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.

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

The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AIM: While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic. METHODS: A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (eg social distancing, mask wearing) were examined. RESULTS: Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9 ± 1.0 versus 11.6 ± 1.0; p < .001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4 ± 1.4 to 13.3 ± 1.4, p = .024) as did those with higher levels of anxiety (from 11.5 ± 1.1 to 13.6 ± 1.1, p < .001). CONCLUSIONS: Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use. IMPLICATIONS: Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

Leveraging the cigarette purchase task to understand relationships between cumulative vulnerabilities, the relative reinforcing effects of smoking, and response to reduced nicotine content cigarettes.

We examined if the relative-reinforcing effects of smoking increase with greater cumulative vulnerability and whether cumulative vulnerability moderates response to reduced nicotine content cigarettes. Participants were 775 adults from randomized clinical trials evaluating research cigarettes differing in nicotine content (0.4, 2.4, 15.8 mg/g). Participants were categorized as having low (0-1), moderate (2-3), or high (≥4) cumulative vulnerability. Vulnerabilities included rural residence, opioid use disorder, affective disorder, low educational attainment, poverty, unemployment, and physical disability. We used the cigarette purchase task (CPT) to assess the relative-reinforcing effects of participants' usual-brand cigarettes at baseline and study cigarettes during the 12-week trial. The CPT is a behavioral-economic task wherein participants estimate likely smoking (demand) over 24 h under escalating cigarette price. Demand is characterized by two factors: Amplitude (demand volume at zero/minimal price) and Persistence (demand sensitivity to price). Greater cumulative vulnerability was associated with greater demand Amplitude (F[2709] = 16.04,p < .0001) and Persistence (F[2709] = 8.35,p = .0003) for usual-brand cigarettes. Demand Amplitude for study cigarettes increased with increasing cumulative vulnerability (F[2619] = 19.59, p < .001) and decreased with decreasing nicotine content ([4879] = 5.45, p < .001). The only evidence of moderation was on demand Persistence (F[8867] = 2.00,p = .04), with larger reductions at the 0.4 mg/g compared to 15.8 mg/g doses among participants with low compared to moderate or high cumulative vulnerability. The relative-reinforcing effects of smoking clearly increase with greater cumulative vulnerability. Reducing nicotine content would likely reduce demand Amplitude across cumulative-vulnerability levels but reductions in demand Persistence may be more limited among those with greater cumulative vulnerability.

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.

Relating individual differences in the reinforcing value of smoking and dependence severity to nicotine exposure levels in vulnerable populations.

Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity.

Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage.

INTRODUCTION: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage. AIMS AND METHODS: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period. RESULTS: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified. CONCLUSIONS: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings. TRIAL REGISTRATION: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered. IMPLICATIONS: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.

Opioid use disorder treatment in rural settings: The primary care perspective.

Despite the efficacy of medications for treating opioid use disorder (OUD), they are underutilized, especially in rural areas. Our objectives were to determine the association between primary care practitioners (PCPs) rurality and concerns for patient substance use, and to identify factors associated with PCP comfort treating OUD, focusing on barriers to treatment. We developed a web-based survey completed by 116 adult-serving PCPs located in Vermont's rural and non-rural counties between April-August 2020. The instrument included PCP-identified concerns for substance use among patients, barriers to treating patients with OUD, and current level of comfort treating patients with OUD. On a scale from 0 to 10, rural PCPs reported higher concern for heroin (mean difference; Mdiff = 1.38, 95% CI: 0.13 to 2.63), fentanyl (Mdiff = 1.52, 95% CI: 0.29 to 2.74), and methamphetamine (Mdiff = 1.61, 95% CI: 0.33 to 2.90) use among patients compared to non-rural PCPs, and practitioners in both settings expressed high concern regarding their patients' use of tobacco (7.6 out of 10) and alcohol (7.0 out of 10). There was no difference in reported comfort in treating patients with OUD among rural vs. non-rural PCPs (Mdiff = 0.65, 95%CI: 0.17 to 1.46; P = 0.119), controlling for higher comfort among male PCPs and those waivered to prescribe buprenorphine (Ps < 0.05). Lack of training/experience and medication diversion were PCP-identified barriers associated with less comfort treating OUD patients, while time constraints was associated with more comfort (Ps < 0.05). Taken together, these data highlight important areas for dissemination of evidence-based training, support, and resources to expand OUD treatment capacity in rural communities.

Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Current smoking as a marker of a high-risk behavioral profile after myocardial infarction.

Continued smoking following myocardial infarction (MI) is strongly associated with increased morbidity and mortality. Patients who continue to smoke may also engage in other behaviors that exacerbate risk. This study sought to characterize the risk profile of a national sample of individuals with previous MI who currently smoke. Data were taken from the 2017 Behavioral Risk Factor Surveillance Survey (United States), with 4.2% of the sample reporting a past MI (N = 26,004). Participants were classified by smoking status (current/former/never) and compared on medical comorbidities and the clustering of modifiable behaviors relevant for secondary prevention (smoking, poor nutrition, problematic alcohol use, physical inactivity, medication adherence). Current smokers were more likely to report other comorbidities including stroke, chronic obstructive pulmonary disease, physical limitations, and poor mental health. Smokers were also less likely to report taking blood pressure and cholesterol medications, and less likely to attend cardiac rehabilitation (examined in a subset of the sample, N = 2181). Current smoking remained an independent predictor of other health-related behaviors even when controlling for age, sex, race, educational attainment, and other comorbidities. In the modifiable risk-factor behavior cluster analysis, the most common pattern among current smokers was having two risk factors, smoking plus one additional risk factor, whereas the most common pattern was zero risk factors among never or former-smokers. Physical inactivity was the most common additional risk factor across smoking statuses. Current smoking is associated with multiple comorbidities and should be considered a marker for a high-risk behavioral profile among patients with a history of MI.

Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations.

We examined whether elucidating underpinning smoking motivation and related pharmacological processes enhances understanding of nicotine dependence among smokers from vulnerable populations. Data were obtained between Oct, 2016 and Sept, 2019 from 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage at University of Vermont, Brown University, Johns Hopkins University. Smoking motivation was assessed using the Cigarette Purchase Task (CPT), a behavioral-economic task that models the relative reinforcing value of smoking under varying monetary constraint. Dependence severity was measured using the Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence total scores (FTND), and FTND total scores minus items 1 and 4 (FTND2,3,5,6). We also assessed associations between dependence severity and smoking motivation with nicotine levels and metabolism rate. Principal Component Analysis was used to examine the latent structure of the conventional five CPT indices; bivariate and multivariable modeling was used to test associations. Factor analysis resulted in a two-factor solution, Amplitude (demand unconstrained by price) and Persistence (price sensitivity). CPT latent factors were associated with each dependence-severity measure (ps ≤ 0.0001), with associations stronger for Amplitude than Persistence across each, especially HSI which was exclusively associated with Amplitude. Amplitude and each dependence measure were associated with nicotine intake (ps ≤ 0.0002); Persistence was not (p = .19). Demand Amplitude more than Persistence appears key to understanding individual differences in dependence severity. Regarding potential application, the results suggest a need for interventions that more effectively target demand Amplitude to make greater headway in reducing smoking in vulnerable populations. Trial Registration:clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Potential Moderating Effects of Sex/Gender on the Acute Relative Reinforcing and Subjective Effects of Reduced Nicotine Content Cigarettes in Vulnerable Populations.

INTRODUCTION: Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking's addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations. METHODS: Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings). RESULTS: Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p's < .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ. CONCLUSIONS: Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes. IMPLICATIONS: A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts.

The effect of executive function on adherence with a cardiac secondary prevention program and its interaction with an incentive-based intervention.

Participation in secondary prevention programs such as cardiac rehabilitation (CR) reduces morbidity, mortality, and hospitalizations while improving quality of life. Executive function (EF) is a complex set of cognitive abilities that control and regulate behavior. EF predicts many health-related behaviors, but how EF interacts with interventions to improve treatment adherence is not well understood. The objective of this study is to examine if EF predicts CR treatment adherence and how EF interacts with an intervention to improve adherence. Data were collected from 2013 to 2018 in Vermont, USA. 130 Medicaid-enrolled individuals who had experienced a qualifying cardiac event were enrolled in a controlled clinical trial and randomized 1:1 to receive financial incentives for completing secondary prevention sessions or to usual care. In this secondary analysis, effects of EF on CR adherence (defined as completing ≥30/36 sessions) were examined in 112 participants (57 usual care, 55 intervention) who completed an EF battery. Delay-discounting, a measure of impulsivity, predicted CR adherence (p = 0.01) and interacted with the incentive intervention, such that those who exhibited greater discounting of future rewards benefitted more from the intervention than those who discounted less (F(1, 104) = 5.23, p = 0.02). Better cognitive flexibility, measured with the trail-making-task, also predicted CR adherence (p = 0.02). While EF has been associated with adherence to a variety of treatment regimens, this interaction between an incentive-based intervention to promote treatment adherence and EF is novel. This work illustrates the value of considering individual differences in EF when designing and implementing interventions to promote health-related behavior change.

Current cigarette smoking among U.S. college graduates.

Although U.S. college graduates are at relatively low risk for smoking, 12-15% of U.S. smokers (~8 million people) are college graduates. Few studies have examined smoking risk among college graduates. To address that gap, the present study examined smoking risk among U.S. college graduates and those who did not graduate from college in a nationally representative sample of adults (National Survey on Drug Use and Health 2011-2017, n = 202,137). We examined smoking risk in association with well-established risk factors: alcohol abuse/dependence, drug abuse/dependence, mental illness, age, sex, race/ethnicity, and poverty status, using group contrasts and Classification and Regression Tree (CART) modeling. Smoking prevalence among U.S. college graduates and non-graduates was 10% and 26%, respectively. College graduates initiated any smoking and daily smoking at a later age and were lighter smokers than smokers who did not graduate college. Within college graduate and non-graduate groups, prevalence rates varied by orders of magnitude across different risk-factor profiles (ranges = 3-37% and 14-73% among graduates and non-graduates, respectively). Past year drug abuse/dependence was a robust predictor of smoking prevalence in both populations. For college graduates, past year alcohol abuse/dependence and mental illness were stronger predictors of smoking compared to those who did not graduate college, for whom race/ethnicity and age were stronger predictors. Overall, smoking risk increases to surprisingly high levels, even among college graduates, when select risk factors co-occur, particularly psychiatric conditions. Socio-demographic risk factors appear to be less robust predictors of smoking risk among college graduates relative to those who did not graduate college.

Examining effects of unit price on preference for reduced nicotine content cigarettes and smoking rate.

Cigarette preference increases as a function of greater nicotine content, but manipulating cost can shift preference. The aims of the present study are to model whether (1) the behavioral-economic metric unit price (cost/reinforcer magnitude) accounts for preference shifts and (2) whether preference shifts toward reduced nicotine content are associated with smoking reductions. In a multisite study between 2015 and 2016, 169 daily smokers from vulnerable populations completed two concurrent-choice conditions examining preference for smoking normal (15.8 mg/g) and reduced (0.4 mg/g) nicotine content cigarettes. In Condition 1, both products were available at 10 responses/choice. In Condition 2, availability of the 0.4 mg/g dose remained at 10 responses/choice while the 15.8 mg/g dose was available on a progressive-ratio (PR) schedule wherein response cost increased following each choice. Unit prices were calculated by dividing dose by response requirement. Results were analyzed using ANOVA and binomial tests (p < .05). Participants preferred the 15.8 over 0.4 mg/g dose in Condition 1, but shifted preference to the 0.4 mg/g dose in Condition 2 (p < .001) immediately before the point in the PR progression where unit price for 15.8 dose exceeded unit price for the 0.4 dose (p < .001). This shift was associated with a reduction in smoking (p < .001). The unit price of nicotine appears to underpin cigarette product preference and may provide a metric for predicting preference and potentially impacting it through tobacco regulations. These results also demonstrate that reduced compared to normal nicotine content cigarettes sustain lower smoking rates discernible even under acute laboratory conditions and in vulnerable populations.

Patterns of tobacco use among smokers prior to hospitalization for an acute cardiac event: Use of combusted and non-combusted products.

Use of tobacco products before or after a cardiac event increases risk of morbidity and mortality. Unlike cigarette smoking, which is generally screened in the healthcare system, identifying the use of other tobacco products remains virtually unexplored. This study aimed at characterizing the use of other non-combusted tobacco products in addition to combusted products among cardiac patients and identifying a profile of patients who are more likely to use non-combusted products. Patients (N = 168) hospitalized for a coronary event who reported being current cigarette smokers completed a survey querying sociodemographics, cardiac diagnoses, use of other tobacco products, and perceptions towards these products. Classification and regression tree (CART) analysis was used to identify which interrelationships of participants characteristics led to profiles of smoking cardiac patients more likely to also be using non-combusted tobacco products. Results showed that non-combusted tobacco product use ranged from 0% to 47% depending on patient characteristic combinations. Younger age and lower perception that cigarette smoking is responsible for their cardiac condition were the strongest predictive factors for use of non-combusted products. Tobacco product use among cardiac patients extends beyond combusted products (13.7% non-combusted product use), and consequently, screening in health care settings should be expanded to encompass other tobacco product use. This study also characterizes patients likely to be using non-combusted products in addition to combusted, a group at high-risk due to their multiple product use, but also a group that may be amenable to harm reduction approaches and evidence-based tobacco treatment strategies.

Reducing the Nicotine Content of Cigarettes: Effects in Smokers With Mental Health Conditions and Socioeconomic Disadvantages.

In this commentary, we review results from laboratory studies and randomized clinical trials that have examined the effects of very low-nicotine-content cigarette use in smokers with mental health conditions and socioeconomic disadvantages. On the basis of scientific evidence to date, we conclude that a reduced-nicotine standard for cigarettes would likely reduce cigarette smoking in these populations, without increasing psychiatric symptoms or compensatory smoking.

Potential Moderating Effects of Psychiatric Diagnosis and Symptom Severity on Subjective and Behavioral Responses to Reduced Nicotine Content Cigarettes.

INTRODUCTION: Given FDA's authority to implement a cigarette nicotine reduction policy, possible outcomes of this regulation must be examined, especially among those who may be most affected, such as those with comorbid psychiatric disorders. METHODS: In this secondary analysis of a multisite, randomized, clinical laboratory study, we used analyses of variance to examine the effects of nicotine dose (0.4, 2.4, 5.2, and 15.8 mg/g of tobacco), depressive and anxiety diagnoses (depression only, anxiety only, both, or neither), and depressive and anxiety symptom severity on cigarette choice, smoke exposure, craving, and withdrawal across three vulnerable populations: socioeconomically disadvantaged women of reproductive age, opioid-dependent individuals, and those with affective disorders (n = 169). RESULTS: Diagnosis and symptom severity largely had no effects on smoking choice, total puff volume, or CO boost. Significant main effects on craving and withdrawal were observed, with higher scores in those with both anxiety and depression diagnoses compared with depression alone or no diagnosis, and in those with more severe depressive symptoms (p's < .001). These factors did not interact with nicotine dose. Cigarettes with <15.8 mg/g nicotine were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses (p's < .01). CONCLUSIONS: Reducing nicotine dose reduced measures of cigarette addiction potential, with little evidence of moderation by either psychiatric diagnosis or symptom severity, providing evidence that those with comorbid psychiatric disorders would respond to a nicotine reduction policy similarly to other smokers. IMPLICATIONS: Thus far, controlled studies in healthy populations of smokers have demonstrated that use of very low nicotine content cigarettes reduces cigarette use and dependence without resulting in compensatory smoking. These analyses extend those findings to a vulnerable population of interest, those with comorbid psychiatric disorders. Cigarettes with very low nicotine content were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses. These nicotine dose effects did not interact with psychiatric diagnosis or mood symptom severity suggesting that smokers in this vulnerable population would respond to a nicotine reduction strategy similarly to other smokers.

Examining Age as a Potential Moderator of Response to Reduced Nicotine Content Cigarettes in Vulnerable Populations.

INTRODUCTION: Young adults (aged 18-24 years) have a higher smoking prevalence than younger and older age groups and young adulthood is an important developmental period during which long-term behavior patterns like cigarette smoking are established. The aim of the current study was to examine how young adult smokers with additional vulnerabilities to smoking respond to reduced nicotine content cigarettes. METHODS: This is a secondary analysis of a double-blind, within-subject experiment conducted with 169 cigarette smokers recruited from populations with comorbid psychiatric conditions or socioeconomic disadvantage assessing acute effects of research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g). Participants were dichotomized by chronological age (18-24 vs. ≥25 years). Across 14 laboratory sessions effects of nicotine content were examined on measures of relative reinforcing efficacy (Cigarette Purchase Task [CPT] and Concurrent Choice testing), subjective effects, craving/withdrawal, and smoking topography. Repeated measures analysis of variances were used to examine potential moderating effects of age. RESULTS: Young adults exhibited lower demand for reduced nicotine content cigarettes than older adults across three of five CPT indices (ps < .05). No differences by age were observed on other measures of reinforcing efficacy, subjective effects, craving/withdrawal, or smoking topography where effects generally decreased as an orderly function of decreasing nicotine content (ps <.05). CONCLUSION: Overall, these findings suggest that reducing the nicotine content of cigarettes would decrease the addiction potential of cigarette smoking in young adult smokers as much or perhaps more than older adult smokers from populations at increased vulnerability to smoking, addiction, and smoking-related health consequences. IMPLICATIONS: Reducing the nicotine content in cigarettes to lower addiction potential of smoking has been proposed as a means to improve overall population health. It is imperative to examine how young adults may respond to a nicotine reduction policy. We saw minimal evidence that age moderates acute response and where there was evidence it was in the direction of reduced nicotine content cigarettes having less addictive potential among young versus older adults (eg, steeper decreases in demand for very low nicotine content cigarettes among young versus older adults). Overall, a nicotine reduction policy has the potential to reduce smoking across age groups.

Understanding individual differences in vulnerability to cigarette smoking is enhanced by attention to the intersection of common risk factors.

While smoking prevalence in the U.S. and other industrialized countries has decreased substantially, this change has been unevenly distributed, with dramatic decreases in certain subpopulations but little change or even increases in others. Accordingly, considerable attention has been fruitfully devoted to identifying important risk factors for smoking (e.g., mental illness, other substance use disorders). However, there has been little research on the intersection of these risk factors. As risk factors rarely occur in isolation, it is important to examine risk-factor profiles as is commonly done in studying other chronic conditions (e.g., cardiovascular disease). The purpose of this Commentary is to encourage greater interest in the intersection of multiple risk factors using cigarette smoking as an exemplar. We focus on the intersection of eight well-established risk factors for smoking (age, gender, race/ethnicity, educational attainment, poverty, drug abuse/dependence, alcohol abuse/dependence, mental illness). Studying the intersection of risk factors is likely to require use of innovative data-analytic methods. We illustrate, using years 2011-2016 of the US National Household Survey on Drug Use and Health, how Classification and Regression Tree (CART) analysis can be an effective tool for identifying risk profiles for smoking. Examination of the intersection of these risk factors elucidates a series of risk profiles with associated, orderly gradations in vulnerability to current smoking, including the striking and reliable strength of a college education as a stand-alone profile predicting low risk for current smoking, and illustrating the potentially increasing importance of drug abuse/dependence as a risk factor.