***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: Abstract . Background : This laboratory study investigated the mechanisms by which the opioid antagonist , naltrexone , reduces the risk of relapse to heavy drinking in individuals with alcohol dependence . Methods : Eighteen alcohol-dependent , non-treatment-seeking volunteers were r and omized to 50 mg naltrexone or placebo for 6 days and participated in an alcohol self-administration experiment on the sixth day . Following baseline assessment s of craving and endocrine levels , subjects were first administered a priming drink design ed to raise blood alcohol levels to 0.03 g/dl and then had the opportunity to drink up to eight additional drinks or to receive US $ 3 for each drink not consumed over a 2-h period . Each additional drink was design ed to raise blood alcohol levels by 0.015 g/dl . Results : At baseline , naltrexone treatment result ed in higher cortisol levels and lower levels of craving than placebo treatment . Although there were no significant differences in response to the priming dose , naltrexone-treated subjects drank fewer drinks , consumed them more slowly , and reported lower levels of alcohol craving during the alcohol self-administration portion of the experiment . Naltrexone also result ed in higher levels of adrenocorticotropic hormone and cortisol than placebo treatment , and levels of cortisol were negatively correlated with intensity of alcohol craving . The number of drinks chosen was positively correlated with level of alcohol craving . Ratings of nausea were low and did not differ between the naltrexone and placebo groups at any point in the study . Conclusions : These results confirm the hypothesis that naltrexone reduces desire to drink and the amount of alcohol consumed in alcohol-dependent subjects . It is hypothesized that naltrexone may reduce drinking via suppressing craving for alcohol and that this effect may be related in part to naltrexone 's ability to activate the hypothalamo – pituitary – adrenocortical axis Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should The opioid antagonist nalmefene offers an alternative to traditional pharmacological treatments for alcoholism . The present study was design ed to investigate the relationship between nalmefene plasma concentration and central μ-opioid receptor occupancy after a clinical ly effective dose ( 20 mg , orally ) . Pharmacokinetics and μ-opioid receptor occupancy of nalmefene after single and repeated dosing over 7 days was studied in 12 healthy subjects . Serial blood sample s were obtained after both dosings , and pharmacokinetic parameters for nalmefene and main metabolites were determined . Central μ-opioid receptor occupancy of nalmefene was measured with positron emission tomography ( PET ) and [11C]carfentanil at four time points ( 3 , 26 , 50 , 74 h ) after both dosings . Nalmefene was rapidly absorbed in all subjects . The mean t1/2 of nalmefene was 13.4 h after single and repeated dosing . The accumulation of nalmefene and its main metabolites in plasma during the repeated dosing period was as expected for a drug with linear pharmacokinetics , and steady-state was reached for all analytes . Both nalmefene dosings result ed in a very high occupancy at μ-opioid receptors ( 87–100 % ) , and the decline in the occupancy was similar after both dosings but clearly slower than the decline in the plasma concentration of nalmefene or metabolites . High nalmefene occupancy ( 83–100 % ) persisted at 26 h after the dosings . The prolonged μ-opioid receptor occupancy by nalmefene indicates slow dissociation of the drug from μ-opioid receptors . These results support the rational of administering nalmefene when needed before alcohol drinking , and they additionally suggest that a high μ-opioid receptor occupancy can be maintained when nalmefene is taken once daily Background Naltrexone is an effective medication for treatment of alcohol dependence , but its efficacy is limited by lack of adherence to the oral dosage form . A long-acting depot formulation of naltrexone may increase adherence . Methods A single site , 6-week open label study was conducted with 16 alcohol dependent subjects each receiving 300 mg of Naltrexone Depot by intramuscular injection .  The main outcomes were safety and tolerability of the Naltrexone Depot formulation , blood levels of naltrexone and its main metabolite 6-beta naltrexol , and self-reported alcohol use . All subjects received weekly individual counseling sessions . Results The medication was well tolerated with 88 % of subjects completing the 6-week trial . The most common side effect experienced was injection site complications . There were no serious adverse events . Subjects had naltrexone and 6-beta-naltrexol concentrations throughout the trial with mean values ranging from 0.58 ng/mL to 2.04 ng/mL and 1.51 ng/mL to 5.52 ng/mL , respectively , at each sampling time following administration . Compared to baseline , subjects had significantly reduced number of drinks per day , heavy drinking days and proportion of drinking days . Conclusion Naltrexone Depot is safe and well tolerated in alcoholics and these findings support the further investigation of its utility in larger double-blind placebo controlled trials Naltrexone , an opiate antagonist medication , has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments . Although the within-treatment efficacy of naltrexone has received primary attention , there has been little published on the outcome of individuals once the medication is discontinued . Animal studies have led to concern regarding a quick rebound to heavy drinking . This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy . Of the 131 subjects evaluated during the treatment phase , 124 ( 95 % ) had up to 14 weeks of posttreatment drinking data available for analysis . Measures of craving and blood markers of heavy drinking were also evaluated . By the end of treatment , naltrexone demonstrated significantly greater efficacy than placebo . However , once the medication was discontinued , there was a gradual increase in relapse rates , heavy drinking days , and drinks per drinking day , and fewer days of abstinence were reported . By the end of the 14-week follow-up period , although naltrexone-treated subjects were , on average , still doing better than control subjects , the effectiveness of naltrexone was no longer statistically significant . There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals . These data suggest that , for a number of alcoholic subjects , continued treatment with naltrexone , or perhaps psychosocial intervention , for longer than 3 months is indicated . Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term This study compared the effects of nefazodone , a serotonergic antidepressant , with the opioid antagonist naltrexone , and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy . Following a single-blind , placebo lead-in period , subjects were r and omly assigned to receive study medication , which they took under double-blind conditions for 11 weeks . Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects , poorer compliance , and a greater rate of treatment attrition . There were no reliable between-group differences in drinking behavior . These results indicate that nefazodone is not efficacious for treatment of alcohol dependence . Furthermore , the clinical utility of naltrexone seems to be limited by its adverse effects , a finding that has important implication s for efforts to develop medications to treat alcohol dependence BACKGROUND Promising treatments for alcoholics include naltrexone ( NTX ) , cue exposure combined with urge-specific coping skills training ( CET ) , and communication skills training ( CST ) . This study investigated the effects of combining these elements as treatment adjuncts . METHODS A 2 x 2 design investigated the effects of CET combined with CST , as compared with an education and relaxation control treatment , during a 2-week partial hospital program ( n = 165 ) followed by 12 weeks of NTX ( 50 mg/day ) or placebo during aftercare ( n = 128 ) . Drinking outcomes were assessed at 3 , 6 , and 12 months after discharge from the partial hospital . Process measures included urge , self-efficacy ( confidence about staying abstinent in risky situations ) , and self-reported coping skills .  Medically eligible alcohol-dependent patients were recruited . RESULTS Among those compliant with medication on at least 70 % of days , those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months . CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12-month follow-ups than patients in the control treatment . Interactions of medication with behavioral treatments were not significant . Process measures showed that NTX result ed in lower weekly urge ratings , and those in CET/CST used more of the prescribed coping skills after treatment , reported fewer cue-elicited urges , and reported more self-efficacy in a posttest role-play test . Drinking reductions at 3 , 6 , and 12 months correlated with more use of coping skills , lower urge , and higher self-efficacy . CONCLUSIONS The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX . They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year . The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes OBJECTIVE The current study investigated the treatment effectiveness , during treatment , of a second-generation cognitive-behavioral therapy for alcoholism -- broad-spectrum treatment (BST)--compared with motivational-enhancement therapy ( MET ) , when both were offered in conjunction with a therapeutic dose of naltrexone ( Revia ) . METHOD One hundred forty-nine alcohol-dependent patients completed a 3-month r and omized , controlled trial of BST and naltrexone versus MET and naltrexone . RESULTS Patients receiving  BST had a significantly higher percentage of days abstinent than patients receiving MET . The superior effect of BST is particularly strong in interaction with support for drinking , suggesting that the advantage of BST is worth the additional cost for patients whose psychosocial networks are supportive of continued drinking . This effect remains significant when controlling for pretreatment percentage of days abstinent . CONCLUSIONS In aggregate , these findings suggest that it is either the combination of naltrexone and BST or the unique properties of BST that account for BST 's superiority to MET and naltrexone . The results of this initial phase of the trial suggest that a second-generation cognitive-behavioral therapy such as BST may have a meaningful clinical advantage over brief interventions such as MET , at least when combined with naltrexone 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 % 
    Output:
    
While a medium-term treatment of NTX gave no benefit in the respect of relapse prevention , it was found to be beneficial on two of four secondary outcomes by increasing time to first drink and diminishing craving .
A medium-term treatment of NTX was superior to acamprosate in reducing relapses , st and ard drinks and craving .
NTX plus an intensive psychosocial treatment ( PST ) was not superior to NTX plus a simple PST on any primary and secondary short-term outcomes .
For a medium-term treatment , NTX plus an intensive PST was superior to NTX plus a simple PST in increasing time to first drink and decreasing craving .
We have not yet known so far how long alcohol-dependent patients who respond to NTX treatment should continue their treatment .
Due to too little evidence , NMF should have no role for the treatment of alcohol dependence