Jasjit S. Ahluwalia

Genome‐wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences

BACKGROUND AND AIMSnThe activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches.nnnDESIGNnGenome-wide association study (GWAS).nnnSETTINGnMultiple sites within Canada and the United States.nnnPARTICIPANTSnAA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; nxa0=xa0504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; nxa0=xa0450).nnnMEASUREMENTSnGenome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates.nnnFINDINGSnMeta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (Pxa0=xa01.47e-39; betaxa0=xa00.59 per C (versus T) allele, SExa0=xa00.045), located ~9.5xa0kb 3 of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; nxa0=xa0480). None of the hits were in UGT or OCT2 genes.nnnCONCLUSIONSnThree independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk.

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

ABSTRACT 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 (nu2009=u20092376). 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 (pu2009<u20090.05). African American nondaily smokers were more likely than Latino and White nondaily smokers (pu2009<u20090.05) to limit their smoking in the past year as a perceived health risk reduction strategy (range: 0 ‘never’ to 5 ‘always’; Meansu2009=u20093.2, 2.9, 3.0, standard deviations [SD]u2009=u20091.1, 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 (pu2009<u20090.01). 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 (pu2009<u20090.01). 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.

Tobacco toxicant exposure in cigarette smokers who use or do not use other tobacco products

BACKGROUNDnNon-cigarette other tobacco products (OTP; e.g., cigarillos, little cigars) are typically used in combination with cigarettes, but limited data exists on the tobacco toxicant exposure profiles of dual cigarette-OTP (Cig-OTP) users. This study examined biomarkers of nicotine and carcinogen exposure in cigarette smokers who used or did not use OTP.nnnMETHODSn111 Cig-OTP and 111 cigarette only (Cig Only) users who smoked equivalent cigarettes per day were matched on age (< 40, >=40), race (African American, White), and gender. Participants reported past 7-day daily use of cigarettes and OTP and provided urine for nicotine, cotinine, total nicotine equivalents (TNE) and total NNAL concentrations.nnnRESULTSnCig-OTP users reported greater past 7-day tobacco use (15.9 versus 13.0 products/day, p<0.01) but had significantly lower creatinine-normalized nicotine (606 versus 1301ng/mg), cotinine (1063 versus 2125ng/mg), TNE (28 versus 57 nmol/mg) and NNAL (251 versus 343pg/mg) than Cig Only users (p<0.001).nnnCONCLUSIONSnCig-OTP users had lower levels of nicotine and metabolites of a lung carcinogen relative to Cig-Only users, but concentrations of toxicants among Cig-OTP users were still at levels that place smokers at great risk from the detrimental health effects of smoking.nnnIMPACTnOur study finds that nicotine and carcinogen exposure in Cig-OTP users are lower compared to cigarette only users, but still likely to be associated with substantial harm. A better understanding of why toxicant levels may be lower in Cig-OTP is an important area for future study.

Children Learning About Secondhand Smoke (CLASS II): A Pilot Cluster Randomized Controlled Trial

Abstract Introduction Children exposed to secondhand smoke (SHS) are at increased risk of respiratory illnesses. We piloted a Smoke Free Intervention (SFI) and trial methods before investigating its effectiveness and cost-effectiveness in primary school children. Methods In a pilot cluster randomized controlled trial in Bangladesh, primary schools were allocated to usual education (control) or SFI, using minimization. Year-5 children were recruited. Masking treatment allocation was not possible. Delivered by schoolteachers, SFI consisted of two 45-min and four 15-min educational sessions. Our primary outcome was SHS exposure at two months post randomization, verified by children’s salivary cotinine. The trial is registered at ISRCTN.com; ISRCTN68690577. Results Between April 1, 2015 and June 30, 2015, we recruited 12 schools. Of the 484 children present in Year-5, 481 consented. Six schools were allocated to both SFI (n = 245) and to usual education only (n = 236). Of them, 450 children (SFI = 229; control = 221) who had cotinine levels indicative of SHS exposure were followed-up. All schools were retained, 91% children (208/229) in SFI and 88% (194/221) in the control arm completed primary outcome assessment. Their mean cotinine at the cluster level was 0.53 ng/ml (SD 0.36) in SFI and 1.84 ng/ml (SD 1.49) in the control arm—a mean difference of −1.31 ng/ml (95% CI = −2.86 to 0.24). Conclusion It was feasible to recruit, randomize, and retain primary schools and children in our trial. Our study, though not powered to detect differences in mean cotinine between the two arms, provides estimates to inform the likely effect size for future trials. Implications In countries with high smoking prevalence, children remain at risk of many conditions due to secondhand smoke exposure. There is little empirical evidence on the effectiveness and cost-effectiveness of interventions that can reduce their exposure to secondhand smoke at homes. CLASS II trial found that a school-based intervention (SFI) has the potential to reduce children’s exposure to SHS—an approach that has been rarely used, but has considerable merit in school-based contexts. CLASS II trial provides key information to conduct a future definitive trial in this area of public health, which despite its importance has so far received little attention.

Tobacco Carcinogen Research to Aid Understanding of Cancer Risk and Influence Policy: Tobacco Carcinogen Research

Education regarding the health effects associated with tobacco use has made important progress worldwide over the last few decades. Still, tobacco remains a significant cause of cancer and other diseases. As a result, significant worldwide morbidity and mortality is still attributable to tobacco use in modern times. Research into tobacco products, the carcinogens they contain, and how users metabolize them is an important benefit to the advancement of research aimed at reducing harm associated with tobacco use. This review summarizes the use of this type of research to study tobacco users’ risk of developing cancer, especially head and neck cancer. In addition, we discuss the use of tobacco research to provide support for increasing levels of federal regulation of tobacco products.

Affordable Care Act’s Medicaid Expansion on Use of Regionalized Surgery at High-Volume Hospitals

BACKGROUNDnThe Affordable Care Act (ACA)s Medicaid expansion has increased access to surgical care overall. Whether it was associated with reduced disparities in use of regionalized surgery at high-volume hospitals (HVH) remains unknown. Quasi-experimental evaluations of this expansion were performed to examine the use of regionalized surgery at HVH among racial/ethnic minorities and low-income populations.nnnSTUDY DESIGNnData from State Inpatient Databases (2012 to 2014), the American Hospital Association Annual Survey Database, and the Area Resource File from Health Resources and Services Administration, were used to examine 166,558 nonelderly (ages 18 to 64) adults at 468 hospitals, who underwent 1 of 4 regionalized surgical procedures in 3 expansion (KY, MD, NJ) and 2 nonexpansion states (NC, FL). Thresholds of HVH were defined using the top quintile of visits per year. Interrupted time series were performed to measure the impact of expansion on use rates of regionalized surgery at HVH overall, by race/ethnicity, and by income.nnnRESULTSnOverall, ACAs expansion was not associated with accelerated use rates of regionalized surgical procedures at HVH (odds ratio [OR] 1.016, pxa0= 0.297). Disparities in use of regionalized surgical procedures at HVH among ethnic/racial minorities and low-income populations were unchanged; minority vs white (OR 1.034 pxa0= 0.100); low-income vs high-income (OR 1.034, pxa0= 0.122).nnnCONCLUSIONSnEarly findings from ACAs Medicaid expansion revealed no impact on the use rates of regionalized surgery at HVH overall or on disparities among vulnerable populations. Although these results need ongoing evaluation, they highlight potential limitations in ACAs expansion in reducing disparities in use of regionalized surgical care.

Cost-effectiveness of enhancing a Quit-and-Win smoking cessation program for college students

ObjectivesWe conducted a cost-effectiveness analysis and model-based cost–utility and cost–benefit analysis of increased dosage (3 vs. 1 consecutive contests) and enhanced content (supplemental smoking-cessation counseling) of the Quit-and-Win contest using data from a randomized control trial enrolling college students in the US.MethodsFor the cost–utility and cost–benefit analyses, we used a microsimulation model of the life course of current and former smokers to translate the distribution of the duration of continuous abstinence among each treatment arm’s participants observed at the end of the trial (Nu2009=u20091217) into expected quality-adjusted life-years (QALYs) and costs and an incremental net monetary benefit (INMB). Missing observations in the trial were classified as smoking. For our reference case, we took a societal perspective and used a 3% discount rate for costs and benefits. A probabilistic sensitivity analysis (PSA) was performed to account for model and trial-estimated parameter uncertainty. We also conducted a cost-effectiveness analysis (cost per additional intermediate cessation) using direct costs of the intervention and two trial-based estimates of intermediate cessation: (a) biochemically verified (BV) 6-month continuous abstinence and (b) BV 30-day point prevalence abstinence at 6xa0months.ResultsMultiple contests resulted in a significantly higher BV 6-month continuous abstinence rate (RDu20090.04), at a cost of

Daily and Nondaily Smoking Varies by Acculturation among English-Speaking, US Latino Men and Women

1275 per additional quit, and increased the duration of continuous abstinence among quitters. In the long run, multiple contests lead to an average gain of 0.03 QALYs and were cost saving. Incorporating parameter uncertainty into the analyses, the expected INMB was greater than

A randomized clinical trial of counseling and nicotine replacement therapy for treatment of African American non-daily smokers: Design, accrual, and baseline characteristics

1000 for any realistic willingness to pay (WTP) for a QALY.ConclusionsAssuming missing values were smoking, multiple contests appear to dominate a single contest from a societal perspective. Funding agencies seeking to promote population health by funding a Quit-and-Win contest in a university setting should strongly consider offering multiple consecutive contests. Further research is needed to evaluate multiple contests compared to no contest.

Varenicline versus placebo for waterpipe smoking cessation: A double‐blind randomised‐controlled trial

BackgroundnHigher smoking prevalence and quantity (cigarettes per day) has been linked to acculturation in the United States among Latinas, but not Latino men. Our study examines variation between a different and increasingly important target behavior, smoking level (nondaily vs daily) and acculturation by sex.nnnMethodsnAn online English-language survey was administered to 786 Latino smokers during July through August 2012. The Brief Acculturation Rating Scale for Mexican Americans-II (ARSMA-II) and other acculturation markers were used. Multinomial logistic regression models were implemented to assess the association between smoking levels (nondaily, light daily, and moderate/heavy daily) with acculturation markers.nnnResultsnGreater ARMSA-II scores (relative risk ratio, RRR=.81, 95% CI: .72-.91) and being born inside the United States (RRR=.42, 95% CI: .24-.74) were associated with lower relative risk of nondaily smoking. Greater Latino orientation (RRR=1.29, 95% CI: 1.11-1.48) and preference for Spanish language (RRR=1.06, 95% CI: 1.02-1.10) and media (RRR=1.12, 95% CI: 1.05-1.20) were associated with higher relative risk of nondaily smoking. The relationship between acculturation and smoking level did not differ by sex.nnnConclusionnThis study found that among both male and female, English-speaking Latino smokers, nondaily smoking was associated with lower acculturation, while daily smoking was linked with higher acculturation.