Background and Purpose— EG-1962 is a sustained release formulation of nimodipine administered via external ventricular drain in patients with aneurysmal subarachnoid hemorrhage. A randomized, open-label, phase 1/2a, dose-escalation study provided impetus for this study to evaluate efficacy and safety of a single intraventricular 600 mg dose of EG-1962 to patients with aneurysmal subarachnoid hemorrhage, compared with standard of care oral nimodipine. Methods— Subjects were World Federation of Neurological Surgeons grades 2–4, modified Fisher grades 2–4 and had an external ventricular drain inserted as part of standard of care. The primary end point was the proportion of subjects with favorable outcome at day 90 after aneurysmal subarachnoid hemorrhage (extended Glasgow outcome scale 6–8). The proportion of subjects with favorable outcome at day 90 on the Montreal cognitive assessment, as well as the incidence of delayed cerebral ischemia and infarction, use of rescue therapy and safety were evaluated. Results— The study was halted by the independent data monitoring board after planned interim analysis of 210 subjects (289 randomized) with day 90 outcome found the study was unlikely to achieve its primary end point. After day 90 follow-up of all subjects, the proportion with favorable outcome on the extended Glasgow outcome scale was 45% (65/144) in the EG-1962 and 42% (62/145) in the placebo group (risk ratio, 1.01 [95% CI, 0.83–1.22], P =0.95). Consistent with its mechanism of action, EG-1962 significantly reduced vasospasm (50% [69/138] EG-1962 versus 63% [91/144], P =0.025) and hypotension (7% [9/138] versus 10% [14/144]). Analysis of prespecified subject strata suggested potential efficacy in World Federation of Neurological Surgeons 3–4 subjects (46% [32/69] EG-1962 versus 32% [24/75] placebo, odds ratio, 1.22 [95% CI, 0.94–1.58], P =0.13). No safety concerns were identified that halted the study or that preclude further development. Conclusions— There was no significant increase in favorable outcome for EG-1962 compared with standard of care in the overall study population. The safety profile was acceptable. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02790632.

Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. Methods: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months. Results: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes ( P <0.01). MIST and mothership had similar median door-to-recanalization times of 192 minutes and 179 minutes, respectively ( P =0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%; P <0.01). MIST had 52.8% of patients with modified Rankin Scale of ≤2 at 3 months compared with 38.9% in DS ( P =0.10). Conclusions: MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03048292.

Background and Purpose: Young patients with malignant cerebral edema have been shown to benefit from early decompressive hemicraniectomy. The impact of concomitant infection with coronavirus disease 2019 (COVID-19) and how this should weigh in on the decision for surgery is unclear. Methods: We retrospectively reviewed all COVID-19–positive patients admitted to the neuroscience intensive care unit for malignant edema monitoring. Patients with >50% of middle cerebral artery involvement on computed tomography imaging were considered at risk for malignant edema. Results: Seven patients were admitted for monitoring of whom 4 died. Cause of death was related to COVID-19 complications, and these were either seen both very early and several days into the intensive care unit course after the typical window of malignant cerebral swelling. Three cases underwent surgery, and 1 patient died postoperatively from cardiac failure. A good outcome was attained in the other 2 cases. Conclusions: COVID-19–positive patients with large hemispheric stroke can have a good outcome with decompressive hemicraniectomy. A positive test for COVID-19 should not be used in isolation to exclude patients from a potentially lifesaving procedure.

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The field of international emergency medicine (IEM) has grown rapidly over the past several decades, with a rise in the number of IEM fellowship positions, sustained growth in the international sections of major emergency medicine organizations, and an increase in the range of topics included under its rubric. One of the greatest obstacles to the continued growth of IEM remains the lack of a high-quality, consolidated, and easily accessible evidence base of literature. In response to this perceived need, members of the Emergency Medicine Residents' Association IEM Committee, in conjunction with members of the Society for Academic Emergency Medicine International Health Interest Group, embarked on the task of creating a recurring review of IEM literature. This article reviews 25 IEM research articles published in 2006. Research articles were selected for the review according to explicit, predetermined criteria that included both methodological quality and perceived impact of the research. It is the authors' hope that this annual review will act as a forum for disseminating best practices while also stimulating further research in the field of IEM.