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Despite its relatively common occurrence and life-threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic-mediated angioedema from bradykinin-mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin-mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM).

Background: Hereditary angioedema (HAE) is a potentially fatal disease characterized by unpredictable, recurrent, often disabling swelling attacks. In a randomized phase 2 study, donidalorsen reduced HAE attack frequency and improved patient quality‐of‐life (ISIS721744‐CS2, NCT04030598). We report the 2‐year interim analysis of the phase 2 open‐label extension (OLE) study (ISIS 721744‐CS3, NCT04307381). Methods: In the OLE, the on‐treatment study period consisted of fixed (weeks 1–13, donidalorsen 80 mg subcutaneously every 4 weeks [Q4W]) and flexible (weeks 17–105, donidalorsen 80 mg Q4W, 80 mg every 8 weeks [Q8W], or 100 mg Q4W) dosing periods. The primary outcome was incidence and severity of treatment‐emergent adverse events (TEAEs). The secondary outcomes included efficacy, pharmacodynamic, and quality‐of‐life assessments. Results: Seventeen patients continued in the OLE study. No serious TEAEs or TEAEs leading to treatment discontinuation were reported. Mean monthly HAE attack rate was 96% lower than the study run‐in baseline rate (mean, 0.06/month; 95% confidence interval [CI], 0.02–0.10; median, 0.04 on‐treatment vs. mean, 2.70/month; 95% CI, 1.94–3.46; median, 2.29 at baseline). Mean monthly attack rate for Q8W dosing (n = 8) was 0.29 (range, 0.0–1.7; 95% CI, −0.21 to 0.79; median, 0.00). Mean plasma prekallikrein and D‐dimer concentrations decreased, and Angioedema Quality of Life Questionnaire total score improved from baseline to week 105 with donidalorsen. Conclusion: The 2‐year interim results of this phase 2 OLE study of donidalorsen in patients with HAE demonstrated no new safety signals; donidalorsen was well tolerated. There was durable efficacy with a 96% reduction in HAE attacks. [ABSTRACT FROM AUTHOR]

Earthquake moment tensors and centroid locations in the catalogue of the Global CMT (gCMT) project, formerly the Harvard CMT project, have become an essential resource for studying active global tectonics, used by many solid-Earth researchers. The catalogue's quality, long duration (1976–present), ease of access and global coverage of earthquakes larger than about Mw 5.5 have transformed our ability to study regional patterns of earthquake locations and focal mechanisms. It also allows researchers to easily identify earthquakes with anomalous mechanisms and depths that stand out from the global or regional patterns, some of which require us to look more closely at accepted interpretations of geodynamics, tectonics or rheology. But, as in all catalogues that are, to some extent and necessarily, produced in a semi-routine fashion, the catalogue may contain anomalies that are in fact errors. Thus, before re-assessing geodynamic, tectonic or rheological understanding on the basis of anomalous earthquake locations or mechanisms in the gCMT catalogue, it is first prudent to check those anomalies are real. The purpose of this paper is to illustrate that necessity in the eastern Himalayas and SE Tibet, where two earthquakes that would otherwise require a radical revision of current geodynamic understanding are shown, in fact, to have gCMT depths (and, in one case, also focal mechanism) that are incorrect. [ABSTRACT FROM AUTHOR]