Cancer-related disease factors and smoking cessation treatment: Analysis of an ongoing clinical trial.

OBJECTIVE: Smoking cessation treatment should be an important aspect of cancer care. In this study, we evaluated whether cancer-related disease factors adversely influence smoking cessation treatment. METHODS: Smokers with cancer (within 5 years of diagnosis, any tumor site) were recruited for an ongoing trial of varenicline for smoking cessation. Disease factors, assessed at baseline, included tumor site, cancer treatment, time since diagnosis, and health-related quality of life. Medication adherence was defined by 132 of 165 pills taken and counseling adherence was defined by 4 of 4 behavioral counseling sessions attended. Abstinence was bioverified at Week 12. Using logistic regression analysis, we assessed the relationship between disease factors and 12-week medication adherence, counseling adherence, and abstinence. RESULTS: Of 144 participants, 56% were medication adherent, 74% were counseling adherent, and 39% were abstinent. Health-related quality of life predicted medication adherence (OR: 1.08, 95% CI, 1.01-1.16, P = .019, d = 0.20) but not counseling adherence or 12-week abstinence. Tumor site, cancer treatment, and time since diagnosis did not predict any smoking cessation treatment outcomes. CONCLUSIONS: Cancer-related disease factors did not predict cancer survivors' engagement or success in smoking cessation treatment. Findings support National Comprehensive Cancer Network Clinical Practice guidelines that recommend smoking cessation treatment for all smokers with cancer, regardless of time since diagnosis.

The nature and consequences of cognitive deficits among tobacco smokers with HIV: a comparison to tobacco smokers without HIV.

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n = 103) and HIV-uninfected smokers (n = 70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p < 0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates "good prediction" for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p = 0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population.

The use of varenicline to treat nicotine dependence among patients with cancer.

BACKGROUND: Continuing to smoke after a cancer diagnosis can adversely influence the prognosis for patients with cancer. However, remarkably few studies have carefully examined the use of first-line FDA-approved medications for nicotine dependence in patients with cancer. This study evaluated the feasibility, safety, and effect on cessation of varenicline for smoking cessation in patients with cancer. METHODS: Data from 132 treatment-seeking smokers who received 12 weeks of open-label varenicline and five brief behavioral counseling sessions were used to evaluate the feasibility, safety, and impact on cessation of varenicline. The effects of abstinence on cognitive function and affect were also explored. RESULTS: Of 459 patients screened, 306 were eligible for the study (66.7%) and 132 entered treatment (43.1%). Retention was 84.1% over 12 weeks. The rate of biochemically verified abstinence at week 12 was 40.2%. Expected side effects were reported (e.g. sleep problems, nausea), but there were no reports of elevated depressed mood, suicidal thoughts, or cardiovascular events. Abstinence was associated with improved cognitive function and reduced negative affect over time (p < 0.05). CONCLUSIONS: Although many patients with cancer who smoke did not enroll in treatment, the side effect profile of varenicline and its effect on short-term cessation converge with what is seen in the general population. Further, as with the general population, abstinence while taking varenicline may lead to improved cognitive function and reduced negative affect. The present data support the use of varenicline to help patients with cancer to quit smoking.

Is the Effect of Anhedonia on Smoking Cessation Greater for Women Versus Men?

INTRODUCTION: Anhedonia has been recognized as a major risk factor for smoking persistence. Potential gender differences in the effect of anhedonia on smoking cessation have not been studied. Using data from a completed clinical trial of maintenance nicotine patch therapy, we hypothesized that gender would moderate the effect of anhedonia on short-term abstinence, such that anhedonic women would be less likely to achieve abstinence. METHODS: Participants (N = 525; 50% female, 48.2% Black/African American, average age: 46 years) received 21mg/day nicotine patch and four brief behavior counseling sessions over 8 weeks. Participants were classified at baseline using the Snaith-Hamilton Pleasure Scale as anhedonic (scores > 2) or hedonic (scores ≤ 2). Bioverified 7-day point prevalence abstinence was measured at week 8. Using logistic regression analysis, we tested the interaction of anhedonia by gender predicting abstinence, adjusting for age, race, nicotine dependence, and baseline depressive symptomatology. RESULTS: Seventy participants (13%) were classified as anhedonic. Men were more likely to be anhedonic than women (16.6% vs. 10.2%, p = .03). Contrary to our hypothesis, the interaction of anhedonic status (hedonic vs. anhedonic) by gender was nonsignificant (p = .18). There was a main effect of hedonic capacity, such that anhedonia predicted abstinence, odds ratio = 3.24, 95% confidence interval = 1.39-7.51, p = .006. CONCLUSION: Both male and female anhedonic smokers were more likely to be abstinent, which contrasts with prior research indicating that anhedonia is a risk factor for difficulty quitting. This unexpected finding may be explained by a possible selective benefit of nicotine patch therapy, which has been observed in some studies to have antidepressant effects. IMPLICATIONS: This is the first study to examine whether the association between pretreatment anhedonia and smoking cessation differs by gender. For both women and men, anhedonia was associated with a greater likelihood of abstinence after 8 weeks of treatment with 21mg/day nicotine patch and behavior counseling. Our findings indicate that the association between anhedonia and smoking cessation is not as clear as has been assumed and may depend in part on the type of treatment delivered.

Factors Associated with Adherence to Transdermal Nicotine Patches within a Smoking Cessation Effectiveness Trial.

BACKGROUND: Adherence to transdermal nicotine patches, one of the most popular and effective treatment for nicotine dependence, remains very low and is a strong predictor of cessation rates. This study examined individual factors related to adherence as well as differences over time between adherent (≥ 80% of daily patch use) and non-adherent participants (< 80% of daily patch use). METHODS: We analyzed data from 440 participants who received 8 weeks of 21mg transdermal nicotine and 4 behavioral counseling sessions within an effectiveness trial that examined the effects of long-term treatment. Multiple logistical regression assessed baseline variables associated with patch adherence and generalized estimating equations (GEE) were used to evaluate changes in craving and withdrawal, depressive and anxiety symptoms, substitute and complementary reinforcers, and side effects between participants who were or were not adherent. RESULTS: In a logistic regression model, being female, living with a child or children, and higher self-reported anxiety symptoms were predictive of lower patch adherence (p < .05). In the GEE analysis, adherence was significantly associated with: a greater reduction in craving, a greater engagement in substitute reinforcers, and a greater decrease in complementary reinforcers over time (p < .05). CONCLUSIONS: Difficulties adhering to transdermal nicotine patches may be related to psychiatric comorbidity, difficulty managing nicotine craving, and challenges with engaging in substitute reinforcers and reducing exposure to complementary reinforcers. These constructs may serve as targets for interventions designed to increase treatment adherence.

Does menthol cigarette use moderate the effect of nicotine metabolism on short-term smoking cessation?

The nicotine metabolite ratio (NMR) has been shown to predict response to the transdermal nicotine patch, such that faster nicotine metabolism is associated with a lower abstinence rate. Menthol cigarette use, versus nonmenthol cigarette use, slows nicotine metabolism and therefore may attenuate the effect of NMR on smoking abstinence. In this study, we evaluated whether cigarette type (menthol vs. nonmenthol) modified the association between NMR and short-term abstinence. This was a secondary analysis examining treatment in the first 8 weeks of 21 mg/day nicotine patch therapy in a completed clinical trial (n = 474). Menthol cigarette use was based on self-report. NMR was defined dichotomously (0 = fast, 1 = slow) to distinguish between fast (≥0.47) versus slow NMR. Using logistic regression analysis, we tested whether cigarette type moderated the association between NMR and bioverified 7-day point prevalence abstinence at Week 8. Covariates include nicotine dependence, age, race, and gender. Three hundred two participants reported smoking menthol cigarettes, of which 234 (77%) were classified as slow NMR. Among the 172 nonmenthol smokers, 136 were classified as slow NMR (79%). Contrary to our expectations, the NMR ×Cigarette Type interaction effect on abstinence was not significant (odds ratio [OR] = 0.91, p = .86). Excluding the interaction variable, fast NMR was associated with decreased likelihood of abstinence (OR = 0.55, p = .03), but menthol cigarette use was not (OR = 1.15, p = .56). Further exploration of risk factors among menthol cigarette smokers, especially among racially diverse and light smokers, could clarify the association between menthol cigarette use and poorer smoking outcomes. (PsycINFO Database Record

Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes.

OBJECTIVES: Little is known about the degree of nicotine replacement across first-generation e-cigarette brands, how e-cigarettes are used, and if there is variation across brands in relevant smoking phenotypes. The objective of this project was to collect data that are critical to better understanding, use, and exposure when using e-cigarettes, which may then inform clinical trials and tobacco regulatory policy. METHODS: Twenty-eight cigarette smokers were randomized to use one of 5 popular brands of e-cigarettes for a 10-day study. Day 1 (own cigarette brand) data established baseline levels for cotinine, carbon monoxide (CO), topography, cigarette liking, withdrawal, and craving. Participants returned on Days 5 and 10 to reassess these measures while exclusively using e-cigarettes. RESULTS: Compared to cigarette smoking, e-cigarettes provided significantly lower nicotine levels (25%-50%), reduced CO exposure, and lower ratings of liking (p < .05). Topography significantly differed between cigarette and e-cigarette sessions (p < .05). All brands significantly reduced withdrawal and craving (p < .05). There were no significant brand differences in outcome measures associated with exposure or use. CONCLUSIONS: E-cigarettes are not liked as much as cigarettes, provide significantly lower nicotine replacement, reduce CO exposure, and mitigate withdrawal and craving. The patterns of use significantly differ compared to cigarette smoking.

Longitudinal changes in smoking abstinence symptoms and alternative reinforcers predict long-term smoking cessation outcomes.

BACKGROUND: Transdermal nicotine, with behavioral counseling, is among the most popular approaches used to quit smoking. Yet, 6-month cessation rates rarely exceed 20-25%. Identifying factors associated with cessation success may help researchers and clinicians develop enhanced interventions that can improve quit rates. This study examined longitudinal changes in withdrawal, craving, depression and anxiety symptoms, and alternative reinforcers, from a baseline assessment to a 6-month outcome, as predictors of 6-month smoking cessation outcomes following 8 weeks of nicotine patch treatment and counseling. METHODS: A sample of 180 smokers, who completed an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Generalized estimating equations evaluated changes in withdrawal and craving, depression and anxiety symptoms, and alternative reinforcers over time, between participants who were smoking at 6-months and participants who were abstinent (confirmed with carbon monoxide) at 6-months. Multiple logistic regression assessed changes in these variables as predictors of relapse. RESULTS: Controlling for covariates associated with cessation (i.e., nicotine dependence, patch adherence, and rate of nicotine metabolism), participants who were abstinent at 6 months showed significantly lower craving and withdrawal and significantly higher substitute reinforcers from baseline to 6 months, vs. those who were smoking at 6 months (p<0.001). An increase in craving predicted relapse to smoking (p<0.05). CONCLUSIONS: These results support continued efforts to strengthen interventions that reduce withdrawal and craving and the development of interventions to address alternative reinforcers in order to promote long-term smoking abstinence following nicotine patch treatment.

Long-term nicotine replacement therapy: a randomized clinical trial.

IMPORTANCE: The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the standard 8 weeks. This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit. OBJECTIVE: To compare 8 (standard), 24 (extended), and 52 (maintenance) weeks of nicotine patch treatment for promoting tobacco abstinence. DESIGN, SETTING, AND PARTICIPANTS: We recruited 525 treatment-seeking smokers for a randomized clinical trial conducted from June 22, 2009, through April 15, 2014, through 2 universities. INTERVENTIONS: Smokers received 12 smoking cessation behavioral counseling sessions and were randomized to 8, 24, or 52 weeks of nicotine patch treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was 7-day point prevalence abstinence, confirmed with breath levels of carbon monoxide at 6 and 12 months (intention to treat). RESULTS: At 24 weeks, 21.7% of participants in the standard treatment arm were abstinent, compared with 27.2% of participants in the extended and maintenance treatment arms (χ(2)(1) = 1.98; P = .17). In a multivariate model controlled for covariates, participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the standard treatment arm (odds ratio [OR], 1.70 [95% CI, 1.03-2.81]; P = .04), had a longer duration of abstinence until relapse (ß = 21.30 [95% CI, 10.30-32.25]; P < .001), reported smoking fewer cigarettes per day if not abstinent (mean [SD], 5.8 [5.3] vs 6.4 [5.1] cigarettes per day; ß = 0.43 [95% CI, 0.06-0.82]; P = .02), and reported more abstinent days (mean [SD], 80.5 [38.1] vs 68.2 [43.7] days; OR, 1.55 [95% CI, 1.06-2.26]; P = .02). At 52 weeks, participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the standard and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE: The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01047527.

Rate of nicotine metabolism and smoking cessation outcomes in a community-based sample of treatment-seeking smokers.

BACKGROUND: In samples from controlled randomized clinical trials, a smoker's rate of nicotine metabolism, measured by the 3-hydroxycotinine to cotinine ratio (NMR), predicts response to transdermal nicotine. Replication of this relationship in community-based samples of treatment-seeking smokers may help guide the implementation of the NMR for personalized treatment for nicotine dependence. METHODS: Data from a community-based sample of treatment seeking smokers (N=499) who received 8weeks of transdermal nicotine and 4 behavioral counseling sessions were used to evaluate associations between the NMR and smoking cessation. Secondary outcomes included withdrawal and craving, depression and anxiety, side effects, and treatment adherence. RESULTS: The NMR was a significant predictor of abstinence (OR=.56, 95% CI: 0.33-0.95, p=.03), with faster metabolizers showing lower quit rates than slower metabolizers (24% vs. 33%). Faster nicotine metabolizers exhibited significantly higher levels of anxiety symptoms over time during treatment, vs. slower metabolizers (NMR x Time interaction: F[3,357]=3.29, p=.02). NMR was not associated with changes in withdrawal, craving, depression, side effects, and treatment adherence (p's>.05). CONCLUSIONS: In a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment program, vs. slower nicotine metabolizers. These results provide further evidence that transdermal nicotine is less effective for faster nicotine metabolizers and suggest the need to address cessation-induced anxiety symptoms among these smokers to increase the chances for successful smoking cessation.