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Objective: Few national estimates are available on the prevalence of tobacco use disorder (TUD) in the United States (US), and most trials exclusively assess daily smoking rather than TUD. We examined the prevalence and trends in cigarette smoking with vs without TUD among adults., Methods: Data came from the 2010-2021 National Survey on Drug Use and Health (n = 483,982), a cross sectional, US representative dataset. A TUD composite variable was created based on established definitions (eg, DSM-5 symptoms). Weighted prevalence of past 30-day cigarette smoking, daily smoking (30/30 days) and nondaily smoking (<30/30 days) with and without TUD, was calculated annually., Results: In 2021, the prevalence of past 30- day overall cigarette smoking was 17%; 11% reported daily cigarette smoking, whereas 6% reported nondaily cigarette smoking. Only 1% of the population reported daily smoking without TUD, whereas 10% reported daily smoking with TUD. Two percent of the population reported nondaily smoking without TUD, and 4% of the population reported nondaily smoking with TUD. Daily smoking with TUD and nondaily smoking with and without TUD decreased significantly from 2010 to 2021 (all P 's < .001). US adults reporting TUD symptoms (vs not) were more likely to be older, identify as White, have lower income and less education, and have a substance use disorder., Conclusions: The prevalence of daily cigarette smoking with TUD was 10× higher than the prevalence of daily cigarette smoking without TUD. Twice as many US adults with nondaily smoking reported TUD than no TUD, illustrating that daily smoking is not necessary for TUD., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Introduction: It is uncertain whether e-cigarettes facilitate smoking cessation in the real world. We aimed to understand whether and how transitions among cigarette, e-cigarette, and dual use are associated with sociodemographics, dependence measures, and biomarkers., Aims and Methods: We followed 380 adult daily cigarette users and dual users every 2 months for up to 2 years. We estimated transition rates between noncurrent, cigarette-only, e-cigarette-only, and dual use states using a multistate transition model. We estimated univariable hazard ratios (HR) for demographics, dependence measures for cigarettes and e-cigarettes, biomarkers, spousal or partner behaviors, and other measures., Results: We estimated that participants transitioned from cigarette-only to e-cigarette-only through a period of dual use. Dual users ceased smoking (transitioning to e-cigarette-only use) at a greater rate than cigarette-only users did (HR 2.44, 95% CI: 1.49, 4.02). However, of the 60% of dual users estimated to transition to single product use in 1 year, 83% would transition to cigarette-only use and only 17% to e-cigarette-only use. E-cigarette dependence measures were generally associated with reduced e-cigarette cessation rather than enhanced cigarette cessation. E-cigarette users motivated by harm or toxicity reduction or because of restrictions on where or when they could smoke had reduced rates of smoking relapse. Cigarette dependence and spousal smoking were barriers to cigarette cessation for dual users, while using e-cigarettes first in the morning, motivation to quit smoking, and sensory, social, and emotional enjoyment of e-cigarettes (secondary dependence motives) were facilitators of smoking cessation among dual users., Conclusions: Tobacco control policy and interventions may be informed by the barriers and facilitators of product transitions., Implications: Although e-cigarettes have the potential to promote smoking cessation, their real-world impact is uncertain. In this cohort, dual users were more likely to quit smoking than cigarette-only users, but the overall impact was small because most dual users returned to cigarette-only use. Moreover, e-cigarette dependence promoted continued dual use rather than smoking cessation. Yet, high motivation to quit smoking and the sensory, social, and emotional enjoyment of e-cigarettes facilitated smoking cessation in dual users. Better understanding the barriers and facilitators of transitions can help to develop regulations and interventions that lead to more effective use of e-cigarettes for smoking cessation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Effective treatments for smoking cessation exist but are underused. Proactive chronic care approaches may enhance the reach of cessation treatment and reduce the prevalence of smoking in healthcare systems. This pragmatic study evaluated a population-based Comprehensive Tobacco Intervention Program (CTIP) implemented in all (6) adult primary care clinics in a Madison, Wisconsin, USA healthcare cooperative, assessing treatment reach, reach equity, and effectiveness in promoting smoking cessation. CTIP launched in 3 waves of 2 clinics each in a multiple baseline design. Electronic health record (EHR) tools facilitated clinician-delivered pharmacotherapy and counseling; guiding tobacco care managers in phone outreach to all patients who smoke; and prompting multimethod bulk outreach to all patients on a smoking registry using an opt-out approach. EHR data were analyzed to assess CTIP reach and effectiveness among 6894 adult patients between January 2018 and February 2020. Cessation treatment reach increased significantly after CTIP launch in 5 of 6 clinics and was significantly higher when clinics were active vs. inactive in CTIP [Odds Ratio (OR) range = 2.0-3.0]. Rates of converting from current to former smoking status were also higher in active vs. inactive clinics (OR range = 2.2-10.5). Telephone treatment reach was particularly high in historically underserved groups, including African-American, Hispanic, and Medicaid-eligible patients. Implementation of a comprehensive, opt-out, chronic-care program aimed at all patients who smoke was associated with increases in the rates of pharmacotherapy and counseling delivery and quitting smoking. Proactive outreach may help reduce disparities in treatment access., Competing Interests: Declaration of Competing Interest Danielle E. McCarthy, Michael C. Fiore, and Timothy B. Baker have all received grant funding from NCI, the institute that sponsors SmokefreeTXT. Michael C. Fiore serves as a consultant to the National Cancer Institute (NCI) on tobacco cessation policy issues. Timothy B. Baker has served as a paid consultant to ICF to evaluate the portfolio of Smokefree resources via monies supplied by NCI. His consulting activities involved suggesting new research directions for digital health interventions and providing feedback to ICF and NCI on research products on such interventions. The research reported in this report was not part of his consulting work with ICF/NCI. Timothy B. Baker is Principal Investigator on a project funded by NHLBI for which Pfizer provided free active and placebo varenicline. Pfizer played no role in the design, implementation, or analysis of the project described in the present manuscript. All other authors have no conflicts to report. The electronic health record tools described in this manuscript are marketed by Epic Systems Corporation., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown., Aims and Methods: We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent)., Results: PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04-1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51-0.99], p = .045)., Conclusions: PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors., Implications: There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There are evidence-based treatments for tobacco dependence, but inequities exist in the access to and reach of these treatments. Traditional models of tobacco treatment delivery are "reactive" and typically provide treatment only to patients who are highly motivated to quit and seek out tobacco treatment. Newer models involve "proactive" outreach, with benefits that include increasing access to tobacco treatment, prompting quit attempts among patients with low motivation, addressing health disparities, and improving population-level quit rates. However, the definition of "proactive" is not clear, and adoption has been slow. This commentary introduces a comprehensive yet flexible model of proactive outreach and describes how proactive outreach can optimize clinical research and care delivery in these domains: (1) identifying the population, (2) offering treatment, and (3) delivering treatment. Dimensions relevant to each domain are the intensity of proactive outreach (low to high) and the extent to which proactive outreach activities rely on human interaction or are facilitated by information technology (IT). Adoption of the proposed proactive outreach model could improve the precision and rigor with which tobacco cessation research and tobacco treatment programs report data, which could have a positive effect on care delivery and patient outcomes., (© 2022. The Author(s).)

Objective: The aim of this study was to examine dependence on combustible and e-cigarettes among users of both products (dual users), which may provide important insights into long-term use patterns. Method: Dual users (smoking daily for 3 months, using e-cigarettes at least once/week for the past month; N = 256; 45% women, 71% White, M age 39.0 years) not interested in quitting either product participated in a longitudinal, 2-year, observational study. At baseline, participants completed measures of combustible and e-cigarette dependence (Fagerström Test of Cigarette Dependence [FTCD], e-FTCD, Wisconsin Inventory of Smoking Dependence Motives [WISDM], e-WISDM, Penn State Cigarette Dependence Index, and Penn State E-Cigarette Dependence Index) and carried a study smartphone for 2 weeks to record cigarette and e-cigarette use events. Results: Most measures of dependence were product specific (e.g., FTCD and e-FTCD were not correlated, r = -0.003) and predicted product-specific outcomes (e.g., long-term use of that product). However, individuals used the two products for some of the same secondary dependence motives (e.g., weight control, cognitive and affective enhancement). These secondary, or instrumental, motives predicted use of both products at 1 year. Which product was used first in the morning was strongly related to product dependence scores and likelihood of continued product use at 1 year. Conclusions: Among dual users of combustible and e-cigarettes, measures of e-cigarette and cigarette dependence tended to be unrelated to one another, but dual users tended to use both products for the same instrumental motives. Which product is used first in the morning may serve as a valuable measure of relative dependence on the two products. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction: The purpose of this study is to examine the predictive utility of polygenic risk scores (PRSs) for smoking behaviors., Aims and Methods: Using summary statistics from the Sequencing Consortium of Alcohol and Nicotine use consortium, we generated PRSs of ever smoking, age of smoking initiation, cigarettes smoked per day, and smoking cessation for participants in the population-based Atherosclerosis Risk in Communities (ARIC) study (N = 8638), and the Collaborative Genetic Study of Nicotine Dependence (COGEND) (N = 1935). The outcomes were ever smoking, age of smoking initiation, heaviness of smoking, and smoking cessation., Results: In the European ancestry cohorts, each PRS was significantly associated with the corresponding smoking behavior outcome. In the ARIC cohort, the PRS z-score for ever smoking predicted smoking (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.31, 1.43); the PRS z-score for age of smoking initiation was associated with age of smoking initiation (OR: 0.87; 95% CI: 0.82, 0.92); the PRS z-score for cigarettes per day was associated with heavier smoking (OR: 1.17; 95% CI: 1.11, 1.25); and the PRS z-score for smoking cessation predicted successful cessation (OR: 1.24; 95% CI: 1.17, 1.32). In the African ancestry cohort, the PRSs did not predict smoking behaviors., Conclusions: Smoking-related PRSs were associated with smoking-related behaviors in European ancestry populations. This improvement in prediction is greatest in the lowest and highest genetic risk categories. The lack of prediction in African ancestry populations highlights the urgent need to increase diversity in research so that scientific advances can be applied to populations other than those of European ancestry., Implications: This study shows that including both genetic ancestry and PRSs in a single model increases the ability to predict smoking behaviors compared with the model including only demographic characteristics. This finding is observed for every smoking-related outcome. Even though adding genetics is more predictive, the demographics alone confer substantial and meaningful predictive power. However, with increasing work in PRSs, the predictive ability will continue to improve., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate how strongly smoking dependence and smoking dependence motives are associated with depressive symptoms among daily smokers and if these associations are independent of measured confounders and shared familial factors., Design: Cross-sectional individual-based and within-pair analyses., Setting: Fourth wave of the population-based Finnish Twin Cohort conducted in 2011., Participants: 918 daily smokers born 1945-1957 (48% men), mean age 59.5 years including 38 twin pairs discordant for depression., Measurements: Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale with a cut off value ≥20 for depression. Smoking dependence was assessed using the Fagerström Test for Cigarette Dependence (FTCD) and smoking dependence motives with three subscales from the multi-dimensional Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM): primary dependence motives (PDM), affective enhancement (AE), and Taste. Logistic regressions, using standardized scores of independent variables and adjusted for multiple confounders with correction for sampling as twin pairs, were used in the individual-based analyses. Conditional logistic regression was used to control for shared familial factors in discordant twin pairs., Findings: Prevalence of depression was 18% (n = 163: 61 [14%] in men, n = 102 [22%] in women). Higher smoking dependence measured by the FTCD (OR 1.45; 95% CI 1.20, 1.75), and dependence motives measured by the PDM (1.56; 1.30, 1.87) and the AE (1.54; 1.28, 1.85) were associated with higher odds of depression. The associations remained after adjusting for individual confounders, except for neuroticism, which attenuated all associations. FTCD, PDM, and AE showed associations with depression within depression-discordant monozygotic pairs, suggesting an association independent of familial factors., Conclusions: Depression appears to be associated with smoking dependence and smoking dependence motives related to heavy, automatic use and use to regulate affective states. The associations appear to be confounded or mediated by neuroticism but are independent of shared familial influences., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Tobacco smoking is an important risk factor for cancer incidence, an effect modifier for cancer treatment, and a negative prognostic factor for disease outcomes. Inadequate implementation of evidence-based smoking cessation treatment in cancer centers, a consequence of numerous patient-, provider-, and system-level barriers, contributes to tobacco-related morbidity and mortality. This study provides data for a paradigm shift from a frequently used specialist referral model to a point-of-care treatment model for tobacco use assessment and cessation treatment for outpatients at a large cancer center. The point-of-care model is enabled by a low-burden strategy, the Electronic Health Record-Enabled Evidence-Based Smoking Cessation Treatment program, which was implemented in the cancer center clinics on June 2, 2018. Five-month pre- and post-implementation data from the electronic health record (EHR) were analyzed. The percentage of cancer patients assessed for tobacco use significantly increased from 48% to 90% (z = 126.57, p < .001), the percentage of smokers referred for cessation counseling increased from 0.72% to 1.91% (z = 3.81, p < .001), and the percentage of smokers with cessation medication significantly increased from 3% to 17% (z = 17.20, p < .001). EHR functionalities may significantly address barriers to point-of-care treatment delivery, improving its consistent implementation and thereby increasing access to and quality of smoking cessation care for cancer center patients., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r g  = 0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking.

Introduction: Greater use of nicotine replacement therapy (NRT) is related to smoking cessation success, but the causal direction is unclear. This study characterized the relationship between NRT use and smoking lapse and relapse., Methods: Participants (N = 416 smokers; 57% female, 85% White) were recruited from primary care for a smoking cessation factorial experiment and analyzed if abstaining ≥1 day in the first 2 weeks post-target quit day (TQD). Participants were randomized to counseling and 8 versus 26 weeks of nicotine patch plus nicotine gum post-TQD. Participants carried electronic dispensers that timestamped each gum use. Participants who lapsed (smoked after abstaining) within 6 weeks post-TQD were matched with nonlapsers (n = 146 pairs) on multiple variables. We compared lapsers' versus matched nonlapsers' gum use in the 5 days before and after the lapsers' first lapse., Results: By week 6 post-TQD, 63% of participants lapsed. Compared with nonlapsers, lapsers used less gum 1 and 2 days pre-"lapse" and on the 5 days post-lapse. Lapsers used less gum during the 5 days post-lapse than the 5 days pre-lapse. Univariate survival analyses with lapsers showed greater gum use during both pre- and post-lapse periods predicted longer latency to relapse in the first 6 weeks., Conclusions: In a smoking cessation attempt using nicotine patch plus gum, lapsers versus matched nonlapsers used less gum immediately preceding and following their first lapse. Lower mean gum use before and after lapses predicted a more rapid escalation to relapse. Decreased nicotine gum use both precedes and follows returns to smoking during cessation attempts., Implications: This research examined electronically monitored nicotine gum use collected in real time and found that among smokers engaged in a quit attempt, lapsers (vs. matched nonlapsers) tended to decrease their gum use 1-2 days prior to lapsing and to further decrease their gum use from pre- to post-lapse. Decreased gum use pre-lapse may signal heightened lapse risk in 1-2 days, with lower level of gum use predicting a more precipitous course of relapse. These results encourage further exploration of objective measures of smoking medication use patterns to examine their signaling properties and to inform understanding of cessation failure., Clinical Trial Registration: ClinicalTrials.gov NCT01120704., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Tobacco cessation after cancer diagnosis leads to better patient outcomes. However, tobacco treatment services are frequently unavailable in cancer care settings, and multilevel implementation challenges can impede uptake of new programs. The National Cancer Institute (NCI) dedicated Cancer Moonshot funding through the Cancer Center Cessation Initiative (C3I) for NCI-Designated Cancer Centers to implement or enhance the implementation of tobacco treatment services. We examined a pragmatic application of the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate tobacco treatment programs implemented within Cancer Centers funded through C3I. Using three C3I-funded Centers as examples, we describe how each RE-AIM construct was operationalized to evaluate the implementation of a wide range of cessation services (e.g., tobacco use screening, counseling, Quitline referral, pharmacotherapy) in this heterogeneous group of cancer care settings. We discuss the practical challenges encountered in assessing RE-AIM constructs in real world situations, including using the electronic health record (EHR) to aid in assessment. Reach and effectiveness evaluation required that Centers define the setting(s) where cessation services were implemented (to determine the "denominator"), enumerate the patient population, report current patient tobacco use, patient engagement in tobacco treatment, and 6-month cessation outcomes. To reduce site heterogeneity, increase data accuracy, and reduce burden, reach was frequently captured via standardized EHR enhancements that improved the identification of current smokers and tobacco treatment referrals. Effectiveness was determined by cessation outcomes (30-day point prevalence abstinence at 6-months post-engagement) assessed through a variety of data collection approaches. Adoption was measured by the characteristics and proportion of targeted cancer care settings and clinicians engaged in cessation service delivery. Implementation was assessed by examining the delivery of tobacco screening assessments and intervention components across sites, and provider-level implementation consistency. Maintenance assessments identified whether tobacco treatment services continued in the setting after implementation and documented the sustainability plan and organizational commitment to continued delivery. In sum, this paper demonstrates a pragmatic approach to using RE-AIM as an evaluation framework that yields relevant outcomes on common implementation metrics across widely differing tobacco treatment approaches and settings., (Copyright © 2020 D'Angelo, Ramsey, Rolland, Chen, Bernstein, Fucito, Webb Hooper, Adsit, Pauk, Rosenblum, Cinciripini, Joseph, Ostroff, Warren, Fiore and Baker.)

Introduction: FTND (Fagerstrӧm test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported., Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts., Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND., Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND., Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Electronic cigarettes (e-cigarettes) have drastically changed the nicotine and tobacco product landscape. However, their potential public health impact is still unclear. A reliable and valid measure of e-cigarette dependence would likely advance assessment and prognostication of the public health impact of e-cigarettes. The aim of this research was to examine the internal consistency, structure, and validity of three e-cigarette dependence scales., Methods: Adult dual users (smokers who also vape, N = 256) enrolled in an observational cohort study (45.1% women, 70.7% white). At baseline, participants completed the e-cigarette Fagerström Test of Cigarette Dependence (e-FTCD), the e-cigarette Wisconsin Inventory of Smoking Dependence Motives (e-WISDM), and the Penn State Electronic Cigarette Dependence Index (PS-ECDI). All participants provided a urine sample for cotinine analysis and reported e-cigarette use at 1 year., Results: The e-WISDM subscales had the highest internal consistency (α = .81-.96), then the PS-ECDI (α = .74) and e-FTCD (α = .51). A single-factor structure for the e-FTCD and an 11-factor structure for the e-WISDM were supported, but the PS-ECDI did not have a single-factor structure. All three e-cigarette dependence scales were highly correlated with validation criteria including continued e-cigarette use at 1 year, but not with e-liquid nicotine concentration or cotinine., Conclusions: The e-WISDM and PS-ECDI had stronger internal consistency than did the e-FTCD, despite the e-FTCD's single-factor structure, but all 3 measures appear to be valid measures of e-cigarette dependence as suggested by their significant relations with self-perceived addiction, heavy use, early use after overnight deprivation, and continued use over time., Implications: This research provides empirical support for three e-cigarette dependence measures: the e-FTCD, the PS-ECDI, and the e-WISDM among dual users of e-cigarettes and combustible cigarettes. The PS-ECDI and e-WISDM are more reliable, but all three measures were strongly correlated with key dependence constructs such as heavy use and continued use over time., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings. Then, we examined the effect of an electronic health record-based smoking cessation module on patient receipt of evidence-based cessation care. As part of a quality improvement project, we retrospectively observed 479,798 unique patients accounting for 1,426,089 outpatient clinical encounters from June 2018-March 2019 across 766 clinics in the greater St. Louis, southern Illinois, and mid-Missouri regions. Smoking prevalence was higher in rural versus urban clinics (20.7% vs. 13.9%, 6.7% [6.3, 7.1], odds ratio = 1.6 [1.6, 1.6], p < 0.0001), and yet rural smokers were nearly three times less likely than their urban counterparts to receive any smoking cessation treatment after adjusting for patients clustering within clinics (9.6% vs. 25.8%, -16.2% [-16.9, -15.5], odds ratio = 0.304 [0.28, 0.33], p < 0.0001). Although not yet scaled up in the rural setting, we examined the effects of a low-burden, point-of-care smoking module currently implemented in cancer clinics. After adjusting for patient clustering within clinics, patients were more likely to receive smoking treatment in clinics that implemented the module versus clinics that did not implement the module (31.2% vs. 17.5% , 13.7% [10.8, 16.6], odds ratio = 2.1 [1.8, 2.6], p < 0.0001). The point-of-care treatment approach offers a promising solution for rural settings, both in and outside the context of cancer care.

Background: Comorbid psychiatric diagnoses have been shown to predict cessation failure. The relative impact of various diagnoses on cessation and other cessation processes is rarely studied, particularly among a general population. The impact of psychiatric history among primary care patients seeking cessation services on nicotine dependence, cessation outcomes, treatment effects and adherence, and withdrawal symptoms was examined., Methods: Secondary data analysis of a multi-site comparative effectiveness smoking cessation trial was conducted. Adult smokers (n  = 1051; 52.5 % Female, 68.1 % white) completed a structured clinical interview at baseline to assess psychiatric diagnostic history (past-year and lifetime). Nicotine dependence was assessed via self-report measures at baseline. Point-prevalence abstinence was assessed at 8 weeks and 6 months post-quit. Withdrawal symptoms were assessed for one week pre- and post-quit using ecological momentary assessment. Treatment adherence was self-reported at 1, 4, 8, and 12 weeks post-quit., Results: Past-year substance use disorder, lifetime mood disorder, and > one lifetime diagnosis, were related to lower rates of short-term, but not long-term, cessation. Lifetime psychiatric diagnosis was related to elevated nicotine dependence, particularly to secondary dependence motives associated with instrumental tobacco use. History of psychiatric diagnosis was associated with increased withdrawal-related craving. There was little evidence that psychiatric diagnostic status moderated the effects of the tested pharmacotherapies on long-term abstinence., Conclusions: Psychiatric diagnoses affect risk factors that exert their effects early in the post-quit process and highlight the potential utility of examining transdiagnostic risk factors to better understand the relations between psychiatric vulnerabilities and the smoking cessation process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: This study examined relations of two affective vulnerabilities, high anxiety sensitivity (AS) and low distress tolerance (DT), with tobacco dependence, withdrawal, smoking cessation, and pharmacotherapy response., Methods: Smokers interested in quitting (N = 1067; 52.2% female, 28.1% African American) were randomized to 12 weeks of nicotine patch, nicotine patch plus nicotine lozenge, or varenicline. Baseline questionnaires assessed AS, DT, negative affect, anxiety, and dependence. Withdrawal was assessed the first-week post-quit via ecological momentary assessment., Results: DT, but not AS, predicted biochemically confirmed point-prevalence abstinence at multiple endpoints: weeks 4, 12, 26, and 52 post-quit (ps < .05); relations remained after controlling for pharmacotherapy treatment, AS, baseline negative affect, anxiety, and anxiety disorder history (ps < .05). Additional exploratory analyses examining week 4 abstinence showed DT predicted abstinence (p = .004) even after controlling for baseline dependence, post-quit withdrawal (craving and negative affect), and treatment. DT moderated treatment effects on abstinence in exploratory analyses (interaction p = .025); those with high DT were especially likely to be abstinent at week 4 with patch plus lozenge versus patch alone., Conclusions: DT, but not AS, predicted abstinence over 1 year post-quit (higher DT was associated with higher quit rates), with little overlap with other affective measures. DT also predicted early abstinence independent of dependence and withdrawal symptoms. Results suggest low DT may play a meaningful role in motivation to use tobacco and constitute an additional affective risk factor for tobacco cessation failure beyond negative affect or clinical affective disorders., Implications: People in a stop-smoking study who reported a greater ability to tolerate distress were more likely to quit smoking and remain smoke-free 1 year later. Smokers with high DT were more likely to be smoke-free 4 weeks after their target quit day if they received nicotine patch plus nicotine lozenge rather than nicotine patch alone., Trial Registration: NCT01553084., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Nonadherence to smoking cessation medication is a frequent problem. Identifying pre-quit predictors of nonadherence may help explain nonadherence and suggest tailored interventions to address it., Aims: Identify and characterize subgroups of smokers based on adherence to nicotine replacement therapy (NRT)., Method: Secondary classification tree analyses of data from a 2-arm randomized controlled trial of Recommended Usual Care (R-UC, n = 315) versus Abstinence-Optimized Treatment (A-OT, n = 308) were conducted. R-UC comprised 8 weeks of nicotine patch plus brief counseling whereas A-OT comprised 3 weeks of pre-quit mini-lozenges, 26 weeks of nicotine patch plus mini-lozenges, 11 counseling contacts, and 7-11 automated reminders to use medication. Analyses identified subgroups of smokers highly adherent to nicotine patch use in both treatment conditions, and identified subgroups of A-OT participants highly adherent to mini-lozenges., Results: Varied facets of nicotine dependence predicted adherence across treatment conditions 4 weeks post-quit and between 4- and 16-weeks post-quit in A-OT, with greater baseline dependence and greater smoking trigger exposure and reactivity predicting greater medication use. Greater quitting motivation and confidence, and believing that stop smoking medication was safe and easy to use were associated with greater adherence., Conclusion: Adherence was especially high in those who were more dependent and more exposed to smoking triggers. Quitting motivation and confidence predicted greater adherence, while negative beliefs about medication safety and acceptability predicted worse adherence. Results suggest that adherent use of medication may reflect a rational appraisal of the likelihood that one will need medication and will benefit from it., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data., Materials & Methods: Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation., Results: Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R 2 range: 9.2-16%; minimum p = 7.6 × 10 -8 ). The GWAS top hit variant rs56113850 significantly predicted nicotine metabolism biomarkers (R 2 range: 14-17%; minimum p = 4.4 × 10 -8 ). There was insufficient evidence for these PRSs predicting smoking quantity and smoking cessation., Conclusion: Results suggest that nicotine metabolism PRSs based on GWAS meta-analyses predict an individual's nicotine metabolism, so does use of the top hit variant. We anticipate that PRSs will enter clinical medicine, but additional research is needed to develop a more comprehensive genetic score to predict smoking behaviors.

Objective: To examine the effects of five intervention components on smokers' adherence to combined nicotine patch and nicotine gum during a quit attempt and assess whether adherence is related to cessation., Method: Smokers interested in quitting (N = 513; 59% female; 87% White) received nicotine patch plus nicotine gum and participated in a 2x2x2x2x2 randomized factorial experiment (i.e., 32 treatment conditions) evaluating five intervention components: (1) medication adherence counseling versus none; (2) automated medication adherence calls versus none; (3) electronic medication monitoring with feedback and counseling versus e-monitoring alone; (4) 26 versus 8 weeks of nicotine patch plus nicotine gum; and (5) maintenance counseling versus none. Adherence was assessed over the first 6 weeks post-target quit day via timeline follow-back (nicotine patch) and electronic medication dispenser (gum)., Results: In the first 6 weeks post-quit day, 12% of participants used no patches or gum, and 40% used the patch every day. Only 1.4% used both patch and gum adherently every day in the 6 weeks post-target quit day. E-monitoring counseling increased gum use (from 1.9 to 2.6 pieces/day; p < .001) but did not increase abstinence. More adherent patch and gum use in the first 6 weeks were each associated with higher point-prevalence abstinence rates through 1 year., Conclusions: This large experiment with electronic monitoring of nicotine gum adherence showed that e-monitoring counseling increased gum use but not abstinence. Adherence to nicotine patch and to gum were each strongly related to abstinence, but it is unclear whether adherence increases abstinence, or relapse causes medication discontinuation., Clinical Trial Registration: ClinicalTrials.gov NCT01120704.

Background: The Fagerström Test for Nicotine Dependence (FTND), a derivation of the Fagerström Tolerance Questionnaire, was first published in 1991. The FTND remains one of the most widely used measures of nicotine dependence for studying genetic and epidemiological risk factors and the likelihood of smoking cessation. However, it is unclear whether secular trends in patterns of smoking alter the psychometric properties of the FTND and its interpretation., Methods: We examined measurement invariance in the lifetime and current FTND scores across birth cohorts using participants drawn from six study samples (N = 13,775)., Results: We found significant (p < 0.05) measurement non-invariance in means and factor loadings of most FTND items by birth cohort, but effect sizes, ranging from r 2  = 0.0001 to r 2  = 0.0035, indicated that less than 0.5% of the model variance was explained by the measurement non-invariance for each factor loading. To assess its impact, we regressed the lifetime FTND latent variable on well-established factors associated with nicotine dependence (quitting smoking and the nicotinic acetylcholine receptor gene [CHRNA5] variant rs16969968, separately), and we observed that the regression coefficients were unchanged between models with and without adjustment for measurement non-invariance., Conclusions: These findings suggest that possible FTND non-invariance that occurs across study samples of various birth years has a negligible impact on study results., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Research shows that abstinence from tobacco leads to a withdrawal-related decrement in responsivity to nondrug rewards (ie, anhedonia). However, it remains unclear how anhedonia relates to other key withdrawal symptoms and withdrawal-related constructs over time. We analyzed ecological momentary assessment data to examine whether a decrement in response to rewards during a 10-day period following quitting shows a pattern of associations with other variables (ie, treatment, tobacco dependence, negative affect, and craving) that is consistent with anhedonia being a tobacco withdrawal symptom., Methods: As part of a randomized controlled trial of smoking cessation therapies, 1122 adults (58% female) were assigned to: placebo (n = 131), bupropion (alone or with nicotine lozenge; n = 401), or nicotine replacement therapy (NRT; lozenge, patch, both; n = 590). Participants completed 4 ecological momentary assessments per day for 10 days postquit, resulting in 22 575 assessments., Results: Time-varying effect modeling showed that anhedonia was significantly greater among those high in dependence relative to lower dependent smokers out to day 9 postquit. The placebo group showed elevated anhedonia immediately postquit, which fell to levels similar to the treatment groups by day 7. NRT effectively reduced anhedonia and its time-varying association with craving early in the quit attempt. The positive association between negative affect and anhedonia was moderate and stable over time for both active treatment groups., Conclusions: These results provide additional support that anhedonia following quitting smoking is a manifestation of the tobacco withdrawal syndrome., Implications: This study supported the hypothesis that diminished responsivity to nondrug rewards (ie, anhedonia) is a symptom of the tobacco withdrawal syndrome. Results showed that anhedonia: (1) was significantly associated with dependence, especially during the early postquit period when withdrawal was at its peak intensity; (2) showed significant time-varying associations with other withdrawal symptoms, especially craving; and (3) was significantly suppressed by agonist administration as was its association with craving over time., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability., Methods: Dual users (cigarettes+e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app., Results: Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression., Discussion: Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender., Competing Interests: No conflict declared., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Although withdrawal processes form a key motivational basis for cigarette use, smoking cessation treatments appear to exert only modest effects on withdrawal. One treatment option for further reducing withdrawal severity would be to provide smokers with withdrawal regulation training. The objective of this study was to pilot a smoking cessation intervention comprising withdrawal exposure with withdrawal regulation training., Methods: Adult smokers (N=80) were randomized to one of two conditions: 1) Withdrawal Exposure with Withdrawal Regulation Training (WT), which included the development and application of individualized withdrawal regulation strategies over four separate sessions that spanned the first four hours of abstinence; 2) or Relaxation Control (RC) training, which controlled for the therapeutic contact of WT. All sessions occurred before the quit date, after which differential treatment was discontinued and all participants received brief counseling, nicotine replacement therapy, and self-help literature. Biochemically-confirmed (CO≤3) seven-day point-prevalence abstinence was assessed at Months 2 and 3 after end-of-treatment., Results: Treatment completion and ratings of credibility and efficacy were high and equivalent across conditions. 22.2% of participants in the WT condition were abstinent at both time points, whereas 0% and 4.2% of participants in the RC condition were abstinent at Months 2 and 3 (Month 3 OR=6.5 [0.73, 59.19]). In-session withdrawal ratings suggested WT improved regulation of withdrawal symptoms, which were in turn associated with abstinence., Conclusions: This small pilot study suggests that WT promotes abstinence by enhancing withdrawal regulation. Results warrant further investigation of this innovative treatment approach., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: To identify promising intervention components that help smokers attain and maintain abstinence during a quit attempt., Design: A 2 × 2 × 2 × 2 × 2 randomized factorial experiment., Setting: Eleven primary care clinics in Wisconsin, USA., Participants: A total of 544 smokers (59% women, 86% white) recruited during primary care visits and motivated to quit., Interventions: Five intervention components designed to help smokers attain and maintain abstinence: (1) extended medication (26 versus 8 weeks of nicotine patch + nicotine gum); (2) maintenance (phone) counseling versus none; (3) medication adherence counseling versus none; (4) automated (medication) adherence calls versus none; and (5) electronic medication monitoring with feedback and counseling versus electronic medication monitoring alone., Measurements: The primary outcome was 7-day self-reported point-prevalence abstinence 1 year after the target quit day., Findings: Only extended medication produced a main effect. Twenty-six versus 8 weeks of medication improved point-prevalence abstinence rates (43 versus 34% at 6 months; 34 versus 27% at 1 year; P = 0.01 for both). There were four interaction effects at 1 year, showing that an intervention component's effectiveness depended upon the components with which it was combined., Conclusions: Twenty-six weeks of nicotine patch + nicotine gum (versus 8 weeks) and maintenance counseling provided by phone are promising intervention components for the cessation and maintenance phases of smoking treatment., (© 2015 Society for the Study of Addiction.)

Aims: To screen promising intervention components designed to reduce smoking and promote abstinence in smokers initially unwilling to quit., Design: A balanced, four-factor, randomized factorial experiment., Setting: Eleven primary care clinics in southern Wisconsin, USA., Participants: A total of 517 adult smokers (63.4% women, 91.1% white) recruited during primary care visits who were willing to reduce their smoking but not quit., Interventions: Four factors contrasted intervention components designed to reduce smoking and promote abstinence: (1) nicotine patch versus none; (2) nicotine gum versus none; (3) motivational interviewing (MI) versus none; and (4) behavioral reduction counseling (BR) versus none. Participants could request cessation treatment at any point during the study., Measurements: The primary outcome was percentage change in cigarettes smoked per day at 26 weeks post-study enrollment; the secondary outcomes were percentage change at 12 weeks and point-prevalence abstinence at 12 and 26 weeks post-study enrollment., Findings: There were few main effects, but a significant four-way interaction at 26 weeks post-study enrollment (P = 0.01, β = 0.12) revealed relatively large smoking reductions by two component combinations: nicotine gum combined with BR and BR combined with MI. Further, BR improved 12-week abstinence rates (P = 0.04), and nicotine gum, when used without MI, increased 26-week abstinence after a subsequent aided quit attempt (P = 0.01)., Conclusions: Motivation-phase nicotine gum and behavioral reduction counseling are promising intervention components for smokers who are initially unwilling to quit., (© 2015 Society for the Study of Addiction.)

Aims: To identify promising intervention components intended to help smokers to attain and maintain abstinence in their quit smoking attempts., Design: A fully crossed, six-factor randomized fractional factorial experiment., Setting: Eleven primary care clinics in southern Wisconsin, USA., Participants: A total of 637 adult smokers (55% women, 88% white) motivated to quit smoking who visited primary care clinics., Interventions: Six intervention components designed to prepare smokers to quit, and achieve and maintain abstinence (i.e. for the preparation, cessation and maintenance phases of smoking treatment): (1) preparation nicotine patch versus none; (2) preparation nicotine gum versus none; (3) preparation counseling versus none; (4) intensive cessation in-person counseling versus minimal; (5) intensive cessation telephone counseling versus minimal; and (6) 16 versus 8 weeks of combination nicotine replacement therapy (nicotine patch  +  nicotine gum)., Measurements: Seven-day self-reported point-prevalence abstinence at 16 weeks., Findings: Preparation counseling significantly improved week 16 abstinence rates (P = .04), while both forms of preparation nicotine replacement therapy interacted synergistically with intensive cessation in-person counseling (P < 0.05). Conversely, intensive cessation phone counseling and intensive cessation in-person counseling interacted antagonistically (P < 0.05)-these components produced higher abstinence rates by themselves than in combination., Conclusions: Preparation counseling and the combination of intensive cessation in-person counseling with preparation nicotine gum or patch are promising intervention components for smoking and should be evaluated as an integrated treatment package., (© 2015 Society for the Study of Addiction.)

Background and Aims: A chronic care strategy could potentially enhance the reach and effectiveness of smoking treatment by providing effective interventions for all smokers, including those who are initially unwilling to quit. This paper describes the conceptual bases of a National Cancer Institute-funded research program designed to develop an optimized, comprehensive, chronic care smoking treatment., Methods: This research is grounded in three methodological approaches: (1) the Phase-Based Model, which guides the selection of intervention components to be experimentally evaluated for the different phases of smoking treatment (motivation, preparation, cessation, and maintenance); (2) the Multiphase Optimization Strategy (MOST), which guides the screening of intervention components via efficient experimental designs and, ultimately, the assembly of promising components into an optimized treatment package; and (3) pragmatic research methods, such as electronic health record recruitment, that facilitate the efficient translation of research findings into clinical practice. Using this foundation and working in primary care clinics, we conducted three factorial experiments (reported in three accompanying papers) to screen 15 motivation, preparation, cessation and maintenance phase intervention components for possible inclusion in a chronic care smoking treatment program., Results: This research identified intervention components with relatively strong evidence of effectiveness at particular phases of smoking treatment and it demonstrated the efficiency of the MOST approach in terms both of the number of intervention components tested and of the richness of the information yielded., Conclusions: A new, synthesized research approach efficiently evaluates multiple intervention components to identify promising components for every phase of smoking treatment. Many intervention components interact with one another, supporting the use of factorial experiments in smoking treatment development., (© 2015 Society for the Study of Addiction.)

Background: This study tests whether the genetic predictor (CHRNA5 nicotine receptor gene variants) and an environmental risk factor (partner smoking) interact in the prediction of smoking reduction., Methods: Subjects were from a community-based, longitudinal study of women (n=1856) who smoked before pregnancy, and a randomized comparative effectiveness smoking cessation trial (n=1065). Smoking reduction was defined as the trajectory of self-reported smoking quantities over time in the observational study, and as the trajectory of alveolar CO levels in the cessation trial., Results: In the pregnancy study, rs16969968 genotype and partner smoking status interacted such that the smoking reduction was lowest for expectant mothers with high genetic risk and partner smoking, and highest for those with high genetic risk but not partner smoking (interaction of genotype×partner smoking on smoking quantity trajectory slope β=0.071, 95%CI=0.013, 0.13, p=0.017). In the clinical trial, a similar interaction was found (interaction β=0.20, 95%CI=0.049, 0.36, p=0.010). Furthermore, these associations were moderated by pharmacotherapy such that the interactive relation of genetic and environmental factors occurred in the placebo group, but not in the active pharmacotherapy group (interaction of genotype×partner smoking×pharmacotherapy on CO trajectory slope β=-0.25, 95%CI=-0.42, -0.091, p=0.0023)., Conclusions: The CHRNA5 genetic risk synergized the effect of partner smoking, producing an especially low likelihood of successful smoking reduction in two complementary studies. This suggests that the genetic vulnerability may be mitigated by altering environmental factors. In addition, cessation pharmacotherapy neutralizes the increase in cessation failure associated with combined genetic and environmental risks, which has possible relevance to treatment algorithms., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This field study tested an intervention that challenged beliefs about the effectiveness of various quit methods held by Salvation Army client smokers from two urban locations (N = 245). Data (surveys administered immediately after and one month post-intervention) were collected 2009-2010 and analyzed using primarily χ(2) and t-tests. The intervention changed client perceptions about the effectiveness of quitting methods. Compared to no-intervention controls, intervention participants reported significantly greater smoking reduction and greater likelihood of contacting the Wisconsin Tobacco Quit Line. Study implications/limitations are discussed and future research directions noted. This research was supported by grant UL1TR000427 from the Clinical and Translational Science Award (CTSA) program of the National Center for Advancing Translational Sciences, NIH.

We report the results of a randomized trial comparing a novel smoking cessation treatment Mindfulness Training for Smokers (MTS) to a usual care therapy (Controls), which included the availability of a tobacco quit line and nicotine patches. Data were collected from 196 low socioeconomic status smokers in 2010-2011 in Madison, Wisconsin. Participants were randomized to either MTS or a telephonic quit line. The primary outcome was 6-month smoking abstinence measured by carbon monoxide breath testing and Time-Line Follow-Back. Among treatment initiators (randomized participants who participated in the intervention), abstinence rates were significantly different between the MTS (38.7%) and control (20.6%, p = .05) groups. Study limitations are also discussed. Results suggest that further study is warranted.

Objective: Although the relation between lifetime depression and smoking cessation outcome has been well studied, the proposition that different symptomatic expressions of depression exert disparate predictive effects on risk of smoking cessation failure has largely gone uninvestigated. This study analyzed the individual contributions of depression's 2 hallmark affective symptoms, anhedonia (i.e., diminished interest in normally enjoyable activities) and depressed mood (i.e., elevated sadness), to the prediction of smoking cessation outcome., Method: Participants were adult daily smokers (N = 1,469; mean age = 45 years, 58% female, 84% White) enrolled in a smoking cessation treatment study. Lifetime history of anhedonia and depressed mood were classified via structured interview prior to quit day. Seven-day point prevalence smoking abstinence was assessed at 8 weeks and 6 months postquit., Results: When examined separately, both lifetime anhedonia, OR (95% CI) = 1.42 (1.16, 1.73), p = .004, and depressed mood, OR (95% CI) = 1.35 (1.11, 1.63), p = .002, predicted increased odds of relapse. These relations remained after adjusting for covariates, including lifetime depressive disorder, which did not predict outcome. After controlling for the covariation between lifetime anhedonia and depressed mood, anhedonia predicted cessation outcome, OR (95% CI) = 1.31 (1.05, 1.62), p = .02, while depressed mood did not (p = .19). Symptom duration (>2 weeks), treatment, and substance use disorder did not modify relations of lifetime anhedonia and depressed mood with cessation outcome., Conclusions: Results suggest that (1) symptoms of affective disturbance capture depression-relevant risk of cessation failure, which is not adequately demarcated by the lifetime depressive disorder diagnosis, and (2) anhedonia is a more sensitive index of this affective disturbance than depressed mood per se. Clinical attention to anhedonia may facilitate smoking cessation., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Genome-wide significant associations with cigarettes per day (CPD) and risk for lung cancer and chronic obstructive pulmonary disease (COPD) were previously reported in a region of 19q13, including CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response). The associated single nucleotide polymorphisms (SNPs) were assumed to be proxies for functional variation in CYP2A6. Here, we demonstrate that when CYP2A6 and EGLN2 genotypes are analyzed together, the key EGLN2 variant, rs3733829, is not associated with nicotine metabolism independent of CYP2A6, but is nevertheless independently associated with CPD, and with breath carbon monoxide (CO), a phenotype associated with cigarette consumption and relevant to hypoxia. SNPs in EGLN2 are also associated with nicotine dependence and with smoking efficiency (CO/CPD). These results indicate a previously unappreciated novel mechanism behind genome-wide significant associations with cigarette consumption and disease risk unrelated to nicotine metabolism.

Introduction: The great majority of smokers relapse when they make quit attempts. Therefore, understanding the process of relapse may guide the development of more effective smoking cessation or relapse prevention treatments. The goal of this research is to extend our understanding of the context of initial lapses that occur within 8 weeks of quitting by using more comprehensive assessments of context, a contemporary sample, and sophisticated analytic techniques., Methods: Participants from a randomized controlled smoking cessation trial completed baseline assessments of demographics and tobacco dependence, a daily smoking calendar to determine latency to lapse and relapse (7 consecutive days of smoking), and an assessment of initial lapse context (affect, location, activity, interpersonal, smoke exposure, and cigarette availability). Latent class analysis (LCA) was used to analyze the 6 early lapse (within the first 8 weeks; N = 551) context dimensions; logistic regression and Cox regression were used to relate context to cessation outcomes., Results: LCA revealed 5 distinct initial lapse context classes (talking, with friends, angry; social; alone; with spouse, angry; and with smoking spouse) that were differentially related to cessation outcome. The easy availability of cigarettes characterized almost 75% of lapses, but being with friends, drinking, and not being at home were associated with a lower likelihood of progression to relapse., Conclusions: Early lapsing is highly related to ultimate relapse, and lapsing in frequently experienced contexts seemed most strongly linked with progression to full relapse.

Importance: Genome-wide hypothesis-free discovery methods have identified loci that are associated with heavy smoking in adulthood. Research is needed to understand developmental processes that link newly discovered genetic risks with adult heavy smoking., Objective: To test how genetic risks discovered in genome-wide association studies of adult smoking influence the developmental progression of smoking behavior from initiation through conversion to daily smoking, progression to heavy smoking, nicotine dependence, and struggles with cessation., Design: A 38-year, prospective, longitudinal study of a representative birth cohort., Setting: The Dunedin Multidisciplinary Health and Development Study of New Zealand., Participants: The study included 1037 male and female participants., Exposure: We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in 3 meta-analyses of genome-wide association studies of smoking quantity phenotypes., Main Outcomes and Measures: Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerström Test of Nicotine Dependence), and cessation difficulties were evaluated at 8 assessments spanning the ages of 11 to 38 years., Results: Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that 2 adolescent developmental phenotypes-early conversion to daily smoking and rapid progression to heavy smoking-mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history., Conclusions and Relevance: Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers.

Research exploring psychological dysfunction as a predictor of smoking cessation success may be limited by nonoptimal predictor variables (i.e., categorical psychodiagnostic measures vs. continuous personality-based manifestations of dysfunction) and imprecise outcomes (i.e., summative point-prevalence abstinence vs. constituent cessation milestone measures). Accordingly, this study evaluated the unique and overlapping relations of broad-spectrum personality traits (positive emotionality, negative emotionality, and constraint) and past-year psychopathology (anxiety, mood, and substance use disorder) to point-prevalence abstinence and three smoking cessation milestones: (a) initiating abstinence, (b) first lapse, and (c) transition from lapse to relapse. Participants were daily smokers (N = 1365) enrolled in a smoking cessation treatment study. In single-predictor regression models, each manifestation of internalizing dysfunction (lower positive emotionality, higher negative emotionality, and anxiety and mood disorder) predicted failure at one or more cessation milestone(s). In simultaneous predictor models, lower positive and higher negative emotionality significantly predicted failure to achieve milestones after controlling for psychopathology. Psychopathology did not predict any outcome when controlling for personality. Negative emotionality showed the most robust and consistent effects, significantly predicting failure to initiate abstinence, earlier lapse, and lower point-prevalence abstinence rates. Substance use disorder and constraint did not predict cessation outcomes, and no single variable predicted lapse-to-relapse transition. These findings suggest that personality-related manifestations of internalizing dysfunction are more accurate markers of affective sources of relapse risk than mood and anxiety disorders. Further, individuals with high trait-negative emotionality may require intensive intervention to promote the initiation and early maintenance of abstinence., (2013 APA, all rights reserved)

Objective: Alcohol consumption is associated with smoking cessation failure in both community and clinical research. However, little is known about the relation between alcohol consumption and smoking cessation milestones (i.e., achieving initial abstinence, avoiding lapses and relapse). Our objective in this research was to examine the relations between pretreatment alcohol consumption patterns (non/infrequent drinker, moderate drinker, binge drinker) and smoking cessation milestones and tobacco dependence., Method: Data were collected from 1,504 smokers (58.2% women; 83.9% White; mean age = 44.67 years, SD = 11.08) making an aided smoking cessation attempt as part of a clinical trial. Alcohol consumption pattern was determined with the Composite International Diagnostic Interview. Tobacco dependence was assessed with the Wisconsin Inventory of Smoking Dependence Motives (WISDM)., Results: Alcohol consumption pattern was significantly associated with initial cessation and lapse, and these findings remained after controlling for the effects of treatment, race, gender, and cigarettes per day. Relative to moderate drinkers, both non/infrequent drinkers and binge drinkers were less likely to achieve initial cessation (p < .05), and binge drinkers were more likely to lapse (p < .01). When drinking categories were compared on tobacco dependence indices, results showed that relative to moderate drinkers, non/infrequent drinkers scored higher on several WISDM Primary Dependence Motives subscales (Tolerance, Loss of Control, and Automaticity) and binge drinkers scored higher on WISDM Secondary Dependence Motives subscales (Cue Exposure and Social-Environmental Goads)., Conclusions: Non/infrequent drinkers' smoking cessation difficulties may be particularly related to core features of tobacco dependence, whereas binge drinkers' difficulties may be related to environmental and social influences.

Measured tobacco dependence is typically only modestly related to tobacco withdrawal severity among regular smokers making a quit attempt. The weak association between dependence and withdrawal is notable because it conflicts with core theories of dependence and because both measures predict cessation outcomes, suggesting they both index a common dependence construct. This study used data from a smoking cessation comparative effectiveness trial (N = 1504) to characterize relations of tobacco dependence with craving and negative affect withdrawal symptoms using multiple dependence measures and analytic methods to detect both additive and interactive effects and to determine whether withdrawal meaningfully mediates the influence of dependence on smoking cessation. We conclude: (a) Although univariate analyses suggest dependence and withdrawal measures are only modestly interrelated, more powerful analytic techniques show they are, in fact, meaningfully related and their shared variance is associated with cessation likelihood; (b) there are clear differences between craving and negative affective withdrawal symptoms, with the former more related to smoking heaviness and the latter related to trait measures of negative affect; moreover, craving more strongly mediates dependence effects on cessation; and (c) both craving and negative affect withdrawal symptoms are strongly related to a pattern of regular smoking that is sensitive to the passage of time and powerfully affected by smoking cues. These findings support models that accord an important role for associative processes and withdrawal symptoms, especially craving, in drug dependence. The findings also support the use of withdrawal variables as criteria for the evaluation of dependence measures., ((PsycINFO Database Record (c) 2012 APA, all rights reserved).)

Objective: People who live in poverty have a high prevalence of smoking, are less likely to engage in evidence-based treatment, and find it harder to quit. Their beliefs about smoking and quitting can serve as barriers to quitting. Little is known about the smoking and quitting beliefs of the very poor (about U.S. $15,000 or less annual family income) because they tend not to be included in research. This study sought to assess beliefs about smoking and quitting by the very poor in relation to past quitting behavior and intention to quit in the future., Method: A survey was administered in person to residents in randomly selected addresses in two very impoverished Milwaukee, WI, ZIP codes during the day to ensure the inclusion of the very poor., Results: Six hundred fifty-four people completed the survey, a response rate of 78.3%. Sixty-eight percent reported annual household incomes of less than $15,000 compared with 30.8% in the community as a whole and 13.0% of households nationally. Self-reported smoking prevalence was 42.1%. Specific beliefs about smoking and quitting were related to past quit attempts and intentions to quit in the future. Both race and income predicted beliefs and quitting-related variables independently and jointly., Conclusions: Continued tobacco-control progress requires addressing specific populations with known high tobacco use. One of these populations is those with low income. Efforts to engage them in treatment will have to address specific beliefs about smoking and quitting.

Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking., Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244., Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success., Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.

Introduction: Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures., Methods: Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined., Results: Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD., Conclusions: CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V.

Aims: This paper aims to identify appropriate criteria for tobacco dependence assessment, evaluate relevant research and suggest revisions that may be incorporated into DSM-5., Methods: Desirable conceptual and psychometric features of tobacco dependence assessments were identified, including the types of outcomes against which such assessment should be validated. DSM-IV criteria were matched against these criteria and compared with other dependence measures., Results: DSM-IV criteria were found to be ambiguous, little used in tobacco research, and have relatively low predictive validity. Other dependence measures were found to have greater validity in the prediction of important dependence features such as relapse likelihood. Strength of urges to smoke on typical smoking days and during abstinence, markers of nicotine intake or frequency of smoking and latency to smoke soon after waking were found to be useful dependence measures., Conclusion: The use and utility of DSM-5 will be enhanced by eliminating most DSM-IV criteria and adding new ones based on smoking pattern, smoking heaviness, and the severity of craving during periods of smoking and withdrawal., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Introduction: Combination pharmacotherapy for smoking cessation has been shown to be more effective than monotherapy in meta-analyses. We address the question of whether combination pharmacotherapy should be used routinely with smokers or if some types of smokers show little or no benefit from combination pharmacotherapy versus monotherapy., Methods: Two smoking cessation trials were conducted using the same assessments and medications (bupropion, nicotine lozenge, nicotine patch, bupropion + lozenge, and patch + lozenge). Participants were smokers presenting either to primary care clinics in southeastern Wisconsin for medical treatment (Effectiveness trial, N = 1,346) or volunteering for smoking cessation treatment at smoking cessation clinics in Madison and Milwaukee, WI (Efficacy trial, N = 1,504). For each trial, decision tree analyses identified variables predicting outcome from combination pharmacotherapy versus monotherapy at the end of treatment (smoking 8 weeks after the target quit day)., Results: All smokers tended to benefit from combination pharmacotherapy except those low in nicotine dependence (longer latency to smoke in the morning as per item 1 of the Fagerström Test of Nicotine Dependence) who also lived with a spouse or partner who smoked., Conclusions: Combination pharmacotherapy was generally more effective than monotherapy among smokers, but one group of smokers, those who were low in nicotine dependence and who lived with a smoking spouse, did not show greater benefit from using combination pharmacotherapy. Use of monotherapy with these smokers might be justified considering the expense and side effects of combination pharmacotherapy.

Objective: This research examined why smokers receiving combination medication for smoking cessation are more likely to quit smoking than are those who receive either single agent (monotherapy) or placebo., Method: Data were collected from 1,504 current smokers (58.2% women, 83.9% White; mean age = 44.67 years, SD = 11.08) participating in a cessation clinical trial who were randomized to 1 of 6 cessation pharmacotherapy conditions (placebo, nicotine patch, nicotine lozenge, bupropion, nicotine patch + nicotine lozenge, and bupropion + nicotine lozenge). Participants completed ecological momentary assessments 4 times a day, concerning 5 hypothesized mediators (negative affect, positive affect, craving, smoking expectations, and withdrawal) of pharmacotherapy effects. Medications were provided for 8-12 weeks post-quit along with 6 individual counseling sessions. Mediational paths were estimated via a novel Bayesian approach with estimation of multiple mediator models., Results: Biochemically confirmed 8-week abstinence was the outcome variable, with the monotherapy and combination pharmacotherapy composites producing 45% (n = 689) and 54% (n = 478) abstinence rates, respectively. The univariate models suggested that the combination treatments produced higher abstinence rates than the monotherapies because of greater suppression of withdrawal, craving, and smoking expectations. However, multiple mediator models showed that the suppression of craving on the quit day produced the strongest mediational effects and could account for the mediational effects of other tested variables., Conclusion: Suppression of craving on the quit day significantly mediates the clinical effects of monotherapies and combination smoking pharmacotherapies, and the higher abstinence rates for combination therapy versus monotherapies appear primarily due to greater craving suppression., ((PsycINFO Database Record (c) 2012 APA, all rights reserved).)

Background: Fax referral programs quickly and economically can link smokers' visiting primary care clinics to state-based telephone quitlines. Yet, it is unclear how to optimize use of this strategy., Purpose: To evaluate the potential of enhanced academic detailing in clinics (i.e., on-site training, technical assistance, and performance feedback) to boost utilization of a fax referral program called Fax to Quit., Design: Participants were randomized to one of two intervention conditions., Setting/participants: Participants were drawn from 49 primary care clinics in southeastern Wisconsin. The sample size was based on a power analysis in which the control intervention condition was estimated to generate 0.5 referrals/clinic/month and the experimental condition 2.0 referrals/clinic/month., Interventions: One of two fax referral program interventions was administered: the control condition Fax to Quit-Only (F2Q-Only) or the experimental condition Fax to Quit plus Enhanced Academic Detailing (F2Q+EAD)., Main Outcome Measures: Clinic- and clinician-specific referral and quality referral rates (those resulting in quitline enrollment) were measured for 13 months post-intervention, starting in March 2009., Results: Mean number of post-intervention referrals/clinician to the Wisconsin Tobacco Quitline was 5.6 times greater for F2Q+EAD (8.5, SD=7.0) compared to F2Q-Only (1.6, SD=3.6, p<0.001). The F2Q+EAD (4.8, SD=4.1) condition produced a greater mean number of quality referrals/clinician than did the F2Q-Only (0.86, SD=1.8, p<0.001) condition. Data were analyzed in 2010., Conclusions: Enhanced academic detailing, which included on-site training, technical assistance, and performance feedback, increased the number of referrals more than fivefold over a fax referral program implemented without such enhanced academic detailing., Trial Registration: This study is registered at Clinicaltrials.gov NCT00989755., (Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale: Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain., Objectives: This research was intended to provide information about two core components of withdrawal (negative affect and craving): (1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and (2) how these dimensions relate to cessation outcome., Methods: Adult smokers (N = 1,504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence., Results: Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse., Conclusions: Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions.