evere infection with COVID-19 has been linked to immune dysregulation, including impaired or delayed production of type I and type III interferons 1-5 , marked lymphopenia [6][7][8][9][10] and a paradoxical increase in pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 1,4,6,[11][12][13] . Alteration of T cell compartments include increases in effector and activated CD4 and CD8 T cells [14][15][16][17] , CD8 + T cells contribute to survival in patients with COVID-19 and hematologic cancer
We analyzed pooled data from two comparable randomized placebo-controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available. A total of 722 smokers across the two trials were randomized to 10 weeks of sustained-release bupropion hydrochloride or placebo. General estimating equation analysis demonstrated a significant gene x drug interaction (B = 0.87, SE = 0.34, p = .009). Smokers with the A2/A2 genotype using bupropion were more than three times as likely, relative to placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; OR = 3.25, 95% CI 2.00-5.28) and at 6 months of follow-up (26.7% vs. 12.2%; OR = 2.81, 95% CI 1.66-4.77), which was attenuated by 12 months (16.3% vs. 10.7%; OR = 1.70, 95% CI 0.95-3.05). We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes. These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype.
Rationale
Variability in the rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is associated with smoking behavior. However, data linking the NMR with nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND) are mixed. Few past studies have examined alternative measures of nicotine dependence and how this relationship may vary by sex and race.
Objective
Using data from smokers undergoing eligibility evaluation for a smoking cessation clinical trial (n=833), this study examined variability in the relationship between NMR and nicotine dependence across sex and race and using three measures of nicotine dependence: FTND, time-to-first-cigarette (TTFC), and the Heaviness of Smoking Index (HSI).
Results
Controlling for sex and race, nicotine metabolism was associated with nicotine dependence only when using the HSI (p < .05). Male normal metabolizers of nicotine were more likely to have high nicotine dependence based on the FTND and HSI (p < .05), but NMR was not related to measures of nicotine dependence in women. For African Americans, the NMR was associated with nicotine dependence only for the TTFC (p < .05) but NMR was not associated with nicotine dependence among Caucasians. Post-hoc analyses indicated that the NMR was associated with cigarettes per day, overall and among men and Caucasians (p < .05).
Conclusions
While there was some variation in the relationship between nicotine metabolism and nicotine dependence across measures and sex and race, the results indicate that this relationship may be more attributable to the association between NMR and cigarettes per day.
Background: Responses following BRCA1/2 genetic testing are relevant for the comprehension of risk status and may play a role in risk management decision making. The objective of this study was to evaluate a psychosocial telephone counseling (PTC) intervention delivered to BRCA1/2 mutation carriers following standard genetic counseling (SGC). We examined the effect of the intervention on distress and the concerns related to genetic testing.Methods: This prospective randomized clinical trial included 90 BRCA1/2 mutation carriers. We measured anxiety, depression, and genetic testing distress outcomes at intervention baseline and 6 and 12 months following disclosure. We evaluated the effects of SGC versus SGC plus PTC on psychological outcomes using intention-to-treat analyses through generalized estimating equations.Results: At 6 months, PTC reduced depressive symptoms (Z = −2.25, P = 0.02) and genetic testing distress (Z = 2.18, P = 0.02) compared with SGC. Furthermore, women in the intervention condition reported less clinically significant anxiety at 6 months (χ
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