***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: Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial Background — Smoking cessation is a key component of secondary cardiovascular disease prevention . Varenicline , a partial & agr;4&bgr;2 nicotinic acetylcholine receptor agonist , is effective for smoking cessation in healthy smokers , but its efficacy and safety in smokers with cardiovascular disease are unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease . Participants received varenicline ( 1 mg twice daily ) or placebo , along with smoking-cessation counseling , for 12 weeks . Follow-up lasted 52 weeks . The primary end point was carbon monoxide – confirmed continuous abstinence rate for weeks 9 through 12 ( last 4 weeks of treatment ) . The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 ( 47.0 % versus 13.9 % ; odds ratio , 6.11 ; 95 % confidence interval [ CI ] , 4.18 to 8.93 ) and weeks 9 through 52 ( 19.2 % versus 7.2 % ; odds ratio , 3.14 ; 95 % CI , 1.93 to 5.11 ) . The varenicline and placebo groups did not differ significantly in cardiovascular mortality ( 0.3 % versus 0.6 % ; difference , −0.3 % ; 95 % CI , −1.3 to 0.7 ) , all-cause mortality ( 0.6 % versus 1.4 % ; difference , −0.8 % ; 95 % CI , −2.3 to 0.6 ) , cardiovascular events ( 7.1 % versus 5.7 % ; difference , 1.4 % ; 95 % CI , −2.3 to 5.0 ) , or serious adverse events ( 6.5 % and 6.0 % ; difference , 0.5 % ; 95 % CI , −3.1 to 4.1 ) . As a result of adverse events , 9.6 % of varenicline and 4.3 % of placebo participants discontinued study drug . Conclusions — Varenicline is effective for smoking cessation in smokers with cardiovascular disease . It was well tolerated and did not increase cardiovascular events or mortality ; however , trial size and duration limit definitive conclusions about safety . Clinical Trial Registration Information— URL : http://www . clinical trials.gov/ct2/show/NCT00282984 . Unique identifier : NCT00282984 BACKGROUND Currently available smoking cessation therapies have limited success rates . Varenicline tartrate is a novel , selective nicotinic receptor partial agonist developed specifically for smoking cessation . This study evaluated the efficacy , tolerability , and safety of 3 varenicline doses for smoking cessation . Bupropion hydrochloride was included as an active control . METHODS A phase 2 , multicenter , r and omized , double-blind , placebo-controlled study of healthy smokers ( 18 - 65 years old ) . Subjects were r and omized to varenicline tartrate , 0.3 mg once daily ( n = 128 ) , 1.0 mg once daily ( n = 128 ) , or 1.0 mg twice daily ( n = 127 ) , for 6 weeks plus placebo for 1 week ; to 150-mg sustained-release bupropion hydrochloride twice daily ( n = 128 ) for 7 weeks ; or to placebo ( n = 127 ) for 7 weeks . RESULTS During the treatment phase , the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate , 1.0 mg twice daily ( 48.0 % ; P<.001 ) and 1.0 mg once daily ( 37.3 % ; P<.001 ) , than for placebo ( 17.1 % ) . The  bupropion  rate was 33.3 % ( P = .002 vs placebo ) . The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate , 1.0 mg twice daily , group compared with the placebo group ( 14.4 % vs 4.9 % ; P = .002 ) . The  bupropion rate was 6.3 % ( P = .60 vs placebo ) . Discontinuation owing to treatment-emergent adverse events was 15.9 % for bupropion , 11.2 % to 14.3 % for varenicline , and 9.8 % for placebo . No dose-related increases occurred in adverse events for varenicline . CONCLUSIONS Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily ) and long-term efficacy ( 1 mg twice daily ) vs placebo . Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation Sixty subjects were run in a study comparing the use of nicotine gum with placebo gum  during cessation from smoking . Subjects were given clinic support and chewed the gum ad libitum . A survival analysis showed the two groups differed significantly in successful abstinence over time ( p less than .03 ) . Differences between groups appeared early ( within weeks ) and , at six months , a 28 % superiority of nicotine over placebo gum was demonstrated with mean success rates of 48 % and 20 % , respectively . Between six months and one year , relapse in the nicotine group accounted for the 30 % vs. 20 % success rates for nicotine and placebo observed at one year . In a pilot study ( " dispensary " ) testing the efficacy of the two gums when intervention was minimal , subjects in both groups resumed smoking within the first two weeks . The enhanced short-term success rates with nicotine gum in the clinic study are attributed to an effective interaction between use of the active preparation and clinic support . Long-term cessation may require extended maintenance procedures and /or an identification of optimal gum use Background : Varenicline , a new treatment for smoking cessation , has demonstrated significantly greater efficacy over placebo and sustained release bupropion ( bupropion SR ) . A study was undertaken to compare a 12-week st and ard regimen of varenicline with a 10-week st and ard regimen of transdermal nicotine replacement therapy ( NRT ) for smoking cessation . Methods : In this 52-week , open-label , r and omised , multicentre , phase 3 trial conducted in Belgium , France , the Netherl and s , UK and USA , participants were r and omly assigned ( 1:1 ) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT ( 21 mg/day reducing to 7 mg/day ) for 10 weeks . Non-treatment follow-up continued to week 52 . The primary outcome was the biochemically confirmed ( exhaled carbon monoxide ⩽10 ppm ) self-reported continuous abstinence rate ( CAR ) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment . Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52 , and measures of craving , withdrawal and smoking satisfaction . Results : A total of 376 and 370 participants assigned to varenicline and NRT , respectively , were eligible for analysis .  The CAR for the last 4 weeks of treatment was significantly greater for varenicline ( 55.9 % ) than NRT ( 43.2 % ; OR 1.70 , 95 % CI 1.26 to 2.28 , p<0.001 ) . The week 52 CAR ( NRT , weeks 8–52 ; varenicline , weeks 9–52 ) was 26.1 % for varenicline and 20.3 % for NRT ( OR 1.40 , 95 % CI 0.99 to 1.99 , p = 0.056 ) . Varenicline significantly reduced craving ( p<0.001 ) , withdrawal symptoms ( p<0.001 ) and smoking satisfaction ( p<0.001 ) compared with NRT . The most frequent adverse event was nausea  ( varenicline , 37.2 % ; NRT , 9.7 % ) . Conclusions : The outcomes of this trial established that abstinence from smoking was greater and craving , withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT . Trial registration number : NCT00143325 Objective - To compare the effectiveness of two different stop smoking interventions . Design - A r and omised , controlled trial . Results based on intention to treat . Setting - Three towns in the south-eastern part of Norway . Interventions - Visits to GP for " practice as usual " ( GP group ) or participation in the behavioural programme SmokEnders ( SE group ) with follow-up 2 weeks , 2 months and 1 year after an agreed stopping date . Subjects - 139 smokers recruited through open invitation . Main outcome measure - Self-reported smoking stop rate 2 weeks , 2 months and 1 year after an agreed stopping date , completed with biochemical indicators by the 1-year registration . Results ? Two weeks after the agreed cessation date , 10/70 ( 14 % ) of the GP group and 46/69 ( 67 % ) of the SE group had stopped smoking . After 2 months , 9/70 ( 13 % ) in the GP group and 37/69 ( 54 % ) in the SE group were non-smokers . One year after cessation 5/70 ( 7 % ) in the GP group and 21/69 ( 30 % ) in the SE group were non-smokers . Conclusions ? Both interventions were effective as measured by the smoking cessation rate . However , the intervention in the SE group was considerably more effective than in the GP group , which suffered from a sizeable number of drop-outs A non-combustible nicotine inhaler , administered orally , has been developed for treatment of smokers . The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking . Subjects were r and omly assigned to  active ( n = 112 ) and placebo ( n = 111 ) groups . Some behavioral intervention occurred as a function of participation . Strict abstinence ( primary outcome criterion ) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year . Survival analysis showed active inhaler was superior to placebo ( p < 0.01 ) . Active vs. placebo  success rates were : 63 % vs. 47 % ( day 3 ) , 46 % vs. 28 % ( week 1 ) , 36 % vs. 19 % ( week 2 ) , 33 % vs. 16 % ( week 3 ) , 29 % vs. 14 % ( week 6 ) , 24 % vs. 10 % ( 3 months ) , 17 % vs. 9 % ( 6 months ) and 13 % vs. 8 % ( 1 year ) . chi 2 analyses were significant through 3 months but not at 6 months ( p < 0.08 ) or 1 year . Craving was relieved with active inhalers at day 3 and week 1 . Subjects averaged six inhalers/day . Cotinine levels were 57 - 61 % of smoking levels . Common side effects included throat/mouth irritation and coughing . Failure was predicted by early slips . The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy . Extended access to the inhaler and relapse prevention training could improve success rates . Another promising approach would be to combine the inhaler with a nicotine patch BACKGROUND Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking . It is not known whether psychological intervention increases the efficacy of these antidepressants . This study compared both drugs with placebo . It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention . METHODS This was a 2 ( medical management vs psychological intervention ) x 3 ( bupropion vs nortriptyline vs placebo ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 36 , and 52 . RESULTS Psychological intervention produced higher 7-day point-pre 
    Output:
    
CONCLUSIONS Evidence suggests that combination therapy benefits may be less than previously thought .
Combined with BT , varenicline increases abstinence more than other pharmacotherapy with BT combinations