***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: BACKGROUND R and omized efficacy clinical trials conducted in research setting s may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical setting s. Effectiveness trials ( eg , in primary care setting s ) are needed to estimate the benefits of cessation treatments in real-world use . METHODS A total of 1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics . Patients were r and omly assigned to 5 active pharmacotherapies : 3 monotherapies ( nicotine patch , nicotine lozenge , and bupropion hydrochloride sustained release [ SR ] ) and 2 combination therapies ( patch + lozenge and bupropion SR + lozenge ) . Patients were referred to a telephone quit line for cessation counseling . Primary outcomes included 7-day point prevalence abstinence at 1 week , 8 weeks , and 6 months after quitting and number of days to relapse . RESULTS Among 7128 eligible smokers ( > or = 10 cigarettes per day ) attending routine primary care appointments , 1346 ( 18.9 % ) were enrolled in the study .  Six-month abstinence rates for the 5 active pharmacotherapies were the following : bupropion SR , 16.8 % ; lozenge , 19.9 % ; patch , 17.7 % ; patch + lozenge , 26.9 % ; and bupropion SR + lozenge , 29.9 % . Bupropion SR + lozenge was superior to all of the monotherapies ( odds ratio , 0.46 - 0.56 ) ; patch + lozenge was superior to patch and bupropion monotherapies ( odds ratio , 0.56 and 0.54 , respectively ) . CONCLUSIONS One in 5 smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence -based counseling and medication . In this comparative effectiveness study of 5 tobacco dependence treatments , combination pharmacotherapy significantly increased abstinence compared with monotherapies . Provision of free cessation medications plus quit line counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit . Trial Registration clinical trials.gov Identifier : NCT00296647 AIM To examine changes in nicotine withdrawal , nicotine craving , self-efficacy to quit smoking , and perceived control over withdrawal symptoms as predictors of smoking cessation following behavioral counseling and nicotine replacement therapy in a sample of smokers . DESIGN AND SETTING The data were ascertained from a r and omized effectiveness trial comparing nicotine patch to nicotine lozenge . Predictors of smoking cessation were assessed at baseline and 5 weeks post-baseline , and 24-hour point prevalence abstinence , biochemically confirmed , was assessed at the end-of-treatment ( week 15 ) and 6 months after a target quit date ( week 27 ) . PARTICIPANTS 642 treatment-seeking smokers r and omized to 12 weeks of nicotine patch or nicotine lozenge . FINDINGS Participants who showed a greater increase in self-efficacy to quit smoking ( OR=1.09 , 95 % CI : 1.02 - 1.16 , p=.01 ) and perceived control over withdrawal symptoms ( OR=1.02 , 95 % CI : 1.00 - 1.04 , p=.05 ) were significantly more likely to have quit smoking at week 15 . Participants who showed a greater increase in self-efficacy to quit smoking ( OR=1.04 , 95 % CI : 1.01 - 1.06 , p=.01 ) were significantly more likely to have quit smoking at week 27 . Changes in withdrawal symptoms and craving were not related to week 15 or week 27 abstinence rates . CONCLUSIONS The results highlight two relatively under-studied potential psychological predictors of abstinence following treatment for nicotine dependence . Behavioral counseling interventions to promote smoking cessation should help smokers develop confidence in their ability to quit smoking and increase their sense of control over withdrawal symptoms to increase their chances for cessation IMPORTANCE The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the st and ard 8 weeks . This decision was based in part on data showing increased efficacy for 24 weeks of treatment . Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit . OBJECTIVE To compare 8 ( st and ard ) , 24 ( extended ) , and 52 ( maintenance ) weeks of nicotine patch treatment for promoting tobacco abstinence . DESIGN , SETTING , AND PARTICIPANTS We recruited 525 treatment-seeking smokers for a r and omized clinical trial conducted from June 22 , 2009 , through April 15 , 2014 , through 2 universities . INTERVENTIONS Smokers received 12 smoking cessation behavioral counseling sessions and were r and omized to 8 , 24 , or 52 weeks of nicotine patch treatment . MAIN OUTCOMES AND MEASURES The primary outcome was 7-day point prevalence abstinence , confirmed with breath levels of carbon monoxide at 6 and 12 months ( intention to treat ) . RESULTS At 24 weeks , 21.7 % of participants in the st and ard treatment arm were abstinent , compared with 27.2 % of participants in the extended and maintenance treatment arms ( χ(2)(1 ) = 1.98 ; P = .17 ) . In a multivariate model controlled for covariates , participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the st and ard treatment arm ( odds ratio [ OR ] , 1.70 [ 95 % CI , 1.03 - 2.81 ] ; P = .04 ) , had a longer duration of abstinence until relapse ( β = 21.30 [ 95 % CI , 10.30 - 32.25 ] ; P < .001 ) , reported smoking fewer cigarettes per day if not abstinent ( mean [ SD ] , 5.8 [ 5.3 ] vs 6.4 [ 5.1 ] cigarettes per day ; β = 0.43 [ 95 % CI , 0.06 - 0.82 ] ; P = .02 ) , and reported more abstinent days ( mean [ SD ] , 80.5 [ 38.1 ] vs 68.2 [ 43.7 ] days ; OR , 1.55 [ 95 % CI , 1.06 - 2.26 ] ; P = .02 ) . At 52 weeks , participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the st and ard and extended treatment arms ( 20.3 % vs 23.8 % ; OR , 1.17 [ 95 % CI , 0.69 - 1.98 ] ; P = .57 ) . Similarly , we found no difference in week 52 abstinence rates between participants in the extended and st and ard treatment arms ( 26.0 % vs 21.7 % ; OR , 1.33 [ 95 % CI , 0.72 - 2.45 ] ; P = .36 ) . Treatment duration was not associated with any adverse effects or adherence to the counseling regimen , but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the st and ard and extended treatment arms ( mean [ SD ] , 3.94 [ 2.5 ] , 4.61 [ 2.0 ] , and 4.7 [ 2.4 ] patches/wk , respectively ; F2,522 = 6.03 ; P = .003 ) . CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment , although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01047527 Background The use of nicotine replacement therapy before quitting smoking is called nicotine preloading . St and ard smoking cessation protocol s suggest commencing nicotine replacement therapy only on the first day of quitting smoking ( quit day ) aim ing to reduce withdrawal symptoms and craving . However , other , more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after . Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward . A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed . Methods / Design This is a study protocol for a multicenter , non-blinded , r and omized controlled trial based in the United Kingdom , enrolling 1786 smokers who want to quit , funded by the National Institute for Health Research , Health Technology Assessment program , and sponsored by the University of Oxford . Participants will primarily be recruited through general practice s and smoking cessation clinics , and r and omized ( 1:1 ) either to use 21 mg nicotine patches  , or  not  , for four weeks before quitting , whilst smoking as normal . All participants will be referred to receive st and ard smoking cessation service support . Follow-ups will take place at one week , four weeks , six months and 12 months after quit day . The primary outcome will be prolonged , biochemically verified six-month abstinence . Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration , side effects , costs of treatment , and markers of potential mediators and moderators of the preloading effect . Discussion This large trial will add substantially to evidence on the effectiveness of nicotine preloading , but also on its cost effectiveness and potential mediators , which have not been investigated in detail previously . A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample , and the multicentre design means that knowledge can be shared between recruitment teams . The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of st and ard smoking cessation service practice .Trial registration Current Controlled Trials IS RCT N33031001 . Registered 27 April 2012 BACKGROUND Smoking is considered as an addiction to nicotine for most subjects consuming 10 cigarettes or more per day . Hence , nicotine replacement therapy by way of gum , patch , or spray has been advocated . The rationale of this study is to evaluate the possible beneficial effects of adding nicotine gum to the routine of subjects using the nicotine patch .  The effect of the nicotine patch against the placebo , both groups receiving placebo nicotine gum , has also been assessed . METHODS Healthy subjects ( 374 ) were r and omized at their work- setting in a 1-year double-blind placebo-controlled trial : 149 subjects to active nicotine patch + active gum ( group 1 ) , 150 to active nicotine patch + placebo gum ( group 2 ) , and 75 to placebo patch + gum ( group 3 ) . Treatment duration was 12 weeks with a 16-hr transdermal patch of 15 mg , followed by a 6 + 6-weeks weaning period on respectively 10 and 5 mg patches . Gum use was not restricted during the first 6 months , with recommendations to use at least four pieces a day . A strict definition of smoking abstinence was used in this study , which did not allow smoking any cigarette after Week 1 .  Nonsmoking status at each visit , as reported by the subjects , was verified by CO below 10 ppm in expired air . RESULTS Abstinence rates in group 1 against group 2 were 34.2 and 22.7 % ( P = 0.027 ) at 12 weeks , 27.5 and 15.3 % ( P = 0.010 ) at 24 weeks , and 18.1 and 12.7 % ( P = 0.191 ) at 52 weeks . In group 3 , abstinence rates were 17.3 , 14.7 , and 13.3 % respectively at 12 , 24 , and 52 weeks . Using logistic regression with adjustment for six baseline covariates , odds ratios for abstinence ( with 95 % CI ) were computed . For group 1/group 2 , OR at 12 , 24 , and 52 weeks were 1.72 ( 1.03 - 2.94 ) ( P = 0.039 ) , 2.04 ( 1.14 - 3.57 ) ( P = 0.018 ) , and 1.47 ( 0.76 - 2.76 ) ( P = 0.125 ) . No significant differences in OR were observed when comparing groups 2 and 3 . Time to relapse is significantly longer in group 1 as compared to that of group 2 ( P = 0.041 ) , whereas no significant differences between groups 2 and 3 were observed . No significant differences between the three groups in systemic and local adverse drug events were observed . CONCLUSION Adding active gum use to active patch use in subjects smoking 10 cigarettes or more a day increased abstinence rates , which are statistically significant up to 24 weeks Objective To assess the impact of instructional guidance in 
    Output:
    
Five studies comparing 4 mg gum to 2 mg gum found a benefit of the higher dose ( RR 1.43 , 95 % CI 1.12 to 1.83 , 5 studies , 856 participants ; I2 = 63 % ) ; however , results of a subgroup analysis suggest that only smokers who are highly dependent may benefit .
Most comparisons found no evidence of an effect on cardiac AEs , SAEs or withdrawals .
There is high-certainty evidence that using combination NRT versus single-form NRT , and 4 mg versus 2 mg nicotine gum , can increase the chances of successfully stopping smoking .
There was no clear evidence of superiority for 42/44 mg over 21/22 mg ( 24-hour ) patches .
Using a fast-acting form of NRT , such as gum or lozenge , result ed in similar quit rates to nicotine patches .