Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study.

INTRODUCTION: Pregnant women exposed chronically to opioids smoked more cigarettes per day (CPD) and had a higher nicotine metabolite ratio (NMR), 3-hydroxycotinine/cotinine, a biomarker of nicotine metabolism and clearance, than those not receiving opioids. We examined CPD and NMR in a group of pregnant smokers, a quarter of whom were receiving opioid agonist therapy (OAT). AIMS AND METHODS: Pregnant smokers recruited to participate in a placebo-controlled trial of bupropion for smoking cessation provided a blood sample for measurement of NMR. RESULTS: Half (52.4%) of the 124 women with NMR data were African American. OAT-treated women (n = 34, 27.4%; 27 receiving methadone and 7 buprenorphine) were more likely to be white (79% vs. 30%, p < .001) and to have a lower mean PHQ-9 total score (2.91 [SD = 2.83] vs. 4.83 [SD = 3.82], p = .007). OAT-treated women reported smoking more CPD (9.50 [SD = 5.26] vs. 7.20 [SD = 3.65], p = .005) and had higher NMR (0.78 [SD = 0.36] vs. 0.56 [SD = 0.25], p = .001) than the non-OAT-treated group. In a linear regression analysis adjusting for race, depression severity, and CPD, NMR was greater in the OAT group (p = .025), among whom the daily methadone-equivalent dosage correlated with NMR (Spearman's ρ = 0.49, p = .003). CONCLUSIONS: Consistent with the findings of Oncken et al. (2019), we found that OAT smokers smoked more and had higher NMR than non-OAT smokers. As higher NMR is associated with a reduced likelihood of smoking cessation, the effects on NMR of both pregnancy and OAT could contribute to a lower smoking cessation rate in pregnant smokers receiving chronic opioid therapy. IMPLICATIONS: We replicated the finding that the NMR is significantly greater among pregnant smokers receiving OAT than those not receiving this treatment for opioid use disorder. Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level. These findings may contribute to a poorer response to smoking cessation treatment in pregnant women treated with OAT, particularly those receiving high-dose therapy, and raise the question of whether novel approaches are needed to treat smoking in this subgroup of pregnant smokers.

A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene­environment interaction

Background: Phenotypic heterogeneity and complicated gene­environment interplay in etiology are among the primary factors that hinder the identification of genetic variants associated with cocaine use disorder. Methods: To detect novel genetic variants associated with cocaine use disorder, we derived disease traits with reduced phenotypic heterogeneity using cluster analysis of a study sample (n = 9965). We then used these traits in genome-wide association tests, performed separately for 2070 African Americans and 1570 European Americans, using a new mixed model that accounted for the moderating effects of 5 childhood environmental factors. We used an independent sample (918 African Americans, 1382 European Americans) for replication. Results: The cluster analysis yielded 5 cocaine use disorder subtypes, of which subtypes 4 (n = 3258) and 5 (n = 1916) comprised heavy cocaine users, had high heritability estimates (h2 = 0.66 and 0.64, respectively) and were used in association tests. Seven of the 13 identified genetic loci in the discovery phase were available in the replication sample. In African Americans, rs114492924 (discovery p = 1.23 × E−8), a single nucleotide polymorphism in LINC01411, was replicated in the replication sample (p = 3.63 × E−3). In a meta-analysis that combined the discovery and replication results, 3 loci in African Americans were significant genome-wide: rs10188036 in TRAK2 (p = 2.95 × E−8), del-1:15511771 in TMEM51 (p = 9.11 × E−10) and rs149843442 near LPHN2 (p = 3.50 × E−8). Limitations: Lack of data prevented us from replicating 6 of the 13 identified loci. Conclusion: Our results demonstrate the importance of considering phenotypic heterogeneity and gene­environment interplay in detecting genetic variations that contribute to cocaine use disorder, because new genetic loci have been identified using our novel analytic method.

Predictors of Treatment Referral after AUDIT-C Screening for Heavy Drinking.

OBJECTIVES: The Veterans Health Administration has implemented annual screening for heavy drinking during primary care encounters using the 3-item Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire and made specialized services available to patients with alcohol use disorders (AUDs). We sought to identify the factors that influence whether a patient who has an elevated AUDIT-C score receives appropriate care in the context of an integrated mental health services program. We focused on higher AUDIT-C scores, as these are seen in individuals who are most likely to have a moderate-to-severe AUD and more severe alcohol-related consequences. METHODS: Utilizing electronic health record data, we conducted a four-year retrospective study of veterans at high-risk for an AUD, based upon an AUDIT-C score >=8 recorded during a primary care encounter at a Veterans Affairs Medical Center and its community-based outpatient clinics. RESULTS: In multivariate analysis, the predictors of treatment referral were younger age, being non-white, higher AUDIT-C score, and main campus location. Among patients referred for treatment, younger age and being white were associated with an increased likelihood of completing a pre-treatment assessment. CONCLUSIONS: Efforts to increase the consistency of treatment referrals, according to established clinical guidelines, could enhance the effectiveness of AUDIT-C screening during primary care visits. Subgroups of patients who may benefit from such efforts include individuals with high-risk but sub-maximal AUDIT-C scores, older patients, and patients who are seen at community-based outpatient clinics.