Gentile, Nina

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

AbstractObjectivesNeurovascular and neurocritical care emergencies constitute a leading cause of morbidity/mortality. There has been great evolution in this field, including but not limited to extended time‐window therapeutic interventions for acute ischemic stroke. The intent of this article is to evaluate the goals and future direction of clinical rotations in neurovascular and neurocritical care for emergency medicine (EM) residents.MethodsA panel of 13 board‐certified emergency physicians from the Society for Academic Emergency Medicine (SAEM) neurologic emergencies interest group (IG) convened in response to a call for publications—three with fellowship training/board certification in stroke and/or neurocritical care; five with advanced research degrees; three who have been authors on national practice guidelines; and six who have held clinical duties within neurology, neurosurgery, or neurocritical care. A mixed‐methods analysis was performed including a review of the literature, a survey of Council of Emergency Medicine Residency Directors (CORD) residency leaders/faculty and SAEM neuro‐IG members, and a consensus review by this panel of select neurology rotations provided by IG faculty.ResultsThirteen articles for residency neurovascular education were identified: three studies on curriculum, three studies evaluating knowledge, and seven studies evaluating knowledge after an educational intervention. Intervention outcomes included the ability to recognize and manage acute strokes, manage intracerebral hemorrhage, calculate National Institutes of Health Stroke Scale (NIHSS), and interpret images. In the survey sent to CORD residency leaders and neuro‐IG faculty, response was obtained from 48 programs. A total of 52.1% indicated having a required rotation (6.2% general neurology, 2% stroke service, 18.8% neurologic intensive care unit, 2% neurosurgery, 22.9% on a combination of services). The majority of programs with required rotations have a combination rotation (residents rotate through multiple services) and evaluations were positive.ConclusionsVariability exists in the availability of neurovascular/neurocritical care rotations for EM trainees. Dedicated clinical time in neurologic education was beneficial to participants. Given recent advancements in the field, augmentation of EM residency training in this area merits strong consideration.

Abstract Rationale Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).