Arnold H. Seto

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).

To determine the relative risk for major malformations associated with antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a literature search of all studies examining the association between antihistamines and major malformations for the period 1960 to 1991 was conducted, followed by meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty-four controlled studies met the inclusion criteria with more than 200,000 participating women. The summary odds ratio of major malformations associated with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60-0.94). This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect. More study is needed to verify the possibility that by preventing vomiting, antihistamines may ensure better metabolic conditions to the fetus and thus may reduce some birth defects. Alternatively, it is possible that pregnancies characterized by vomiting are associated with better outcome due to other reasons, such as hormonal status or placental function. Women suffering from morning sickness which is not controlled by nonpharmacological methods can safely use antihistamines.