College of the Holy CrossObjective: To identify scalable interventions for improving sexual minority mental health and health-risk behavior, this study tested the efficacy of two self-guided online writing interventions-expressive writing and self-affirmation. To reach sexual minority young adults living in high-stigma, low-resource settings, we developed and tested these interventions in Appalachian Tennessee. Method: In consultation with sexual minority young adults (n ϭ 10) and stakeholders (n ϭ 10) living in Appalachian Tennessee, we adapted these two writing interventions that we then delivered to 108 local sexual minority young adults (M age ϭ 23.68, SD ϭ 3.11). Participants, representing diverse sexual and gender identities and socioeconomic backgrounds, were randomly assigned to participate in a 3-session expressive writing intervention, self-affirmation intervention, or neutral control. Participants completed mental health and health-risk behavior measures at baseline, postintervention, and 3-month follow-up. Results: Compared to the neutral control, expressive writing exerted 3-month improvements in depressive symptoms (d ϭ 0.48) and general psychological distress (d ϭ 0.36) whereas self-affirmation exerted improvement in suicidal ideation (d ϭ 0.62) and drug abuse (d ϭ 0.59). Participants who were exposed to greater contextual minority stressors common in rural regions (i.e., discrimination and victimization) experienced significantly greater 3-month reductions in depression from expressive writing and self-affirmation compared to control. Those who experienced greater discrimination also experienced significantly greater 3-month reductions in suicidality from self-affirmation compared to control. Conclusion: Brief writing interventions exert significant impact on the mental health of young adult sexual minorities, especially those exposed to minority stress. Future research can consider strategies for population-level implementation, especially in high-stigma, low-resource settings. What is the public health significance of this article?This study responds to the pressing need for efficacious interventions to improve sexual minority young adult mental and behavioral health. We find evidence that two brief online writing interven-

AimsTo assess the pharmacokinetic and pharmacodynamic effects of co-administration of a combined oral contraceptive (ethinyloestradiol plus levonorgestrel) and lamotrig ine. MethodsOver a period of 130 days, healthy female subjects took lamotrigine (titrated up to 300 mg day − 1 ) and the combined oral contraceptive, either individually or as cotherapy. Plasma ethinyloestradiol and levonorgestrel concentrations were measured in the presence and absence of lamotrigine, and serum lamotrigine concentrations were measured in the presence and absence of the combined oral contraceptive. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, oestradiol and sex hormone binding globulin were also determined. ResultsOf the 22 enrolled subjects, 16 had evaluable pharmacokinetic data. The mean (90% CI) ratios of lamotrigine area under the concentration-time curve from 0 to 24 h (AUC(0,24 h)) and maximum observed concentration ( C max ) of lamotrigine when it was given with the combined oral contraceptive and during monotherapy were 0.48 (0.44, 0.53) and 0.61 (0.57, 0.66), respectively. Ethinyloestradiol pharmacokinetics were unchanged by lamotrigine, the mean combined oral contraceptive + lamotrigine : combined oral contraceptive alone ratios (90% CI) of the AUC(0,24 h) and C max of levonorgestrel were 0.81 (0.76, 0.86) and 0.88 (0.82, 0.93), respectively. FSH and LH concentrations were increased (by 4.7-fold and 3.4-fold, respectively) in the presence of lamotrigine, but the low serum progesterone concentrations suggested that suppression of ovulation was maintained. Intermenstrual bleeding was reported by 7/22 (32%) of subjects during co-administration of lamotrigine and combined oral contraceptive. ConclusionsA clinically relevant pharmacokinetic interaction was observed during co-administration of a combined oral contraceptive and lamotrigine. A dosage adjustment for lamotrigine may need to be considered when these agents are co-administered. A modest decrease in the plasma concentration of levonorgestrel was also observed but there was no corresponding hormonal evidence of ovulation. Jagdev Sidhu et al. 19261 :2 Br J Clin Pharmacol

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drugs that inhibit the human cardiac delayed rectifier potassium current may lead to prolongation of the cardiac QT interval and are associated with a fatal, polymorphic, ventricular tachycardia known as torsades de pointes. • Lamotrigine is indicated in the treatment of epilepsy and the prevention of mood episodes in patients with bipolar disorder. • Lamotrigine inhibits the human cardiac delayed rectifier potassium current in vitro, and it has been hypothesized that QT prolongation may contribute to the risk of sudden unexpected death in epilepsy patients. WHAT THIS STUDY ADDS • This is the first reported thorough QT/QTc study with lamotrigine conducted to International Conference on Harmonization guidelines. • The mean QTc interval was not prolonged by lamotrigine in healthy subjects, as assessed by the standard heart rate correction methods (Fridericia's and Bazett's). • The in vitro inhibition of the delayed rectifier potassium current does not translate into an effect on QT in man. AIM To characterize the effects of lamotrigine on QT interval in healthy subjects. METHODS Healthy subjects received a single oral dose of moxifloxacin (400 mg) or placebo in crossover design, followed by a dose‐escalating regimen of lamotrigine (n = 76) over a 77‐day period, or matched placebo (n = 76). Blood samples were taken for determination of moxifloxacin and lamotrigine concentrations and digital 12‐lead ECGs were recorded. The relationships between individual QT values and respective individual moxifloxacin or lamotrigine concentrations were explored using population pharmacokinetic–pharmacodynamic (PK–PD) modelling. RESULTS Moxifloxacin was associated with a maximum mean increase from baseline in QTcF of 14.81 ms [90% confidence interval (CI) 13.50, 16.11] 2.5 h after dosing. Steady‐state exposure to lamotrigine (50, 150 or 200 mg b.d.) was not associated with an increase in QTc interval. Small reductions in QTcF (maximum mean difference from placebo −7.48 ms, 90% CI −10.49, −4.46) and small increases in heart rate (maximum mean difference from placebo 5.94 bpm, 90% CI 3.81, 8.06) were observed with lamotrigine 200 mg b.d. vs. placebo. No effect of lamotrigine on QRS duration or blood pressure was observed. No outliers with QTcF > 450 ms, or with an increase from baseline of >60 ms were observed in the lamotrigine group. PK–PD modelling indicated statistically significant decreases in individually corrected QT intervals for lamotrigine and statistically significant increases in individually corrected QT intervals for moxifloxacin over the concentration ranges studied. CONCLUSIONS Therapeutic doses of lamotrigine (50–200 mg b.d.) were not associated with QT prolongation in healthy subjects.

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This study puts forth a critical deconstructed quantitative analysis process that systematically interrogated elements of a quantitative study (research questions/hypotheses, sample, measures, analysis, interpretation) in an effort to evaluate and improve intersectional research on sexual and gender minority stress and mental health. Our quantitative study used minority stress processes (anticipated discrimination, social support) as indirect explanations for mental health disparities found between: (1) sexual and gender minorities (n = 167), and (2) sexual minorities only (n = 148) and explored community connectedness as a moderator of these processes. We then applied Cole's (2009) intersectionality framework questions in our critical deconstructed analysis to evaluate our study. Our quantitative results revealed sexual and gender minorities (compared to sexual minorities only) were at risk for worse mental health due to increased exposure to minority stress processes. However, findings were tempered by limitations, which became evident when systematically evaluating our study using an intersectionality framework. We offer recommendations for future minority stress research and policy, including that researchers implement a critical deconstructed quantitative analysis a priori when designing quantitative studies, in order to better apply an intersectionality framework and improve research.