***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 Pathological gambling is a disabling disorder experienced by about 1 % of adults . We r and omised 233 participants ( 41.6 % women ) 1:1:1 to nalmefene ( 20 or 40 mg ) or placebo . In analyses performed using an intention-to-treat ( ITT ) population , nalmefene failed to show statistically significant differences from placebo on primary and secondary outcomes . Post hoc analyses of only participants who received a full titration of the medication for at least 1 week demonstrated that nalmefene 40 mg/day result ed in significantly greater reductions on the primary outcome measure . These findings suggest that medication dosing may be an important consideration in achieving symptom control BACKGROUND Despite the relative success of opiate antagonist medication within controlled clinical trials for alcoholism , laboratory studies have not fully examined potential mechanisms for their efficacy in alcohol-dependent persons . The present study evaluated the impact of naltrexone and nalmefene on craving and subjective effects after a moderate alcohol dose among non-treatment-seeking alcoholics ( n = 125 ) and social drinkers ( n = 90 ) . METHODS Participants were r and omly assigned to receive placebo , naltrexone ( titrated to 50 mg/day ) , or nalmefene ( titrated to 40 mg/day ) for seven days before an alcohol challenge clinical laboratory session . During the clinical laboratory session , a drink of alcohol ( 0.4 mg/kg for men , 0.34 mg/kg for women ) was provided in a bar-like setting . The effects of the alcohol dose on subjective craving , stimulation , and sedation were measured before having free access to alcohol . RESULTS Alcoholics reported higher levels of craving than social drinkers before and after the drink as well as higher levels of alcohol-induced stimulation . Both opiate antagonist medications suppressed initial increases in craving and stimulation . CONCLUSIONS These findings demonstrate that both naltrexone and nalmefene are associated with reduced alcohol-induced craving and stimulation among alcoholics who are not actively attempting to reduce drinking . These data provide insights into potential mechanisms that may underlie opiate antagonists ' effects in the context of treatment 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 No studies have assessed the dose-effect or duration of opioid blockade in opioid abusers produced by oral nalmefene , a micro-opioid antagonist . The present study examined the profile and time course of oral nalmefene blockade of subjective and physiological effects produced by intravenous morphine . To assess these effects , seven opioid abusers received oral nalmefene ( 0 , 50 and 100 mg ) followed by intravenous morphine ( 0 , 10 and 20 mg ) challenges every 24 h for 96 h using a Latin square r and omized cross-over design . The duration of blockade varied by measure and dose . Both 50 and 100 mg nalmefene blocked morphine 's effects up to 48 OBJECTIVE Pathological gambling is a disabling disorder experienced by approximately 1%-2 % of adults and for which there are few empirically vali date d treatments . The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling . METHOD A 16-week , r and omized , dose-ranging , double-blind , placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003 . Two hundred seven persons with DSM-IV pathological gambling were r and omly assigned to receive nalmefene ( 25 mg/day , 50 mg/day , or 100 mg/day ) or placebo . Scores on the primary outcome measure ( Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling ) were analyzed by using a linear mixed-effects model . RESULTS Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling , compared to the placebo group . A total of 59.2 % of the subjects who received 25 mg/day of nalmefene were rated as " much improved " or " very much improved " at the last evaluation , compared to 34.0 % of those who received placebo . Adverse experiences included nausea , dizziness , and insomnia . CONCLUSIONS Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling . Low-dose nalmefene ( 25 mg/day ) appeared efficacious and was associated with few adverse events . Higher doses ( 50 mg/day and 100 mg/day ) result ed in intolerable side effects Abstract Objective To ascertain the current burden of adverse drug reactions ( ADRs ) through a prospect i ve analysis of all admissions to hospital . Design Prospect i ve observational study . Setting Two large general hospitals in Merseyside , Engl and . Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission . Main outcome measures Prevalence of admissions due to an ADR , length of stay , avoidability , and outcome . Results There were 1225 admissions related to an ADR , giving a prevalence of 6.5 % , with the ADR directly leading to the admission in 80 % of cases . The median bed stay was eight days , accounting for 4 % of the hospital bed capacity . The projected annual cost of such admissions to the NHS is £ 466 m ( € 706 m , $ 847 m ) . The overall fatality was 0.15 % . Most reactions were either definitely or possibly avoidable . Drugs most commonly implicated in causing these admissions included low dose aspirin , diuretics , warfarin , and non-steroidal anti-inflammatory drugs other than aspirin , the most common reaction being gastrointestinal bleeding . Conclusion The burden of ADRs on the NHS is high , accounting for considerable morbidity , mortality , and extra costs . Although many of the implicated drugs have proved benefit , measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit : harm ratio of the drugs 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 Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in 
    Output:
    
AND RELEVANCE The three-fold increased risk of withdrawal from treatment on nalmefene due to adverse events is a matter of safety concern .