A comparison of alternative ranking methods in two-stage clinical trials with multiple interventions: An application to the anxiolysis for laceration repair in children trial.

BACKGROUND/AIMS: Multi-arm, multi-stage trials frequently include a standard care to which all interventions are compared. This may increase costs and hinders comparisons among the experimental arms. Furthermore, the standard care may not be evident, particularly when there is a large variation in standard practice. Thus, we aimed to develop an adaptive clinical trial that drops ineffective interventions following an interim analysis before selecting the best intervention at the final stage without requiring a standard care. METHODS: We used Bayesian methods to develop a multi-arm, two-stage adaptive trial and evaluated two different methods for ranking interventions, the probability that each intervention was optimal (Pbest) and using the surface under the cumulative ranking curve (SUCRA), at both the interim and final analysis. The proposed trial design determines the maximum sample size for each intervention using the Average Length Criteria. The interim analysis takes place at approximately half the pre-specified maximum sample size and aims to drop interventions for futility if either Pbest or the SUCRA is below a pre-specified threshold. The final analysis compares all remaining interventions at the maximum sample size to conclude superiority based on either Pbest or the SUCRA. The two ranking methods were compared across 12 scenarios that vary the number of interventions and the assumed differences between the interventions. The thresholds for futility and superiority were chosen to control type 1 error, and then the predictive power and expected sample size were evaluated across scenarios. A trial comparing three interventions that aim to reduce anxiety for children undergoing a laceration repair in the emergency department was then designed, known as the Anxiolysis for Laceration Repair in Children Trial (ALICE) trial. RESULTS: As the number of interventions increases, the SUCRA results in a higher predictive power compared with Pbest. Using Pbest results in a lower expected sample size when there is an effective intervention. Using the Average Length Criterion, the ALICE trial has a maximum sample size for each arm of 100 patients. This sample size results in a 86% and 85% predictive power using Pbest and the SUCRA, respectively. Thus, we chose Pbest as the ranking method for the ALICE trial. CONCLUSION: Bayesian ranking methods can be used in multi-arm, multi-stage trials with no clear control intervention. When more interventions are included, the SUCRA results in a higher power than Pbest. Future work should consider whether other ranking methods may also be relevant for clinical trial design.

Nitrous oxide use in Canadian pediatric emergency departments: a survey of physician's knowledge, attitudes, and practices.

OBJECTIVES: Nitrous oxide (N2O) is an inhaled analgesic/ anxiolytic gas with evidence supporting its safety and efficacy for distressing procedures in children. Despite this, its use is not consistent across Canadian pediatric emergency departments (EDs). We aimed to characterize a) physicians' knowledge and practices with N2O and b) site-specific N2O protocols in Canadian pediatric EDs to help optimize its use nationally. METHODS: This cross-sectional survey was distributed to physician members of Pediatric Emergency Research Canada (PERC) in early 2021. Survey items addressed practice patterns, clinician comfort, and perceived barriers/ facilitators to use. Further, a representative from each ED completed a site-specific inventory of N2O policies and procedures. RESULTS: N2O was available in 40.0% of 15 pediatric EDs, with 83.3% of these sites having written policies in place. Of 230 distributed surveys, 67.8% were completed with mean (SD) attending experience of 14.7 (8.6) years and 70.1% having pediatric emergency subspecialty training. Of the 156 respondents, 48.7% used N2O in their clinical practice. The most common indications for use were digit fracture/ dislocation reduction (69.7%), wound closure (60.5%), and incision & drainage (59.2%). Commonly perceived facilitators were N2O equipment availability (73.0% of 156) and previous clinical experience (71.7% of 156). Of the 51.3% of physicians who reported not using N2O, 93.7% did not have availability at their site; importantly, the majority indicated a desire to acquire access. They identified concerns about ventilation/ scavenging systems (71.2% of 80) and unfamiliarity with equipment (52.5% of 80) as the most common barriers to use. CONCLUSIONS: Despite evidence to support its use, only half of Canadian pediatric ED physicians surveyed use N2O in their clinical practice for treating procedure-related pain and distress. Increased availability of N2O equipment, protocols, and training may improve clinicians' abilities to better manage pediatric acute pain and distress in the ED.

RéSUMé: OBJECTIFS: Le protoxyde d'azote (N2O) est un gaz analgésique/anxiolytique inhalé dont l'innocuité et l'efficacité ont été démontrées lors d'interventions pénibles chez l'enfant. Malgré cela, son utilisation n'est pas uniforme dans les services d'urgences pédiatriques (SU) du Canada. Nous avons cherché à caractériser a) les connaissances et les pratiques des médecins en matière de N2O et b) les protocoles de N2O spécifiques à un site dans les urgences pédiatriques canadiennes afin d'aider à optimiser son utilisation à l'échelle nationale. MéTHODES: Cette enquête transversale a été distribuée aux médecins membres de Recherche d'urgence pédiatrique Canada (PERC) au début de 2021. Les questions de l'enquête portaient sur les modes de pratique, l'aisance du clinicien et les obstacles/facilitateurs perçus pour l'utilisation. En outre, un représentant de chaque SU a dressé un inventaire des politiques et procédures N2O propres à chaque site. RéSULTATS: La N2O était disponible dans 40,0% des 15 services d'urgence pédiatriques, et 83,3% de ces sites avaient mis en place des politiques écrites. Sur 230 enquêtes distribuées, 67,8% ont été réalisées avec une expérience moyenne (SD) de 14,7 (8,6) ans et 70,1% ont suivi une formation en surspécialité pédiatrique d'urgence. Sur les 156 répondants, 48,7% utilisaient le N2O dans leur pratique clinique. Les indications les plus courantes étaient la réduction des fractures digitales et des luxations (69,7%), la fermeture des plaies (60,5%) et l'incision et le drainage (59,2%). Les facilitateurs généralement perçus étaient la disponibilité de l'équipement N2O (73,0% sur 156) et l'expérience clinique antérieure (71,7% sur 156). Parmi les 51,3% de médecins qui ont déclaré ne pas utiliser de N2O, 93,7% n'avaient pas de disponibilité sur leur site; il est important de noter que la majorité d'entre eux ont indiqué qu'ils souhaitaient y avoir accès. Ils ont identifié les préoccupations concernant les systèmes de ventilation/de récupération (71,2% sur 80) et la méconnaissance de l'équipement (52,5% sur 80) comme étant les obstacles les plus courants à l'utilisation de l'appareil. CONCLUSIONS: Malgré les données probantes à l'appui de son utilisation, seulement la moitié des médecins canadiens des urgences pédiatriques interrogés utilisent le N2O dans leur pratique clinique pour traiter la douleur et la détresse liées à l'intervention. Une plus grande disponibilité de l'équipement N2O, des protocoles et de la formation peut améliorer les capacités des cliniciens à mieux gérer la douleur aiguë et la détresse pédiatrique aux urgences.

Pharmacologic Procedural Distress Management During Laceration Repair in Children: A Systematic Review.

OBJECTIVES: To systematically appraise the literature on the relative effectiveness of pharmacologic procedural distress management agents for children undergoing laceration repair. METHODS: Six databases were searched in August 2021, and the search was updated in January 2023. We included completed randomized or quasi-randomized trials involving ( a ) children younger than 15 years undergoing laceration repair in the emergency department; ( b ) randomization to at least one anxiolytic, sedative, and/or analgesic agent versus any comparator agent or placebo; ( c ) efficacy of procedural distress management measured on any scale. Secondary outcomes were pain during the procedure, administration acceptance, sedation duration, additional sedation, length of stay, and stakeholder satisfaction. Cochrane Collaboration's risk-of-bias tool assessed individual studies. Ranges and proportions summarized results where applicable. RESULTS: Among 21 trials (n = 1621 participants), the most commonly studied anxiolytic agents were midazolam, ketamine, and N 2 O. Oral midazolam, oral ketamine, and N 2 O were found to reduce procedural distress more effectively than their comparators in 4, 3, and 2 studies, respectively. Eight studies comparing routes, doses, or volumes of administration of the same agent led to indeterminate results. Meta-analysis was not performed because of heterogeneity in comparators, routes, and outcome measures across studies. CONCLUSIONS: Based on procedural distress reduction, this study favors oral midazolam and oral ketamine. However, this finding should be interpreted with caution because of heterogeneous comparators across studies and minor conflicting results. An optimal agent for procedural distress management cannot be recommended based on the limited evidence. Future research should seek to identify the minimal, essential measures of patient distress during pharmacologic anxiolysis and/or sedation in laceration repair to guide future trials and reviews.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

Post-COVID-19 Condition in Children 6 and 12 Months After Infection.

Importance: There is a need to understand the long-term outcomes among children infected with SARS-CoV-2. Objective: To quantify the prevalence of post-COVID-19 condition (PCC) among children tested for SARS-CoV-2 infection in pediatric emergency departments (EDs). Design, Setting, and Participants: Multicenter, prospective cohort study at 14 Canadian tertiary pediatric EDs that are members of the Pediatric Emergency Research Canada network with 90-day, 6-month, and 12-month follow-up. Participants were children younger than 18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. Data were analyzed from May to November 2023. Exposure: The presence of SARS-CoV-2 infection at or within 14 days of the index ED visit. Main Outcomes and Measures: Presence of symptoms and QoL reductions that meet the PCC definition. This includes any symptom with onset within 3 months of infection that is ongoing at the time of follow-up and affects everyday functioning. The outcome was quantified at 6 and 12 months following the index ED visit. Results: Among the 5147 children at 6 months (1152 with SARS-CoV-2 positive tests and 3995 with negative tests) and 5563 children at 12 months (1192 with SARS-CoV-2 positive tests and 4371 with negative tests) who had sufficient data regarding the primary outcome to enable PCC classification, the median (IQR) age was 2.0 (0.9-5.0) years, and 2956 of 5563 (53.1%) were male. At 6-month follow-up, symptoms and QoL changes consistent with the PCC definition were present in 6 of 1152 children with positive SARS-CoV-2 tests (0.52%) and 4 of 3995 children with negative SARS-CoV-2 tests (0.10%; absolute risk difference, 0.42%; 95% CI, 0.02% to 0.94%). The PCC definition was met at 12 months by 8 of 1192 children with positive SARS-CoV-2 tests (0.67%) and 7 of 4371 children with negative SARS-CoV-2 tests (0.16%; absolute risk difference, 0.51%; 95% CI, 0.06 to 1.08%). At 12 months, the median (IQR) PedsQL Generic Core Scale scores were 98.4 (90.0-100) among children with positive SARS-CoV-2 tests and 98.8 (91.7-100) among children with negative SARS-CoV-2 tests (difference, -0.3; 95% CI, -1.5 to 0.8; P = .56). Among the 8 children with SARS-CoV-2 positive tests and PCC at 12-month follow-up, children reported respiratory (7 of 8 patients [88%]), systemic (3 of 8 patients [38%]), and neurologic (1 of 8 patients [13%]) symptoms. Conclusions and Relevance: In this cohort study of children tested for SARS-CoV-2 infection in Canadian pediatric EDs, although children infected with SARS-CoV-2 reported increased chronic symptoms, few of these children developed PCC, and overall QoL did not differ from children with negative SARS-CoV-2 tests.

Family caregivers' emotional and communication needs in Canadian pediatric emergency departments.

OBJECTIVES: To describe the extent to which caregivers' emotional and communication needs were met during pediatric emergency department (PED) visits. Secondary objectives included describing the association of caregiver emotional needs, satisfaction with care, and comfort in caring for their child's illness at the time of discharge with demographic characteristics, caregiver experiences, and ED visit details. STUDY DESIGN: Electronic surveys with medical record review were deployed at ten Canadian PEDs from October 2018 -March 2020. A convenience sample of families with children <18 years presenting to a PED were enrolled, for one week every three months, for one year per site. Caregivers completed one in-PED survey and a follow-up survey, up to seven days post-visit. RESULTS: This study recruited 2005 caregivers who self-identified as mothers (74.3%, 1462/1969); mean age was 37.8 years (SD 7.7). 71.7% (1081/1507) of caregivers felt their emotional needs were met. 86.4% (1293/1496) identified communication with the doctor as good/very good and 83.4% (1249/1498) with their child's nurse. Caregiver involvement in their child's care was reported as good/very good 85.6% (1271/1485) of the time. 81.8% (1074/1313) of caregivers felt comfortable in caring for their child at home at the time of discharge. Lower caregiver anxiety scores, caregiver involvement in their child's care, satisfactory updates, and having questions adequately addressed positively impacted caregiver emotional needs and increased caregiver comfort in caring for their child's illness at home. CONCLUSION: Approximately 30% of caregivers presenting to PEDs have unmet emotional needs, over 15% had unmet communication needs, and 15% felt inadequately involved in their child's care. Family caregiver involvement in care and good communication from PED staff are key elements in improving overall patient experience and satisfaction.

Nasal Suctioning Therapy Among Infants With Bronchiolitis Discharged Home From the Emergency Department: A Randomized Clinical Trial.

Importance: Although nasal suctioning is the most frequently used supportive management for bronchiolitis, its benefit remains unknown. Objective: To evaluate the effectiveness of enhanced vs minimal nasal suctioning in treating infants with bronchiolitis after discharge from the emergency department (ED). Design, Setting, and Participants: This single-blind, parallel-group, randomized clinical trial was conducted from March 6, 2020, to December 15, 2022, at 4 tertiary-care Canadian pediatric EDs. Participants included otherwise healthy infants aged 1 to 11 months with a diagnosis of bronchiolitis who were discharged home from the ED. Interventions: Participants were randomized to minimal suctioning via bulb or enhanced suctioning via a battery-operated device before feeding for 72 hours. Main Outcomes and Measures: The primary outcome was additional resource use, a composite of unscheduled revisits for bronchiolitis or use of additional suctioning devices for feeding and/or breathing concerns. Secondary outcomes included health care utilization, feeding and sleeping adequacy, and satisfaction. Results: Of 884 screened patients, 352 were excluded for criteria, 79 declined participation, 81 were otherwise excluded, 372 were randomized (185 to the minimal suction group and 187 to the enhanced suction group), and 367 (median [IQR] age, 4 [2-6] months; 221 boys [60.2%]) completed the trial (184 in the minimal suction and 183 in the enhanced suction group). Additional resource use occurred for 68 of 184 minimal suction participants (37.0%) vs 48 of 183 enhanced suction participants (26.2%) (absolute risk difference, 0.11; 95% CI, 0.01 to 0.20; P = .03). Unscheduled revisits occurred for 47 of 184 minimal suction participants (25.5%) vs 40 of 183 enhanced suction participants (21.9%) (absolute risk difference, 0.04; 95% CI, -0.05 to 0.12; P = .46). A total of 33 of 184 parents in the minimal suction group (17.9%) used additional suctioning devices vs 11 of 183 parents in the enhanced suction group (6.0%) (absolute risk difference, 0.12; 95% CI, 0.05 to 0.19; P < .001). No significant between-group differences were observed for all bronchiolitis revisits (absolute risk difference, 0.07; 95% CI, -0.02 to 0.16; P = .15), ED revisits (absolute risk difference, 0.04; 95% CI, -0.03 to 0.12; P = .30), parental care satisfaction (absolute risk difference, -0.02; 95% CI, -0.10 to 0.06; P = .70), and changes from baseline to 72 hours in normal feeding (difference in differences, 0.03; 95% CI, -0.10 to 0.17; P = .62), normal sleeping (difference in differences, 0.05; 95% CI, -0.08 to 0.18; P = .47), or normal parental sleeping (difference in differences, 0.10; 95% CI, -0.02 to 0.23; P = .09). Parents in the minimal suction group were less satisfied with the assigned device (62 of 184 [33.7%]) than parents in the enhanced suction group (145 of 183 [79.2%]) (risk difference, 0.45; 95% CI, 0.36 to 0.54; P < .001). Conclusions and Relevance: Compared with minimal suctioning, enhanced suctioning after ED discharge with bronchiolitis did not alter the disease course because there were no group differences in revisits or feeding and sleeping adequacy. Minimal suctioning resulted in higher use of nonassigned suctioning devices and lower parental satisfaction with the assigned device. Trial Registration: ClinicalTrials.gov Identifier: NCT03361371.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Emergency department visits and hospital admissions for suicidal ideation, self-poisoning and self-harm among adolescents in Canada during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic had profound effects on the mental wellbeing of adolescents. We sought to evaluate pandemic-related changes in health care use for suicidal ideation, self-poisoning and self-harm. METHODS: We obtained data from the Canadian Institute for Health Information on emergency department visits and hospital admissions from April 2015 to March 2022 among adolescents aged 10-18 years in Canada. We calculated the quarterly percentage of emergency department visits and hospital admissions for a composite outcome comprising suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits and hospital admissions. We used interrupted time-series methods to compare changes in levels and trends of these outcomes between the prepandemic (Apr. 1, 2015-Mar. 1, 2020) and pandemic (Apr. 1, 2020-Mar. 31, 2022) periods. RESULTS: The average quarterly percentage of emergency department visits for suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits was 2.30% during the prepandemic period and 3.52% during the pandemic period. The level (0.08%, 95% confidence interval [CI] -0.79% to 0.95%) or trend (0.07% per quarter, 95% CI -0.14% to 0.28%) of this percentage did not change significantly between periods. The average quarterly percentage of hospital admissions for the composite outcome relative to all-cause admissions was 7.18% during the prepandemic period and 8.96% during the pandemic period. This percentage showed no significant change in level (-0.70%, 95% CI -1.90% to 0.50%), but did show a significantly increasing trend (0.36% per quarter; 95% 0.07% to 0.65%) during the pandemic versus prepandemic periods, specifically among females aged 10-14 years (0.76% per quarter, 95% CI 0.22% to 1.30%) and females aged 15-18 years (0.56% per quarter, 95% CI 0.31% to 0.81%). INTERPRETATION: The quarterly change in the percentage of hospital admissions for suicidal ideation, self-poisoning and self-harm increased among adolescent females in Canada during the first 2 years of the COVID-19 pandemic. This underscores the need to promote public health policies that mitigate the impact of the pandemic on adolescent mental health.

Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a protocol for a pilot randomized controlled trial.

BACKGROUND: Current guidelines for diabetic ketoacidosis (DKA) recommend treatment with normal saline (NS). However, NS, with its high chloride concentrations, may worsen acidosis and contribute to a hyperchloremic metabolic acidosis. Alternatives to NS are balanced crystalloids (e.g. Ringer's Lactate [RL]) which have chloride concentrations similar to human plasma; therefore, treatment with balanced crystalloids may lead to faster DKA resolution. A recent systematic review and meta-analysis by Catahay et al. (2022) demonstrated the need for more blinded, high-quality trials comparing NS versus RL in the treatment of DKA. METHODS: We describe a protocol for BRISK-ED (Balanced crystalloids [RInger's lactate] versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department). Our study is a single-centre, triple-blind, pilot randomized controlled trial (RCT) of adults (≥ 18 years) with DKA presenting to an academic tertiary care ED in London, Canada. Patients with clinical suspicion for DKA will be screened and those found to not meet DKA criteria or have euglycemic DKA will be excluded. We will aim to recruit 52 patients with DKA and will randomize them 1:1 to receive intravenous RL or NS. The primary feasibility outcome will be recruitment rate, and the primary efficacy outcome will be time elapsed from ED presentation to DKA resolution. Secondary outcomes include time to insulin infusion discontinuation, intensive care unit admission, in-hospital death, and major adverse kidney events within 30 days, defined as a composite of: i) death, ii) new renal replacement therapy, or iii) final serum creatinine ≥ 200% baseline at the earliest of hospital discharge or 30 days after ED presentation. Patients, clinicians, and outcome assessors will be blinded to allocation group. We will follow an intention-to-treat analysis. Gehan-Wilcoxon, Mann-Whitney U, or chi-square tests will be used to compare groups as appropriate. DISCUSSION: The results of this pilot study will inform the design and feasibility of a full-scale, multicentre RCT to assess fluid choice in adult ED patients with DKA. If proven to demonstrate faster resolution of DKA, administration of balanced crystalloids may replace NS in diabetes treatment guidelines and improve patient and health systems outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, Registration # NCT04926740; Registered June 15, 2021.

Sedation and Analgesia for Reduction of Pediatric Ileocolic Intussusception.

Importance: Ileocolic intussusception is an important cause of intestinal obstruction in children. Reduction of ileocolic intussusception using air or fluid enema is the standard of care. This likely distressing procedure is usually performed without sedation or analgesia, but practice variation exists. Objective: To characterize the prevalence of opioid analgesia and sedation and assess their association with intestinal perforation and failed reduction. Design, Setting, and Participants: This cross-sectional study reviewed medical records of children aged 4 to 48 months with attempted reduction of ileocolic intussusception at 86 pediatric tertiary care institutions in 14 countries from January 2017 to December 2019. Of 3555 eligible medical records, 352 were excluded, and 3203 medical records were eligible. Data were analyzed in August 2022. Exposures: Reduction of ileocolic intussusception. Main outcomes and measures: The primary outcomes were opioid analgesia within 120 minutes of reduction based on the therapeutic window of IV morphine and sedation immediately before reduction of intussusception. Results: We included 3203 patients (median [IQR] age, 17 [9-27] months; 2054 of 3203 [64.1%] males). Opioid use was documented in 395 of 3134 patients (12.6%), sedation 334 of 3161 patients (10.6%), and opioids plus sedation in 178 of 3134 patients (5.7%). Perforation was uncommon and occurred in 13 of 3203 patients (0.4%). In the unadjusted analysis, opioids plus sedation (odds ratio [OR], 5.92; 95% CI, 1.28-27.42; P = .02) and a greater number of reduction attempts (OR, 1.48; 95% CI, 1.03-2.11; P = .03) were significantly associated with perforation. In the adjusted analysis, neither of these covariates remained significant. Reductions were successful in 2700 of 3184 attempts (84.8%). In the unadjusted analysis, younger age, no pain assessment at triage, opioids, longer duration of symptoms, hydrostatic enema, and gastrointestinal anomaly were significantly associated with failed reduction. In the adjusted analysis, only younger age (OR, 1.05 per month; 95% CI, 1.03-1.06 per month; P < .001), shorter duration of symptoms (OR, 0.96 per hour; 95% CI, 0.94-0.99 per hour; P = .002), and gastrointestinal anomaly (OR, 6.50; 95% CI, 2.04-20.64; P = .002) remained significant. Conclusions and Relevance: This cross-sectional study of pediatric ileocolic intussusception found that more than two-thirds of patients received neither analgesia nor sedation. Neither was associated with intestinal perforation or failed reduction, challenging the widespread practice of withholding analgesia and sedation for reduction of ileocolic intussusception in children.

Inhaled nitrous oxide for painful procedures in children and youth: a systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to synthesize indication-based evidence for N2O for distress and pain in children. STUDY DESIGN: We included trials of N2O in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting N2O or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively. RESULTS: We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% N2O (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I2 = 0%) and 50% N2O plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I2 = 43%) were superior to EMLA. 50% N2O was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I2 = 15%). For distress and pain during laceration repair, N2O was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), N2O was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), N2O was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), N2O was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), N2O plus EMLA was "favorable" versus N2O and EMLA alone. Common adverse effects of N2O included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with N2O alone (278/1147 (24.2%)) versus N2O plus midazolam (48/52 (92.3%)) and N2O plus fentanyl (123/201 (61.2%)). CONCLUSIONS: There is sufficient evidence to recommend N2O plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.

RéSUMé: OBJECTIFS: Synthétiser les données probantes fondées sur l'indication pour le N2O pour la détresse et la douleur chez les enfants. Plan d'étude : Nous avons inclus des essais de N2O chez des participants âgés de 0 à 21 ans, signalant une détresse ou une douleur pour les procédures des services d'urgence. Le critère de jugement principal était la détresse procédurale. Lorsqu'une méta-analyse n'était pas possible, nous avons utilisé la classification de Tricco et al. "neutre" (p>0,05), "favorable" ou "défavorable" (p<0,05, en faveur de la N2O ou du comparateur, respectivement). Nous avons utilisé l'outil risque de biais de la Collaboration Cochrane et le système Grading of Recommendations Assessment, Development, and Evaluation pour évaluer respectivement le risque de biais et la qualité des preuves. RéSULTATS: Nous avons inclus 30 essais. Pour la douleur sur l'échelle visuelle analogique (0-100 mm) pendant l'insertion IV, 70 % de N2O (delta : -16,5 ; IC à 95% : -28,6 à -4,4 ; p = 0,008 ; trois essais ; I2 = 0 %) et 50 % de N2O plus un mélange eutectique d'anesthésiques locaux (EMLA) (delta : -1,2 ; IC à 95 % : -2,1 à -0,3 ; p = 0,007 ; deux essais ; I2 = 43 %) étaient supérieurs à l'EMLA. La N2O à 50 % n'était pas supérieure à l'EMLA (delta : -0,4 ; IC à 95 % : -1,2 à 0,3 ; p = 0,26 ; deux essais ; I2 = 15 %). En ce qui concerne la détresse et la douleur pendant la réparation des lacérations, le N2O était "favorable" par rapport à la lidocaïne SC, à l'oxygène et au midazolam oral, mais "neutre" par rapport à la kétamine IV (cinq essais). Pour la détresse et la douleur pendant la réduction des fractures (trois essais), le N2O était « neutre ¼ par rapport à la mépéridine IM plus prométhazine, l'anesthésie régionale et la kétamine IV plus midazolam. Pour la détresse et la douleur lors de la ponction lombaire (un essai), le N2O était "favorable" par rapport à l'oxygène. Pour la détresse et la douleur pendant le cathétérisme urétral (un essai), N2O était "neutre" par rapport au midazolam oral. Pour la douleur pendant l'injection intramusculaire (un essai), le N2O plus EMLA était « favorable ¼ par rapport au N2O et à l'EMLA seuls. Les effets indésirables les plus fréquents de la N2O étaient les nausées (4,4 %), l'agitation (3,7 %) et les vomissements (3,6 %). Les EI étaient moins fréquents avec la N2O seule (278/1147 (24,2 %)) par rapport au N2O plus midazolam (48/52 (92,3 %)) et le N2O plus fentanyl (123/201 (61,2 %)). CONCLUSIONS: Il existe suffisamment de preuves pour recommander le N2O plus un anesthésique topique pour l'insertion intraveineuse et la réparation des lacérations. Les effets indésirables sont plus importants lorsqu'ils sont combinés avec d'autres agents sédatifs.

What influences physician opioid prescribing for children with acute pain?

Background: Pain is one of the most common symptoms encountered in the healthcare system, and opioids are among the top three medications used to treat it. Understanding the reasoning behind physicians' opioid prescribing practices is vital to safe practice. The primary objective of our study was to describe pediatric emergency physicians' decision-making process when prescribing opioids for children's acute pain management. Methods: This study employed qualitative methodology, using one-on-one semi-structured interviews within a grounded theory analytic framework. We employed purposeful sampling to recruit pediatric emergency physicians from across Canada. Interviews were conducted by telephone (December 2019-January 2021). Transcript analysis occurred concurrently with data collection, supporting data saturation and theory development considerations. Results: Eleven interviews were completed with participants representing each of Canada's geographic regions. Nine major themes emerged: (1) practice setting and outpatient opioid use, (2) condition-specific considerations, (3) physician confidence in medical evidence, (4) pain assessment challenges, (5) patient and family perspectives, (6) opioid safety concerns, (7) personal biases and experiences, (8) personal practice context, and (9) the Opioid Crisis/media influence. Most clinicians felt that they limited opioid use to those who needed it most; all participants described challenges managing acute pain, emphasizing the need for accurate pain measurement and better guidelines, evidence-based data, and knowledge translation. Clinicians were more comfortable treating pain in the emergency department, compared to discharge prescribing. They recognized the importance of co-therapy with non-opioids and the need for opioid risk assessment when prescribing. A family centered approach was recognized as the goal of practice. Conclusion: Clinicians are less comfortable prescribing opioids to children for at-home use and find pain assessment and lack of clear guidelines to be barriers to pain care. Knowledge translation strategies for safer practice and optimal acute pain management could support responsible and judicious opioid use.

Factors Influencing Parental Decision-Making Regarding Analgesia for Children with Musculoskeletal Injury-Related Pain: A Qualitative Study.

OBJECTIVES: To explore and understand parental decision-making relating to acute pain management for their children presenting to the emergency department. STUDY DESIGN: This study employed one-on-one semistructured interviews. Parents of children with acute musculoskeletal injuries were recruited from 3 Canadian pediatric emergency departments. Interviews were conducted via telephone from June 2019 to March 2021. Verbatim transcription and thematic analyses occurred concurrently with data collection, supporting data saturation and theory development considerations. RESULTS: Twenty-seven interviews were completed. Five major themes regarding pain care emerged: (1) my child's comfort is a priority, (2) every situation is unique, (3) opioids only if necessary, (4) considerations when choosing opioids, and (5) pain research is important. Overall, parents were highly comfortable with their assessment of their child's pain. Participants' willingness to use opioid analgesia for their children was primarily dependent on perceptions of injury and pain severity. Opioid-averse and opioid-accepting families had similar considerations when making analgesic decisions but weighed risks and benefits differently. CONCLUSIONS: Parents assess and manage their children's pain globally and multimodally, with comfort being prioritized. For most parents, the desire to relieve their children's pain outweighed concerns of substance use disorder, misuse, and adverse events when making decisions about opioid analgesia for short-term use. These results can inform evidence-based family-centered approaches to co-decision-making of analgesic plans for children with acute pain.

Optimal Dose of Intranasal Dexmedetomidine for Laceration Repair in Children: A Phase II Dose-Ranging Study.

STUDY OBJECTIVE: To determine the optimal sedative dose of intranasal dexmedetomidine for children undergoing laceration repair. METHODS: This dose-ranging study employing the Bayesian Continual Reassessment Method enrolled children aged 0 to 10 years with a single laceration (<5 cm), requiring single-layer closure, who received topical anesthetic. Children were administered 1, 2, 3, or 4 mcg/kg intranasal dexmedetomidine. The primary outcome was the proportion with adequate sedation (Pediatric Sedation State Scale score of 2 or 3 for ≥90% of the time from sterile preparation to tying of the last suture). Secondary outcomes included the Observational Scale of Behavior Distress-Revised (range: 0 [no distress] to 23.5 [maximal distress]), postprocedure length of stay, and adverse events. RESULTS: We enrolled 55 children (35/55 [64%] males; median [interquartile range {IQR}] age 4 [2, 6] years). At 1, 2, 3, and 4 mcg/kg intranasal dexmedetomidine, respectively, the proportion of participants "adequately" sedated was 1/3 (33%), 2/9 (22%), 13/21 (62%), and 12/21 (57%); the posterior mean (95% equitailed credible intervals) for the probability of adequate sedation was 0.38 (0.04, 0.82), 0.25 (0.05, 0.54), 0.61 (0.41, 0.80), and 0.57 (0.36, 0.76); the median (IQR) Observational Scale of Behavior Distress-Revised scores during suturing was 2.7 (0.3, 3), 0 (0, 3.8), 0.6 (0, 5), and 0 (0, 3.7); the median (IQR) postprocedure length of stay was 67 (60, 78), 76 (60, 100), 89 (76, 109), and 113 (76, 150) minutes. There was 1 adverse event, a decrease in oxygen saturation at 4 mcg/kg, which resolved with head repositioning. CONCLUSION: Despite limitations, such as our limited sample size and subjectivity in Pediatric Sedation State Scale scoring, sedation efficacy for 3 and 4 mcg/kg were similarly based on equitailed credible intervals suggesting either could be considered optimal.

Adolescent and Caregiver Perspectives on Living With a Limb Fracture: A Qualitative Study.

BACKGROUND: Fractures occur in up to half of children by age 16 years. After initial emergency care for a fracture, function is universally impaired in children, and impacts extend to the immediate family. Knowledge of expected functional limitations is key to providing proper discharge instructions and anticipatory guidance to families. OBJECTIVES: The primary objective of this study was to understand how changes in functional ability impact youth with fractures. METHODS: We conducted individual, semistructured interviews from June 2019 to November 2020 with adolescents and their caregivers 7 to 14 days following their initial visit to a pediatric emergency department. We used qualitative content analysis methodology; recruitment proceeded until thematic saturation was achieved. Coding and analysis were concurrent with recruitment and interviews. The interview script was modified in an iterative process, to reflect emerging themes. RESULTS: Twenty-nine interviews were completed. The most frequently affected functions were ( a ) showering and hygiene (requiring the most caregiver support), ( b ) sleep (due to pain and cast-related discomfort), and ( c ) exclusion from sports/activities. Many adolescents experienced disruptions to social activities and gatherings. Youth valued independence and took more time to complete tasks, regardless of inconvenience. Both adolescents and caregivers reported feelings of frustration from day-to-day impacts of the injury. Generally, caregivers' perspectives were in keeping with the experiences that adolescents described for themselves. Notable family impacts included "sibling burden," or conflicts that arose when a sibling had to take on extra chores/tasks. CONCLUSIONS: Overall, caregivers' perspectives were congruent with the self-described experiences of adolescents. Key messages for optimized discharge instructions include pain and sleep management, allowing extra time to complete tasks independently, considering impact on siblings, preparing for changes in activities and social dynamics, and normalizing frustration. These themes highlight an opportunity to better tailor discharge instructions for adolescents with fractures.

Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial.

BACKGROUND: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). METHODS: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts. RESULTS: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. CONCLUSIONS: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada.

Importance: Clinical manifestations of SARS-CoV-2 variants have not been systematically compared in children. Objective: To compare symptoms, emergency department (ED) chest radiography, treatments, and outcomes among children with different SARS-CoV-2 variants. Design, Setting, and Participants: This multicenter cohort study was performed at 14 Canadian pediatric EDs. Participants included children and adolescents younger than 18 years (hereinafter referred to as children) tested for SARS-CoV-2 infection in an ED between August 4, 2020, and February 22, 2022, with 14 days of follow-up. Exposure(s): SARS-CoV-2 variants detected on a specimen collected from the nasopharynx, nares, or throat. Main Outcomes and Measures: The primary outcome was presence and number of presenting symptoms. The secondary outcomes were presence of core COVID-19 symptoms, chest radiography findings, treatments, and 14-day outcomes. Results: Among 7272 participants presenting to an ED, 1440 (19.8%) had test results positive for SARS-CoV-2 infection. Of these, 801 (55.6%) were boys, with a median age of 2.0 (IQR, 0.6-7.0) years. Children with the Alpha variant reported the fewest core COVID-19 symptoms (195 of 237 [82.3%]), which were most often reported by participants with Omicron variant infection (434 of 468 [92.7%]; difference, 10.5% [95% CI, 5.1%-15.9%]). In a multivariable model with the original type as the referent, the Omicron and Delta variants were associated with fever (odds ratios [ORs], 2.00 [95% CI, 1.43-2.80] and 1.93 [95% CI, 1.33-2.78], respectively) and cough (ORs, 1.42 [95% CI, 1.06-1.91] and 1.57 [95% CI, 1.13-2.17], respectively). Upper respiratory tract symptoms were associated with Delta infection (OR, 1.96 [95% CI, 1.38-2.79]); lower respiratory tract and systemic symptoms were associated with Omicron variant infection (ORs, 1.42 [95% CI, 1.04-1.92] and 1.77 [95% CI, 1.24-2.52], respectively). Children with Omicron infection most often had chest radiography performed and received treatments; compared with those who had Delta infection, they were more likely to have chest radiography performed (difference, 9.7% [95% CI, 4.7%-14.8%]), to receive intravenous fluids (difference, 5.6% [95% CI, 1.0%-10.2%]) and corticosteroids (difference, 7.9% [95% CI, 3.2%-12.7%]), and to have an ED revisit (difference, 8.8% [95% CI, 3.5%-14.1%]). The proportions of children admitted to the hospital and intensive care unit did not differ between variants. Conclusions and Relevance: The findings of this cohort study of SARS-CoV-2 variants suggest that the Omicron and Delta variants were more strongly associated with fever and cough than the original-type virus and the Alpha variant. Children with Omicron variant infection were more likely to report lower respiratory tract symptoms and systemic manifestations, undergo chest radiography, and receive interventions. No differences were found in undesirable outcomes (ie, hospitalization, intensive care unit admission) across variants.