Differential effects of cigarette smoking on cardiovascular disease in females: A narrative review and call to action.

OBJECTIVE: Cigarette smoking continues to be a major driver in the incidence and progression of cardiovascular disease (CVD). As females become an increasingly larger fraction of those who smoke it is imperative that the sex-specific effects of smoking be further explored and acted upon. METHODS: This narrative review describes current evidence on the differential effects of smoking on CVD in females and the need to improve treatment. RESULTS: Evidence to date suggests that smoking has disproportionately negative effects on the cardiovascular (CV) system in females, especially in those who are younger. Usually, the onset of CVD is later in females than males, but smoking decreases or eliminates this gap. Females are also more likely to develop types of CVD closely tied to smoking, such as ST-elevated myocardial infarctions, with even higher rates among those who are younger. Possible mechanisms for these worse outcomes in females include a complex interplay between nicotine, other products of combusted cigarettes, and hormones. Sex differences also exist in treatment for smoking. In females, Varenicline appears more effective than either Bupropion or nicotine replacement therapy while in males, all three therapies show similar efficacy. Disparities in smoking are also apparent in secondary prevention settings. Females and males are entering secondary prevention with equal rates of smoking, with potentially higher levels of exposure to the byproducts of smoking in females. CONCLUSIONS: These disproportionately negative outcomes for females who smoke require additional research and these persisting rates of smoking suggest a need for female-specific approaches for treating smoking.

Electronic nicotine delivery systems (ENDS): Frequency of use and smoking-cessation efforts among U.S. women of reproductive age.

OBJECTIVE: Reducing harm from combustible cigarette use among women of reproductive age (WRA) is critical given their potential vulnerability to multigenerational adverse impacts of cigarette smoking. Although electronic nicotine delivery systems (ENDS) are not approved smoking cessation aids in the US, many WRA who smoke report using ENDS to help quit smoking. Associations between ENDS use patterns and smoking-cessation efforts among US WRA remain unclear. METHODS: Using the Population Assessment of Tobacco and Health (PATH) Study, we examined whether baseline (Wave 3 or 4) ENDS use frequency predicted (a) making a cigarette quit attempt (QA) and (b) successful quitting by follow-up (Wave 4 or 5, respectively) among WRA (N = 2834; 72.1% non-Hispanic White). RESULTS: Daily ENDS use predicted greater adjusted odds of making a QA than non-daily (AOR = 1.63, 95% CI = 1.03, 2.59) and no ENDS use (AOR = 1.97, 95% CI = 1.23, 3.14), and greater odds of successful smoking cessation than non-daily use (AOR = 2.37, 95% CI = 1.31, 4.26). Daily ENDS use did not significantly improve odds of successful smoking cessation compared to no ENDS use (AOR = 1.62, 95% CI = 0.97, 2.69). Non-daily ENDS use did not significantly improve odds of making a QA (AOR = 1.21, 95% CI = 0.94, 1.56) and hindered successful smoking cessation compared to no ENDS use (AOR = 0.68, 95% CI = 0.48, 0.98). CONCLUSIONS: These findings suggest that benefits of ENDS for smoking cessation in WRA may be greatest among those who use ENDS daily. WRA who choose to use ENDS to help quit would be well-informed by evidence that non-daily ENDS use may impede smoking cessation.

Sex differences in tobacco use, attempts to quit smoking, and cessation among dual users of cigarettes and e-cigarettes: Longitudinal findings from the US Population Assessment of Tobacco and Health Study.

SIGNIFICANCE: A growing number of adults use more than one tobacco product, with dual use of cigarettes and e-cigarettes being the most common combination. Monitoring sex disparities in tobacco use is a public health priority. However, little is known regarding whether dual users differ by sex. METHODS: Data came from Waves 4-6 (12/2016-11/2021) of the Population Assessment of Tobacco and Health Study, a US nationally-representative longitudinal survey. This analysis included current adult dual users of cigarettes and e-cigarettes. We used weighted generalized estimating equations to assess the association between sex and (1) making a cigarette quit attempt (n = 1882 observations from n = 1526 individuals) and (2) smoking cessation (n = 2081 observations from n = 1688 individuals) across two wave pairs, adjusting for age, education, ethnicity, time-to-first cigarette after waking, and e-cigarette use frequency. RESULTS: Among US dual users, 14.1% (95% Confidence Intervals [Cl] = 11.9-16.4) of females and 23.4% (20.0-26.9) of males were young adults (aged 18-24), 11.7% (9.2-14.2) of females and 14.4% (11.6-17.2) of males had

A call to action: Contingency management to improve post-release treatment engagement among people with opioid use disorder who are incarcerated.

People with opioid use disorder (OUD) are overrepresented in US correctional facilities and experience disproportionately high risk for illicit opioid use and overdose after release. A growing number of correctional facilities offer medication for OUD (MOUD), which is effective in reducing these risks. However, a recent evaluation found that <50% of those prescribed MOUD during incarceration continued MOUD within 30 days after release, demonstrating a need to improve post-release continuity of care. We describe available evidence on contingency management (CM), an intervention wherein patients receive incentives contingent on behavior change, to achieve this goal. A prior systematic review reported strong evidence in support of CM for increasing treatment adherence in MOUD programs, but the trials reviewed did not include incarcerated participants. Research on CM to increase treatment adherence among participants in the criminal justice system is limited with mixed findings. However, in comparison to the trials that supported CM's efficacy in the community, CM trials in the criminal justice system provided smaller rewards with greater delays in the delivery of rewards to patients, which likely contributed to null findings. Indeed, a prior meta-analysis demonstrates a dose-response relationship between the magnitude and immediacy of reward and CM effectiveness. Thus, CM involving larger and more immediately delivered rewards are likely necessary to improve MOUD adherence during the critical period following release from incarceration. Future research on the effectiveness and implementation of CM to improve MOUD retention after release from incarceration is warranted.

Interest in quitting e-cigarette use by device type and smoking history in US adults.

BACKGROUND: The use of e-cigarettes has been increasing, especially since the introduction of 'pod' devices to the marketplace since 2018. Most adults who vape report interest in quitting. The present study examined level of interest in e-cigarette cessation between users with varying cigarette smoking histories and device types. METHODS: Data obtained from wave 5 (2018-2019) of the Population Assessment of Tobacco and Health study (n=34 309). Analyses were conducted on adult current established e-cigarette users, categorised on cigarette smoking history (current, former or never) and device type (disposable, cartridge/pod, tank or mod). Participants reported if they planned to ever quit e-cigarettes, attempted to quit in the past year and attempted to quit by cutting back in the past year. RESULTS: Of the 2922 established e-cigarette users, 68.21% reported plans to quit vaping; 17.27% reported attempting to quit e-cigarettes in the past year; and 29.28% reported attempting to quit by cutting back in the past year. Cartridge users had higher odds of interest in quitting than tank and mod users. Disposable and cartridge users had higher odds of reporting a past year quit attempt than tank and mod users. Individuals with no smoking history had higher odds of reporting a past year quit attempt or cutting back relative to those reporting dual use (of both e-cigarettes and cigarettes) and former smoking. CONCLUSIONS: Tobacco control should consider the type of e-cigarette device that is being used, alongside users' cigarette smoking history, when developing interventions and other resources for vaping cessation.

Antidepressants for smoking cessation.

BACKGROUND: The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. OBJECTIVES: To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropouts due to treatment. We carried out meta-analyses where appropriate. MAIN RESULTS: We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results.  There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. AUTHORS' CONCLUSIONS: There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.

Latent Classes of Perceived Addictiveness Predict Marijuana, Alcohol, and Tobacco Use in Youth and Young Adults.

Background: Mass media substance use prevention efforts target addiction perceptions in young people. This study examined youth and young adults' (YAs) perceived addictiveness across several substances and the associations between addiction perceptions and substance use. Methods: Data were collected in 2019 in an online cohort study of Vermonters aged 12-25. Latent class analyses grouped participants by perceived addictiveness of nicotine, caffeine, alcohol, marijuana, cigarettes, electronic vapor products (EVPs), and opioids. Bivariate multinomial logistic and modified Poisson regression estimated associations between sociodemographics, substance use correlates, and subsequent use across latent classes. Results: Four latent classes captured addiction perceptions: high perceived addictiveness of EVPs, cigarettes, marijuana, and alcohol (Class 1: n = 317; 31.3%), low perceived addictiveness of marijuana, alcohol, and caffeine (Class 2: n = 151; 14.3%), low perceived addictiveness of marijuana (Class 3: n = 581; 46.5%), and low perceived addictiveness of nicotine, cigarettes, and EVPs (Class 4: n = 83; 7.9%). For each year increase in age, there was a 36% increased likelihood of being in Class 2 (vs. Class 1) and a 148% increased likelihood of belonging to Class 3 (vs. Class 1). Low perceived addictiveness classes were associated with ever and past 30-day marijuana and alcohol use and predicted past 30-day alcohol use at three-month follow-up. Membership in Classes 2 and 3 also predicted past 30-day marijuana use at Wave 3. Discussion: The strong association between age and latent classes defined by low perceived addictiveness suggests age group differences in addiction perceptions. Findings suggest that YAs may benefit from prevention messaging on addictiveness.

Tailored text message and web intervention for smoking cessation in U.S. socioeconomically-disadvantaged young adults: A randomized controlled trial.

The prevalence of cigarette smoking in young adults is higher among those with socioeconomic disadvantage than those without. Low treatment-seeking among young adult smokers is compounded by few efficacious smoking cessation interventions for this group, particularly socioeconomically-disadvantaged young adults (SDYA) who smoke cigarettes. The goal of this study was to test a tailored smoking-cessation intervention for SDYA. 343 SDYA aged 18-30 living in the U.S. (85% female) who smoke cigarettes with access to a smartphone and interest in quitting smoking in the next six months were recruited online in Spring 2020 and randomized to referral to online quit resources (usual care control; n = 171) or a 12-week tailored text message smoking-cessation program with a companion web-based intervention (n = 172). Intent to treat analyses examined associations between study condition, self-reported 30-day point prevalence abstinence (PPA), and confidence to quit smoking at 12 weeks, controlling for potential confounders. Intervention group participants had greater self-reported 30-day PPA at 12-weeks than controls (adjusted relative risk 3.93, 95% CI 2.14-7.24). Among those who continued smoking, the intervention increased confidence to quit (0.81 points, 95% confidence interval 0.08-1.53). Weekly engagement in the intervention predicted greater cessation. A tailored text message intervention for SDYA increased smoking abstinence and confidence to quit at the end-of-treatment. Findings may have been influenced by recruitment at the start of the COVID pandemic but suggest that text messaging is an acceptable and efficacious cessation strategy for SDYA smokers. Future studies should examine the impact on longer-term smoking-cessation and importance of intervention tailoring for SDYA.

Smoking abstinence and cessation-related outcomes one month after an immediate versus gradual reduction in nicotine content of cigarettes.

The United States Food and Drug Administration has the authority to reduce the nicotine content in cigarettes to minimal or non-addictive levels and could do so immediately or gradually over time. A large clinical trial compared the two approaches. This secondary analysis assesses abstinence and cessation-related outcomes one month after the trial concluded, when participants no longer had access to very low nicotine content (VLNC) research cigarettes. Smokers not interested in quitting (N = 1250) were recruited for the parent trial from 2014 to 2016 across 10 sites throughout the US and randomized to a 20-week study period during which they immediately switched to VLNC cigarettes, gradually transitioned to VLNC cigarettes with five monthly dose reductions, or smoked normal nicotine research cigarettes (control). At the one-month follow-up, both immediate and gradual reduction resulted in greater mean cigarette-free days (4.7 and 4.6 respectively) than the control group (3.2, both p < .05). Immediate reduction resulted in fewer mean cigarettes per day (CPD = 10.3) and lower Fagerström Test for Cigarette Dependence (FTCD = 3.7) than the gradual (CPD = 11.7, p = .001; FTCD = 3.8, p = .039) and control (CPD = 13.5, p < .001; FTCD = 4.0, p < .001) groups. Compared to controls, gradual reduction resulted in reduced CPD (p = .012) but not FTCD (p = .13). Differences in CO-verified 7-day point-prevalence abstinence were not significant. Findings demonstrate that switching to VLNC cigarettes resulted in reduced smoking and nicotine dependence severity that was sustained for at least a month after the VLNC trial period in smokers who were not interested in cessation. The greatest harm reduction endpoints were observed in those who immediately transitioned to VLNC cigarettes.

Trajectories of ENDS and cigarette use among dual users: analysis of waves 1 to 5 of the PATH Study.

INTRODUCTION: Concurrent electronic nicotine delivery system (ENDS) and cigarette (dual) use is harmful. Identifying longitudinal trajectories of ENDS and cigarette use among dual users can help to determine the public health impact of ENDS and inform tobacco control policies and interventions. OBJECTIVES: (1) To identify independent and joint trajectories of ENDS and cigarette use among wave (W) 1 adult dual users across W1 to W5 of the Population Assessment of Tobacco and Health (PATH) Study; and (2) identify W1 predictors of ENDS and cigarette joint trajectory group membership. METHODS: We used group-based trajectory modelling to estimate independent and joint trajectories of ENDS and cigarette use from wave 1 (W1; 2013-2014) to wave 5 (W5; 2018-2019) among W1 adult established dual users of ENDS and cigarettes (n=545) from the PATH Study. We used multinomial logistic regression to identify W1 predictors of joint trajectories. RESULTS: Two ENDS (early quitters=66.0%, stable users=34.0%) and three cigarette (stable users=55.2%, gradual quitters=27.3%, early quitters=17.5%) trajectories of W1 were identified. In joint trajectory analysis, 41.6% of participants were early ENDS quitters and stable cigarette users; 14.8% early ENDS quitters and gradual cigarette quitters; 14.6% stable ENDS users and stable cigarette users; 11.2% stable ENDS users and gradual cigarette quitters; 10.3% early ENDS quitters and early cigarette quitters; and 7.4% stable ENDS users and early cigarette quitters. Cigarette and ENDS use frequency, nicotine dependence, cannabis use and other non-combusted tobacco product use predicted trajectory group membership (p values <0.05). CONCLUSIONS: Most dual users maintained long-term cigarette smoking or dual use, highlighting the need to address cessation of both products. Continued monitoring of trajectories and their predictors is needed, given ongoing changes to the ENDS marketplace.

Looking to the empirical literature on the potential for financial incentives to enhance adherence with COVID-19 vaccination.

COVID-19 vaccination efforts are underway offering hope for saving lives and eliminating the pandemic. The most promising vaccines require two injections separated 3-4 weeks apart. To achieve heard immunity, 70-90% of the population or perhaps more must be inoculated. Anticipation of adherence challenges has generated commentaries on strategies to enhance adherence including financial incentives. A notable gap in these commentaries is any discussion of the scientific evidence regarding the efficacy of financial incentives for increasing vaccine adherence. This commentary addresses that gap. There is a body of controlled trials on incentivizing vaccine adherence, mostly to the hepatitis B virus (HBV) vaccine among injection drug users (IDUs). Prevalence of HBV infection is increasing as part of the opioid addiction crisis. The HBV vaccine entails a three-dose regimen (typically 0, 1, and 6 months) which has created adherence challenges among IDUs. Systematic literature reviews document significant benefit of financial incentives. For example, a 2019 meta-analysis (Tressler & Bhandari, 2019) examined 11 controlled trials examining HBV-vaccine adherence strategies, including financial incentives, accelerated dosing schedules, and case-management/enhanced services. Financial incentives were most effective resulting in a 7-fold increase in adherence to the vaccination regimen relative to no financial incentives (OR, 7.01; 95% CI, 2.88-17.06). Additional reviews provide further support for the efficacy of financial incentives for promoting adherence with vaccination (HBV & influenza). Overall, this literature suggests that financial incentives could be helpful in promoting the high levels of adherence to COVID-19 vaccines that experts project will be necessary for herd immunity.

State-level rurality and cigarette smoking-associated cancer incidence and mortality: Do individual-level trends translate to population-level outcomes?

County-level analyses demonstrate that overall cancer incidence is generally lower in rural areas, though incidence and mortality from tobacco-associated cancers are higher than in non-rural areas and have experienced slower declines over time. The goal of our study was to examine state-level rurality and smoking-related cancer outcomes. We used publicly-available national data to quantify rurality, cigarette smoking prevalence, and smoking-attributable cancer incidence and mortality at the state level and to estimate the population-attributable fraction of cancer deaths attributable to smoking for each state, overall and by gender, for 12 smoking-associated cancers. Accounting for a 15-year lag between smoking exposure and cancer diagnosis, the median proportion of smoking-attributable cancer deaths was 28.2% in Virginia (24.6% rural) and ranged from 19.9% in Utah (9.4% rural) to 35.1% in Kentucky (41.6% rural). By gender, the highest proportion of smoking-attributable cancer deaths for women (29.5%) was in a largely urban state (Nevada, 5.8% rural) and for men (38.0%) in a largely rural state (Kentucky). Regression analyses categorizing state-level rurality into low (0-13.9%), moderate (15.3-29.9%) and high (33.6-61.3%) levels showed that high rurality was associated with 5.8% higher cigarette smoking prevalence, higher age-adjusted smoking-associated cancer incidence (44.3 more cases per 100,000 population), higher smoking-associated cancer mortality (29.8 more deaths per 100,000 population), and 3.4% higher proportion of smoking-attributable cancer deaths compared with low rurality. Our findings highlight the magnitude of the relationship between state-level rurality and smoking-attributable cancer outcomes and the importance of tobacco control in reducing cancer disparities in rural populations.

Tobacco and Nicotine Use Among US Adult "Never Smokers" in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: A common criterion for being labeled a "never smoker" is having smoked <100 lifetime cigarettes. This category is often used as an unexposed reference group to estimate the relative harm from cigarettes. We examined the amount of current and past cigarette and non-cigarette tobacco/nicotine use among adults who met this "never smoker" criterion. METHODS: We analyzed cross-sectional data from 17 179 adult "never smokers" (ie, reported <100 lifetime cigarettes) in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health (PATH) Study, a United States nationally representative sample. We used PATH-derived variables to describe "never smokers'" demographics as well as cigarette and non-cigarette tobacco/nicotine use. RESULTS: Approximately half of "never smokers" were young adults (49.3%). Most were white (68.6%) with some college or more (64.4%). Most "never smokers" had tried any cigarette or non-cigarette tobacco/nicotine in their lifetime (66.7%), 8.5% smoked cigarettes in the past 30 days, and 5.3% were current experimental (ie, some days or every day) cigarette smokers. By definition, "never smokers" reported smoking <100 lifetime cigarettes. One fifth (22.8%) had a lifetime history of established regular non-cigarette tobacco/nicotine use and 8.6% were current established regular non-cigarette tobacco/nicotine users. In total, 9.4% of "never smokers" were current experimental or established regular users of combustible tobacco. CONCLUSIONS: The 100-cigarette lifetime threshold includes substantial amounts of current and past tobacco use and thus does not represent lack of exposure to cigarette or non-cigarette tobacco. "Never smoker" reference groups may produce underestimates of the relative harms from cigarettes. IMPLICATIONS: The <100 lifetime cigarettes criterion may not capture what many would consider true "never smokers." Relying on the current definition of "never smokers" as a reference group will include a substantial number of those currently and recently using combustible tobacco and thus produce data that may underestimate the relative harm from cigarettes. Prospective longitudinal research is needed to compare how the 100-cigarette lifetime threshold versus other definitions of regular cigarette smoking differ in predictive validity of clinically meaningful outcomes and health harms to determine the optimal criteria to define established cigarette smoking.

Possible New Symptoms of Tobacco Withdrawal III: Reduced Positive Affect-A Review and Meta-analysis.

INTRODUCTION: Most descriptions of tobacco withdrawal have not changed in >30 years despite new research. This meta-analysis tested whether abstinence leads to decreased positive affect (PA) because abstinence-induced symptom changes are a core feature of the tobacco withdrawal syndrome. In addition, we examined whether reduced PA was due to withdrawal (ie, temporary decrease in a "U-shaped" curve) or offset (ie, return to baseline) effect. METHODS: Our main inclusion criterion was a prospective within-participant test of change in PA during abstinence conditions among people who smoke cigarettes daily who were not using a cessation medication. Our search of PubMed, PsycINFO, and personal libraries yielded a total of 32 tests with 2054 participants. RESULTS: There was a medium effect size indicating an overall decrease in PA following abstinence from cigarettes (Cohen's d = -0.40, 95% CI = -0.30 to -0.49). There was large heterogeneity (I2 = 70.7%). Most (79%) of the 24 trials that conducted significance tests reported that reduction in PA was significant. Seven tests were adequately designed to detect a withdrawal versus offset effect. Over half (57%) displayed a U-shaped curve for abstinence-induced change in PA indicative of a withdrawal symptom rather than offset effect. CONCLUSIONS: Abstinence from cigarettes is associated with a decrease in PA. Whether low PA should be added to withdrawal measures and diagnostic criteria requires replication of the time-course of change in PA and tests of whether abstinence-induced changes in PA and negative affect occur independently. IMPLICATIONS: Though there was substantial heterogeneity among trials, our findings suggest that (1) abstinence from cigarettes decreases positive affect and (2) this decrease may represent a withdrawal effect (vs. an offset effect). However, it is unclear whether abstinence-induced losses in positive affect are independent from increased negative affect.

Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation.

BACKGROUND: Understanding study characteristics' influence on treatment efficacy could improve interpretation of trials' outcomes. We examined study characteristics as predictors of outcomes in clinical trials of medications for tobacco use. METHODS: We obtained and analyzed data on 44 trials of nicotine gum, 37 trials of nicotine patch, 27 trials of varenicline, and 43 trials of bupropion from Cochrane reviews. We extracted and analyzed data for 15 study characteristics, odds ratios (ORs), and percent abstinent in control and medication conditions. We used general linear models to determine which study characteristics explained the variability among outcomes after controlling for medication characteristics. RESULTS: Study characteristics accounted for 12% of the variance in odds ratios among patch trials, 16% among gum trials, 16% among varenicline trials, and 34% among bupropion trials above and beyond medication characteristics. Patch and gum trials with industry funding had larger odds ratios than those without. Among patch trials, this appeared to be due to less abstinence in industry-funded trials' control conditions. Bupropion trials published earlier had larger odds ratios, which appeared to be due to less abstinence in control conditions. The reason for study characteristics' influence on varenicline trials was unclear. DISCUSSION: Study characteristics influenced the assessment of treatment efficacy above and beyond medication characteristics in smoking cessation trials. Our findings that study characteristics are associated with higher or lower efficacy does not suggest that the effect size under one versus another condition is the more valid outcome. Future studies are needed to determine which study characteristics reliably influence efficacy because this would help investigators and clinicians interpret trials. IMPLICATIONS: Study characteristics influenced the estimates of treatment efficacy but individual characteristics' influence on efficacy appeared to differ among different medications for smoking cessation. We encourage researchers to report study characteristics to improve interpretation of findings and systematic reviews, and to account for nontreatment-related variables to better estimate the efficacy of treatments.

Possible New Symptoms of Tobacco Withdrawal II: Anhedonia-A Systematic Review.

INTRODUCTION: When animals undergo nicotine deprivation, rewards become less rewarding (ie, anhedonia occurs). We searched for tests of whether anhedonia occurs in abstinent smokers. METHODS: The major inclusion criterion was a within-participants comparison of behavioral measures of reward sensitivity or self-reported anhedonia during smoking versus during abstinence among daily smokers. A computerized search of PubMed, PsychInfo, and Cochrane databases and other methods located 13 studies. All but one were laboratory studies. RESULTS: The number of studies and participants were small and the results mixed. In terms of anticipatory anhedonia (ie, wanting a reward), abstinence appeared to decrease willingness to work for immediately available rewards, but did not appear to influence how much adding rewards to a task increased responding. Abstinence also appeared to produce small increases in self-reported anticipatory anhedonia. In terms of consummatory anhedonia (ie, liking a reward), self-report measures found anhedonia decreased pleasure from rewards in some but not all tests. In terms of learning (ie, learning to choose a more frequent reward), abstinence did not reliably decrease allocating responding to high versus low frequency reward options. CONCLUSIONS: Although results were mixed, abstinence appears to increase anticipatory anhedonia. It is unclear if abstinence increases consummatory or reward learning-based anhedonia. Further studies of anhedonia in clinical settings are needed (1) to estimate the reliability and clinical significance of anhedonia as a symptom of tobacco withdrawal, (2) to assess if effects represent withdrawal versus offset processes, and (3) to assess if anhedonia interferes with the ability to stop smoking. IMPLICATIONS: Anticipatory anhedonia appears to be a symptom of tobacco withdrawal and should be added to tobacco withdrawal checklists and diagnostic criteria. Further study of consummatory and learning-based anhedonia is warranted.

Predictors of Smoking Cessation Attempts and Success Following Motivation-Phase Interventions Among People Initially Unwilling to Quit Smoking.

INTRODUCTION: Most people who smoke cigarettes are not willing (ie, not ready) to make a quit attempt (QA) at any given time. Unfortunately, interventions intended to increase QAs and the success of QAs are only modestly effective. Identifying processes leading to QAs and quitting success could guide intervention development. AIMS AND METHODS: This is a secondary analysis of a randomized factorial trial of 6 weeks of motivation-phase interventions among primary care patients (N = 517) who were initially unwilling to quit but were willing to reduce their smoking. Using logistic regression, we controlled for treatment condition and tested whether baseline or change in smoking-related constructs after 6 weeks of treatment predicted (1) making an at least 24 h QA between weeks 6 and 26 and (2) quitting success at week 26 (7-day point-prevalence abstinence among those who made a QA). Predictors included cigarettes/day, time to first cigarette, motivation to quit, quitting self-efficacy, anticipated urges to smoke if quit, positive affect, negative affect, and time spent around others who smoke. RESULTS: In multivariable models that included all smoking-related constructs, changes in the following variables predicted initiating a QA above and beyond other variables: greater baseline time to first cigarette (odds ratio [OR] = 1.60), increases in time to first cigarette (OR = 1.27), and increases in quitting self-efficacy (OR = 1.14). Increased motivation to quit predicted conversion of a QA into quitting success at 26 weeks (OR = 1.36). CONCLUSION: Predictors of making a QA differed from predictors of quitting success. Predictors of QAs and success could each serve as important treatment targets of motivation-phase interventions. IMPLICATIONS: Motivation-phase interventions for people initially unwilling to quit smoking cigarettes may be improved by striving to increase their (1) time to first cigarette and quitting self-efficacy to promote QAs and (2) motivation to quit to promote quit success. Future experimental tests of such interventions are needed to identify causal determinants of QAs and quitting success.

Recruiting and Retaining Youth and Young Adults in the Policy and Communication Evaluation (PACE) Vermont Study: Randomized Controlled Trial of Participant Compensation.

BACKGROUND: The standard approach for evaluating the effects of population-level substance use prevention efforts on youth and young adult perceptions and behaviors has been to compare outcomes across states using national surveillance data. Novel surveillance methods that follow individuals over shorter time intervals and capture awareness of substance use prevention policy and communication efforts may provide a stronger basis for their evaluation than annual cross-sectional studies. OBJECTIVE: This study aimed to identify a combination of strategies to recruit a sample of youth and young adults sufficiently representative of the Vermont population and determine how best to retain a web-based panel of youth and young adults over a 6-month period. METHODS: Eligible participants were Vermont residents aged 12 to 25 years who were willing to complete three 10 to 15-minute web-based surveys over a 6-month period. Recruitment was conducted via the following three main mechanisms: (1) web-based recruitment (paid and unpaid), (2) community-based recruitment through partners, and (3) participant referrals via a personalized link. Upon completion of the baseline survey, participants were randomly assigned to one of the following three retention incentive conditions: (1) guaranteed incentive (US $10), (2) lottery incentive (US $50 weekly lottery drawing), and (3) preferred method (guaranteed or lottery). Analyses examined cost per survey start by recruitment source, distribution of demographic characteristics across incentive conditions, and retention by study condition at 3-month and 6-month follow-ups. RESULTS: Over a 10-week period in 2019, we recruited 480 eligible youth (aged 12-17 years) and 1037 eligible young adults (aged 18-25 years) to the Policy and Communication Evaluation (PACE) Vermont Study. Facebook and Instagram advertising produced the greatest number of survey starts (n=2013), followed by posts to a state-wide web-based neighborhood forum (n=822) and Google advertisements (n=749). Retention was 78.11% (1185/1517) at 3 months and 72.18% (1095/1517) at 6 months. Retention was equivalent across all incentive study conditions at both waves, despite a strong stated preference among study participants for the guaranteed payment at baseline. Youth had greater retention than young adults at both waves (wave 2: 395/480, 82.3% vs 790/1037, 76.18%; wave 3: 366/480, 76.3% vs 729/1037, 70.30%). Substance use prevalence in this cohort was similar to national and state-level surveillance estimates for young adults, but was lower than state-level surveillance estimates for youth. Most participants retained at wave 3 provided positive qualitative feedback on their experience. CONCLUSIONS: Our study supports the feasibility of recruiting a web-based cohort of youth and young adults with representation across an entire state to evaluate substance use prevention efforts. Findings suggest that a guaranteed payment immediately upon survey completion coupled with a bonus for completing all survey waves and weekly survey reminders may facilitate retention in a cohort of youth and young adults.

Increasing Quit Attempts by Transitioning to Very Low Nicotine Content Cigarettes Versus Reducing Number of Cigarettes Per Day: A Secondary Analysis of an Exploratory Randomized Trial.

INTRODUCTION: The Food and Drug Administration (FDA) has proposed reducing nicotine with very low nicotine content (VLNC) cigarettes. In contrast, reducing nicotine by reducing number of cigarettes per day (CPD) is common. Our prior findings demonstrate that VLNC cigarettes decreased dependence more and were more acceptable than reducing CPD. This secondary analysis explored which reduction strategy increased quit attempts (QA), self-efficacy, or intention to quit more. METHODS: This is a secondary analysis of 68 adult daily smokers not ready to quit randomized to smoke VLNC cigarettes versus reduce CPD over 5 weeks. All participants smoked study cigarettes with nicotine yield similar to most commercial cigarettes ad lib for 1 week (baseline). Participants were then randomized to gradually reduce to 70%, 35%, 15%, and 3% of baseline nicotine over 4 weeks by either (1) transitioning to lower nicotine VLNC cigarettes or (2) reducing the number of full nicotine CPD. All participants received nicotine patches to aid reduction. We assessed (1) QAs using nightly and weekly self-reports, (2) Velicer's Self-Efficacy to Quit measure weekly, and (3) the Intention-to-Quit Ladder nightly. RESULTS: More CPD (41%) than VLNC (17%) participants made any QA (odds ratio = 3.4, 95% confidence interval = 1.1, 10.5). There was no difference in QAs ≥24 h. Self-efficacy increased for VLNC but not CPD participants (interaction: F = 3.7, p < .01). The condition by time interaction for intention-to-quit was not significant. CONCLUSIONS: Reducing number of CPD increased QAs more than reducing nicotine via switching to VLNC cigarettes. The lack of difference in longer QAs suggests replication tests are needed. IMPLICATIONS: Reducing the frequency of smoking behavior (ie, CPD) could be a more effective strategy to increase QAs than reducing the magnitude of nicotine in each cigarette (ie, VLNC) per se.

Reduction in Cigarettes per Day Prospectively Predicts Making a Quit Attempt: A Fine-Grained Secondary Analysis of a Natural History Study.

INTRODUCTION: Reducing cigarettes per day (CPD) aided by medication increases quit attempts (QA) among smokers not trying to quit. If this is due to reducing CPD per se, then a greater reduction should predict making a QA. AIMS AND METHODS: In this secondary analysis, 132 smokers completed nightly calls to report CPD, intention to quit tomorrow, and QAs over 12 weeks. We provided no treatment. We identified episodes of reduction and tested whether (1) percent reduction in CPD, (2) absolute reduction in CPD, (3) duration of reduction, or (4) CPD on the final day predicted a QA immediately after a reduction episode. We tested this separately among reduction episodes that began with and without an intention to quit. RESULTS: Among the 1179 episodes that began without intention to quit, all four measures of reduction predicted making a QA. Greater percent reduction, longer duration, and fewer CPD on the final day were retained in a multivariate model (all p < .05). Among the 85 episodes that began with intention to quit, greater percent reduction and greater absolute reduction predicted making a QA. Only mean percent reduction was retained in a multivariate model (p < .001). CONCLUSIONS: Our results replicate and extend earlier studies by using fine-grained analyses and examining immediately proximal QAs in a sample of self-quitters. Findings suggest that reducing CPD per se increases the probability of a QA among smokers without intention to quit in a dose-related manner. Whether this is the case among smokers who intend to quit remains unclear. IMPLICATIONS: Reducing CPD appears to be an effective strategy to increase the probability of making a QA for the majority of smokers who do not intend to quit in the near future. However, our findings are mixed regarding the effectiveness of reducing among smokers who intend to quit. Clinical interventions and policies that promote reducing CPD are likely to be an effective way to increase QAs. Reduction may be especially helpful for smokers who have not responded to traditional advice to stop abruptly.