Genotyping, characterization, and imputation of known and novel CYP2A6 structural variants using SNP array data.

CYP2A6 metabolically inactivates nicotine. Faster CYP2A6 activity is associated with heavier smoking and higher lung cancer risk. The CYP2A6 gene is polymorphic, including functional structural variants (SV) such as gene deletions (CYP2A6*4), duplications (CYP2A6*1 × 2), and hybrids with the CYP2A7 pseudogene (CYP2A6*12, CYP2A6*34). SVs are challenging to genotype due to their complex genetic architecture. Our aims were to develop a reliable protocol for SV genotyping, functionally phenotype known and novel SVs, and investigate the feasibility of CYP2A6 SV imputation from SNP array data in two ancestry populations. European- (EUR; n = 935) and African- (AFR; n = 964) ancestry individuals from smoking cessation trials were genotyped for SNPs using an Illumina array and for CYP2A6 SVs using Taqman copy number (CN) assays. SV-specific PCR amplification and Sanger sequencing was used to characterize a novel SV. Individuals with SVs were phenotyped using the nicotine metabolite ratio, a biomarker of CYP2A6 activity. SV diplotype and SNP array data were integrated and phased to generate ancestry-specific SV reference panels. Leave-one-out cross-validation was used to investigate the feasibility of CYP2A6 SV imputation. A minimal protocol requiring three Taqman CN assays for CYP2A6 SV genotyping was developed and known SV associations with activity were replicated. The first domain swap CYP2A6-CYP2A7 hybrid SV, CYP2A6*53, was identified, sequenced, and associated with lower CYP2A6 activity. In both EURs and AFRs, most SV alleles were identified using imputation (>70% and >60%, respectively); importantly, false positive rates were <1%. These results confirm that CYP2A6 SV imputation can identify most SV alleles, including a novel SV.

Effectiveness of Recruitment Strategies of Latino Smokers: Secondary Analysis of a Mobile Health Smoking Cessation Randomized Clinical Trial.

BACKGROUND: Latinos remain disproportionately underrepresented in clinical trials, comprising only 2%-3% of research participants. In order to address health disparities, it is critically important to increase enrollment of Latino smokers in smoking cessation trials. There is limited research examining effective recruitment strategies for this population. OBJECTIVE: The purpose of this study was to compare the effectiveness of direct versus mass and high- versus low-effort recruitment strategies on recruitment and retention of Latino smokers to a randomized smoking cessation trial. We also examine how the type of recruitment might have influenced the characteristics of enrolled participants. METHODS: Latino smokers were enrolled into Decídetexto from 4 states-New Jersey, Kansas, Missouri, and New York. Participants were recruited from August 2018 until March 2021. Mass recruitment strategies included English and Spanish advertisements to the Latino community via flyers, Facebook ads, newspapers, television, radio, church bulletins, and our Decídetexto website. Direct, high-effort strategies included referrals from clinics or community-based organizations with whom we partnered, in-person community outreach, and patient registry calls. Direct, low-effort strategies included texting or emailing pre-existing lists of patients who smoked. A team of trained bilingual (English and Spanish) recruiters from 9 different Spanish-speaking countries of origin conducted recruitment, assessed eligibility, and enrolled participants into the trial. RESULTS: Of 1112 individuals who were screened, 895 (80.5%) met eligibility criteria, and 457 (457/895, 51.1%) enrolled in the trial. Within the pool of screened individuals, those recruited by low-effort recruitment strategies (both mass and direct) were significantly more likely to be eligible (odds ratio [OR] 1.67, 95% CI 1.01-2.76 and OR 1.70, 95% CI 0.98-2.96, respectively) and enrolled in the trial (OR 2.60, 95% CI 1.81-3.73 and OR 3.02, 95% CI 2.03-4.51, respectively) compared with those enrolled by direct, high-effort strategies. Among participants enrolled, the retention rates at 3 months and 6 months among participants recruited via low-effort strategies (both mass and direct) were similar to participants recruited via direct, high-effort methods. Compared with enrolled participants recruited via direct (high- and low-effort) strategies, participants recruited via mass strategies were less likely to have health insurance (44.0% vs 71.2% and 71.7%, respectively; P<.001), lived fewer years in the United States (22.4 years vs 32.4 years and 30.3 years, respectively; P<.001), more likely to be 1st generation (92.7% vs 76.5% and 77.5%, respectively; P=.007), more likely to primarily speak Spanish (89.3% vs 65.8% and 66.3%, respectively), and more likely to be at high risk for alcohol abuse (5.8 mean score vs 3.8 mean score and 3.9 mean score, respectively; P<.001). CONCLUSIONS: Although most participants were recruited via direct, high-effort strategies, direct low-effort recruitment strategies yielded a screening pool more likely to be eligible for the trial. Mass recruitment strategies were associated with fewer acculturated enrollees with lower access to health services-groups who might benefit a great deal from the intervention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03586596; https://clinicaltrials.gov/ct2/show/NCT03586596. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-DOI: 10.1016/j.cct.2020.106188.

Effect of Varenicline Added to Counseling on Smoking Cessation Among African American Daily Smokers: The Kick It at Swope IV Randomized Clinical Trial.

Importance: African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels. Objectives: To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers. Design, Setting, and Participants: The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018. Interventions: Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]). Main Outcomes and Measures: The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d). Results: Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]). Conclusions and Relevance: Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers. Trial Registration: ClinicalTrials.gov Identifier: NCT02360631.

Urine Metabolites for Estimating Daily Intake of Nicotine From Cigarette Smoking.

INTRODUCTION: Accurate measurement of nicotine exposure from cigarette smoke is important in studying disease risk and level of dependence. Urine total nicotine equivalents, the molar sum of nicotine and six metabolites (NE7), accounts for more than 90% of a nicotine dose and is independent of individual metabolic differences. However, measuring NE7 is technically difficult and costly. We compared NE7, the gold standard of nicotine intake, with different combinations of fewer urinary nicotine metabolites. We also examined the impact of individual differences in nicotine metabolic rate, sex, and race on strength of association with NE7. METHODS: Urine samples from 796 daily smokers, who participated across five clinical studies, were assayed for nicotine and/or metabolites. Associations with NE7 were assessed by regression and Bland-Altman analyses. RESULTS: Overall, the molar sum of urine [cotinine + 3'-hydroxycotinine (3HC)] (NE2) and [nicotine + cotinine + 3HC] (NE3) were strongly correlated with NE7 (r = .97 and .99, respectively). However, in slow metabolizers NE2 was less predictive of NE7, whereas NE3 was equally robust. Urine total cotinine was also strongly correlated with NE7 (r = .87). CONCLUSIONS: Urine NE3 is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, whereas NE2 is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies. IMPLICATIONS: The molar sum of urine total nicotine, cotinine and 3HC (NE3) is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, and performs as well as measuring seven nicotine metabolites (NE7). The sum of cotinine and 3HC (NE2) is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.

Impact of Adding Telephone-Based Care Coordination to Standard Telephone-Based Smoking Cessation Counseling Post-hospital Discharge: a Randomized Controlled Trial.

BACKGROUND: Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. OBJECTIVE: To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. DESIGN: Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6 months post-hospitalization, persistent smokers were re-engaged with either CCC or C. MAIN MEASURES: Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12 months post-discharge. KEY RESULTS: Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6 months (55.2%) and between 6 and 12 months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12 months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). CONCLUSION: Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6 months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. TRIAL REGISTRATION: NCT01063972.

Intent to quit, quit attempts, and perceived health risk reduction among African American, Latino, and White nondaily and daily smokers in the United States.

Objective: Ethnic and racial differences in smoking patterns and behaviors have been well documented and most African American and Latino smokers are nondaily or light smokers. However, differences within smoking levels are understudied. Our primary aim was to determine whether there are racial and ethnic differences among African American, Latino, and White nondaily, light daily, and moderate to heavy daily smokers on (1) perceived health risk reduction, (2) intentions to quit, and (3) past year quit attempts. Design: Smokers were recruited through an online research panel for a cross-sectional survey (n = 2376). Sampling quotas were used to obtain equal numbers of African American, Latino, and White nondaily and daily smokers. Results: African American (59.6%) and Latino (54%) nondaily smokers were more likely than White nondaily smokers (45%) to currently limit their cigarettes per day (cpd) as a perceived health risk reduction strategy (p < 0.05). African American nondaily smokers were more likely than Latino and White nondaily smokers (p < 0.05) to limit their smoking in the past year as a perceived health risk reduction strategy (range: 0 'never' to 5 'always'; Means = 3.2, 2.9, 3.0, standard deviations [SD] = 1.1, 1.1, 1.2, respectively). African American nondaily smokers (15%) were more likely than either Latinos (7.8%) or Whites (8.5%) to intend to quit in the next 30 days (p < 0.01). African American (61.6%) and Latino (60.3%) nondaily smokers were more likely than Whites (49%) to have made a quit attempt in the past year (p < 0.01). Fewer racial and ethnic differences were found among daily smokers. Conclusions: Racial and ethnic group differences were more pronounced among nondaily smokers compared to light daily smoker and moderate to heavy daily smokers. Smoking level is an important consideration in understanding racial and ethnic variation in perceived health risk reduction and cessation-related behaviors.

Comparison of native light daily smokers and light daily smokers who were former heavy smokers.

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.

Comparative and cost effectiveness of telemedicine versus telephone counseling for smoking cessation.

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: Clinicaltrials.gov NCT00843505; http://clinicaltrials.gov/ct2/show/NCT00843505 (Archived by WebCite at http://www.webcitation.org/6YKSinVZ9).

Gene variants in CYP2C19 are associated with altered in vivo bupropion pharmacokinetics but not bupropion-assisted smoking cessation outcomes.

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 area under the plasma concentration-time curve (AUC), but similar hydroxybupropion AUC. The mean bupropion AUC was 771 versus 670 hours⋅ng/ml 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.

Factors associated with discontinuation of bupropion and counseling among African American light smokers in a randomized clinical trial.

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.

"I'm a transgender man I have to quit smoking for treatment and surgery": Describing the experience of a Latino transgender man during his attempt to quit smoking.

OBJECTIVE: To describe the experience of a Latino transgender man during his attempt to quit smoking using a text messaging intervention. METHODS: A Latino transgender man enrolled in a smoking cessation randomized controlled trial for Latino smokers. The participant was randomized to Decídetexto, a smoking cessation mobile intervention. The participant received a 24-week text messaging intervention. We assessed text messaging interactivity with the program, satisfaction, and self-reported abstinence at Week 12 and Month 6. RESULTS: During the 24-week intervention period, the participant sent a total of 287 text messages to the program. When analyzing the content of the text messages sent by the participants, four important themes were identified: 1) gender identity, 2) low social support, 3) stressors (e.g., gender dysphoria), and 4) gender affirmation surgery as a reason to quit smoking. At both Week 12 and Month 6, the participant reported being extremely satisfied with the intervention and self-reported cigarette use. CONCLUSION: A smoking cessation mobile intervention generated high satisfaction and frequent interactivity among a Latino transgender man. This case report provides important insights into the experience of one Latino transgender man during his attempt to quit smoking. There is an urgent need to develop or adapt existing smoking cessation interventions to better meet the needs of transgender people.

Development and Demonstration of Tobacco Treatment Measures for Cancer Registries: Novel Metrics for Quality Improvement.

BACKGROUND: Individuals undergoing cancer treatment have better outcomes when they discontinue tobacco use. Few cancer centers systematically provide evidence-based cessation services. As part of a national quality improvement initiative [Cancer Center Cessation Initiative (C3i)], we collaborated with our cancer registry to develop and implement two tobacco treatment metrics for tracking the provision of behavioral support and pharmacotherapy. METHODS: Post-development, the tobacco treatment metrics were integrated into the registry for all future patients. We used means and frequencies to summarize tobacco treatment for cases treated between 2017 and 2019, coinciding with the timeframe of C3i participation. RESULTS: Of 17,735 cancer cases reviewed, both measures were captured on 17,654 (99.5%) of patients, with 3,091 (17.4%) identified as users of tobacco. Across the 3 years, 557 (18%) of individuals who used tobacco received either tobacco cessation pharmacotherapy or behavioral support; with 478 (15.5%) receiving behavioral counseling, 352 (11.4%) receiving pharmacotherapy, and 273 (8.8%) receiving both-considered gold standard care. Tobacco treatment varied substantially across cancer types. The odds of receiving gold standard care were 2.37 times greater in 2019 compared with 2017. (OR, 2.37; 95% confidence interval, 1.63-3.46; P < 0.0001). CONCLUSIONS: The new metrics demonstrated high completion rates and their potential to track quality improvement efforts over time. They identified suboptimal treatment reach, but a potential increase in treatment over time and greater treatment among tobacco-related versus nontobacco-related cancers. IMPACT: Continued tobacco use worsens cancer care outcomes. Integrating measures into cancer registries is a viable option for tracking tobacco treatment and cessation in the context of cancer care.

Multiple Pharmacotherapy Adaptations for Smoking Cessation Based on Treatment Response in Black Adults Who Smoke: A Randomized Clinical Trial.

Importance: Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. Objective: To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily. Design, Setting, and Participants: This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023. Interventions: Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment. Main Outcomes and Measures: Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data. Results: Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001). Conclusions and Relevance: In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03897439.

Evaluation of the brief questionnaire of smoking urges in Black light smokers.

INTRODUCTION: This study evaluated the factor structure of the Brief Questionnaire of Smoking Urges (QSU-Brief) within a sample of Black light smokers (1-10 cigarettes per day). METHODS: The QSU-Brief was administered to 540 (mean age = 46.5; 66.1% women) urban Black light smokers upon entering a smoking cessation clinical trial. An exploratory factor analysis (EFA) was conducted to evaluate the factor structure of this 10-item measure. RESULTS: An EFA indicated that as in other samples, the construct of craving in a Black sample is defined by 2 factors; 1 factor emphasizing the positive reinforcement of smoking and the other factor emphasizing the negative reinforcement properties of smoking. CONCLUSIONS: Findings largely replicate a 2-factor structure of craving seen in smokers from other racial/ethnic groups, demonstrating the clinical utility of the QSU-Brief in measuring craving in Black light smokers.

Adherence to varenicline among African American smokers: an exploratory analysis comparing plasma concentration, pill count, and self-report.

INTRODUCTION: 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. METHODS: 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"). RESULTS: 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. CONCLUSIONS: 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.

Effects of menthol on the pharmacokinetics of bupropion among Black smokers.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Hospital-based tobacco treatment for inpatients with a history of cancer.

OBJECTIVE: To describe treatment engagement and outcomes of patients who smoke with cancer and received tobacco cessation treatment during hospitalization. METHOD: We analyzed treatment engagement and cessation outcomes for hospitalized patients who smoke with a current or former history of cancer receiving treatment from an inpatient tobacco treatment service between July, 2018 to October, 2019. RESULTS: The service treated 407 inpatients. Patients had an overall high level of interest in quitting (7.6, 0-10 scale). One in three accepted cessation pharmacotherapies during hospitalization or at discharge (35%) and/or referral to the state tobacco quitline (37%). Of 189 patients reached at one-month post-discharge, 73 (39%) reported tobacco abstinence (18% intent to treat-ITT-quit rate); 35.5% had used cessation pharmacotherapy and 6.5% had engaged in quitline counseling. Of 151 patients reached at 6 months post-discharge, 29% reported abstinence (11%, ITT). CONCLUSION: Inpatients with a history of cancer are interested in quitting. Post-discharge quit rates and pharmacotherapy use were high but quitline use was low. Hospitalization is an under-utilized, prime treatment opportunity and teachable moment for people with a history of cancer who continue to use tobacco.

The effect of area-level disadvantage and race on smoking abstinence in a clinical trial.

Reasons for Black-White disparities in smoking abstinence are not well understood. This study examined area-level socioeconomic disadvantage as a contributor to lower quit rates for Blacks who smoke among 223 Black and 221 White low-income individuals who smoke enrolled in a smoking cessation trial. Outcome was cotinine-verified abstinence at week 26. Census tract-level disadvantage was measured using 5-year estimates linked to participants' home address and included percentage of: female headed households; public assistance; unemployed; < 100% of the federal poverty level; and whether there was > 25% having less than a high school education. A neighborhood disadvantage index score (DIS) was calculated as the sum of z scores for each variable. Black participants lived in more disadvantaged areas than White participants [DIS mean (SD): 3.2 (4.3), -1.0 (3.2), p < .001]. Similar rates of abstinence were observed at the same level of disadvantage [DIS ≥ 50th percentile (less disadvantage): 21.9% Blacks, 26.2% Whites, p = .50; DIS < 50th percentile (more disadvantage): 10.7% Blacks, 15.8% Whites, p = .31]. Only DIS but neither race nor the interaction was retained in the final model predicting abstinence; each unit increase in DIS was associated with 9% reduced odds of abstinence, OR: 0.91, 95% CI [0.87,0.96]. Findings point to the importance of examining factors associated with race that contribute to health inequities and underscore the need to consider how consequences of systemic racism, such as neighborhood context and other consequences not captured by the DIS, can constrain or facilitate smoking cessation when developing interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion-aided smoking cessation in African Americans? A moderated mediation analysis.

BACKGROUND AND AIMS: CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion-aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion-aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex. DESIGN AND SETTING: Secondary analysis of a smoking cessation clinical trial (NCT00666978). PARTICIPANTS/CASES: African American light smokers (≤ 10 cigarettes/day). INTERVENTIONS: Participants were treated with bupropion for 7 weeks. MEASUREMENTS: Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased-function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow-up (26 weeks). FINDINGS: Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample. CONCLUSIONS: In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.