Three Perspectives on a Successful Succession.

Leadership succession does not need to be extremely difficult. However, it does require time, a carefully planned process, well-defined roles, and the intent of all parties to achieve a successful transition-along with the trust to make these various aspects come together. In a CEO succession, the work does not begin at the time of an announced retirement or departure but rather well in advance. The outgoing CEO must want to make the upcoming transition as smooth as possible for everyone involved. The organization must already be committed to the ongoing education of its board, medical staff, and administrators so that all stakeholders are well prepared to execute the transition. Candidates for the CEO role in transition also must be confident in the knowledge of their own needs as well as the needs of the organization. When everyone's best interests come together to create a good fit, the succession can be successful.In this article, the leadership transition at one healthcare system is recounted from the perspectives of three principal players: the outgoing president and CEO, the chair of the board of trustees search committee, and the incoming president and CEO.

Nicotine replacement therapy versus control for smoking cessation.

BACKGROUND: Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. OBJECTIVES: To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017. SELECTION CRITERIA: Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews. DATA COLLECTION AND ANALYSIS: Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare. AUTHORS' CONCLUSIONS: There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.

Individual behavioural counselling for smoking cessation.

BACKGROUND: Individual counselling from a smoking cessation specialist may help smokers to make a successful attempt to stop smoking. OBJECTIVES: The review addresses the following hypotheses:1. Individual counselling is more effective than no treatment or brief advice in promoting smoking cessation.2. Individual counselling is more effective than self-help materials in promoting smoking cessation.3. A more intensive counselling intervention is more effective than a less intensive intervention. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register for studies with counsel* in any field in May 2016. SELECTION CRITERIA: Randomized or quasi-randomized trials with at least one treatment arm consisting of face-to-face individual counselling from a healthcare worker not involved in routine clinical care. The outcome was smoking cessation at follow-up at least six months after the start of counselling. DATA COLLECTION AND ANALYSIS: Both authors extracted data in duplicate. We recorded characteristics of the intervention and the target population, method of randomization and completeness of follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically-validated rates where available. In analysis, we assumed that participants lost to follow-up continued to smoke. We expressed effects as a risk ratio (RR) for cessation. Where possible, we performed meta-analysis using a fixed-effect (Mantel-Haenszel) model. We assessed the quality of evidence within each study using the Cochrane 'Risk of bias' tool and the GRADE approach. MAIN RESULTS: We identified 49 trials with around 19,000 participants. Thirty-three trials compared individual counselling to a minimal behavioural intervention. There was high-quality evidence that individual counselling was more effective than a minimal contact control (brief advice, usual care, or provision of self-help materials) when pharmacotherapy was not offered to any participants (RR 1.57, 95% confidence interval (CI) 1.40 to 1.77; 27 studies, 11,100 participants; I2 = 50%). There was moderate-quality evidence (downgraded due to imprecision) of a benefit of counselling when all participants received pharmacotherapy (nicotine replacement therapy) (RR 1.24, 95% CI 1.01 to 1.51; 6 studies, 2662 participants; I2 = 0%). There was moderate-quality evidence (downgraded due to imprecision) for a small benefit of more intensive counselling compared to brief counselling (RR 1.29, 95% CI 1.09 to 1.53; 11 studies, 2920 participants; I2 = 48%). None of the five other trials that compared different counselling models of similar intensity detected significant differences. AUTHORS' CONCLUSIONS: There is high-quality evidence that individually-delivered smoking cessation counselling can assist smokers to quit. There is moderate-quality evidence of a smaller relative benefit when counselling is used in addition to pharmacotherapy, and of more intensive counselling compared to a brief counselling intervention.

Group behaviour therapy programmes for smoking cessation.

BACKGROUND: Group therapy offers individuals the opportunity to learn behavioural techniques for smoking cessation, and to provide each other with mutual support. OBJECTIVES: To determine the effect of group-delivered behavioural interventions in achieving long-term smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, using the terms 'behavior therapy', 'cognitive therapy', 'psychotherapy' or 'group therapy', in May 2016. SELECTION CRITERIA: Randomized trials that compared group therapy with self-help, individual counselling, another intervention or no intervention (including usual care or a waiting-list control). We also considered trials that compared more than one group programme. We included those trials with a minimum of two group meetings, and follow-up of smoking status at least six months after the start of the programme. We excluded trials in which group therapy was provided to both active therapy and placebo arms of trials of pharmacotherapies, unless they had a factorial design. DATA COLLECTION AND ANALYSIS: Two review authors extracted data in duplicate on the participants, the interventions provided to the groups and the controls, including programme length, intensity and main components, the outcome measures, method of randomization, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in participants smoking at baseline. We used the most rigorous definition of abstinence in each trial, and biochemically-validated rates where available. We analysed participants lost to follow-up as continuing smokers. We expressed effects as a risk ratio for cessation. Where possible, we performed meta-analysis using a fixed-effect (Mantel-Haenszel) model. We assessed the quality of evidence within each study and comparison, using the Cochrane 'Risk of bias' tool and GRADE criteria. MAIN RESULTS: Sixty-six trials met our inclusion criteria for one or more of the comparisons in the review. Thirteen trials compared a group programme with a self-help programme; there was an increase in cessation with the use of a group programme (N = 4395, risk ratio (RR) 1.88, 95% confidence interval (CI) 1.52 to 2.33, I2 = 0%). We judged the GRADE quality of evidence to be moderate, downgraded due to there being few studies at low risk of bias. Fourteen trials compared a group programme with brief support from a health care provider. There was a small increase in cessation (N = 7286, RR 1.22, 95% CI 1.03 to 1.43, I2 = 59%). We judged the GRADE quality of evidence to be low, downgraded due to inconsistency in addition to risk of bias. There was also low quality evidence of benefit of a group programme compared to no-intervention controls, (9 trials, N = 1098, RR 2.60, 95% CI 1.80 to 3.76 I2 = 55%). We did not detect evidence that group therapy was more effective than a similar intensity of individual counselling (6 trials, N = 980, RR 0.99, 95% CI 0.76 to 1.28, I2 = 9%). Programmes which included components for increasing cognitive and behavioural skills were not shown to be more effective than same-length or shorter programmes without these components. AUTHORS' CONCLUSIONS: Group therapy is better for helping people stop smoking than self-help, and other less intensive interventions. There is not enough evidence to evaluate whether groups are more effective, or cost-effective, than intensive individual counselling. There is not enough evidence to support the use of particular psychological components in a programme beyond the support and skills training normally included.

Combined pharmacotherapy and behavioural interventions for smoking cessation.

BACKGROUND: Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are effective in helping people to stop smoking. Combining both treatment approaches is recommended where possible, but the size of the treatment effect with different combinations and in different settings and populations is unclear. OBJECTIVES: To assess the effect of combining behavioural support and medication to aid smoking cessation, compared to a minimal intervention or usual care, and to identify whether there are different effects depending on characteristics of the treatment setting, intervention, population treated, or take-up of treatment. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2015 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating combinations of pharmacotherapy and behavioural support for smoking cessation, compared to a control receiving usual care or brief advice or less intensive behavioural support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by two authors. Data was extracted by one author and checked by another.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: Fifty-three studies with a total of more than 25,000 participants met the inclusion criteria. A large proportion of studies recruited people in healthcare settings or with specific health needs. Most studies provided NRT. Behavioural support was typically provided by specialists in cessation counselling, who offered between four and eight contact sessions. The planned maximum duration of contact was typically more than 30 minutes but less than 300 minutes. Overall, studies were at low or unclear risk of bias, and findings were not sensitive to the exclusion of any of the six studies rated at high risk of bias in one domain. One large study (the Lung Health Study) contributed heterogeneity due to a substantially larger treatment effect than seen in other studies (RR 3.88, 95% CI 3.35 to 4.50). Since this study used a particularly intensive intervention which included extended availability of nicotine gum, multiple group sessions and long term maintenance and recycling contacts, the results may not be comparable with the interventions used in other studies, and hence it was not pooled in other analyses. Based on the remaining 52 studies (19,488 participants) there was high quality evidence (using GRADE) for a benefit of combined pharmacotherapy and behavioural treatment compared to usual care, brief advice or less intensive behavioural support (RR 1.83, 95% CI 1.68 to 1.98) with moderate statistical heterogeneity (I² = 36%).The pooled estimate for 43 trials that recruited participants in healthcare settings (RR 1.97, 95% CI 1.79 to 2.18) was higher than for eight trials with community-based recruitment (RR 1.53, 95% CI 1.33 to 1.76). Compared to the first version of the review, previous weak evidence of differences in other subgroup analyses has disappeared. We did not detect differences between subgroups defined by motivation to quit, treatment provider, number or duration of support sessions, or take-up of treatment. AUTHORS' CONCLUSIONS: Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care. Updating this review with an additional 12 studies (5,000 participants) did not materially change the effect estimate. Although trials differed in the details of their populations and interventions, we did not detect any factors that modified treatment effects apart from the recruitment setting. We did not find evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects.

Nicotine receptor partial agonists for smoking cessation.

BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). OBJECTIVES: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development.We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. 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. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. AUTHORS' CONCLUSIONS: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. 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. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.Future trials of cytisine may test extended regimens and more intensive behavioural support.

Interventions to reduce harm from continued tobacco use.

BACKGROUND: Although smoking cessation is currently the only guaranteed way to reduce the harm caused by tobacco smoking, a reasonable secondary tobacco control approach may be to try and reduce the harm from continued tobacco use amongst smokers unable or unwilling to quit. Possible approaches to reduce the exposure to toxins from smoking include reducing the amount of tobacco used, and using less toxic products, such as pharmaceutical, nicotine and potential reduced-exposure tobacco products (PREPs), as an alternative to cigarettes. OBJECTIVES: To assess the effects of interventions intended to reduce the harm to health of continued tobacco use, we considered the following specific questions: do interventions intended to reduce harm have an effect on long-term health status?; do they lead to a reduction in the number of cigarettes smoked?; do they have an effect on smoking abstinence?; do they have an effect on biomarkers of tobacco exposure?; and do they have an effect on biomarkers of damage caused by tobacco? SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Trials Register (CRS) on the 21st October 2015, using free-text and MeSH terms for harm reduction, smoking reduction and cigarette reduction. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of interventions to reduce the amount smoked, or to reduce harm from smoking by means other than cessation. We include studies carried out in smokers with no immediate desire to quit all tobacco use. Primary outcomes were change in cigarette consumption, smoking cessation and any markers of damage or benefit to health, measured at least six months from the start of the intervention. DATA COLLECTION AND ANALYSIS: We assessed study eligibility for inclusion using standard Cochrane methods. We pooled trials with similar interventions and outcomes (> 50% reduction in cigarettes a day (CPD) and long-term smoking abstinence), using fixed-effect models. Where it was not possible to meta-analyse data, we summarized findings narratively. MAIN RESULTS: Twenty-four trials evaluated interventions to help those who smoke to cut down the amount smoked or to replace their regular cigarettes with PREPs, compared to placebo, brief intervention, or a comparison intervention. None of these trials directly tested whether harm reduction strategies reduced the harms to health caused by smoking. Most trials (14/24) tested nicotine replacement therapy (NRT) as an intervention to assist reduction. In a pooled analysis of eight trials, NRT significantly increased the likelihood of reducing CPD by at least 50% for people using nicotine gum or inhaler or a choice of product compared to placebo (risk ratio (RR) 1.75, 95% confidence interval (CI) 1.44 to 2.13; 3081 participants). Where average changes from baseline were compared for different measures, carbon monoxide (CO) and cotinine generally showed smaller reductions than CPD. Use of NRT versus placebo also significantly increased the likelihood of ultimately quitting smoking (RR 1.87, 95% CI 1.43 to 2.44; 8 trials, 3081 participants; quality of the evidence: low). Two trials comparing NRT and behavioural support to brief advice found a significant effect on reduction, but no significant effect on cessation. We found one trial investigating each of the following harm reduction intervention aids: bupropion, varenicline, electronic cigarettes, snus, plus another of nicotine patches to facilitate temporary abstinence. The evidence for all five intervention types was therefore imprecise, and it is unclear whether or not these aids increase the likelihood of smoking reduction or cessation. Two trials investigating two different types of behavioural advice and instructions on reducing CPD also provided imprecise evidence. Therefore, the evidence base for this comparison is inadequate to support the use of these types of behavioural advice to reduce smoking. Four studies of PREPs (cigarettes with reduced levels of tar, carbon and nicotine, and in one case delivered using an electronically-heated cigarette smoking system) showed some reduction in exposure to some toxicants, but it is unclear whether this would substantially alter the risk of harm. We judged the included studies to be generally at a low or unclear risk of bias; however, there were some ratings of high risk, due to a lack of blinding and the potential for detection bias. Using the GRADE system, we rated the overall quality of the evidence for our cessation outcomes as 'low' or 'very low', due to imprecision and indirectness. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. AUTHORS' CONCLUSIONS: People who do not wish to quit can be helped to cut down the number of cigarettes they smoke and to quit smoking in the long term, using NRT, despite original intentions not to do so. However, we rated the evidence contributing to the cessation outcome for NRT as 'low' by GRADE standards. There is a lack of evidence to support the use of other harm reduction aids to reduce the harm caused by continued tobacco smoking. This could simply be due to the lack of high-quality studies (our confidence in cessation outcomes for these aids is rated 'low' or 'very low' due to imprecision by GRADE standards), meaning that we may have missed a worthwhile effect, or due to a lack of effect on reduction or quit rates. It is therefore important that more high-quality RCTs are conducted, and that these also measure the long-term health effects of treatments.

Additional behavioural support as an adjunct to pharmacotherapy for smoking cessation.

BACKGROUND: Effective pharmacotherapies are available to help people who are trying to stop smoking, but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further. OBJECTIVES: To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register in May 2015 for records with any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline that evaluated the addition of personal support or compared two or more intensities of behavioural support. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount of behavioural support. The intervention condition had to involve person-to-person contact. The control condition could receive less intensive personal contact, or just written information. We did not include studies that used a contact-matched control to evaluate differences between types or components of support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: One author prescreened search results and two authors agreed inclusion or exclusion of potentially relevant trials. One author extracted data and another checked them.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically-validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: Forty-seven studies met the inclusion criteria with over 18,000 participants in the relevant arms. There was little evidence of statistical heterogeneity (I² = 18%) so we pooled all studies in the main analysis. There was evidence of a small but statistically significant benefit from more intensive support (RR 1.17, 95% CI 1.11 to 1.24) for abstinence at longest follow-up. All but four of the included studies provided four or more sessions of support to the intervention group. Most trials used NRT. We did not detect significant effects for studies where the pharmacotherapy was nortriptyline (two trials) or varenicline (one trial), but this reflects the absence of evidence.In subgroup analyses, studies that provided at least four sessions of personal contact for the intervention and no personal contact for the control had slightly larger estimated effects (RR 1.25, 95% CI 1.08 to 1.45; 6 trials, 3762 participants), although a formal test for subgroup differences was not significant. Studies where all intervention counselling was via telephone (RR 1.28, 95% CI 1.17 to 1.41; 6 trials, 5311 participants) also had slightly larger effects, and the test for subgroup differences was significant, but this subgroup analysis was not prespecified. In this update, the benefit of providing additional behavioural support was similar for the subgroup of trials in which all participants, including controls, had at least 30 minutes of personal contact (RR 1.18, 95% CI 1.06 to 1.32; 21 trials, 5166 participants); previously the evidence of benefit in this subgroup had been weaker. This subgroup was not prespecified and a test for subgroup differences was not significant. We judged the quality of the evidence to be high, using the GRADE approach. We judged a small number of trials to be at high risk of bias on one or more domains, but findings were not sensitive to their exclusion. AUTHORS' CONCLUSIONS: Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 25%, based on a pooled estimate from 47 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support.

Workplace interventions for smoking cessation.

BACKGROUND: The workplace has potential as a setting through which large groups of people can be reached to encourage smoking cessation. OBJECTIVES: 1. To categorize workplace interventions for smoking cessation tested in controlled studies and to determine the extent to which they help workers to stop smoking.2. To collect and evaluate data on costs and cost effectiveness associated with workplace interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register (July 2013), MEDLINE (1966 - July 2013), EMBASE (1985 - June 2013), and PsycINFO (to June 2013), amongst others. We searched abstracts from international conferences on tobacco and the bibliographies of identified studies and reviews for additional references. SELECTION CRITERIA: We selected interventions conducted in the workplace to promote smoking cessation. We included only randomized and quasi-randomized controlled trials allocating individuals, workplaces, or companies to intervention or control conditions. DATA COLLECTION AND ANALYSIS: One author extracted information relating to the characteristics and content of all kinds of interventions, participants, outcomes and methods of the studies, and a second author checked them. For this update we have conducted meta-analyses of the main interventions, using the generic inverse variance method to generate odds ratios and 95% confidence intervals. MAIN RESULTS: We include 57 studies (61 comparisons) in this updated review. We found 31 studies of workplace interventions aimed at individual workers, covering group therapy, individual counselling, self-help materials, nicotine replacement therapy, and social support, and 30 studies testing interventions applied to the workplace as a whole, i.e. environmental cues, incentives, and comprehensive programmes. The trials were generally of moderate to high quality, with results that were consistent with those found in other settings. Group therapy programmes (odds ratio (OR) for cessation 1.71, 95% confidence interval (CI) 1.05 to 2.80; eight trials, 1309 participants), individual counselling (OR 1.96, 95% CI 1.51 to 2.54; eight trials, 3516 participants), pharmacotherapies (OR 1.98, 95% CI 1.26 to 3.11; five trials, 1092 participants), and multiple intervention programmes aimed mainly or solely at smoking cessation (OR 1.55, 95% CI 1.13 to 2.13; six trials, 5018 participants) all increased cessation rates in comparison to no treatment or minimal intervention controls. Self-help materials were less effective (OR 1.16, 95% CI 0.74 to 1.82; six trials, 1906 participants), and two relapse prevention programmes (484 participants) did not help to sustain long-term abstinence. Incentives did not appear to improve the odds of quitting, apart from one study which found a sustained positive benefit. There was a lack of evidence that comprehensive programmes targeting multiple risk factors reduced the prevalence of smoking. AUTHORS' CONCLUSIONS: 1. We found strong evidence that some interventions directed towards individual smokers increase the likelihood of quitting smoking. These include individual and group counselling, pharmacological treatment to overcome nicotine addiction, and multiple interventions targeting smoking cessation as the primary or only outcome. All these interventions show similar effects whether offered in the workplace or elsewhere. Self-help interventions and social support are less effective. Although people taking up these interventions are more likely to stop, the absolute numbers who quit are low.2. We failed to detect an effect of comprehensive programmes targeting multiple risk factors in reducing the prevalence of smoking, although this finding was not based on meta-analysed data. 3. There was limited evidence that participation in programmes can be increased by competitions and incentives organized by the employer, although one trial demonstrated a sustained effect of financial rewards for attending a smoking cessation course and for long-term quitting. Further research is needed to establish which components of this trial contributed to the improvement in success rates.4. Further research would be valuable in low-income and developing countries, where high rates of smoking prevail and smoke-free legislation is not widely accepted or enforced.

Print-based self-help interventions for smoking cessation.

BACKGROUND: Many smokers give up smoking on their own, but materials giving advice and information may help them and increase the number who quit successfully. OBJECTIVES: The aims of this review were to determine: the effectiveness of different forms of print-based self-help materials, compared with no treatment and with other minimal contact strategies; the effectiveness of adjuncts to print-based self help, such as computer-generated feedback, telephone hotlines and pharmacotherapy; and the effectiveness of approaches tailored to the individual compared with non-tailored materials. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register. Date of the most recent search April 2014. SELECTION CRITERIA: We included randomized trials of smoking cessation with follow-up of at least six months, where at least one arm tested a print-based self-help intervention. We defined self help as structured programming for smokers trying to quit without intensive contact with a therapist. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the participants, the nature of the self-help materials, the amount of face-to-face contact given to intervention and to control conditions, outcome measures, method of randomization, and completeness of follow-up.The main outcome measure was abstinence from smoking after at least six months follow-up in people smoking at baseline. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates when available. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: We identified 74 trials which met the inclusion criteria. Many study reports did not include sufficient detail to judge risk of bias for some domains. Twenty-eight studies (38%) were judged at high risk of bias for one or more domains but the overall risk of bias across all included studies was judged to be moderate, and unlikely to alter the conclusions.Thirty-four trials evaluated the effect of standard, non-tailored self-help materials. Pooling 11 of these trials in which there was no face-to-face contact and provision of structured self-help materials was compared to no intervention gave an estimate of benefit that just reached statistical significance (n = 13,241, risk ratio [RR] 1.19, 95% confidence interval [CI] 1.04 to 1.37). This analysis excluded two trials with strongly positive outcomes that introduced significant heterogeneity. Six further trials without face-to-face contact in which the control group received alternative written materials did not show evidence for an effect of the smoking self-help materials (n = 7023, RR 0.88, 95% CI 0.74 to 1.04). When these two subgroups were pooled, there was no longer evidence for a benefit of standard structured materials (n = 20,264, RR 1.06, 95% CI 0.95 to 1.18). We failed to find evidence of benefit from providing standard self-help materials when there was brief contact with all participants (5 trials, n = 3866, RR 1.17, 95% CI 0.96 to 1.42), or face-to-face advice for all participants (11 trials, n = 5365, RR 0.97, 95% CI 0.80 to 1.18).Thirty-one trials offered materials tailored for the characteristics of individual smokers, with controls receiving either no materials, or stage matched or non-tailored materials. Most of the trials used more than one mailing. Pooling these showed a benefit of tailored materials (n = 40,890, RR 1.28, 95% CI 1.18 to 1.37) with moderate heterogeneity (I² = 32%). The evidence is strongest for the subgroup of nine trials in which tailored materials were compared to no intervention (n = 13,437, RR 1.35, 95% CI 1.19 to 1.53), but also supports tailored materials as more helpful than standard materials. Part of this effect could be due to the additional contact or assessment required to obtain individual data, since the subgroup of 10 trials where the number of contacts was matched did not detect an effect (n = 11,024, RR 1.06, 95% CI 0.94 to 1.20). In two trials including a direct comparison between tailored materials and brief advice from a health care provider, there was no evidence of a difference, but confidence intervals were wide (n = 2992, RR 1.13, 95% CI 0.86 to 1.49).Only four studies evaluated self-help materials as an adjunct to nicotine replacement therapy, with no evidence of additional benefit (n = 2291, RR 1.05, 95% CI 0.88 to 1.25). A small number of other trials failed to detect benefits from using additional materials or targeted materials, or to find differences between different self-help programmes. AUTHORS' CONCLUSIONS: Standard, print-based self-help materials increase quit rates compared to no intervention, but the effect is likely to be small. We did not find evidence that they have an additional benefit when used alongside other interventions such as advice from a healthcare professional, or nicotine replacement therapy. There is evidence that materials that are tailored for individual smokers are more effective than non-tailored materials, although the absolute size of effect is still small. Available evidence tested self-help interventions in high income countries; further research is needed to investigate their effect in contexts where more intensive support is not available.

Antidepressants for smoking cessation.

BACKGROUND: There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction. OBJECTIVES: The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: Twenty-four new trials were identified since the 2009 update, bringing the total number of included trials to 90. There were 65 trials of bupropion and ten trials of nortriptyline, with the majority at low or unclear risk of bias. There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76). There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit. Based on a limited amount of data from direct comparisons, bupropion and nortriptyline appear to be equally effective and of similar efficacy to NRT (bupropion versus nortriptyline 3 trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N = 4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline and NRT). Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (N = 1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant increase in the rate of serious adverse events amongst participants taking bupropion, though the confidence interval only narrowly missed statistical significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation.There was no evidence of a significant effect for selective serotonin reuptake inhibitors on their own (RR 0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1 sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70, 95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5 selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22, 95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N = 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N = 120, RR 0.70, 95% CI 0.24 to 2.07). AUTHORS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Evidence also suggests that bupropion is less effective than varenicline, but further research is needed to confirm this finding. Evidence suggests that neither selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase inhibitors aid cessation.

Pharmacological treatments for smoking cessation.

CLINICAL QUESTION: Among the 3 first-line smoking cessation treatments (nicotine replacement therapy [NRT], bupropion, and varenicline), which is most effective in helping people who smoke achieve and maintain abstinence from smoking for at least 6 months, and what serious adverse events are associated with each? BOTTOM LINE: Higher rates of smoking cessation were associated with NRT (17.6%) and bupropion (19.1%) compared with placebo (10.6%). Varenicline (27.6%) and combination NRT (31.5%) (eg, patch plus inhaler) were most effective for achieving smoking cessation. None of the therapies was associated with an increased rate of serious adverse events.

Pharmacological interventions for smoking cessation: an overview and network meta-analysis.

BACKGROUND: Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness. OBJECTIVES: How do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)? How do the remaining treatments compare with placebo in achieving long-term abstinence? How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits? METHODS: The overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments. We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events. MAIN RESULTS: We identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectively). Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% CredI 2.40 to 3.47). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46). Cytisine (a nicotine receptor partial agonist) returned positive findings (risk ratio (RR) 3.98; 95% CI 2.01 to 7.87), without significant adverse events or SAEs. Across the 82 included and excluded bupropion trials, our estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1:1000), at about 1:1500. SAE meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59). SAE meta-analysis of 14 varenicline trials found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56). Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone. Clonidine increased the chances of quitting (RR 1.63; 95% CI 1.22 to 2.18), but this was offset by a dose-dependent rise in adverse events. Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive. Other treatments failed to demonstrate a benefit compared with placebo. Nicotine vaccines are not yet licensed for use as an aid to smoking cessation or relapse prevention. Nicobrevin's UK license is now revoked, and the manufacturers of rimonabant, taranabant and dianicline are no longer supporting the development or testing of these treatments. AUTHORS' CONCLUSIONS: NRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use. Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.

Telephone counselling for smoking cessation.

BACKGROUND: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. OBJECTIVES: To evaluate the effect of proactive and reactive telephone support via helplines and in other settings to help smokers quit. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register for studies of telephone counselling, using search terms including 'hotlines' or 'quitline' or 'helpline'. Date of the most recent search: May 2013. SELECTION CRITERIA: randomized or quasi-randomised controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters. DATA COLLECTION AND ANALYSIS: One author identified and data extracted trials, and a second author checked them. The main outcome measure was the risk ratio for abstinence from smoking after at least six months follow-up. We selected the strictest measure of abstinence, using biochemically validated rates where available. We considered participants lost to follow-up to be continuing smokers. Where trials had more than one arm with a less intensive intervention we used only the most similar intervention without the telephone component as the control group in the primary analysis. We assessed statistical heterogeneity amongst subgroups of clinically comparable studies using the I² statistic. We considered trials recruiting callers to quitlines separately from studies recruiting in other settings. Where appropriate, we pooled studies using a fixed-effect model. We used a meta-regression to investigate the effect of differences in planned number of calls, selection for motivation, and the nature of the control condition (self help only, minimal intervention, pharmacotherapy) in the group of studies recruiting in non-quitline settings. MAIN RESULTS: Seventy-seven trials met the inclusion criteria. Some trials were judged to be at risk of bias in some domains but overall we did not judge the results to be at high risk of bias. Among smokers who contacted helplines, quit rates were higher for groups randomized to receive multiple sessions of proactive counselling (nine studies, > 24,000 participants, risk ratio (RR) for cessation at longest follow-up 1.37, 95% confidence interval (CI) 1.26 to 1.50). There was mixed evidence about whether increasing the number of calls altered quit rates but most trials used more than two calls. Three studies comparing different counselling approaches during a single quitline contact did not detect significant differences. Of three studies that tested the provision of access to a hotline two detected a significant benefit and one did not.Telephone counselling not initiated by calls to helplines also increased quitting (51 studies, > 30,000 participants, RR 1.27; 95% CI 1.20 to 1.36). In a meta-regression controlling for other factors the effect was estimated to be slightly larger if more calls were offered, and in trials that specifically recruited smokers motivated to try to quit. The relative extra benefit of counselling was smaller when it was provided in addition to pharmacotherapy (usually nicotine replacement therapy) than when the control group only received self-help material or a brief intervention.A further eight studies were too diverse to contribute to meta-analyses and are discussed separately. Two compared different intensities of counselling, both of which detected a dose response; one of these detected a benefit of multiple counselling sessions over a single call for people prescribed bupropion. The others tested a variety of interventions largely involving offering telephone counselling as part of a referral or systems change and none detected evidence of effect. AUTHORS' CONCLUSIONS: Proactive telephone counselling aids smokers who seek help from quitlines. Telephone quitlines provide an important route of access to support for smokers, and call-back counselling enhances their usefulness. There is limited evidence about the optimal number of calls. Proactive telephone counselling also helps people who receive it in other settings. There is some evidence of a dose response; one or two brief calls are less likely to provide a measurable benefit. Three or more calls increase the chances of quitting compared to a minimal intervention such as providing standard self-help materials, or brief advice, or compared to pharmacotherapy alone.

Opioid antagonists for smoking cessation.

BACKGROUND: The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking. OBJECTIVES: To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of MEDLINE using 'Narcotic antagonists' and smoking terms in April 2013. We also contacted investigators, when possible, for information on unpublished studies. SELECTION CRITERIA: We considered randomised controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included in the meta-analysis only those trials which reported data on abstinence for a minimum of six months. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psycho-biological mediating variables associated with nicotine dependence. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. Abstinence at end of treatment was a secondary outcome. We extracted cotinine- or carbon monoxide-verified abstinence where available. Where appropriate, we performed meta-analysis, pooling risk ratios using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: Eight trials of naltrexone met inclusion criteria for meta-analysis of long-term cessation. One trial used a factorial design so five trials compared naltrexone versus placebo and four trials compared naltrexone plus nicotine replacement therapy (NRT) versus placebo plus NRT. Results from 250 participants in one long-term trial remain unpublished. No significant difference was detected between naltrexone and placebo (risk ratio (RR) 1.00; 95% confidence interval (CI) 0.66 to 1.51, 445 participants), or between naltrexone and placebo as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30, 768 participants). The estimate was similar when all eight trials were pooled (RR 0.97; 95% CI 0.76 to 1.24, 1213 participants). In a secondary analysis of abstinence at end of treatment, there was also no evidence of any early treatment effect, (RR 1.03; 95% CI 0.88 to 1.22, 1213 participants). No trials of naloxone or buprenorphine reported abstinence outcomes. AUTHORS' CONCLUSIONS: Based on data from eight trials and over 1200 individuals, there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence, with a point estimate strongly suggesting no effect and confidence intervals that make a clinically important effect of treatment unlikely. Although further trials might narrow the confidence intervals they are unlikely to be a good use of resources.

Physician advice for smoking cessation.

BACKGROUND: Healthcare professionals frequently advise people to improve their health by stopping smoking. Such advice may be brief, or part of more intensive interventions. OBJECTIVES: The aims of this review were to assess the effectiveness of advice from physicians in promoting smoking cessation; to compare minimal interventions by physicians with more intensive interventions; to assess the effectiveness of various aids to advice in promoting smoking cessation, and to determine the effect of anti-smoking advice on disease-specific and all-cause mortality. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register in January 2013 for trials of interventions involving physicians. We also searched Latin American databases through BVS (Virtual Library in Health) in February 2013. SELECTION CRITERIA: Randomised trials of smoking cessation advice from a medical practitioner in which abstinence was assessed at least six months after advice was first provided. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the setting in which advice was given, type of advice given (minimal or intensive), and whether aids to advice were used, the outcome measures, method of randomisation and completeness of follow-up.The main outcome measure was abstinence from smoking after at least six months follow-up. We also considered the effect of advice on mortality where long-term follow-up data were available. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. People lost to follow-up were counted as smokers. Effects were expressed as relative risks. Where possible, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: We identified 42 trials, conducted between 1972 and 2012, including over 31,000 smokers. In some trials, participants were at risk of specified diseases (chest disease, diabetes, ischaemic heart disease), but most were from unselected populations. The most common setting for delivery of advice was primary care. Other settings included hospital wards and outpatient clinics, and industrial clinics.Pooled data from 17 trials of brief advice versus no advice (or usual care) detected a significant increase in the rate of quitting (relative risk (RR) 1.66, 95% confidence interval (CI) 1.42 to 1.94). Amongst 11 trials where the intervention was judged to be more intensive the estimated effect was higher (RR 1.84, 95% CI 1.60 to 2.13) but there was no statistical difference between the intensive and minimal subgroups. Direct comparison of intensive versus minimal advice showed a small advantage of intensive advice (RR 1.37, 95% CI 1.20 to 1.56). Direct comparison also suggested a small benefit of follow-up visits. Only one study determined the effect of smoking advice on mortality. This study found no statistically significant differences in death rates at 20 years follow-up. AUTHORS' CONCLUSIONS: Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Relapse prevention interventions for smoking cessation.

BACKGROUND: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. MAIN RESULTS: Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted. AUTHORS' CONCLUSIONS: At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation.

BACKGROUND: Effective pharmacotherapies are available to help people who are trying to stop smoking, but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further. OBJECTIVES: To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2012 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline that evaluated the addition of personal support or compared two or more intensities of behavioural support. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount of behavioural support. Controls could receive less intensive personal contact, or just written information. We did not include studies that used a contact matched control to evaluate differences between types or components of support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by both authors. Data were extracted by one author and checked by the other.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: Thirty-eight studies met the inclusion criteria with over 15,000 participants in the relevant arms. There was very little evidence of statistical heterogeneity (I² = 3%) so all studies were pooled in the main analysis. There was evidence of a small but statistically significant benefit from more intensive support (RR 1.16, 95% CI 1.09 to 1.24) for abstinence at longest follow-up. All but two of the included studies provided four or more sessions of support. Most trials used nicotine replacement therapy. Significant effects were not detected for studies where the pharmacotherapy was nortriptyline (two trials) or varenicline (one trial), but this reflects the absence of evidence. In subgroup analyses, studies that provided at least four sessions of personal contact for the intervention and no personal contact for the control had slightly larger effects (six trials, RR 1.25, 95% CI 1.08 to 1.45), as did studies where all intervention counselling was via telephone (six trials, RR 1.28, 95% CI 1.17 to 1.41). Weaker evidence for a benefit of providing additional behavioural support was seen in the trials where all participants, including those in the control condition, had at least 30 minutes of personal contact (18 trials, RR 1.11, 95% CI 0.99 to 1.25). None of the differences between subgroups were significant, and the last two subgroup analyses were not prespecified. No trials were judged at high risk of bias on any domain. AUTHORS' CONCLUSIONS: Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect. Increasing the amount of behavioural support is likely to increase the chance of success by about 10 to 25%, based on a pooled estimate from 38 trials. A subgroup analysis of a small number of trials suggests the benefit could be a little greater when the contrast is between a no contact control and a behavioural intervention that provides at least four sessions of contact. Subgroup analysis also suggests that there may be a smaller incremental benefit from providing even more intensive support via more or longer sessions over and above some personal contact.

Silver acetate for smoking cessation.

BACKGROUND: Silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus. It has been marketed in various forms with the aim of extinguishing the urge to smoke, by pairing the urge with an unpleasant stimulus. OBJECTIVES: The aim of this review was to determine the effectiveness of silver acetate products (gum, lozenge, spray) in promoting smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group specialised trials register. Most recent search was in July 2012. SELECTION CRITERIA: We included randomised trials of silver acetate for smoking cessation with reports of smoking status at least six months after the beginning of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and form of silver acetate, the outcome measures, method of randomisation, and completeness of follow-up.The main outcome measure was biochemically validated abstinence from smoking after at least six months follow-up in patients smoking at baseline. Subjects lost to follow-up were counted as continuing smokers. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: Two studies provided long-term follow-up data on patients randomised to silver acetate or placebo. In one of these studies, there was a third arm, randomised to 2mg nicotine gum. The pooled risk ratio for quitting for silver acetate vs placebo was 1.04 (95% confidence interval 0.69 to 1.57). AUTHORS' CONCLUSIONS: Existing trials show little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the ratio are quite wide. However, the upper limit of the confidence intervals for a positive effect equates to an absolute increase in the smoking cessation rate of about 4%. Any effect of this agent is therefore likely to be smaller than nicotine replacement therapy. The lack of effect of silver acetate may reflect poor compliance with a treatment whose rationale is to create an unpleasant stimulus.

Combined pharmacotherapy and behavioural interventions for smoking cessation.

BACKGROUND: Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are effective in helping people to stop smoking. Combining both treatment approaches is recommended where possible, but the size of the treatment effect with different combinations and in different settings and populations is unclear. OBJECTIVES: To assess the effect of combining behavioural support and medication to aid smoking cessation, compared to a minimal intervention or usual care, and to identify whether there are different effects depending on characteristics of the treatment setting, intervention, population treated, or take-up of treatment. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2012 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating combinations of pharmacotherapy and behavioural support for smoking cessation, compared to a control receiving usual care or brief advice or less intensive behavioural support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by both authors. Data was extracted by one author and checked by the other.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS: Forty-one studies with a total of more than 20,000 participants met the inclusion criteria. A large proportion of studies recruited people in healthcare settings or with specific health needs. Most studies provided NRT. Behavioural support was typically provided by specialists in cessation counselling, who offered between four and eight contact sessions. The planned maximum duration of contact was typically more than 30 minutes but less than 300 minutes. Overall, studies were at low or unclear risk of bias, and findings were not sensitive to the exclusion of any of the three studies rated at high risk of bias in one domain. One large study (the Lung Health Study) contributed heterogeneity due to a substantially larger treatment effect than seen in other studies (RR 3.88, 95% CI 3.35 to 4.50). Since this study used a particularly intensive intervention which included extended availability of nicotine gum, multiple group sessions and long term maintenance and recycling contacts, the results may not be comparable with the interventions used in other studies, and hence it was not pooled in other analyses. Based on the remaining 40 studies (15,021 participants) there was good evidence for a benefit of combination pharmacotherapy and behavioural treatment compared to usual care or brief advice or less intensive behavioural support (RR 1.82, 95% CI 1.66 to 2.00) with moderate statistical heterogeneity (I² = 40%). The pooled estimate for 31 trials that recruited participants in healthcare settings (RR 2.06, 95% CI 1.81 to 2.34) was higher than for eight trials with community-based recruitment (RR 1.53, 95% CI 1.33 to 1.76). Pooled estimates were lower in a subgroup of trials where the behavioural intervention was provided by specialist counsellors versus trials where counselling was linked to usual care (specialist: RR 1.73, 95% CI 1.55 to 1.93, 28 trials; usual provider: RR 2.41, 95% CI 1.91 to 3.02, 8 trials) but this was largely attributable to the small effect size in two trials using specialist counsellors where the take-up of the planned intervention was low, and one usual provider trial with alarge effect. There was little indirect evidence that the relative effect of an intervention differed according to whether participants in a trial were required to be motivated to make a quit attempt or not. There was only weak evidence that studies offering more sessions had larger effects and there was not clear evidence that increasing the duration of contact increased the effect, but there was more evidence of a dose-response relationship when analyses were limited to trials where the take-up of treatment was high. AUTHORS' CONCLUSIONS: Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care. Further trials would be unlikely to change this conclusion. We did not find strong evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects but this could be because intensive interventions are less likely to be delivered in full.