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  • Nicotine preloading for smoking cessation: the Preloading RCT.

    16 August 2018

    BACKGROUND: Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data. OBJECTIVES: To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading. DESIGN: Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis. SETTING: NHS smoking cessation clinics. PARTICIPANTS: People seeking help to stop smoking. INTERVENTIONS: Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators. MAIN OUTCOME MEASURES: The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model. RESULTS: In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) -0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI -£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving. LIMITATIONS: The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified. CONCLUSIONS: Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33031001. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.

  • Experiences of Reframing during Self-Directed Weight Loss and Weight Loss Maintenance: Systematic Review of Qualitative Studies.

    3 July 2018

    BACKGROUND: Reframing means changing the way that a person thinks or feels about a weight loss attempt or weight loss maintenance to enhance its experience or facilitate its success. Although participants have described this, it has not been explored in the academic literature. Here, we set out to systematically review qualitative studies to examine the ways in which people use and experience reframing in self-directed weight loss. METHODS: Seven electronic databases were searched to January 2017 for qualitative studies of adults with overweight or obesity attempting to lose weight or maintain weight loss through self-directed behavior change. Studies must have contained some information pertinent to reframing. Thematic synthesis was used to identify descriptive and analytical themes from the available data. RESULTS: We included 23 studies, representing 723 participants. No study focused specifically on reframing. Most studies involved people who had tried to lose weight previously. In the most common examples of reframing, participants spoke of construing previous weight management attempts as "dieting", whereas in current attempts they used reframing to move away from this concept. Participants spoke of finding reframing helpful because it removed the sense of depriving themselves and instead allowed them to construe the food choices as healthful. Likewise, the language of dieting created a sense of temporary effort, while construing this as a way of life allowed continuation of conscious control over energy balance without the feeling of undue effort. In some cases, these changes were bolstered by change in self-identity. CONCLUSIONS: Some people construe deliberate weight loss as a form of deprivation and cognitively reframe to avoid the negative emotions this creates and to prevent relapse. Reframing the dietary regimen as about healthy eating and a new way of life made weight control seem less burdensome for these participants and they felt able to maintain their efforts.

  • Macrophage heterogeneity in the immunopathogenesis of tuberculosis

    16 July 2018

    © 2018 Marakalala, Martinez, Plüddemann and Gordon. Macrophages play a central role in tuberculosis, as the site of primary infection, inducers and effectors of inflammation, innate and adaptive immunity, as well as mediators of tissue destruction and repair. Early descriptions by pathologists have emphasized their morphological heterogeneity in granulomas, followed by delineation of T lymphocyte-dependent activation of anti-mycobacterial resistance. More recently, powerful genetic and molecular tools have become available to describe macrophage cellular properties and their role in host-pathogen interactions. In this review we discuss aspects of macrophage heterogeneity relevant to the pathogenesis of tuberculosis and, conversely, lessons that can be learnt from mycobacterial infection, with regard to the immunobiological functions of macrophages in homeostasis and disease.

  • Nicotine replacement therapy versus control for smoking cessation

    3 July 2018

    © 2018 The Cochrane Collaboration. 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.

  • EBM DataLab

    25 April 2017

  • Cancer Research

    26 June 2012

  • Heart Failure

    26 June 2012

    Our research focuses on heart failure in primary care. We explore the burden of heart failure in primary care populations and the impact on patients. We have a particular interest in heart failure diagnosis and screening in primary care settings.

  • Stroke Prevention and Atrial Fibrillation

    26 June 2012

    Reducing the risk of stroke is vital to improving the health of older people. We research ‘funny turns’ that are a warning sign of stroke (termed ‘transient ischaemic attacks’) and the detection and treatment of major risk factors for stroke - high blood pressure and atrial fibrillation.

  • Primary Care for the Developing World

    26 June 2012

    Our aim is to support the provision of high quality primary health care in countries with limited economic resources, undertaking research and policy development in collaboration with academic institutions, NGOs and government agencies.

  • Monitoring and Diagnosis (MaDOx)

    26 June 2012

    Our aim is to improve monitoring and diagnostics used in primary care and community settings.

  • Infectious Diseases Research Group

    26 June 2012

    We investigate infectious diseases in primary care to find out how we can identify patients with serious infection in primary care, and more effective ways of diagnosing and treating patients with common infections.

  • Medical Statistics Group

    26 June 2012

    Our aim is to support clinical research in primary care and to advance the way we answer clinical questions using statistics to improve healthcare worldwide.

  • Paediatric Research Group

    26 June 2012

    We carry out research to find ways for parents and healthcare professionals to diagnose serious illness in children as early as possible and to manage common childhood illness in the most appropriate way.