Lisa Sanderson Cox

University of Kansas, Lawrence, Kansas, United States

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Publications (69)248.46 Total impact

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    ABSTRACT: Background: African-Americans smoke fewer cigarettes per day than Whites but experience greater smoking attributable morbidity and mortality. African-American-White differences may also exist in cessation but rigorously designed studies have not been conducted to empirically answer this question. Methods/design: Quit2Live is, to our knowledge, the first head-to-head trial designed with the primary aim of examining African-American-White disparities in quitting smoking. Secondary aims are to identify mechanisms that mediate and/or moderate the relationship between race and quitting. The study is ongoing. Study aims are accomplished through a 5-year prospective cohort intervention study designed to recruit equal numbers of African-Americans (n=224) and Whites (n=224) stratified on age (<40, ≥40) and gender, key factors known to impact cessation, and all within a restricted income range (≤400% federal poverty level). All participants will receive 12weeks of varenicline in combination with smoking cessation counseling. The primary outcome is cotinine-verified 7-day point prevalence abstinence from smoking at week 26. Secondary outcomes are cotinine-verified 7-day point prevalence abstinence from smoking at weeks 4 and 12. Discussion: Findings from Quit2Live will not only address if African-American-White disparities in quitting smoking exist but, more importantly, will examine mechanisms underlying the difference. Attention to proximal, modifiable mechanisms (e.g., adherence, response to treatment, depression, stress) maximizes Quit2Live's potential to inform practice. Findings will provide an empirically-derived approach that will guide researchers and clinicians in identifying specific factors to address to improve cessation outcomes and reduce tobacco-related morbidity and mortality in African-American and White smokers. Trial registration number: NCT01836276.
    No preview · Article · Dec 2015 · Contemporary clinical trials
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    ABSTRACT: Background: In rural America, cigarette smoking is prevalent and health care providers lack the time and resources to help smokers quit. Telephone quitlines are important avenues for cessation services in rural areas, but they are poorly integrated with local health care resources. Objective: The intent of the study was to assess the comparative effectiveness and cost effectiveness of two models for delivering expert tobacco treatment at a distance: telemedicine counseling that was integrated into smokers' primary care clinics (Integrated Telemedicine-ITM) versus telephone counseling, similar to telephone quitline counseling, delivered to smokers in their homes (Phone). Methods: Smokers (n=566) were recruited offline from 20 primary care and safety net clinics across Kansas. They were randomly assigned to receive 4 sessions of ITM or 4 sessions of Phone counseling. Patients in ITM received real-time video counseling, similar to Skype, delivered by computer/webcams in clinic exam rooms. Three full-time equivalent trained counselors delivered the counseling. The counseling duration and content was the same in both groups and was available in Spanish or English. Both groups also received identical materials and assistance in selecting and obtaining cessation medications. The primary outcome was verified 7-day point prevalence smoking abstinence at month 12, using an intent-to-treat analysis. Results: There were no significant baseline differences between groups, and the trial achieved 88% follow-up at 12 months. Verified abstinence at 12 months did not significantly differ between ITM or Phone (9.8%, 27/280 vs 12%, 34/286; P=.406). Phone participants completed somewhat more counseling sessions than ITM (mean 2.6, SD 1.5 vs mean 2.4, SD 1.5; P=.0837); however, participants in ITM were significantly more likely to use cessation medications than participants in Phone (55.9%, 128/280 vs 46.1%, 107/286; P=.03). Compared to Phone participants, ITM participants were significantly more likely to recommend the program to a family member or friend (P=.0075). From the combined provider plus participant (societal) perspective, Phone was significantly less costly than ITM. Participants in ITM had to incur time and mileage costs to travel to clinics for ITM sessions. From the provider perspective, counseling costs were similar between ITM (US $45.46, SD 31.50) and Phone (US $49.58, SD 33.35); however, total provider costs varied widely depending on how the clinic space for delivering ITM was valued. Conclusions: Findings did not support the superiority of ITM over telephone counseling for helping rural patients quit smoking. ITM increased utilization of cessation pharmacotherapy and produced higher participant satisfaction, but Phone counseling was significantly less expensive. Future interventions could combine elements of both approaches to optimize pharmacotherapy utilization, counseling adherence, and satisfaction. Such an approach could commence with a telemedicine-delivered clinic office visit for pharmacotherapy guidance, and continue with telephone or real-time video counseling delivered via mobile phones to flexibly deliver behavioral support to patients where they most need it-in their homes and communities. Trial registration: NCT00843505; (Archived by WebCite at
    No preview · Article · May 2015 · Journal of Medical Internet Research
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    ABSTRACT: A number of candidate gene and genome-wide association studies have identified significant associations between single nucleotide polymorphisms, particularly in FTO and MC4R, and body weight. However, the association between copy number variation and body weight is less understood. Anabolic androgenic steroids, such as testosterone, can regulate body weight. In humans, UDP-glucuronosyltransferase 2B17 (UGT2B17) metabolizes testosterone to a metabolite, which is readily excreted in urine. We investigate the association between genetic and phenotypic variation in UGT2B17 and body weight. UGT2B17 deletion was genotyped and in-vivo UGT2B17 enzymatic activity (as measured by the 3-hydroxycotinine glucuronide to free 3-hydroxycotinine ratio) was measured in 400 Alaska Native individuals and 540 African Americans. In Alaska Native people, UGT2B17 deletion was strongly associated with lower BMI in male individuals (P<0.001), but not in female individuals, consistent with testosterone being a male dominant steroid. The sex-specific association between UGT2B17 deletion and lower BMI was also observed in African Americans (P=0.01 in male individuals). In both populations, UGT2B17 deletion was significantly associated with lower measured in-vivo UGT2B17 activity. In male individuals, lower in-vivo UGT2B17 activity was associated with lower BMI, as observed in the sex-specific genotypic association. These data suggest that UGT2B17 deletion leads to reduced UGT2B17 activity, and lower BMI in male individuals. This is consistent with the hypothesis that reduced UGT2B17-mediated testosterone excretion results in higher testosterone levels. Future studies could confirm this hypothesis by directly measuring serum testosterone levels.
    No preview · Article · Mar 2015 · Pharmacogenetics and Genomics
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    ABSTRACT: The Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM) is a multi-dimensional smoking dependence measure that assesses primary dependence motives (PDM; e.g., core dependence marked by tolerance, craving) and secondary dependence motives (SDM; e.g., auxiliary dependence motives such as cognitive enhancement, weight control). However, the relationship between PDM, SDM, and smoking level remains unclear. Thus, we examined these scales across smoking levels in a diverse sample of smokers. Participants were 2376 African American, Latino, and non-Hispanic White smokers recruited using an online panel research company. The sample included 297 native nondaily smokers (never smoked daily), 297 converted nondaily smoker (previously smoked daily for ≥six months), 578 light daily smokers (≤10 cigarettes per day [cpd]), and 597 moderate to heavy daily smokers (>10cpd). Results of a multinomial logistic regression showed that for each unit increase in SDM, after controlling for PDM, the odds of being a native nondaily, converted nondaily or light smoker vs. moderate to heavy smoker increased by 29% to 56% (ps<0.001). In the model, higher PDM scores were associated with lower odds of being a native nondaily, converted nondaily, or light smoker vs. a moderate to heavy daily smoker (ps<0.001). Nondaily and light smokers endorse higher secondary dependence motives relative to their primary dependence motives. Smoking cessation trials for nondaily and light smokers might address these secondary motives within the context of counseling intervention to enhance abstinence. Copyright © 2014 Elsevier Ltd. All rights reserved.
    No preview · Article · Nov 2014 · Addictive Behaviors
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    ABSTRACT: Bupropion is used clinically to treat depression and to promote smoking cessation. It is metabolized by CYP2B6 to its active metabolite hydroxybupropion, yet alterations in CYP2B6 activity have little impact on bupropion plasma levels. Furthermore, less than 10% of a bupropion dose is excreted as urinary bupropion and its characterized metabolites hydroxybupropion, threohydrobupropion and erythrohydrobupropion, suggesting that alternative metabolic pathways may exist. In vitro data suggested CYP2C19 could metabolize bupropion. The current study investigated the impact of functional CYP2C19 genetic variants on bupropion pharmacokinetics and treatment outcomes. In 42 healthy volunteers, CYP2C19*2 (a reduced activity allele) was associated with higher bupropion AUC, but similar hydroxybupropion AUC. The mean bupropion AUC was 771 versus in individuals with, and without, CYP2C19*2 respectively (P=0.017). CYP2C19*2 was also associated with higher threohydrobupropion and erythrohydrobupropion AUC (P<0.005). Adjusting for CYP2B6 genotype did not alter these associations, and CYP2C19 variants did not alter the utility of the hydroxybupropion/bupropion ratio as a measure of CYP2B6 activity. Finally, in a clinical trial of 540 smokers, CYP2C19 genotype was not associated with smoking cessation outcomes supporting the hypothesis that bupropion response is mediated by hydroxybupropion, which is not altered by CYP2C19. In conclusion, our study reports the first in vivo evidence that reduced CYP2C19 activity significantly increases the steady state exposure to bupropion and its reductive metabolites threohydrobupropion and erythrohydrobupropion. These pharmacokinetic changes were not associated with differences in bupropion's ability to promote smoking cessation in smokers, but may influence the side effects and toxicity associated with bupropion.
    No preview · Article · Sep 2014 · Drug metabolism and disposition: the biological fate of chemicals
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    ABSTRACT: Introduction: An increasing proportion of daily smokers are light smokers (≤10 cigarettes per day). Some light smokers have never smoked more than 10 cigarettes per day (native light smokers) and others smoked at higher levels but have cut down (converted light smokers). It is important that we expand our understanding of these distinct subgroups of light smokers in order to develop effective interventions. Methods: Data for this report come from a larger sample of smokers who completed a cross-sectional survey administered through an online panel survey service. The sample of 522 light smokers included 256 native light smokers and 266 as converted light smokers. The goal of the analysis was to examine demographic, smoking, and psychosocial factors that differentiate between native and converted light smokers. Results: Multivariable logistic regression results showed 4 variables that differentiated between native and converted light smokers. Native light smokers were more likely to be Black than White, smoke fewer cigarettes per day, smoked fewer total years, and had higher perceived risk of heart disease than converted light smokers. Conclusions: Native and converted light smokers are similar in many ways and also differ on some important characteristics. Further exploration of group difference is needed and could help to inform for cessation strategies for daily light smokers.
    No preview · Article · Sep 2014 · Nicotine & Tobacco Research
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    ABSTRACT: In rural America cigarette smoking is prevalent, few cessation services are available, and healthcare providers lack the time and resources to help smokers quit. This paper describes the design and participant characteristics of Connect2Quit (C2Q), a randomized control trial (RCT) that tests the effectiveness and cost-effectiveness of integrated telemedicine counseling delivered by 2-way webcams mounted on desktop computers in participant's physician office examining rooms (ITM) versus quitline counseling delivered by telephone in participant's homes (Phone) for helping rural smokers quit. /Design C2Q was implemented in twenty primary care and safety net clinics. Integrated Telemedicine consisted of real-time video counseling, delivered to patients in their primary care physician's (PCP) office. Phone counseling, was delivered to patients in their homes. All participants received educational materials and guidance in selecting cessation medications. The 566 participants were predominantly Caucasian (92%); 9% were Latino. Most (65%) earned<200% of federal poverty level. One out of three lacked home internet access, 40% were not comfortable using computers, and only 4% had been seen by a doctor via telemedicine in the past. Hypertension, chronic lung disease, and diabetes were highly prevalent. Participants smoked nearly a pack a day and were highly motivated to quit. C2Q is reaching a rural low-income population, with comorbid chronic diseases, that would benefit greatly from quitting smoking. ITM is a good delivery model, which integrates care by holding counseling sessions in the patient's PCP office and keeps the primary care team updated on patients' progress. Trial registration Clinical Trials Registration: NCT00843505.
    No preview · Article · Apr 2014 · Contemporary clinical trials
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    ABSTRACT: Associations between CHRNA5-A3-B4 variants and smoking behaviors exist, however the association with smoking abstinence is less understood, particularly among African Americans. In 1295 African Americans enrolled in two clinical trials, we investigated the association between CHRNA5-A3-B4 and smoking abstinence. Rs2056527[A] was associated with lower abstinence with active pharmacotherapy (during-treatment: OR=0.42&P<0.001; end of treatment (EOT): OR=0.55&P=0.004), or with nicotine gum alone (during-treatment: OR=0.31&P<0.001; EOT: OR=0.51&P=0.02), but not significantly with bupropion, although similar directions and magnitudes were observed (during-treatment: OR=0.54&P=0.05; EOT: OR=0.59&P=0.08). Additionally, rs588765[T] was associated with abstinence with gum during treatment (OR=2.31&P<0.01). Rs16969968 occurred at a low frequency and was not consistently associated with abstinence. CHRNA5-A3-B4 variants were not associated with tobacco consumption and adjustments for smoking behaviors did not alter the associations with smoking abstinence. Together, our data suggest that in African Americans CHRNA5-A3-B4 variants are not associated with baseline smoking, but can influence smoking abstinence during active pharmacotherapy.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 14 April 2014; doi:10.1038/clpt.2014.88.
    No preview · Article · Apr 2014 · Clinical Pharmacology &#38 Therapeutics
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    ABSTRACT: Introduction: Despite smoking fewer cigarettes per day, African American smokers have greater difficulty quitting compared to Caucasian smokers. Further elucidating the impact of smoking motivations on smoking behaviour would contribute to understanding the factors that maintain smoking. Aims: This study examined the factor structure of a brief assessment examining smoking dependence motives among a sample of African American light smokers. Methods: Data from a double-blind, placebo-controlled randomised smoking cessation trial involving 540 participants. Results were analysed using an exploratory factor analysis (EFA) and a randomly split EFA. Results/Findings: Findings from the initial EFA analysis produced an eight-factor model, explaining 69% of the variation in responses. The overall Measure of Sampling Adequacy (MSA) was 0.88 with item level MSA ranging 0.68–0.94 across the 30 items. Results from the randomly split EFA replicated the findings of the original EFA; with the exception of the item ‘I smoke within the first 30 minutes of awakening in the morning’. Conclusions: These findings support the hypothesis of a multidimensional approach to conceptualising nicotine dependence, and provide information regarding characteristics of nicotine dependence in African American light smokers which may be helpful in identifying targets for cessation treatment in this population of smokers.
    Full-text · Article · Mar 2014 · The Journal of Smoking Cessation
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    ABSTRACT: The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic variants in an additional nicotine-metabolizing enzyme, flavin-containing monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme, cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3 158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6 metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V are minor sources of nicotine metabolism variation, insufficient to appreciably alter smoking.
    No preview · Article · Jan 2014 · Pharmacogenetics and Genomics
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    ABSTRACT: Nicotine, the main addictive ingredient in tobacco, is metabolically inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Considerable genetic variation in the CYP2A6 gene results in large variation in the rates of nicotine metabolism, which in turn alters smoking behaviours (e.g. amount of cigarettes smoked, risk for dependence and success in smoking cessation). The aim of this study was to identify and characterize novel variants in CYP2A6. The CYP2A6 gene from African American phenotypically slow nicotine metabolizers was sequenced and seven novel variants were identified [CYP2A6*39 (V68M), CYP2A6*40 (I149M), CYP2A6*41 (R265Q), CYP2A6*42 (I268T), CYP2A6*43 (T303I), CYP2A6*44 (E390K), CYP2A6*44 (L462P)]. Variants were introduced into a bi-cistronic cDNA expression construct containing CYP2A6 and P450 oxidoreductase and assessed for protein expression, enzymatic activity and stability as evaluated using western blotting and nicotine metabolism. Genotyping assays were developed and allelic frequencies were assessed in 534 African Americans. The variants showed significantly lower protein expression (P<0.001) when compared with the wild-type as well as reduced metabolism of nicotine to cotinine when controlling for cDNA expression using P450 oxidoreductase (P<0.001). The variants also showed reduced stability at 37°C. Allelic frequencies ranged from 0.1 to 0.6% with a collective genotype frequency of 3.2%; the impact in vitro correlated significantly with in-vivo activity (R=0.40-0.48, P<0.05). Together, those with a novel variant had significantly lower nicotine metabolism in vivo than those without genetic variants (P<0.01). Here, we identified a number of novel variants with reduced/loss of CYP2A6 activity, increasing our understanding of CYP2A6 genetic variability.
    No preview · Article · Dec 2013 · Pharmacogenetics and Genomics
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    ABSTRACT: CYP2A6 metabolizes nicotine to its primary metabolite cotinine and also mediates the metabolism of cotinine to trans-3'-hydroxycotinine (3HC). The ratio of 3HC to cotinine (the "nicotine metabolite ratio", NMR) is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. The clearance of 3HC, which affects the NMR, occurs via renal excretion and metabolism by UGT2B17, and possibly UGT2B10, to 3HC-glucuronide. We investigated whether slower 3HC glucuronidation alters NMR, altering its ability to predict CYP2A6 activity and reducing its clinical utility. Plasma NMR, three urinary NMRs, three urinary 3HC glucuronidation phenotypes and total nicotine equivalents were examined in 540 African American smokers. The UGT2B17 gene deletion and UGT2B10*2 were genotyped. The UGT2B17 gene deletion, but not UGT2B10*2 genotype, was associated with slower 3HC glucuronidation (indicated by three 3HC-glucuronidation phenotypes), indicating its role in this glucuronidation pathway. However, neither lower rates of 3HC glucuronidation, nor the presence of a UGT2B17 and UGT2B10 reduced function allele, altered plasma or urinary NMRs or levels of smoking. Variation in 3HC glucuronidation activity, including these caused by UGT2B17 gene deletions, did not significantly alter NMR and is therefore unlikely to affect the clinical utility of NMR in smoking behavior and cessation studies. This study demonstrates that NMR is not altered by differences in the rate of 3HC glucuronidation, providing further support that NMR is a reliable indicator of CYP2A6 mediated nicotine metabolism.
    Full-text · Article · Aug 2013 · PLoS ONE
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    ABSTRACT: Background African Americans are at risk of inadequate adherence to smoking cessation treatment, yet little is known about what leads to treatment discontinuation. Purpose The purpose of this study was to examine the factors associated with discontinuation of treatment in African American light smokers (≤10 cigarettes per day). Methods Bupropion plasma levels and counseling attendance were measured among 540 African American light smokers in a placebo-controlled randomized trial of bupropion. Results By week 3, 28.0 % of subjects in the bupropion arm had discontinued bupropion, and only moderate associations were found between the plasma levels and self-reported bupropion use (r s = 0.38). By week 16, 36.9 % of all subjects had discontinued counseling. Males had greater odds of discontinuing medication (OR = 2.02, 95% CI = 1.10–3.71, p = 0.02), and older adults had lower odds of discontinuing counseling (OR = 0.96, 95% CI = 0.94–0.97, p < 0.0001). Conclusions Bupropion and smoking cessation counseling are underutilized even when provided within the context of a randomized trial. Future research is needed to examine strategies for improving treatment utilization among African American smokers. Trial Registration No. NCT00666978 (www. clinicaltrials. gov).
    Full-text · Article · Jun 2013 · Annals of Behavioral Medicine
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    ABSTRACT: Latino immigrants are less likely to be involved in addressing health-related issues affecting their own community. Community health workers have played a significant role in addressing the health of underserved communities in several countries. The objective of this article is to describe the development, implementation and evaluation of a community-based training program that empowers promotores to identify the health needs of recent Latino immigrants. Promotores were able to develop interventions based on the needs of recent Latino immigrants. Latino community members participated in a 30-hour training program. Training was provided in 15 two-hour sessions over 3 months. Training included field work accompanied by skills development in leadership, organization, interpersonal communication, and survey implementation. Upon completion of the training, promotores conducted household surveys designed to identify community health needs. The evaluation employed quantitative measures to track promotores' canvassing activities and assessment of health behaviors. Out of the 22 promotores enrolled in the training program, 15 (68.18%) completed the training program. Within 3 months, promotores administered 105 household surveys and identified poor access to health care, lack of insurance (78.6%), low daily consumption of fruits (73%) and vegetables (37.5%) and frequent exposure to tobacco smoke (31.7%). Our study demonstrated the feasibility of recruiting and engaging promotores to identify health priorities within the Latino community. This initial step will inform the development of future community-based interventions.
    No preview · Article · Jan 2013 · Journal of Immigrant & Refugee Studies
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    ABSTRACT: Background: This is the first study to examine predictors of successful cessation in African American (AA) light smokers treated within a placebo-controlled trial of bupropion. Methods: We analyzed data from a randomized, double-blind, placebo-controlled trial of bupropion and health education for 540 African American light smokers. African American light smokers (≤10 cigarettes per day, cpd) were randomly assigned to receive 150mg bid bupropion SR (n=270) or placebo (n=270) for 7weeks. All participants received health education counseling at weeks 0, 1, 3, 5 and 7. Using chi-square tests, two sample t-tests, and multiple logistic regression analyses, we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment (Week 7) and at the end of follow-up (Week 26). Results: Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo (OR=2.72, 95% CI=1.60-4.62, P=0.0002). Greater study session attendance (OR=2.47, 95% CI=1.76-3.46, P=0.0001), and smoking non-menthol cigarettes increased the likelihood of quitting (OR=1.84, 95% CI=1.01-3.36, P=0.05); while longer years of smoking (OR=0.98, 95% CI=0.96-1.00, P=0.05) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.002) significantly reduced the odds of quitting at Week 7. Conversely, at the end of follow-up (Week 26), treatment with bupropion vs. placebo (OR=1.14, 95% CI=0.65-2.02, P=0.64) was not significantly associated with quitting and type of cigarette smoked (menthol vs. non-menthol) did not appear in the final logistic regression model. Greater study session attendance (OR=1.96, 95% CI=1.44-2.66, P=0.0001); BMI (OR=1.03, 95% CI=1.00-1.07, P=0.04); and weight efficacy (OR=1.03, 95% CI=1.01-1.05, P=0.01) increased the likelihood of quitting at Week 26. Similar to our findings at Week 7, longer years of smoking (OR=0.96, 95% CI=0.94-0.99, P=0.01) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.02) significantly reduced the odds of quitting at Week 26. Conclusions: Baseline cotinine levels, number of years smoked and study session attendance are associated with both short- and long-term smoking cessation, while bupropion and the type of cigarette smoked were associated with quitting on short term only.
    Full-text · Article · Nov 2012 · Addictive behaviors
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    ABSTRACT: Bupropion is indicated to promote smoking cessation. Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite, hydroxybupropion. We measured plasma bupropion and its metabolite levels in a double-blind, placebo controlled, randomized smoking-cessation trial. Among the treatment-adherent individuals, higher hydroxybupropion concentrations (per μg/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds ratio (OR) = 2.82, 2.96, and 2.37, respectively, P = 0.005-0.040); this was not observed with bupropion levels (OR = 1.00-1.03, P = 0.59-0.90). Genetic variation in CYP2B6, the enzyme that metabolizes bupropion to hydroxybupropion, was identified as a significant source of variability in hydroxybupropion formation. Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation, and that variability in response to bupropion treatment is related to variability in CYP2B6-mediated hydroxybupropion formation. These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion's cessation outcomes.Clinical Pharmacology & Therapeutics (2012); advance online publication 14 November 2012. doi:10.1038/clpt.2012.186.
    Full-text · Article · Nov 2012 · Clinical Pharmacology &#38 Therapeutics
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    ABSTRACT: Introduction: Psychoactive effects of smoking cessation medi cations such as bupropion may allow participants in smoking cessation clinical trials to correctly guess their treatment assignment at rates greater than chance. Previous research has found an association between perceived treatment assignment and smoking cessation rates among moderate to heavy smokers (≥ 10 cigarettes per day [cpd]) in two bupropion clinical trials. Methods: The aim of this study was to determine the impact of perceived treatment assignment on end-of-treatment cotinine-verified smoking abstinence at Week 7 and Week 26 among African American light smokers (≤ 10 cpd) enrolled in a double-blind, placebo-controlled study of bupropion. Participants (n = 390) included in this study reported their perceived treatment assignment on the end-of-treatment (Week 7) survey. Results: Participants were predominantly female (63.1%), 48.1 years of age (SD = 11.2), and smoked an average of 8 cpd (SD = 2.5). Participants given bupropion were more likely to correctly guess their treatment assignment (69%; 140/203) than those assigned to placebo (51.3%; 96/187) (p < .0001). After adjusting for treatment condition, participants who perceived assignment to bupropion versus placebo were not more likely to be abstinent than those who perceived assignment to placebo at Week 7 or at Week 26. The interaction between treatment and perceived treatment assignment was also nonsignificant. Conclusions: Consistent with two previous studies testing bupropion, participants assigned to bupropion were more likely to correctly guess their treatment assignment than those assigned to placebo. However, in contrast to previous studies with heavier smokers, perceived treatment assignment did not significantly impact cotinine-verified abstinence in light smokers.
    Full-text · Article · Sep 2012 · Nicotine & Tobacco Research
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    ABSTRACT: Measuring adherence to smoking cessation pharmacotherapy is important to evaluating its effectiveness. Blood levels are considered the most accurate measure of adherence but are invasive and costly. Pill counts and self-report are more practical, but little is known about their relationship to blood levels. This study compared the validity of pill count and self-report against plasma varenicline concentration for measuring pharmacotherapy adherence. Data were obtained from a randomized pilot study of varenicline for smoking cessation among African American smokers. Adherence was measured on Day 12 via plasma varenicline concentration, pill count, 3-day recall, and a visual analogue scale (VAS; adherence was represented on a line with two extremes "no pills" and "all pills"). The sample consisted of 55 African American moderate to heavy smokers (average 16.8 cigarettes/day, SD = 5.6) and 63.6% were female. Significant correlations (p < .05) were found between plasma varenicline concentration and pill count (r = .56), 3-day recall (r = .46), and VAS (r = .29). Using plasma varenicline concentration of 2.0 ng/ml as the cutpoint for adherence, pill count demonstrated the largest area under the receiver operating characteristic curve (AUC = 0.85, p = .01) and had 88% sensitivity (95% CI = 75.0-95.0) and 80% specificity (95% CI = 30.0-99.0) for detecting adherence. Of 3 commonly used adherence measures, pill count was the most valid for identifying adherence in this sample of African American smokers. Pill count has been used across other health domains and could be incorporated into treatment to identify nonadherence, which, in turn, could maximize smoking cessation pharmacotherapy use and improve abstinence rates.
    No preview · Article · Feb 2012 · Nicotine & Tobacco Research
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    ABSTRACT: Previous research demonstrated the efficacy of sustained release bupropion (bupropion SR) for smoking cessation in whites as well as moderate to heavy (≥10 cigarettes per day [CPD]) African American smokers. We evaluated whether bupropion SR was effective for smoking cessation among African American light smokers (≤10 CPD). A randomized, double-blind placebo-controlled trial was conducted from December 27, 2007, to May 13, 2010. All participants were African American light smokers (≤10 CPD), aged 18 years or older. Participants were randomly assigned to receive 300 mg bupropion SR (150 mg once daily for 3 days and then 150 mg twice daily) (n = 270 participants) or placebo (n = 270 participants) for 7 weeks, and up to six sessions of health education counseling. Serum cotinine was measured at baseline (week 0). The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26; a cut point of 15 ng/mL differentiated smokers from nonsmokers. Salivary cotinine-verified smoking abstinence at end of medication treatment at week 7 was also examined. Odds ratios (OR) for smoking abstinence and 95% confidence intervals (CIs) were calculated using logistic regression models. All statistical tests were two-sided. Participants at baseline visit (week 0) smoked an average of 8.0 CPD and had a mean serum cotinine level of 275.8 ng/mL (SD = 155.8 ng/mL); most used menthol cigarettes (83.7%) and smoked within 30 minutes of waking (72.2%). After imputing those lost to follow-up as smokers, no statistically significant difference in long-term smoking abstinence rates at week 26 was observed between bupropion SR and placebo groups (13.3% vs 10.0%, OR = 1.39, 95% CI = 0.82 to 2.35, P = .23). Cotinine-verified smoking abstinence rate at end of medication week 7 was higher in the bupropion SR vs placebo group (23.7% vs 9.6%, OR = 2.92, 95% CI = 1.78 to 4.77, P < .001). Bupropion SR was effective in promoting smoking cessation during the medication phase of treatment but showed no effect on long-term smoking cessation among African American light smokers. More research is needed to identify strategies for sustaining abstinence among African American light smokers.
    Full-text · Article · Feb 2012 · Journal of the National Cancer Institute
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    ABSTRACT: Despite the widespread use of mentholated cigarettes, lower cessation rates, and disproportionately high smoking-related morbidity among Blacks, the possible role of menthol in smokers' response to pharmacotherapy has not been well-studied. This study examined the effects of menthol on the pharmacokinetic (PK) profiles of bupropion and its principal metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion among Black smokers. After a 7-day placebo run-in period, participants received 150 mg bid sustained-release bupropion for 20-25 days. Blood samples were drawn for PK analysis on 2 occasions, 10-15 days after the commencement of bupropion while participants were still smoking (smoking phase) and at days 20-25 when they were asked not to smoke (nonsmoking phase). 18 smokers of nonmenthol cigarettes and 23 smokers of menthol cigarettes were enrolled in this study. No differences were found by menthol smoking status in the Cmax and area under the plasma concentration versus time curve (AUC) of bupropion and its metabolites in the smoking or nonsmoking phases. However, among menthol smokers, the AUC ratios of metabolite/bupropion were lower in the nonsmoking phase compared with the smoking phase (hydro/bup = 31.49 ± 18.84 vs. 22.95 ± 13.27, p = .04; erythro/bup = 1.99 ± 1.02 vs. 1.76 ± 0.75, p = .016; threo/bup = 11.77 ± 8.90 vs. 10.44 ± 5.63, p = .034). No significant differences were found in the metabolite/bup ratios between smoking and nonsmoking conditions among nonmenthol smokers. We did not find a significant effect of menthol compared with nonmenthol cigarette smoking on the PKs of bupropion and metabolites at steady state. More research is needed to advance the understanding of mechanisms underlying disparities in smoking cessation outcomes related to smoking of menthol cigarettes.
    Full-text · Article · Feb 2012 · Nicotine & Tobacco Research

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  • 2008-2015
    • University of Kansas
      • Department of Preventive Medicine and Public Health
      Lawrence, Kansas, United States
  • 2014
    • Vanderbilt University
      • Department of Psychology
      Nashville, Michigan, United States
  • 2011-2014
    • Kansas City University of Medicine and Biosciences
      Kansas City, Missouri, United States
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 2006-2014
    • Kansas City VA Medical Center
      Kansas City, Missouri, United States
  • 2007
    • University of Minnesota Twin Cities
      • Department of Medicine
      Minneapolis, Minnesota, United States
  • 2003-2005
    • Georgetown University
      • • Department of Oncology
      • • Lombardi Cancer Center
      Washington, Washington, D.C., United States
  • 2001-2004
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 1997-2001
    • Purdue University
      • Department of Psychological Sciences
      ウェストラファイエット, Indiana, United States