Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial.

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).

Return visit rates after an emergency department discharge for children with sickle cell pain episodes.

BACKGROUND: High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown. PROCEDURE: A seven-site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry. Visits between January 2017 and November 2021 were identified using previously validated criteria. The primary outcome was the 14-day return visit rate, with 3- and 7-day rates also calculated. Modified Poisson regression was used to analyze associations for age, sex, initial hospitalization rate, and a visit during the COVID-19 pandemic with return visit rates. RESULTS: Of 2548 eligible ED visits, approximately 52% were patients less than 12 years old, 50% were female, and over 95% were non-Hispanic Black. The overall 14-day return visit rate was 29.1% (95% confidence interval [CI]: 27.4%-30.9%; site range 22.7%-31.7%); the 7- and 3-day return visit rates were 23.0% (95% CI: 21.3%-24.6%) and 16.7% (95% CI: 15.3%-18.2%), respectively. Younger children had slightly lower 14-day return visit rates (27.3% vs. 31.1%); there were no associations for site hospitalization rate, sex, and a visit occurring during the pandemic with 14-day returns. CONCLUSION: Nearly 30% of ED discharged visits after SCD pain treatment had a return visit within 14 days. Increased efforts are needed to identify causes for high ED return visit rates and ensure optimal ED and post-ED care.

Video Education Intervention in the Emergency Department.

INTRODUCTION: After discharge from the emergency department (ED), pain management challenges parents, who have been shown to undertreat their children's pain. Our goal was to evaluate the effectiveness of a five-minute instructional video for parents on pain treatment in the home setting to address common misconceptions about home pediatric pain management. METHODS: We conducted a randomized, single-blinded clinical trial of parents of children ages 1-18 years who presented with a painful condition, were evaluated, and were discharged home from a large, tertiary care pediatric ED. Parents were randomized to a pain management intervention video or an injury prevention control video. The primary outcome was the proportion of parents that gave their child pain medication at home after discharge. These data were recorded in a home pain diary and analyzed using the chi square test to determine significant difference. Parents' knowledge about components of at-home pain treatment were tested before, immediately following, and two days after intervention. We used McNemar's test statistic to compare incorrect pretest/correct post-test answers between intervention and control groups. RESULTS: A total of 100 parents were enrolled: 59 parents watched the pain education video, and 41 the control video. Overall, 75% of parents completed follow-up, providing information about home medication use. Significantly more parents provided pain medication to their children after watching the educational video: 96% vs 80% (difference 16%; 95% CI 7.8-31.3%). Significantly more parents had correct pain treatment knowledge immediately following the educational video about pain scores (P = 0.04); the positive effects of analgesics (P <0.01); and pain medication misconceptions (P = 0.02). Most differences in knowledge remained two days after the video intervention. CONCLUSION: The five-minute educational video about home pain treatment viewed by parents in the ED prior to discharge significantly increased the proportion of children receiving pain medication at home as well as parents' knowledge about at-home pain management.

An evaluation of short anxiety measures for use in the emergency department.

BACKGROUND: The emergency department (ED) is a stressful environment for children. Few studies assess pediatric anxiety in the ED. "Gold standard" for measuring state-anxiety, Spielberger's State-Trait Anxiety Inventory for Children (STAI-C state), is lengthy and of limited use in this setting. OBJECTIVE: The objective was to evaluate agreement between STAI-C, Likert, and modified Yale Preoperative Anxiety Scale (m-YPAS) and determine if shorter measures may be adequate replacements for STAI-C in the ED. METHODS: This is a secondary analysis of data from a previous observational cohort study of a convenience sample of children 5-17 years old presenting to the ED. Anxiety was measured using STAI-C, Likert, and m-YPAS. Spearman correlations were used to evaluate agreement between STAI-C and the brief scales. A sub-analysis evaluated agreement between scales for children ≥9 years old to assess the impact of age. RESULTS: Eighty children were included. Median (IQR) STAI-C state score was 32.5 (30.0, 37.8). This represents moderate state anxiety with 30% of children exhibiting elevated state anxiety. Median (IQR) Likert score was 2.0 (1.0, 2.0). Correlation between the Likert and STAI-C was moderate (rs = 0.51; p < 0.0001). Median (IQR) m-YPAS was 28.3 (24.2, 33.3). The m-YPAS and STAI-C were unrelated (rs = 0.12; p > 0.05). For children ≥9 years old, correlation between Likert and STAI-C remained moderate (rs = 0.52; p < 0.0001); STAI-C and m-YPAS were unrelated (rs = 0.10; p > 0.05). CONCLUSIONS: Children in the ED experienced moderate-elevated state anxiety. Likert scale may be an acceptable substitute for STAI-C state. Further studies of this scale will aid in identifying patients with anxiety to facilitate timely management.

Five days of fever and myocardial inflammation.

Multisystem inflammatory syndrome in children is an emerging pediatric illness associated with severe acute respiratory syndrome coronavirus 2 infection. The syndrome is rare, and evidence-based guidelines are lacking. This report reviews a patient who presented for medical care multiple times early in the course of his illness, thus offering near-daily documentation of symptoms and laboratory abnormalities. The patient did not have thrombocytopenia, anemia, or myocardial inflammation until the fifth day of fever. These laboratory abnormalities coincided with the onset of rash, conjunctival injection, vomiting, and diarrhea: clinical signs that could serve as indicators for when to obtain blood tests. The timing of this patient's onset of multisystem involvement suggests that testing for multisystem inflammatory syndrome in children after only 24 h of fever, as the Centers for Disease Control and Prevention recommends, may yield false-negative results. Testing for multisystem inflammatory syndrome in children after 4 days of fever may be more reliable.