BACKGROUND:Many studies have shown that depression increases mortality risk. We aimed to investigate the duration of time over which depression is associated with increased risk of mortality, secular trends in the association between depression and mortality, and sex differences in the association between depression and mortality.

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nticoagulant-associated hemorrhage is one of the most common adverse drug reactions requiring hospitalization among individuals of advanced age, with a 2-fold increase among those older than 75 years. 1 Identification and avoidance of dangerous drug-drug interactions are associated with a significant reduction in adverse events and improvement in evidence-based prescription patterns.During the last decade, direct oral anticoagulants (DO-ACs) have supplanted traditional vitamin K antagonists as the anticoagulation drugs of choice. 2 Large phase 3 trials have demonstrated noninferiority or superiority of DOACs relative to traditional anticoagulants (warfarin) for effectiveness in stroke prevention for those who have atrial fibrillation and for pre-vention and treatment of venous thromboembolism. [3][4][5][6][7][8][9][10][11] Patient preferences for DOACs are based on their simplicity of use, with no need for routine bloodwork monitoring. 12 As such, recent guidelines recommend DOACs as the first-line agents for the prevention of stroke in patients with nonvalvular atrial fibrillation (strong recommendation; high-quality evidence) and the treatment of venous thromboembolism. 13,14 Direct oral anticoagulants have 2 predominant mechanisms of metabolism: P-glycoprotein (Pgp) cell transporters, which are involved in transcellular transportation, and the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism in the human liver. 15 Dabigatran etexilate mesylate requires efflux transportation by the Pgp system but is independent of the cytochrome P450 enzyme system. 16 Apixaban and rivar-IMPORTANCE Clarithromycin is a commonly prescribed antibiotic associated with higher levels of direct oral anticoagulants (DOACs) in the blood, with the potential to increase the risk of hemorrhage.OBJECTIVE To assess the 30-day risk of a hospital admission with hemorrhage after coprescription of clarithromycin compared with azithromycin among older adults taking a DOAC. DESIGN, SETTING, AND PARTICIPANTSThis population-based, retrospective cohort study was conducted among adults of advanced age (mean [SD] age, 77.6 [7.2] years) who were newly coprescribed clarithromycin (n = 6592) vs azithromycin (n = 18 351) while taking a DOAC (dabigatran, apixaban, or rivaroxaban) in Ontario, Canada, from June 23, 2009, to December 31, 2016. Cox proportional hazards regression was used to examine the association between hemorrhage and antibiotic use (clarithromycin vs azithromycin). Statistical analysis was performed from December 23, 2019, to March 25, 2020. MAIN OUTCOMES AND MEASURES Hospital admission with major hemorrhage (upper or lower gastrointestinal tract or intracranial). Outcomes were assessed within 30 days of a coprescription. RESULTS Among the 24 943 patients (12 493 women; mean [SD] age, 77.6 [7.2] years) in the study, rivaroxaban was the most commonly prescribed DOAC (9972 patients [40.0%]), followed by apixaban (7953 [31.9%]) and dabigatran (7018 [28.1%]). Coprescribing clarithromycin vs azithromycin with a DOAC was associa...

Objectives: The purpose of the present study was to assess longitudinal associations between positive and harsh parenting in childhood and adolescent mental and behavioral difficulties. Methods: Data were drawn from Canada’s population-based National Longitudinal Survey of Children and Youth (data collected from 1994 to 2009, analyzed 2018). The sample included 9,882 adolescents aged 12/13 years old. Parents self-reported positive and harsh parenting when children were 6/7, 8/9, and 10/11 years old. Symptoms of depression/anxiety, hyperactivity, physical aggression, social aggression, and suicidal ideation were self-reported by adolescents at age 12/13. Linear regression was used to examine the associations between parenting behaviors at each age and adolescent psychiatric symptoms, adjusted for children’s baseline symptoms. Results: Harsh parenting at 10/11 was associated with elevated symptoms of early-adolescent physical aggression, social aggression, and suicidal ideation for boys only, and for all children at earlier ages. Beginning at age 8/9, harsh discipline was associated with elevated symptoms of depression/anxiety for boys only. Overall, positive parenting at age 6/7 was protective against depression/anxiety, physical aggression, and social aggression. Significant sex differences emerged beginning at age 8/9, with positive parenting associated with higher symptoms of depression/anxiety for boys only. Positive parenting at age 10/11 was associated with increased depression/anxiety, physical aggression, social aggression, and suicidal ideation among boys, but decreased symptoms of physical aggression, social aggression, and suicidal ideation among girls. Conclusions: Results suggest that the impact of positive and harsh parenting may depend on age and sex, with harsh parenting being more detrimental to boys as they approach adolescence.