How does gender-affirming hormone therapy affect QOL in transgender patients?

There are modest effects on depression but not anxiety. Gender-affirming hormone therapy (GAHT) is associated with modest improvements in standardized scores for quality of life (QOL) and depression in adult male-to-female and female-to-male transgender people and modest improvements in depression scores in transgender adolescents, but the effect on anxiety is uncertain (strength of recommendation [SOR]: B, based on a preponderance of low-quality prospective cohort studies with inconsistent results). GAHT is associated with reduced gender dysphoria and decreased suicidality (SOR: B, based on a prospective cohort study). However, there is insufficient evidence to determine any effect on suicide completion. No studies associated GAHT with worsened QOL, depression, or anxiety scores.

Is event-driven PrEP dosing for HIV as effective as daily dosing?

PROBABLY, although there are no head-to-head trials comparing the 2 dosing regimens. Event-driven pre-exposure prophylaxis (PrEP) dosing reduces HIV conversion by 86% compared to placebo (strength of recommendation [SOR]: B, large randomized controlled trial [RCT]). Daily PrEP reduces HIV conversion by 44% to 86% (SOR: B, based on open-label RCTs).Event-driven PrEP regimens may be associated with lower adherence when compared with daily PrEP regimens (average of 70% for event-driven PrEP vs average of 92% for daily PrEP) (SOR: B, based on open-label and cohort trials). Event-driven PrEP regimens have lower medication costs, and they are associated with no difference in the rate of sexually transmitted infections (STIs) (SOR: B, based on prospective cohort studies). Patients may prefer them to daily regimens (75% choose event driven PrEP vs 25% choose daily PrEP) (SOR: BB, based on the preponderance of prospective cohort studies with conflicting results).

Is ketamine effective and safe for treatment-resistant depression?

MAYBE, but it's too soon to tell. There is limited evidence that ketamine by itself is effective in the very short term. Single-dose intravenous (IV) ketamine is more likely than placebo (odds ratio = 11-13) to produce improvement (> 50%) in standardized depression scores in 1 to 3 days, lasting up to a week. Twice- or thriceweekly IV ketamine improves symptom scores by 20%-25% over 2 weeks (strength of recommendation [SOR]: B, meta-analysis of small, low-quality, randomized controlled trials [RCTs] and a single small RCT).Augmentation of sertraline with daily oral ketamine moderately improves symptom scores for 6 weeks in patients with moderate depression (SOR: B, small, lowquality RCTs).Augmentation of oral antidepressants (duloxetine, escitalopram, sertraline, venlafaxine) with intranasal esketamine spray improves response and remission rates at 4 weeks (16% for both outcomes) in patients with predominantly treatment-resistant major depression (SOR: A, meta-analysis of RCTs).Ketamine therapy is associated with confusion, emotional blunting, headache, dizziness, and blurred vision (SOR: A, metaanalyses).Nasal esketamine spray produces the adverse effects of dizziness, vertigo, and blurred vision severe enough to cause discontinuation in 4% of patients; it also can produce transient elevation of blood pressure (SOR: A, meta-analyses).

Is metformin effective for reducing weight in obese or overweight adolescents?

YES, TO SOME DEGREE-BUT IT IS OF UNCERTAIN CLINICAL SIGNIFICANCE. OVER A PERIOD OF 6 MONTHS, METFORMIN MODESTLY REDUCED WEIGHT (-2.1 KG) AND BODY FAT MASS (-1.9%), BUT NOT BODY MASS INDEX (BMI) OR LEAN BODY MASS, IN ADOLESCENTS WHO WERE OVERWEIGHT OR OBESE. THIS IS COMPARABLE TO LIFESTYLE INTERVENTIONS (DIET AND EXERCISE) SUPPORTED WITH > 26 HOURS OF COUNSELING, WHICH MODESTLY IMPROVED BMI BUT NOT WEIGHT. (STRENGTH OF RECOMMENDATION [SOR]: A, BASED ON A LARGE META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS [RCTS] OF VARIABLE QUALITY).

Does concurrent use of clopidogrel and PPIs increase CV risk in patients with ACS?

No. Adding a proton pump inhibitor (PPI) in patients taking antiplatelet medications such as clopidogrel for acute coronary syndrome (ACS) doesn't increase the composite risk of cardiovascular (CV) events: CV death, myocardial infarction (MI), and cerebrovascular accident (CVA) (strength of recommendation: B, randomized, controlled trial [RCT] and prepon-derance of posthoc analyses of large RCTs).

Does using e-cigarettes increase cigarette smoking in adolescents?

Probably. Electronic cigarette (e-cigarette) use by adolescents is associated with a 2- to 4-fold increase in cigarette smoking over the next year (strength of recommendation: A, meta-analysis and subsequent prospective cohort studies).

Clinical Inquiries: How well do POLST forms assure that patients get the end-of-life care they requested?

Quite well, for cardiopulmonary resuscitation (CPR). Most patients (91%-100%) who select "do not resuscitate" (DNR) on their physician's orders for life-sustaining treatment (POLST) forms are allowed a natural death without attempted CPR across a variety of settings (community, skilled nursing facilities, emergency medical services, and hospice). Few patients (6%) who select "comfort measures only" die in the hospital, whereas more (22%) who choose "limited interventions," and still more (34%) without a POLST form, die in the hospital (strength of recommendation [SOR]: B, large, consistent cross-sectional and cohort studies).

Clinical Inquiry: What effects--if any--does marijuana use during pregnancy have on the fetus or child?

The effects are unclear. Marijuana use during pregnancy is associated with clinically unimportant lower birth weights (growth differences of approximately 100 g), but no differences in preterm births or congenital anomalies.