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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.

Smokers are often reluctant to quit because they fear long-lasting withdrawal. Yet little research prospectively examines smokers' withdrawal longer than 1 month post-quit.The aim of this study was to compare successful versus unsuccessful quitters' withdrawal, positive affect/pleasure, and lifestyle at 1 year post-quit.Smokers (N = 572) in a cessation trial completed ecological momentary assessments four times a day for 1 week pre-quit, 1 week post-quit, and 1 week at 1 year post-quit.From pre-quit to 1 year later, only quitters reported sizeable declines in craving and restlessness, and fewer stressful events. At 1 year, quitters, on average, reported no significant craving. Continuing smokers reduced their cigarette consumption considerably from pre-quit to 1 year later.Contrary to smokers' worries, long-term quitters reported less craving and restlessness than when they smoked (perhaps because cessation eliminates the acute nicotine withdrawal smokers experience between cigarettes). This information may encourage smokers to quit and endure withdrawal.

This paper examines the use of system identification to describe time-varying phenomena in a smoking cessation intervention. The analysis is facilitated by the availability of intensive longitudinal data that enables the application of system identification techniques. Two model structures are considered; one involves the concept of statistical mediation, while the other describes a feedback mechanism. In fitting these models to intensive longitudinal data from a University of Wisconsin clinical trial that studied bupropion and counseling as smoking cessation aids, we focus on the relationship between craving and smoking. Here, we find craving features inverse response and smoking behavior features a dramatic reduction on the quit date, followed by a resumption in smoking. Analyzing the resulting models, we find that they differ in how they describe smoking resumption , and the case is made that the feedback mechanism more appropriately describes the relationship between craving and smoking.

When smokers were separated by their nicotinic receptor gene variants, those with the low-risk genotype responded equally well to pharmacological treatments, including both nicotine replacement and bupropion, and nonpharmacological therapies. Those with the high-risk genotype, as identified by DNA sequencing, responded only to pharmacological treatments. Clinicians advising patients on smoking cessation can suspect genetic risk on the basis of early onset of heavy smoking and direct those smokers specifically to pharmacological treatments.

Smoking cessation intervention is a key means of reducing the human and economic costs of tobacco use. Mounting evidence suggests that combining smoking cessation pharmacotherapies (i.e., using combination pharmacotherapy) improves cessation rates over those achieved by use of individual smoking cessation medications (i.e., monotherapy). For instance, both the 2008 PHS Guideline: Treating Tobacco Use and Dependence (Fiore et al., 2008) and a Cochrane report (Stead, Perera, Bullen, Mant, & Lancaster, 2008) presented meta-analyses showing that combinations of nicotine replacement therapies (NRT’s) produce higher long-term abstinence rates than do single NRT’s (also see Shah, Wilken, Winkler, & Lin, 2008). In addition, two recent, large comparative effectiveness trials demonstrated that combination pharmacotherapy interventions tended to produce higher success rates than did monotherapies (Piper et al., 2009; Smith et al., 2009; also see Blondal, Gudmundsson, Olafsdottir, Gustavsson, & Westin, 1999; Cooney et al., 2009; Kornitzer, Boutsen, Dramaix, Thijs, & Gustavsson, 1995; Puska et al., 1995; Sweeney, Fant, Fagerstrom, McGovern, & Henningfield, 2001); although cf. (Ingersoll & Cohen, 2005). There is some evidence that the type of medication involved in the combination treatment makes a difference. Specifically, evidence suggests that combinations of NRT’s (e.g., the nicotine patch + nicotine gum or lozenge) increase cessation rates beyond combinations comprising a non-NRT medication (e.g., NRT + bupropion). In analyses reported in the 2008 PHS Guideline (see Fiore, et al., 2008); also cf. (Jorenby et al., 1999) only the combination of NRT agents, and not NRT+bupropion, produced significantly higher success rates than did the nicotine patch by itself. However, there is evidence that the combination of NRT + bupropion is also efficacious relative to monotherapy. For instance, in one of the large, recent comparative effectiveness trials (Smith, et al., 2009) a combination of bupropion + nicotine lozenge produced significantly higher 6-month abstinence rates (29.9%) than did any of the tested monotherapies (the nicotine patch, nicotine lozenge, bupropion: 16.8 – 19.9%). The abstinence rate of the bupropion + NRT combination was also modestly higher than the combination of the nicotine patch + nicotine lozenge in that study (29.9% vs. 26.9%) but not significantly so. In the second major, recent comparative effectiveness trial, both the bupropion + nicotine lozenge and the nicotine patch + nicotine lozenge combinations produced significantly higher abstinence rates at end-of-treatment than did the monotherapies (Piper, et al., 2009). In sum, there is evidence that both combination NRT and the NRT+bupropion combination produce greater success than monotherapies, although the evidence is somewhat stronger with regard to the former. It is unknown why combination pharmacotherapies produce greater benefit than monotherapies (i.e., what therapeutic mechanisms account for their superior effects on abstinence). This issue can be addressed through formal mediation analysis. Such analyses can reveal whether the relation between a treatment (an independent variable) and a clinically important outcome (the dependent variable), is partly or wholly due to treatment effects on potentially mediating variables. Such information can shed light on the determinants of success and failure, reveal what treatments do and do not do, and may be used for purposes such as the development of treatment algorithms and the determination of treatment “dosing” (ascertaining when a person has had a sufficient dose of treatment, based on mediator status (McCarthy, Bolt, & Baker, 2007). The study of mediation demands that investigators hypothesize a causal path leading from treatment to a clinically important outcome, identifying variables that should index intermediate change in that path. Such variables, or mediators, should be substantively and/or empirically linked with inferred causal processes. Very little research exists on the mediation of smoking cessation pharmacotherapy, and virtually all that does exist concerns monotherapies (i.e., single medications1). The extant research reveals a relatively small group of variables that has been implicated, albeit inconsistently, in mediating pharmacotherapy effects on long-term abstinence. McCarthy et al., (McCarthy et al., 2008) reported that bupropion’s impact on abstinence was partially mediated by its effects on craving and positive affect, but not by its effects on overall withdrawal2, negative affect, or effects associated with smoking a lapse cigarette. McCarthy et al., also found that some of the effects of pharmacotherapy may be related to effects on self-efficacy and motivation, which themselves could reflect changes in multiple individual symptoms and diverse appraisal processes (McCarthy, et al., 2008). Another study using bupropion implicated negative affect as a mediator, but not withdrawal or positive affect (Lerman et al., 2002), and a third study reported bupropion mediation via withdrawal and craving suppression, but not via effects on negative or positive affect (Piper, Federman, et al., 2008). Only two studies have addressed NRT mediation. One study (Ferguson, Shiffman, & Gwaltney, 2006) reported that the increased time to first lapse caused by NRT was mediated by reductions in withdrawal and craving, especially the latter. While NRT produced other effects, such as reducing negative affect and attention disturbance and increasing positive affect, these did not mediate treatment effects on lapse latency. A second study with smokers with HIV/AIDS (Stanton, Lloyd-Richardson, Papandonatos, de Dios, & Niaura, 2009) reported that self-efficacy and decisional balance (a motivational measure), significantly mediated NRT effects on cessation outcomes. In sum, research has most consistently implicated craving as mediating the clinical effects of single agents (monotherapy); it less consistently implicates other variables such as positive affect, negative affect, withdrawal and motivation. However, it is important to note that this characterization is based on only a few studies, these studies used different methods (e.g., different outcomes, different dosings, different analytic strategies), and in all cases the mediator accounted for only a portion of the agent’s therapeutic effects – often a modest portion. The current study sought to yield additional insight into the mediation of smoking cessation pharmacotherapy effects by identifying the proximal actions of combination therapy that account for its superior clinical outcomes. The mediators examined in this research were craving, withdrawal, negative affect, positive affect, and expectation of smoking reward. The first four variables were chosen because: (1) there is some prior evidence that these mediated the effects of monotherapies, and (2) empirical evidence and theory suggest that they should be affected by nicotine abstinence and should affect the likelihood of remaining abstinent (Baker, Piper, McCarthy, Majeskie, & Fiore, 2004; D’Souza & Markou, 2010; Hughes, 2007; McCarthy, et al., 2008). The fifth potential mediator, expectancy of smoking reward, was selected for analysis because it has been shown to be related to relapse and smoking motivation (Gwaltney, Shiffman, Balabanis, & Paty, 2005; Herd & Borland, 2009; Kirchner & Sayette, 2007), and because prior research (McCarthy, et al., 2008; Stanton, et al., 2009) suggested that such motivational factors might mediate pharmacotherapy effects. This study used data generated by one of the large recent comparative effectiveness studies cited earlier (Piper, et al., 2009); the other comparative effectiveness study by Smith et al., (Smith, et al., 2009) did not comprise measures of potential mediators. The advantages of the former study are that it had a large sample size, involved several types of pharmacotherapy, including two different types of combination pharmacotherapy, and offered measures of diverse potential mediators assessed in real time. The current work uses a Bayesian approach to mediation analysis (Yuan & MacKinnon, 2009) that has not previously been used to characterize the effects of smoking cessation interventions. The complexity of mediational modeling, especially in the use of repeated measures, can make model estimation a challenge. Fortunately such complexity can be handled in a straightforward fashion through the use of Bayesian estimation techniques. A Bayesian approach to mediation has many advantages, including the ability to incorporate prior information into the analysis, the capacity to construct credible confidence intervals for mediation effects, as well as the potential to accommodate multilevel data structures (Yuan & MacKinnon, 2009). The latter two advantages are of particular relevance in the current analysis. Further, the use of a Bayesian approach facilitated our testing multiple mediator models, which allowed the estimation of the magnitude of orthogonal mediational paths. In sum, this research uses real-time measures of multiple potential mediators, which were selected on theoretical and empirical grounds, and which were modeled as latent variables in a discontinuous piecewise model that allowed for estimation of quit day increases as well as post-quit symptom trajectories. These data were analyzed using a novel, Bayesian mediation approach, which permitted the estimation of multiple mediator models. This research was intended to provide insight into why combination therapy results in superior cessation outcome relative to monotherapy; insight that can be used to develop new treatments or use existing treatments more efficiently.

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.

Background There has been limited research addressing changes in subjective well-being as a result of quitting smoking.

Purpose. Smoking prevalence among Medicaid enrollees is higher than among the general population, but use of evidence-based cessation treatment is low. We evaluated whether a communications campaign improved cessation treatment utilization. Design. Quasi-experimental. Setting. Wisconsin. Subjects. Enrollees in the Wisconsin Family Medicaid program. The average monthly enrollment during the study period was approximately 170,000 individuals. Intervention. Print materials for clinicians and consumers distributed to 13 health maintenance organizations (HMOs) serving Wisconsin Medicaid HMO enrollees. Measures. Wisconsin Medicaid pharmacy claims data for smoking cessation medications were analyzed before and after a targeted communications campaign. HMO enrollees were the intervention group. Fee-for-service enrollees were a quasi-experimental comparison group. Quit Line utilization data were also analyzed. Analysis. Pharmacotherapy claims and number of registered Quit Line callers were compared precampaign and postcampaign. Results. Precampaign, cessation pharmacotherapy claims declined for the intervention group and increased slightly for the comparison group (t = 2.29, p = .03). Postcampaign, claims increased in both groups. However, the rate of increase in the intervention group was significantly greater than in the comparison group (t = −2.2, p = .04). A statistically significant increase was also seen in the average monthly number of Medicaid enrollees that registered for Quit Line services postcampaign compared to precampaign (F [1,22] = 7.19, p = .01). Conclusion. This natural experiment demonstrated statistically significant improvements in both pharmacotherapy claims and Quit Line registrations among Medicaid enrollees. These findings may help inform other states' efforts to improve cessation treatment utilization.

Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. 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. 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. 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. 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.

the effects of smoking and smoking cessation on lipoproteins have not been studied in a large contemporary group of smokers. This study was designed to determine the effects of smoking cessation on lipoproteins.this was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained before and 1 year after the target smoking cessation date. The effects of smoking cessation and predictors of changes in lipoproteins after 1 year were identified by multivariable regression.the 1,504 current smokers were (mean [SD]) 45.4 (11.3) years old and smoked 21.4 (8.9) cigarettes per day at baseline. Of the 923 adult smokers who returned at 1 year, 334 (36.2%) had quit smoking. Despite gaining more weight (4.6 kg [5.7] vs 0.7 kg [5.1], P.001], abstainers had increases in high-density lipoprotein cholesterol (HDL-C) (2.4 [8.3] vs 0.1 [8.8] mg/dL, P.001), total HDL (1.0 [4.6] vs -0.3 micromol/L [5.0], P.001), and large HDL (0.6 [2.2] vs 0.1 [2.1] micromol/L, P = .003) particles compared with continuing smokers. Significant changes in low-density lipoprotein (LDL) cholesterol and particles were not observed. After adjustment, abstinence from smoking (P.001) was independently associated with increases in HDL-C and total HDL particles. These effects were stronger in women.despite weight gain, smoking cessation improved HDL-C, total HDL, and large HDL particles, especially in women. Smoking cessation did not affect LDL or LDL size. Increases in HDL may mediate part of the reduced cardiovascular disease risk observed after smoking cessation.

The multiphase optimization strategy (MOST) is a new methodological approach for building, optimizing, and evaluating multicomponent interventions. Conceptually rooted in engineering, MOST emphasizes efficiency and careful management of resources to move intervention science forward steadily and incrementally. MOST can be used to guide the evaluation of research evidence, develop an optimal intervention (the best set of intervention components), and enhance the translation of research findings, particularly type II translation. This article uses an ongoing study to illustrate the application of MOST in the evaluation of diverse intervention components derived from the phase-based framework reviewed in the companion article by Baker et al. (Ann Behav Med, in press, 2011). The article also discusses considerations, challenges, and potential benefits associated with using MOST and similar principled approaches to improving intervention efficacy, effectiveness, and cost-effectiveness. The applicability of this methodology may extend beyond smoking cessation to the development of behavioral interventions for other chronic health challenges.

Despite advances in tobacco dependence treatment in the past two decades, progress has been inconsistent and slow. This paper reviews pervasive methodological issues that may contribute to the lack of timely progress in tobacco treatment science including the lack of a dynamic model or framework of the cessation process, inefficient study designs, and the use of distal outcome measures that poorly index treatment effects. The authors then present a phase-based cessation framework that partitions the cessation process into four discrete phases based on current theories of cessation and empirical data. These phases include: (1) Motivation, (2) Precessation, (3) Cessation, and (4) Maintenance.Within this framework, it is possible to identify phase-specific challenges that a smoker would encounter while quitting smoking, intervention components that would address these phase-specific challenges, mechanisms via which such interventions would exert their effects, and optimal outcome measures linked to these phase-specific interventions. Investigation of phase-based interventions can be accelerated by using efficient study designs that would permit more timely development of an optimal smoking cessation treatment package.

Attentional biases and executive control deficits may play a role in smoking cessation failure.The object of this study was to determine whether smokers' pre-quit reaction times on a computerized modified Simon task (which assesses attentional biases and executive control deficits) predict abstinence following a quit attempt.Participants (N = 365) in a larger smoking cessation clinical trial completed the modified Simon task twice (while 10-h nicotine-deprived vs. not deprived). In the task, two photographs (i.e., two digital slides) were displayed—one always neutral, the other positive, negative, smoking-relevant, or neutral. A probe (or) then appeared to the left or right of center, and participants indicated the arrow's direction (left or right) which was either congruent or incongruent with the arrow's location on the screen. The incongruency effect, a measure of executive control, was calculated by subtracting the reaction time to congruent probes from the reaction time to incongruent probes.Greater impairment in executive control (i.e., greater probe incongruency effects) after viewing positive and smoking slides relative to negative slides predicted an inability to establish initial cessation and to maintain abstinence up to 8 weeks post-quit.These effects may be because smokers who avoid/escape from processing negative affect are more likely to fail in a cessation attempt. Differences in relatively automatic responses to affective cues distinguish smokers who are successful and unsuccessful in their smoking cessation attempts, but effects were modest in size.

Aims To understand the relations among anxiety disorders and tobacco dependence, withdrawal symptoms, response to smoking cessation pharmacotherapy and ability to quit smoking. Design Randomized placebo-controlled clinical trial. Participants received six 10-minute individual counseling sessions and either: placebo, bupropion SR, nicotine patch, nicotine lozenge, bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge. Setting Two urban research sites. Participants Data were collected from 1504 daily smokers (>9 cigarettes per day) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use. Measurements Participants completed baseline assessments, the Composite International Diagnostic Interview and ecological momentary assessments for 2 weeks. Findings A structured clinical interview identified participants who ever met criteria for a panic attack (n = 455), social anxiety (n = 199) or generalized anxiety disorder (n = 99), and those who qualified for no anxiety diagnosis (n = 891). Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms. Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect. Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies. Conclusions Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke, elevated withdrawal, lack of response to pharmacotherapy and impaired ability to quit smoking. These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses.

Cigarette smoking has been associated with increases in C-reactive protein (CRP) and leukocyte counts (white blood cell [WBC]); however, the effects of smoking intensity and smoking cessation on inflammatory markers have not been evaluated prospectively in a large, modern cohort of current smokers.White blood cell count and high-sensitivity CRP were measured in current smokers enrolled in a randomized, prospective clinical trial of 5 smoking cessation pharmacotherapies. Smoking intensity parameters included cigarettes per day, pack-years, Fagerström Test of Nicotine Dependence score, and carbon monoxide levels. C-reactive protein also was measured after 1 year with assessment of abstinence status.The 1,504 current smokers (58% female) were (mean [SD]) 44.7 (11.1) years old, smoked 21.4 (8.9) cigarettes per day, and had a smoking burden of 29.4 (20.4) pack-years. Log(CRP) was not associated with any marker of smoking intensity, except for a weak correlation with pack-years (r = 0.05, P = .047). In contrast, statistically significant correlations were observed between all 4 markers of smoking intensity and WBC count (all P ≤ .011). In multivariable models, waist circumference (P.001) and triglycerides (P.05), but no markers of smoking intensity, were associated with log(CRP). However, pack-years (P = .002), cigarettes per day (P = .013), carbon monoxide (P.001), and Fagerström Test of Nicotine Dependence (P.001) were independently associated with WBC count. After 1 year, log(CRP) (P = .296) and changes in log(CRP) (P = .455) did not differ between abstainers and continuing smokers.Smoking intensity is associated with increased WBC count, but not CRP levels. Smoking cessation does not reduce CRP. The relationship between CRP and smoking intensity may be masked by CRP's stronger relationship with adiposity.

Prior analyses of the Wisconsin Inventory of Smoking Dependence Motives implicated four subscales as “Primary Dependence Motives” (PDM) indexing the core features of tobacco dependence, with the remaining subscales reflecting “Secondary Dependence Motives” (SDM; Piper, Bolt, Kim, Japuntich, Smith, Niedereppe, Cannon & Baker, 2008). The current study extended this work by examining the correlates of PDM, SDM, their subscales, and other indicators of dependence in an operant self-administration paradigm. Smokers (N=58) worked for cigarette puffs under differing fixed ratio schedules. Analyses focused on predicting self-administration under conditions of minimal constraint on tobacco access, and on withdrawal and craving under conditions of severe constraint. Results support a two-factor model of dependence, with the PDM factor showing relatively stronger relations with tobacco self-administration, and SDM showing relatively stronger relations with withdrawal symptomatology and distress-related craving. The PDM appears to index core features of tobacco dependence, but susceptibility to deprivation-contingent distress and craving may be better indexed by SDM.

Objectives The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation (FMD) of the brachial artery. Background The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously. Methods This was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date. Cessation was verified by exhaled carbon monoxide levels. ΔFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke. Predictors of baseline FMD and ΔFMD were identified by multivariable regression. Results The 1,504 current smokers (58% female, 84% white) were 44.7 ± 11.1 years of age and smoked 21.4 ± 8.9 cigarettes/day. Baseline FMD was similar in each treatment arm (p = 0.499) and was predicted by BA diameter (p Conclusions Despite weight gain, smoking cessation leads to prolonged improvements in endothelial function, which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation. (Smoking Cessation Medications: Efficacy, Mechanisms and Algorithms; NCT00332644 )

The 68-item Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) is a theoretically derived measure of tobacco dependence consisting of 13 subscales measuring a variety of smoking motives. The WISDM-68 subscales have demonstrated good psychometric characteristics and have the potential to elucidate diverse nicotine dependence factors and mechanisms. The present research aimed to shorten the WISDM to reduce assessment burden while maintaining or enhancing its psychometric properties.Data from three independent samples (one longitudinal observational study and two randomized clinical trials) were used to select subscales and reduced sets of items in order to develop and test a brief version of the WISDM-68. The full-item and reduced-item versions of the WISDM were then compared in terms of reliability, validity, and model fit (via confirmatory factor analysis) in the three independent samples.Thirty-one items were dropped from the WISDM, the Behavioral Choice-Melioration subscale was dropped, and the Negative and Positive Reinforcement subscales were consolidated. This resulted in a new WISDM short form (Brief WISDM) comprising 37 items that load onto 11 subscales. The psychometric properties of the reduced-item WISDM subscales were found to be comparable with the full-item subscales in terms of internal consistency, long-term stability, concurrent validity, predictive validity, and model fit.These analyses provide good evidence that the 37-item Brief WISDM can be used in place of the original 68-item WISDM if researchers desire to reduce participant assessment burden.

Objective: The present research examined the relation of psychiatric disorders to tobacco dependence and cessation outcomes. 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. Psychiatric diagnoses were determined with the Composite International Diagnostic Interview structured clinical interview. Tobacco dependence was assessed with the Fagerstrom Test of Nicotine Dependence (FTND) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). Results: Diagnostic groups included those who were never diagnosed, those who had ever been diagnosed (at any time, including in the past year), and those with past-year diagnoses (with or without prior diagnosis). Some diagnostic groups had lower follow-up abstinence rates than did the never diagnosed group (ps < .05). At 8 weeks after quitting, strong associations were found between cessation outcome and both past-year mood disorder and ever diagnosed anxiety disorder. At 6 months after quitting, those ever diagnosed with an anxiety disorder (OR = .72, p = .02) and those ever diagnosed with more than one psychiatric diagnosis (OR = .74, p = .03) had lower abstinence rates. The diagnostic categories did not differ in smoking heaviness or the FTND, but they did differ in dependence motives assessed with the WISDM. Conclusion: Information on recent or lifetime psychiatric disorders may help clinicians gauge relapse risk and may suggest dependence motives that are particularly relevant to affected patients. These findings also illustrate the importance of using multidimensional tobacco dependence assessments.

Few studies have examined whether nicotine dependence self-report questionnaires can predict specific behaviors and symptoms at specific points in time. The present study used data from a randomized clinical trial (N = 608; M. E. Piper et al., 2007) to assess the construct validity of scales and items from 3 nicotine dependence measures: the Fagerstrom Test for Nicotine Dependence (T. F. Heatherton, L. T. Kozlowski, R. C. Frecker & K.-O. Fagerstrom, 1991), the Nicotine Dependence Syndrome Scale (S. Shiffman, A. J. Waters, & M. Hickcox, 2004), and the Wisconsin Inventory of Smoking Dependence Motives (M. E. Piper et al., 2004). Scales from these measures were used to predict participants' reports on real-time measures of withdrawal symptoms and smoking behavior and retrospective self-report questionnaires to assess convergent and discriminative validity. The nicotine dependence measures' scales and items generally predicted the real-time measures of similar constructs, but the percent of variance accounted for was low. The nicotine dependence measures did, however, show evidence of discriminative validity. Thus, this study provides modest support for the construct validity of these nicotine dependence scales.

Background Smoking is associated with decreased high-density lipoprotein cholesterol (HDL-C) and increased levels of triglycerides. Objective We sought to evaluate the effects of five markers of smoking intensity on lipoprotein concentrations and particle sizes in a large, modern cohort of current smokers. Methods Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained in a large cohort of current smokers enrolled in a smoking-cessation trial. Multivariate linear regression models were constructed to determine predictors of lipoprotein fractions. Models included age, sex, race, waist circumference, level of physical activity, and alcohol consumption. Smoking intensity parameters included current cigarettes smoked/day, pack-years, the Fagerstrom Test of Nicotine Dependence score, and carbon monoxide (CO) levels. Results The 1504 subjects (58% women, 84% white) had a mean (standard deviation) age of 45 (11.0) years. They smoked 21.4 (8.9) cigarettes/day (29.4 [20.4] pack-years). HDL-C (42.0 [13.5] mg/dL) and total HDL particles (30.3 [5.9] μmol/L) were low. Cigarettes smoked/day independently predicted greater total cholesterol ( P =.009), low-density lipoprotein cholesterol ( P =.023), and triglycerides ( P =.002). CO levels predicted lower HDL-C ( P =.027) and total HDL particles ( P =.009). However, the incremental R 2 for each marker of smoking intensity on each lipoprotein was small. Relationships between the Fagerstrom Test of Nicotine Dependence score and lipoproteins were weak and inconsistent. Participants in the lowest quintiles of current smoking, pack-years, and CO had more favorable lipoproteins (all P Conclusions Among current smokers, increased smoking burden is associated with small increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Increased recent smoke exposure is associated with small decreases in HDL-C and HDL particles.

Obesity and smoking represent the leading preventable causes of morbidity and mortality in the United States. This study compared the prevalence of obesity among smokers seeking cessation treatment (n = 1428) versus a general population (n = 4081) of never smokers, former smoker, and current smokers. Data from treatment-seeking smokers in the Wisconsin Smokers’ Health Study (WSHS) and individuals who completed the National Health and Nutrition Examination Survey (NHANES) 2005-06 were pooled and obesity rates and other health characteristics were compared. The prevalence of obesity was significantly higher among WSHS treatment-seeking smokers (36.8%) versus NHANES current smokers (29.6%), but the obesity rates of WSHS treatment-seeking smokers did not differ from NHANES former smokers (36.5%) or never smokers (36.5%). Treatment-seeking smokers were more likely to be female and to have higher educational attainment compared to NHANES participants. Analysis of health characteristics revealed treatment-seeking smokers had higher levels of dietary fiber and vitamin C and lower blood levels of total cholesterol, triglycerides, and fasting glucose compared to NHANES current smokers. Results suggest that treatment-seeking smokers may have a different health profile than current smokers in the general population. Health care providers should be aware of underlying heath issues, particularly obesity, in patients seeking smoking cessation treatment.

Introduction Previous research revealed significant associations between haplotypes in the CHRNA5-A3-B4 subunit cluster and scores on the Fagerstrom Test for Nicotine Dependence among individuals reporting daily smoking by age 17. The present study used subsamples of participants from that study to investigate associations between the CHRNA5-A3-B4 haplotypes and an array of phenotypes not analyzed previously (i.e., withdrawal severity, ability to stop smoking, and specific scales on the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) that reflect loss of control, strong craving, and heavy smoking. Methods Two cohorts of current or former smokers (N = 886) provided both self-report data and DNA samples. One sample (Wisconsin) comprised smokers making a quit smoking attempt, which permitted the assessment of withdrawal and relapse during the attempt. The other sample (Utah) comprised participants studied for risk factors for nicotine dependence and chronic obstructive pulmonary disease and included individuals originally recruited in the Lung Health Study. Results The CHRNA5-A3-B4 haplotypes were significantly associated with the targeted WISDM-68 scales (Tolerance, Craving, Loss of Control) in both samples of participants but only among individuals who began smoking early in life. The haplotypes were significantly associated with relapse likelihood and withdrawal severity, but these associations showed no evidence of an interaction with age at daily smoking. Discussion The CHRNA5-A3-B4 haplotypes are associated with a broad range of nicotine dependence phenotypes, but these associations are not consistently moderated by age at initial smoking.

Relapse is the most common smoking cessation outcome. Accurate prediction of relapse likelihood could be an important clinical tool used to influence treatment selection or duration. The aim of this research was to develop a brief clinical relapse proneness questionnaire to be used with smokers interested in quitting in a clinical setting where time is at a premium.Diverse items assessing constructs shown in previous research to be related to relapse risk, such as nicotine dependence and self-efficacy, were evaluated to determine their independent contributions to relapse prediction. In an exploratory dataset, candidate items were assessed among smokers motivated to quit smoking who enrolled in one of three randomized controlled smoking cessation trials. A cross-validation dataset was used to compare the relative predictive power of the new instrument against the Fagerström Test for Nicotine Dependence (FTND) at 1-week, 8-week, and 6-month postquit assessments.We selected seven items with relatively nonoverlapping content for the Wisconsin Predicting Patient's Relapse (WI-PREPARE) measure, a brief, seven-item questionnaire that taps physical dependence, environmental factors, and individual difference characteristics. Cross-validation analyses suggested that the WI-PREPARE demonstrated a stronger prediction of relapse at 1-week and 8-week postquit assessments than the FTND and comparable prediction to the FTND at a 6-month postquit assessment.The WI-PREPARE is easy to score, suggests the nature of a patient's relapse risk, and predicts short- and medium-term relapse better than the FTND.

The construct of tobacco dependence is important from both scientific and public health perspectives, but it is poorly understood. The current research integrates person-centered analyses (e.g., latent profile analysis) and variable-centered analyses (e.g., exploratory factor analysis) to understand better the latent structure of dependence and to guide distillation of the phenotype. Using data from four samples of smokers (including treatment and non-treatment samples), latent profiles were derived using the Wisconsin Inventory of Smoking Dependence Motives (WISDM) subscale scores. Across all four samples, results revealed a unique latent profile that had relative elevations on four dependence motive subscales (Automaticity, Craving, Loss of Control, and Tolerance). Variable-centered analyses supported the uniqueness of these four subscales both as measures of a common factor distinct from that underlying the other nine subscales, and as the strongest predictors of relapse, withdrawal and other dependence criteria. Conversely, the remaining nine motives carried little unique predictive validity regarding dependence. Applications of a factor mixture model further support the presence of a unique class of smokers in relation to a common factor underlying the four subscales. The results illustrate how person-centered analyses may be useful as a supplement to variable-centered analyses for uncovering variables that are necessary and/or sufficient predictors of disorder criteria, as they may uncover small segments of a population in which the variables are uniquely distributed. The results also suggest that severe dependence is associated with a pattern of smoking that is heavy, pervasive, automatic and relatively unresponsive to instrumental contingencies.

Various theories have proposed mechanisms for drug motivation and relapse. For instance, negative reinforcement theories focus on the alleviation of withdrawal. However, other theories and some data cast doubt on the importance of withdrawal as a motivator of addictive drug use. Using data from a randomized double-blind placebo-controlled smoking cessation treatment study (N=608), this research examined the impact of withdrawal on drug motivation and the ability to maintain abstinence. Withdrawal was experimentally manipulated by randomly assigning participants to receive active bupropion versus placebo. Mediation analyses revealed that active bupropion reduced the amount of withdrawal and craving that individuals reported in the 1st week post quit; modest support was also found for smaller declines in positive affect. These effects, in turn, were all positively associated with posttreatment abstinence. These results implicate withdrawal as an important factor in motivating persistent tobacco use.

In this double-blind placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at one week, end of treatment and six months, but not twelve months post-quit. After the first week post-quit there were no differences in abstinence rates between the AA and AP groups. There were no significant individual difference variables that moderated outcome beyond one week post-quit.

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.

Smoking affects comorbid disease outcomes, and patients with comorbid conditions may have unique characteristics that are important to consider when treating tobacco use. However, addressing tobacco in patients being treated for comorbid conditions is not a consistent practice. Recognizing the need for a "call-to-action" to address tobacco use in people with comorbid conditions, the Tobacco Treatment Network within the Society for Research on Nicotine and Tobacco (SRNT) convened a Comorbidities Workgroup to explore the relationship between smoking and comorbid disease to identify common themes including: the harms associated with continued tobacco use, the frequency of comorbid disease and tobacco use, the potential effect of comorbid disease on the ability to quit tobacco use, the association between tobacco use and suboptimal disease-specific treatment response, and evidence regarding potential approaches to improve addressing tobacco use in patients with comorbid disease. Five candidate conditions (psychiatric, cancer, cardiovascular, pulmonary, and human immunodeficiency virus infected patients) were explored. Across comorbid conditions, smoking adversely affects treatment efficacy and promotes other adverse health conditions. People with comorbid conditions who smoke are motivated to quit and respond to evidence-based smoking cessation treatments. However, tobacco cessation is not regularly incorporated into the clinical care of many individuals with comorbidities. Optimal strategies for addressing tobacco use within each comorbid disease are also not well defined. Further work is needed to disseminate evidence-based care into clinical practice for smokers with comorbid disease and addiction research should consider comorbid conditions as an important construct to explore.This article explores how physical and psychiatric conditions may interact in the treatment of tobacco dependence, and discusses the need for smoking cessation as a critical component of comorbid condition management. Five common comorbid domains-psychiatric, cancer, pulmonary, cardiovascular, and human immunodeficiency virus (HIV)-are highlighted to illustrate how these different conditions might interact with smoking with respect to prevalence and harm, motivation to quit, and cessation treatment utilization and success.

Tobacco dependence is a key construct in tobacco research. This paper describes a construct validation approach to dependence assessment and describes key conceptual and psychometric criteria on which to evaluate putative measures of dependence. Five current dependence scales-the Fagerström Test for Nicotine Dependence; the Diagnostic and Statistical Manual of Mental Disorders (4th ed.); the Cigarette Dependence Scale; the Nicotine Dependence Syndrome Scale; and the Wisconsin Inventory of Smoking Dependence Motives-are examined with respect to these critical dimensions. Recommendations are made regarding the use of each measure.

This report used emotion-modulated startle to refine theoretically critical claims about negative affect during tobacco withdrawal. Forty-eight dependent smokers (assigned to either a 24-hr nicotine withdrawal condition or a continued smoking condition) and 48 nonsmokers participated in this study. Participants viewed a series of neutral and unpleasant photographic images and were instructed to enhance, suppress, or maintain their emotional response during specific trials. Participants' startle response was measured before and after this regulation instruction to index 2 components of emotional response: initial negative emotional response intensity and emotion regulation. Compared with the nonwithdrawn groups (continuing smokers and nonsmokers), withdrawal significantly increased self-reported negative affect. However, startle response indicated that emotional response intensity and emotion regulation success were not affected by withdrawal. These results are important because they constrain interpretation of the predominantly self-report literature on the affective consequences of tobacco withdrawal.

Objective Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. Method In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. Results For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X2 = 8.15, df = 2, omnibus-p = 0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald = 3.94, df = 1, p = 0.047), this non-replication can alter the interpretation of pharmacogenetic findings. Conclusions Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking.

Phenotypic evidence indicates that the ability to taste the bitter compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p = .001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence.

The dependence construct fills an important explanatory role in motivational accounts of smoking and relapse. Frequently used measures of dependence are either atheoretical or grounded in a unidimensional model of physical dependence. This research creates a multidimensional measure of dependence that is based on theoretically grounded motives for drug use and is intended to reflect mechanisms underlying dependence. Data collected from a large sample of smokers (N = 775) indicated that all 13 subscales of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) have acceptable internal consistency, are differentially present across levels of smoking heaviness, and have a multidimensional structure. Validity analyses indicated the WISDM-68 subscales are significantly related to dependence criteria such as smoking heaviness and to 4th edition Diagnostic and Statistical Manual of Mental Disorders symptoms of dependence and relapse.

Introduction Alcohol and nicotine are commonly used substances in the U.S., with significant impacts on health. Using both substances concurrently impacts quit attempts. While studies have sought to examine changes in alcohol use co-occurring with tobacco cessation, results have not been consistent. Understanding these changes has clinical implications. The objective of this study is to identify changes in alcohol consumption that occur following tobacco cessation, as well as predictors of alcohol use patterns following a smoking cessation attempt. Methods A secondary analysis of a randomized, placebo-controlled trial evaluating the efficacy of five tobacco cessation pharmacotherapies. Participants ( N = 1301) reported their smoking and alcohol consumption daily for two weeks prior to, and two weeks after, the target quit date (TQD). Results Generally, alcohol use decreased post-TQD. Smokers who reported less pre-quit alcohol use, as well as smokers who were female, non-white, and had a history of alcohol dependence tended to use less alcohol post-quit. Pre- and post-quit alcohol use were more strongly related among men and among those without a history of alcohol dependence. Conclusions For most smokers alcohol use decreased following smoking cessation. These results suggest that the expectation should be of decreased alcohol use post cessation. However, attention may be warranted for those who drink higher amounts of alcohol pre-cessation because they may be more likely to drink more in the post-quit period which may influence smoking cessation success.

Rationale: The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking. Objectives: To compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors. Methods: A total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied. Measurements and Main Results: Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study–significantly associated with CO (β = 2.66; 95% confidence interval [CI], 1.74–3.58; P = 1.65 × 10−8), and this association remains strong after adjusting for smoking behavior (β = 2.18; 95% CI, 1.32–3.04; P = 7.47 × 10−7). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 × 10−4) in African Americans (r = 0.14; 95% CI, 0.02–0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31–0.40; P = 0.0001). Conclusions: Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.

Objectives. We examined national trends in smoke-free home rules among US veterans and nonveterans. Methods. We used data from the 2001–2002 and 2010–2011 Tobacco Use Supplement to the Current Population Survey to estimate and compare the existence of smoke-free home rules among veterans and nonveterans for each survey period. Results. The prevalence of a complete smoke-free home rule among veterans increased from 64.0% to 79.7% between 2001 and 2011 (P Conclusions. Despite the general increase in the adoption of smoke-free home rules, veterans lag behind the rest of the US population. Interventions promoting the adoption of complete smoke-free home rules are necessary to protect veterans and their families and to reduce disparities.

The chronic, relapsing nature of tobacco use represents a major challenge in smoking cessation treatment. Recently, novel intervention paradigms have emerged that seek to adjust treatments over time in order to meet a patient’s changing needs. This article demonstrates that Hybrid Model Predictive Control (HMPC) offers an appealing framework for designing these optimized, time-varying smoking cessation interventions. HMPC is a particularly appropriate approach as it recognizes that intervention doses must be assigned in predetermined, discrete units while retaining receding-horizon, constraint-handling, and combined feedback and feedforward capabilities. Specifically, an intervention algorithm is developed here in which counseling and two pharmacotherapies are manipulated to reduce daily smoking and craving levels. The potential usefulness of such an intervention is illustrated through simulated treatment of a quit attempt in a hypothetical patient, which highlights that prioritizing reduction in craving over total daily smoking levels significantly reduces craving levels, suppresses relapse, and successfully rejects time-varying disturbances such as stress, all while adhering to several practical operational constraints and resource use considerations.

This special issue presents a series of articles on the use of ecological momentary assessment (EMA; Shiffman, 2009) methods, which involve collecting real-time data in real-time settings, to study tobacco use and dependence. EMA methods have particular utility for understanding tobacco use because they enable microanalyses of use and can shed light on how behavior unfolds over time. The motivation for this special issue grew out of a workshop on EMA methods and related data-analytic methods, held in connection with the 2012 annual meeting of the Society for Research on Nicotine and Tobacco, sponsored by the Penn State Methodology Center (STL and MEP, organizers). There was great interest and enthusiasm for the methodological issues discussed at the workshop and the identification of important, previously unanswerable questions that can now be addressed using EMA data and new analytic techniques. This inspired us to develop the current special issue of Nicotine & Tobacco Research (NTR). This special issue, sponsored by the National Cancer Institute and the Office of Behavioral and Social Science Research at the National Institutes of Health, is devoted to the novel topic of collecting and analyzing data from EMA studies. Our hope is that readers of this issue will recognize the unique light that can be shed on tobacco use, dependence, and treatment by studies using EMA. Perhaps readers who have never collected EMA data will be inspired to do so, and others who have access to existing EMA data will identify new approaches to analyzing the data that address novel, important questions about processes that unfold over the course of a study. In other words, the goal of this special issue is to encourage readers to think broadly and creatively about research questions that can now be answered using EMA methods and analytic approaches illustrated in this special issue. The response to our request for articles was excellent, and even after rigorous peer review, we had to make many difficult decisions about which manuscripts to include. All of the articles were peer reviewed (and papers by the editors were independently reviewed). We favored articles that (a) advanced the methodology of EMA data collection, (b) presented novel statistical methods that can be applied to analyze EMA data, or (c) illustrated a creative application of EMA data to questions about tobacco use. Several other excellent articles using EMA were not selected to appear in this issue but were accepted for publication in the general pages of NTR. The issue begins with a brief commentary by four individuals from the National Institutes of Health (Ginexi, Riley, Atienza, and Mabry) about how EMA can advance behavioral research related to nicotine and tobacco. Next, Shiffman provides a conceptual overview that places the collection and analysis of EMA data into context, both in history and in relation to various statistical methodologies. The remainder of the issue is comprised of articles that were submitted in response to a call for articles, and includes explanations and demonstrations of data-analytic methods, as well as articles using EMA data to address substantive questions in tobacco science. The first section begins with an investigation of factors associated with both event- and signal-contingent compliance with an EMA smoking study protocol that was conducted by Schuez and colleagues. This is followed by three articles that incorporate other types of innovative data with EMA. Watkins and colleagues conducted a study in which participants carried smartphones that recorded Global Positioning System (GPS) data and urge ratings. They were then able to understand how tobacco retail outlets, identified via GPS data, influenced EMA reports of urges during a cessation attempt. Wilson and Smyth review the conceptual basis for integrating brain imaging methods with EMA data to gain a better understanding of tobacco dependence and present preliminary evidence for how the combination of EMA and functional magnetic resonance imaging can provide novel insights into understanding and treating tobacco dependence. Finally, Waters, Szeto, Wetter, Cinciripini, and Li use an EMA paradigm to assess attentional bias to smoking cues via the Stroop response time test in real-world settings; these measures were related to craving during the early part of a cessation attempt. These articles illustrate ways in which EMA methods can be used to collect data that are not self-report, and can be integrated with other kinds of data to achieve a deeper understanding of tobacco use. The second section presents six innovative approaches to analyzing data from EMA studies. Piasecki, Trela, Hedeker, and Mermelstein provide an exemplary demonstration of multilevel modeling for effectively separating within-person variability over time from between-person variability. They found that antecedents of adolescent smoking shifted as individuals progressed to higher levels of tobacco dependence. Three articles present variations of a novel statistical framework, the time-varying effect model (TVEM), for examining how associations between constructs can change as a function of time. Lanza, Vasilenko, Liu, Li, and Piper provide an accessible introduction to this statistical model and demonstrate how both baseline characteristics and time-varying constructs such as negative affect can have effects on urge that vary during the course of a quit attempt and, further, how these time-varying effects can be influenced by treatment. Vasilenko, Lanza, Liu, Yang, Li, and Piper present a generalization of TVEM for estimating time-varying effects on a binary outcome, an essential development given the importance of binary outcomes in smoking research (i.e., smoking or abstinent). The authors found that, over the course of the first 2 weeks of a quit attempt, pharmacotherapies were more effective at reducing smoking during earlier days, whereas the effects of craving and negative affect on smoking strengthened with time. Shiyko, Naab, Shiffman, and Li use TVEM to examine how the effect of negative affect on high smoking urge shifted across a time lag. The magnitude of the effect was strongest for the shortest time lags and diminished over a time lag of about 7hr. Pugach, Hedeker, and Mermelstein examine positive and negative mood variation and covariation in adolescent smokers using an innovative extension of multilevel models, the bivariate location-scale mixed-effects model. As smoking level increased, both positive and negative moods were more consistent over time within individuals. Within-person association between positive and negative affect was weaker among adolescents who smoked more heavily. Finally, Timms, Rivera, Collins, and Piper present a dynamical systems model to describe smoking as a self-regulatory process. The authors modeled the dynamic relation between daily craving and smoking levels in adults during a quit attempt; a comparison of the estimated processes across treatment conditions suggest new insights into how pharmacological treatment affects individuals. These articles illustrate how novel and sophisticated analytic methods can exploit the richness of EMA data to model more complex associations among variables and how those associations unfold over time. The future is likely to see more and more sophisticated applications of EMA. As technology advances, novel methodologies are developed, and new products such as electronic cigarettes are developed, tobacco use rates are stagnating. Tobacco science is well-positioned to develop and use EMA methodologies and analytic approaches to better understand the initiation of tobacco use, the development of dependence, and tobacco treatment mechanisms. The ability of EMA to focus on contact in real time, in real-world settings is already being extended to intervention: researchers are developing ecological momentary interventions that can target an intervention based on the patient’s current circumstances (e.g., Heron & Smyth, 2010; McTavish, Chih, Shah, & Gustafson, 2012). Such innovations could be used to build on the current knowledge base and further tailor tobacco treatment. These powerful methodologies have the potential to significantly advance tobacco science and subsequently improve public health. The goals of this special issue are to share our enthusiasm and to acquaint the readership of NTR with the potential for EMA data. EMA data, particularly when analyzed using innovative methodological and analytic techniques, offers researchers the ability to address complex questions regarding the etiology of tobacco use, the development of dependence, withdrawal phenomena, treatment effects, the relapse process, and systems science. We hope you find this issue useful in your own research.

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.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.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).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.

Weight gain after smoking cessation may increase diabetes mellitus and impaired fasting glucose (IFG) risk. This study evaluated associations between smoking cessation and continued smoking with incident diabetes and IFG three years after a quit attempt. The 1504 smokers (58% female) were mean (standard deviation) 44.7 (11.1) years old and smoked 21.4 (8.9) cigarettes/day. Of 914 participants with year 3 data, the 238 abstainers had greater weight gain, increase in waist circumference, and increase in fasting glucose levels than the 676 continuing smokers (p≤0.008). In univariate analyses, Year 3 abstinence was associated with incident diabetes (OR = 2.60, 95% CI 1.44–4.67, p = .002; 4.3% absolute excess) and IFG (OR = 2.43, 95% CI 1.74–3.41, p

The preparation of the Public Health Service Report, Treating Tobacco Use and Dependence, brought to light a substantial gap in the smoking cessation literature; there is little or no research evidence regarding the success of formal tobacco-dependence treatment specific to gender or racial/ethnic status. Of the 192 articles included in the meta-analyses of the evidence-based PHS Report, none included results based on racial/ethnic group and only four reported results by gender. This commentary identifies tobacco use as a problem that crosses gender and racial/ethnic boundaries, reviews reasons that the different genders or racial/ethnic groups might require different tobacco-dependence treatments, provides suggestive evidence that both gender and racial/ethnic status influence tobacco-dependence treatment efficacy, and recommends changes and directions for future clinical research that will address gender and racial/ethnicity effects.

Introduction Advancing the understanding of smoking cessation requires a complex and nuanced understanding of behavior change. To this end, ecological momentary assessments (EMA) are now being collected extensively. The time-varying effect model (TVEM) is a statistical technique ideally suited to model processes that unfold as behavior and nicotine dependence change. Coefficients are expressed dynamically over time and are represented as smooth functions of time. Methods The TVEM approach is demonstrated using data from a smoking-cessation trial. Time-varying effects of baseline nicotine dependence (a time-invariant covariate) and negative affect (a time-varying covariate) on urge to smoke during a quit attempt were estimated for monotherapy, combination therapy, and placebo groups. SAS syntax for conducting TVEM is provided so that readers can adapt it for their research. Results During the first 2 days after quitting, the association between negative affect and craving was significantly stronger among individuals in the placebo group, suggesting an early positive impact of treatment. For the monotherapy and combination therapy groups, during the second week of the quit attempt, baseline dependence was less strongly related to craving compared with the placebo group, indicating a different positive impact of treatments later in the quit attempt. Conclusions The results reveal information about the underlying dynamics that unfold during a quit attempt and how monotherapy and combination therapy impact those processes. This suggests possible mechanisms to target in an intervention and indicates timepoints that hold the greatest promise for effective treatment. TVEM is a straightforward approach to examining time-varying processes embedded in EMA.

Introduction Cardiovascular disease (CVD) can be detected and quantified by analysis of the electrocardiogram (ECG); however the effects of smoking and smoking cessation on the ECG have not been characterized. Methods Standard 12-lead ECGs were performed at baseline and 3 years after subjects enrolled in a prospective, randomized, placebo-controlled clinical trial of smoking cessation pharmacotherapies. ECGs were interpreted using the Minnesota Code ECG Classification. The effects of (i) smoking burden on the prevalence of ECG findings at baseline, and (ii) smoking and smoking cessation on ECG changes after 3 years were investigated by multivariable and multinomial regression analyses. Results At baseline, 532 smokers were (mean [SD]) 43.3 (11.5) years old, smoked 20.6 (7.9) cigarettes/day, with a smoking burden of 26.7 (18.6) pack-years. Major and minor ECG criteria were identified in 87 (16.4%) and 131 (24.6%) of subjects, respectively. After adjusting for demographic data and known CVD risk factors, higher pack-years was associated with major ECG abnormalities (p = 0.02), but current cigarettes/day (p = 0.23) was not. After 3 years, 42.9% of subjects were abstinent from smoking. New major and minor ECG criteria were observed in 7.2% and 15.6% of subjects respectively, but in similar numbers of abstinent subjects and continuing smokers (p>0.2 for both). Continuing smokers showed significant reduction in current smoking (–8.4 [8.8] cigarettes/day, p

Importance Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality. Objective To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates. Design, Setting, and Participants Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization. Interventions Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered. Main Outcomes and Measures The primary outcome was carbon monoxide–confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide–confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52. Results Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, −0.76% (95% CI, −7.4% to 5.9%); for patch vs C-NRT, −4.0% (95% CI, −10.8% to 2.8%); and for varenicline vs C-NRT, −3.3% (95% CI, −9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion. Conclusions and Relevance Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies. Trial Registration clinicaltrials.gov Identifier:NCT01553084

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.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).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).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.

Background The mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial. Methodology/Principal Findings Subjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMTmax) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMTmax and research site) were analyzed. Among 795 subjects (45.2±10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p

The long-term effects of smoking and smoking cessation on markers of cardiovascular disease (CVD) prognosis obtained during treadmill stress testing (TST) are unknown. The purpose of this study was to evaluate the long-term effects of smoking cessation and continued smoking on TST parameters that predict CVD risk.In a prospective, double-blind, randomized, placebo-controlled trial of 5 smoking cessation pharmacotherapies, symptom-limited TST was performed to determine peak METs, rate-pressure product (RPP), heart rate (HR) increase, HR reserve, and 60-second HR recovery, before and 3 years after the target smoking cessation date. Relationships between TST parameters and treatments among successful abstainers and continuing smokers were evaluated using multivariable analyses.At baseline, the 600 current smokers (61% women) had a mean age of 43.4 (SD 11.5) years and smoked 20.7 (8.4) cigarettes per day. Their exercise capacity was 8.7 (2.3) METs, HR reserve was 86.6 (9.6)%, HR increase was 81.1 (20.9) beats/min, and HR recovery was 22.3 (11.3) beats. Cigarettes per day and pack-years were independently and inversely associated with baseline peak METs (P.001), RPP (P.01, pack-years only), HR increase (P.05), and HR reserve (P.01). After 3 years, 168 (28%) had quit smoking. Abstainers had greater improvements than continuing smokers (all P.001) in RPP (2,055 mm Hg beats/min), HR increase (5.9 beats/min), and HR reserve (3.7%), even after statistical adjustment (all P.001).Smokers with a higher smoking burden have lower exercise capacity, lower HR reserve, and a blunted exercise HR response. After 3 years, TST improvements suggestive of improved CVD prognosis were observed among successful abstainers.

Most smoking cessation studies have used long-term abstinence as their primary outcome measure. Recent research has suggested that long-term abstinence may be an insensitive index of important smoking cessation mechanisms. The goal of the current study was to examine the effects of 5 smoking cessation pharmacotherapies using Shiffman et al.'s (2006) approach of examining the effect of smoking cessation medications on 3 process markers of cessation or smoking cessation milestones: initial abstinence, lapse, and the lapse-relapse transition.The current study (N = 1,504; 58.2% female and 41.8% male; 83.9% Caucasian, 13.6% African American, 2.5% other races) examined the effect of 5 smoking cessation pharmacotherapy treatments versus placebo (bupropion, nicotine lozenge, nicotine patch, bupropion + lozenge, patch + lozenge) on Shiffman et al.'s smoking cessation milestones over 8 weeks following a quit attempt.Results show that all 5 medication conditions decreased rates of failure to achieve initial abstinence and most (with the exception of the nicotine lozenge) decreased lapse risk; however, only the nicotine patch and bupropion + lozenge conditions affected the lapse-relapse transition.These findings demonstrate that medications are effective at aiding initial abstinence and decreasing lapse risk but that they generally do not decrease relapse risk following a lapse. The analysis of cessation milestones sheds light on important impediments to long-term smoking abstinence, suggests potential mechanisms of action of smoking cessation pharmacotherapies, and identifies targets for future treatment development.