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.

Randomised controlled trial and economic evaluation of a task-based weight management group programme.

BACKGROUND: Obesity is a rising global threat to health and a major contributor to health inequalities. Weight management programmes that are effective, economical and reach underprivileged groups are needed. We examined whether a multi-modal group intervention structured to cater for clients from disadvantaged communities (Weight Action Programme; WAP) has better one-year outcomes than a primary care standard weight management intervention delivered by practice nurses (PNI). METHODS: In this randomised controlled trial, 330 obese adults were recruited from general practices in London and allocated (2:1) to WAP (N = 221) delivered over eight weekly group sessions or PNI (N = 109) who received four sessions over eight weeks. Both interventions covered diet, physical activity and self-monitoring. The primary outcome was the change in weight from baseline at 12 months. To indicate value to the NHS, a cost effectiveness analysis estimated group differences in cost and Quality-Adjusted Life-Years (QALYs) related to WAP. RESULTS: Participants were recruited from September 2012 to January 2014 with follow-up completed in February 2015. Most participants were not in paid employment and 60% were from ethnic minorities. 88% of participants in each study arm provided at least one recorded outcome and were included in the primary analysis. Compared with the PNI, WAP was associated with greater weight loss overall (- 4·2 kg vs. - 2·3 kg; difference = - 1·9 kg, 95% CI: -3·7 to - 0·1; P = 0·04) and was more likely to generate a weight loss of at least 5% at 12 months (41% vs. 27%, OR = 14·61 95% CI: 2·32 to 91·96, P = 0·004). With an incremental cost-effectiveness ratio (ICER) of £7742/QALY, WAP would be considered highly cost effective compared to PNI. CONCLUSIONS: The task-based programme evaluated in this study can provide a template for an effective and economical approach to weight management that can reach clients from disadvantaged communities. TRIAL REGISTRATION: ISRCTN ISRCTN45820471 . Registered 12/10/2012 (retrospectively registered).

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.

Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial.

BACKGROUND: Nicotine replacement therapy (NRT) and varenicline are both effective in helping smokers quit. There is growing interest in combining the two treatments to improve treatment outcomes, but no experimental data exist on whether this is efficacious. This double-blind randomised controlled trial was designed to evaluate whether adding nicotine patches to varenicline improves withdrawal relief and short-term abstinence rates. METHODS: 117 participants seeking help to stop smoking were randomly allocated to varenicline plus placebo patch or varenicline plus nicotine patch (15 mg/16 hour). Varenicline use commenced one week prior to the target quit date (TQD), patch use started on the TQD. Ratings of urges to smoke and cigarette withdrawal symptoms were collected weekly over 4 weeks post-TQD. Medication use and smoking status were established at 1, 4 and 12 weeks. Participants lost to follow-up were included as continuing smokers. RESULTS: 92% of participants used both medications during the first week after the TQD. The combination treatment generated no increase in nausea or other adverse effects. It had no overall effect on urges to smoke or on other withdrawal symptoms. The combination treatment did not improve biochemically validated abstinence rates at 1 week and 4 weeks post-TQD (69% vs 59%, p=0.28 and 60% vs 59%, p=0.91, in the nicotine patch and placebo patch arm, respectively), or self reported abstinence rates at 12 weeks (36% vs. 29%, p=0.39, NS). CONCLUSIONS: The efficacy of varenicline was not enhanced by the addition of nicotine patches, although further trials would be useful to exclude the possibility of type II error. TRIAL REGISTRATION: Clinicaltrials.gov REGISTRATION NUMBER: NCT01184664.

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.

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.

Effects of Switching to Electronic Cigarettes with and without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein.

Concern has been raised about the presence of toxicants in electronic cigarette (EC) aerosol, particularly carbonyl compounds (e.g., acrolein) that can be produced by heating glycerol and glycols used in e-liquids. We investigated exposure to carbon monoxide (CO), nicotine (by measuring cotinine in urine), and to acrolein (by measuring its primary metabolite, S-(3-hydroxypropyl)mercapturic acid (3-HPMA) in urine) before and after 4 weeks of EC (green smoke, a "cig-a-like" EC, labeled 2.4% nicotine by volume) use, in 40 smokers. Thirty-three participants were using EC at 4 weeks after quitting, 16 (48%) were abstinent (CO-validated) from smoking during the previous week (EC only users), and 17 (52%) were "dual users." A significant reduction in CO was observed in EC-only users [-12 ppm, 95% confidence interval (CI), -16 to -7, 80% decrease) and dual users (-12 ppm, 95%CI, -19 to -6, 52% decrease). Cotinine levels also declined, but to a lesser extent (EC-only users: -184 ng/mg creatinine; 95% CI, -733 to -365, 17% decrease; and dual users: -976 ng/mg creatinine; 95%CI, -1,682 to -270, 44% decrease). Mean 3-HPMA levels had decreased at 4 weeks by 1,280 ng/mg creatinine (95%CI, -1,699 to -861, 79% decrease) in EC-only users and by 1,474 ng/mg creatinine (95%CI, -2,101 to -847, 60% decrease) in dual users. In dual users, EC use significantly reduced exposure to CO and acrolein because of a reduction in smoke intake. EC may reduce harm even in smokers who continue to smoke, but long-term follow-up studies are needed to confirm this.