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.

A Randomized Trial of Incentivization to Maximize Retention for Real-Time Symptom and Activity Monitoring Using Ecological Momentary Assessment in Pediatric Concussion.

OBJECTIVE: The aims of this study were to determine the incentivization strategy that maximizes patient adherence to report symptoms and activity via ecological momentary assessment (EMA) after pediatric concussion, and assess the feasibility of tracking concussed youth using EMA from the emergency department (ED) setting. METHODS: This study was a randomized controlled trial of participants ages 13 to 18 years with concussion presenting to an urban, academic pediatric ED within 5 days of injury. Participants were randomized to 1 of 4 incentive arms: 2 dynamic (loss-based and streak) and 2 control flat-rate (monetary and electronic device). Participants reported symptoms 3 times per day and cognitive activity once each evening for 3 weeks. Physical activity (step count) and sleep were monitored using a Fitbit (kept by participants in the device flat-rate arm). The primary outcome was proportion of prompts to which participants responded. Secondary outcomes included differential response rates by demographics, and comparison of outcome determination between EMA and subsequent clinical visits. RESULTS: Thirty participants were enrolled, with a median age of 15.5 years and 60% female. Median cumulative proportion of prompts responded to was 68.3% (interquartile range, 47.6%-82.5%) in the dynamic arms versus 54.0% (interquartile range. 20.6%-68.3%) in the flat-rate arms, P = 0.065. There were nonsignificant differences in median response by sex (65.9% for female vs 40.0% for male, P = 0.072), race/ethnicity (61.9% for non-Hispanic White vs 43.7% for non-Hispanic Black participants, P = 0.097), and insurance (61.9% for private insurance vs 47.6% for public insurance, P = 0.305). Recovery at 3 weeks was discernible for all but 2 participants (93.3%) using EMA data, compared with only 9 participants (30.0%) ( P < 0.001) from clinical visits. CONCLUSIONS: Dynamic incentivization showed higher rates of response to tridaily symptom prompts compared with flat-rate incentivization. These data show tracking concussed youth using EMA from the ED is feasible using a dynamic incentivization strategy, with improved ability to discern outcomes compared with prospective monitoring using follow-up clinical visits.

Characteristics and Outcomes for Delayed Diagnosis of Concussion in Pediatric Patients Presenting to the Emergency Department.

BACKGROUND: Concussions are common pediatric injuries. Previous studies have found concussed youth may be underdiagnosed in the emergency department (ED), but outcomes for those with delayed diagnosis have yet to be described. OBJECTIVE: Our aim was to compare visit characteristics and outcomes of patients who present to the ED with head injury who receive immediate vs. delayed diagnosis. METHODS: Retrospective chart review of patients aged 6 to 18 years diagnosed with concussion on their first ED or urgent care (UC) visit and patients requiring a second visit for diagnosis between July 1, 2017 and June 20, 2019. We compared demographic information, ED or UC visit features, and recovery outcomes using χ2 tests, Student's t-tests, and Wilcoxon rank-sum tests. RESULTS: Overall, we included 85 patients with delayed concussion diagnosis and 159 with immediate diagnosis. Those with immediate diagnosis had more symptoms inquired at initial visit (5 vs. 4; p = 0.003) and a higher likelihood of receiving concussion-specific physical examinations (80% vs. 36.5%; p < 0.001); 76.5% of delayed diagnosis patients had at least 1 symptom at follow-up visit that was not inquired about at initial visit. Those with delayed diagnosis had more medical visits during recovery (3 vs. 2; p < 0.001), longer average time to symptom resolution (21 vs. 11 days; p = 0.004), and a higher likelihood of having persistent concussion symptoms (odds ratio 2.9; 95% confidence interval 1.4-5.9). CONCLUSIONS: Concussed children evaluated acutely for head injury who do not receive an immediate diagnosis may be at risk for persistent symptoms. Performance of a concussion-specific physical examination and use of a standardized symptom scale may aid in identification of concussed youth acutely.