Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Unintended Consequences of Incentive Provision for Behaviour Change and Maintenance around Childbirth

Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation

A mixed methods feasibility study of nicotine-assisted smoking reduction programmes delivered by community pharmacists – The RedPharm study

BACKGROUND: Pivotal trials have established that, among people who have no immediate intention to quit smoking, nicotine replacement therapy (NRT) helps people reduce and eventually stop smoking. The prime aim of this trial was to investigate the feasibility of implementing such a programme in community pharmacies. In addition, we investigated the effectiveness of providing behavioural support compared with self-help methods and of shorter compared with standard length reduction programmes. METHODS: Pharmacists were trained to deliver a smoking reduction programme and opportunistically invite people to participate in the programme. In a 2 × 2 factorial design, eligible volunteers were randomised to either receive in-person behavioural support or a self-help booklet. In both cases, participants were supported to set targets to reduce their smoking and use behavioural techniques to assist reduction. In addition, participants were randomised to cut down and stop over 4 weeks or over 16 weeks, but in either case continue NRT for up to nine months. We assessed uptake and adherence to the programme and smoking cessation four weeks and six months after a quit day and reduction in the three months following programme end and incorporated a qualitative processes assessment. RESULTS: Only 68 of the planned 160 smokers could be recruited. Pharmacists were deterred by the bureaucracy of trial enrolment and that many smokers did not return for further support. Pharmacists sometimes subverted the randomisation or provided support to participants in the self-help arm. Smokers stayed in the programme for an average of 6 weeks rather than the 9 months envisaged. Rates of follow-up declined to around 20% of participants by 12 months. There was insufficient evidence to assess whether support or speed of reduction enhanced cessation or reduction but cessation and reduction were less common overall than in the pivotal trials for licensing NRT for this indication. CONCLUSIONS: This programme of smoking reduction and the trial design to assess its effectiveness proved unpopular to potential participants and pharmacists. As a result, the trial produced no evidence on the effectiveness of behavioural support or speed or smoking reduction. A trial of this programme in this context is unfeasible

Evaluation of a student-run smoking cessation clinic for a medically underserved population

<p>Abstract</p> <p>Background</p> <p>Smoking is common among medically underserved populations. Accessible resources to encourage and support smoking cessation among these patients are limited. Volunteer medical student-run free smoking cessation clinics may provide an effective option to help these individuals achieve smoking abstinence. In order to demonstrate the feasibility and cost-effectiveness of a student-run clinic, we analyzed a case series of patients receiving care in a medical student-run Smoking Cessation Clinic (SCC) at the Rochester, Minnesota Salvation Army Good Samaritan Health Clinic (GSHC).</p> <p>Findings</p> <p>Between January 2005 and March 2009, 282 cigarette smokers seeking care at the SCC were analyzed. Student providers at the SCC conducted 1652 weekly individual counseling sessions averaging 18 minutes per encounter. Patients were offered a choice of pharmacotherapies including nicotine replacement therapy (NRT), bupropion, and varenicline for up to 12 weeks. Smoking abstinence was confirmed with exhaled carbon monoxide (CO). Thirty-two patients completed the entire 12-week program (11.3%). At last contact, 94 patients (33.3%) abstained from smoking for ≥ 7 days and 39 patients (13.8%) were continuously abstinent for ≥ 4 weeks. The 7-day point prevalence abstinence rates at last contact were 58.6% for varenicline, 41.2% for bupropion, 33.9% for NRT, and 23.5% for bupropion and NRT. Analyzing missing patients as smoking, the 7-day point prevalence abstinence rates were 7.1%, 8.9%, and 8.2%, at 1 month, 2 months, and 3 months after program enrollment, respectively. No serious adverse drug reactions were recorded.</p> <p>Conclusions</p> <p>Our medical student-run smoking cessation clinic provided an effective and safe experience for medically underserved patients who might not otherwise have access to conventional smoking cessation programs because of high cost, lack of insurance, or other disparities. Similar medical student initiatives focusing on healthy lifestyles may be feasible and beneficial for individuals with limited access to healthcare resources.</p

A Randomized Placebo-Controlled Trial of Varenicline for Smoking Cessation Allowing Flexible Quit Dates

Introduction: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. Methods: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. Results: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). Conclusions: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (~3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55–1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60–1.99), NRT gum (OR 1.60, 95% CI, 1.37–1.86) or patch (OR 1.63, 95% CI, 1.41–1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77–2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10–2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72–2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20–6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12–4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65–5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22–2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16–2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17–2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22–2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness

Genome-wide association study of a nicotine metabolism biomarker in African American smokers:impact of chromosome 19 genetic influences

BACKGROUND AND AIMS: The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches. DESIGN: Genome-wide association study (GWAS). SETTING: Multiple sites within Canada and the United States. PARTICIPANTS: AA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; n = 504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; n = 450). MEASUREMENTS: Genome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates. FINDINGS: Meta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (P = 1.47e-39; beta = 0.59 per C (versus T) allele, SE = 0.045), located ~9.5 kb 3' of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; n = 480). None of the hits were in UGT or OCT2 genes. CONCLUSIONS: Three independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk