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).

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.

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.

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.

Clinical Inquiry: Which patients with metabolic syndrome benefit from metformin?

In patients with metabolic syndrome who are in the highest-risk quartile for progression to diabetes (predicted mean 3-year risk, 60%), metformin, 850 mg twice daily, reduces the absolute risk by about 20% over a 3-year period. Metformin doesn't reduce the incidence in patients at lower risk of progression.

Clinical Inquiry: Does knuckle popping lead to arthritis?

Habitual knuckle popping, or cracking (over the course of several decades) isn't associated with clinical or radiographic evidence of osteoarthritis.

Clinical Inquiry: Which nonhormonal treatments are effective for hot flashes?

Selective serotonin reuptake inhibitors (SSRIs [fluoxetine, sertraline, paroxetine]) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine, as well as clonidine and gabapentin, reduce hot flashes by about 25% (approximately one per day) in women with and without a history of breast cancer. No studies compare medications against each other to determine a single best option.

Clinical Inquiry: Does caffeine intake during pregnancy affect birth weight?

No. Reducing caffeinated coffee consumption by 180 mg of caffeine (the equivalent of 2 cups) per day after 16 weeks' gestation doesn't affect birth weight. Consuming more than 300 mg of caffeine per day is associated with a clinically trivial, and statistically insignificant (less than 1 ounce), reduction in birth weight, compared with consuming no caffeine.