Does vaginal estrogen use increase the risk for adverse cardiovascular outcomes?

NO. In general, nonoral estrogen use for menopausal symptoms is associated with a lower cardiovascular (CV) risk profile than oral estrogen use (strength of recommendation [SOR], B; meta-analysis of cohort studies). Vaginal estrogen use is associated with lower risk for coronary heart disease (CHD) and similar risk for myocardial infarction (MI), stroke, and deep vein thrombosis/pulmonary embolism (DVT/ PE) compared with nonuse (SOR, B; cohort studies). Vaginal estrogen therapy also is associated with lower CV-related mortality for 3 to 5 years compared withnonuse (SOR, B; cohort study). No high-quality randomized trials address this topic.

How accurate is transcutaneous bilirubin testing in newborns with darker skin tones?

Fairly accurate. Photometric transcutaneous bilirubin (TcB) testing may overestimate total serum bilirubin (TSB) in neonates with darker skin tones by a mean of 0.68 to > 2 mg/dL (strength of recommendation [SOR]: C, diagnostic cohort studies with differing reference standards).Overall, TcB meters retain accept able accuracy in infants of all skin tones across a range of bilirubin levels, despite being more likely to underestimate lighter skin tones and overestimate darker ones (SOR: C, diagnostic cohort studies with differing reference standards). It is unclear if the higher readings prompt an increase in blood draws or otherwise alter care.

Does an early COPD diagnosis improve long-term outcomes?

It depends. A diagnosis of chronic obstructive pulmonary disease (COPD) made using screening spirometry in patients without symptoms does not change the course of the disease or alter smoking rates (strength of recommendation [SOR]: A, preponderance of evidence from multiple randomized controlled trials [RCTs]). However, once a patient develops symptoms of lung disease, a delayed diagnosis is associated with poorer outcomes (SOR: B, cohort studies). Active case finding (including the use of spirometry) is recommended for patients with risk factors for COPD who present with consistent symptoms (SOR: C, expert opinion).

Is bicarbonate therapy effective in preventing CKD progression?

YES. Long-term sodium bicarbonate therapy slightly slows the loss of renal function in patients with chronic kidney disease (CKD) and may moderately reduce progression to end-stage renal disease (strength of recommendation [SOR]: B, meta-analyses of lower-quality randomized controlled trails [RCTs]). Therapy duration of 1 year or less may not be beneficial (SOR: C, secondary analyses in meta-analyses).

Does adjunctive oxytocin infusion during balloon cervical ripening improve labor induction?

Evidence-Based Answer: Yes. Compared to the use of a transcervical balloon alone, combined cervical ripening with a balloon catheter and oxytocin shortens the time to overall delivery by 3 hours and the time to vaginal delivery by 4 hours, without altering the rate of cesarean section (strength of recommendation [SOR]: A, network meta-analysis). The effect is more pronounced in nulliparous patients (SOR: A, meta-analysis).When combined therapy is used, 6 hours of balloon time may result in faster delivery than 12 hours (SOR: B, single randomized controlled trial [RCT]). Fixed-dose oxytocin and titrated oxytocin appear to have similar effect when combined with a cervical ripening balloon (SOR: C, underpowered RCT).

Can family physicians accurately screen for AAA with point-of-care ultrasound?

Likely yes. Point-of-care ultrasound (POCUS) screening for abdominal aortic aneurysm (AAA) by nonradiologist physicians is 98% sensitive and 99% specific, compared with imaging performed by radiologists (strength of recommendation [SOR]: B, meta-analysis of diagnostic accuracy studies mostly involving emergency medicine physicians). European family physicians demonstrated 100% concordance with radiologist readings (SOR: C, very small subsequent diagnostic accuracy studies).

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).

Does inadequate sleep increase obesity risk in children?

Yes, a link has been established but not a cause-effect relationship. Shorter reported sleep duration in childhood is associated with an increased risk of overweight or obesity years later (strength of recommendation [SOR]: B, meta-analyses of prospective cohort trials with high heterogeneity). In toddlers, accelerometer documentation of short sleep duration is associated with elevation of body mass index (BMI) at 1-year follow-up (SOR: B, prospective cohort). Adequate sleep is recommended to help prevent excessive weight gain in children (SOR: C, expert opinion).

Clinical Inquiries: How effective and safe is fecal microbial transplant in preventing C difficile recurrence?

Fecal microbial transplant (fmt) is reasonably safe and effective. In patients who have had multiple Clostridium difficile infections (CDIs), fecal microbial transplant (FMT) results in a 65% to 80% cure rate with one treatment and 90% to 95% cure rate with repeated treatments compared with a 25% to 27% cure rate for antibiotics (strength of recommendation [SOR]: B, small open-label randomized controlled trials [RCTs]). Fresh and frozen donor feces, administered by either nasogastric tube or colonoscope, produce equal results (SOR B, RCTs). FMT has an overall adverse event rate of 30%, primarily involving abdominal discomfort, but also, rarely, severe infections (0.7%) and death (0.1%) (SOR: B, systematic review not limited to RCTs).

Clinical Inquiries: Which interventions are effective in managing parental vaccine refusal?

It's unclear whether educational initiatives alone alter vaccine refusal. Although about a third of parents cite herd immunity as motivation for vaccination, its efficacy in addressing vaccine hesitancy isn't clear. Multifaceted interventions (encompassing improved access to vaccines, immunization mandates, and patient education) may produce a ≥25% increase in vaccine uptake in groups with vaccine hesitancy and low utilization. Correcting false information about influenza vaccination improves perceptions about the vaccine, but may decrease intention to vaccinate in parents who already have strong concerns about safety. Discussions about vaccines that are more paternalistic (presumptive rather than participatory) are associated with higher vaccination rates, but lower visit satisfaction. Providers should thoroughly address patient concerns about safety and encourage vaccine use.