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.

Changes in weight among individuals with psychiatric conditions or socioeconomic disadvantage assigned to smoke very low nicotine content cigarettes.

Nicotine abstinence leads to weight gain, which could be an unintended consequence of a nicotine reduction policy. This secondary analysis used weekly assessments of weight and ratings of "increased appetite/hunger/weight gain" collected in three 12-week, randomized controlled trials evaluating the effects of cigarettes differing in nicotine dose (15.8, 2.4, or 0.4 mg/g) among individuals with affective disorders, opioid use disorder (OUD), and socioeconomically disadvantaged women. Linear mixed models tested differences by dose and time. Analyses first collapsed across populations and then separated out individuals with OUD because biomarkers suggested they used substantially more noncombusted nicotine. Across populations, weight increased significantly over time, averaging 1.03 kg (p < .001), but did not vary by dose nor was there any interaction of dose/time. "Increased appetite/hunger/weight gain" ratings increased significantly as a function of dose, with differences between low and high doses (1.95 and 1.73, respectively, p = .01), but not by time nor any interaction. In the combined group of individuals with affective disorders and socioeconomically disadvantaged women, weight and "increased appetite/hunger/weight gain" ratings increased significantly by dose, with differences between low and high doses (1.43 vs. 0.73 kg, p = .003 and 2.00 vs. 1.76, p = .02, respectively). Among individuals with OUD, there were no significant effects of any kind on either outcome. Individuals with affective disorders and socioeconomically disadvantaged women gained weight and reported more subjective appetite/weight gain when given 0.4, but not 2.4 mg/g cigarettes, despite comparable decreases in nicotine exposure. However, neither change was clinically significant, suggesting minimal short-term adverse consequences of a nicotine reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Randomized clinical trial examining financial incentives for smoking cessation among mothers of young children and possible impacts on child secondhand smoke exposure.

This randomized clinical trial examined whether financial-incentives increase smoking cessation among mothers of young children and potential impacts on child secondhand-smoke exposure (SHSe). 198 women-child dyads were enrolled and assigned to one of three treatment conditions: best practices (BP, N = 68), best practices plus financial incentives (BP + FI, N = 63), or best practices, financial incentives, and nicotine replacement therapy (BP + FI + NRT, N = 67). The trial was completed in Vermont, USA between June 2015 and October 2020. BP entailed staff referral to the state tobacco quitline; financial incentives entailed mothers earning vouchers exchangeable for retail items for 12 weeks contingent on biochemically-verified smoking abstinence; NRT involved mothers receiving 10 weeks of free transdermal nicotine and nicotine lozenges/gum. Baseline, 6-, 12-, 24-, and 48-week assessments were conducted. Primary outcomes were maternal 7-day point-prevalence abstinence and child SHSe through the 24-week assessment with the 48-week assessment exploratory. Results were analyzed using mixed model repeated measures for categorical data. Odds of maternal abstinence were greater among mothers in BP + FI and BP + FI + NRT compared to BP at the 6- and 12-week assessments (ORs ≥ 7.30; 95% CIs: 2.35-22.71); only abstinence in BP + FI remained greater than BP at the 24-week assessment (OR = 2.95; 95% CIs: 1.06-8.25). Abstinence did not differ significantly between treatment conditions at the 48-week assesssment. There was a significant effect of treatment condition (F[2109] = 3.64, P = .029) on SHSe with levels in BP and BP + FI significantly below BP + FI + NRT (ts[109] ≥ -2.30, Ps ≤ 0.023). Financial incentives for smoking abstinence are efficacious for increasing maternal cessation but that alone was insufficient for reducing child SHSe. ClinicalTrials.gov:NCT05740098.

Alteration of brain function and systemic inflammatory tone in older adults by decreasing the dietary palmitic acid intake.

Prior studies in younger adults showed that reducing the normally high intake of the saturated fatty acid, palmitic acid (PA), in the North American diet by replacing it with the monounsaturated fatty acid, oleic acid (OA), decreased blood concentrations and secretion by peripheral blood mononuclear cells (PBMCs) of interleukin (IL)-1ß and IL-6 and changed brain activation in regions of the working memory network. We examined the effects of these fatty acid manipulations in the diet of older adults. Ten subjects, aged 65-75 years, participated in a randomized, cross-over trial comparing 1-week high PA versus low PA/high OA diets. We evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory and a resting state scan, cytokine secretion by lipopolysaccharide (LPS)-stimulated PBMCs, and plasma cytokine concentrations. During the low PA compared to the high PA diet, we observed increased activation for the 2-back minus 0-back conditions in the right dorsolateral prefrontal cortex (Broadman Area (BA) 9; p < 0.005), but the effect of diet on working memory performance was not significant (p = 0.09). We observed increased connectivity between anterior regions of the salience network during the low PA/high OA diet (p < 0.001). The concentrations of IL-1ß (p = 0.026), IL-8 (p = 0.013), and IL-6 (p = 0.009) in conditioned media from LPS-stimulated PBMCs were lower during the low PA/high OA diet. This study suggests that lowering the dietary intake of PA down-regulated pro-inflammatory cytokine secretion and altered working memory, task-based activation and resting state functional connectivity in older adults.

E-cigarette cessation and transitions in combusted tobacco smoking status: longitudinal findings from the US FDA PATH Study.

BACKGROUND AND AIMS: Electronic nicotine delivery systems (ENDS) can help people to quit smoking combusted tobacco products (CTPs), but most current and former smokers who use ENDS also intend to quit ENDS. This analysis measured whether ENDS cessation among current and former CTP smokers is associated with changes in CTP smoking or abstinence. DESIGN: Regression analysis of a nationally representative cohort from waves 4 (W4) and 5 (W5) of the Population Assessment of Tobacco and Health Study (December 2016-November 2019). SETTING: United States. PARTICIPANTS: Adults (n = 1525) who reported W4 current or former use of ≥ 1 CTP and either currently using ENDS or quitting ENDS in the past year were included. MEASUREMENTS: Logistic regressions were performed separately among W4 current and former CTP smokers, controlling for demographic and tobacco use characteristics. First, we analyzed proximal outcomes by testing the association between ENDS quit status and CTP abstinence, both occurring during W5. Next, we analyzed long-term outcomes by testing W4 ENDS quit status as a predictor of CTP abstinence at W5, approximately 1 year later. FINDINGS: Among W4 current CTP smokers, there was no evidence that CTP smoking abstinence differed between those quitting or continuing using ENDS, both in our proximal [adjusted odds ratio (aOR) = 1.37, 95% confidence interval (CI) = 0.90, 2.10] and long-term (aOR = 0.90, 95% CI = 0.52, 1.53) analyses. Among former CTP smokers, quitting ENDS was associated with less CTP abstinence in our proximal analysis (aOR = 0.42, 95% CI = 0.20, 0.89), but there was no evidence that CTP smoking abstinence differed between those quitting or continuing using ENDS in our long-term analysis (aOR = 0.86, 95% CI = 0.44, 1.67). CONCLUSIONS: There is no evidence that ENDS cessation is associated with CTP abstinence among current smokers, although mixed findings among former smokers indicate a possible risk for relapse to smoking associated with quitting ENDS.

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.

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.

Effects of total knee arthroplasty on skeletal muscle structure and function at the cellular, organellar, and molecular levels.

Total knee arthroplasty (TKA) is an important treatment option for knee osteoarthritis (OA) that improves self-reported pain and physical function, but objectively measured physical function typically remains reduced for years after surgery due, in part, to precipitous reductions in lower extremity neuromuscular function early after surgery. The present study examined intrinsic skeletal muscle adaptations during the first 5 weeks post-TKA to identify skeletal muscle attributes that may contribute to functional disability. Patients with advanced stage knee OA were evaluated prior to TKA and 5 weeks after surgery. Biopsies of the vastus lateralis were performed to assess muscle fiber size, contractility, and mitochondrial content, along with assessments of whole muscle size and function. TKA was accompanied by marked reductions in whole muscle size and strength. At the fiber (i.e., cellular) level, TKA caused profound muscle atrophy that was approximately twofold higher than that observed at the whole muscle level. TKA markedly reduced muscle fiber force production, contractile velocity, and power production, with force deficits persisting in myosin heavy chain (MHC) II fibers after expression relative to fiber size. Molecular level assessments suggest reduced strongly bound myosin-actin cross bridges and myofilament lattice stiffness as a mechanism underlying reduced force per unit fiber size. Finally, marked reductions in mitochondrial content were apparent and more prominent in the subsarcolemmal compartment. Our study represents the most comprehensive evaluation of skeletal muscle cellular adaptations to TKA and uncovers novel effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.NEW & NOTEWORTHY We report the first evaluation of the effects of total knee arthroplasty (TKA) on skeletal muscle at the cellular and subcellular levels. We found marked effects of TKA to cause skeletal muscle fiber atrophy and contractile dysfunction in older adults, as well as molecular mechanisms underlying impaired contractility. Our results reveal profound effects of TKA on muscle fiber size and intrinsic contractility early after surgery that may contribute to functional disability.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

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.

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.

Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance.

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers.

Use of electronic nicotine delivery systems (ENDS) among U.S. women of reproductive age: Prevalence, reported reasons for use, and toxin exposure.

Given the rapidly expanding marketplace for Electronic Nicotine Delivery Systems (ENDS), it is important to monitor patterns of use, particularly among vulnerable populations. This study examined ENDS prevalence, reasons for use (i.e., to help quit smoking and for appealing flavors), and toxin exposure among U.S. women of reproductive age using data from the Population Assessment of Tobacco and Health (PATH) Study (2013-17). Exclusive ENDS users, dual users of ENDS and cigarettes, and exclusive cigarette smokers were compared within and between pregnant and not-pregnant women. Among pregnant women, prevalence of exclusive ENDS and dual use was similar (0.8%; 95%CI = 0.4-1.2% vs. 1.4%; 95%CI = 0.9-2.0%, respectively), but exclusive ENDS use was less prevalent than dual use among not-pregnant women (1.1%; 95%CI = 0.9-1.4% vs. 3.7%; 95%CI = 3.3-4.0%, respectively). Most women reported ENDs were used to help quit smoking (66.5-90.0%) and for appealing flavors (57.6-87.4%), and endorsement rates did not differ by use pattern or pregnancy status. Except for metals, toxin exposure was substantially lower for exclusive ENDS users relative to dual users and exclusive cigarette smokers regardless of pregnancy status. Pregnant and not-pregnant U.S. women regularly report using ENDS for help with quitting smoking and for appealing flavors. Although no type or pattern of tobacco/nicotine use is safe, especially during pregnancy, using ENDS exclusively is consistent with lower overall toxin exposure for pregnant and not-pregnant women. This study advances understanding of ENDS use and toxin exposure in women of reproductive age, a population highly vulnerable to the effects of nicotine/tobacco consumption.

Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials.

Importance: This study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels. Objective: To examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage. Design, Setting, and Participants: These 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated: individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifying smokers with socioeconomic disadvantage. Data were analyzed from September 2019 to July 2020. Interventions: Random assignment to 1 of 3 study cigarettes provided weekly at no cost for 12 weeks. Main Outcomes and Measures: The primary outcome was between-group differences in mean total cigarettes smoked daily (CPD) during week 12; secondary outcomes included CPD for study and nonstudy cigarettes and dependence severity across weeks analyzed using analysis of covariance, random coefficients growth modeling, or repeated measures analysis of variance. Results: A total of 775 participants were included (mean [SD] age, 35.59 [11.05] years; 551 [71.10%] women [owing to 1 population being exclusively women]); participants smoked a mean (SD) of 17.79 (9.18) CPD at study intake. A total of 286 participants were randomized to 0.4 mg/g, 235 participants were randomized to 2.4 mg/g, and 254 participants were randomized to 15.8 mg/g. Participants randomized to VLNC cigarettes had decreased mean [SEM] total CPD during week 12 across populations (Cohen d = 0.61; P < .001). At week 12, mean (SEM) CPD decreased to 17.96 (0.98) CPD in the 0.4 mg/g group and to 19.53 (1.07) CPD in the 2.4 mg/g group, both of which were significantly different from the 15.8 mg/g group (25.08 [1.08] CPD at week 12) but not each other (0.4 mg/g adjusted mean difference: -7.54 [95%CI, -9.51 to -5.57]; 2.4 mg/g adjusted mean difference: -5.34 [95% CI, 7.41 to -3.26]). Several secondary outcomes differed across populations randomized to VLNCs, including mean total CPD across weeks, with linear trends lower in participants receiving 0.4 mg/g (-0.28 [95%CI, -0.39 to -0.18]; P < .001) and 2.4 mg/g (-0.13 [95%CI, -0.25 to -0.01]; P < .001) doses compared with those receiving the 15.8 mg/g dose (0.30 [95% CI, 0.19 to 0.41]). Fagerström Test of Nicotine Dependence mean total scores were significantly lower in participants who received VLNCs (Cohen d = 0.12; P < .001), with those who received the 0.4 mg/g dose (mean [SD] score, 3.99 [0.06]; P < .001 vs 15.8 mg/g) or 2.4 mg/g dose (mean [SD] score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other. Conclusions and Relevance: These findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation. Trial Registration: ClinicalTrials.gov Identifiers: NCT02232737, NCT02250664, NCT02250534.

Abuse liability of cigarettes with very low nicotine content in pregnant cigarette smokers.

The U.S. Food and Drug Administration has proposed reducing the nicotine content of cigarettes to a minimally-addictive level. To our knowledge, this study is the first to examine how pregnant smokers respond to very low nicotine content (VLNC) cigarettes. In Phase 1, participants blindly sampled two VLNC cigarettes (0.4 and 2.4 mg/g of tobacco) and their usual brand (UB) cigarette in separate sessions, then completed a behavioral economic simulation task and measures of subjective effects, craving/withdrawal, and smoking topography. Phase 2 directly compared the relative reinforcing effects of the cigarettes using concurrent choice testing. All possible dose-pair combinations were tested in separate sessions where puffs were earned ad libitum by clicking the code associated with their preferred cigarette 10 times. Phase 3 tested the 0.4 mg/g-UB dose-pair where UB puffs could be earned with a progressively incremented number of clicks (maximum 8400). Ten pregnant smokers in Burlington, VT and Baltimore, MD participated in 2017-2018. Regarding abuse liability, participants chose the 0.4-mg/g dose less than UB (22% vs. 78%) during concurrent choice testing and the 0.4-mg/g dose sustained less demand than the 2.4-mg/g and UB doses on the simulation task. Positive subjective effects were also lower for both VLNC cigarettes vs. UB. Each cigarette reduced nicotine craving/withdrawal and no significant changes indicative of compensatory smoking were noted. Reducing the nicotine content of cigarettes may decrease their abuse liability in pregnant smokers without causing untoward craving/withdrawal or compensatory smoking. Studies of extended exposure to VLNCs in pregnant women are warranted.

Comparing participant estimated demand intensity on the cigarette Purchase Task to consumption when usual-brand cigarettes were provided free.

Accumulating evidence suggests that the hypothetical Cigarette Purchase Task (CPT), especially its demand Intensity index (i.e., estimated cigarettes participants would smoke if free), is associated with individual differences in smoking risk. Nevertheless, few studies have examined the extent to which hypothetical CPT demand Intensity may differ from consumption when participants are provided with free cigarettes. That topic is the overarching focus of the present study. Participants were 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage. CPT was administered for usual-brand cigarettes prior to providing participants with seven days of their usual-brand cigarettes free of cost and consumption was recorded daily via an Interactive Voice Response (IVR) System. Demand Intensity was correlated with IVR smoking rate (rs 0.670-0.696, ps < 0.001) but estimates consistently exceeded IVR smoking rates by an average of 4.4 cigarettes per day (ps < 0.001). Importantly, both measures were comparably sensitive to discerning well-established differences in smoking risk, including greater cigarettes per day among men versus women (F(1,732) = 18.74, p < 0.001), those with versus without opioid-dependence (F(1,732) = 168.37, p < 0.001), younger versus older adults (F(2,730) = 32.93, p < 0.001), and those with lower versus greater educational attainment (F(1,732) = 38.26, p < 0.001). Overall, CPT demand Intensity appears to overestimate consumption rates relative to those observed when participants are provided with free cigarettes, but those deviations are systematic (i.e., consistent in magnitude and direction, Fs all <1.63; ps > 0.19 for all interactions with subgroups). This suggests that demand Intensity was sensitive to established group differences in smoking rate, supporting its utility as an important measure of addiction potential.

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.

Using the Cigarette Purchase Task to examine the relative reinforcing value of cigarettes among mothers with versus without opioid dependence.

The Cigarette Purchase Task (CPT), in which participants estimate the number of cigarettes they would smoke across increasing cigarette prices, measures the relative reinforcing value of cigarettes. Although opioid-dependent individuals are particularly vulnerable to tobacco addiction, more research is needed to elucidate whether and to what extent their motivation to smoke differs from not-opioid-dependent smokers controlling for potential sociodemographic differences. Participants were 173 women (65 opioid-dependent) in an ongoing clinical trial for smoking cessation. Baseline CPT responses were compared between opioid-dependent and not-opioid-dependent women using five demand indices: Demand Intensity; Omax; Pmax; Breakpoint (BP); and α, and two latent factors: Amplitude and Persistence. Final regression models adjusted for sociodemographic characteristics differing between the two groups. Opioid-dependent women had greater demand Intensity (i.e., number of cigarettes they would smoke if they were free) than not-opioid dependent women in the adjusted model, F(1, 156) = 6.93, p = .016. No other demand indices differed significantly. Regarding latent factors, demand Amplitude (i.e., volumetric consumption), but not Persistence (i.e., price insensitivity), was greater for opioid-dependent women in the adjusted model, F(1, 146) = 4.04, p = .046. These results further demonstrate that the CPT is a highly sensitive task that can illuminate potentially important individual and population differences in the relative reinforcing value of smoking. Greater demand Intensity and Amplitude differentiated smokers with comorbid opioid dependence; thus, decreasing smoking prevalence among opioid-dependent populations may require policies and interventions that can decrease cigarette demand Intensity and Amplitude. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Smoking prevalence among U.S. national samples of pregnant women.

Several data sources exist for estimating U.S. smoking prevalence among pregnant women, yet each differs in ways that have the potential to impact the estimates. In the present study we used the Population Assessment of Tobacco and Health (PATH), the National Survey on Drug use and Health (NSDUH), and the Pregnancy Risk Assessment Monitoring System (PRAMS), three common data sources, to evaluate the following questions about estimating U.S. smoking prevalence among pregnant women: To what extent are estimates impacted by differences in whether the samples include younger (<18 years) or older (>44 years) women, represent smoking in any trimester or only the 3rd, and use data from nationally representative or more selected national samples. Among the factors examined, inclusion of younger or older women does not appear to meaningfully alter prevalence estimates. Focusing on only the third trimester likely underestimates smoking prevalence, while the influence of basing estimates on selected national subgroups of women (i.e., only women who delivered live born infants) rather than nationally representative surveys has little discernible influence. Going forward, this research area would benefit from greater consistency in explicitly discussing the sampling methods used and how these various methods may have influenced the estimates reported.

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.