metformin ( p = 0.116 ) . The incidence of gastrointestinal-related adverse experiences was substantially lower with sitagliptin ( 11.6 % ) compared with metformin ( 20.7 % ) ( difference in incidence [ 95 % CI ] = -9.1 % [ -13.6,-4.7 ] ) , primarily because of significantly decreased incidences of diarrhoea ( 3.6 vs. 10.9 % ; p < 0.001 ) and nausea ( 1.1 vs. 3.1 % ; p = 0.032 ) . Body weight was reduced from baseline with both sitagliptin ( LS mean change [ 95 % CI ] = -0.6 kg [ -0.9,-0.4 ] ) and metformin ( -1.9 kg [ -2.2 , -1.7 ] ) ( p < 0.001 for sitagliptin vs. metformin ) . CONCLUSIONS In this 24-week monotherapy study , sitagliptin was non-inferior to metformin in improving HbA(1c ) in treatment-naïve patients with type 2 diabetes . Although both treatments were generally well tolerated , a lower incidence of gastrointestinal-related adverse experiences was observed with sitagliptin AIM To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [ haemoglobin A(1c ) ( HbA(1c ) ) 7 - 11 % ] on metformin monotherapy . METHODS Patients ( n = 273 ) on metformin ( > /=1500 mg/day ) were r and omized to receive the addition of once-daily placebo , sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks . The efficacy analysis was based on the all- patients -treated population using an analysis of co-variance with change in HbA(1c ) from baseline as the primary endpoint . RESULTS The mean baseline HbA(1c ) was 7.7 % for the entire cohort . After 18 weeks , both active add-on therapies led to greater improvements in HbA(1c ) from baseline : -0.73 % for sitagliptin ( p < 0.001 vs. placebo ) and -0.79 % for rosiglitazone compared with -0.22 % for placebo . No difference was observed between the sitagliptin and rosiglitazone treatments ( 0.06 % [ 95 % confidence interval ( CI ) : -0.14 to 0.25 ] ) . The proportion of patients achieving an HbA(1c ) < 7 % was greater with sitagliptin ( 55 % ) and rosiglitazone ( 63 % ) compared with placebo ( 38 % ) . Body weight increased from baseline with rosiglitazone ( 1.5 kg ) compared with body weight reduction with sitagliptin ( -0.4 kg ) and placebo ( -0.8 kg ) . The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg ( 95 % CI : 1.3 - 2.5 ) . In a prespecified analysis , the proportion of patients experiencing a greater than 3-kg increase in body weight was 21 % in the rosiglitazone group compared with 2 % in both the sitagliptin and placebo groups . Both active treatments were generally well tolerated , with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo . CONCLUSIONS In this 18-week study , the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy . Treatment with sitagliptin produced similar reductions in HbA(1c ) compared with the addition of rosiglitazone BACKGROUND The present study was conducted to evaluate the efficacy , safety and tolerability of sitagliptin added to ongoing metformin therapy in Chinese patients with type 2 diabetes ( T2DM ) who failed to achieve adequate glycemic control with metformin monotherapy . METHODS After a metformin titration/stabilization period and a 2-week , single-blind , placebo run-in period , 395 Chinese patients with T2DM aged 25 - 77 years ( baseline HbA1c 8.5 % ) were r and omized ( 1:1 ) to double-blind placebo or sitagliptin 100 mg q.d . added to ongoing open-label metformin ( 1000 or 1700 mg/day ) for 24 weeks . RESULTS Significant ( P < 0.001 ) changes from baseline in HbA1c ( -0.9 % ) , fasting plasma glucose ( -1.2 mmol/L ) , and 2-h post-meal plasma glucose ( -1.9 mmol/L ) were seen with sitagliptin compared with placebo . There were no significant differences between sitagliptin and placebo in the incidence of hypoglycemia or gastrointestinal adverse events . A small decrease from baseline body weight was observed in the placebo group compared with no change in the sitagliptin group ( between-group difference 0.5 kg ; P=0.018 ) . CONCLUSIONS The addition of sitagliptin 100 mg to ongoing metformin therapy significantly improved glycemic control and was generally well tolerated in Chinese patients with T2DM who had inadequate glycemic control on metformin alone BACKGROUND New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes ( T2D ) , a progressive disorder that often requires combination therapy . The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D . METHODS The present study was a r and omized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America , Europe , and Asia in 278 patients with HbA1c ranging from ≥7.5 % to ≤11.0 % despite ongoing combination therapy with metformin ( ≥1500 mg/day ) and rosiglitazone ( ≥4 mg/day ) . Patients were r and omized ( 2:1 ) to receive sitagliptin 100 mg or placebo once daily . The main outcome measure was change from baseline in HbA1c at Week 18 . RESULTS Mean baseline HbA1c was 8.8 % . The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was -0.7 % ( P < 0.001 ) at Week 18 and -0.8 % ( P < 0.001 ) at Week 54 . There were also significant ( P < 0.001 ) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54 . Significantly higher proportions of sitagliptin- than placebo-treated patients had HbA1c<7.0 % at Weeks 18 ( 22 % vs 9 % ; P = 0.003 ) and 54 ( 26 % vs 14 % ; P = 0.015 ) . Changes in body weight and the rates of adverse events overall , hypoglycemia , and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study . CONCLUSIONS In patients with T2D , the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo BACKGROUND Most patients with type 2 diabetes begin pharmacotherapy with metformin , but eventually need additional treatment . We assessed the safety and efficacy of once weekly exenatide , a glucagon-like peptide 1 receptor agonist , versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor , sitagliptin , or the thiazolidinedione , pioglitazone , in patients treated with metformin . METHODS In this 26-week r and omised , double-blind , double-dummy , superiority trial , patients with type 2 diabetes who had been treated with metformin , and at baseline had mean glycosylated haemoglobin ( HbA(1c ) ) of 8.5 % ( SD 1.1 ) , fasting plasma glucose of 9.1 mmol/L ( 2.6 ) , and weight of 88.0 kg ( 20.1 ) , were enrolled and treated at 72 sites in the USA , India , and Mexico . Patients were r and omly assigned to receive : 2 mg injected exenatide once weekly plus oral placebo once daily ; 100 mg oral sitagliptin once daily plus injected placebo once weekly ; or 45 mg oral pioglitazone once daily plus injected placebo once weekly . Primary endpoint was change in HbA(1c ) between baseline and week 26 . Analysis was by intention to treat , for all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT00637273 . FINDINGS 170 patients were assigned to receive once weekly exenatide , 172 to receive sitagliptin , and 172 to receive pioglitazone . 491 patients received at least one dose of study drug and were included in the intention-to-treat analysis ( 160 on exenatide , 166 on sitagliptin , and 165 on pioglitazone ) . Treatment with exenatide reduced HbA(1c ) ( least square mean -1.5 % , 95 % CI -1.7 to -1.4 ) significantly more than did sitagliptin ( -0.9 % , -1.1 to -0.7 ) or pioglitazone ( -1.2 % , -1.4 to -1.0 ) . Treatment differences were -0.6 % ( 95 % CI -0.9 to -0.4 , p<0.0001 ) for exenatide versus sitagliptin , and -0.3 % ( -0.6 to -0.1 , p=0.0165 ) for exenatide versus pioglitazone . Weight loss with exenatide ( -2.3 kg , 95 % CI-2.9 to -1.7 ) was significantly greater than with sitagliptin ( difference -1.5 kg , 95 % CI -2.4 to -0.7 , p=0.0002 ) or pioglitazone ( difference -5.1 kg , -5.9 to -4.3 , p<0.0001 ) . No episodes of major hypoglycaemia occurred . The most frequent adverse events with exenatide and sitagliptin were nausea ( n=38 , 24 % , and n=16 , 10 % , respectively ) and diarrhoea ( n=29 , 18 % , and n=16 , 10 % , respectively ) ; upper-respiratory-tract infection ( n=17 , 10 % ) and peripheral oedema ( n=13 , 8 % ) were the most frequent events with pioglitazone . INTERPRETATION The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes . Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone . FUNDING Amylin Pharmaceuticals and Eli Lilly AIMS /HYPOTHESIS The dipeptidyl peptidase IV inhibitor , vildagliptin , increases levels of intact glucagon-like peptide-1 ( GLP-1 ) and improves glycemic control in patients with type 2 diabetes . Although GLP-1 is known to stimulate insulin secretion , vildagliptin does not affect plasma insulin levels in diabetic patients , suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function . METHODS This study examined the effects of 28-d treatment with vildagliptin ( 100 mg , twice daily ; n = 9 ) vs. placebo ( n = 11 ) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels ( beta-cell dose response ) , the change in glucose with time ( derivative component ) , and a potentiation factor , which is a function of time and may reflect the actions of nonglucose secretagogues and other factors . RESULTS Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose ( secretory tone ) , calculated from the dose response ; the difference in least squares mean ( deltaLSM ) was 101 + /- 51 pmol.min(-1).m(-2 ) ( P = 0.002 ) . The slope of the beta-cell dose response , the derivative component , and the potentiation factor were not affected . Vildagliptin also significantly decreased mean pr and ial glucose ( deltaLSM , -1.2 + /- 0.4 mmol/liter ; P = 0.01 ) and glucagon ( deltaLSM , -10.7 + /- 4.8 ng/liter ; P = 0.03 ) levels and increased plasma levels of intact GLP-1 ( deltaLSM , + 10.8 + /- 1.6 pmol/liter ; P < 0.0001 ) and gastric inhibitory polypeptide ( deltaLSM , + 43.4 + /- 9.4 pmol/liter ; P < 0.0001 ) relative to placebo . CONCLUSION Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone OBJECTIVES To evaluate the 2-year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes . METHODS Patients who were on a stable dose of metformin ( > or = 1500 mg/day ) for at least 8 weeks were r and omised in a double-blind manner to receive either sitagliptin 100 mg q.d . ( N = 588 ) or glipizide 5 mg/day ( up-titrated up to 20 mg/day based upon prespecified glycaemic criteria ) ( N = 584 ) . The efficacy analysis assessed the change in HbA(1c ) from baseline using the per- protocol ( PP ) population . RESULTS For the PP cohort , mean baseline HbA(1c ) was 7.3 % in both groups . After 2 years , the least squares ( LS ) mean change in HbA(1c ) from baseline [ 95 % confidence interval ( CI ) ] was -0.54 % ( -0.64 , -0.45 ) with sitagliptin ( n = 248 ) and -0.51 % ( -0.60 , -0.42 ) with glipizide ( n = 256 ) . The rise in HbA(1c ) from week 24 to week 104 [ i.e. coefficient of durability ( COD ) ] was smaller with sitagliptin [ COD ( 95 % CI ) 0.16%/year ( 0.10 , 0.21 ) ] compared with glipizide [ 0.26%/year ( 0.21 , 0.31 ) ] . The proportion of patients with an HbA(1c ) < 7 % was 63 % and 59 % with sitagliptin and glipizide , respectively . The beta-cell responsiveness to a meal challenge was maintained with sitagliptin and decreased with glipizide . The proportion of patients who reported hypoglycaemia was 5 % with sitagliptin and 34 % with glipizide [ difference in proportions ( 95 % CI ) = -29 % ( -33 , -25 ) ] . Relative to baseline , sitagliptin was associated with weight loss ( -1.6 kg ) compared with weight gain ( + 0.7 kg ) with glipizide . CONCLUSION In patients with type 2 diabetes , adding sitagliptin to metformin monotherapy improved glycaemic control over 2 years , similar to the glucose-lowering efficacy observed with adding glipizide , but with greater durability and generally better maintenance of beta-cell function . Sitagliptin was generally well tolerated with a lower risk of hypoglycaemia and weight loss compared with weight gain observed with glipizide BACKGROUND Early initiation of combination therapy using antihyperglycemic agents is recommended for treating type 2 diabetes ( T2D ) . The present multicenter double-blind r and omized parallel-group study examined the efficacy and safety of a sitagliptin and metformin fixed-dose combination ( Sita/Met ) compared with glimepiride in T2D patients as initial treatment . METHODS Type 2 diabetes patients ( aged ≥18 years ) were r and omized to Sita/Met or glimepiride for 30 weeks after a wash-off run-in period . The primary endpoint was change from baseline ( CFB ) in HbA1c . Secondary endpoints included the proportion of patients achieving target goal ( HbA1c < 7.0 % [ 53 mmol/mol ] ) and CFB in fasting plasma glucose ( FPG ) . Safety assessment s comprised weight gain from baseline and the incidence of adverse events ( AEs ) . RESULTS In total , 292 patients were r and omized to Sita/Met ( n = 147 ) or glimepiride ( n = 145 ) . After 30 weeks , Sita/Met demonstrated superiority over glimepiride in reducing HbA1c ( -1.49 % vs -0.71 % , respectively ; between-group difference - 0.78 % ; P < 0.001 ) . A significantly higher proportion of patients achieved the target goal with Sita/Met ( 81.2 % ) than with glimepiride ( 40.1 % ; P < 0.001 ) . Greater reduction in FPG occurred with Sita/Met than with glimepiride ( least-squares mean difference - 23.5 mg/dL ; P < 0.001 ) . Both drugs were generally well tolerated . Hypoglycemia events and weight gain were significantly lower in patients with Sita/Met than with glimepiride ( 5.5 % vs 20.1 % and -0.83 vs + 0.90 kg , respectively ; both P < 0.001 ) . No serious drug-related AEs or deaths were reported . CONCLUSIONS Compared with glimepiride , Sita/Met as an initial treatment led to significantly greater improvements in glycemic control and body weight changes , with a lower incidence of hypoglycemia , over 30 weeks CONTEXT In response to a meal , glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic peptide ( GIP ) are released and modulate glycemic control . Normally these incretins are rapidly de grade d by dipeptidyl peptidase-4 ( DPP-4 ) . DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes . The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test ( OGTT ) were evaluated . OBJECTIVE The objective of the study was to examine the pharmacodynamics , pharmacokinetics , and tolerability of sitagliptin . DESIGN This was a r and omized , double-blind , placebo-controlled , three-period , single-dose crossover study . SETTING The study was conducted at six investigational sites . PATIENTS The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents . INTERVENTIONS Interventions included sitagliptin 25 mg , sitagliptin 200 mg , or placebo . MAIN OUTCOME MEASURES Measurements included plasma DPP-4 activity ; post-OGTT glucose excursion ; active and total incretin GIP levels ; insulin , C-peptide , and glucagon concentrations ; and sitagliptin pharmacokinetics . RESULTS Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h , enhanced active GLP-1 and GIP levels , increased insulin/C-peptide , decreased glucagon , and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin . Sitagliptin was generally well tolerated , with no hypoglycemic events . CONCLUSIONS In this study in patients with type 2 diabetes , near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80 % or greater , corresponding to a plasma sitagliptin concentration of 100 nm or greater , and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT Aims To investigate the difference in the efficacy among dipeptidyl peptidase-4 ( DPP-4 ) inhibitors in Chinese adults with newly diagnosed diabetes . Material s and methods In a multicenter , r and omized study , we enrolled adults who were either treatment naive or off prior anti-hyperglycemic therapy for at least 3 months . Eligible patients had hemoglobin A1c ( HbA1c ) concentrations of 6.5–9.5 % . Three hundred patients had been r and omly allocated to sitagliptin 100 mg , once daily ; vildagliptin 50 mg , twice daily and saxagliptin 5 mg , once daily for 12 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c at week 12 . This study was completed and registered with Clinical Trials.gov , number NCT 01703637 . Results Totally 277 patients were enrolled in the final analysis , and 93 patients received sitagliptin , 94 received vildagliptin and 90 received saxagliptin . Compared with baseline , adjusted mean differences in change from baseline HbA1c at week 12 were −0.50 % ( 95 % CI : −0.20 to −0.90 ) , −0.65 % ( 95 % CI : −0.40 to −1.40 ) , −0.70 ( 95 % CI : −0.50 to −1.00 ) for sitagliptin , vildagliptin and saxagliptin group , respectively . The overall HbA1c-lowering effect was similar for all three selected DPP-4 inhibitors after adjustment for age and baseline HbA1c . Notably , in secondary outcome analysis , patients in vildagliptin group showed a significant decrease in total cholesterol levels , compared with participants in sitagliptin and saxagliptin groups . No significant between-group difference was shown in adverse events ( AE ) . Conclusions The overall HbA1c-lowering effect and incidence of AE were similar for sitagliptin , vildagliptin and saxagliptin in Chinese adults with newly diagnosed diabetes Background : Consistent evidence is still lacking on which one , glimepiride plus metformin or repaglinide plus metformin , is better in treating type 2 diabetes mellitus ( T2DM ) . Therefore , this study was conducted to compare the short-term efficacy and safety of these two methods in treating T2DM . Methods : The literature research dating up to August 2018 was conducted in the electronic data bases . The r and omized controlled trials ( RCTs ) comparing the short-term ( treatment period ≤12 weeks ) efficacy and safety of these two methods in treating patients with T2DM were included . No language limitation was used in this study . The decreased hemoglobin A1c ( HbA1c ) , fasting plasma glucose ( FPG ) , and 2h plasma glucose ( 2hPG ) levels were used as the primary outcome to assess the efficacy , and the adverse events and hypoglycemia were used as the secondary outcome to assess the safety . Results : In total , 11 RCTs composed of 844 T2DM patients were included . The results showed that there were no significant differences in decreasing HbA1c and FPG levels between the two methods , but the estimated st and ardized mean differences favored the repaglinide plus metformin . Meanwhile , the repaglinide plus metformin was significantly more effective in decreasing 2hPG levels than glimepiride plus metformin . In addition , fewer patients reported adverse events and experienced hypoglycemia in the repaglinide plus metformin group . Conclusion : These results indicated that the repaglinide plus metformin might have some advantages over glimepiride plus metformin in the short-term treatment of patients with T2DM , and should be further explored |
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