Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy.

Background: Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives: To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design: A pragmatic multi-centre randomised controlled trial. Setting: Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants: One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions: Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures: The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results: Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Limitations: Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. Conclusions: E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Future work: Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. Trial registration: This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.

Like many other smokers in the UK, some pregnant smokers try to limit or stop smoking with the help of e-cigarettes. It is not known whether this helps with stopping smoking and whether using e-cigarettes has any bad effects on the baby. We recruited 1140 pregnant smokers who wanted to quit. A random half were given nicotine patches, which are commonly used to help smokers quit. The other half were given an e-cigarette. They also received six weekly phone calls to support them in stopping smoking. We then looked at how many in each group stopped smoking by the end of pregnancy. More women stopped smoking in the group that was given an e-cigarette, but the difference was small and could be due to chance. However, some of the women in the nicotine patch group who had successfully stopped smoking were using e-cigarettes rather than patches. When these (and women in the e-cigarette group who used patches) were not counted, e-cigarettes helped almost twice as many women stop smoking than patches. E-cigarettes were better than patches in preventing low birthweight (having babies who weigh less than 2.5 kg). Otherwise, women given patches and those given e-cigarettes (and their babies) had similar numbers of medical complications. For pregnant women who smoke and need help to quit, e-cigarettes are probably more helpful than nicotine patches, and do not pose any additional risks to women or their babies.

Electronic cigarettes versus nicotine patches for smoking cessation in pregnancy: a randomized controlled trial.

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report the results of a randomized controlled trial in 1,140 participants comparing refillable e-cigarettes with nicotine patches. Pregnant women who smoked were randomized to e-cigarettes (n = 569) or nicotine patches (n = 571). In the unadjusted analysis of the primary outcome, validated prolonged quit rates at the end of pregnancy in the two study arms were not significantly different (6.8% versus 4.4% in the e-cigarette and patch arms, respectively; relative risk (RR) = 1.55, 95%CI: 0.95-2.53, P = 0.08). However, some participants in the nicotine patch group also used e-cigarettes during the study. In a pre-specified sensitivity analysis excluding abstinent participants who used non-allocated products, e-cigarettes were more effective than patches (6.8% versus 3.6%; RR = 1.93, 95%CI: 1.14-3.26, P = 0.02). Safety outcomes included adverse events and maternal and birth outcomes. The safety profile was found to be similar for both study products, however, low birthweight (<2,500 g) was less frequent in the e-cigarette arm (14.8% versus 9.6%; RR = 0.65, 95%CI: 0.47-0.90, P = 0.01). Other adverse events and birth outcomes were similar in the two study arms. E-cigarettes might help women who are pregnant to stop smoking, and their safety for use in pregnancy is similar to that of nicotine patches. ISRCTN62025374.

E-cigarettes versus nicotine replacement treatment as harm reduction interventions for smokers who find quitting difficult: randomized controlled trial.

BACKGROUND AND AIMS: The majority of smokers accessing the current best treatments continue to smoke. We aimed to test if e-cigarettes (EC) compared with nicotine replacement treatment (NRT) can help such smokers to reduce smoking. DESIGN: Randomized controlled trial of EC (n = 68) versus NRT (n = 67) with 6-month follow-up. SETTING: Stop smoking service in London, UK. PARTICIPANTS: A total of 135 smokers (median age = 40 years, 51% male) previously unable to stop smoking with conventional treatments. INTERVENTIONS: Participants received either NRT of their choice (8-week supply) or an EC starter pack and instructions to purchase further e-liquids of strength and flavours of their choice themselves. Products were accompanied by minimal behavioural support. MEASUREMENTS: Participants who reported that they stopped smoking or reduced their daily cigarette consumption by at least 50% at 6-month follow-up were invited to provide a carbon monoxide (CO) reading. The primary outcome was biochemically validated reduction in smoke intake of at least 50% at 6 months and the main secondary outcome was sustained validated abstinence at 6 months. Drop-outs were included as 'non-reducers'. FINDINGS: Validated smoking reduction (including cessation) was achieved by 26.5 versus 6.0% of participants in the EC and NRT study arms, respectively [relative risk (RR) = 4.4, P = 0.005, 95% confidence interval (CI) = 1.6-12.4]. Sustained validated abstinence rates at 6 months were 19.1 versus 3.0% (RR = 6.4, P = 0.01, 95% CI = 1.5-27.3). Product use was high and equal in both study arms initially, but at 6 months allocated product use was 47% in the EC arm versus 10% in the NRT arm (χ2(1)  = 22.0, P < 0.001), respectively. Adverse events were minor and infrequent. CONCLUSIONS: In smokers unable to quit using conventional methods, e-cigarettes were more effective than nicotine replacement therapy in facilitating validated long-term smoking reduction and smoking cessation when limited other support was provided.

A randomised controlled trial of the 5:2 diet.

OBJECTIVE: The 5:2 diet is a popular intermittent energy restriction method of weight management that awaits further evaluation. We compared the effects of one-off 5:2 instructions with the effects of one-off standard multicomponent weight-management advice; and also examined whether additional behavioural support enhances 5:2 adherence and efficacy compared to one-off instructions. METHODS: Three hundred adults with obesity were randomised to receive a Standard Brief Advice (SBA) covering diet and physical activity (N = 100); 5:2 self-help instructions (5:2SH) (N = 100); or 5:2SH plus six once-weekly group support sessions (N = 100). Participants were followed up for one year. RESULTS: Adherence to 5:2SH was initially high (74% at 6 weeks), but it declined over time (31% at 6 months and 22% at one year). 5:2SH and SBA achieved similar weight-loss at six months (-1.8kg (SD = 3.5) vs -1.7kg (SD = 4.4); b = 0.23, 95%CI:-0.79-1.27, p = 0.7) and at one year (-1.9kg (SD = 4.9) vs -1.8kg (SD = 5.7), b = 0.20, 95%CI:-1.21-1.60, p = 0.79), with 18% vs 15% participants losing ≥5% of their body weight with 5:2SH and SBA, respectively at one year (RR = 0.83, 95%CI:0.44-1.54, p = 0.55). Both interventions received positive ratings, but 5:2SH ratings were significantly higher. 5:2SH had no negative effect on fat and fiber intake and physical activity compared to SBA. Compared to 5:2SH, 5:2G generated a greater weight loss at 6 weeks (-2.3kg vs -1.5kg; b = 0.74, 95%CI:1.37-0.11, p = 0.02), but by one year, the difference was no longer significant (-2.6kg vs -1.9kg, p = 0.37; ≥5% body weight loss 28% vs 18%, p = 0.10). CONCLUSIONS: Simple 5:2 advice and multicomponent weight management advice generated similar modest results. The 5:2 diet did not undermine other health behaviours, and it received more favourable ratings. Adding initial group support enhanced 5:2 adherence and effects, but the impact diminished over time. Health professionals who provide brief weight management advice may consider including the 5:2 advice as an option. TRIAL REGISTRATION: ISRCTN registry (ISRCTN79408248).

A Qualitative Study of Factors Influencing Adherence among Pregnant Women Taking Part in a Trial of E-Cigarettes for Smoking Cessation.

Use of e-cigarettes (vaping) has potential to help pregnant women stop smoking. This study explored factors influencing adherence among participants in the vaping arm of the first trial of vaping for smoking cessation in pregnancy. We conducted semi-structured telephone interviews (n = 28) with women at three-months postpartum. Interviews were analysed using thematic analysis, informed by the Theoretical-Domains Framework, Necessity-Concerns Framework and Perceptions and Practicalities Approach. Interviewees generally reported high levels of vaping. We found that: (1) intervention adherence was driven by four necessity beliefs-stopping smoking for the baby, and vaping for harm reduction, smoking cessation or as a last resort; (2) necessity beliefs outweighed vaping concerns, such as dependence and safety; (3) adherence was linked to four practicalities themes, acting as barriers and facilitators to vaping-device and e-liquid perceptions, resources and support, whether vaping became habitual, and social and environmental factors; and (4) intentional non-adherence was rare; unintentional non-adherence was due to device failures, forgetting to vape, and personal circumstances and stress. Pregnant smokers provided with e-cigarettes, and with generally high levels of vaping, had positive beliefs about the necessity of vaping for smoking cessation which outweighed concerns about vaping. Non-adherence was mainly due to unintentional factors.

Nicotine delivery and users' reactions to Juul compared with cigarettes and other e-cigarette products.

AIMS: To assess the pharmacokinetic (PK) profile of, and users' reactions to, Juul (59 mg nicotine/ml) as an indication of its therapeutic and dependence potential. DESIGN: Cross-over, within-subjects study in which participants attended after overnight abstinence on separate sessions and smoked a cigarette or used Juul or eight other types of e-cigarettes (EC) ad libitum for 5 minutes. The Juul product used was the version available in the United States that has more nicotine in the e-liquid than the one available in the European Union. SETTING: Laboratory setting in the United Kingdom. PARTICIPANTS: Twenty dual users (smokers who also vape) provided data on Juul and cigarettes, with eight also providing data on other EC products. MEASUREMENTS: At each session, number of puffs taken was counted during the 5-minute product use period and blood samples were taken at baseline and at 2, 4, 6, 8, 10 and 30 minutes after starting smoking/vaping and analysed for nicotine. Participants also monitored their urges to smoke and rated the products on a range of characteristics. FINDINGS: Juul's PK profile was close to the PK profile of cigarettes [maximum concentration (Cmax ) = 20.4 versus 19.2 ng/ml; time to maximum concentration (Tmax ) = 4 versus 6 minutes; area under the curve (AUC): 307.9 versus 312.6, respectively]. Compared with other EC products, Juul had shorter Tmax [4 minutes, (IQR = 2.5-4.0) versus 6.3 minutes, (IQR = 4.7 - 8.1), P = 0.012] and higher Cmax (28.9 (SD = 15.6) versus 10.6 (SD = 5.5), P = 0.013) despite a lower number of puffs (12.5 (SD = 4.2) versus 17.0 (SD = 4.2), P = 0.084). Compared with other e-cigarette products, it also provided faster reduction of urges to smoke and obtained more favourable subjective ratings. CONCLUSION: Juul's PK profile and user ratings suggest that it could be more effective than other EC products in helping smokers to quit smoking, but it may also have a higher potential to generate regular use in non-smokers.

Cost-effectiveness of e-cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial.

AIM: To evaluate the cost-effectiveness of e-cigarettes as a smoking cessation aid used in routine stop smoking services in England. DESIGN: Cost-effectiveness analysis was performed from the National Health Service (NHS) and Personal Social Services (PSS) perspective for 12-month periods and life-time. Costs, including that of both treatments, other smoking cessation help and health-care services, and health benefits, estimated from EQ-5D-5L and measured in quality-adjusted life-years (QALYs), for the 12-month analysis, came from a randomized controlled trial. Life-time analysis was model-based with input from both trial data and published secondary data sources. Cost-effectiveness was measured by an incremental cost-effectiveness ratio (ICER). SETTING: Three stop-smoking service sites in England. PARTICIPANTS: Adult smokers (n = 886) who sought help to quit in the participating sites. INTERVENTION AND COMPARATOR: An e-cigarette (EC) starter kit versus provision of nicotine replacement therapy (NRT) for up to 3 months, both with standard behavioural support. A total of 886 participants were randomized (439 in the EC arm, 447 in the NRT arm). Excluding one death in each arm, the 1-year quit rate was 18.0 and 9.9%, respectively. MEASUREMENTS: Cost of treatments was estimated from the treatment log. Costs of other smoking cessation help and health-care services and EQ-5D-5 L were collected at baseline, 6- and 12-month follow-ups. Incremental costs and incremental QALYs were estimated using regression adjusting for baseline covariates and their respective baseline values. FINDINGS: The ICER was £1100 per QALY gained at the 12 months after quit date (87% probability below £20 000/QALY). Markov model estimated the life-time ICER of EC to be £65 per QALY (85% probability below £20 000/QALY). CONCLUSION: Using e-cigarettes as a smoking cessation aid with standard behavioural support in stop-smoking services in England is likely to be more cost-effective than using nicotine replacement therapy in the same setting.

A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.

BACKGROUND: E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments. METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms. RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath. CONCLUSIONS: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

Tackling obesity in areas of high social deprivation: clinical effectiveness and cost-effectiveness of a task-based weight management group programme - a randomised controlled trial and economic evaluation.

BACKGROUND: An increasing number of people require help to manage their weight. The NHS recommends weight loss advice by general practitioners and/or a referral to a practice nurse. Although this is helpful for some, more effective approaches that can be disseminated economically on a large scale are needed. OBJECTIVE: To assess whether or not a task-based weight management programme [Weight Action Programme (WAP)] has better long-term effects than a 'best practice' intervention provided in primary care by practice nurses. DESIGN: Randomised controlled trial with cost-effectiveness analysis. SETTING: General practices in east London, UK. PARTICIPANTS: Three hundred and thirty adults with a body mass index (BMI) of ≥ 30 kg/m2 or a BMI of ≥ 28 kg/m2 plus comorbidities were recruited from local general practices and via media publicity. Those who had a BMI of > 45 kg/m2, had lost > 5% of their body weight in the previous 6 months, were currently pregnant or taking psychiatric medications were excluded. Participants were randomised (2 : 1) to the WAP or nurse arms. INTERVENTIONS: The WAP intervention was delivered in eight weekly group sessions that combined dietary and physical activity, advice and self-monitoring in a group-oriented intervention. The initial course was followed by 10 monthly group maintenance sessions open to all participants in this study arm. The practice nurse intervention (best usual care) consisted of four one-to-one sessions delivered over 8 weeks, and included standard advice on diet and physical activity based on NHS 'Change4Life' materials and motivational support. MAIN OUTCOME MEASURES: The primary outcome measure was weight change at 12 months. Secondary outcome measures included change in BMI, waist circumference and blood pressure, and proportion of participants losing at least 5% and 10% of baseline body weight. Staff collecting measurements at the 6- and 12-month follow-ups were blinded to treatment allocation. The primary outcome measure was analysed according to the intention-to-treat principle, and included all participants with at least one recorded outcome at either 1, 2, 6 or 12 months. The analysis employed a mixed-effects linear regression model, adjusted for baseline weight, age, sex, ethnicity, smoking status and general practice. The European Quality of Life-5 Dimensions-5 Levels questionnaire was completed and used to estimate quality-adjusted life-years (QALYs) within the cost-effectiveness analysis. RESULTS: There were 330 participants (WAP arm, n = 221; nurse arm, n = 109; 72% women). A total of 291 (88%) participants (WAP arm, n = 194; nurse arm, n = 97) were included in the main analysis for the primary outcome. Weight loss at 12 months was greater in the WAP arm than in the nurse intervention arm [-4.2 kg vs. -2.3 kg; difference -1.9 kg, 95% confidence interval (CI) -3.7 to -0.1 kg; p = 0.04]. Participants in the WAP arm were more likely than participants in the nurse arm to have lost at least 5% of their baseline body weight at 12 months (41% vs. 27%; odds ratio 14.61, 95% CI 2.32 to 91.96; p = 0.004). The incremental cost-effectiveness ratio for WAP over and above the nurse arm is £7742 per QALY. CONCLUSIONS: A WAP delivered in general practice better promotes weight loss over 12 months than a best usual practice nurse-led weight loss programme. LIMITATIONS: The trial recruited mostly women. Research is needed into factors that would make weight loss programmes more attractive to men. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45820471. 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. 20, No. 79. See the NIHR Journals Library website for further project information.

Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use.

INTRODUCTION: Electronic cigarettes (EC) have the potential to generate a substantial public health benefit if there is a switch from smoking to EC use on a population scale. The nicotine delivery from EC is likely to play a major role in their attractiveness to smokers. We assessed nicotine delivery from a first-generation EC and the effect of experience with its use on nicotine intake. METHODS: Six smokers provided pharmacokinetic (PK) data after their first use of EC and again following 4 weeks of use. RESULTS: The peak nicotine levels were achieved within 5 min of starting the EC use, which suggests that EC may provide nicotine via pulmonary absorption. There were large individual differences in nicotine intake. Compared with the PK profile when using EC for the first time, 4 weeks of practice generated a 24% increase in the peak plasma concentrations (from 4.6 to 5.7 ng/ml; nonsignificant) and a 79% increase in overall nicotine intake (AUC(0 → inf) increased from 115 to 206 ng*min/ml; p < .05). CONCLUSIONS: First-generation EC provide faster nicotine absorption than nicotine replacement products, but to compete successfully with conventional cigarettes, EC may need to provide higher doses of nicotine. Nicotine intake from EC can increase with practice, but further studies are needed to confirm this effect.

Development of an Evidence-Based mHealth Weight Management Program Using a Formative Research Process.

BACKGROUND: There is a critical need for weight management programs that are effective, cost efficient, accessible, and acceptable to adults from diverse ethnic and socioeconomic backgrounds. mHealth (delivered via mobile phone and Internet) weight management programs have potential to address this need. To maximize the success and cost-effectiveness of such an mHealth approach it is vital to develop program content based on effective behavior change techniques, proven weight management programs, and closely aligned with participants' needs. OBJECTIVE: This study aims to develop an evidence-based mHealth weight management program (Horizon) using formative research and a structured content development process. METHODS: The Horizon mHealth weight management program involved the modification of the group-based UK Weight Action Program (WAP) for delivery via short message service (SMS) and the Internet. We used an iterative development process with mixed methods entailing two phases: (1) expert input on evidence of effective programs and behavior change theory; and (2) target population input via focus group (n=20 participants), one-on-one phone interviews (n=5), and a quantitative online survey (n=120). RESULTS: Expert review determined that core components of a successful program should include: (1) self-monitoring of behavior; (2) prompting intention formation; (3) promoting specific goal setting; (4) providing feedback on performance; and (5) promoting review of behavioral goals. Subsequent target group input confirmed that participants liked the concept of an mHealth weight management program and expressed preferences for the program to be personalized, with immediate (prompt) and informative text messages, practical and localized physical activity and dietary information, culturally appropriate language and messages, offer social support (group activities or blogs) and weight tracking functions. Most target users expressed a preference for at least one text message per day. We present the prototype mHealth weight management program (Horizon) that aligns with those inputs. CONCLUSIONS: The Horizon prototype described in this paper could be used as a basis for other mHealth weight management programs. The next priority will be to further develop the program and conduct a full randomized controlled trial of effectiveness.