***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: Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts . We report data that vali date a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances . In a cessation study , v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66 . About 43 % vs 13 % quit in the upper vs lower genotype score terciles . Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use . Higher v1.0 scores were associated with ( a ) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence ( P=0.0004 ) and ( b ) lower probabilities of membership in a class that reported escalating use ( P=0.001 ) . These results indicate that : ( a ) we have identified genetic predictors of smoking cessation success , ( b ) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and ( c ) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts Abstract Alcohol and nicotine dependence are common in schizophrenia .  Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers . The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia . Out patients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week , double-blind , r and omized , placebo-controlled trial . Alcohol use and smoking were assessed using self-report ( Timeline Follow-Back ) and biological measures . Adverse events were recorded . Changes in the number of st and ard drinks per week and cigarettes per week were compared in the 2 groups . Because of safety concerns or loss to follow-up , of 55 patients enrolled , only 10 started study medication , 5 each on varenicline and placebo .  Gastrointestinal adverse effects , such as severe abdominal pain , limited study completion to only 4 subjects . Number of st and ard alcoholic drinks consumed per week decreased by [ mean ( SD ) ] 16.6 ( 20.1 ) in the varenicline group and by 2.4 ( 27.4 ) in the placebo group . Mean ( SD ) number of cigarettes smoked per week decreased by 66 ( 65 ) in the varenicline group and by 47 ( 77 ) in the placebo group . Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability ( gastrointestinal adverse effects ) limiting retention . There was no increased number of serious neuropsychiatric adverse events in the varenicline group . Based on this small sample , concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline INTRODUCTION Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist , a class of drugs that includes varenicline and cytisine . Varenicline is efficacious for smoking cessation , while cytisine has not been studied systematic ally . The efficacy of dianicline has not been previously tested in an adequately powered study . METHODS In a r and omized , double-blind , parallel group placebo-controlled trial , 602 generally healthy cigarette smokers were assigned to dianicline ( n = 300 ) or placebo ( n = 302 ) for 7 weeks followed by a 19-week off drug follow-up period . RESULTS Exhaled carbon monoxide and cotinine-confirmed continuous abstinence rates for Weeks 4 - 7 were 24.0 % for dianicline versus 20.5 % for placebo ( odds ratio 1.22 ; 95 % CI , 0.83 - 1.80 ; p = .307 ) . For Weeks 4 - 26 , the abstinence rates were 16.7 % for dianicline versus 13.9 % for placebo ( odds ratio 1.24 ; 95 % CI , 0.79 - 1.93 ; p = .366 ) . Craving for a cigarettes was reduced by dianicline compared with placebo after 7 weeks ( p = .0175 ) . Nicotine withdrawal symptoms measured by the Hughes and Hatsukami Minnesota Withdrawal Scale were lower for dianicline compared with placebo in the first 3 weeks of treatment during which time quit rates were also higher in the dianicline-treated group . CONCLUSIONS Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment . However , self-reported craving and nicotine withdrawal symptoms were reduced BACKGROUND Varenicline is approved as an aid to smoking cessation in adults aged > or = 18 years . OBJECTIVE The goal of this study was to characterize the multiple-dose pharmacokinetics , safety , and tolerability of varenicline in adolescent smokers . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study enrolled healthy 12- to 16-year-old smokers ( > or =3 cigarettes daily ) into high-body-weight ( > 55 kg ) and low-body-weight ( < or = 55 kg ) groups . Subjects were r and omized to receive 14 days of treatment with a high dose of varenicline , a low dose of varenicline , or placebo . The varenicline doses in the high-body-weight group were 1 mg BID and 0.5 mg BID ; the varenicline doses in the low-body-weight group were 0.5 mg BID and 0.5 mg once daily . The apparent renal clearance ( CL/F ) and volume of distribution ( V/F ) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling . RESULTS The high-body-weight group consisted of 35 subjects ( 65.7 % male ; 77.1 % white ; mean age , 15.2 years ) . The low-body-weight group consisted of 37 subjects ( 37.8 % male ; 48.6 % white ; mean age , 14.3 years ) . The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d . The CL/F for a 70-kg adolescent was 10.4 L/h , comparable to that in a 70-kg adult . The estimated varenicline V/F was decreased in individuals of small body size , thus predicting a varenicline C(max ) approximately 30 % greater in low-body-weight subjects than in high-body-weight subjects . In high-body-weight subjects , steady-state varenicline exposure , as represented by the AUC(0 - 24 ) , was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID , consistent with values reported previously in adult smokers at the equivalent doses . In low-body-weight subjects , varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily , values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID , respectively . Among high-body-weight subjects , adverse events ( AEs ) were reported by 57.1 % of subjects in both the high- and low-dose varenicline groups and by 14.3 % of subjects in the placebo group ; among low-body-weight subjects , AEs were reported by 64.3 % , 73.3 % , and 12.5 % of subjects in the high-dose varenicline , low-dose varenicline , and placebo groups , respectively . The most common AEs were nausea , headache , vomiting , and dizziness . Psychiatric AEs that were considered treatment related included abnormal dreams in 2 subjects and mild , transient anger in 1 subject . Of the AEs reported by > or = 1 subject in any treatment group , > or = 92 % were mild in intensity . No subject discontinued the study because of an AE . CONCLUSIONS Varenicline steady-state exposure in study subjects weighing > 55 kg was similar to that observed previously in adults . The body-weight effect on varenicline pharmacokinetics , which result ed in higher exposure in individuals of smaller body size ( < or = 55 kg ) , was adequately offset by administration of half the varenicline dose recommended in adults . Varenicline was generally well tolerated during the 14-day treatment period . Clinical Trials Identification Number : NCT00463918 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 UNLABELLED There are few data concerning changes in lung function and respiratory symptoms in smokers with chronic obstructive pulmonary disease ( COPD ) weeks to months after quitting smoking . We examined serial changes in spirometry and Clinical COPD Question naire ( CCQ ) scores ( measuring respiratory symptoms and health-related quality of life ) in COPD participants by smoking status during a smoking cessation trial . In this r and omized , double-blind trial , smokers with mild-to-moderate COPD were treated with varenicline 1 mg b.i.d . or placebo for 12 weeks and followed to Week 52 . Primary endpoints of abstinence were previously reported . Secondary endpoints were mean changes from baseline in post-bronchodilator forced expired volume in 1 s ( FEV(1 ) ) and CCQ scores . Change from baseline in post-bronchodilator FEV(1 ) was significantly improved in continuous abstainers ( 121.8 mL ) vs. continuous smokers ( 37.9 mL ) at Week 12 ( P = 0.0069 ) , but not at Weeks 24 or 52 . Mean change from baseline at Week 12 in CCQ Total Score was significantly better in continuous abstainers ( -1.04 ) vs. continuous smokers ( -0.53 ; P < 0.0001 ) : this improvement was sustained at Weeks 24 and 52 . In a 1-year cessation trial of smokers with COPD , continuous abstinence compared with continuous smoking significantly improved post-bronchodilator FEV(1 ) at Week 12 ( although the difference narrowed subsequently ) and 
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However , subsequent observational cohort studies and meta-analyses have not confirmed these fears , and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders , including suicidal ideation and suicidal behaviour .
The evidence is not conclusive , however , in people with past or current psychiatric disorders .
Lower dose regimens also conferred benefits for cessation , while reducing the incidence of adverse events .
Limited evidence suggests that varenicline may have a role to play in relapse prevention .
The most frequently recorded adverse effect of varenicline is nausea , but mostly at mild to moderate levels and tending to subside over time .