Hayden McRobbie

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

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. Cancer Prev Res; 8(9); 873–8. ©2015 AACR.

Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit

AIMS We reviewed available research on the use, content and safety of electronic cigarettes (EC), and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. METHODS Studies were identified by systematic database searches and screening references to February 2014. RESULTS EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. CONCLUSIONS Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use.

Nicotine content of electronic cigarettes, its release in vapour and its consistency across batches: regulatory implications.

BACKGROUND AND AIMS Electronic cigarettes (EC) may have a potential for public health benefit as a safer alternative to smoking, but questions have been raised about whether EC should be licensed as a medicine, with accurate labelling of nicotine content. This study determined the nicotine content of the cartridges of the most popular EC brands in the United Kingdom and the nicotine levels they deliver in the vapour, and estimated the safety and consistency of nicotine delivery across batches of the same product as a proxy for quality control for individual brands and within the industry. METHODS We studied five UK brands (six products) with high internet popularity. MEASUREMENTS Two samples of each brand were purchased 4 weeks apart, and analysed for nicotine content in the cartridges and nicotine delivery in vapour. RESULTS The nicotine content of cartridges within the same batch varied by up to 12% relative standard deviation (RSD) and the mean difference between different batches of the same brand ranged from 1% [95% confidence interval (CI) = -5 to 7%] to 20% (95% CI=14-25%) for five brands and 31% (95% CI=21-39%) for the sixth. The puffing schedule used in this study vaporized 10-81% of the nicotine present in the cartridges. The nicotine delivery from 300 puffs ranged from ∼2 mg to ∼15 mg and was not related significantly to the variation of nicotine content in e-liquid (r=0.06, P=0.92). None of the tested products allowed access to e-liquid or produced vapour nicotine concentrations as high as conventional cigarettes. CONCLUSIONS There is very little risk of nicotine toxicity from major electronic cigarette (EC) brands in the United Kingdom. Variation in nicotine concentration in the vapour from a given brand is low. Nicotine concentration in e-liquid is not well related to nicotine in vapour. Other EC brands may be of lower quality and consumer protection regulation needs to be implemented, but in terms of accuracy of labelling of nicotine content and risks of nicotine overdose, regulation over and above such safeguards seems unnecessary.

A Theory-Based Video Messaging Mobile Phone Intervention for Smoking Cessation: Randomized Controlled Trial

Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones. This social cognitive theory-based intervention (called “STUB IT”) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques. Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation. Methods A randomized controlled trial was conducted with 6-month follow-up. Participants had to be 16 years of age or over, be current daily smokers, be ready to quit, and have a video message-capable phone. Recruitment targeted younger adults predominantly through radio and online advertising. Registration and data collection were completed online, prompted by text messages. The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date, role model, and timing of messages. Extra messages were available on demand to beat cravings and address lapses. The control group also set a quit date and received a general health video message sent to their phone every 2 weeks. Results The target sample size was not achieved due to difficulty recruiting young adult quitters. Of the 226 randomized participants, 47% (107/226) were female and 24% (54/226) were Maori (indigenous population of New Zealand). Their mean age was 27 years (SD 8.7), and there was a high level of nicotine addiction. Continuous abstinence at 6 months was 26.4% (29/110) in the intervention group and 27.6% (32/116) in the control group (P = .8). Feedback from participants indicated that the support provided by the video role models was important and appreciated. Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone. However, there was sufficient positive feedback about the ease of use of this novel intervention, and the support obtained by observing the role model video messages, to warrant further investigation. Trial registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000476538; http://www.anzctr.org.au/trial_view.aspx?ID=81688 (Archived by WebCite at http://www.webcitation.org/5umMU4sZi)

Stopping Smoking Shortly Before Surgery and Postoperative Complications A Systematic Review and Meta-analysis

OBJECTIVE To examine existing smoking studies that compare surgical patients who have recently quit smoking with those who continue to smoke to provide an evidence-based recommendation for front-line staff. Concerns have been expressed that stopping smoking within 8 weeks before surgery may be detrimental to postoperative outcomes. This has generated considerable uncertainty even in health care systems that consider smoking cessation advice in the hospital setting an important priority. Smokers who stop smoking shortly before surgery (recent quitters) have been reported to have worse surgical outcomes than early quitters, but this may indicate only that recent quitting is less beneficial than early quitting, not that it is risky. DESIGN Systematic review with meta-analysis. DATA SOURCES British Nursing Index (BNI), The Cochrane Library database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PsycINFO to May 2010, and reference lists of included studies. STUDY SELECTION Studies were included that allow a comparison of postoperative complications in patients undergoing any type of surgery who stopped smoking within 8 weeks prior to surgery and those who continued to smoke. DATA EXTRACTION Two reviewers independently screened potential studies and assessed their methodologic quality. Data were entered into 3 separate meta-analyses that considered all available studies, studies with a low risk of bias that validated self-reported abstinence (to assess possible benefits), and studies of pulmonary complications only (to assess possible risks). Results were combined by using a random-effects model, and heterogeneity was evaluated by using the I(2) statistic. RESULTS Nine studies met the inclusion criteria. One found a beneficial effect of recent quitting compared with continuing smoking, and none identified any detrimental effects. In meta-analyses, quitting smoking within 8 weeks before surgery was not associated with an increase or decrease in overall postoperative complications for all available studies (relative risk [RR], 0.78; 95% confidence interval [CI], 0.57-1.07), for a group of 3 studies with high-quality scores (RR, 0.57; 95% CI, 0.16-2.01), or for a group of 4 studies that specifically evaluated pulmonary complications (RR, 1.18; 95% CI, 0.95-1.46). CONCLUSIONS Existing data indicate that the concern that stopping smoking only a few weeks prior to surgery might worsen clinical outcomes is unfounded. Further larger studies would be useful to arrive at a more robust conclusion. Patients should be advised to stop smoking as early as possible, but there is no evidence to suggest that health professionals should not be advising smokers to quit at any time prior to surgery.

Diagnostic Accuracy of Nicalert Cotinine Test Strips in Saliva for Verifying Smoking Status

Semiquantitative immunoassay technology, in the form of rapid test strips, offers a less time-consuming and less costly alternative to other methods of verifying self-reported smoking status, such as gas chromatography-nitrogen phosphorus detection (GC). Unfortunately, information on the validity and reliability of some test strips in urine and saliva samples is not always available. This paper describes the diagnostic accuracy of one type of test strip currently available (NicAlert cotinine test strips; NCTS). GC was used as the reference standard and saliva as the sample medium. The study involved 86 people (41 smokers and 45 nonsmokers) aged 18 years or over, who were able to understand written English and provide written consent. Pregnant women, women with infants less than 6 weeks old, and people who had eaten 30 min prior to sample collection were excluded. Two saliva samples were collected simultaneously from each participant, with one sample tested using NCTS and the other by GC analysis. People with at least 10 ng/ml cotinine (in both tests) in their saliva were considered smokers. NCTS were found to have a specificity of 95% (95% CI 89%-100%), a sensitivity of 93% (95% CI 85%-100%), a positive predictive value of 95% (95% CI 89%-100%), and a negative predictive value of 93% (95% CI 86%-100%). The use of NCTS is a valid and reliable method, compared with GC, to test saliva samples for verification of smoking status.

Health-care interventions to promote and assist tobacco cessation: A review of efficacy, effectiveness and affordability for use in national guideline development

Abstract Aims This paper provides a concise review of the efficacy, effectiveness and affordability of health‐care interventions to promote and assist tobacco cessation, in order to inform national guideline development and assist countries in planning their provision of tobacco cessation support. Methods Cochrane reviews of randomized controlled trials (RCTs) of major health‐care tobacco cessation interventions were used to derive efficacy estimates in terms of percentage‐point increases relative to comparison conditions in 6–12‐month continuous abstinence rates. This was combined with analysis and evidence from ‘real world’ studies to form a judgement on the probable effectiveness of each intervention in different settings. The affordability of each intervention was assessed for exemplar countries in each World Bank income category (low, lower middle, upper middle, high). Based on World Health Organization (WHO) criteria, an intervention was judged as affordable for a given income category if the estimated extra cost of saving a life‐year was less than or equal to the per‐capita gross domestic product for that category of country. Results Brief advice from a health‐care worker given opportunistically to smokers attending health‐care services can promote smoking cessation, and is affordable for countries in all World Bank income categories (i.e. globally). Proactive telephone support, automated text messaging programmes and printed self‐help materials can assist smokers wanting help with a quit attempt and are affordable globally. Multi‐session, face‐to‐face behavioural support can increase quit success for cigarettes and smokeless tobacco and is affordable in middle‐ and high‐income countries. Nicotine replacement therapy, bupropion, nortriptyline, varenicline and cytisine can all aid quitting smoking when given with at least some behavioural support; of these, cytisine and nortriptyline are affordable globally. Conclusions Brief advice from a health‐care worker, telephone helplines, automated text messaging, printed self‐help materials, cytisine and nortriptyline are globally affordable health‐care interventions to promote and assist smoking cessation. Evidence on smokeless tobacco cessation suggests that face‐to‐face behavioural support and varenicline can promote cessation.

The effect of stopping smoking on perceived stress levels

AIMS Many smokers believe that smoking helps them to cope with stress, and that stopping smoking would deprive them of an effective stress management tool. Changes in stress levels following long-term smoking cessation are not well mapped. This longitudinal project was designed to provide more robust data on post-cessation changes in perceived stress levels by following a cohort of smokers admitted to hospital after myocardial infarction (MI) or for coronary artery bypass (CAB) surgery, as such patients typically achieve higher continuous abstinence rates than other comparable samples. DESIGN A total of 469 smokers hospitalized after MI or CAB surgery and wanting to stop smoking were seen in the hospital and completed 1-year follow-ups. Ratings of helpfulness of smoking in managing stress at baseline, smoking status (validated by salivary cotinine concentration) and ratings of perceived stress at baseline and at 1-year follow-up were collected. FINDINGS Of the patients, 41% (n = 194) maintained abstinence for 1 year. Future abstainers and future smokers did not differ in baseline stress levels or in their perception of coping properties of smoking. However, abstainers recorded a significantly larger decrease in perceived stress than continuing smokers, and the result held when possible confounding factors were controlled for (P < 0.001). CONCLUSIONS In highly dependent smokers who report that smoking helps them cope with stress, smoking cessation is associated with lowering of stress. Whatever immediate effects smoking may have on perceived stress, overall it may generate or aggravate negative emotional states. The results provide reassurance to smokers worried that stopping smoking may deprive them of a valuable coping resource.