Pyuria in Children with Diabetic Ketoacidosis.

Acute kidney injury occurs frequently during pediatric diabetic ketoacidosis (DKA). We reviewed urinalyses from 561 children with DKA; pyuria was detected in 19% overall and in 40% of children with more comprehensive urine testing (≥3 urinalyses) during DKA.

Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. RESULTS: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. CONCLUSIONS: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).

Assessment of primary outcome measures for a clinical trial of pediatric hemorrhagic injuries.

OBJECTIVE: We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians. METHODS: We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated. RESULTS: 73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL. CONCLUSIONS: The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants.

Hypertension during Diabetic Ketoacidosis in Children.

OBJECTIVES: To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. STUDY DESIGN: This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension. RESULTS: Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment. CONCLUSIONS: Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.

Videography in Pediatric Emergency Research: Establishing a Multicenter Collaborative and Resuscitation Registry.

OBJECTIVES: High-quality clinical research of resuscitations in a pediatric emergency department is challenging because of the limitations of traditional methods of data collection (chart review, self-report) and the low frequency of cases in a single center. To facilitate valid and reliable research for resuscitations in the pediatric emergency department, investigators from 3 pediatric centers, each with experience completing successful single-center, video-based studies, formed the Videography In Pediatric Emergency Research (VIPER) collaborative. METHODS: Our initial effort was the development of a multicenter, video-based registry and simulation-based testing of the feasibility and reliability of the VIPER registry. Feasibility of data collection was assessed by the frequency of an indeterminate response for all data elements in the registry. Reliability was assessed by the calculation of Cohen κ for dichotomous data elements and intraclass correlation coefficients for continuous data elements. RESULTS: Video-based data collection was completed for 8 simulated pediatric resuscitations, with at least 2 reviewers per case. Data were labeled as indeterminate by at least 1 reviewer for 18 (3%) of 524 relevant data fields. The Cohen κ for all dichotomous data fields together was 0.81 (95% confidence interval, 0.61-1.0). For all continuous (time-based) variables combined, the intraclass correlation coefficient was 0.88 (95% confidence interval, 0.70-0.96). CONCLUSIONS: Initial simulation-based testing suggests video-based data collection using the VIPER registry is feasible and reliable. Our next step is to assess feasibility and reliability for actual pediatric resuscitations and to complete several prospective, hypothesis-based studies of specific aspects of resuscitative care, including of cardiopulmonary resuscitation, tracheal intubation, and teamwork and communication.

Reasons for Interfacility Emergency Department Transfer and Care at the Receiving Facility.

OBJECTIVES: The aims of this study were to (1) assess the reasons for pediatric interfacility transfers as identified by transferring providers and review the emergency medical care delivered at the receiving facilities and (2) investigate the emergency department (ED) care among the subpopulation of patients discharged from the receiving facility. METHODS: We performed a multicenter, cross-sectional survey of ED medical providers transferring patients younger than 18 years to 1 of 4 US tertiary care pediatric hospitals with a subsequent medical record review at the receiving facility. Referring providers completed surveys detailing reasons for transfer. RESULTS: Eight hundred thirty-nine surveys were completed by 641 providers for 25 months. The median patient age was 5.7 years. Sixty-two percent of the patients required admission. The most common reasons for transfer as cited by referring providers were subspecialist consultation (62%) and admission to a pediatric inpatient (17%) or intensive care (6%) unit. For discharged patients, plain radiography (26%) and ultrasonography (12%) were the most common radiologic studies. Procedural sedation (16%) was the most common ED procedure for discharged patients, and 55% had a subspecialist consult at the receiving facility. Ten percent of interfacility transfers did not require subspecialty consult, ED procedure, radiologic study, or admission. CONCLUSIONS: Approximately 4 of 10 interfacility transfers are discharged by the receiving facility, suggesting an opportunity to provide more comprehensive care at referring facilities. On the basis of the care provided at the receiving facility, potential interventions might include increased subspecialty access and developing both ultrasound and sedation capabilities.

Quality improvement and crisis resource management in pediatric resuscitation.

PURPOSE OF REVIEW: The pediatric resuscitation environment is a high-stakes, environment in which a multidisciplinary team must work together with patient outcomes dependent, at least in part, on the performance of that team. Given constraints of the environment and the nature of these events, quality improvement work in pediatric resuscitation can be challenging. Ongoing collection of accurate and reliable data on team performance is necessary to inform and evaluate change. RECENT FINDINGS: Despite the relative difficulty of quality improvement analysis and intervention implementation in the resuscitation environment, these efforts can have significant impact on patient outcomes. Although there are barriers to accurate data collection in real-life resuscitation, team performance of both technical and nontechnical skills can be reliably measured in video-based quality improvement programs. Training of nontechnical skills, using crisis resource management principles, can improve care delivery in resuscitation. SUMMARY: Striving toward a learning healthcare system model in resuscitation care delivery can allow for efficient performance improvement. Given the possible impacts on mortality and quality of life of care delivered in the resuscitation environment, all providers who could possibly face a resuscitation event - no matter how rare - should consider how they are evaluating the quality of their care delivery in this arena.

A National Analysis of Pediatric Trauma Care Utilization and Outcomes in the United States.

OBJECTIVES: More childhood deaths are attributed to trauma than all other causes combined. Our objectives were to provide the first national description of the proportion of injured children treated at pediatric trauma centers (TCs), and to provide clarity to the presumed benefit of pediatric TC verification by comparing injury mortality across hospital types. METHODS: We performed a population-based cohort study using the 2006 Healthcare Cost and Utilization Project Kids Inpatient Database combined with national TC inventories. We included pediatric discharges (≤16 y) with the International Classification of Diseases, Ninth Revision code(s) for injury. Descriptive analyses were performed evaluating proportions of injured children cared for by TC level. Multivariable logistic regression models were used to estimate differences in in-hospital mortality by TC type (among level-1 TCs only). Analyses were survey-weighted using Healthcare Cost and Utilization Project sampling weights. RESULTS: Of 153,380 injured children, 22.3% were admitted to pediatric TCs, 45.2% to general TCs, and 32.6% to non-TCs. Overall mortality was 0.9%. Among level-1 TCs, raw mortality was 1.0% pediatric TC, 1.4% dual TC, and 2.1% general TC. In adjusted analyses, treatment at level-1 pediatric TCs was associated with a significant mortality decrease compared to level-1 general TCs (adjusted odds ratio, 0.6; 95% confidence intervals, 0.4-0.9). CONCLUSIONS: Our results provide the first national evidence that treatment at verified pediatric TCs may improve outcomes, supporting a survival benefit with pediatric trauma verification. Given lack of similar survival advantage found for level-1 dual TCs (both general/pediatric verified), we highlight the need for further investigation to understand factors responsible for the survival advantage at pediatric-only TCs, refine pediatric accreditation guidelines, and disseminate best practices.

Profile of Interfacility Emergency Department Transfers: Transferring Medical Providers and Reasons for Transfer.

OBJECTIVES: The aim of this study was to determine the reasons for pediatric emergency department (ED) transfers and the professional characteristics of transferring providers. METHODS: We performed a multicenter, cross-sectional survey of ED medical providers transferring patients younger than 18 years to 1 of 4 tertiary care children's hospitals. Referring providers completed surveys detailing the primary reasons for transfer and their medical training. RESULTS: The survey data were collected for 25 months, during which 641 medical providers completed 890 surveys, with an overall response rate of 25%. Most pediatric patients were seen by physicians (89.4%) with predominantly general emergency medicine training (64.2%). The median age of patients seen was 5.6 years. The 3 most common diagnoses were closed extremity fracture (12.2%), appendicitis (11.6%), and pneumonia (3.7%). The 3 most common reasons for transfer were need for medical/surgical subspecialist consultation (62.6%), admission to the inpatient unit (17.1%), and admission to the intensive care unit (6.5%). When asked about the need for supportive pediatric services, referring providers ranked pediatric subspecialty and pediatric inpatient unit availability as the highest. CONCLUSIONS: Most pediatric interfacility ED transfers are referred by general emergency medicine physicians who often transfer for inpatient admission or subspecialty consultation. Understanding the needs of the community-based ED providers is an important step to forming more collaborative efforts for regionalized pediatric emergency care.

The influence of insurance type on interfacility pediatric emergency department transfers.

BACKGROUND: Disparities exist in the care children receive in the emergency department (ED) based on their insurance type. It is unknown if these differences exist among children transferred from outside EDs to pediatric tertiary care EDs. OBJECTIVE: To compare reasons for transfer and services received at pediatric tertiary care EDs between children with private and public insurance. METHODS: We performed a secondary analysis of a multicenter survey of ED providers transferring patients to pediatric tertiary care EDs in three major U.S. cities. Risk differences (RD) and 95% confidence intervals (CI) were calculated to compare reasons for transfer and care received at pediatric tertiary care EDs based on insurance type. RESULTS: There were 561 surveys completed by transferring providers describing reasons for transfer to pediatric tertiary care EDs with 52.2% of patients with private insurance and 47.8% with public insurance. We found no significant differences between privately and publicly insured children in reason for transfer for subspecialty consultation or need for admission. We found no significant differences in frequency of admission, radiologic studies, or ED procedures at the receiving facilities. However, a greater proportion of privately insured children had a subspecialty consultation at receiving facilities compared to publicly insured children (RD 9.7, 95% CI 2.0 to 17.4). CONCLUSIONS: Transferred pediatric patients with private insurance were more likely to have subspecialty consultations than children with public insurance. Further studies are needed to better characterize the interplay between patients' insurance type and both the request for, and the provision of, ED subspecialty consultations.

Lacerations and Embedded Needles Caused by Epinephrine Autoinjector Use in Children.

STUDY OBJECTIVE: Epinephrine autoinjector use for anaphylaxis is increasing. There are reports of digit injections because of incorrect autoinjector use, but no previous reports of lacerations, to our knowledge. We report complications of epinephrine autoinjector use in children and discuss features of these devices, and their instructions for use, and how these may contribute to injuries. METHODS: We queried emergency medicine e-mail discussion lists and social media allergy groups to identify epinephrine autoinjector injuries involving children. RESULTS: Twenty-two cases of epinephrine autoinjector-related injuries are described. Twenty-one occurred during intentional use for the child's allergic reaction. Seventeen children experienced lacerations. In 4 cases, the needle stuck in the child's limb. In 1 case, the device lacerated a nurse's finger. The device associated with the injury was operated by health care providers (6 cases), the patient's parent (12 cases, including 2 nurses), educators (3 cases), and the patient (1 case). Of the 3 epinephrine autoinjectors currently available in North America, none include instructions to immobilize the child's leg. Only 1 has a needle that self-retracts; the others have needles that remain in the thigh during the 10 seconds that the user is instructed to hold the device against the leg. Instructions do not caution against reinjection if the needle is dislodged during these 10 seconds. CONCLUSION: Epinephrine autoinjectors are lifesaving devices in the management of anaphylaxis. However, some have caused lacerations and other injuries in children. Minimizing needle injection time, improving device design, and providing instructions to immobilize the leg before use may decrease the risk of these injuries.

Performance in Trauma Resuscitation at an Urban Tertiary Level I Pediatric Trauma Center.

BACKGROUND: The role of the surveyor in trauma resuscitations is to identify life-threatening injuries and is meant to be conducted by a set protocol for every patient. Optimal performance of the trauma survey is known to be a challenge in pediatric trauma resuscitation. A postulated reason for this observation is that many trainees, such as pediatric residents, who perform the trauma survey have minimal experience and do not have formal advanced trauma life support training. The assessment of factors that may be obstacles in performing the trauma survey has not been studied robustly. OBJECTIVE: The objective of this retrospective cohort study was to use video review of resuscitation of real-life traumatically injured children to (1) describe the characteristics of the trauma patient, the surveyor, and the trauma response team in its current state of function at a tertiary level I trauma center, (2) describe current performance of primary and secondary surveys, as measured by an assessment tool, and (3) determine whether there are specific characteristics associated with reduced quality, completeness, or timeliness of the assessment of an injured child. METHODS: Retrospective review of emergency department (ED) trauma activations captured by video recording between June 2009 and January 2012. Video-recorded resuscitations were reviewed, and survey performance was scored using a novel assessment tool applying a scoring system (0, 1, or 2 points) for each essential element (airway, breathing, circulation, etc.) accounting for quality, sequence, and timing of assessments. Maximum score was 8 points for the primary survey and 22 points for the secondary survey. Time to completion of survey elements was recorded. Chart review identified surveyor characteristics (level of training and type of training program) and patient data fields (age, mechanism of injury, trauma level, Glasgow Coma Score, time of encounter, disposition, and number of procedures). Descriptive statistics and univariate analysis were performed. RESULTS: Of 749 eligible trauma activations, 228 activations were enrolled in the study with complete data for 202 patients. Most activations met level II criteria and involved blunt trauma. Most patients had a Glasgow Coma Score of 15 and were non-ICU inpatient admissions. PGY-3 residents performed the most surveys (53% of surveys done by residents). Pediatric residents performed 46% of surveys; emergency medicine (EM) residents, 41%; and pediatric EM fellows, 6%. Median scores on primary and secondary surveys were 7 and 12, respectively; median time to completion was 82 seconds and 265 seconds, respectively. Only 22% of primary surveys and 0% of secondary surveys were performed completely. Pediatric EM fellows had the highest mean score on primary and secondary survey. Pediatric EM fellows took longest to perform primary survey and shortest to complete secondary survey. Mean scores on primary and secondary survey were not significantly different between pediatric and EM residents (6.7 vs 6.7; 12.5 vs 11.6). There was no association between survey scores and level or type of training. Emergency medicine residents spent less time on the trauma survey, but this difference did not reach statistical significance. CONCLUSIONS: Primary and secondary surveys are frequently performed incompletely and inefficiently regardless of level of training or type of training program. There is no difference in measured performance among different types of residency programs. The impact of trauma resuscitation education on improved survey performance should be studied prospectively.

Custom injury prevention priority scoring: Local ranking procedures to assess unique community needs: Local Pediatric Injury Prevention Priority Scoring.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in children. Many traumatic injuries are preventable and trauma centers play a major role in directing population-level injury prevention strategies. Given the constraint of finite resources, calculating priorities for injury prevention at an institutional level is essential. The Injury Prevention and Priority Score (IPPS) is a widely applicable tool that is more robust than simple prevalence rankings and considers injury severity - an important factor when developing prevention strategies. We developed an adapted-IPPS methodology to define our local injury prevention priorities using our institution's patient population. METHODS: The institution-specific trauma registry was used, which includes patients presenting to a level 1 pediatric trauma center July 2018 - June 2022. Causes of injury were categorized into injury mechanisms based on external cause codes. Mechanisms of injury were ranked by frequency and severity (based on mean Injury Severity Score, ISS). An IPPS was calculated for each of the injury mechanisms, which were then ranked from highest to lowest priority injury mechanism. RESULTS: In ranking injury mechanisms by IPPS, "falls" remain the top priority mechanism despite their relatively low severity, given their overwhelming frequency (n = 1993, mean ISS = 5.9). The injury mechanisms "motor vehicle" (n = 434, mean ISS = 10.9) and "pedestrian" (n = 13, mean ISS = 15), become higher priority given their injury severity, despite lower frequency. "Pedestrian" includes non-traffic incidents such as patients run over by cars in driveways or rural settings. CONCLUSIONS: Computing the IPPS for each injury mechanism, using data collected routinely for trauma registries, enables trauma centers to use local data to inform injury prevention efforts in their communities. Calculating rankings based on an injury mechanism's relative frequency and severity allows a more robust understanding of their impact. LEVEL OF EVIDENCE: IV.

Pediatric capacity crisis: A framework and strategies to prepare for a pediatric surge.

A pediatric capacity crisis developed across the country in the Fall and Winter of 2022 due to a combination of factors, including a surge in respiratory viruses, staffing shortages, and historical closures of inpatient pediatric units. The COVID-19 pandemic and associated surge in critically ill adult patients demonstrated that health care systems and health care workers can quickly implement creative and collaborative system-wide solutions to deliver the best care possible during a capacity crisis. Similar solutions are needed to respond to future surges in pediatric volume and to maintain a high standard of care during such a surge. This paper aims to build upon insights from the COVID-19 and H1N1 pandemic responses and the 2022 pediatric capacity crisis. We provide specific recommendations addressing governmental/policy, hospital/health care system, and individual clinician strategies that can be implemented to manage future surges in pediatric patient volume.

Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults.

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.