Effects of liquid nicotine concentration and flavour on the acceptability of electronic nicotine delivery systems (ENDS) among people who smoke participating in a randomised controlled trial to reduce cigarette consumption.

BACKGROUND: Research is needed to understand the acceptability of electronic nicotine delivery systems (ENDS) as a smoking reduction aid. This study examines the acceptability of ENDS by liquid nicotine concentration and flavour among people who smoke using ENDS to reduce their smoking. METHODS: People who smoke cigarettes but were naïve to ENDS participated in a double-blind randomised controlled trial to reduce conventional cigarette smoking. Participants were randomised to either a control cigarette substitute (CS) or one of three ENDS groups; 0 mg/mL, 8 mg/mL or 36 mg/mL nicotine concentration. ENDS flavour was chosen by the participant (tobacco or menthol). Participants reported their CS, ENDS and cigarettes per day (CPD) from the past 7 days at 1-month, 3-month and 6-month follow-up visits. Participants also reported side effects and measures of satisfaction, psychological reward, aversion and craving relief. Outcome variables were modelled using linear mixed effects by the following groups: liquid nicotine concentration, flavour and a flavour-nicotine concentration interaction. RESULTS: Participants (n=520) were 41.2% male, 67.3% white, had a mean age of 46.2 years and smoked a mean of 18.6 CPD (SD=7.74) at baseline. All flavour and concentration groups decreased CPD from baseline to all follow-up visits with the 36 mg/mL experiencing the greatest reduction, compared with the 0 mg/mL and 8 mg/mL groups. All groups except the 36 mg/mL group decreased their product use over time. The use of menthol flavour was associated with fewer side effects at 3 months (p=0.02) and lesser aversion at 1 month (p=0.03) compared with tobacco-flavoured ENDS. The 36 mg/mL group experienced the greatest craving relief and greatest aversion compared with other groups. CONCLUSIONS: Both nicotine concentration and flavour appear to have independent, as well as interactive, effects that influence ENDS acceptability among people who use cigarettes.

Gardening and subjective cognitive decline: a cross-sectional study and mediation analyses of 136,748 adults aged 45+ years.

BACKGROUND: Given the benefits of gardening for physical and psychological health, we explored whether gardening was associated with lower risks of subjective cognitive decline (SCD), a precursor of dementia, and SCD-related functional limitations. METHODS: Included in this cross-sectional study were 136,748 participants aged 45 + years old from the Behavioral Risk Factor Surveillance System 2019 survey, who were then categorized into three groups according to self-reported exercise status: non-exercisers, gardeners, and other exercisers. SCD was assessed via a questionnaire, and SCD-related functional limitations were referred to as having difficulties in engaging in household or social activities due to SCD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the associations of gardening with SCD and SCD-related functional limitations, adjusted for age, sex, socioeconomic status, lifestyle factors, and health status. Mediation analyses were conducted to examine whether the observed association between gardening and SCD was mediated by energy expenditure (MET-hours/week), depression status, and consumption of fruits and vegetables. RESULTS: Overall, 11.1% and 5.4% of participants self-reported experiencing SCD and SCD-related functional limitations, respectively. The adjusted OR for gardeners vs. non-exercisers, was 0.72 (95% CI 0.62-0.83) for SCD and 0.57 (95% CI 0.44-0.73) for SCD-related functional limitations. The observed association between gardening and SCD was explained by higher energy expenditure (39.0%), lower likelihood of having depression (21.5%), and higher consumption of fruits and vegetables (3.4%) (P<0.05 for all). Similar patterns were observed for SCD-related functional limitations. CONCLUSION: In this nationally representative sample, gardening was associated with better cognitive status, which may be mainly attributed to better depression status and energy expenditure.

Training the Next Generation of Local Public Health Leaders: A Case Study of Community Health Organizers in Pennsylvania.

Few short-term training programs exist for persons with limited experience or training in public health to support public health initiatives. We describe a public health training designed by the Pennsylvania (PA) Training Center for Health Equity for the PA Community Health Organizer (CHO) program. The CHO program was created to address the immediate needs of underserved communities and promote lasting health equity during the pandemic. CHOs are professionals who promote community action and align efforts with local organizations to build sustainable public health infrastructure and apply evidence-based practices to program policy, planning, and development. The training content, delivered by Project Extension for Community Healthcare Outcomes (ECHO) in 12 monthly sessions, focused upon foundational public health concepts in a novel community case study approach. The ECHO All Teach, All Learn training model was successful in providing relevant public health information to this new workforce, and the pre-/post-training evaluation demonstrated a positive increase in knowledge across all domains.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

Influence of social and behavioral determinants on health-related quality of life among cancer survivors in the USA.

PURPOSE: Cancer survivors experience a worse health-related quality of life (HRQoL) than non-cancer survivors. However, it is not fully understood whether social determinants of health (SDOH) and health behaviors are significantly associated with HRQoL among cancer survivors. The purpose of this study was to investigate the influence of SDOH and health behaviors on HRQoL among cancer survivors. METHODS: We identified adult (18 years or older) cancer survivors (n = 5784) in the 2017 and 2019 Behavioral Risk Factor Surveillance System. The primary outcome (HRQoL) was defined as whether cancer survivors reported having poor mental or physical health (e.g., 14 or more mentally or physically unhealthy days). Unadjusted and adjusted logistic regression was used to compute the odds ratios and 95% CIs of factors associated with poor HRQoL among the cancer survivors. RESULTS: More than half of the cancer survivors were non-Hispanic White, female, and 65 years or older. In the adjusted multivariable logistic regression models, cancer survivors who were physically active and who did not avoid care because of costs had a lower risk of poor mental and physical health. Current smokers were more likely to report poor physical health. Homeowners were less likely to report poor mental health. Daily fruit and vegetable consumption and healthcare coverage were not associated with poor HRQoL. CONCLUSIONS: Some SDOH (healthcare access, economic stability, and the neighborhood and built environment) and health behavior (physical activity) are associated with lower likelihood of experiencing poor mental and/or physical health in the cancer survivors. The study findings can be used to target survivors who experience suboptimal HRQoL and to inform research, public health policies, and/or programs.

Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers With Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC). METHODS: A 33 week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. RESULTS: The RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%). CONCLUSIONS: This study supports a VLNC standard in cigarettes. IMPLICATIONS: Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.

Alcohol consumption and risk of cardiovascular disease, cancer and mortality: a prospective cohort study.

BACKGROUND: Studies regarding whether light to moderate alcohol consumption is associated with a lower risk of cardiovascular diseases (CVD) have generated mixed results. Further, few studies have examined the potential impact of alcohol consumption on diverse disease outcomes simultaneously. We aimed to prospectively study the dose-response association between alcohol consumption and risk of CVD, cancer, and mortality. METHODS: This study included 83,732 adult Chinese participants, free of CVD and cancer at baseline. Participants were categorized into 6 groups based on self-report alcohol consumption: 0, 1-25, 26-150, 151-350, 351-750, and > 750 g alcohol/wk. Incident cases of CVD, cancers, and mortality were confirmed by medical records. Hazard ratios (HRs) for the composite risk of these three outcomes, and each individual outcome, were calculated using Cox proportional hazard model. RESULTS: During a median follow-up of 10.0 years, there were 6411 incident cases of CVD, 2947 cancers and 6646 deaths. We observed a J-shaped relation between alcohol intake and risk of CVD, cancer, and mortality, with the lowest risk at 25 g/wk., which is equivalent to ~ 2 servings/wk. Compared to consuming 1-25 g/wk., the adjusted HR for composite outcomes was 1.38 (95% confidence interval (CI):1.29-1.49) for non-drinker, 1.15 (95% CI: 1.04-1.27) for 26-150 g/wk., 1.22 (95% CI: 1.10-1.34) for 151-350 g/wk., 1.33 (95% CI: 1.21-1.46) for 351-750 g/wk., and 1.57 (95% CI: 1.30-1.90) for > 750 g/wk., after adjusting for age, sex, lifestyle, social economic status, and medication use. CONCLUSIONS: Light alcohol consumption at ~ 25 g/wk was associated with lower risk of CVD, cancer, and mortality than none or higher consumption in Chinese adults.

A Systematic Scoping Review of How Healthcare Organizations Are Facilitating Access to Fruits and Vegetables in Their Patient Populations.

BACKGROUND: There is compelling evidence on the impact of diet as preventative medicine, and with rising health care costs healthcare organizations are attempting to identify interventions to improve patient health outcomes. OBJECTIVES: The purpose of this systematic scoping review was to characterize existing healthcare organization-based interventions to improve access to fruits and vegetables (F&V) for their patient populations. In addition, we aimed to review the impact of identified interventions on dietary intake and health outcomes. METHODS: Titles and abstracts were searched in PubMed® (MEDLINE®), Embase®, CINAHL®, and the Cochrane Library® from 1 January 1990 to 31 December 2019. To be selected for inclusion, original studies must have included a healthcare organization and have had a programmatic focus on increasing access to or providing fresh F&V to patients in an outpatient, naturalistic setting. The Effective Public Health Practice Project tool was used to assess study quality in 6 domains (selection bias, study design, confounders, blinding, data collection methods, and withdrawals and dropouts). RESULTS: A total of 8876 abstracts were screened, yielding 44 manuscripts or abstracts from 27 programs. Six program models were identified: 1) a cash-back rebate program, 2) F&V voucher programs, 3) garden-based programs, 4) subsidized food box programs, 5) home-delivery meal programs, and 6) collaborative food pantry-clinical programs. Only 6 of 27 studies included a control group. The overall quality of the studies was weak due to participant selection bias and incomplete reporting on data collection tools, confounders, and dropouts. Given the heterogeneity of outcomes measured and weak study quality, conclusions regarding dietary and health-related outcomes were limited. CONCLUSIONS: Healthcare-based initiatives to improve patient access to F&V are novel and have promise. However, future studies will need rigorous study designs and validated data collection tools, particularly related to dietary intake, to better determine the effect of these interventions on health-related outcomes.

Measurement of Electronic Cigarette Frequency of Use Among Smokers Participating in a Randomized Controlled Trial.

BACKGROUND: The United States Food and Drug Administration has prioritized understanding the dependence potential of electronic cigarettes (e-cigs). Dependence is often estimated in part by examining frequency of use; however measures of e-cig use are not well developed because of varying product types. This study used an e-cig automatic puff counter to evaluate the value of self-reported e-cig use measures in predicting actual use (puffs). METHODS: Data were collected from a two-site randomized placebo-controlled trial evaluating the effects of e-cigs on toxicant exposure in smokers attempting to reduce their cigarette consumption. Participants randomized to an e-cig condition self-reported their e-cig frequency of use (times per day-one "time" consists of around 15 puffs or lasts around 10 minutes) on the Penn State Electronic Cigarette Dependence Index (PSECDI) and kept daily diary records of the number of puffs per day from the e-cig automatic puff counter. A linear mixed-effects model was used to determine the predictive value of the times per day measure. Correlations were used to further investigate the relationship. RESULTS: A total of 259 participants with 1165 observations of e-cig use were analyzed. Self-reported e-cig use in times per day was a significant predictor of e-cig puffs per day (p < .01). The Spearman correlation between measures was r equal to .58. Examination of individual participant responses revealed some potential difficulties reporting and interpreting times per day because of the difference in use patterns between cigarettes and e-cigs. CONCLUSION: This study provides evidence that the self-reported PSECDI measure of times per day is a significant predictor of actual frequency of e-cig puffs taken. IMPLICATIONS: Self-reported measures of e-cig frequency of use are predictive of actual use, but quantifying e-cig use in patterns similar to cigarettes is problematic.

Characteristics of Adult Cigarette Smokers Who "Relight" and the Effects of Exposure to Tobacco Smoke Constituents.

INTRODUCTION: About half of smokers relight their cigarette, a habit that is a risk factor for chronic bronchitis and possibly lung cancer. Little is known about the characteristics of smokers who relight and their dependence on nicotine. It is unknown whether relighting affects exposure to tobacco smoke constituents. This study examined the characteristics of relighters of usual brand cigarettes and whether relighting affects exposure to selected tobacco smoke constituents. METHODS: We explored relighting status and frequency, using baseline data from 248 adult smokers participating in studies of reduced nicotine cigarettes in relation to demographic and cigarette characteristics, smoking behaviors, nicotine dependence, biomarkers of exposure (exhaled carbon monoxide, blood cotinine), and biomarkers of oxidative stress (ratio of oxidized/reduced glutathione). RESULTS: 69.4% (n = 172) of subjects reported relighting, and they relit an average of five cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 cigarettes per day (p = .6). Relighting was significantly associated with higher nicotine dependence, use of longer rod cigarettes, older age, lower income, and unemployment. There were no significant associations between relighting and blood cotinine, exhaled carbon monoxide or measures of oxidized/reduced blood glutathione. CONCLUSIONS: The majority of subjects were relighters, who had higher levels of nicotine dependence than non-relighters. Relighters had similar levels of plasma cotinine and exhaled carbon monoxide to non-relighters. IMPLICATIONS: No study has compared the cigarette characteristics and biomarkers of exposure of adult cigarette smokers who relight with those who do not. Relighting behavior was common in our sample and was associated with low income, not currently working, higher nicotine dependence, cigarette rod length, daily cigarette use years, and a lifetime history of depressed mood.

E-cigarette users commonly stealth vape in places where e-cigarette use is prohibited.

INTRODUCTION: 'Stealth vaping' is the practice of vaping discreetly in places where electronic cigarette (e-cigarette) use is prohibited. While anecdotal evidence suggests that stealth vaping is common, there have been no formal studies of the behaviour. The purpose of this study is to examine stealth vaping behaviour among experienced e-cigarette users. METHODS: Data were collected from the follow-up survey of a large longitudinal cohort study of adult experienced e-cigarette users conducted in January 2017. To measure stealth vaping behaviour, participants were asked 'Have you ever 'stealth vaped', that is to say, used an e-cig in a public place where it was not approved and attempted to conceal your e-cig use? (yes/no)'. Participants indicating yes completed additional questions about the frequency of stealth vaping and were asked to select all the locations where they commonly stealth vape. Frequencies were used to examine the overall prevalence, frequency and common locations for stealth vaping. A logistic regression model was run to predict stealth vaping. RESULTS: Approximately two-thirds (64.3%, n=297/462) of the sample reported ever stealth vaping, of which 52.5% (n=156/297) reported stealth vaping in the past week. Among stealth vapers (n=297), 31% reported owning a smaller device solely for stealth vaping. The most common places to stealth vape included at work (46.8%), followed by bars/nightclubs (42.1%), restaurants (37.7%), at the movies (35.4%) and in airports/on airplanes (11.7%). Predictors of stealth vaping were greater dependence and owning a smaller device solely for stealth vaping. CONCLUSIONS: Stealth vaping is a common behaviour for many experienced e-cigarette users. More research is needed to understand the reasons for stealth vaping and its potential health and safety implications. This information could help researchers and regulators to design interventions to minimise the public health impact of stealth vaping.

Pilot Randomized Trial of an Automated Smoking Cessation Intervention via Mobile Phone Text Messages as an Adjunct to Varenicline in Primary Care.

OBJECTIVE: Varenicline is a safe and effective aid to smoking cessation but most trials have involved frequent visits or intensive behavioral support unlike that typically provided in primary care. The current study examined if motivational text messages, sent via cellphone, would increase quit rates in smokers being treated with varenicline and 3 brief sessions in a family practice setting. METHODS: This study was a randomized controlled, parallel-group smoking cessation trial. Intervention group participants (n = 74) received daily motivational text messages, additional texted tips in response to keywords, and weekly study questions while control group participants (n = 76) received only weekly study questions. Both groups received individualized counseling. Self-reported non-smoking and exhaled breath CO <10ppm were used to validate smoking abstinence at 3 weeks and 12 weeks. RESULTS: Overall, 30.7% (46/150) of participants were abstinent at the 12 week follow-up and the abstinence rate did not differ between groups (INT 31.1% v. CON 30.3%, p = .91). The only predictor of abstinence at 12 weeks was use of varenicline during a previous quit attempt (p = .01). Intervention group participants were more likely to rate the text messaging program as good or excellent (p < .01), to recommend a similar program to family or friends (p < .01), and to complete positive smoking cessation activities (p = .04), when compared with the control group. CONCLUSION: Although there were no differences in quit rates between the intervention and control group, intervention group participants rated the text messaging system more favorably, were more likely to recommend the program to others, and were more likely to complete positive smoking cessation activities.

Tobacco Use Among Middle and High School Students in Pennsylvania.

We analyzed data from the 2014-2015 Pennsylvania Youth Tobacco Survey to determine prevalence of tobacco use among middle and high school students. For the first time, questions on current (past 30-day) use of electronic cigarettes (e-cigarettes) were included in the survey. For current use, e-cigarettes were the most commonly used tobacco product among middle school students (2.3%; 95% confidence interval [CI], 1.4%-3.2%), and cigarettes were the most commonly used tobacco product among high school students (11.0%; 95% CI, 8.1%-13.8%). Given the changing landscape of tobacco products, collection of comprehensive data on tobacco use, including frequency, is important for monitoring behaviors among adolescents.

A Method for Classifying User-Reported Electronic Cigarette Liquid Flavors.

BACKGROUND: Along with the growth in popularity of electronic cigarette devices (e-cigs), the variety of e-cig liquids (e-liquid) available to users has also grown. Although some studies have published data about the use of flavored e-liquid, there is no standardized way to group flavors, making it difficult to interpret the data and replicate results across studies. The current study describes a method to classify user-reported e-liquid flavors and presents the resulting proportion of users in each flavor group in a large online survey of e-cig users. METHODS: Three thousand seven hundred sixteen participants completed an online survey about their e-cig use and responded to the following open-ended question regarding their use of e-liquid, "What is your favorite flavor and what brand of flavored liquid do you prefer?" Researchers used a 3 step method to determine the flavor attributes present in the e-liquids reported using an online search engine. Once all flavor attributes were identified, researchers used the constant comparative method to group the flavor attributes and delineate how to classify flavors with mixed components (eg, cinnamon Red Hots as a candy not a spice). RESULTS: The resulting classification scheme and proportions of e-liquids in each category were as follows: Tobacco (23.7%), Menthol/mint (14.8%), Fruit (20.3%), Dessert/sweets (20.7%), Alcohol (2.8%), Nuts/spices (2.0%), Candy (2.1%), Coffee/tea (4.3%), Beverage (3.1%), Unflavored (0.4%), and Don't Know/Other (5.8%). CONCLUSION: To better understand the use of flavored e-liquids, standardized methods to classify the flavors could facilitate data interpretation and comparison across studies. This study proposes a method for classifying the characterizing flavors in e-liquids used most commonly by experienced e-cig users. IMPLICATIONS: Current studies on the use of flavored e-liquid have used unclear methods to collect and report information on the use of flavors. This study adds a proposed method for classifying the flavors in the e-liquids used most commonly by experienced e-cig users. With a clear and explicit method for classifying self-reported flavors, future study results may be more easily compared.

Should electronic cigarette use be covered by clean indoor air laws?

BACKGROUND: Some jurisdictions have passed legislation that bans electronic cigarette (e-cig) use (vaping) in public places similarly to smoking. Many other jurisdictions have not yet determined how to regulate vaping in public places. This study examined the proportion of current e-cig users who find their vaping restricted in public places and further evaluated factors associated with the differences between restricted and unrestricted vapers. METHODS: 3960 experienced exclusive e-cig users completed an online survey from December 2012 to May 2014 about their e-cig use. Restricted vapers were defined as those who reported not being able to vape in places where smoking is typically banned. Unrestricted vapers were defined as those who reported being able vape in places where smoking is typically banned. χ2 and two-sided t-tests were used as appropriate to determine differences between variables of interest. RESULTS: Participants were a mean age of 40.3 years, 72.0% male, 91.8% white and 85.1% were from the USA. 26.1% (n=1034) of users reported restricted vaping, while 73.9% (n=2926) reported unrestricted vaping. Restricted vapers used less frequently (p<0.001) and were less dependent compared with unrestricted vapers (p=0.001). Of the restricted vapers, only 12% (n=124) reported finding it difficult to refrain from vaping in places where they were not supposed to. These users were more dependent (p<0.001) and more likely to experience strong cravings (p<0.001), compared with users who did not find it difficult to refrain from vaping. CONCLUSIONS: This study found that most vapers report unrestricted use of their e-cig. Of the restricted vapers, the majority (88%) do not find it difficult to refrain from vaping in places where they are not supposed to vape.

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol.

BACKGROUND: The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks. METHODS: Adult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms). DISCUSSION: Results from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes. TRIAL REGISTRATION: TRN: NCT01928758 , registered August 21, 2013.

A transdisciplinary model to inform randomized clinical trial methods for electronic cigarette evaluation.

BACKGROUND: This study is a systematic evaluation of a novel tobacco product, electronic cigarettes (ECIGs) using a two-site, four-arm, 6-month, parallel-group randomized controlled trial (RCT) with a follow-up to 9 months. Virginia Commonwealth University is the primary site and Penn State University is the secondary site. This RCT design is important because it is informed by analytical work, clinical laboratory results, and qualitative/quantitative findings regarding the specific ECIG products used. METHODS: Participants (N = 520) will be randomized across sites and must be healthy smokers of >9 cigarettes for at least one year, who have not had a quit attempt in the prior month, are not planning to quit in the next 6 months, and are interested in reducing cigarette intake. Participants will be randomized into one of four 24-week conditions: a cigarette substitute that does not produce an inhalable aerosol; or one of three ECIG conditions that differ by nicotine concentration 0, 8, or 36 mg/ml. Blocked randomization will be accomplished with a 1:1:1:1 ratio of condition assignments at each site. Specific aims are to: characterize ECIG influence on toxicants, biomarkers, health indicators, and disease risk; determine tobacco abstinence symptom and adverse event profile associated with real-world ECIG use; and examine the influence of ECIG use on conventional tobacco product use. Liquid nicotine concentration-related differences on these study outcomes are predicted. Participants and research staff in contact with participants will be blinded to the nicotine concentration in the ECIG conditions. DISCUSSION: Results from this study will inform knowledge concerning ECIG use as well as demonstrate a model that may be applied to other novel tobacco products. The model of using prior empirical testing of ECIG devices should be considered in other RCT evaluations. TRIAL REGISTRATION: TRN: NCT02342795 , registered December 16, 2014.

Views of Experienced Electronic Cigarette Users.

BACKGROUND: Awareness and use of electronic cigarettes (e-cigs) has increased significantly in the last five years, but little is known about the experiences, satisfaction, opinions and preferences of e-cigs users. METHOD: 1177 participants completed an online survey about their electronic cigarette preferences, of which 200 were randomly selected for analysis. The data was analyzed using both qualitative and quantitative methods. RESULTS: Participants found the design, the ability to customize, and the quality of vapor to be the most important characteristics of the device. Participants thought the most positive aspects of e-cig use were help to quit smoking, improved overall health, and reduced cost. The negative aspects associated with use were mainly related to side effects, such as dry mouth. When asked to explain how e-cigs were used differently than cigarettes, participants reported puffing more regularly, but taking fewer puffs per session. CONCLUSIONS: Experienced e-cig users stated that initiating e-cig use helped them to quit or reduce their conventional smoking, which they believe reduced their health risks. In comparison to cigarette smoking, e-cig users reported using their e-cig more times per day, but with fewer puffs at each use time. Users acknowledged that more research is needed to understand the safety and long-term effects of use. They mentioned dry mouth as a common side effect and common problems with reliability of e-cigs. Understanding these views may help health professionals to assess and assist e-cig users, and in the future, may help regulators to improve quality and reduce risks.

Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users.

INTRODUCTION: Electronic cigarettes (e-cigs) are becoming increasingly popular, but little is known about their dependence potential. This study aimed to assess ratings of dependence on electronic cigarettes and retrospectively compare them with rated dependence on tobacco cigarettes among a large sample of ex-smokers who switched to e-cigs. METHODS: A total of 3,609 current users of e-cigs who were ex-cigarette smokers completed a 158-item online survey about their e-cig use, including 10 items designed to assess their previous dependence on cigarettes and 10 almost identical items, worded to assess their current dependence on e-cigs (range 0-20). RESULTS: Scores on the 10-item Penn State (PS) Cigarette Dependence Index were significantly higher than on the comparable PS Electronic Cigarette Dependence Index (14.5 vs. 8.1, p < .0001). In multivariate analysis, those who had used e-cigs longer had higher e-cig dependence scores, as did those using more advanced e-cigs that were larger than a cigarette and had a manual button. Those using zero nicotine liquid had significantly lower e-cig dependence scores than those using 1-12 mg/ml, who scored significantly lower than those using 13 or greater mg/ml nicotine liquid (p < .003). CONCLUSIONS: Current e-cigarette users reported being less dependent on e-cigarettes than they retrospectively reported having been dependent on cigarettes prior to switching. E-cig dependence appears to vary by product characteristics and liquid nicotine concentration, and it may increase over time.

Factors Associated With Electronic Cigarette Users' Device Preferences and Transition From First Generation to Advanced Generation Devices.

INTRODUCTION: Electronic cigarettes (e-cigs) are becoming increasingly popular but little is known about how e-cig users' transition between the different device types and what device characteristics and preferences may influence the transition. METHODS: Four thousand four hundred twenty-one experienced e-cig users completed an online survey about their e-cig use, devices, and preferences. Participants included in analysis were ever cigarette smokers who used an e-cig at least 30 days in their lifetime and who reported the type of their first and current e-cig device and the nicotine concentration of their liquid. Analyses focused on transitions between "first generation" devices (same size as a cigarette with no button) and "advanced generation" devices (larger than a cigarette with a manual button) and differences between current users of each device type. RESULTS: Most e-cig users (n = 2603, 58.9%) began use with a first generation device, and of these users, 63.7% subsequently transitioned to current use of an advanced generation device. Among users who began use with an advanced generation device (n = 1818, 41.1%), only 5.7% transitioned to a first generation device. Seventy-seven percent of current advanced generation e-cig users switched to their current device in order to obtain a "more satisfying hit." Battery capabilities and liquid flavor choices also influenced device choice. CONCLUSION: E-cig users commonly begin use with a device shaped like a cigarette and transition to a larger device with a more powerful battery, a button for manual activation and a wider choice of liquid flavors.