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Objectives: Determine SARS-CoV-2 IgG antibody incidence over time in unvaccinated pediatric healthcare workers (pHCWs)., Design: A prospective longitudinal cohort of unvaccinated pHCWs measuring the incidence of new infection after initial prevalence was established at 4.1% with seropositive predominance in emergency department (ED)-based pHCWs. Serum samples were collected at follow-up visits to detect new SARS-CoV-2 seropositivity. Univariate analysis was performed to estimate different incidence rates between participant demographics, job, employment location, and community risk factors. Anxiety levels about COVID-19 were collected. SARS-CoV-2 antibody decay postinfection and neutralization antibodies were evaluated. Log-linear Poisson regression models were used to estimate incidence., Results: Of 642 initially enrolled, 390 pHCWs presented for at least one follow-up serology test after baseline analysis. The incidence of SARS-CoV-2 seropositivity was 8.2%. The seropositive cohort, like the negative one, consisted mainly of females in non-ED settings and nonphysician roles. There were no statistically significant differences in incidence across variables. Seropositive participants dropped antibody titers by 50% at 3 months. Neutralization antibodies correlated to SARS-CoV-2 binding antibodies (r = 0.43, P < 0.0001)., Conclusion: The incidence of seropositivity was 8.2%. Although seropositivity was higher among ED staff during the early stages of the pandemic, this difference declined over time, likely due to the universal adoption of personal protective equipment., Competing Interests: Declarations of competing interest We declare no conflicts of interest. Claudia R. Morris, MD, is the inventor or co-inventor of several UCSF-Benioff Children's Hospital Oakland patents that include nutritional supplements, and is an inventor of Emory University School of Medicine patents/patent applications for nutritional supplements for autism, coronaviruses and pain, is a consultant for Roche and CSL Behring, is on the Scientific Advisory Board of TRILITY, is an editor the Sickle Cell Disease-Fever and Sickle Cell Disease-Pain reference for UpToDate, and is the Founder and Executive Director for Food as Medicine Therapeutics, LLC. Miriam B. Vos, MD, MSPH serves (or had in the past 12 months) as a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Intercept, Takeda, and Alberio. She has stock or stock options in Thiogenesis and Tern Pharmaceuticals. Her institution has received research grants (or in-kind research services) from Target Real World Evidence, Quest, Labcorp, and Sonic Incytes Medical Corp., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults., Methods: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant's randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE., Discussion: Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children., Trial Registration: The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study., (© 2023 Wiley Periodicals LLC.)