Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.

Varenicline, the most efficacious smoking cessation monotherapy, produces abnormal dreams. Although genetic contributions to varenicline-associated nausea and cessation have been identified, the role of genetics in abnormal dreams is unknown. We conducted a genomewide association study (GWAS) of abnormal dreams in 188 European ancestry smokers treated with varenicline (NCT01314001). Additive genetic models examined the likelihood of experiencing abnormal dreams 2 weeks following varenicline initiation. For the top locus, we tested for selectivity to varenicline, effects on cessation, replication, and generalizability to African ancestry (AA) individuals. The top GWAS variant associated with abnormal dreams was rs901886, mapping to intron 2 of ICAM5 on chromosome 19. The prevalence of abnormal dreams in those with rs901886 CC, CT, and TT genotypes was 15%, 36%, and 62%, respectively (odds ratio = 2.94 for T vs. C, 95% confidence interval = 1.92-4.55, P = 2.03e-7; T allele frequency = 52%). This rs901886 association was selective to varenicline (P values > 0.05 on nicotine patch and placebo). There were also positive associations for rs901886 T (vs. C allele, P = 0.03) and for abnormal dreams (P = 0.06) with varenicline-aided cessation. Neither rs901886 (P = 0.40) nor abnormal dreams (P = 0.24) were associated with adherence. A similar direction of effect of rs901886 on abnormal dreams was observed in a second varenicline trial (NCT01836276). In AA individuals (n = 137), rs901886 was not associated with abnormal dreams (P = 0.41), but there was an association for a variant located ~ 74.4 kb 5' of ICAM5 (P = 2.56e-3). Variation in ICAM5 may influence abnormal dreams and cessation on varenicline. These findings provide additional support for genetically optimized smoking cessation approaches.

A preliminary randomized trial of reinforcement contingencies to improve compliance with ecological momentary assessment.

Ecological Momentary Assessment (EMA) methods are increasingly used by translational scientists to study real-world behavior and experience. The ability to draw meaningful conclusions from EMA research depends upon participant compliance with assessment completion. Most EMA studies provide financial compensation for compliance, but little empirical evidence addresses the impact of reinforcement parameters on the level of compliance. The purpose of this study-within-a-trial was to determine the effects of varying the amount and frequency of reinforcement on EMA compliance in a clinical sample of individuals seeking treatment for cigarette smoking. In the parent clinical trial, participants were asked to complete 9 weeks of EMA (1 daily Morning Assessment and 4 daily Random Assessments). Following a 5-week Standard Payment phase for EMA compliance, 61 individuals seeking treatment for cigarette smoking enrolled in the larger clinical trial were randomized to receive Standard ($1 per assessment, paid biweekly), Frequent ($1 per assessment, paid 3 times per week), or Large ($2 per assessment, paid biweekly) payments for EMA compliance during a 4-week Payment Manipulation Phase. Overall, receiving Frequent or Large payments did not improve EMA compliance compared to Standard payments, Ps > .30. Varying frequency and amount of remuneration for EMA compliance did not generally improve compliance in an ongoing clinical trial, raising further questions about the importance of reinforcement parameters in promoting EMA compliance.

Previous studies have addressed the idea that monetary compensation for participation in research is an effective way to encourage individuals to complete the studies. However, there has been limited exploration as whether the amount and frequency of compensation has an influence on participant adherence. We recruited adults who were seeking cigarette smoking treatment and asked them to complete multiple assessments each day on a smartphone app for 9 weeks. Following completion of the assessments, participants were given monetary compensation. A change after 5 weeks led to some persons receiving $1 per assessment paid three times a week (Frequent Payment Group), while others received $2 per assessment paid biweekly (Large Payment Group), and some continued to receive $1 per assessment paid biweekly (Standard Payment Group) for the next 4 weeks. We found that the experimental payment variations did not significantly change compliance with the assessments. These preliminary findings serve as a benchmark for further research.

Relationship Between Tobacco Product Use and Health-Related Quality of Life Among Individuals With COPD in Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study.

Introduction: We examined the association between tobacco product use and health-related quality of life (HRQoL) among individuals with chronic obstructive pulmonary disease (COPD) in Waves 1-5 of the Population Assessment of Tobacco and Health (PATH) Study. Methods: Adults ≥40 years with an ever COPD diagnosis were included in cross-sectional (Wave 5) and longitudinal (Waves 1 to 5) analyses. Tobacco use included 13 mutually exclusive categories of past 30-day (P30D) single use and polyuse with P30D exclusive cigarette use and ≥5-year cigarette cessation as reference groups. Multivariable linear regression and generalized estimating equations (GEE) were used to examine the association between tobacco use and HRQoL as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 questionnaire. Results: Of 1670 adults, 79.4% ever used cigarettes; mean (standard error [SE]) pack years was 30.9 (1.1). In cross-sectional analysis, P30D exclusive cigarette use, and e-cigarette/cigarette dual use were associated with worse HRQoL compared to ≥5-year cigarette cessation. Compared to P30D exclusive cigarette use, never tobacco use and ≥5-year cigarette cessation were associated with better HRQoL, while e-cigarette/cigarette dual use had worse HRQoL. Longitudinally (n=686), e-cigarette/cigarette dual use was associated with worsening HRQoL compared to both reference groups. Only never tobacco use was associated with higher HRQoL over time compared to P30D exclusive cigarette use. Conclusions: E-cigarette/cigarette dual use was associated with worse HRQoL compared to ≥5-year cigarette cessation and exclusive cigarette use. Never use and ≥5-year cigarette cessation were the only categories associated with higher HRQoL compared to exclusive cigarette use. Findings highlight the importance of complete smoking cessation for individuals with COPD.

Relationships Between the Nicotine Metabolite Ratio (NMR) and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.

INTRODUCTION: People who metabolize nicotine more quickly are generally less successful at quitting smoking. However, the mechanisms that link individual differences in the nicotine metabolite ratio (NMR), a phenotypic biomarker of the rate of nicotine clearance, to smoking outcomes are unclear. We tested the hypotheses that higher NMR is associated with greater smoking reinforcement, general craving, and cue-induced cigarette craving in a treatment-seeking sample. METHODS: Participants were 252 adults who smoke cigarettes enrolled in a randomized controlled smoking cessation trial (NCT03262662) conducted in Buffalo, New York, USA. Participants completed the Choice Behavior Under Cued Conditions (CBUCC) paradigm, a laboratory choice procedure, ~1 week before the first cessation treatment visit, at which time a saliva sample was collected for NMR assessment. On each CBUCC trial, participants reported cigarette craving during cue presentation (cigarette, water) and spent $0.01-0.25 for a chance (5%-95%) to sample the cue (1 puff, sip), providing measures of smoking reinforcement (spending for cigarettes vs. water), general cigarette craving (averaged across cigarette and water cues), and cue-specific craving (cigarette craving during cigarette vs. water cues). RESULTS: As observed in prior work, the NMR was significantly higher among white and female participants. As expected, both spending and cigarette craving were significantly greater on cigarette compared to water trials. However, contrary to our hypotheses, higher NMR was not associated with greater smoking reinforcement, general craving, or cue-specific craving. CONCLUSIONS: The present data do not support that smoking reinforcement or craving are related to nicotine metabolism among individuals seeking to quit smoking. IMPLICATIONS: Though greater smoking reinforcement, general craving, and cue-specific craving are hypothesized to be linked to faster nicotine metabolism, there was no evidence of such relationships in the present sample of adults seeking to quit smoking. Further research, including replication and consideration of alternate hypotheses, is warranted to elucidate the mechanisms by which the NMR is related to smoking cessation.

Perceived research burden of a novel therapeutic intervention: A study of transcranial magnetic stimulation for smoking cessation.

Background: Translating repetitive transcranial magnetic stimulation (rTMS) into evidence-based clinical applications relies on research volunteers with different perspectives on the burden of study participation. Additionally, clinical applications of rTMS require multiple visits over weeks or months, the impact of research burden is an important component for these studies and translation of these findings to clinical practice. High frequency rTMS has significant potential to be developed as an evidence-based treatment for smoking cessation, however, the optimal rTMS dosing strategies have yet to be determined. Participant burden is an important component of determining optimal dosing strategy for rTMS as a treatment for long-term smoking cessation. Methods: In this double-blinded, sham-controlled, randomized design, the effects of treatment duration, intensity, and active/sham assignment of rTMS on research burden were examined. Results: Overall level of perceived research burden was low. Experienced burden (M = 26.50) was significantly lower than anticipated burden (M = 34.12). Research burden did not vary by race or income. Conclusions: Overall research burden was relatively low. Contrary to our hypotheses, we found little evidence of added significant burden for increasing the duration or intensity of rTMS, and we found little evidence for differences in research burden by race or income. Clinical Trial Registration: identifier NCT03865472.

The Roswell eND scale: Brief, valid assessment of nicotine dependence adults seeking to discontinue e-cigarette use.

BACKGROUND: Most adults who regularly use e-cigarettes or Electronic Nicotine Delivery Systems (ENDS) desire to discontinue use. ENDS use can result symptoms of nicotine withdrawal and dependence which can make it more difficult to discontinue use. Brief, valid assessment of nicotine dependence among adults who use ENDS is needed to guide treatment for nicotine dependence in this group. We sought to develop a brief, valid instrument to measure nicotine dependence among adults seeking to discontinue ENDS in a busy Quitline. METHODS: In this cross-sectional design, we examined content, construct, and concurrent validity of the Roswell ENDS Nicotine Dependence Scale (Roswell eND Scale) and the Penn State E-Cigarette Dependence Index (Penn State eCDI). Participants who called the New York Quitline from November 2019 to June 2020 seeking to discontinue ENDS use were invited to participate. Construct validity was examined with exploratory and confirmatory factor analyses. Instrument and factor scores were then correlated with cotinine, a biomarker of nicotine exposure. RESULTS: All participants (n = 209) were highly dependent and co-used combustible cigarettes to varying degrees. Both instruments demonstrated content validity and construct validity, however only the 5-item Roswell eND Scale demonstrated criterion-related validity by showing a significant positive correlation with salivary cotinine levels. CONCLUSIONS: The 5-item Roswell eND Scale can briefly and effectively assess nicotine dependence among treatment-seeking adults who co-use ENDS and cigarettes. These preliminary psychometric findings have the potential to be generalizable to other adults seeking to discontinue ENDS use, many of whom currently or formerly smoked cigarettes.

Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial.

Importance: Even with varenicline, the leading monotherapy for tobacco dependence, smoking abstinence rates remain low. Preliminary evidence suggests that extending the duration of varenicline treatment before quitting may increase abstinence. Objective: To test the hypotheses that, compared with standard run-in varenicline treatment (1 week before quitting), extended run-in varenicline treatment (4 weeks before quitting) reduces smoking exposure before the target quit date (TQD) and enhances abstinence, particularly among women. Design, Setting, and Participants: This double-blind, randomized, placebo-controlled clinical trial enrolled participants from October 2, 2017, to December 9, 2020, at a single-site research clinic in Buffalo, New York. Of 1385 people screened, 320 adults reporting smoking 5 or more cigarettes per day (CPD) were randomized and followed up for 28 weeks. Data were analyzed from August 2021 to June 2022. Interventions: In the pre-TQD period (weeks 1-4), the extended run-in group received 4 weeks of varenicline; the standard run-in group received 3 weeks of placebo followed by 1 week of varenicline. Both groups received open-label varenicline during weeks 5 to 15 and brief quit counseling at 6 clinic visits. Main Outcomes and Measures: The primary outcome consisted of cotinine-verified (at end of treatment [EOT]) self-reported continuous abstinence from smoking (in CPD) during the last 4 weeks of treatment. Secondary outcomes included bioverified self-report of continuous abstinence at the 6-month follow-up and percentage of reduction in self-reported smoking rate during the prequit period (week 1 vs week 4). Results: A total of 320 participants were randomized, including 179 women (55.9%) and 141 men (44.1%), with a mean (SD) age of 53.7 (10.1) years. Continuous abstinence during the final 4 weeks of treatment (weeks 12-15; EOT) was not greater in the extended run-in group (64 of 163 [39.3%]) compared with the standard run-in group (57 of 157 [36.3%]; odds ratio [OR], 1.13 [95% CI, 0.72-1.78]), nor was the hypothesized group × sex interaction significant (OR, 0.52 [95% CI, 0.21-1.28]). Similar nonsignificant results were obtained for continuous abstinence at the 6-month follow-up. The mean (SE) decrease in self-reported smoking rate during the prequit period was greater in the extended run-in group (-38.8% [2.8%]) compared with the standard run-in group (-17.5% [2.7%]). Conclusions and Relevance: Among adult daily smokers, extending the duration of prequit varenicline treatment beyond the standard 1-week run-in period reduced prequit smoking exposure but, more importantly, did not significantly improve continuous abstinence rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03262662.

Association of tobacco product use with chronic obstructive pulmonary disease (COPD) prevalence and incidence in Waves 1 through 5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: We examined the association of non-cigarette tobacco use on chronic obstructive pulmonary disease (COPD) risk in the Population Assessment of Tobacco and Health (PATH) Study. METHODS: There were 13,752 participants ≥ 40 years with Wave 1 (W1) data for prevalence analyses, including 6945 adults without COPD for incidence analyses; W1-5 (2013-2019) data were analyzed. W1 tobacco use was modeled as 12 mutually-exclusive categories of past 30-day (P30D) single and polyuse, with two reference categories (current exclusive cigarette and never tobacco). Prevalence and incidence ratios of self-reported physician-diagnosed COPD were estimated using weighted multivariable Poisson regression. RESULTS: W1 mean (SE) age was 58.1(0.1) years; mean cigarette pack-years was similar for all categories involving cigarettes and exclusive use of e-cigarettes (all > 20), greater than exclusive cigar users (< 10); and COPD prevalence was 7.7%. Compared to P30D cigarette use, never tobacco, former tobacco, and cigar use were associated with lower COPD prevalence (RR = 0.33, (95% confidence interval-CI) [0.26, 0.42]; RR = 0.57, CI [0.47, 0.70]; RR = 0.46, CI [0.28, 0.76], respectively); compared to never tobacco use, all categories except cigar and smokeless tobacco use were associated with higher COPD prevalence (RR former = 1.72, CI [1.33, 2.23]; RR cigarette = 3.00, CI [2.37, 3.80]; RR e-cigarette = 2.22, CI [1.44, 3.42]; RR cigarette + e-cigarette = 3.10, CI [2.39, 4.02]; RR polycombusted = 3.37, CI [2.44, 4.65]; RR polycombusted plus noncombusted = 2.75, CI]1.99, 3.81]). COPD incidence from W2-5 was 5.8%. Never and former tobacco users had lower COPD risk compared to current cigarette smokers (RR = 0.52, CI [0.35, 0.77]; RR = 0.47, CI [0.32, 0.70], respectively). Compared to never use, cigarette, smokeless, cigarette plus e-cigarette, and polycombusted tobacco use were associated with higher COPD incidence (RR = 1.92, CI [1.29, 2.86]; RR = 2.08, CI [1.07, 4.03]; RR = 1.99, CI [1.29, 3.07]; RR = 2.59, CI [1.60, 4.21], respectively); exclusive use of e-cigarettes was not (RR = 1.36, CI [0.55, 3.39]). CONCLUSIONS: E-cigarettes and all use categories involving cigarettes were associated with higher COPD prevalence compared to never use, reflecting, in part, the high burden of cigarette exposure in these groups. Cigarette-but not exclusive e-cigarette-use was also strongly associated with higher COPD incidence. Compared to cigarette use, only quitting tobacco was protective against COPD development.

A Psychometric Evaluation of the Stanford Expectations of Treatment Scale (SETS) in the Context of a Smoking Cessation Trial.

INTRODUCTION: Although treatment outcome expectancies (TOEs) may influence clinical outcomes, TOEs are rarely reported in the smoking cessation literature, in part because of the lack of validated measures. Therefore, we conducted a psychometric evaluation of TOEs scores with the Stanford Expectations of Treatment Scale (SETS) in the context of a smoking cessation clinical trial. METHODS: Participants were 320 adults enrolled in a randomized controlled trial of extended versus standard pre-quit varenicline treatment for smoking cessation (clinicaltrials.gov ID: NCT03262662). Across an 8-week treatment period, we examined the nature and stability of the factor structure using confirmatory factor analysis (CFA), evaluated discriminant validity by examining correlations with abstinence self-efficacy and positive/negative affect (PA/NA), and assessed internal consistency and test-retest reliability of SETS scores. RESULTS: CFAs supported a 2-factor structure that was stable (ie, invariant) across weeks. Positive and negative TOEs were each reflected in three-item subscales that exhibited acceptable to excellent internal consistency (Cronbach's alphas ≥ .77). Positive and negative TOEs were modestly correlated with PA and NA (all |rs| <.27, p < .05). Positive TOEs, but not negative TOEs, were moderately correlated with abstinence self-efficacy (rs = .45 to .61, p < .01). Both positive and negative TOEs scores demonstrated moderate test-retest reliability between assessments (rs = .54 to .72). CONCLUSIONS: SETS scores generally reflect a valid and reliable assessment of positive and negative TOEs in a sample of adults enrolled in a smoking cessation trial. The SETS appears to be a reasonable option for assessing TOEs in future smoking treatment studies. IMPLICATIONS: Assessments of treatment outcome expectancies are rarely reported in the smoking cessation literature. The present results support the validity and reliability of the SETS scores among adults seeking treatment for their smoking behavior.

Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic. Methods: In a 3 × 2 randomized factorial design, participants (n = 23) received 900 pulses of 20 Hz rTMS to the left dorsolateral prefrontal cortex (PFC) in one of three Durations (8, 12, or 16 days of stimulation) and two Intensities (1 or 2 sessions per day). We examined direction and magnitude of the effect sizes on latency to relapse, 6-month point-prevalence abstinence rates, research burden, and delay discounting rates. Results: A large effect size was found for Duration and a medium for Intensity for latency to relapse. Increasing Duration increased the odds of abstinence 7-8-fold while increasing Intensity doubled the odds of abstinence. A large effect size was found for Duration, a small for Intensity for delay discounting rate. Increasing Duration and Intensity had a small effect on participant burden. Conclusion: Findings provide preliminary support for delay discounting as a therapeutic target and for increasing Duration and Intensity to achieve larger effect sizes for long-term smoking cessation and will provide a pre-pandemic comparison for data collected during the pandemic. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03865472].

Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving.

INTRODUCTION: Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation. AIMS AND METHODS: Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1-week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD. RESULTS: Across time, NA peaked 1-week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: .01 to .30) and lower mean craving at 1-week post-quit (CI: .06 to .50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation but was not a significant mediator. CONCLUSIONS: These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported NA and craving as plausible treatment mechanisms of varenicline. IMPLICATIONS: The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline's efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Furthermore, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.

Cardiovascular Outcomes among Combustible-Tobacco and Electronic Nicotine Delivery System (ENDS) Users in Waves 1 through 5 of the Population Assessment of Tobacco and Health (PATH) Study, 2013-2019.

BACKGROUND: Prior studies have not clearly established risk of cardiovascular disease (CVD) among smokers who switch to exclusive use of electronic nicotine delivery systems (ENDS). We compared cardiovascular disease incidence in combustible-tobacco users, those who transitioned to ENDS use, and those who quit tobacco with never tobacco users. METHODS: This prospective cohort study analyzes five waves of Population Assessment of Tobacco and Health (PATH) Study data, Wave 1 (2013-2014) through Wave 5 (2018-2019). Cardiovascular disease (CVD) incidence was captured over three intervals (Waves 1 to 3, Waves 2 to 4, and Waves 3 to 5). Participants were adults (40+ years old) without a history of CVD for the first two waves of any interval. Change in tobacco use status, from exclusive past 30 day use of any combustible-tobacco product to either exclusive past 30 day ENDS use, dual past 30 day use of ENDS and combustible-tobacco, or no past 30 day use of any tobacco, between the first two waves of an interval was used to predict onset of CVD between the second and third waves in the interval. CVD incidence was defined as a new self-report of being told by a health professional that they had congestive heart failure, stroke, or a myocardial infarction. Generalized estimating equation (GEE) analyses combined 10,548 observations across intervals from 7820 eligible respondents. RESULTS: Overall, there were 191 observations of CVD among 10,548 total observations (1.7%, standard error (SE) = 0.2), with 40 among 3014 never users of tobacco (1.5%, SE = 0.3). In multivariable models, CVD incidence was not significantly different for any tobacco user groups compared to never users. There were 126 observations of CVD among 6263 continuing exclusive combustible-tobacco users (adjusted odds ratio [AOR] = 1.44; 95% confidence interval (CI) 0.87-2.39), 15 observations of CVD among 565 who transitioned to dual use (AOR = 1.85; 0.78-4.37), and 10 observations of CVD among 654 who quit using tobacco (AOR = 1.18; 0.33-4.26). There were no observations of CVD among 53 who transitioned to exclusive ENDS use. CONCLUSIONS: This study found no difference in CVD incidence by tobacco status over three 3 year intervals, even for tobacco quitters. It is possible that additional waves of PATH Study data, combined with information from other large longitudinal cohorts with careful tracking of ENDS use patterns may help to further clarify this relationship.

Cardiovascular Risk Factor and Disease Measures from the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: Cardiovascular disease is a key health condition associated with tobacco use; however, clinical measures are not typically possible in population-based studies. In this paper, we assess the reliability and validity of self-reported cardiovascular risk factors and diseases in a large nationally representative study of tobacco use and health outcomes. METHODS: This paper analyzes self-reported cardiovascular risk factors and disease among adults age 40 years and older based on U.S. nationally representative data from the Population Assessment of Tobacco and Health (PATH) Study. Prevalence of cardiovascular risk factors (self-reported high blood pressure, high cholesterol, diabetes and family history of premature heart disease, BMI ≥ 35, and tobacco use) and cardiovascular disease (self-reported heart attack, stroke and/or congestive heart failure (CHF)) were considered along with ratings of physical functioning, fatigue, and general health. RESULTS: Self-reported cardiovascular disease was found to be associated with functional health measures (walking up a flight of stairs) and general ratings of health. Prospective analyses found strong correlations between sequential data collection waves for history of hypertension, elevated cholesterol and CHF, while more modest correlations were noted for stroke and heart attack. The overall prevalence of cardiovascular disease and hypertension was comparable to those from the National Health and Nutrition Examination Survey (NHANES). CONCLUSIONS: These analyses suggest reliability and concurrent validity regarding self-reported cardiovascular risk factors and disease assessed in the PATH Study.

Designing an exercise intervention for adult survivors of childhood cancers.

BACKGROUND: This study examined current physical activity levels and preferences for exercise settings and activities among adult survivors of childhood cancers as a strategy to inform the feasibility and design of such programs. METHODS: A mixed-methods design was used to investigate current activity levels as well as barriers to and preferences for physical activity among 20 adult survivors of pediatric cancer. RESULTS: One-half of participants reported engaging in regular physical activity, although the frequency, intensity, and duration varied. Overall, 17 of the 20 participants (85%) stated they would be interested in participating in a structured exercise intervention, and they expressed a strong interest in walking (76%), bicycling (53%), and weight training (53%). Common barriers to participation in a potential structured exercise program were insufficient time, current health issues, and program location/distance. Nearly all participants agreed that information on nutrition and diet should be included as part of an exercise intervention. CONCLUSIONS: These findings will help inform the design and implementation of future exercise programs to enhance physical activity among this high-risk group of cancer survivors.

The impact of three weeks of pre-quit varenicline on reinforcing value and craving for cigarettes in a laboratory choice procedure.

RATIONALE: Varenicline, a partial nicotinic agonist, is theorized to attenuate pre-quit smoking reinforcement and post-quit withdrawal and craving. However, the mechanisms of action have not been fully characterized, as most studies employ only retrospective self-report measures, hypothetical indices of reinforcing value, and/or nontreatment-seeking samples. OBJECTIVES: The current research examined the impact of pre-quit varenicline (vs. placebo) on laboratory measures of smoking and food (vs. water) reinforcement and craving. METHODS: Participants were 162 treatment-seeking smokers enrolled in a randomized controlled trial of smoking cessation ( clinicaltrials.gov ID: NCT03262662). Participants completed two laboratory sessions: a pre-treatment session, ~ 1 week prior to beginning varenicline or placebo, and an active treatment session, after ~ 3 weeks of treatment. At each session, participants completed a laboratory choice procedure; on each of 36 trials, a lit cigarette, food item, or cup of water was randomly presented. Participants reported level of craving and spent $0.01-0.25 to have a corresponding 5-95% chance to sample the cue. RESULTS: As predicted, spending was significantly higher on cigarette trials than water trials, and varenicline resulted in a greater between-session decline in spending on cigarette trials (but not water) than did placebo. Cigarette craving was enhanced in the presence of smoking cues compared to water, but neither average (tonic) cigarette craving nor cue-specific cigarette craving was significantly influenced by varenicline. Food spending and craving were generally unaffected by varenicline treatment. CONCLUSIONS: These laboratory data from treatment-seeking smokers provide the strongest evidence to date that varenicline selectively attenuates smoking reinforcement prior to quitting.

Making lemonade from SARS coronavirus-2 lemons: Transitioning a smoking cessation trial to a virtual platform.

Clinical trials represent an essential component of improving treatment for substance use disorders (SUD). The SARS coronavirus-2 pandemic disrupted our ongoing clinical trial of smoking cessation and forced us to rapidly implement changes to assure participants access to ongoing counseling and monitoring via telephone calls and/or video chat sessions. Our experiences suggest that this pandemic will lead to changes for both future clinical trial participants and project staff. While challenges remain, it will be important to assessing the impact of these changes with regard to participant experiences and treatment outcomes.

Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center.

Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.

Dosing parameters for the effects of high-frequency transcranial magnetic stimulation on smoking cessation: study protocol for a randomized factorial sham-controlled clinical trial.

BACKGROUND: Despite the considerable success of comprehensive tobacco control efforts, tobacco use remains one of the greatest preventable causes of death and disease today. Over half of all smokers in the US make quit attempts every year, but over 90% relapse within 12 months, choosing the immediate reinforcement of smoking over the long-term benefits of quitting. Conceptual and empirical evidence supports continued investigation of high frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in reducing relapse and decreasing cigarette consumption. While this evidence is compelling, an optimal dosing strategy must be determined before a long-term efficacy trial can be conducted. The goal of this study is to determine a dosing strategy for 20 Hz rTMS that will produce the best long-term abstinence outcomes with the fewest undesirable effects. METHODS: This is a fully crossed, double-blinded, sham-controlled, 3x2x2 randomized factorial study. The three factors are duration (stimulation days: 8, 12, and 16); intensity (900 or 1800 pulses per day); and sham control. Participants (n = 258) will consist of adults (18-65) who are motivated to quit smoking cigarettes and who will be followed for 6 months post-quit. Outcomes include latency to relapse, point prevalence abstinence rates, delay discounting rates, cognitive-behavioral skills acquisition, and multiple measures of potential undesirable effects that impact participant compliance. DISCUSSION: This study integrates existing theoretical concepts and methodologies from neuropsychology, behavioral economics, brain stimulation, clinical psychology, and the evidence-based treatment of tobacco dependence in the development of a promising and innovative approach to treat tobacco dependence. This study will establish an optimal dosing regimen for efficacy testing. Findings are expected to have a significant influence on advancing this approach as well as informing future research on clinical approaches that combine rTMS with other evidence-based treatments for tobacco dependence and perhaps other addictions. TRIAL REGISTRATION: Clinical Trials NCT03865472 (retrospectively registered). The first participant was fully enrolled on November 26, 2018. Registration was posted on March 7, 2019.

Menthol Cigarettes and Smoking Cessation among Adult Smokers in the US.

Objectives: In this study, we identified differences in cessation, nicotine dependence, and quit attempts between smokers using non-menthol cigarettes and smokers using menthol cigarettes differing in menthol delivery method (eg, menthol in the tobacco only, crushable capsules only or both). Methods: We analyzed data from the Population Assessment of Tobacco and Health Study, Waves 1 and 2 (W1 and W2), to determine associations of delivery method of menthol with cessation, nicotine dependence, and quit attempts among current adult cigarette smokers. Results: Nearly 40% of US smokers reported using a mentholated cigarette product with most using a product mentholated in the tobacco only. Smokers included in this analysis had a moderate to low heaviness of smoking index score. The lowest average score was among those using products mentholated in a filter capsule only (1.3, SE = .10), and the highest among those using non-mentholated products (2.4, SE = .03). About 12% of smokers quit between W1 and W2. Cessation, nicotine dependence, and quit attempts at W2 were not associated with delivery method of menthol at W1. Conclusions: Method of menthol delivery did not impact cessation, nicotine dependence, and quit attempts.

Menthol, Nicotine, and Flavoring Content of Capsule Cigarettes in the US.

OBJECTIVES: Characterize physical design features of cigarette brands sold in the US according to the delivery method of menthol that may affect sensory perception among users. METHODS: Twelve cigarette brands, mentholated and non-mentholated, were purchased for analyses of the physical design characteristics, quantification of nicotine and menthol, and identification of flavor additives. RESULTS: Physical design characteristics did not differ significantly between the various cigarette brands. However, significant differences were seen in levels of menthol. Menthol levels were greatest in products that had dual delivery methods of menthol (6.7mg/cigarette; SE=0.27) followed by products mentholated in a filter capsule only (5.7mg/cigarette; SE=0.25), and those mentholated in the tobacco only (3.8mg/cigarette; SE=0.12); products that were not mentholated had the least (0.38mg/cigarette; SE=0.31). Finally, flavor additives with a mint flavor profile other than menthol were identified, such as pulegone and limonene, and differed between cigarette brands, which are likely contributing to the menthol flavor experience associated with use of these products. CONCLUSIONS: The regulation of menthol delivery method, flavorings added to the capsule, and/or menthol concentration may be beneficial for the public health as these factors are likely creating unique sensory experiences.