Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center

Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning

ObjectiveClinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce.MethodMeasures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO2 > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan.ResultsThe LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the “moderate” and “severe” categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study).ConclusionDistinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery

A Consensus Parameter for the Evaluation and Management of Angioedema in the Emergency Department

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)

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission