***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: CONTEXT Hypothetically , topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol 's reinforcing effects through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system . OBJECTIVE To determine if topiramate is a safe and efficacious treatment for alcohol dependence . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled , 14-week trial of 371 men and women aged 18 to 65 years diagnosed with alcohol dependence , conducted between January 27 , 2004 , and August 4 , 2006 , at 17 US sites . INTERVENTIONS Up to 300 mg/d of topiramate ( n = 183 ) or placebo ( n = 188 ) , along with a weekly compliance enhancement intervention . MAIN OUTCOME MEASURES Primary efficacy variable was self-reported percentage of heavy drinking days . Secondary outcomes included other self-reported drinking measures ( percentage of days abstinent and drinks per drinking day ) along with the laboratory measure of alcohol consumption ( plasma gamma-glutamyltransferase ) . RESULTS Treating all dropouts as relapse to baseline , topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 ( mean difference , 8.44 % ; 95 % confidence interval , 3.07%-13.80 % ; P = .002 ) . Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days ( mean difference , 16.19 % ; 95 % confidence interval , 10.79%-21.60 % ; P < .001 ) and all other drinking outcomes ( P < .001 for all comparisons ) . Adverse events that were more common with topiramate vs placebo , respectively , included paresthesia ( 50.8 % vs 10.6 % ) , taste perversion ( 23.0 % vs 4.8 % ) , anorexia ( 19.7 % vs 6.9 % ) , and difficulty with concentration ( 14.8 % vs 3.2 % ) . CONCLUSION Topiramate is a promising treatment for alcohol dependence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00210925 BACKGROUND Initiation of a relapse prevention medication is crucial at the end of alcohol detoxification . This study aim ed to examine the efficacy and safety of topiramate for alcoholism in patients receiving a residential treatment program of alcohol detoxification and post-acute treatment . METHODS This was a 12-week , r and omized , double-blind , placebo-controlled trial of topiramate for alcoholism in patients receiving a residential treatment program . Individuals with DSM-IV alcohol dependence with minimal withdrawal were enrolled . Participants were r and omly assigned to receive either 100 - 300 mg/day of topiramate or placebo . Primary outcomes were given as percentages of heavy drinking days and time to first day of heavy drinking . Other drinking outcomes , craving , and health-related quality of life were evaluated . RESULTS A total of 106 participants were r and omized to receive topiramate ( n=53 ) or placebo ( n=53 ) . Twenty-eight participants of the topiramate group ( 52.8 % ) and 25 participants of the placebo group ( 47.2 % ) completed the study . Averaged over the trial period , there was no significant difference between groups on the mean percentages of heavy drinking days [ 1.96 ( -1.62 to 5.54 ) , p=.28 ] . Log rank survival analysis found no difference of time to first day of heavy drinking  between topiramate and placebo groups ( 61.8 vs. 57.5 days , respectively ; χ(2)=0.61 , d.f.=1 , p=.81 ) . Other secondary outcomes were not significantly different between groups . CONCLUSIONS By using a conservative model for data analysis , we could not detect the effectiveness of topiramate in this particular population . As the sensitivity analysis showed a trend of its benefit , further studies in larger sample sizes are still warranted BACKGROUND Topiramate , a sulphamate fructopyranose derivative , might antagonise alcohol 's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function . We aim ed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence . METHODS We did a double-blind r and omised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence . Of these 150 individuals , 75 were assigned to receive topiramate ( escalating dose of 25 - 300 mg per day ) and 75 had placebo as an adjunct to weekly st and ardised medication compliance management . Primary efficacy variables were : self-reported drinking ( drinks per day , drinks per drinking day , percentage of heavy drinking days , percentage of days abstinent ) and plasma gamma-glutamyl transferase , an objective index of alcohol consumption . The secondary efficacy variable was self-reported craving . FINDINGS At study end , participants on topiramate , compared with those on placebo , had 2.88 ( 95 % CI -4.50 to -1.27 ) fewer drinks per day ( p=0.0006 ) , 3.10 ( -4.88 to -1.31 ) fewer drinks per drinking day ( p=0.0009 ) , 27.6 % fewer heavy drinking days ( p=0.0003 ) , 26.2 % more days abstinent ( p=0.0003 ) , and a log plasma gamma-glutamyl transferase ratio of 0.07 ( -0.11 to -0.02 ) less ( p=0.0046 ) . Topiramate-induced differences in craving were also significantly greater than those of placebo , of similar magnitude to the self-reported drinking changes , and highly correlated with them . INTERPRETATION Topiramate ( up to 300 mg per day ) is more efficacious than placebo as an adjunct to st and ardised medication compliance management in treatment of alcohol dependence CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs BACKGROUND More than half of all individuals with bipolar disorder have a substance abuse problem at some point in their lifetime . Patients with comorbid substance abuse disorders often are excluded from clinical trials . Thus , treatments targeting this high-risk clinical population are lacking . OBJECTIVE To evaluate the efficacy of divalproex sodium ( hereafter referred to as valproate ) in decreasing alcohol use and stabilizing mood symptoms in acutely ill patients with bipolar disorder and alcoholism . DESIGN A 24-week , double-blind , placebo-controlled , r and omized parallel-group trial . SETTING A university hospital serving as a primary catchment-area hospital and tertiary-care facility . PARTICIPANTS Fifty-nine subjects with diagnoses of bipolar I disorder and alcohol dependence . Intervention All study subjects received treatment as usual , including lithium carbonate and psychosocial interventions , and were r and omized to receive valproate or placebo . MAIN OUTCOME MEASURES Primary alcohol use outcomes included changes in alcohol use as indicated by changes in proportion of heavy drinking days and number of drinks per heavy drinking day . Other alcohol use outcomes included proportion of any drinking days , number of drinks per drinking day , and relapse to sustained heavy drinking . Mood outcomes included changes in depressive and manic symptoms . We used the mixed model to analyze longitudinal data . The first model used time of assessment , bipolar subtype ( mixed , manic , or depressed ) , and treatment group ( placebo or valproate ) as covariates . The second nested model included the additional covariate of medication adherence . RESULTS The valproate group had a significantly lower proportion of heavy drinking days ( P = .02 ) and a trend toward fewer drinks per heavy drinking day ( P = .055 ) than the placebo group . When medication adherence was added as covariate , the valproate group had significantly fewer drinks per heavy drinking day ( P = .02 ) and fewer drinks per drinking day ( P = .02 ) . Higher  valproate serum concentration significantly correlated with improved alcohol use outcomes . Manic and depressive symptoms improved equally in both groups . Level of gamma-glutamyl transpeptidase was significantly higher in the placebo group compared with the valproate group . CONCLUSIONS Valproate therapy decreases heavy drinking in patients with comorbid bipolar disorder and alcohol dependence . The results of this study indicate the potential clinical utility of the anticonvulsant mood stabilizer , valproate , in bipolar disorder with co-occurring alcohol dependence Although drinking urges and cravings are commonly reported by alcoholics , prospect i ve studies have found inconsistent associations between such urges and drinking relapses . Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity . To permit improved evaluation of hypotheses regarding alcohol craving , a 49-item question naire that reflects several urge-related domains was developed and pretested . Items assessed subjects ' desire for a drink , expectations of positive effects following drinking , relief of withdrawal and negative affect following drinking , and intention to drink . Exploratory and confirmatory factor analyses of the responses of 351 abstinent , treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor . Based on these analyses , an internally consistent , reliable , and psychometrically valid 8-item scale , the Alcohol Urge Question naire ( AUQ ) , was developed . Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol , and that they declined with prolonged abstinence . The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations Pregabalin ( PRE ) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels . In this r and omised , double-blind comparison trial with naltrexone ( NAL ) , we aim ed to investigate the efficacy of PRE on  alcohol drinking indices . Craving reduction and improvement of psychiatric symptoms were the secondary endpoints . Seventy-one alcohol-dependent subjects were detoxified and subsequently r and omised into two groups , receiving 50 mg of NAL or 150—450 mg of PRE .  Craving ( VAS ; OCDS ) , withdrawal ( CIWA-Ar ) and psychiatric symptoms ( SCL-90-R ) rating scales were applied . Alcohol drinking indices and craving scores were not significantly different between groups . Compared with NAL , PRE result ed in greater improvement of specific symptoms in the areas of anxiety , hostility and psychoticism , and survival function ( duration of abstinence from alcohol )  . PRE also result ed in better outcome in patients reporting a comorbid psychiatric disorder . Results from this study globally place PRE within the same range of efficacy as that of NAL . The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomat 
    Output:
    
The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate .