Murray Laugesen

Electronic cigarettes for smoking cessation: a randomised controlled trial

BACKGROUND Electronic cigarettes (e-cigarettes) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts. We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit. METHODS We did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (≥18 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [Māori; Pacific; or non-Māori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or ≤5 Fagerström test for nicotine dependence]) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks after quit day, with low intensity behavioural support via voluntary telephone counselling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000866000. FINDINGS 657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1·51 [95% CI -2·49 to 5·51]; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [95% CI -2·29 to 8·61]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product. INTERPRETATION E-cigarettes, with or without nicotine, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels. FUNDING Health Research Council of New Zealand.

Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial

Objectives To measure the short-term effects of an electronic nicotine delivery device (“e cigarette”, ENDD) on desire to smoke, withdrawal symptoms, acceptability, pharmacokinetic properties and adverse effects. Design Single blind randomised repeated measures cross-over trial of the Ruyan V8 ENDD. Setting University research centre in Auckland, New Zealand. Participants 40 adult dependent smokers of 10 or more cigarettes per day. Interventions Participants were randomised to use ENDDs containing 16 mg nicotine or 0 mg capsules, Nicorette nicotine inhalator or their usual cigarette on each of four study days 3 days apart, with overnight smoking abstinence before use of each product. Main outcome measures The primary outcome was change in desire to smoke, measured as “area under the curve” on an 11-point visual analogue scale before and at intervals over 1 h of use. Secondary outcomes included withdrawal symptoms, acceptability and adverse events. In nine participants, serum nicotine levels were also measured. Results Over 60 min, participants using 16 mg ENDD recorded 0.82 units less desire to smoke than the placebo ENDD (p=0.006). No difference in desire to smoke was found between 16 mg ENDD and inhalator. ENDDs were more pleasant to use than inhalator (p=0.016) and produced less irritation of mouth and throat (p<0.001). On average, the ENDD increased serum nicotine to a peak of 1.3 mg/ml in 19.6 min, the inhalator to 2.1 ng/ml in 32 min and cigarettes to 13.4 ng/ml in 14.3 min. Conclusions The 16 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence, was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette. Evaluation of the ENDD for longer-term safety, potential for long-term use and efficacy as a cessation aid is needed. Trial registration No.12607000587404, Australia and New Zealand Clinical Trials Register

Electronic nicotine delivery systems: a research agenda

Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

Diminished autonomy over tobacco can appear with the first cigarettes

Individuals have lost full autonomy over their smoking when quitting becomes unpleasant or difficult. We examined autonomy in relation to smoking frequency and lifetime cigarette use. A self-administered questionnaire was completed by three convenience samples of Year 10 students (ages 14-15) in New Zealand between 2002 and 2004 (n=96,156). The Hooked On Nicotine Checklist was used to measure diminished autonomy. Diminished autonomy was reported by 46% of subjects who smoked less often than monthly and by 25%-30% of current smokers who had smoked only one cigarette in total. The prevalence of diminished autonomy increased with increasing frequency of current use and with increasing lifetime use. Symptoms developed earlier among girls than boys. The data confirm previous reports that diminished autonomy appears soon after the onset of intermittent tobacco use and extends this literature by providing the first description of how diminished autonomy develops in relation to the total number of cigarettes smoked. These data suggest that smoking one cigarette in total can prompt a loss of autonomy.

How many deaths are caused by second hand cigarette smoke

OBJECTIVES To estimate the number of deaths attributable to second hand smoke (SHS), to distinguish attributable and potentially avoidable burdens of mortality, and to identify the most important sources of uncertainty in these estimates. METHOD A case study approach, using exposure and mortality data for New Zealand. RESULTS In New Zealand, deaths caused by past exposures to second hand smoke currently number about 347 per year. On the basis of present exposures, we estimate there will be about 325 potentially avoidable deaths caused by SHS in New Zealand each year in the future. We have explored the effect of varying certain assumptions on which the calculations are based, and suggest a plausible range (174–490 avoidable deaths per year). CONCLUSION Attributable risk estimates provide an indication for policy makers and health educators of the magnitude of a health problem; they are not precise predictions. As a cause of death in New Zealand, we estimate that second hand smoke lies between melanoma of the skin (200 deaths per year) and road crashes (about 500 deaths per year).

Influence of smoking by family and best friend on adolescent tobacco smoking: results from the 2002 New Zealand national survey of Year 10 students

Objective: To compare the relative importance on adolescent smoking of the influence from parental smoking and peer smoking.

Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation.

BackgroundElectronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study.Methods/designDesign: Parallel group, 3-arm, randomised controlled trial. Participants: People aged ≥18 years resident in Auckland, New Zealand (NZ) who want to quit smoking. Intervention: Stratified blocked randomisation to allocate participants to either Elusion™ e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. Participants randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline. Primary outcome: Biochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day. Sample size: 657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups.DiscussionThis trial will inform international debate and policy on the regulation and availability of e-cigarettes. If shown to be efficacious and safe, these devices could help many smokers as an alternative smoking cessation aid to standard nicotine products.Trial registrationAustralian NZ Clinical Trials Registry (ACTRN12610000866000).

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial

AIM To determine the combined effect of very low nicotine content (VLNC) cigarettes and usual Quitline care [nicotine replacement therapy (NRT) and behavioural support] on smoking abstinence, in smokers motivated to quit. DESIGN Single-blind, parallel randomized trial. SETTING New Zealand. PARTICIPANTS Smokers who called the Quitline for quitting support were randomized to either VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after their quit date, in combination with usual Quitline care (8 weeks of NRT patches and/or gum or lozenges, plus behavioural support) or to usual Quitline care alone. MEASUREMENTS The primary outcome was 7-day point-prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, self-efficacy, alcohol use, serious adverse events and views on the use of the VLNC cigarettes at 3 and 6 weeks and 3 and 6 months. FINDINGS A total of 1410 participants were randomized (705 in each arm), with a 24% loss to follow-up at 6 months. Participants in the intervention group were more likely to have quit smoking at 6 months compared to the usual care group [7-day point-prevalence abstinence 33 versus 28%, relative risk (RR) = 1.18, 95% confidence interval (CI): 1.01, 1.39, P = 0.037; continuous abstinence 23 versus 15%, RR = 1.50, 95% CI: 1.20, 1.87, P = 0.0003]. The median time to relapse in the intervention group was 2 months compared to 2 weeks in the usual care group (P < 0.0001). CONCLUSIONS Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.

Estimating cross-price elasticity of e-cigarettes using a simulated demand procedure.

INTRODUCTION Our goal was to measure the cross-price elasticity of electronic cigarettes (e-cigarettes) and simulated demand for tobacco cigarettes both in the presence and absence of e-cigarette availability. METHOD A sample of New Zealand smokers (N = 210) completed a Cigarette Purchase Task to indicate their demand for tobacco at a range of prices. They sampled an e-cigarette and rated it and their own-brand tobacco for favorability, and indicated how many e-cigarettes and regular cigarettes they would purchase at 0.5×, 1×, and 2× the current market price for regular cigarettes, assuming that the price of e-cigarettes remained constant. RESULTS Cross-price elasticity for e-cigarettes was estimated as 0.16, and was significantly positive, indicating that e-cigarettes were partially substitutable for regular cigarettes. Simulated demand for regular cigarettes at current market prices decreased by 42.8% when e-cigarettes were available, and e-cigarettes were rated 81% as favorably as own-brand tobacco. However when cigarettes cost 2× the current market price, significantly more smokers said they would quit (50.2%) if e-cigarettes were not available than if they were available (30.0%). CONCLUSION Results show that e-cigarettes are potentially substitutable for regular cigarettes and their availability will reduce tobacco consumption. However, e-cigarettes may discourage smokers from quitting entirely as cigarette price increases, so policy makers should consider maintaining a constant relative price differential between e-cigarettes and tobacco cigarettes.

A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfaction

AIMS To determine effects on craving, user satisfaction, and consumption patterns of two new nicotine replacement therapies (NRT) used for eight hours after overnight tobacco abstinence. DESIGN In a within-subject, cross-over trial participants were randomly assigned Zonnic nicotine mouth spray (1 mg/spray), Zonnic nicotine lozenge (2.5 mg), Nicorette gum (4 mg) and placebo lozenge on each of four study days. SETTING University research unit. PARTICIPANTS Forty-seven dependent adult smokers. MEASUREMENTS Participants rated their urges to smoke, irritability, concentration and restlessness before and during the first hour of product use on a 100-point scale. A subsample of 11 participants provided blood samples for nicotine analysis. FINDINGS All active products reduced craving significantly more than placebo (mean reductions of 28.6, 25.8, 24.7 and 8.9 points for mouth spray, gum, lozenge and placebo). Mouth spray relieved craving faster than placebo and gum with significant reductions within five minutes of use (mean differences of -14.5 (95% CI: -23.0 to -6.0) and -10.6 (95% CI: -19.1 to -2.1) with placebo and gum respectively. Mouth spray produced a faster time to maximum plasma nicotine concentration (14.5 minutes, 95% CI: 8.0 to 21.0) compared to the lozenge (30.3 minutes, 95% CI: 21.1 to 39.5) and gum (45.8 minutes, 95% CI: 36.2 to 55.4). Maximum concentrations of blood nicotine were higher with mouth spray (10.0 ng/ml) and lozenge (10.8 ng/ml) compared to gum (7.8 ng/ml). Both lozenge and mouth spray were well tolerated. CONCLUSIONS The mouth spray and lozenge are at least as effective as 4 mg nicotine gum in relieving craving suggesting that they are likely to be effective in aiding smoking cessation. The mouth spray may be particularly useful for acute craving relief.