Characterizing Interest in and Uptake of Preexposure Prophylaxis for HIV Prevention Among Men in a US State Correctional System.

BACKGROUND: People experiencing incarceration are disproportionately impacted by HIV and are potential candidates for HIV preexposure prophylaxis (PrEP). We explored factors associated with PrEP interest and PrEP uptake and described barriers to PrEP uptake among incarcerated men in a state correctional system. METHODS: From September 2019 to July 2022, incarcerated men at the Rhode Island Department of Corrections were screened for PrEP eligibility and referred to a PrEP initiation study. We used bivariate analyses and multivariable logistic regression models to explore factors associated with PrEP interest and uptake in the screening sample. RESULTS: Of the men screened and determined to be eligible for PrEP, approximately half (50%) were interested in taking PrEP. Individuals identifying as men who have sex with men (adjusted odds ratio, 4.46; 95% confidence interval, 1.86-11.4) and having multiple female sex partners (adjusted odds ratio, 2.98; 95% confidence interval, 1.47-6.27) were more likely to express interest in PrEP (interested/not interested) than those not reporting these behavioral factors. Preexposure prophylaxis uptake (yes/no) was 38%. Lack of PrEP interest, low self-perceived risk of HIV acquisition, and unpredictable lengths of incarceration were the most frequently encountered barriers to PrEP uptake. CONCLUSIONS: Men reporting sexual transmission behaviors were more interested in PrEP and had higher uptake than other men. Preexposure prophylaxis interest and HIV risk factors were both moderately high, which suggests that men experiencing incarceration should be screened for and offered PrEP as part of standard clinical care. Study findings have important implications for research and practice to adapt PrEP care to correctional systems.

Using pod based e-cigarettes and nicotine pouches to reduce harm for adults with low socioeconomic status who smoke: A pilot randomized controlled trial.

INTRODUCTION: Alternative Nicotine Delivery Systems (ANDS) such as e-cigarettes (EC) and oral nicotine pouches (ONP) may facilitate the substitution of smoking for those unwilling to quit. This pilot study assesses the harm reduction potential of EC and ONP among smokers with low socioeconomic status (SES). METHODS: Adults who smoked daily in the past 6 months, had a household income < 250% federal poverty level and had no intention of quitting smoking in the next 30 days were randomized 2:2:1 to 8 Weeks of 5% nicotine EC; 4mg ONP or assessment-only control (CC). The primary outcome was a within-group change in cigarettes per day (CPD) from Baseline to Week 8. RESULTS: 45 individuals were randomized (EC: N=18; ONP: N=18; CC: N=9). Analyses included 33 participants who completed the Week 8 visit. Mean age was 50.2 years (SD:10.7) and average CPD at baseline was 13.9 (SD: 10.1). For those randomized to EC, average CPD decreased from 14.7 (95%CI: 10.3; 19.1) at Baseline to 2.9 (95%CI: 0.09; 5.79) at Week 8 (p-value <0.001). For those randomized to ONP, average CPD decreased from 15.0 (95%CI: 5.02; 24.93) to 8.3 (95%CI: 1.34; 15.18) by Week 8 (p-value =0.01). In the EC and ONP groups, respectively, 4 (28.6%) and 1 (8.3%) participant fully switched from smoking to the ANDS product by Week 8. CONCLUSIONS: Individuals with low SES who smoke had lower CPD after switching to EC or ONP. These findings show the potential of ANDS in helping smokers switch to less harmful devices. IMPLICATIONS: This study provides novel evidence that e-cigarettes and nicotine pouches can be a harm reduction tool for individuals with lower SES who smoke and are not willing to quit smoking, contributing to reducing tobacco-related disparities in this population.

Nicotine Delivery and Changes in Withdrawal and Craving During Acute Electronic Cigarette, Heated Tobacco Product, and Cigarette Use Among a Sample of Black and White People Who Smoke.

INTRODUCTION: E-cigarettes and heated tobacco products (HTPs) may serve as potential options for harm reduction for smokers if they possess reward profiles similar to cigarettes. Little is known about the abuse liability of HTPs and e-cigarettes versus cigarettes in racial/ethnic minority smokers. AIMS AND METHODS: Twenty-two nicotine-deprived people who smoke (black [n = 12] and white [n = 10]) completed three visits that included a standardized 10-puff bout followed by a 50-minute ad libitum use assessment with their usual brand cigarette (UBC), an e-cigarette, and HTP. Visits were completed in a randomized crossover design and were separated by a minimum 48-hour washout period. Assessments included plasma nicotine, Cmax, and reductions in craving and withdrawal. RESULTS: UBC delivered significantly greater levels of nicotine compared to the e-cigarette (p < .001) and HTP (p < .01) during both the standardized and ad libitum sessions. HTP delivered more nicotine than the e-cigarette during the standardized puffing session (p = .047) but not the ad libitum session. Only craving during the standardized puffing session and not the ad libitum session showed significant differences across products (p < .001) such that UBC resulted in the greatest reduction followed by HTP and e-cigarette. CONCLUSIONS: Despite greater nicotine delivery from the UBC compared to e-cigarette and HTP, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. IMPLICATIONS: Use of participant's UBCs (UBC) resulted in greater nicotine delivery compared to both the e-cigarette and HTP. Despite this relative difference in nicotine delivery, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. These findings suggest that in this sample of black and white people who smoke, HTPs and e-cigarettes provided significant relief from negative symptoms that maintain smoking.

Perception of pregnant individuals, health providers and decision makers on interventions to cease substance consumption during pregnancy: a qualitative study.

BACKGROUND: Despite multiple recommendations and strategies implemented at a national and international level, cigarette smoking, alcohol consumption, and cannabis use during pregnancy remains high in most countries. The objective of this study was to examine key stakeholders' perception of the treatment interventions adopted in Spain, to identify political, organizational and personal factors associated with successful implementation, and to propose strategies for improvement. METHODS: A qualitative study with a phenomenological approach was conducted in 2022. The target groups were: (1) clinical decision makers in the field of addiction science, (2) health professionals who carry out treatment interventions, and (3) pregnant individuals who use tobacco, alcohol or cannabis. Two focus groups and eight in-depth interviews were conducted, recorded, and transcribed. Exploratory analysis and inductive open coding was performed, codes were merged into categories, and subcategories were identified. RESULTS: The analysis resulted in 10 subcategories which were further merged into three main categories: (1) Degree of adoption and utility of treatment interventions implemented; (2) Needs and demands with respect to the organization of treatment interventions; and, (3) Personal barriers to and facilitators for treatment. Respondents reported that despite multiple national and regional cessation initiatives, treatment interventions were rarely adopted in clinical practice. Health care administrators demanded reliable records to quantify substance use for better planning of activities. Health care professionals advocated for additional time and training and both echoed the importance of integrating cessation interventions into routine prenatal care and creating in-house specialized units. The difficulty in quitting, lack of awareness of risk for foetus and child and the controversial advice were identified as barriers by pregnant individuals. CONCLUSIONS: Consistent with previous work, this study found that cessation strategies implemented by the health authorities are not effective if they are not accompanied by organizational and behavioral changes. The current study identifies a set of factors that could be pivotal in ensuring the success of treatment interventions targeting tobacco, alcohol and cannabis use among pregnant individuals.

Impact of the use of small-area models on estimation of attributable mortality at a regional level.

The objective of this study is to assess the impact of applying prevalences derived from a small-area model at a regional level on smoking-attributable mortality (SAM). A prevalence-dependent method was used to estimate SAM. Prevalences of tobacco use were derived from a small-area model. SAM and population attributable fraction (PAF) estimates were compared against those calculated by pooling data from three national health surveys conducted in Spain (2011-2014-2017). We calculated the relative changes between the two estimates and assessed the width of the 95% CI of the PAF. Applying surveys-based prevalences, tobacco use was estimated to cause 53 825 (95% CI: 53 182-54 342) deaths in Spain in 2017, a figure 3.8% lower obtained with the small-area model prevalences. The lowest relative change was observed in the Castile-La Mancha region (1.1%) and the highest in Navarre (14.1%). The median relative change between regions was higher for women (26.1%), population aged ≥65 years (6.6%), and cardiometabolic diseases (9.0%). The differences between PAF by cause of death were never greater than 2%. Overall, the differences between estimates of SAM, PAF, and confidence interval width are small when using prevalences from both sources. Having these data available by region will allow decision-makers to implement smoking control measures based on more accurate data.

Recency of Cannabis Vaping in Sexual Minorities in Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: Cannabis vaping is increasing in the United States. Among populations at-risk are sexual minorities (SM) who are more likely to vape cannabis compared to their heterosexual counterparts. Cannabis vaping has been associated with negative health outcomes and concomitant use of other substances with increased risk with more recent use. OBJECTIVES: This study examined the association between SM identification and recency of cannabis vaping (the last occasion that a participant used their vape device with cannabis) and number of puffs (the count of puffs that the participant took during their most recent use of their vape device with cannabis) using Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study. RESULTS: In a weighted sample of participants who reported ever vaping cannabis (N = 5,331), 15% identified as SM, about 60% vaped cannabis in the past 3 or more days, and the mean number of puffs was 2 (SE = 0.17). Using multinomial logistic regression and zero-inflated negative binomial regression, the results showed that compared to heterosexual adults who reported not recently vaping cannabis, SM had higher probabilities of vaping cannabis in the past 3 or more days, 1-2 days, and the day of interview. CONCLUSION: SM individuals were more likely to recently vape cannabis, placing them at higher risk for respiratory diseases and use of other substances. Public health researchers and practitioners need to identify reasons for cannabis vaping in this population and implement targeted public health messaging to inform SM communities of the potential health effects of cannabis vaping.

Factors Associated With Successful E-Cigarette Cessation Among a Convenience Sample of Adult Users.

Background: A growing body of literature suggests that many people who use e-cigarettes become dependent and have difficulty quitting. Most people who use e-cigarettes have interest in quitting, yet there is currently a lack of evidence to inform interventions for e-cigarette cessation. Objective: The purpose of this study was to identify factors associated with successful e-cigarette quit attempts among a large sample of people who use e-cigarettes. Methods: Participants (n=586) were people who use e-cigarettes who reported at least one lifetime attempt to quit their e-cigarette use. Adjusted logistic regression models were performed to examine differences in e-cigarette use characteristics and quit methods between people who currently use e-cigarettes and who quit e-cigarettes. Results: Most participants were people who currently use e-cigarettes and only 27.5% reported successfully quitting. Most participants (90.6%) used e-cigarettes that contained nicotine, and over half (54.0%) used closed-system e-cigarette devices with replaceable pre-filled pods or cartridges. The quit method most commonly used overall (63.1%) and for people who quit e-cigarettes (70.8%) was cold turkey. Past 30-day cigarette use and past 30-day other tobacco use was significantly associated with reduced odds of quitting, and there were no e-cigarette characteristics significantly associated with successful cessation. Nicotine replacement therapy was the only e-cigarette cessation method that was significantly associated with increased odds of quitting after adjusting for past 30-day cigarette and other tobacco use. Conclusions: These results suggests that cigarette use, other tobacco use, and quit method used may significantly influence the likelihood of e-cigarette cessation. Future research is needed to determine the effectiveness of interventions for e-cigarette cessation using nicotine replacement therapy.

Varenicline and counseling for vaping cessation: a double-blind, randomized, parallel-group, placebo-controlled trial.

BACKGROUND: Vaping cessation is virtually unexplored. The efficacy and safety of varenicline for vaping cessation has not been studied and rigorous research is required to advance best practice and outcomes for people who use electronic cigarettes (EC) and want to quit. The objective is to evaluate the efficacy and safety of varenicline (1 mg BID, administered for 12 weeks, with follow-up to week 24) combined with vaping cessation counseling in exclusive daily EC users intending to quit vaping. METHODS: Design: Double-blind, randomized, parallel-group, placebo-controlled trial. SETTING: The study took place at a University-run smoking cessation center. PARTICIPANTS: People who exclusively use ECs daily and intend to quit vaping. INTERVENTION: A total of 140 subjects were randomized to either varenicline (1 mg, administered twice daily for 12 weeks) plus counseling or placebo treatment (administered twice daily, for 12 weeks) plus counseling. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up, nontreatment phase. MAIN OUTCOMES AND MEASURES: The primary efficacy endpoint of the study was biochemically validated continuous abstinence rate (CAR) at weeks 4 to 12. Secondary efficacy end points were CAR at weeks 4 to 24 and 7-day point prevalence of vaping abstinence at weeks 12 and 24. RESULTS: CAR was significantly higher for varenicline vs placebo at each interval: weeks 4-12, 40.0% and 20.0%, respectively (OR = 2.67, 95% CI = [1.25-5.68], P = 0.011); weeks 4-24, 34.3% for varenicline with counseling and 17.2% for placebo with counseling (OR = 2.52, 95% CI = [1.14-5.58], P = 0.0224). The 7-day point prevalence of vaping abstinence was also higher for the varenicline than placebo at each time point. Serious adverse events were infrequent in both groups and not treatment-related. CONCLUSIONS: The findings of the present RCT indicate that inclusion of varenicline in a vaping cessation program for people who use electronic cigarettes and intending to quit may result in prolonged abstinence. These positive findings establish a benchmark of intervention effectiveness, may support the use of varenicline combined with counseling in vaping cessation programs, and may also help guiding future recommendations by health authorities and healthcare providers. TRIAL REGISTRATION: The study has been registered in EUDRACT with Trial registration ID: 2016-000339-42.

Genotyping, characterization, and imputation of known and novel CYP2A6 structural variants using SNP array data.

CYP2A6 metabolically inactivates nicotine. Faster CYP2A6 activity is associated with heavier smoking and higher lung cancer risk. The CYP2A6 gene is polymorphic, including functional structural variants (SV) such as gene deletions (CYP2A6*4), duplications (CYP2A6*1 × 2), and hybrids with the CYP2A7 pseudogene (CYP2A6*12, CYP2A6*34). SVs are challenging to genotype due to their complex genetic architecture. Our aims were to develop a reliable protocol for SV genotyping, functionally phenotype known and novel SVs, and investigate the feasibility of CYP2A6 SV imputation from SNP array data in two ancestry populations. European- (EUR; n = 935) and African- (AFR; n = 964) ancestry individuals from smoking cessation trials were genotyped for SNPs using an Illumina array and for CYP2A6 SVs using Taqman copy number (CN) assays. SV-specific PCR amplification and Sanger sequencing was used to characterize a novel SV. Individuals with SVs were phenotyped using the nicotine metabolite ratio, a biomarker of CYP2A6 activity. SV diplotype and SNP array data were integrated and phased to generate ancestry-specific SV reference panels. Leave-one-out cross-validation was used to investigate the feasibility of CYP2A6 SV imputation. A minimal protocol requiring three Taqman CN assays for CYP2A6 SV genotyping was developed and known SV associations with activity were replicated. The first domain swap CYP2A6-CYP2A7 hybrid SV, CYP2A6*53, was identified, sequenced, and associated with lower CYP2A6 activity. In both EURs and AFRs, most SV alleles were identified using imputation (>70% and >60%, respectively); importantly, false positive rates were <1%. These results confirm that CYP2A6 SV imputation can identify most SV alleles, including a novel SV.

Concurrent Choice Assessment of Preference and Substitutability of E-cigarettes and Heated Tobacco Products for Combustible Cigarettes Among African American and White Smokers.

INTRODUCTION: Alternative nicotine delivery products, including electronic cigarettes (e-cigarettes) and heated tobacco products (HTPs), contain fewer toxicants than combustible cigarettes and offer a potential for harm reduction. Research on the substitutability of e-cigarettes and HTPs is crucial for understanding their impact on public health. This study examined subjective and behavioral preferences for an e-cigarette and HTP relative to participants' usual brand combustible cigarette (UBC) in African American and White smokers naïve to alternative products. AIMS AND METHODS: Twenty-two adult African American (n = 12) and White (n = 10) smokers completed randomized study sessions with their UBC and study provided e-cigarette and HTP. A concurrent choice task allowed participants to earn puffs of the products but placed UBC on a progressive ratio schedule, making puffs harder to earn, and e-cigarette and HTP on a fixed ratio schedule to assess behavioral preference for the products. Behavioral preference was then compared to self-reported subjective preference. RESULTS: Most participants had a subjective preference for UBC (n = 11, 52.4%), followed by an equal preference for e-cigarette (n = 5, 23.8%) and HTP (n = 5, 23.8%). During the concurrent choice task, participants showed a behavioral preference (i.e., more earned puffs) for the e-cigarette (n = 9, 42.9%), followed by HTP (n = 8, 38.1%), and UBC (n = 4, 19.1%). Participants earned significantly more puffs of the alternative products compared to UBC (p = .011) with no difference in earned puffs between e-cigarettes and HTP (p = .806). CONCLUSIONS: In a simulated lab setting, African American and White smokers were willing to substitute UBC for an e-cigarette or HTP when the attainment of UBC became more difficult. TRIAL REGISTRATION: NCT04646668. IMPLICATIONS: Findings suggest that African American and White smokers are willing to substitute their UBC for an alternative nicotine delivery product (e-cigarette or HTP) when the attainment of cigarettes became more difficult in a simulated lab setting. Findings require confirmation among a larger sample under real-world conditions but add to growing evidence suggesting the acceptability of alternative nicotine delivery products among racially diverse smokers. These data are important as policies that limit the availability or appeal of combustible cigarettes are considered or enacted.

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial.

BACKGROUND: As the US Food and Drug Administration takes regulatory action on menthol cigarettes, debate continues about how restricting menthol e-liquids might impact adult menthol smokers in switching to e-cigarettes. METHODS: Switching patterns and e-cigarette acceptability were assessed at week 6 among 64 black and Latinx menthol cigarette smokers who used JUUL menthol (n=39) or non-menthol e-cigarettes ((n=25), primarily mint or mango) as part of a randomised switching trial. RESULTS: No clear evidence of effects was found between menthol versus non-menthol e-cigarettes on use or subjective effects/acceptability, effect sizes for all comparisons were small (effect size=0.0-0.2), and Bayes factor ranged from 0.10 to 0.15. Specifically, 82.1% of participants who used menthol-flavoured e-cigarettes fully or partially switched to e-cigarettes compared with 88.0% of participants who used a non-menthol (p=0.75). Further, both groups demonstrated substantial reductions in cigarettes per day (menthol e-cigarettes: -8.5±10.4 vs non-menthol e-cigarettes: -8.8±5.8, p=0.87), comparable grams of e-liquid consumed (menthol e-cigarettes: 9.2±9.8 g vs non-menthol e-cigarettes: 11.0±11.0 g, p=0.47), and positive subjective effects, including 'just right' throat hit (menthol e-cigarettes: 70.7% vs non-menthol e-cigarettes: 66.7%, p=0.93) and flavour liking (menthol e-cigarettes: 75.6% vs non-menthol e-cigarettes: 66.7%, p=0.32). CONCLUSIONS: Both menthol and non-menthol e-cigarettes were associated with high rates of use and acceptability among menthol smokers. Findings require confirmation in a fully powered non-inferiority or equivalence study but provide preliminary evidence to inform regulatory action on menthol e-cigarettes that could slow youth initiation without impacting black and Latinx menthol cigarette smokers interested in switching to e-cigarettes. TRIAL REGISTRATION NUMBER: NCT03511001.

Maternal smoking in pregnancy and blood pressure during childhood and adolescence: a meta-analysis.

Arterial hypertension during childhood or adolescence is rising, and smoking during pregnancy may constitute a modifiable risk factor. This study aims to evaluate the effect of maternal smoking during pregnancy on diastolic (DBP) and systolic blood pressure (SBP) in childhood and adolescence. A bibliographic search was conducted in PubMed, Embase, and CENTRAL databases in March 2022. Meta-analysis was performed with the difference in mean-adjusted SBP/DBP of children and adolescents aged 3-17 years, according to maternal smoking/non-smoking in pregnancy. A random effects model was applied; a leave-one-out analysis and meta-analysis by subgroups were performed. A modified Newcastle-Ottawa scale was used to assess the quality of the studies. Evidence levels were rated using the GRADE system. Fifteen studies were included in the meta-analysis; all of them evaluated the mean-adjusted SBP difference in children or adolescents (N = 73,448), and 6 also that of DBP (N = 31,459). Results showed that maternal smoking during pregnancy significantly increased SBP (ß = 0.31 mmHg 95% CI 0.14-0.49). A greater increase in mean-adjusted SBP was observed in those studies that completed the recruitment before 1990, were conducted in non-European countries, used standard mercury or manual sphygmomanometry, adjusted for birth weight, and were in the lowest quality subgroup. No significant association was found for DBP. The GRADE level of evidence was low for SBP and very low for DBP. CONCLUSION: Smoking in pregnancy might increase SBP in childhood and adolescence. Due to the low level of evidence, solid inferences cannot be drawn about the clinical relevance of these findings. WHAT IS KNOWN: • AHT is the leading cause of premature death among adults worldwide. • Deleterious effects derived from SHS exposure on children's health have been documented since early 1970. To date, there are contradictory results about the effects of prenatal SHS exposure on children's BP. WHAT IS NEW: • Smoking in pregnancy may increase SBP during childhood and adolescence. • Maternal smoking during pregnancy could have greater influence on their offspring's SBP than on DBP.

Short- and Long-Term Cigarette and Tobacco Abstinence Among Daily and Nondaily Older Smokers.

INTRODUCTION: There is mixed evidence regarding whether older (vs. younger) smokers are more or less likely to quit smoking. We examined how age is associated with cigarette and all tobacco product abstinence and the potential moderating effects of smoking frequency. AIMS AND METHODS: Data from a 4-year cohort of the Population Assessment of Tobacco and Health (PATH) study were used, including 7512 smokers at Wave 1 who had smoking status data at Wave 4. Logistic regression models were used to examine the effects of age (18-24, 25-34, 35-44, 45-54, and ≥55 years) on Wave 4, 30-day and 12-month cigarette and all tobacco product abstinence, adjusting for covariates and the interaction between age and cigarette use frequency (nondaily, light daily, and heavy daily). RESULTS: Older smokers (≥55 years) were more likely to be heavy daily smokers than younger smokers 18-24 and 25-34 years, but were less likely to have a past-year cigarette quit attempt. Younger smokers 45-54 years were less likely to report 12-month cigarette abstinence than older smokers (odds ratio = 0.72 [0.54-0.95]). Younger smokers 18-24 and 45-54 years were less likely to report 12-month tobacco product abstinence than older smokers (odds ratio = 0.65 [0.45-0.93]; odds ratio = 0.73 [0.55-0.96], respectively). Thirty-day cigarette abstinence significantly decreased as age increased for nondaily smokers, significantly increased for heavier daily smokers, but remained similar across age for light daily smokers. CONCLUSIONS: Older smokers were more likely to report 12-month cigarette and tobacco abstinence than younger smokers 45-54 years old, and the effect of age on abstinence differed by smoking frequency/intensity. Smoking cessation interventions need to be age specific and consider smoking frequency. IMPLICATIONS: This study shows that although older smokers are more likely to be heavy smokers and less likely to have a quit attempt at baseline, they are more likely to have 12-month cigarette and tobacco abstinence than younger smokers. Furthermore, 30-day cigarette abstinence significantly decreases as age increases for nondaily smokers and significantly increases for heavy daily smokers, suggesting that the effect of cigarette smoking frequency and intensity changes with age. Smoking cessation interventions need to be age specific as well as consider the smoking frequency/intensity of each age group. Younger smokers may need more targeted cessation interventions to successfully quit.

Effects of Marijuana Use on Smokers Switching to E-Cigarettes in a Randomized Clinical Trial.

INTRODUCTION: Co-use of tobacco and marijuana is common, and research suggests that marijuana use may be a barrier to smoking cessation. Research to date has not evaluated how marijuana use affects e-cigarette switching behaviors and related outcomes in a harm reduction trial. AIMS AND METHODS: This secondary analysis includes African American (48%) and Latinx (52%) adult smokers randomized to the e-cigarette group (N = 114) of a harm reduction clinical trial from 2018 to 2019. Participants were provided JUUL e-cigarettes and encouraged to make an exclusive switch for 6 weeks. Our primary outcome was cigarettes smoked per week. Secondary health outcomes were e-cigarette substitution (calculated by measuring e-cigarette pod use), expired carbon monoxide (CO), and respiratory symptoms. Marijuana products were recorded at three timepoints and coded for combustion. RESULTS: Marijuana use during the study (n = 52, 46%) was not associated with week 6 cigarettes smoked or e-cigarette substitution, and combustible marijuana use was not associated with week 6 respiratory symptoms (ps > .05). After controlling for cigarettes smoked at week 6, combustible marijuana use was significantly associated with a 4.4 ppm increase in CO compared with no use of marijuana (p = .001). CONCLUSIONS: Marijuana use was not a barrier to switching to e-cigarettes in this 6-week trial. Marijuana use contributed to elevated CO, reflecting greater exposure to toxic combustion products, beyond the effects of cigarette smoking. Marijuana co-use may increase risk of adverse health outcomes and may be a confounding factor when using CO as an endpoint to bioverify exclusive e-cigarette use. IMPLICATIONS: This is the first known study to examine the effects of marijuana use on smokers switching to e-cigarettes. Marijuana use was not a barrier to cigarette reduction in a 6-week randomized clinical trial. Marijuana use uniquely contributed to higher carbon monoxide among cigarette smokers, indicating greater exposure to toxic combustion products, which could increase risk of adverse health outcomes. Furthermore, combustible marijuana use may be a confounding factor when CO is used as an endpoint to bioverify exclusive e-cigarette use.

Effect of Varenicline Added to Counseling on Smoking Cessation Among African American Daily Smokers: The Kick It at Swope IV Randomized Clinical Trial.

Importance: African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels. Objectives: To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers. Design, Setting, and Participants: The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018. Interventions: Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]). Main Outcomes and Measures: The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d). Results: Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]). Conclusions and Relevance: Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers. Trial Registration: ClinicalTrials.gov Identifier: NCT02360631.

Harm Reduction Associated with Dual Use of Cigarettes and e-Cigarettes in Black and Latino Smokers: Secondary Analyses from a Randomized Controlled e-Cigarette Switching Trial.

INTRODUCTION: Most adult cigarette smokers who use e-cigarettes are dual cigarette and e-cigarette (CC-EC) users, yet little is known about relative consumption of cigarettes to e-cigarettes and any associated harm reduction. METHODS: Rate of substitution from cigarettes to e-cigarettes at week 6 and change in biomarkers of exposure and potential harm were examined among dual dual cigarette and e-cigarette users [64/114 (56%); 35 Black, 29 Latino] in an e-cigarette switching randomized trial. RESULTS: Dual users averaged 79% substitution of cigarettes for e-cigarettes at week 6, resulting in a reduction from baseline of 70.0 ± 54.1 cigarettes per week (p < .001). Total nicotine consumption remained stable (baseline: 1160.5 ± 1042.1 pg/mL of cotinine, week 6: 1312.5 ± 1725.9 pg/mL of cotinine, p = .47), while significant reductions were seen in the potent lung carcinogen 4-(methylnitrosamino)-1-(3-pyridul)-1-butanol (NNAL) (-55.9 ± 88.6 ng/ml, p < .001), carbon monoxide (-6.3 ± 8.6 ppm, p < .001), and self-reported respiratory symptoms (-3.3 ± 8.0, p = .002). No significant changes were found in blood pressure or spirometry. Greater substitution from cigarettes to e-cigarettes was associated with larger reductions in NNAL (r = -.29, p = .02). CONCLUSIONS: The predominant dual-use pattern was characterized by regular e-cigarette and intermittent cigarette use. Findings demonstrate the short-term harm reduction potential of this dual-use pattern in Black and Latino smokers and suggest that the greatest benefit, aside from cessation of both products, is achieved by higher substitution of e-cigarettes for cigarettes. Findings need confirmation in a larger sample with longer follow-up in dual users with greater variability in the rate of substitution. CLINICALTRIALS.GOV IDENTIFIER: NCT03511001. IMPLICATIONS: Findings suggest short-term harm reduction potential of dual cigarette-e-cigarette use for Black and Latino smokers. Results also demonstrate the heterogeneity of dual-use, with the greatest harm reduction seen in dual users with higher rates of substitution from cigarettes to e-cigarettes. Study results should be confirmed in a full clinical trial with long-term follow-up to evaluate maintenance of dual-use patterns and associated harm reduction potential over time.

"It is the One Thing that has Worked": facilitators and barriers to switching to nicotine salt pod system e-cigarettes among African American and Latinx people who smoke: a content analysis.

BACKGROUND: Electronic cigarettes are a harm reduction strategy for individuals who smoke cigarettes who cannot or do not want to quit using FDA-approved cessation methods. Identifying perceived facilitators and barriers to switching among people who smoke cigarettes is critical to optimizing health impact. This is particularly important for the most dominant e-cigarette device, nicotine salt pod electronic cigarettes. We investigate the experience using pod electronic cigarettes among African American and Latinx individuals who smoke, the two largest racial/ethnic minority groups who experience significant health disparities. METHODS: From July 2018 to May 2019, adults who smoked cigarettes, age 21 + (N = 114; M age = 44.6, 59.6% male, 52.6% African American from Kansas City, 47.4% Latinx from San Diego) received JUUL-brand electronic cigarettes (referred to hereafter as JUUL) for 6 weeks and answered interview questions at week six. We inquired what they liked and disliked about using JUUL, what helped with switching and made switching difficult, future intentions for continued JUUL use, and how JUUL compared to past smoking reduction methods. Responses were coded into themes by independent raters. Theme frequencies were analyzed separately by race/ethnicity and week 6 use trajectory (exclusive JUUL use, dual JUUL and cigarette use, exclusive cigarette use). RESULTS: Clean/smell was the aspect of using JUUL most commonly liked (23%), followed by convenience (19%). Coughing/harshness was a more common barrier to switching for African American (44%) than Latinx (9%), and for continuing cigarette use (56%) than for those who exclusively switched or dually used JUUL and combustible cigarettes (15-21%). Most (78% African American; 90% Latinx) reported that the benefits of using JUUL outweighed barriers, and this varied by JUUL use trajectory: 94% exclusive switch, 86% dual use, and 42% continued cigarette use. The majority said they would continue using JUUL to replace cigarettes (83% African American; 94% Latinx) and that JUUL worked better than other methods to reduce cigarettes (72%). CONCLUSION: African American and Latinx individuals who smoked experience using pod electronic cigarettes was generally positive. Understanding facilitators and impediments to switching to electronic cigarettes among racial/ethnic minority people who smoke can inform harm reduction interventions and reduce tobacco-related health disparities. Trial Registration ClinicalTrials.gov Identifier: NCT03511001 posted April 27, 2018.

Children Learning About Secondhand Smoke (CLASS II): A Pilot Cluster Randomized Controlled Trial.

INTRODUCTION: Children exposed to secondhand smoke (SHS) are at increased risk of respiratory illnesses. We piloted a Smoke Free Intervention (SFI) and trial methods before investigating its effectiveness and cost-effectiveness in primary school children. METHODS: In a pilot cluster randomized controlled trial in Bangladesh, primary schools were allocated to usual education (control) or SFI, using minimization. Year-5 children were recruited. Masking treatment allocation was not possible. Delivered by schoolteachers, SFI consisted of two 45-min and four 15-min educational sessions. Our primary outcome was SHS exposure at two months post randomization, verified by children's salivary cotinine. The trial is registered at ISRCTN.com; ISRCTN68690577. RESULTS: Between April 1, 2015 and June 30, 2015, we recruited 12 schools. Of the 484 children present in Year-5, 481 consented. Six schools were allocated to both SFI (n = 245) and to usual education only (n = 236). Of them, 450 children (SFI = 229; control = 221) who had cotinine levels indicative of SHS exposure were followed-up. All schools were retained, 91% children (208/229) in SFI and 88% (194/221) in the control arm completed primary outcome assessment. Their mean cotinine at the cluster level was 0.53 ng/ml (SD 0.36) in SFI and 1.84 ng/ml (SD 1.49) in the control arm-a mean difference of -1.31 ng/ml (95% CI = -2.86 to 0.24). CONCLUSION: It was feasible to recruit, randomize, and retain primary schools and children in our trial. Our study, though not powered to detect differences in mean cotinine between the two arms, provides estimates to inform the likely effect size for future trials. IMPLICATIONS: In countries with high smoking prevalence, children remain at risk of many conditions due to secondhand smoke exposure. There is little empirical evidence on the effectiveness and cost-effectiveness of interventions that can reduce their exposure to secondhand smoke at homes. CLASS II trial found that a school-based intervention (SFI) has the potential to reduce children's exposure to SHS-an approach that has been rarely used, but has considerable merit in school-based contexts. CLASS II trial provides key information to conduct a future definitive trial in this area of public health, which despite its importance has so far received little attention.

Intent to quit, quit attempts, and perceived health risk reduction among African American, Latino, and White nondaily and daily smokers in the United States.

Objective: Ethnic and racial differences in smoking patterns and behaviors have been well documented and most African American and Latino smokers are nondaily or light smokers. However, differences within smoking levels are understudied. Our primary aim was to determine whether there are racial and ethnic differences among African American, Latino, and White nondaily, light daily, and moderate to heavy daily smokers on (1) perceived health risk reduction, (2) intentions to quit, and (3) past year quit attempts. Design: Smokers were recruited through an online research panel for a cross-sectional survey (n = 2376). Sampling quotas were used to obtain equal numbers of African American, Latino, and White nondaily and daily smokers. Results: African American (59.6%) and Latino (54%) nondaily smokers were more likely than White nondaily smokers (45%) to currently limit their cigarettes per day (cpd) as a perceived health risk reduction strategy (p < 0.05). African American nondaily smokers were more likely than Latino and White nondaily smokers (p < 0.05) to limit their smoking in the past year as a perceived health risk reduction strategy (range: 0 'never' to 5 'always'; Means = 3.2, 2.9, 3.0, standard deviations [SD] = 1.1, 1.1, 1.2, respectively). African American nondaily smokers (15%) were more likely than either Latinos (7.8%) or Whites (8.5%) to intend to quit in the next 30 days (p < 0.01). African American (61.6%) and Latino (60.3%) nondaily smokers were more likely than Whites (49%) to have made a quit attempt in the past year (p < 0.01). Fewer racial and ethnic differences were found among daily smokers. Conclusions: Racial and ethnic group differences were more pronounced among nondaily smokers compared to light daily smoker and moderate to heavy daily smokers. Smoking level is an important consideration in understanding racial and ethnic variation in perceived health risk reduction and cessation-related behaviors.

Analysis of self-report and biochemically verified tobacco abstinence outcomes with missing data: a sensitivity analysis using two-stage imputation.

BACKGROUND: Missing data are common in tobacco studies. It is well known that from the observed data alone, it is impossible to distinguish between missing mechanisms such as missing at random (MAR) and missing not at random (MNAR). In this paper, we propose a sensitivity analysis method to accommodate different missing mechanisms in cessation outcomes determined by self-report and urine validation results. METHODS: We propose a two-stage imputation procedure, allowing survey and urine data to be missing under different mechanisms. The motivating data were from a tobacco cessation trial examining the effects of the extended vs. standard Quit and Win contests and counseling vs. no counseling under a 2-by-2 factorial design. The primary outcome was 6-month biochemically verified tobacco abstinence. RESULTS: Our proposed method covers a wide spectrum of missing scenarios, including the widely adopted "missing = smoking" imputation by assuming a perfect smoking-missing correlation (an extreme case of MNAR), the MAR case by assuming a zero smoking-missing correlation, and many more in between. The analysis of the data example shows that the estimated effects of the studied interventions are sensitive to the different missing assumptions on the survey and urine data. CONCLUSIONS: Sensitivity analysis has played a crucial role in assessing the robustness of the findings in clinical trials with missing data. The proposed method provides an effective tool for analyzing missing data introduced at two different stages of outcome assessment, the self-report and validation time. Our methods are applicable to trials studying biochemically verified abstinence from alcohol and other substances.