Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy: Secondary analysis of the Pregnancy Trial of E-cigarettes and Patches (PREP) randomized controlled trial.

AIMS: The aim of this study was to examine the safety of e-cigarettes (EC) and nicotine patches (NRT) when used to help pregnant smokers quit. DESIGN: A recent trial of EC versus NRT reported safety outcomes in the randomized arms. We conducted a further analysis based on product use. SETTING: Twenty-three hospitals in England and a stop-smoking service in Scotland took part. PARTICIPANTS: The participants comprised 1140 pregnant smokers. INTERVENTIONS: We compared women using and not using EC and NRT regularly during pregnancy. MEASUREMENTS: Measurements included nicotine intake compared with baseline, birth weight, other pregnancy outcomes, adverse events, maternal respiratory symptoms and relapse in early abstainers. FINDINGS: Use of EC was more common than use of NRT (47.3% vs 21.6%, P < 0.001). Women who stopped smoking (abstainers) and used EC at the end-of-pregnancy (EOP) reduced their salivary cotinine by 45% [49.3 ng/ml, 95% confidence interval (CI) = -79.8 to -10]. Only one abstainer used NRT at EOP. In dual users, cotinine increased by 19% (24 ng/ml, 95% CI = 3.5-68). In women reporting a reduction of at least 50% in cigarette consumption, cotinine levels increased by 10% in those using nicotine products and by 9% in those who did not. Birth weights in dual users and exclusive smokers were the same (3.1 kg). Birth weight in abstainers using either nicotine product was higher than in smokers [3.3 kg, standard deviation (SD) = 0.7] versus 3.1 kg, SD = 0.6; difference = 0.15 kg, 95% CI = 0.05-0.25) and not different from abstainers not using nicotine products (3.1 kg, SD = 0.8). Abstainers and smokers using nicotine products had no worse pregnancy outcomes or more adverse events than abstainers and smokers not using them. EC users reported more improvements than non-users in cough [adjusted relative risk (aRR) = 0.59, 95% CI = 0.37-0.93] and phlegm (aRR = 0.53, 95% CI = 0.31-0.92), controlling for smoking status. EC or NRT use had no association with relapse. CONCLUSIONS: Regular use of e-cigarettes or nicotine patches by pregnant smokers does not appear to be associated with any adverse outcomes.

Effects of reduced-risk nicotine-delivery products on smoking prevalence and cigarette sales: an observational study.

Background: It is not currently clear what impact alternative nicotine-delivery products (electronic cigarettes, heated tobacco products and snus) have on smoking rates and cigarette sales. Objective: To assess whether access to these products promotes smoking in the population. Design and data sources: We examined associations of alternative nicotine product use and sales with smoking rates and cigarette sales overall, and in different age and socioeconomic groups, and compared smoking prevalence over time in countries with contrasting regulations of these products. For electronic cigarettes, we examined data from countries with historically similar smoking trajectories but differing current electronic cigarette regulations (United Kingdom and United States of America vs. Australia, where sales of nicotine-containing electronic cigarettes are banned); for heated tobacco, we used data from countries with state tobacco monopolies, where cigarette and heated tobacco sales data are available (Japan, South Korea), and for snus we used data from Sweden. Analysis methods: We pre-specified dynamic time series analyses to explore associations between use and sales of alternative nicotine-delivery products and smoking prevalence and cigarette sales, and time series analyses to compare trends of smoking prevalence in countries with different nicotine product policies. Results: Because of data and analysis limitations (see below), results are only tentative and need to be interpreted with caution. Only a few findings reached statistical significance and for most results the Bayes factor indicated inconclusive evidence. We did not find an association between rates of smoking and rates of the use of alternative nicotine products. The increase in heated tobacco product sales in Japan was accompanied by a decrease in cigarette sales. The decline in smoking prevalence seems to have been slower in Australia than in the United Kingdom overall, and slower than in both the United Kingdom and the United States of America among young people and also in lower socioeconomic groups. The decline in cigarette sales has also accelerated faster in the United Kingdom than in Australia. Limitations: Most of the available data had insufficient data points for robust time series analyses. The assumption of our statistical approach that causal interactions are more likely to be detected when longer-term changes are screened out may not apply for short time series and in product interaction scenarios, where short-term fluctuations can be caused by, for example, fluctuations in prosperity or product supplies. In addition, due to dual use, prevalence figures for smoking and alternative product use overlap. The ecological study design limits the causal inferences that can be made. Longer time periods are needed for any effects of exclusive use of the new products on smoking prevalence to emerge. Conclusions: We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses. Future work: As further prevalence and sales data emerge the analyses will become more informative. Accessing sales figures in particular is the current research priority. Study registration: The project is registered on Open Science Framework https://osf.io/bd3ah. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR129968) and will be published in full in Public Health Research; Vol. 11, No. 7. See the NIHR Journals Library website for further project information.

Alternative nicotine-delivery products are now available which are much less hazardous than cigarettes. These include electronic cigarettes (which contain no tobacco), Swedish snus (oral tobacco with low levels of cancer-causing chemicals) and heated tobacco products. There is concern that these products attract young people to smoking and discourage smokers from quitting (i.e. increase smoking), but it is also possible that they help smokers quit and steer young people who find nicotine attractive away from smoking, or that they have no effect on smoking. To clarify which of these end results is likely, we looked at data on smoking and on the use of these alternative products over time, and also compared data on smoking from countries that have similar tobacco control history, but that either allow (i.e. United Kingdom and United States of America) or ban the sale of electronic cigarettes (i.e. Australia). As the sale of heated tobacco products increased in Japan, sales of cigarettes seem to have gone down, suggesting that this product is competing with cigarettes rather than encouraging their use. We also found that the drop in smoking may have been slower in Australia than in the United Kingdom. For young people and those on low income specifically, the reduction in smoking was slower in Australia than in both the United Kingdom and United States of America. Allowing alternative nicotine products to be sold seems to have been linked with lowered rather than increased rates of smoking. Our findings, however, are uncertain because only limited data were available. Clearer conclusions will become possible as more data on the use and especially on the sales of alternative nicotine products are collected.

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).

Nicotine Delivery and User Ratings of IQOS Heated Tobacco System Compared With Cigarettes, Juul, and Refillable E-Cigarettes.

INTRODUCTION: Reduced-risk nicotine products are more likely to replace smoking if they match cigarettes in nicotine delivery and user satisfaction. AIMS AND METHODS: We examined the nicotine delivery profile and user ratings of IQOS heated tobacco system and compared it with own brand cigarettes (OBC), Juul, and refillable e-cigarettes (EC).Participants (N = 22) who were daily vapers smoking <1 cigarette per day on average, attended after overnight abstinence from smoking and vaping, to test at separate sessions OBC, IQOS, and Juul. Eight participants also tested two refillable EC using e-liquid with 20 mg/mL nicotine. At each session, a baseline blood sample was taken before participants used the product ad libitum for 5 minutes. Further samples were taken at 2, 4, 6, 8, 10, and 30 minutes. Maximum nicotine concentration (Cmax), time to Cmax (Tmax), and nicotine delivered over 30 minutes (AUC0->30) were calculated. Participants rated their urge to smoke and product characteristics. RESULTS: IQOS delivered less nicotine than OBC (AUC0->30: z = -2.73, p = .006), and than Juul (AUC0->30: z = -3.08, p = .002; Cmax: z = -2.65, p = .008), and received less favorable ratings than Juul (effect on urges to smoke: z = -3.23, p = .001; speed of urge relief: z = -2.75, p = .006; recommendation to friends: z = -2.45, p = .014). Compared with refillable EC, IQOS delivered nicotine faster (Tmax: z = -2.37, p = .018), but received less favorable overall ratings (recommended to friends: z = -2.32, p = .021). CONCLUSIONS: IQOS' pharmacokinetic profile suggests that it may be less effective than Juul for smoking cessation, but at least as effective as refillable EC; although participants, who were experienced vapers rather than IQOS users, preferred refillable EC. IMPLICATIONS: Because IQOS provided less efficient nicotine delivery than cigarettes and Juul in this sample, and also had a weaker effect on urges to smoke than Juul, it could be less helpful than Juul in assisting such dual users, and possibly smokers generally, to switch to an alternative product. IQOS, however, provided nicotine faster than refillable EC products, although participants preferred EC.

Time restricted eating as a weight loss intervention in adults with obesity.

OBJECTIVES: Time-restricted eating (TRE) is a weight management approach in which food is consumed only within a specific period each day. The simplicity of this approach is appealing, but its efficacy is not known. The aim of this pilot cohort study was to assess adherence to TRE and its effects on weight and lipid profile. METHODS: Fifty participants with obesity attempted to follow TRE for 12 weeks. Surveys were conducted weekly over the phone to assess treatment adherence and ratings; and at 6 and 12 weeks, participants attended the clinic to be weighed, have their blood pressure taken and provide a blood sample for lipid profile. Treatment results were compared with data from previous comparable cohorts using other weight management methods. RESULTS: Mean age of the participants was 50 (SD = 12.0), mean weight 97kg (SD = 17.1), mean BMI = 35 (SD = 4.0) and most were female (74%). At weeks 6 and 12, 64% and 58% of participants continued to practice TRE on at least five days/week. Using the 'last observation carried forward' imputation, mean (SD) weight loss was 2.0 (1.7) kg and 2.6 (2.6) kg at 6 and 12 weeks. Among participants who provided follow-up data, those who adhered to the intervention for at least five days/week recorded greater weight loss than those with lower adherence (week 6: 2.5 (1.7) vs 1.0 (1.3), p = 0.003; week 12: 3.5 (2.7) vs 1.3 (2.0), p = 0.001). A total of 26% of the sample lost at least 5% of their body weight at 12 weeks. The intervention had no effect on blood pressure or lipid profile. CONCLUSIONS: TRE results were modest, but at least on par with those achieved with more complex interventions, and weight loss did not decline at 12 weeks. A formal trial of the intervention is warranted.

Nicotine delivery and user reactions to Juul EU (20 mg/ml) compared with Juul US (59 mg/ml), cigarettes and other e-cigarette products.

RATIONALE: The degree to which the EU version of Juul with 20 mg/ml nicotine (Juul EU) delivers nicotine to users is likely to determine its treatment potential. OBJECTIVES: To compare the pharmacokinetic profile and user ratings of Juul EU, Juul US (59 mg/ml nicotine), cigarettes and other e-cigarette (EC) products. METHODS: In a within-subjects crossover design, 18 vapers used, at separate sessions, their own brand cigarette (OBC), Juul US and Juul EU for 5 min ad libitum, after overnight abstinence. Seven of the participants also tested eight other EC previously. Blood samples were taken at baseline and 2, 4, 6, 8, 10 and 30 min after initiating product use. Products were rated on a range of characteristics. RESULTS: Juul EU delivered less nicotine than OBC (t(13) = -4.64 p < .001) and than Juul US (t(13) = -6.40, p < .001): AUC0 ≥ 30 77.3, 324.8 and 355.9, respectively. Maximum nicotine concentration (Cmax) was also much lower for Juul EU than Juul US (z = -3.59, p < .001): Cmax 3.8 ng/ml vs 21.1 ng/ml, respectively. Juul EU was perceived to relieve urges to smoke less than Juul US (z = -2.29, p = .022) and to provide less nicotine (z = -2.57. p = 0.010). Juul EU delivered less nicotine than refillable EC (Cmax: t(6) = 3.02, p = 0.023; AUC0 ≥ 30: z = -2.20, p = 0.028) and also less than cig-a-like EC, though the difference did not reach significance (Cmax: t(6) = 2.49, p = 0.047; AUC0 ≥ 30: z = -1.99, p = 0.046). Subjective ratings of Juul EU and other EC products were similar. CONCLUSIONS: Juul EU delivers much less nicotine to users than Juul US, and also less than refillable EC products. It may thus have more limited potential to help smokers quit.

Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT.

BACKGROUND: Relapse remains an unresolved issue in smoking cessation. Extended stop smoking medication use can help, but uptake is low and several behavioural relapse prevention interventions have been found to be ineffective. However, opportunistic 'emergency' use of fast-acting nicotine replacement treatment or electronic cigarettes may be more attractive and effective, and an online behavioural Structured Planning and Prompting Protocol has shown promise. The present trial aimed to evaluate the clinical effectiveness and cost-effectiveness of these two interventions. DESIGN: A randomised controlled trial. SETTING: English stop smoking services and Australian quitlines, Australian social media and St Vincent's Hospital Melbourne, Fitzroy, VIC. PARTICIPANTS: Ex-smokers abstinent for at least 4 weeks, with some participants in Australia also recruited from 1 week post quit date. The planned sample size was 1400, but the trial was curtailed when 235 participants were recruited. INTERVENTIONS: Participants were randomised in permuted blocks of random sizes to (1) oral nicotine replacement treatment/electronic cigarettes to use if at risk of relapse, plus static text messages (n = 60), (2) the Structured Planning and Prompting Protocol and interactive text messages (n = 57), (3) oral nicotine replacement treatment/electronic cigarettes plus the Structured Planning and Prompting Protocol with interactive text messages (n = 58) or (4) usual care plus static text messages (n = 59). OUTCOME MEASURES: Owing to delays in study set-up and recruitment issues, the study was curtailed and the primary outcome was revised. The original objective was to determine whether or not the two interventions, together or separately, reduced relapse rates at 12 months compared with usual care. The revised primary objective was to determine whether or not number of interventions received (i.e. none, one or two) affects relapse rate at 6 months (not biochemically validated because of study curtailment). Relapse was defined as smoking on at least 7 consecutive days, or any smoking in the last month at final follow-up for both the original and curtailed outcomes. Participants with missing outcome data were included as smokers. Secondary outcomes included sustained abstinence (i.e. no more than five cigarettes smoked over the 6 months), nicotine product preferences (e.g. electronic cigarettes or nicotine replacement treatment) and Structured Planning and Prompting Protocol coping strategies used. Two substudies assessed reactions to interventions quantitatively and qualitatively. The trial statistician remained blinded until analysis was complete. RESULTS: The 6-month relapse rates were 60.0%, 43.5% and 49.2% in the usual-care arm, one-intervention arm and the two-intervention arm, respectively (p = 0.11). Sustained abstinence rates were 41.7%, 54.8% and 50.9%, respectively (p = 0.17). Electronic cigarettes were chosen more frequently than nicotine replacement treatment in Australia (71.1% vs. 29.0%; p = 0.001), but not in England (54.0% vs. 46.0%; p = 0.57). Of participants allocated to nicotine products, 23.1% were using them daily at 6 months. The online intervention received positive ratings from 63% of participants at 6 months, but the majority of participants (72%) completed one assessment only. Coping strategies taught in the Structured Planning and Prompting Protocol were used with similar frequency in all study arms, suggesting that these are strategies people had already acquired. Only one participant used the interactive texting, and interactive and static messages received virtually identical ratings. LIMITATIONS: The inability to recruit sufficient participants resulted in a lack of power to detect clinically relevant differences. Self-reported abstinence was not biochemically validated in the curtailed trial, and the ecological momentary assessment substudy was perceived by some as an intervention. CONCLUSIONS: Recruiting recent ex-smokers into an interventional study proved problematic. Both interventions were well received and safe. Combining the interventions did not surpass the effects of each intervention alone. There was a trend in favour of single interventions reducing relapse, but it did not reach significance and there are reasons to interpret the trend with caution. FUTURE WORK: Further studies of both interventions are warranted, using simpler study designs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11111428. 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. 24, No. 68. See the NIHR Journals Library website for further project information. Funding was also provided by the National Health and Medical Research Council, Canberra, ACT, Australia (NHMRC APP1095880). Public Health England provided the funds to purchase the nicotine products in England.

Stop smoking services help people to stop smoking over a short period of time. However, nearly three-quarters of quitters return to smoking (i.e. relapse) within 1 year. Effective relapse prevention strategies are needed. Traditional behavioural relapse prevention strategies (e.g. teaching techniques to resist having a cigarette) have not proved effective. However, an earlier study showed that an online programme guiding smokers in stopping smoking and remaining abstinent reduced relapse between 1 week and 6 months. Long-term use of stop smoking medications (e.g. nicotine replacement treatment) can also help, but most successful quitters do not continue to use them. Nicotine mouth spray, lozenges or electronic cigarettes that can quickly help relieve urges to smoke and that ex-smokers can use 'in emergencies' could be a more attractive option. We planned to test these two interventions, on their own and together, in 1400 participants who had quit ≥ 4 weeks previously and who were recruited from English stop smoking services and Australian quitlines. We would then compare these participants with the participants following usual care (i.e. access to stop smoking medications used during the quit attempt for up to 3 months). Owing to delays in study set-up and difficulties in recruiting, the study recruited only 234 participants (n = 131 in Australia and n = 103 in England). We studied participants' reactions to the two interventions and to their combination, and how clinically effective the interventions were. Both interventions were rated positively by most participants. Among the participants in Australia, electronic cigarettes were more popular than medical nicotine products. In England, both products were equally popular. Participants in the online intervention group appreciated the advice on coping strategies, but they rarely completed repeat assessments. In addition, participants who were not in this group used the strategies just as much. There were hints that the interventions may be helpful in preventing relapse. There is an indication that the two interventions combined did not do any better than each on its own, but this requires replication in a larger study. Although the interventions show promise, the small number of participants recruited means that we are unable to make strong conclusions. The study identified areas for future work.

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.

E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT.

BACKGROUND: Over the past few years, a large number of smokers in the UK have stopped smoking with the help of e-cigarettes. So far, UK Stop Smoking Services (SSSs) have been reluctant to include e-cigarettes among their treatment options because data on their efficacy compared with the licensed medications are lacking. OBJECTIVE: The objective was to compare the efficacy of refillable e-cigarettes and nicotine replacement therapy (NRT) products, when accompanied by weekly behavioural support. DESIGN: A randomised controlled trial comparing e-cigarettes and NRT. SETTING: Three sites that provide local SSSs. PARTICIPANTS: The participants were 886 smokers seeking help to quit smoking, aged ≥ 18 years, not pregnant or breastfeeding, with no strong preference to use or not to use NRT or e-cigarettes in their quit attempt, and currently not using NRT or e-cigarettes. A total of 886 participants were randomised but two died during the study (one in each study arm) and were not included in the analysis. INTERVENTIONS: The NRT arm (n = 446) received NRT of their choice (single or combination), provided for up to 12 weeks. The e-cigarette arm (n = 438) received an e-cigarette starter pack and were encouraged to buy addtional e-liquids and e-cigarette products of their choice. Both arms received the same standard behavioural support. Participants attended weekly sessions at their SSS and provided outcome data at 4 weeks. They were then followed up by telephone at 6 and 12 months. Participants reporting abstinence or at least 50% reduction in cigarette consumption at 12 months were invited to attend for carbon monoxide (CO) validation. Participants/researchers could not be blinded to the intervention. MAIN OUTCOME MEASURES: The primary outcome was CO-validated sustained abstinence rates at 52 weeks. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included abstinence at other time points, reduction in smoke intake, treatment adherence and ratings, elicited adverse reactions, and changes in self-reported respiratory health. A cost-efficacy analysis of the intervention was also conducted. RESULTS: The 1-year quit rate was 9.9% in the NRT arm and 18.0% in the e-cigarette arm (risk ratio 1.83, 95% confidence interval 1.30 to 2.58; p < 0.001). The e-cigarette arm had significantly higher validated quit rates at all time points. Participants in the e-cigarette arm showed significantly better adherence and experienced fewer urges to smoke throughout the initial 4 weeks of their quit attempt than those in the NRT arm, and gave their allocated product more favourable ratings. They were also more likely to be still using their allocated product at 1 year (39.5% vs. 4.3%, χ2 = 161.4; p < 0.001). Participants assigned to e-cigarettes reported significantly less coughing and phlegm at 1 year than those assigned to NRT (controlling for smoking status). A detailed economic analysis confirmed that, because e-cigarettes incur lower NHS costs than NRT and generate a higher quit rate, e-cigarette use is more cost-effective. LIMITATIONS: The results may not be generalisable to other types of smokers or settings, or to cartridge-based e-cigarettes. CONCLUSIONS: Within the context of multisession treatment for smokers seeking help, e-cigarettes were significantly more effective than NRT. If SSSs provide e-cigarette starter packs, it is likely to boost their success rates and improve their cost-efficacy. FUTURE WORK: The efficacy of e-cigarettes provided with different levels of support will show whether smokers should be encouraged to switch to vaping within support services or whether e-cigarettes can be recommended with less intensive or no support. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60477608. 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. 23, No. 43. See the NIHR Journals Library website for further project information. The trial was supported by the Cancer Research UK Prevention Trials Unit (grant A16893).

Alarge number of smokers in the UK have stopped smoking with the help of e-cigarettes, but it is not known if e-cigarettes are as helpful as stop smoking medications that are provided by the UK Stop Smoking Services (SSSs). This information is needed to decide whether or not SSSs should include e-cigarettes among their treatment options. A total of 886 smokers who were seeking help with quitting and did not mind whether they would use nicotine replacement therapy (NRT), such as nicotine patches, or e-cigarettes were recruited at three SSSs. The smokers were randomly allocated (by chance) to receive weekly behavioural support and either a NRT of their choice (a single NRT product or product combinations) (n = 447) or a starter pack of e-cigarettes (n = 439). The trial ran from May 2015 to February 2018. The participants were followed up for 1 year to see how many stopped smoking in each group. Smokers using e-cigarettes suffered less cigarette withdrawal discomfort early on and had higher quit rates at all time points. At 1 year, 10% of participants in the NRT trial arm had been abstinent for the whole year, compared with 18% in the e-cigarette arm; regarding abstinence for at least 6 months, the figures were 12% in the NRT arm and 21% in the e-cigarette arm. Of interest, coughs and phlegm production also reduced more in people quitting with e-cigarettes than those quitting with NRT. This supports previous reports suggesting that an ingredient in e-cigarettes (i.e. propylene glycol) may protect vapers from airborne infections. E-cigarette starter packs cost much less than NRT and so, if SSSs provide them, their use is likely to boost the success rates and reduce the costs of SSSs.

Are 'dual users' who smoke and use e-cigarettes interested in using varenicline to stop smoking altogether, and can they benefit from it? A cohort study of UK vapers.

OBJECTIVES: Smokers who use e-cigarettes (EC) do so mostly to stop smoking, but many continue to use both products. It is not known whether these 'dual users' are interested in stop-smoking medications and whether they can benefit from them. SETTING, PARTICIPANTS AND MEASURES: Dual users were recruited over social media and posted study questionnaire and saliva kits at baseline, 3 and 6 months. Those interested in varenicline were posted the medication and received weekly calls over the first 6 weeks, followed by three calls at fortnightly intervals. RESULTS: Of 204 participants, 124 (61%, CI=54% to 68%) expressed interest in receiving varenicline and 80 (39%, CI=32% to 45%) started varenicline (varenicline users, VU). VU were more dependent smokers (F=6.2, p=0.01) with higher cigarette consumption (F=8.7, p<0.01) who were using stronger nicotine e-liquids (F=13.9, p<0.001) than dual users not opting for varenicline (varenicline non-users, VN). In terms of abstinence for at least 3 months at the 6-month follow-up, VU were more likely than VN to report abstinence from smoking (17.5% vs 4.8%, p=0.006, RR=3.6, CI:1.4 to 9.0), vaping (12.5% vs 1.6%, p=0.007, RR=7.8, CI:1.7 to 34.5) and both smoking and vaping (8.8% vs 0.8%, p=0.02, RR=10.9, CI:1.4 to 86.6). The differences were significant across sensitivity analyses (RRs=4.9 to 14.0; p=0.02 to p<0.001 at 3 months; RRs=3.0 to 14.0; p=0.01 to p<0.001 at 6 months). VU reported a greater reduction in enjoyment of vaping by the end of the varenicline use period (F=4.1, p=0.04) and recorded a significantly greater reduction in nicotine intake than VN at 3 months (F=13.9, p<0.001) and 6 months (F=26.5, p<0.001). CONCLUSION: Varenicline offered to dual users is likely to promote successful abstinence from both smoking and vaping, although a randomised trial is needed to confirm this. Among dual users who want to stop smoking, there seems to be a high level of interest in smoking-cessation treatments.

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 .).

Initial ratings of different types of e-cigarettes and relationships between product appeal and nicotine delivery.

AIMS: Little is known about features of e-cigarettes (EC) that facilitate or hinder the switch from smoking to vaping. We tested eight brands of EC to determine how nicotine delivery and other product characteristics influence user's initial reactions. METHODS: Fifteen vapers tested each product after overnight abstinence from both smoking and vaping. At each session, participant's vaped ad lib for 5 min. Blood samples were taken at baseline and at 2, 4, 6, 8, 10 and 30 min after starting vaping. Participants rated the products on a range of characteristics. The products tested included six 'cig-a-like' and two refillable products, one with variable voltage. We also tested participants' own EC. RESULTS: All products significantly reduced urges to smoke. Refillable products delivered more nicotine and received generally superior ratings in terms of craving relief, subjective nicotine delivery, throat hit and vapour production but in overall ratings, they were joined by a cig-a-like, Blu. Participants puffed more on low nicotine delivery products. Participants' estimates of nicotine delivery from different EC were closely linked to 'throat hit'. Nicotine delivery was less important in the initial product ratings than draw resistance, mouthpiece comfort and effects on reducing urge to smoke. CONCLUSIONS: All EC products reduced urges to smoke. Refillable products received generally more favourable ratings than 'cig-a-likes' with similar nicotine content. Perception of nicotine delivery was guided by throat sensations. Lower nicotine delivery was associated with more frequent puffing. The first impressions of EC products are guided less by nicotine delivery than by sensory signals.