The National Lung Matrix Trial of personalized therapy in lung cancer.

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1-3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.

Publisher Correction: The National Lung Matrix Trial of personalized therapy in lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

A Systematic Review of Approaches for Continuous Quality Improvement Capacity-Building.

CONTEXT: Continuous quality improvement (CQI) has become prominent in public health settings; yet, little consolidated guidance exists for building CQI capacity of community-based organizations. OBJECTIVE: To synthesize relevant literature to identify guiding principles and core components critical to building the capacity of organizations to adopt and use CQI. DESIGN: We employed a systematic review approach to assess guiding principles and core components for CQI capacity-building as outlined in the literature. ELIGIBILITY CRITERIA: Studies meeting the following criteria were eligible for review: (1) empirical, peer-reviewed journal article, evaluation study, review, or systematic review; (2) published in 2010 or later; and (3) capacity-building activities were described in enough detail to be replicable. Studies not including human subjects, published in a language other than English, or for which full text was not available were excluded. STUDY SELECTION: The initial return of records included 6557 articles, of which 1455 were duplicates. The research team single-screened titles and abstracts of 5102 studies, resulting in the exclusion of 4842 studies. Two hundred sixty-two studies were double-screened during full-text review, yielding a final sample of 61 studies from which data were extracted. MAIN OUTCOME MEASURES: Outcome measures of interest were operationalized descriptions of guiding principles and core components of the CQI capacity-building approach. RESULTS: Results yielded articles from medical education, health care, and public health settings. Findings included guiding principles and core components of CQI capacity-building identified in current practice, as well as infrastructural and contextual elements needed to build CQI capacity. CONCLUSIONS: This consolidation of guiding principles and core components for CQI capacity-building is valuable for public health and related workforces. Despite the uneven distribution of articles from health care, medical education, and public health settings, our findings can be used to guide public health organizations in building CQI capacity in a well-informed, systematic manner.

Interventions for preventing weight gain after smoking cessation.

BACKGROUND: Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting. OBJECTIVES: To systematically review the effects of: (1) interventions targeting post-cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post-cessation weight gain (referred to as 'Part 2'). SEARCH METHODS: Part 1 - We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020. Part 2 - We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e-cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists. SELECTION CRITERIA: Part 1 - trials of interventions that targeted post-cessation weight gain and had measured weight at any follow-up point or smoking cessation, or both, six or more months after quit day. Part 2 - trials included in the selected parent Cochrane reviews reporting weight change at any time point. DATA COLLECTION AND ANALYSIS: Screening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow-up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta-analysis using the inverse variance method for weight, and Mantel-Haenszel method for smoking. MAIN RESULTS: Part 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk.  An intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) -3.70 kg, 95% confidence interval (CI) -4.82 to -2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD -1.30 kg, 95% CI -3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study  found that no-one completed the VLCD intervention or achieved abstinence. Interventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I2 = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I2 = 26%). Some pharmacological interventions tested for limiting post-cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low-certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD -1.11 kg, 95% CI -1.93 to -0.29; 3 studies, 121 participants; I2 = 0%), but no evidence in the longer-term 12 months (MD -0.44 kg, 95% CI -2.34 to 1.46; 4 studies, 530 participants; I2 = 41%). There was low to very low-certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD -0.21 kg, 95% CI -2.28 to 1.86; 2 studies, 61 participants; I2 = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I2 = 0%). Part 2: We include 83 completed studies, 27 of which are new to this update. There was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD -0.25 kg, 95% CI -0.78 to 0.29; 4 studies, 404 participants; I2 = 0%). However, weight was reduced at 12 months (MD -2.07 kg, 95% CI -3.78 to -0.36; 3 studies, 182 participants; I2 = 0%). Both bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD -1.01 kg, 95% CI -1.35 to -0.67; 10 studies, 1098 participants; I2 = 3%); (fluoxetine MD -1.01 kg, 95% CI -1.49 to -0.53; 2 studies, 144 participants; I2 = 38%; low- and very low-certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD -0.26 kg, 95% CI -1.31 to 0.78; 7 studies, 471 participants; I2 = 0%). No studies of fluoxetine provided data at 12 months. There was moderate-certainty that NRT reduced weight at end of treatment (MD -0.52 kg, 95% CI -0.99 to -0.05; 21 studies, 2784 participants; I2 = 81%) and moderate-certainty that the effect may be similar at 12 months (MD -0.37 kg, 95% CI -0.86 to 0.11; 17 studies, 1463 participants; I2 = 0%), although the estimates are too imprecise to assess long-term benefit. There was mixed evidence of the effect of varenicline on weight, with high-certainty evidence that weight change was very modestly lower at the end of treatment (MD -0.23 kg, 95% CI -0.53 to 0.06; 14 studies, 2566 participants; I2 = 32%); a low-certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI -0.58 to 2.69; 3 studies, 237 participants; I2 = 0%). AUTHORS' CONCLUSIONS: Overall, there is no intervention for which there is moderate certainty of a clinically useful effect on long-term weight gain. There is also no moderate- or high-certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.

Smoking cessation for improving mental health.

BACKGROUND: There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self-medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health. OBJECTIVES: To examine the association between tobacco smoking cessation and change in mental health. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously-conducted non-Cochrane review where searches were conducted from database inception to 13 April 2012.  SELECTION CRITERIA: We included controlled before-after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow-up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow-up. Secondary outcomes  included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders. We assessed the risk of bias for the primary outcomes using a modified ROBINS-I tool.  For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow-up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta-analyses we used a generic inverse variance random-effects model and quantified statistical heterogeneity using I2. We conducted subgroup analyses to investigate any differences in associations between sub-populations, i.e. unselected people with mental illness, people with physical chronic diseases. We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non-randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose-response gradient). MAIN RESULTS: We included 102 studies representing over 169,500 participants. Sixty-two of these were identified in the updated search for this review and 40 were included in the original version of the review.  Sixty-three studies provided data on change in mental health, 10 were included in meta-analyses of incidence of mental health disorders, and 31 were synthesised narratively.  For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD -0.28, 95% CI -0.43 to -0.13; 15 studies, 3141 participants; I2 = 69%; low-certainty evidence); depression symptoms: (SMD -0.30, 95% CI -0.39 to -0.21; 34 studies, 7156 participants; I2 = 69%' very low-certainty evidence);  mixed anxiety and depression symptoms (SMD -0.31, 95% CI -0.40 to -0.22; 8 studies, 2829 participants; I2 = 0%; moderate certainty evidence).  These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time-varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate. For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD -0.19, 95% CI -0.34 to -0.04; 4 studies, 1792 participants; I2 = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I2 = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I2 = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I2 = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I2 = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I2 = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I2 = 87%). AUTHORS' CONCLUSIONS: Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low- to moderate-certainty evidence that smoking cessation is associated with small to moderate improvements in mental health.  These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time-varying confounding would strengthen the evidence in this area.

Smoking behaviours and attitudes towards campus-wide tobacco control policies among staff and students: a cross-sectional survey at the University of Birmingham.

BACKGROUND: Tobacco control policies have potential to be an effective strategy for the reduction of smoking prevalence and secondhand smoke (SHS) exposure in tertiary educational settings worldwide. The aims of this study were to collect baseline data among staff and students, to measure smoking behaviours and attitudes towards introduction of campus-wide tobacco control policies within a UK higher education setting. METHODS: Cross-sectional study using data collected by web-based questionnaire administered to employed staff and enrolled students (undergraduate/postgraduate) at the University of Birmingham from May 2016 to April 2017. Information was obtained regarding demographic characteristics, tobacco usage patterns and attitudes towards a revised campus tobacco control policy using a 21-item survey tool. Logistic regression analyses were used to explore associations between participant characteristics and support for smoke-free or tobacco-free campus policy options, evaluated by crude and adjusted Odds Radios (OR) after controlling for confounding factors (significance level: P < 0.05). RESULTS: A total of 934 survey responses were received, of whom 780 participants provided complete information on staff or student status and were included in the present analysis. Current smoking prevalence was 14% (N = 109; 95% confidence interval (CI) 11.6-16.6). Overall, 66.3% (95% CI: 62.9-69.7) of participants supported a smoke-free campus; 68.5% (95% CI: 65.2-71.8) endorsed restrictions for tobacco sales and just under half of respondents (47.3%; 95% CI: 43.8-50.9) supported a ban for electronic cigarettes/vaping device use on campus. Smoking status was an independent predictor of support for tobacco control, with the lowest level of support for a smoke-free campus among daily (adjusted OR 0.02; 95% CI: 0.01-0.05) and intermittent smokers (adjusted OR 0.06; 95% CI: 0.02-0.16). CONCLUSIONS: Overall, the majority of staff and students participating in this baseline survey supported implementation of a smoke-free or comprehensive tobacco-free campus policy. These findings may inform the development and future implementation of a revised tobacco control policy at the university which reflects contemporary attitudes and considers a broad range of implementation issues, including behaviour change and environmental adaptations.

Screening and brief intervention for obesity in primary care: cost-effectiveness analysis in the BWeL trial.

BACKGROUND: The Brief Intervention for Weight Loss Trial enrolled 1882 consecutively attending primary care patients who were obese and participants were randomised to physicians opportunistically endorsing, offering, and facilitating a referral to a weight loss programme (support) or recommending weight loss (advice). After one year, the support group lost 1.4 kg more (95%CI 0.9 to 2.0): 2.4 kg versus 1.0 kg. We use a cohort simulation to predict effects on disease incidence, quality of life, and healthcare costs over 20 years. METHODS: Randomly sampling from the trial population, we created a virtual cohort of 20 million adults and assigned baseline morbidity. We applied the weight loss observed in the trial and assumed weight regain over four years. Using epidemiological data, we assigned the incidence of 12 weight-related diseases depending on baseline disease status, age, gender, body mass index. From a healthcare perspective, we calculated the quality adjusted life years (QALYs) accruing and calculated the incremental difference between trial arms in costs expended in delivering the intervention and healthcare costs accruing. We discounted future costs and benefits at 1.5% over 20 years. RESULTS: Compared with advice, the support intervention reduced the cumulative incidence of weight-related disease by 722/100,000 people, 0.33% of all weight-related disease. The incremental cost of support over advice was £2.01million/100,000. However, the support intervention reduced health service costs by £5.86 million/100,000 leading to a net saving of £3.85 million/100,000. The support intervention produced 992 QALYs/100,000 people relative to advice. CONCLUSIONS: A brief intervention in which physicians opportunistically endorse, offer, and facilitate a referral to a behavioural weight management service to patients with a BMI of at least 30 kg/m2 reduces healthcare costs and improves health more than advising weight loss.

Primary Care Healthcare Professionals' Knowledge, Attitudes, and Practices Towards Promoting the Reduction of Children's Secondhand Smoke Exposure: A Mixed-Methods Review and Synthesis.

INTRODUCTION: Secondhand smoke exposure (SHSe) leads to increased mortality and morbidity. Primary care healthcare professionals (HCPs) are well placed to support patients to reduce SHSe. This paper explores HCPs': (1) knowledge around SHSe; (2) current practices to promote SHSe reduction; (3) beliefs and experiences regarding delivering interventions to reduce SHSe; and (4) identified factors that influence the delivery of SHSe-related interventions. METHODS: Six electronic databases were searched for relevant literature published January 1980-February 2016. 17 quantitative and 3 qualitative studies were included in this mixed-methods review. Data synthesis followed the method outlined by the Joanna Briggs Institute. This segregated approach involved independent syntheses of the quantitative and qualitative data followed by an overall mixed-methods synthesis. RESULTS: Primary care HCPs had a basic understanding of the risks associated with SHSe but required training to help them intervene. It was more common for HCPs to ask about SHSe or provide advice than to act to facilitate SHSe reduction. SHSe was viewed as an issue of high importance and considered relevant to the role of the primary care HCPs. However, barriers such as the priority given to the issue and the desire to protect the professional relationship with patients prevented HCPs from intervening around SHSe. CONCLUSIONS: Primary care HCPs require training, guidance, and support to enable them to intervene and support patients to effectively reduce SHSe. IMPLICATIONS: This review used rigorous methods to explore the current, global literature on how children's exposure to secondhand smoke is being addressed in primary care settings. The review findings highlight healthcare professionals' need for further training and support, which would enable them to better translate their knowledge of the risks associated with secondhand smoke exposure into actual clinical practices. The review identified a lack of practical action taken to address secondhand smoke exposure, even once it has been identified as an issue.

Interventions to increase adherence to medications for tobacco dependence.

BACKGROUND: Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may address motivation to use medication, such as influencing beliefs about the value of taking medications, or provide support to overcome problems with maintaining adherence. OBJECTIVES: To assess the effectiveness of interventions aiming to increase adherence to medications for smoking cessation on medication adherence and smoking abstinence compared with a control group typically receiving standard care. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, and clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) to the 3 September 2018. We also conducted forward and backward citation searches. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised studies in which adults using active pharmacological treatment for smoking cessation were allocated to an intervention arm where there was a principal focus on increasing adherence to medications for tobacco dependence, or a control arm providing standard care. Dependent on setting, standard care may have comprised minimal support or varying degrees of behavioural support. Included studies used a measure that allowed assessment of the degree of medication adherence. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data for included studies and assessed risk of bias. For continuous outcome measures, we calculated effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we calculated effect sizes as risk ratios (RRs). In meta-analyses for adherence outcomes, we combined dichotomous and continuous data using the generic inverse variance method and reported pooled effect sizes as SMDs; for abstinence outcomes, we reported and pooled dichotomous outcomes. We obtained pooled effect sizes with 95% confidence intervals (CIs) using random-effects models. We conducted subgroup analyses to assess whether the primary focus of the adherence treatment ('practicalities' versus 'perceptions' versus both), the delivery approach (participant versus clinician-centred) or the medication type were associated with effectiveness. MAIN RESULTS: We identified two new studies, giving a total of 10 studies, involving 3655 participants. The medication adherence interventions studied were all provided in addition to standard behavioural support.They typically provided further information on the rationale for, and emphasised the importance of, adherence to medication or supported the development of strategies to overcome problems with maintaining adherence (or both). Seven studies targeted adherence to NRT, two to bupropion and one to varenicline. Most studies were judged to be at high or unclear risk of bias, with four of these studies judged at high risk of attrition or detection bias. Only one study was judged to be at low risk of bias.Meta-analysis of all 10 included studies (12 comparisons) provided moderate-certainty evidence that adherence interventions led to small improvements in adherence (i.e. the mean amount of medication consumed; SMD 0.10, 95% CI 0.03 to 0.18; I² = 6%; n = 3655), limited by risk of bias. Subgroup analyses for the primary outcome identified no significant subgroup effects, with effect sizes for subgroups imprecisely estimated. However, there was a very weak indication that interventions focused on the 'practicalities' of adhering to treatment (i.e. capabilities, resources, levels of support or skills) may be effective (SMD 0.21, 95% CI 0.03 to 0.38; I² = 39%; n = 1752), whereas interventions focused on treatment 'perceptions' (i.e. beliefs, cognitions, concerns and preferences; SMD 0.10, 95% CI -0.03 to 0.24; I² = 0%; n = 839) or on both (SMD 0.04, 95% CI -0.08 to 0.16; I² = 0%; n = 1064), may not be effective. Participant-centred interventions may be effective (SMD 0.12, 95% CI 0.02 to 0.23; I² = 20%; n = 2791), whereas those that are clinician-centred may not (SMD 0.09, 95% CI -0.05 to 0.23; I² = 0%; n = 864).Five studies assessed short-term smoking abstinence (five comparisons), while an overlapping set of five studies (seven comparisons) assessed long-term smoking abstinence of six months or more. Meta-analyses resulted in low-certainty evidence that adherence interventions may slightly increase short-term smoking cessation rates (RR 1.08, 95% CI 0.96 to 1.21; I² = 0%; n = 1795) and long-term smoking cessation rates (RR 1.16, 95% CI 0.96 to 1.40; I² = 48%; n = 3593). In both cases, the evidence was limited by risk of bias and imprecision, with CIs encompassing minimal harm as well as moderate benefit, and a high likelihood that further evidence will change the estimate of the effect. There was no evidence that interventions to increase adherence to medication led to any adverse events. Studies did not report on factors plausibly associated with increases in adherence, such as self-efficacy, understanding of and attitudes toward treatment, and motivation and intentions to quit. AUTHORS' CONCLUSIONS: In people who are stopping smoking and receiving behavioural support, there is moderate-certainty evidence that enhanced behavioural support focusing on adherence to smoking cessation medications can modestly improve adherence. There is only low-certainty evidence that this may slightly improve the likelihood of cessation in the shorter or longer-term. Interventions to increase adherence can aim to address the practicalities of taking medication, change perceptions about medication, such as reasons to take it or concerns about doing so, or both. However, there is currently insufficient evidence to confirm which approach is more effective. There is no evidence on whether such interventions are effective for people who are stopping smoking without standard behavioural support.

Birth-Related Perineal Trauma in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

Introduction Birth-related perineal trauma (BPT) is a common consequence of vaginal births. When poorly managed, BPT can result in increased morbidity and mortality due to infections, haemorrhage, and incontinence. This review aims to collect data on rates of BPT in low- and middle-income countries (LMICs), through a systematic review and meta-analysis. Methods The following databases were searched: Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACs), and the World Health Organization (WHO) regional databases, from 2004 to 2016. Cross-sectional data on the proportion of vaginal births that resulted in episiotomy, second degree tears or obstetric anal sphincter injuries (OASI) were extracted from studies carried out in LMICs by two independent reviewers. Estimates were meta-analysed using a random effects model; results were presented by type of BPT, parity, and mode of birth. Results Of the 1182 citations reviewed, 74 studies providing data on 334,054 births in 41 countries were included. Five studies reported outcomes of births in the community. In LMICs, the overall rates of BPT were 46% (95% CI 36-55%), 24% (95% CI 17-32%), and 1.4% (95% CI 1.2-1.7%) for episiotomies, second degree tears, and OASI, respectively. Studies were highly heterogeneous with respect to study design and population. The overall reporting quality was inadequate. Discussion Compared to high-income settings, episiotomy rates are high in LMIC medical facilities. There is an urgent need to improve reporting of BPT in LMICs particularly with regards to births taking in community settings.

Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial.

BACKGROUND: Obesity is a common cause of non-communicable disease. Guidelines recommend that physicians screen and offer brief advice to motivate weight loss through referral to behavioural weight loss programmes. However, physicians rarely intervene and no trials have been done on the subject. We did this trial to establish whether physician brief intervention is acceptable and effective for reducing bodyweight in patients with obesity. METHODS: In this parallel, two-arm, randomised trial, patients who consulted 137 primary care physicians in England were screened for obesity. Individuals could be enrolled if they were aged at least 18 years, had a body-mass index of at least 30 kg/m2 (or at least 25 kg/m2 if of Asian ethnicity), and had a raised body fat percentage. At the end of the consultation, the physician randomly assigned participants (1:1) to one of two 30 s interventions. Randomisation was done via preprepared randomisation cards labelled with a code representing the allocation, which were placed in opaque sealed envelopes and given to physicians to open at the time of treatment assignment. In the active intervention, the physician offered referral to a weight management group (12 sessions of 1 h each, once per week) and, if the referral was accepted, the physician ensured the patient made an appointment and offered follow-up. In the control intervention, the physician advised the patient that their health would benefit from weight loss. The primary outcome was weight change at 12 months in the intention-to-treat population, which was assessed blinded to treatment allocation. We also assessed asked patients' about their feelings on discussing their weight when they have visited their general practitioner for other reasons. Given the nature of the intervention, we did not anticipate any adverse events in the usual sense, so safety outcomes were not assessed. This trial is registered with the ISRCTN Registry, number ISRCTN26563137. FINDINGS: Between June 4, 2013, and Dec 23, 2014, we screened 8403 patients, of whom 2728 (32%) were obese. Of these obese patients, 2256 (83%) agreed to participate and 1882 were eligible, enrolled, and included in the intention-to-treat analysis, with 940 individuals in the support group and 942 individuals in the advice group. 722 (77%) individuals assigned to the support intervention agreed to attend the weight management group and 379 (40%) of these individuals attended, compared with 82 (9%) participants who were allocated the advice intervention. In the entire study population, mean weight change at 12 months was 2·43 kg with the support intervention and 1·04 kg with the advice intervention, giving an adjusted difference of 1·43 kg (95% CI 0·89-1·97). The reactions of the patients to the general practitioners' brief interventions did not differ significantly between the study groups in terms of appropriateness (adjusted odds ratio 0·89, 95% CI 0·75-1·07, p=0·21) or helpfulness (1·05, 0·89-1·26, p=0·54); overall, four (<1%) patients thought their intervention was inappropriate and unhelpful and 1530 (81%) patients thought it was appropriate and helpful. INTERPRETATION: A behaviourally-informed, very brief, physician-delivered opportunistic intervention is acceptable to patients and an effective way to reduce population mean weight. FUNDING: The UK National Prevention Research Initiative.

Physician Support of Smoking Cessation After Diagnosis of Lung, Bladder, or Upper Aerodigestive Tract Cancer.

PURPOSE: Smoking cessation after a diagnosis of lung, bladder, and upper aerodigestive tract cancer appears to improve survival, and support to quit would improve cessation. The aims of this study were to assess how often general practitioners provide active smoking cessation support for these patients and whether physician behavior is influenced by incentive payments. METHODS: Using electronic primary care records from the UK Clinical Practice Research Datalink, 12,393 patients with incident cases of cancer diagnosed between 1999 and 2013 were matched 1 to 1 to patients with incident cases of coronary heart disease (CHD) diagnosed during the same time. We assessed differences in the proportion for whom physicians updated smoking status, advised quitting, and prescribed cessation medications, as well as the proportion of patients who stopped smoking within a year of diagnosis. We further examined whether any differences arose because the physicians were offered incentives to address smoking in patients with CHD and not cancer. RESULTS: At diagnosis, 32.0% of patients with cancer and 18.2% of patients with CHD smoked tobacco. Patients with cancer were less likely than patients with CHD to have their general practitioners update smoking status (OR = 0.18; 95% CI, 0.17-0.19), advise quitting (OR = 0.38; 95% CI, 0.36-0.40), or prescribe medication (OR = 0.67; 95% CI, 0.63-0.73), and they were less likely to have stopped smoking (OR = 0.76; 95% CI, 0.69-0.84). One year later 61.7% of patients with cancer and 55.4% with CHD who were smoking at diagnosis were still smoking. Introducing incentive payments was associated with more frequent interventions, but not for patients with CHD specifically. CONCLUSIONS: General practitioners were less likely to support smoking cessation in patients with cancer than with CHD, and patients with cancer were less likely to stop smoking. This finding is not due to the difference in incentive payments.

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. TRIAL REGISTRATION: ISRCTN 54805841 . Registered 18 March 2010.

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.

Interventions to increase adherence to medications for tobacco dependence.

BACKGROUND: Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is therefore important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may include further educating individuals about the value of taking medications and providing additional support to overcome problems with maintaining adherence. OBJECTIVES: The primary objective of this review was to assess the effectiveness of interventions to increase adherence to medications for smoking cessation, such as NRT, bupropion, nortriptyline and varenicline (and combination regimens). This was considered in comparison to a control group, typically representing standard care. Secondary objectives were to i) assess which intervention approaches are most effective; ii) determine the impact of interventions on potential precursors of adherence, such as understanding of the treatment and efficacy perceptions; and iii) evaluate key outcomes influenced by prior adherence, principally smoking cessation. SEARCH METHODS: We searched the following databases using keywords and medical subject headings: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OVID SP) (1946 to July Week 3 2014), EMBASE (OVID SP) (1980 to Week 29 2014), and PsycINFO (OVID SP) (1806 to July Week 4 2014). The Cochrane Tobacco Addiction Group Specialized Register was searched on 9th July 2014. We conducted forward and backward citation searches. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised studies in which participants using active pharmacological treatment for smoking cessation are allocated to an intervention arm or a control arm. Eligible participants were adult (18+) smokers. Eligible interventions comprised any intervention that differed from standard care, and where the intervention content had a clear principal focus on increasing adherence to medications for tobacco dependence. Acceptable comparison groups were those that provided standard care, which depending on setting may comprise minimal support or varying degrees of behavioural support. Included studies used a measure of adherence behaviour that allowed some assessment of the degree of adherence. DATA COLLECTION AND ANALYSIS: Two review authors searched for studies and independently extracted data for included studies. Risk of bias was assessed according to the Cochrane Handbook guidance. For continuous outcome measures, we report effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we report effect sizes as relative risks (RRs). We obtained pooled effect sizes with 95% confidence intervals (CIs) using the fixed effects model. MAIN RESULTS: Our search strategy retrieved 3165 unique references and we identified 31 studies as potentially eligible for inclusion. Of these, 23 studies were excluded at full-text screening stage or identified as studies awaiting classification subject to further information. We included eight studies involving 3336 randomised participants. The interventions were all additional to standard behavioural support and typically provided further information on the rationale for, and emphasised the importance of, adherence to medication, and supported the development of strategies to overcome problems with maintaining adherence.Five studies reported on whether or not participants achieved a specified satisfactory level of adherence to medication. There was evidence that adherence interventions led to modest improvements in adherence, with a relative risk (RR) of 1.14 (95% CI, 1.02 to 1.28, P = 0.02, n = 1630). Four studies reported continuous measures of adherence to medication. Although the standardised mean difference (SMD) favoured adherence interventions, the effect was small and not statistically significant (SMD 0.07, 95% CI, -0.03 to 0.17, n = 1529). Applying the GRADE system, the quality of evidence for these results was assessed as moderate and low, respectively.There was evidence that adherence interventions led to modest improvements in rates of cessation. The relative risk for achieving abstinence was similar to that for improved adherence. It was not significant in meta-analysis of four studies providing short-term abstinence: RR = 1.07 (95% CI 0.95 to 1.21, n = 1755), but there was statistically significant evidence of improved abstinence at six months or more from a different set of four studies: RR = 1.16 (95% CI, 1.01 to 1.34, P = 0.03, n = 3049). Applying the GRADE system, the quality of evidence for these results was assessed as low for both.As interventions were similar in nature and the number of studies was low, it was not possible to investigate whether different types of intervention approaches were more effective than others. Relevant outcomes other than adherence or cessation were not reported.There was no evidence that interventions to increase adherence to medication led to any adverse events. All included studies were assessed as at high or unclear risk of bias. This was often due to a lack of clarity in reporting - meaning assessments were unclear - rather than clear evidence of failing to sufficiently safeguard against the risk of bias. AUTHORS' CONCLUSIONS: There is some evidence that interventions that devote special attention to improving adherence to smoking cessation medication through providing information and facilitating problem-solving can improve adherence, though the evidence for this is not strong and is limited in both quality and quantity. There is some evidence that such interventions improve the chances of achieving abstinence but again the evidence for this is relatively weak.

The UK National Recovery Survey: nationally representative survey of people overcoming a drug or alcohol problem.

BACKGROUND: Alcohol or drug (AOD) problems are a significant health burden in the UK population, and understanding pathways to remission is important. AIMS: To determine the UK population prevalence of overcoming an AOD problem and the prevalence and correlates of 'assisted' pathways to problem resolution. METHOD: Stage 1: a screening question was administered in a national telephone survey to provide (a) an estimate of the UK prevalence of AOD problem resolution; and (b) a demographic profile of those reporting problem resolution. Stage 2: social surveying organisation YouGov used the demographic data from stage 1 to guide the administration of the UK National Recovery Survey to a representative subsample from its online panel. RESULTS: In stage 1 (n = 2061), 102 (5%) reported lifetime AOD problem resolution. In the weighted sample (n = 1373) who completed the survey in stage 2, 49.9% reported 'assisted' pathway use via formal treatment (35.0%), mutual help (29.7%) and/or recovery support services (22.6%). Use of an assisted pathway was strongly correlated with lifetime AOD diagnosis (adjusted odds ratio [AOR] = 9.54) and arrest in the past year (AOR = 7.88) and inversely correlated with absence of lifetime psychiatric diagnosis (AOR = 0.17). Those with cocaine (AOR = 2.44) or opioid problems (AOR = 3.21) were more likely to use assisted pathways compared with those with primary alcohol problems. CONCLUSION: Nearly three million people have resolved an AOD problem in the UK. Findings challenge the therapeutic pessimism sometimes associated with these problems and suggest a need to learn from community-based self-change that can supplement and enhance existing treatment modalities.

How the experiences of implementation support recipients contribute to implementation outcomes.

Introduction: There is a growing body of literature on the activities and competencies of implementation support practitioners (ISPs) and the outcomes of engaging ISPs to support implementation efforts. However, there remains limited knowledge about the experiences of implementation support recipients who engage with ISPs and how these experiences shape the trajectory of implementation and contribute to implementation outcomes. This study aimed to extend the research on ISPs by describing the experiences of professionals who received implementation support and inform our understanding of the mechanisms by which ISPs produce behavior change and contribute to implementation outcomes. Methods: Thirteen individuals with roles in supporting implementation efforts at a private foundation participated in semi-structured interviews. Data were analyzed using qualitative narrative analysis and episode profile analysis approaches. Iterative diagramming was used to visualize the pathway of experiences of implementation support recipients evidenced by the interview data. Results: The majority of recipients described how positive experiences and trusting relationships with ISPs increased acceptance of implementation science throughout the foundation and increased the perception of implementation science as both an appropriate and feasible approach for strengthening the impact of foundation strategies. As perceptions of appropriateness and feasibility increased, recipients of implementation support described increasing knowledge and application of implementation science in their funding engagements and internal foundation strategies. Finally, recipients reported that the application of implementation science across the foundation led to sustained implementation capacity and better outcomes. Discussion: The experiences of implementation support recipients described in this paper provide a source for further understanding the mechanisms of change for delivering effective implementation support leading to better implementation quality. Insights from these experiences can enhance our understanding for building implementation capacity and the rationales for evolving approaches that emphasize the dynamic, emotional, and highly relational nature of supporting others to use evidence in practice.

Systematic review and meta-analysis: influence of smoking cessation on incidence of pneumonia in HIV.

BACKGROUND: Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for pneumonia in people with HIV and whether smoking cessation ameliorates excess risk. METHODS: We performed MEDLINE and Embase database searches and included cohort or case-control studies conducted in adult patients infected with HIV extracting a hazard ratio (HR) or odds ratio (OR) that compared the incidence of bacterial pneumonia or pneumonia caused by Pneumocystis jiroveci (PCP) between two smoking categories. Studies were appraised for quality and combined using inverse variance meta-analysis. RESULTS: Fourteen cohort and case-control studies were included. Assessment of outcome was good, but assessment of exposure status was poor. Current smokers were at higher risk of bacterial pneumonia than former smokers: HR 1.37 (95% confidence interval (CI): 1.06, 1.78). There was no evidence that former smokers were at higher risk than never smokers: HR 1.24 (95%CI: 0.96, 1.60). Current smokers were at higher risk of bacterial pneumonia than current non-smokers: HR of 1.73 (95%CI: 1.44, 2.06). There was no evidence that smoking increased the incidence of PCP. The HR for current versus non-smokers was 0.94 (95%CI: 0.79, 1.12), but from case-control studies the OR was 1.76 (95%CI: 1.25, 2.48) with heterogeneity. Confined to higher quality studies, the OR was 0.97 (95%CI: 0.81, 1.16). Residual confounding is possible, but available data suggest this is not an adequate explanation. CONCLUSIONS: Smoking is a risk factor for bacterial pneumonia but not PCP and smoking cessation reduces this risk.See related article: http://www.biomedcentral.com/1741-7015/11/16.