***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania . METHOD Patients with DSM-IV bipolar I disorder experiencing an acute manic episode ( baseline Young Mania Rating Scale score > /== " BORDER="0">20 ) were r and omly assigned to 3 weeks of treatment with risperidone ( flexible dose : 1 - 6 mg/day ) or placebo . The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale . Secondary efficacy measures included the Clinical Global Impression ( CGI ) severity rating and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and Global Assessment Scale ( GAS ) . Safety assessment s consisted of monitoring adverse events , vital signs , electrocardiogram and laboratory results , and scores on the Extrapyramidal Symptom Rating Scale . RESULTS Subjects ( N=259 ) received treatment with either risperidone ( N=134 ) or placebo ( N=125 ) . The mean modal dose of risperidone was 4.1 mg/day . Improvement in mean Young Mania Rating Scale total score ( adjusted for covariates ) was significantly greater in the risperidone than in the placebo group at endpoint ( mean change=-10.6 [ SD=9.5 ] versus -4.8 [ SD=9.5 ] , respectively ) , with significant between-group differences seen as early as 3 days after start of treatment ( change with risperidone : mean=-6.8 [ SD=5.8 ] ; change with placebo : mean=-4.0 [ SD=5.8 ] ) and continuing throughout all time points . Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and GAS were also significantly greater among patients receiving risperidone than those given placebo . The most common adverse event reported among risperidone patients was somnolence . While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone , mean total and subscale scores were low . CONCLUSIONS Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action . Risperidone was well tolerated by patients in this study The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid‐related disease Background — Clinical trials have demonstrated that , compared with placebo , intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease . However , no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes . Methods and Results — A total of 893 ambulatory coronary artery disease patients ( 30 % women ) 65 to 85 years of age with ≥1 episode of myocardial ischemia that lasted ≥3 minutes during 48-hour ambulatory ECG at screening were r and omized to atorvastatin  80 mg/d or pravastatin  40 mg/d and followed up for 12 months . The primary efficacy parameter ( absolute change from baseline in total duration of ischemia at month 12 ) was significantly reduced in both groups at month 3 and month 12 ( both P<0.001 for each treatment group ) with no significant difference between the treatment groups . Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients , a trend toward fewer major acute cardiovascular events ( hazard ratio , 0.71 ; 95 % confidence interval , 0.46 , 1.09 ; P=0.114 ) , and a significantly greater reduction in all-cause death ( hazard ratio , 0.33 ; 95 % confidence interval , 0.13 , 0.83 ; P=0.014 ) . Conclusions — Compared with moderate pravastatin therapy , intensive atorvastatin therapy was associated with reductions in cholesterol , major acute cardiovascular events , and death in addition to the reductions in ischemia observed with both therapies . The contrast between the therapies ’ differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol – lowering thresholds for ischemia and major acute cardiovascular events may differ . The Study Assessing Goals in the Elderly ( SAGE ) demonstrates that older men and women with coronary artery disease  benefit from intensive statin therapy BACKGROUND Despite the use of aspirin , there is still a risk of ischaemic events after percutaneous coronary intervention ( PCI ) . We aim ed to find out whether , in addition to aspirin , pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI . METHODS 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been r and omly assigned double-blind treatment with clopidogrel ( n=1313 ) or placebo ( n=1345 ) . Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission , and for a median of 10 days overall . After PCI , most patients ( > 80 % ) in both groups received open-label thienopyridine for about 4 weeks , after which study drug was restarted for a mean of 8 months . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , or urgent target-vessel revascularisation within 30 days of PCI . The main analysis was by intention to treat . FINDINGS There were no drop-outs . 59 ( 4.5 % ) patients in the clopidogrel group had the primary endpoint , compared with 86 ( 6.4 % ) in the placebo group ( relative risk 0.70 [ 95 % CI 0.50 - 0.97 ] , p=0.03 ) . Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death , myocardial infa rct ion , or any revascularisation ( p=0.03 ) , and of cardiovascular death or myocardial infa rct ion ( p=0.047 ) . Overall ( including events before and after PCI ) there was a 31 % reduction cardiovascular death or myocardial infa rct ion ( p=0.002 ) . There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group ( p=0.001 ) . At follow-up , there was no significant difference in major bleeding between the groups ( p=0.64 ) . INTERPRETATION In patients with acute coronary syndrome receiving aspirin  , a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events , compared with placebo BACKGROUND The objective of the current study was to examine possible clinical predictors of positive response to lamotrigine or gabapentin monotherapy in treatment-refractory affectively ill patients . METHODS Forty-five patients with treatment refractory bipolar ( n = 35 ) or unipolar ( n = 10 ) affective disorder participated in a clinical study evaluating six weeks of treatment with lamotrigine , gabapentin , or placebo monotherapy given in a double-blind , r and omized fashion with two subsequent cross-overs to the other agents . Patients received daily mood ratings and weekly cross-sectional scales . Much or very much improved on the Clinical Global Impression scale modified for bipolar illness was considered a positive response . Degree of response was correlated with a number of baseline demographic and course of illness variables in a univariate analysis and then by linear regression . RESULTS Response rates to lamotrigine ( 51 % ) exceeded those to gabapentin ( 28 % ) and placebo ( 21 % ) . A positive response to lamotrigine monotherapy was associated with a bipolar diagnosis ; fewer hospitalizations ; fewer prior medication trials ; and male gender ( of which the latter two variables survived logistic regression ) . For gabapentin , degree of response correlated with shorter duration of illness ; younger age ; and lower baseline weight ( with the latter two surviving linear regression ) . CONCLUSIONS In this highly treatment-refractory population , lamotrigine appeared most effective for male patients with fewer prior medication trials . Gabapentin monotherapy , although not better than placebo , appeared most effective in those with younger age and lower baseline weight . These preliminary data in a treatment refractory subgroup may help in the further definition of the range of clinical utility of these widely used anticonvulsants OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy  were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features AIM To compare the efficacy , safety and tolerability of a fixed combination glyburide/metformin preparation with those of glyburide or metformin alone in patients with type 2 diabetes inadequately controlled by sulphonylurea , diet and exercise . METHODS In this 16-week , r and omized , double-blind , parallel group study , 639 patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea  were r and omly assigned to : glyburide 10 mg b.i.d . ( n = 164 ) ; metformin 500 mg ( n = 153 ) ; glyburide/metformin 2.5 mg/500 mg ( n = 160 ) ; or glyburide/metformin 5 mg/500 mg ( n = 162 ) . Titration was allowed to maximum doses of 2000 mg for metformin or 10 mg/2000 mg and 20 mg/2000 mg for glyburide/metformin 2.5 mg/500 mg and 5 mg/500 mg respectively . The primary outcome measure was HbA1c level after 16 weeks ; secondary end-points included fasting and 2-h post-pr and ial plasma glucose . Adverse events ( AEs ) were recorded and summarized by treatment group . RESULTS Both strengths of glyburide/metformin equally reduced mean HbA1c by 1.7 % more than did glyburide alone ( p < 0.001 ) , and by 1.9 % more than did metformin alone ( p < 0.001 ) . Final mean fasting plasma glucose concentrations were also lower in both glyburide/metformin groups than in the glyburide ( -2.8 mmol/l , -51.3 mg/dl ; p < 0.001 ) and metformin groups ( -3.6 mmol/l , -64.2 mg/dl ; p < 0.001 ) . Safety and tolerability were similar across all treatment groups , except for a higher incidence of gastrointestinal AEs in the metformin monotherapy group , and more patients reporting mild or moderate symptoms of hypoglycaemia while taking glyburide/metformin . CONCLUSIONS Both glyburide/metformin tablet strengths produced , with equal efficacy , significantly better glycaemic control than monotherapy with either agent . These data also confirm that glycaemic efficacy does not require maximal sulphonylurea doses in combination with metformin AIMS In observational studies , prolonged lower blood total cholesterol levels - down at least to 3 mmol . l-1 - are associated 
    Output:
    
Findings , based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women .
Some clinical ly important exceptions , however , were apparent : women experienced substantially lower response rates with newer antiemetics than men ( 45 % vs. 58 % ; relative risk 1.49 , 95 % confidence interval 1.35 - 1.64 ) ; men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder ; women discontinued lovastatin more frequently than men because of adverse events .
Overall , for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment .