A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Lessons learned from the London Exercise and Pregnant (LEAP) Smokers randomised controlled trial process evaluation : implications for the design of physical activity for smoking cessation interventions during pregnancy

BACKGROUND: The challenges of delivering interventions for pregnant smokers have been poorly documented. Also, the process of promoting a physical activity intervention for pregnant smokers has not been previously recorded. This study describes the experiences of researchers conducting a randomised controlled trial of physical activity as an aid to smoking cessation during pregnancy and explores how the effectiveness of future interventions could be improved. METHODS: Two focus groups, with independent facilitators, were conducted with six researchers who had enrolled pregnant smokers in the LEAP trial, provided the interventions, and administered the research measures. Topics included recruitment, retention and how the physical activity intervention for pregnant smokers was delivered and how it was adapted when necessary to suit the women. The focus groups were audio-recorded, transcribed verbatim and subjected to thematic analysis. RESULTS: Five themes emerged related to barriers or enablers to intervention delivery: (1) nature of the intervention; (2) personal characteristics of trial participants; (3) practical issues; (4) researchers' engagement with participants; (5) training and support needs. Researchers perceived that participants may have been deterred by the intensive and generic nature of the intervention and the need to simultaneously quit smoking and increase physical activity. Women also appeared hampered by pregnancy ailments, social deprivation, and poor mental health. Researchers observed that their status as health professionals was valued by participants but it was challenging to maintain contact with participants. Training and support needs were identified for dealing with pregnant teenagers, participants' friends and family, and post-natal return to smoking. CONCLUSIONS: Future exercise interventions for smoking cessation in pregnancy may benefit by increased tailoring of the intervention to the characteristics of the women, including their psychological profile, socio-economic background, pregnancy ailments and exercise preferences. Delivering an effective physical activity intervention for smoking cessation in pregnancy may require more comprehensive training for those delivering the intervention, particularly with regard to dealing with teenage smokers and smokers' friends and family, as well as for avoiding post-natal return to smoking. TRIAL REGISTRATION: ISRCTN48600346 , date of registration: 21/07/2008

Using a Modified Intervention Mapping Approach to Develop and Refine a Single-Session Motivational Intervention for Methamphetamine-Using Men Who Have Sex With Men

There is an ongoing need for the development and adaptation of behavioral interventions to address behaviors related to acquisition and transmission of infectious diseases and for preventing the onset of chronic diseases. This paper describes the application of an established systematic approach to the development of a behavioral intervention to reduce sexual risk behaviors for HIV among men who have sex with men and who use methamphetamine. The approach includes six steps: (1) a needs assessment; (2) preparing matrices of proximal program objectives; (3) selecting theory-based methods and practical strategies; (4) producing program components and materials; (5) planning for program adoption, implementation, and sustainability; and (6) planning for evaluation. The focus of this article is on the intervention development process; therefore the article does not describe steps 5 and 6. Overall the process worked well, although it had to be adapted to fit the sequence of events associated with a funded research project. This project demonstrates that systematic approaches to intervention development can be applied even in research projects where some of the steps occur during the proposal writing process rather than during the actual project. However, intervention developers must remain flexible and be prepared to adapt the process to the situation. This includes being ready to make choices regarding intervention efficacy versus feasibility and being willing to select the best intervention that is likely to be delivered with available resources rather than an ideal intervention that may not be practical

Pharmacological interventions for promoting smoking cessation during pregnancy

Background Smoking in pregnancy is a public health problem. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion and varenicline) are effective for smoking cessation, however, their efficacy and safety in pregnancy remains unknown. Electronic Nicotine Delivery Systems (ENDS), or e-cigarettes, are becoming widely used but their efficacy and safety when used for smoking cessation in pregnancy are also unknown. Objectives To determine the efficacy and safety of smoking cessation pharmacotherapies (including NRT, varenicline and bupropion), other medications, or ENDS when used for smoking cessation in pregnancy. Search methods We searched the Pregnancy and Childbirth Group's Trials Register (11 July 2015), checked references of retrieved studies, and contacted authors. Selection criteria Randomised controlled trials (RCTs) conducted in pregnant women with designs that permit the independent effects of any type of pharmacotherapy or ENDS on smoking cessation to be ascertained were eligible for inclusion. The following RCT designs are included. Placebo-RCTs: any form of NRT, other pharmacotherapy, or ENDS, with or without behavioural support/cognitive behaviour therapy (CBT), or brief advice, compared with an identical placebo and behavioural support of similar intensity. RCTs providing a comparison between i) any form of NRT, other pharmacotherapy, or ENDS added to behavioural support/CBT, or brief advice and ii) behavioural support of similar (ideally identical) intensity. Parallel- or cluster-randomised trials were eligible for inclusion. Quasi-randomised, cross-over and within-participant designs were not, due to the potential biases associated with these designs. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias and also independently extracted data and cross checked individual outcomes of this process to ensure accuracy. The primary efficacy outcome was smoking cessation in later pregnancy (in all but one trial, at or around delivery); safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being; and we also collated data on adherence with trial treatments. Main results This review includes a total of nine trials which enrolled 2210 pregnant smokers: eight trials of NRT and one trial of bupropion as adjuncts to behavioural support/CBT. The risk of bias was generally low across trials with virtually all domains of the 'Risk of bias' assessment tool being satisfied for the majority of studies. We found no trials investigating varenicline or ENDS. Compared to placebo and non-placebo controls, there was a difference in smoking rates observed in later pregnancy favouring use of NRT (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.03 to 1.93, eight studies, 2199 women). However, subgroup analysis of placebo-RCTs provided a lower RR in favour of NRT (RR 1.28, 95% CI 0.99 to 1.66, five studies, 1926 women), whereas within the two non-placebo RCTs there was a strong positive effect of NRT, (RR 8.51, 95% CI 2.05 to 35.28, three studies, 273 women; P value for random-effects subgroup interaction test = 0.01). There were no differences between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities or neonatal death. Compared to placebo group infants, at two years of age, infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' (one trial). Generally, adherence with trial NRT regimens was low. Non-serious side effects observed with NRT included headache, nausea and local reactions (e.g. skin irritation from patches or foul taste from gum), but these data could not be pooled. Authors' conclusions NRT used in pregnancy for smoking cessation increases smoking cessation rates measured in late pregnancy by approximately 40%. There is evidence, suggesting that when potentially-biased, non-placebo RCTs are excluded from analyses, NRT is no more effective than placebo. There is no evidence that NRT used for smoking cessation in pregnancy has either positive or negative impacts on birth outcomes. However, evidence from the only trial to have followed up infants after birth, suggests use of NRT promotes healthy developmental outcomes in infants. Further research evidence on NRT efficacy and safety is needed, ideally from placebo-controlled RCTs which achieve higher adherence rates and which monitor infants' outcomes into childhood. Accruing data suggests that it would be ethical for future RCTs to investigate higher doses of NRT than those tested in the included studies

Psychosocial interventions for supporting women to stop smoking in pregnancy

Background: Tobacco smoking remains one of the few preventable factors associated with complications in pregnancy, and has serious long-term implications for women and babies. Smoking in pregnancy is decreasing in high-income countries, but is strongly associated with poverty and is increasing in low- to middle-income countries. Objectives: To assess the effects of smoking cessation interventions during pregnancy on smoking behaviour and perinatal health outcomes. Search methods: In this sixth update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 November 2015), checked reference lists of retrieved studies and contacted trial authors. Selection criteria: Randomised controlled trials, cluster-randomised trials, and quasi-randomised controlled trials of psychosocial smoking cessation interventions during pregnancy. Data collection and analysis: Two review authors independently assessed trials for inclusion and trial quality, and extracted data. Direct comparisons were conducted in RevMan, with meta-regression conducted in STATA 14. Main results: The overall quality of evidence was moderate to high, with reductions in confidence due to imprecision and heterogeneity for some outcomes. One hundred and two trials with 120 intervention arms (studies) were included, with 88 trials (involving over 28,000 women) providing data on smoking abstinence in late pregnancy. Interventions were categorised as counselling, health education, feedback, incentives, social support, exercise and dissemination. In separate comparisons, there is high-quality evidence that counselling increased smoking cessation in late pregnancy compared with usual care (30 studies; average risk ratio (RR) 1.44, 95% confidence interval (CI) 1.19 to 1.73) and less intensive interventions (18 studies; average RR 1.25, 95% CI 1.07 to 1.47). There was uncertainty whether counselling increased the chance of smoking cessation when provided as one component of a broader maternal health intervention or comparing one type of counselling with another. In studies comparing counselling and usual care (largest comparison), it was unclear whether interventions prevented smoking relapse among women who had stopped smoking spontaneously in early pregnancy. However, a clear effect was seen in smoking abstinence at zero to five months postpartum (11 studies; average RR 1.59, 95% CI 1.26 to 2.01) and 12 to 17 months (two studies, average RR 2.20, 95% CI 1.23 to 3.96), with a borderline effect at six to 11 months (six studies; average RR 1.33, 95% CI 1.00 to 1.77). In other comparisons, the effect was unclear for most secondary outcomes, but sample sizes were small. Evidence suggests a borderline effect of health education compared with usual care (five studies; average RR 1.59, 95% CI 0.99 to 2.55), but the quality was downgraded to moderate as the effect was unclear when compared with less intensive interventions (four studies; average RR 1.20, 95% CI 0.85 to 1.70), alternative interventions (one study; RR 1.88, 95% CI 0.19 to 18.60), or when smoking cessation health education was provided as one component of a broader maternal health intervention. There was evidence feedback increased smoking cessation when compared with usual care and provided in conjunction with other strategies, such as counselling (average RR 4.39, 95% CI 1.89 to 10.21), but the confidence in the quality of evidence was downgraded to moderate as this was based on only two studies and the effect was uncertain when feedback was compared to less intensive interventions (three studies; average RR 1.29, 95% CI 0.75 to 2.20). High-quality evidence suggests incentive-based interventions are effective when compared with an alternative (non-contingent incentive) intervention (four studies; RR 2.36, 95% CI 1.36 to 4.09). However pooled effects were not calculable for comparisons with usual care or less intensive interventions (substantial heterogeneity, I2 = 93%). High-quality evidence suggests the effect is unclear in social support interventions provided by peers (six studies; average RR 1.42, 95% CI 0.98 to 2.07), in a single trial of support provided by partners, or when social support for smoking cessation was provided as part of a broader intervention to improve maternal health. The effect was unclear in single interventions of exercise compared to usual care (RR 1.20, 95% CI 0.72 to 2.01) and dissemination of counselling (RR 1.63, 95% CI 0.62 to 4.32). Importantly, high-quality evidence from pooled results demonstrated that women who received psychosocial interventions had a 17% reduction in infants born with low birthweight, a significantly higher mean birthweight (mean difference (MD) 55.60 g, 95% CI 29.82 to 81.38 g higher) and a 22% reduction in neonatal intensive care admissions. However the difference in preterm births and stillbirths was unclear. There did not appear to be adverse psychological effects from the interventions. The intensity of support women received in both the intervention and comparison groups has increased over time, with higher-intensity interventions more likely to have higher-intensity comparisons, potentially explaining why no clear differences were seen with increasing intervention intensity in meta-regression analyses. Among meta-regression analyses: studies classified as having 'unclear' implementation and unequal baseline characteristics were less effective than other studies. There was no clear difference between trials implemented by researchers (efficacy studies), and those implemented by routine pregnancy staff (effectiveness studies), however there was uncertainty in the effectiveness of counselling in four dissemination trials where the focus on the intervention was at an organisational level. The pooled effects were similar in interventions provided for women classified as having predominantly low socio-economic status, compared to other women. The effect was significant in interventions among women from ethnic minority groups; however not among indigenous women. There were similar effect sizes in trials with biochemically validated smoking abstinence and those with self-reported abstinence. It was unclear whether incorporating use of self-help manuals or telephone support increased the effectiveness of interventions. Authors' conclusions: Psychosocial interventions to support women to stop smoking in pregnancy can increase the proportion of women who stop smoking in late pregnancy and the proportion of infants born low birthweight. Counselling, feedback and incentives appear to be effective, however the characteristics and context of the interventions should be carefully considered. The effect of health education and social support is less clear. New trials have been published during the preparation of this review and will be included in the next update

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide (10panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia