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OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom.METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information.RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose.CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.

Background Antigen testing using lateral flow devices (LFDs) plays an important role in the management of the novel coronavirus pandemic of 2019 (COVID-19) by rapidly identifying individuals who are asymptomatically carrying high levels of the virus. By January 2021, LFD community testing sites were set up across English local authority areas to support the management and containment of regional COVID-19 cases, initially targeting essential workers unable to work from home during the national lockdown. This study aimed to examine the characteristics and motivations of individuals accessing community LFD testing across two local authority areas (LAAs) in the South West of England. Methods Data were collected as part of a service evaluation from December 22nd 2020 until March 15th 2021 for two LAAs. Demographic and postcode data were collected from an online test appointment booking platform and the National Health Service testing service online system, with data accessed from Public Health England. An online survey was sent to individuals who made a testing appointment at an LAA1 site using the online booking platform, consisting of 12 questions to collect data on individual’s motivations for and experiences of testing. Results Data were available for individuals who completed 12,516 tests in LAA1 and 12,327 tests in LAA2. Most individuals who engaged with testing were female, working age, white, and worked as early years or education staff, health and social care staff, and supermarket or food production staff. 1249 individuals completed the survey with 60% of respondents reported getting tested for work-related reasons. Individuals first heard about LFD testing through various channels including work, media, and word of mouth, and decided to get tested based on the ease and convenience of testing, workplace communications, and to identify asymptomatic cases to help stop the spread. Most tests were completed by individuals living in less deprived areas based on national deciles of deprivation. Conclusions While national and local COVID-19 testing strategies have evolved, community and personal LFD testing remains a crucial pillar of the testing strategy. Future studies should collect quantitative and qualitative data from residents to most effectively shape testing offers based on the needs and preferences of their population.

Background Cigarette smoking is one of the leading causes of early death. Varenicline [Champix (UK), Pfizer Europe MA EEIG, Brussels, Belgium; or Chantix (USA), Pfizer Inc., Mission, KS, USA], bupropion (Zyban; GlaxoSmithKline, Brentford, UK) and nicotine replacement therapy are licensed aids for quitting smoking in the UK. Although not licensed, e-cigarettes may also be used in English smoking cessation services. Concerns have been raised about the safety of these medicines and e-cigarettes. Objectives To determine the clinical effectiveness, safety and cost-effectiveness of smoking cessation medicines and e-cigarettes. Design Systematic reviews, network meta-analyses and cost-effectiveness analysis informed by the network meta-analysis results. Setting Primary care practices, hospitals, clinics, universities, workplaces, nursing or residential homes. Participants Smokers aged ≥ 18 years of all ethnicities using UK-licensed smoking cessation therapies and/or e-cigarettes. Interventions Varenicline, bupropion and nicotine replacement therapy as monotherapies and in combination treatments at standard, low or high dose, combination nicotine replacement therapy and e-cigarette monotherapies. Main outcome measures Effectiveness – continuous or sustained abstinence. Safety – serious adverse events, major adverse cardiovascular events and major adverse neuropsychiatric events. Data sources Ten databases, reference lists of relevant research articles and previous reviews. Searches were performed from inception until 16 March 2017 and updated on 19 February 2019. Review methods Three reviewers screened the search results. Data were extracted and risk of bias was assessed by one reviewer and checked by the other reviewers. Network meta-analyses were conducted for effectiveness and safety outcomes. Cost-effectiveness was evaluated using an amended version of the Benefits of Smoking Cessation on Outcomes model. Results Most monotherapies and combination treatments were more effective than placebo at achieving sustained abstinence. Varenicline standard plus nicotine replacement therapy standard (odds ratio 5.75, 95% credible interval 2.27 to 14.90) was ranked first for sustained abstinence, followed by e-cigarette low (odds ratio 3.22, 95% credible interval 0.97 to 12.60), although these estimates have high uncertainty. We found effect modification for counselling and dependence, with a higher proportion of smokers who received counselling achieving sustained abstinence than those who did not receive counselling, and higher odds of sustained abstinence among participants with higher average dependence scores. We found that bupropion standard increased odds of serious adverse events compared with placebo (odds ratio 1.27, 95% credible interval 1.04 to 1.58). There were no differences between interventions in terms of major adverse cardiovascular events. There was evidence of increased odds of major adverse neuropsychiatric events for smokers randomised to varenicline standard compared with those randomised to bupropion standard (odds ratio 1.43, 95% credible interval 1.02 to 2.09). There was a high level of uncertainty about the most cost-effective intervention, although all were cost-effective compared with nicotine replacement therapy low at the £20,000 per quality-adjusted life-year threshold. E-cigarette low appeared to be most cost-effective in the base case, followed by varenicline standard plus nicotine replacement therapy standard. When the impact of major adverse neuropsychiatric events was excluded, varenicline standard plus nicotine replacement therapy standard was most cost-effective, followed by varenicline low plus nicotine replacement therapy standard. When limited to licensed interventions in the UK, nicotine replacement therapy standard was most cost-effective, followed by varenicline standard. Limitations Comparisons between active interventions were informed almost exclusively by indirect evidence. Findings were imprecise because of the small numbers of adverse events identified. Conclusions Combined therapies of medicines are among the most clinically effective, safe and cost-effective treatment options for smokers. Although the combined therapy of nicotine replacement therapy and varenicline at standard doses was the most effective treatment, this is currently unlicensed for use in the UK. Future work Researchers should examine the use of these treatments alongside counselling and continue investigating the long-term effectiveness and safety of e-cigarettes for smoking cessation compared with active interventions such as nicotine replacement therapy. Study registration This study is registered as PROSPERO CRD42016041302. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 59. See the NIHR Journals Library website for further project information.

AIM: To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety.METHOD: Systematic reviews and Bayesian network meta-analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e-cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow-up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta-regression to explore covariates.RESULTS: We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34-3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27-14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second-best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04-1.58), and we found no evidence of effect modification.CONCLUSIONS: Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.

IMPORTANCEDepression is a debilitating and highly prevalent mental health disorder. There is a need for new, effective, and scalable treatments for depression, and cognitive bias modification (CBM) of negative emotional processing biases has been suggested as one possibility. Such treatments may form the basis of ‘digital therapeutics’, that could be administered remotely and at low cost, should they prove to be effective.OBJECTIVESStudy one was designed to determine neural correlates of a recently developed CBM technique for emotion recognition training; specifically, our aim was to compare the effects of training vs placebo on pre-specified regions of interest involved in emotion processing that are known to be sensitive to antidepressant treatment. Study two aimed to investigate efficacy of training on mood measures at 2 and 6-week follow-up and was powered to replicate and extend earlier findings.DESIGN, SETTING, AND PARTICIPANTSBoth studies were double blind RCTs, in which participants completed five sessions of emotion recognition training or sham training, in the laboratory, over a one-week period. In study one (N=37), following this training, participants completed a novel emotion recognition task whilst undergoing fMRI. In study two (N=190), measures of mood were assessed post training, and at 2-week and 6-week follow-up. Both studies recruited analogue samples of healthy volunteers with high levels of depressive symptoms (BDI-ii > 14).MAIN OUTCOMES AND MEASURESIn study one, our primary outcome was neural activation in the following pre-specified regions of interest: the bilateral amygdala, the mPFC, bilateral dlPFC, and the occipital cortex. In study two, our primary outcome was depressive symptoms over the last 2 weeks assessed using the BDI-ii at 6-week follow-up. Secondary outcomes included depressive symptoms measured using the HAM-D, and positive and negative affect assessed using the PANAS.RESULTSIn both studies, CBM resulted in a change in emotion recognition bias, which (in study two) persisted for 6 weeks after the end of the CBM phase. In study one, CBM resulted in increases neural activation to happy faces compared to sad faces, with this effect driven by an increase in neural activity for happy faces. We saw this increase in activation for this contrast at both the whole brain level and among our a priori ROIs, specifically the mPFC and bilateral amygdala. In study two, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias.CONCLUSIONS AND RELEVANCECBM of emotion recognition appears to have effects on neural activity that are similar in some respects to those induced by SSRI administration (study one), but we find no evidence that this has any effect on self-reported mood in an analogue sample of healthy volunteers with low mood (study two).

Background The co-location of expertise in public health, social care, and place services in local authorities facilitates tackling the wider determinants of health using transdisciplinary approaches. Local authority research systems are needed to enable local authorities to become research active, co-produce research, evaluate their impact, and produce and use evidence to shape practice and policy at pace. We aimed to explore and recommend what is necessary for a South Gloucestershire Council (SGC) research system to sustainably produce impactful research activity. Methods We did qualitative interviews with elected members and senior leadership of SGC and key stakeholders from local National Institute for Health Research (NIHR) infrastructure and organisations identified by expert sampling. Interviews were semi-structured with tailored topic guides exploring several topics, including relationships between SGC and local partners, resource and support, co-production, social care research, and the impact of COVID-19. Data from interviews were electronically transcribed verbatim using Otter.ai and coded using NVivo qualitative data analysis software. Data were analysed using the framework method and recommendations were proposed based on the findings. Ethical approval was granted by the University of Bristol's Faculty of Health Science Research Ethics Committee. Findings We interviewed 27 participants (five from SGC, 22 from local research organisations). Participants identified a need for a SGC research lead to facilitate collaboration and relationship building, and more joint posts across the local authority and external organisations. There was a need for collaborative cross-boundary working, as SGC works with other local authorities in their Sustainability and Transformation Partnership and Clinical Commissioning Group. Challenges included difficulties identifying SGC's priorities and population needs, data, staff training, and collaboration with academic researchers. They also reported resource issues exacerbated by COVID-19. Participants did not express conflicting views on these findings. Interpretation We recommended the creation of a local authority research lead post working across Council directorates, local authority research networks, support for joint posts, increased accessibility and use of local authority data, cross-boundary research systems, and infrastructure to support research to respond to local authority needs. We also suggested increased funding and incentivisation for academics to engage with local authority research. Potential barriers to these recommendations include local authority funding and staff capacity challenges. This study was limited by its recruitment method, sample size, and data collection and analyses completed by a single researcher. Future research should explore what types of evidence local authorities consider most relevant and useful. Funding NIHR Public Health Research (grant number NIHR131952).

Many cognitive bias modification (CBM) tasks use facial expressions of emotion as stimuli. Some tasks use unique facial stimuli, while others use composite stimuli, given evidence that emotion is encoded prototypically. However, CBM using composite stimuli may be identity- or emotion-specific, and may not generalise to other stimuli. We investigated the generalisability of effects using composite faces in two experiments. Healthy adults in each study were randomised to one of four training conditions: two stimulus-congruent conditions, where same faces were used during all phases of the task, and two stimulus-incongruent conditions, where faces of the opposite sex (Experiment 1) or faces depicting another emotion (Experiment 2) were used after the modification phase. Our results suggested that training effects generalised across identities. However, our results indicated only partial generalisation across emotions. These findings suggest effects obtained using composite stimuli may extend beyond the stimuli used in the task but remain emotion-specific.

INTRODUCTION: Cigarette smoking is one of the leading causes of early death in the UK and worldwide. Public health guidance recommends the use of varenicline, bupropion and nicotine replacement therapy (NRT) as smoking cessation aids in the UK. Additionally, the first electronic cigarette has been licensed for use as a smoking cessation medicine. However, there are ongoing concerns about the safety of these medicines. We present a protocol for a systematic review and network meta-analysis (NMA) to determine how these smoking cessation medicines compare to each other with respect to their neuropsychiatric safety in adult smokers. Secondary aims include updating the evidence regarding the effectiveness and cardiovascular safety of these medicines for use in a cost-effectiveness analysis.METHODS AND ANALYSIS: We will include randomised controlled trials and observational studies with control groups comparing monotherapy with varenicline, bupropion, NRT or electronic cigarette and combination therapies to each other, placebo or usual care. The primary composite safety outcome will be serious adverse events, defined as events that resulted in death, were life threatening, required hospitalisation or resulted in significant disability or congenital/birth defect. The preferred effectiveness outcome will be sustained smoking cessation defined as abstinence for a minimum of 6 months as determined by biochemical validation. We will include trials identified by previous reviews and search relevant databases for newly published trials as well as contacting study authors to identify unpublished information. We will conduct fixed-effect and random-effect meta-analyses for each pairwise comparison of treatments and outcome; where these estimates differ, we will consider reasons for heterogeneity, quantified using the between-study variance (τ(2)). For each outcome, we will construct a NMA in a Bayesian framework which will be compared with the pair-wise results, allowing us to rank treatments. The effectiveness estimates from the NMA will be entered into a probabilistic economic model.ETHICS AND DISSEMINATION: Ethics approval is not required for this evidence synthesis study as it involves analysis of secondary data from randomised controlled trials and observational studies. The review will make an important contribution to the knowledge base around the effectiveness, safety and cost-effectiveness of smoking cessation medicines. Results will be disseminated to the general public, healthcare practitioners and clinicians, academics, industry and policy makers.PROSPERO REGISTRATION NUMBER: CRD42016041302.