Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

Comparison of biomarkers of exposure among US adult smokers, users of electronic nicotine delivery systems, dual users and nonusers, 2018-2019.

The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers'; 9 BOEs were not significantly different from nonusers. Among dual users smoking < 10 cigarettes/day, 15 of 18 non-nicotine BOEs were significantly lower than smokers', whereas in dual users smoking ≥ 10 cigarettes per day none of the BOEs significantly differed from smokers'. In this representative sample of US adults, exclusive use of ENDS (vs. cigarette smoking) was associated with much lower exposures to many harmful chemicals associated with smoking-related disease. BOE levels in dual users were directly related to their cigarette consumption. These BOE data provide further evidence that ENDS expose users to substantially lower levels of toxicants than combustible cigarettes, confirming their potential for harm reduction.

US adult smokers' perceived relative risk on ENDS and its effects on their transitions between cigarettes and ENDS.

BACKGROUND: Perceived risk reduction motivates smokers to switch to electronic nicotine delivery systems (ENDS). This research examines US smokers' relative risk perceptions and their prospective association with various behavioral stages of switching to ENDS. METHODS: Data from the nationally representative, longitudinal Population Assessment of Tobacco and Health (PATH) Adult survey, Waves 1 (2014) through 5 (2019), were analyzed. We assessed the association between the perceived risk of ENDS relative to cigarettes ("less harmful" vs. "equally harmful" or "more harmful") and 1) adoption of ENDS (among never-ENDS-using smokers), 2) complete switching to ENDS (i.e., stopping smoking, among ever-ENDS-using smokers), and 3) avoiding reversion to smoking (among smokers who had switched to ENDS), at the next wave. RESULTS: The proportion of US smokers perceiving ENDS as less harmful than cigarettes continually decreased, reaching 17.4% in Wave 5 (2019). Current smokers with such belief were more likely to adopt ENDS (aOR 1.31; 95% CI 1.15-1.50) and switch completely to ENDS (aOR 2.24; 95% CI 1.89-2.65) in the subsequent wave. Among smokers who had switched within the past year, such beliefs predicted avoidance of resumption of smoking in the next wave (aOR 0.55; 95% CI 0.33-0.93). CONCLUSIONS: Smokers' beliefs about the relative risk of ENDS compared to cigarettes had a strong and consistent association with transitions between smoking and ENDS use. Addressing the growing misperception about ENDS has the potential to contribute to public health by encouraging smokers' switching to ENDS.

The Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study: Methods and Analysis of Loss-to-Follow-up.

Objectives: The Adult JUUL System User Switching and Smoking Trajectories (ADJUSST) study assessed the smoking and JUUL use trajectories of adults who purchased JUUL. In this paper, we describe study methods, characterize the sample, and assesses potential for bias due to loss to follow-up. Methods: We entered 55,414 US adults (≥ age 21) who purchased a JUUL Starter Kit for the first time (online or at retail) in 2018 into a naturalistic, longitudinal observational study, irrespective of baseline smoking status. Participants were invited for follow-ups 1, 2, 3, 6, 9, and 12 months later, focused on assessing past-30-day smoking and JUUL use. Analyses assessed potential bias due to non-response. Results: Over 90% of participants had a history of smoking; 62.8% were past-30-day smokers; 23.3% were former smokers. Participants' average age was 30; 75% were white. Most participants (77.6%) completed some follow-ups; 25% completed all follow-ups. Baseline differences among complete responders (N = 13,729), partial responders (N = 29,252), and complete non-responders (N = 12,433) were small. When recontacted, few 12-month non-responders said their non-response was due to smoking; many reported no past-30-day smoking. Conclusions: The study may elucidate smoking trajectories of adult JUUL users. The potential for bias due to loss to follow-up in ADJUSST was limited.

Assessing comprehension and perceptions of modified-risk information for snus among adult current cigarette smokers, former tobacco users, and never tobacco users.

INTRODUCTION: Snus, a low nitrosamine smokeless tobacco product, presents less risks to health than cigarettes. Effectively communicating such risk information could facilitate smokers switching completely to snus, thereby benefiting public health. METHODS: This study assessed comprehension and perceptions of modified-risk information regarding snus. Adult cigarette smokers, former tobacco users, and never tobacco users (N = 3,922) from a US internet panel viewed an advertisement stating that smokers who switched completely to snus could greatly reduce risk of lung cancer, respiratory disease, heart disease, and oral cancer. Respondents answered questions regarding the modified-risk information and rated perceived risks of snus relative to cigarettes and other smokeless tobacco products. RESULTS: Across the four diseases mentioned in the advertisement, most respondents (49.7%-68.6%, across tobacco user groups) understood that snus presents less risk than cigarettes but is not completely safe. Some indicated snus presents the same risk as cigarettes; this was highest for oral cancer (33.7%-42.02%) and lowest for lung cancer (15.4%-23.1%) and respiratory disease (15.6%-23.4%). Majorities understood snus is addictive (77.7%-87.9%), quitting all tobacco is the best option for smokers (83.6%-93.1%), and non-users of tobacco should not use snus (80.4%-87.8%). Only 2.1%-5.8% indicated smokers would receive a health benefit if they continued to smoke while using snus. CONCLUSIONS: The modified-risk information, conveying that snus presents less risk than cigarettes but is not completely safe, was understood by majorities of respondents. Differential risk beliefs across diseases suggest responses were shaped not only by the modified-risk information, but also by intuitions and pre-existing beliefs about tobacco products.

Dependence on e-cigarettes and cigarettes in a cross-sectional study of US adults.

BACKGROUND AND AIMS: Cigarette smoking often results in nicotine dependence. With use of electronic cigarettes as an alternative source of nicotine, it is important to assess dependence associated with e-cigarette use. This study assesses dependence among current and former adult e-cigarette users on cigarettes and e-cigarettes, compared with dependence on cigarettes. DESIGN: Cross-sectional data from the Population Assessment of Tobacco and Health (PATH) study from 2013-2016. Psychometrically assessed dependence was compared for cigarettes and e-cigarettes among current and former exclusive and dual users of the products and among e-cigarette users who had and had not recently stopped smoking. Setting A population-based representative sample of US adults. Participants Participants were 13 311 US adults (18+) in Waves 1-3 of PATH reporting current established smoking, current use of e-cigarettes, or stopping use of either product in the past year who were administered dependence assessments for cigarettes and/or e-cigarettes. Measurements A 16-item scale assessing tobacco dependence (on a 1-5 scale), previously validated for assessment and comparison of dependence on varied tobacco products, including cigarettes and e-cigarettes, with a variation assessing residual dependence among users who stopped in the past year. Findings Among current users, dependence on e-cigarettes was significantly lower than dependence on cigarettes, in within-subjects comparisons among dual users of both e-cigarettes and cigarettes (1.58 [SE = 0.05] vs. 2.76 [0.04]), P < 0.0001), and in separate groups of e-cigarette users and cigarette smokers (1.95 [0.05] vs. 2.52 [0.02], P < 0.0001), and among both daily and non-daily users of each product. Among former users, residual symptoms were significantly lower for e-cigarettes than cigarettes, both among former dual users (1.23 [0.07] vs. 1.41 [0.06], P < 0.001) and among users of one product (1.28 [0.03] vs. 1.53 [0.03], P < 0.0001). The highest level of e-cigarette dependence was among e-cigarette users who had stopped smoking (2.17 [0.08]). Conclusion Use of e-cigarettes appears to be consistently associated with lower nicotine dependence than cigarette smoking.

Trends in serious quit attempts in the United States, 2009-14.

BACKGROUND AND AIMS: Quitting smoking is the most potent way to reduce the health risks associated with smoking cigarettes, and public health objectives in the United States include dramatic increases in the proportion of smokers making a serious quit attempt each year. The US Centers for Disease Control and Prevention (CDC) has, since 2000, set as its Healthy People 2020 objective to encourage 80% of smokers to make a serious quit attempt per year. This study assessed the trend in quit attempts from 2009 to 2014. DESIGN: We examined the percentage of US smokers making a serious quit attempt each year from 2009 to 2014 from the repeating cross-sectional National Health Interview Survey (NHIS). SETTING: United States. PARTICIPANTS: The number of qualifying respondents per year ranged from 5748 in 2010 to 7219 in 2012, with a total of 40 362 respondents included in the analysis. MEASUREMENTS: Respondents were deemed to have made a serious quit attempt if they were either current smokers who reported that they stopped smoking for more than 1 day in the past 12 months because they were trying to quit smoking, or reported being former smokers (smoked 100+ cigarettes life-time, but now not smoking) who quit in the past year. FINDINGS: Analyses of trends from 2009 to 2014 showed an overall linear increase in quit attempts [odds ratio (OR) = 1.02, 95% confidence interval (CI) = 1.01-1.04, P = 0.0075], but also a quadratic trend (OR = 1.01, 95% CI = 1.00-1.02, P = 0.0189). CONCLUSIONS: The proportion of US smokers making a serious quit attempt has increased since 2009, due to an upward trend since 2011. The 2014 serious quit attempt rate was 55.0%. These rates are still below the Healthy People 2020 objective of 80% of smokers making a serious quit attempt per year.

The Impact of Flavor Descriptors on Nonsmoking Teens' and Adult Smokers' Interest in Electronic Cigarettes.

INTRODUCTION: Smokers switching completely from combustible cigarettes to electronic cigarettes (e-cigarettes) are likely to reduce health risk, suggesting that e-cigarettes should be made appealing to adult smokers. However, uptake of e-cigarettes by nonsmoking teens would add risk without benefit and should be avoided. Although e-cigarette flavors may appeal to adult smokers, the concern is that flavors might attract nonsmoking teens. METHODS: Nonsmoking teens (n = 216, ages 13-17, no tobacco in past 6 months) and adult smokers (n = 432, ages 19-80, smoking 3+ years; could have used e-cigarettes) were recruited from an Internet research panel. In assessments completed online (May 22, 2014 to June 13, 2014), participants indicated their interest (0-10 scale) in e-cigarettes paired with various flavor descriptors. These were mixed (order balanced) with similar flavor offerings for ice cream and bottled water to mask the focus on e-cigarettes and validate the assessment. Mixed models contrasted interest between teens and adults and among adults by e-cigarette history. RESULTS: Nonsmoking teens' interest in e-cigarettes was very low (mean = 0.41 ± 0.14 [SE] on 0-10 scale). Adult smokers' interest (1.73 ± 0.10), while modest, was significantly higher overall (p < .0001) and for each flavor (most p values < .0001). Teen interest did not vary by flavor (p = .75), but adult interest did (p < .0001). Past-30-day adult e-cigarette users had the greatest interest in e-cigarettes, and their interest was most affected by flavor. Adults who never tried e-cigarettes had the lowest interest, yet still higher than nonsmoking teens' interest (p < .0001). CONCLUSION: The e-cigarette flavors tested appealed more to adult smokers than to nonsmoking teens, but interest in flavors was low for both groups.

Assigning dose of nicotine gum by time to first cigarette.

INTRODUCTION: Nicotine gum, a proven effective aid to cessation, comes in two doses: 2-mg and 4-mg. Assignment to the higher dose has traditionally been based on daily cigarette consumption. This paper evaluates efficacy of the gum when the 4-mg dose is assigned based on time to first cigarette (TTFC) being ≤ 30 min. METHODS: In a secondary analysis of a randomized, double-blind, placebo-controlled trial that allocated smokers randomly to placebo, 2-mg, or 4-mg gum (Garvey, A. J., Kinnunen, T., Nordstrom, B. L., Utman, C. H., Doherty, K., Rosner, B., et al. (2000). Effects of nicotine gum dose by level of nicotine dependence. Nicotine & Tobacco Research, 2, 53-63. doi:10.1080/14622200050011303), we evaluated outcomes when 4-mg gum was given to subjects with TTFC ≤ 30 (n = 158, placebo n = 159). RESULTS: Active treatment doubled or tripled abstinence rates versus placebo. This also held among smokers with a history of treatment failure. The effect of 4-mg gum was significant among light smokers (<25 CPD) with TTFC ≤ 30; 2-mg gum was not. CONCLUSION: This analysis suggests that assigning dose of nicotine gum based on TTFC is an effective and appropriate means of dose allocation.

Providing accurate safety information may increase a smoker's willingness to use nicotine replacement therapy as part of a quit attempt.

AIM: Previous studies have reported that smokers who are misinformed about the safety of Nicotine Replacement Therapy (NRT) are less likely to report using it. In this study, we examined whether providing information that counters these concerns might impact on intentions to use NRT. PARTICIPANTS: 900 smokers recruited from a market research database. DESIGN AND SETTING: Participants completed an online survey that asked about their views about NRT. Smokers with safety and efficacy concerns were queried to determine whether accurate information might increase their interest in using NRT. FINDINGS: Misperceptions of NRT safety were common: 93% of smokers did not know that smoking while wearing the nicotine patch does not cause heart attacks; 76% that nicotine gum/lozenge are not as addictive as cigarettes; and 69% that NRT products are not as dangerous as cigarettes. Over half of the smokers with misperceptions reported that they would be more likely to use NRT to help them quit smoking if they were exposed to information correcting their concerns (53%, 58% and 66%, respectively, for each of the misperceptions). CONCLUSIONS: These data suggest that while a sizeable proportion of smokers are still misinformed about the safety of NRT, misinformed smokers would increase consideration of NRT if these misperceptions are addressed by corrective information.

Prediction of abstinence at 10 weeks based on smoking status at 2 weeks during a quit attempt: secondary analysis of two parallel, 10-week, randomized, double-blind, placebo-controlled clinical trials of 21-mg nicotine patch in adult smokers.

BACKGROUND: Smoking cessation outcomes are calculated as the probability of abstinence at follow-up among all enrolled smokers, but it is also useful to estimate the probability of success for those who experienced success or failure at earlier time points. OBJECTIVES: The primary aims were to estimate the probability of maintaining abstinence through week 10 among subjects who were abstinent at week 2, and to assess the effect of active treatment with a nicotine patch. We also examined outcomes at week 6 and, among subjects who smoked during the first 2 weeks of treatment, the probability of reestablishing abstinence later, as well as the effect of active treatment on this outcome. METHODS: We analyzed pooled data from 2 previously published, parallel, double-blind studies in which subjects were initially randomized to receive an active nicotine patch (starting at 21 mg) or a placebo patch. Subjects randomized to active treatment followed a double-blind step-down dosing regimen: 24-h/21-mg patches for the first 6 weeks of treatment, followed by 14- and 7-mg patches for successive 2-week periods. Biochemically verified abstinence (exhaled carbon monoxide

Weight management advice: what do doctors recommend to their patients?

OBJECTIVE: To examine the weight management interventions that a broad population of adults reported receiving from physicians and assess what drug-related and behavioral information physicians provided when they prescribe weight loss medications. METHODS: A random-digit dialed telephone survey was conducted in 2005-2006 with a representative sample of 3,500 American adults. RESULTS: The most frequently reported interventions were having a doctor tell them about the health problems associated with being overweight (48.0%), or suggesting diet and exercise (46.5%). Few respondents reported having been referred to a formal diet program (5.2%), prescribed a weight loss medication (4.0%), recommended a non-prescription weight loss product (1.8%), or recommended stomach bypass surgery (1.5%). The proportion of individuals who reported each intervention increased across levels of body mass index (p<0.001). Of those who reported being prescribed a weight loss medication (n=155), only 29.5% (n=44) reported receiving all six counseling interventions that were assessed. CONCLUSIONS: Many overweight patients have not been advised to lose weight, diet, or exercise, and physicians have been particularly reluctant to recommend medications. When physicians do prescribe medications, appropriate counseling too often fails to accompany the prescription. Efforts are needed to increase the involvement of physicians in guiding patients to effective weight management approaches.

Unplanned quit attempts--results from a U.S. sample of smokers and ex-smokers.

INTRODUCTION: Traditionally, smokers have been encouraged to prepare for cessation in advance of a preset quit date, with the expectation that preparation would improve their chance of success. However, a recent survey of U.K. smokers found that a substantial proportion of attempts involved no preplanning and that these spontaneous attempts were actually more likely to succeed. We set out to explore further the nature of unplanned quit attempts among U.S. smokers. METHODS: Nine hundred smokers and 800 ex-smokers were recruited from a market research database for an online survey and asked about the planning involved in their most recent attempt. RESULTS: In all, 39.7% of subjects reported that their most recent quit attempt involved no preplanning (smokers: 29.5%; ex-smokers: 52.4%). Subjects who made an unplanned quit attempt were more likely to be non-white, have no college education, report smoking their first cigarette of the day more than 30 min after waking, and report no use of pharmacotherapy during their quit attempt. Controlling for these variables, the odds of a "spontaneous" quit attempt lasting for 6 months or longer were twice that of preplanned attempts (71.7% vs. 45.6%; adjusted odds ratio = 2.62, 95% CI = 1.99-3.45). Similar results were seen in a survival analysis. DISCUSSION: The results suggest, similar to previous research, that a substantial proportion of quit attempts are unplanned and that such attempts can be a successful route to cessation. Given the frequency of such attempts, methods of making treatment available to assist unplanned quitting should be considered.

Relationship between adherence to daily nicotine patch use and treatment efficacy: secondary analysis of a 10-week randomized, double-blind, placebo-controlled clinical trial simulating over-the-counter use in adult smokers.

BACKGROUND: It has been reported that the efficacy of acute forms of nicotine replacement therapy, such as nicotine gum and lozenges, improves when sufficient quantities of medication are used. OBJECTIVE: This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smoking abstinence. METHODS: This was a secondary analysis of data from a double-blind study in which subjects were randomized to receive either an active nicotine patch or a placebo patch under simulated over-the-counter conditions. Subjects were asked to complete a daily diary on their patch use and smoking. Logistic regression, controlling for smoking in the first 3 weeks of treatment, was used to evaluate the likelihood of abstinence at 6 weeks as a function of treatment assignment (active vs placebo) and adherence (ie, patch wear for >or=20 of the first 21 days of treatment). The relationship between reported adverse events and adherence was also examined. RESULTS: This analysis involved data from 371 subjects, 204 using the active patch and 167 using the placebo patch. The study population was mainly white (87.3%), had a mean age of 42.8 years, a mean weight of 77.3 kg, had been smoking for a mean of 24.4 years, and smoked a mean of 25.2 cigarettes per day. Two hundred fifty-three subjects were classified as adherent. Rates of adherence did not differ significantly between the active and placebo groups (139 [68.1%] and 114 [68.3%], respectively). The likelihood of experiencing an adverse event did not differ significantly between adherent and nonadherent subjects in either group. Among active patch users, 61.5% of nonadherent subjects experienced an adverse event, compared with 59.7% of adherent subjects; among placebo patch users, the corresponding proportions were 41.5% and 43.9%. Among active patch users, the odds of abstinence at 6 weeks were more than 3 times greater for adherent versus nonadherent subjects (53.2% vs 21.5%, respectively; adjusted odds ratio [OR] = 3.25; 95% CI, 1.30-8.09; P = 0.011); no benefit of adherence over nonadherence was seen among users of the placebo patch (16.7% vs 15.1%; adjusted OR = 0.60; 95% CI, 0.16-2.31). The interaction between treatment group and adherence was statistically significant (P = 0.022). CONCLUSION: Under conditions simulating over-the-counter use, adherence to daily nicotine patch wear within the first 3 weeks of treatment was associated with an improved likelihood of achieving smoking abstinence at 6 weeks.