***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: This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence . Seven hundred and eighteen patients ( placebo=360 ; nalmefene=358 ) , ≥ 18 years of age , with a diagnosis of alcohol dependence , ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening , were r and omised ( 1:1 ) to 24 weeks of as-needed  placebo or nalmefene 18 mg/day . The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days ( group difference : -1.7 days/month [ 95 % CI -3.1 ; -0.4 ] ; p=0.012 ) and a better but not significant effect in reducing total alcohol consumption ( group difference : -5.0 g/day last month [ 95 % CI -10.6 ; 0.7 ] ; p=0.088 ) . A subgroup analysis showed that patients who did not reduce their drinking prior to r and omisation benefitted more from nalmefene . Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group . Adverse events were more common with nalmefene ; the incidence of adverse events leading to dropout was similar in both groups . This study provides evidence for the efficacy of nalmefene , which constitutes a new pharmacological treatment paradigm in terms of treatment goal ( reduced drinking ) and dosing regimen ( as-needed ) , in alcohol dependent patients unable to reduce alcohol consumption on their own Recognition of the broad consequences of adolescent substance abuse has led to increased emphasis on balancing traditional measures of treatment effectiveness , such as frequency of substance use , with measures of patient functioning and quality of life ( QOL ) . This study evaluated the longitudinal association between frequency of use and QOL among adolescent substance abusers receiving a brief outpatient intervention . Participants were 106 adolescents , aged 13 to 21 years , who met criteria for substance abuse or dependence and completed 4 assessment s over a 12 month period . Results of a parallel-process latent growth curve model indicated a moderate longitudinal association , such that reduced frequency of use was associated with QOL improvement . Elaboration of the temporal ordering of this association via a cross-lagged panel model revealed that frequency of substance use predicted subsequent QOL , but that QOL did not predict subsequent frequency of use . Implication s pertaining to the assessment of comprehensive outcomes and the setting of treatment expectations are discussed Objectives To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels ( DRLs ) as defined by the WHO , and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases , injuries and deaths . Design Decision modelling using Markov chains compared costs and effects over 5 years . Setting The analysis was from the perspective of the National Health Service ( NHS ) in Engl and and Wales . Participants The model considered the licensed population for nalmefene , specifically adults with both alcohol dependence and high/very high DRLs , who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment . Data sources We modelled treatment effect using data from three clinical trials for nalmefene ( ESENSE 1 ( NCT00811720 ) , ESENSE 2 ( NCT00812461 ) and SENSE ( NCT00811941 ) ) . Baseline characteristics of the model population , treatment re source utilisation and utilities were from these trials . We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies . Health-related costs were from UK sources . Main outcome measures We measured incremental cost per quality -adjusted life year ( QALY ) gained and number of alcohol-attributable harmful events avoided .  Results Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio ( ICER ) of £ 5204 per QALY gained , and was therefore cost-effective at the £ 20 000 per QALY gained decision threshold . Sensitivity analyses showed that the conclusion was robust . Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years . Conclusions Nalmefene can be seen as a cost-effective treatment for alcohol dependence , with substantial public health benefits . Trial registration numbers This cost-effectiveness analysis was developed based on data from three r and omised clinical trials : ESENSE 1 ( NCT00811720 ) , ESENSE 2 ( NCT00812461 ) and SENSE ( NCT00811941 ) Aims : The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment , i.e. the pooled subgroup of patients with at least a high drinking risk level ( men : > 60 g/day ; women : > 40 g/day ) at both screening and r and omization from the two r and omized controlled 6-month studies ESENSE 1 ( NCT00811720 ) and ESENSE 2 ( NCT00812461 ) . Methods : Nalmefene 18 mg and placebo were taken on an as-needed basis . All the patients also received a motivational and adherence-enhancing intervention ( BRENDA ) . The co- primary outcomes were number of heavy drinking days ( HDDs ) and mean total alcohol consumption ( g/day ) in Month 6 measured using the Timeline Follow-back method . Additionally , data on clinical improvement , liver function and safety were collected throughout the study . Results : The pooled population consisted of 667 patients : placebo n = 332 ; nalmefene  n = 335 . There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [ treatment difference : −3.2 days ( 95 % CI : −4.8 ; −1.6 ) ; P < 0.0001 ] and total alcohol consumption [ treatment difference : −14.3 g/day ( −20.8 ; −7.8 ) ; P < 0.0001 ] at Month 6 . Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group . Adverse events and adverse events leading to dropout were more common with nalmefene than placebo . Conclusion : As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and r and omization , and the effect in this subgroup was larger than in the total population BACKGROUND Clinical studies with opioid antagonists for treatment of  problem drinking  have mainly been conducted in specialized alcohol treatment centers , included structured psychosocial treatment , and have focused on maintaining abstinence after a period of abstinence from alcohol . METHODS This multisite , r and omized double-blind study investigated targeted nalmefene in reducing heavy drinking . Specialized alcohol treatment centers and private general practice s enrolled 403 subjects ( 328 men , 75 women ) . Subjects were instructed to take nalmefene 10 to 40 mg ( n=242 ) or placebo ( n=161 ) when they believed drinking to be imminent . After 28 weeks , 57 subjects from the nalmefene group continued into a 24-week r and omized withdrawal extension . Concomitant psychosocial intervention was minimal and no treatment goals were imposed . Alcohol consumption was recorded using the time-line follow-back method . Biochemical indicators of alcohol use were also measured . RESULTS The mean monthly number of heavy drinking days ( HDDs ) during the 12-week period before inclusion was 15.5 ( SD 6.9 ) in the nalmefene group and 16.2 ( SD 6.9 ) in the placebo group . During treatment , the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group ( p=0.0065 ) . The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group ( p=0.0088 and 0.0023 ) . During the r and omized withdrawal period , subjects r and omized to placebo apparently returned to heavier drinking . Subjects receiving  nalmefene  reported more nausea , insomnia , fatigue , dizziness , and malaise than subjects on placebo . CONCLUSIONS Nalmefene appears to be effective and safe in reducing heavy drinking , even when accompanied by minimal psychosocial support This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing  alcohol consumption . We r and omised ( 1:3 ) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day : A total of 112 patients ( 68 % ) in the placebo group and 310 ( 62 % ) in the nalmefene group completed the study . At month 6 , the co- primary outcome variables showed no statistically-significant differences between the treatment groups ; but at month 13 , nalmefene was more effective than placebo , both in the reduction of the number of heavy drinking days ( HDDs ) ( − 1.6 days/month ( 95 % CI − 2.9 ; − 0.3 ) ; p = 0.017 ) and the reduction of total alcohol consumption ( TAC ) ( − 6.5 g/day last month ( 95 % CI − 12.5 ; − 0.4 ) ; p = 0.036 ) . In a subgroup analysis of patients with high/very high drinking risk levels at screening and at r and omisation ( the target population ) , there was a significant effect in favour of nalmefene  on TAC at month 6 , and on both HDD and TAC at month 13 . Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene , compared to placebo . Most adverse events were mild or moderate , and transient ; adverse events , including those leading to dropout , were more common with nalmefene . This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily , following a brief intervention Abstract : The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals . This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene ( 5 , 20 , or 40 mg ) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals . Participants concomitantly received 4 sessions of a motivational enhancement therapy ( with a medication compliance component ) delivered from trained counselors . Although more subjects in the active medication groups terminated the study early secondary to adverse events , the rates did not differ significantly from that of placebo . The 20-mg/d group experienced more insomnia , dizziness , and confusion , while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group . Most of these symptoms were mild and improved over time . Although all subjects had a reduction in heavy drinking days , craving , γ-glutamyl transferase , and carbohydrate-deficient transferrin concentrations over the course of the study , there was no difference between the active medication and placebo groups on these measures . The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups . This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics . However , possibly because of variation among the sites or the comparatively small sample size , there was no evidence of superior efficacy outcomes with nalmefene treatment BACKGROUND Nalmefene is a newer opioid antagonist that is structurally similar to naltrexone but with a number of potential pharmacological advantages for the treatment of alcohol dependence , including no dose-dependent association with toxic effects to the liver , greater oral bioavailability , longer duration of antagonist action , and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking . METHODS A double-blind , placebo-controlled trial was conducted to evaluate the safety and efficacy of 2 doses of oral nalmefene for alcohol dependence . The 105 outpatient volunteers were abstinent for a mean of 2 weeks prior to r and om assignment to the placebo or 20- or 80-mg/d dose nalmefene groups for 12 weeks . Cognitive behavioral therapy was provided weekly during treatment . Self-reported drinking or abstinence was confirmed by determinations of breath alcohol concentration and by collateral informant reports . RESULTS Outcomes did not differ between the 20- and 80-mg dose nalmefene groups . Significantly fewer patients treated with nalmefene than patients given placebo  relapsed to heavy drinking through 12 weeks of treatment ( P 
    Output:
    
Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo , but the weight of these results should not be overestimated , as the BOCF approach to managing withdrawals was used .
The value of nalmefene for treatment of alcohol addiction is not established .
At best , nalmefene has limited efficacy in reducing alcohol consumption