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Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Children with sickle cell disease commonly experience vaso-occlusive pain episodes due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. There study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n=75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, P0.001). The rapid onset of action and ease of delivery without IV access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with sickle cell disease presenting with vaso-occlusive pain episodes in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study. This article is protected by copyright. All rights reserved.

Background Access to multiplex molecular diagnostic tests for the rapid and accurate diagnosis of pharyngitis and other respiratory infections is limited in the near patient setting, but has potential to improve patient outcomes and antibiotic stewardship. The BioFire® Respiratory/Sore Throat (R/ST) Panel (bioMérieux, Salt Lake City, UT), designed for use with the BioFire® SpotFire System, is an Investigational Use Only (IUO) PCR-based sample-to-answer diagnostic test that identifies four bacteria and 10 viruses from nasopharyngeal swabs or throat swabs in ∼16 minutes. This study evaluated the ease of use and operator performance of the IUO R/ST Panel in the near patient setting. Methods A total of 35 test operators representative of the intended users in the near patient setting (i.e. non-laboratory professionals) participated across five study sites in the US and UK. Only Instrument and Panel Quick Guide training materials were provided during the eight months of R/ST Panel testing. Upon study completion, anonymous questionnaires were administered to assess operators’ perceived ease of use of the BioFire SpotFire System, R/ST Panel testing, and training materials; the accuracy of results interpretations were also evaluated. Further, results obtained by operators in the near patient setting and trained laboratory personnel were evaluated for reproducibility. Results Overall, 96.9% of operators reported that the system and panel were easy to use and that the provided training materials were sufficient to allow the user to perform the testing. The success rate of obtaining valid results on the initial test was 96.9%, similar to the rates observed for trained laboratory personnel. Reproducibility between site operators and trained laboratory personnel demonstrated an overall positive percent agreement of 99.0%. Conclusion The BioFire SpotFire System is an easy to use system that can be installed and operated in a near patient setting with minimal training. The R/ST Panel is also easy to use with minimal risk for user error. Implementation of this new system may aid in timely diagnosis and appropriate management of pharyngitis and other respiratory infections. Data presented are from assays that have not been cleared or approved for diagnostic use. Disclosures Ashley Ky, MLS(ASCP), bioMérieux: Employee|bioMérieux: Stocks/Bonds Jeffrey Bastar, PhD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Hana Bay, BS, Biomerieux: Employee|Biomerieux: Stocks/Bonds Tiffani Jones, PhD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.

Background Limited availability of multiplex molecular tests in the near-patient setting can impact the rapid diagnosis and treatment of patients experiencing symptoms of respiratory tract infections, including pharyngitis. The BioFire® Respiratory/Sore Throat (R/ST) Panel (bioMérieux, Salt Lake City, UT), designed for use with the BioFire® SpotFire System, is a PCR-based sample-to-answer diagnostic test that identifies four bacteria and 10 viruses (including SARS-CoV-2) from nasopharyngeal swab (NPS) or throat swab (TS) specimens in about 16 minutes. This study evaluated the performance of an Investigational Use Only (IUO) version of the BioFire R/ST Panel in the near patient setting. Methods NPS and TS specimens were prospectively enrolled from symptomatic consented/assented volunteers of all ages, or obtained as residual leftover specimens. Enrollment was conducted between December 2020 and September 2021 at five study sites in the US and UK (adult and pediatric emergency departments or urgent care clinics) with testing performed by personnel representative of the intended users (non-laboratory professionals). Several analytes that were not circulating during the COVID-19 pandemic were supplemented with archived specimens of known analyte composition. Performance was determined for both sample types by comparison to FDA cleared multiplex PCR tests or culture and PCR followed by sequencing of isolates (Streptococcus from throat swabs). Results A total of 1131 NPS and 452 TS prospectively collected specimens and 542 NPS and 128 TS archived specimens were tested with the BioFire R/ST Panel. For NPS specimens (prospective and archived) overall positive percent agreement (PPA) was 98.7% and negative percent agreement (NPA) was 99.1%, and for TS specimens (prospective and archived) overall PPA was 95.9% and NPA was 99.2%. Conclusion The BioFire R/ST Panel is a sensitive, specific, and robust test for rapid detection of a wide range of organisms in NPS and TS specimens in the near-patient setting. This test is expected to aid in the timely diagnosis and appropriate management of pharyngitis and other respiratory infections. Data presented are from assays that have not been cleared or approved for diagnostic use. Disclosures Jeffrey Bastar, PhD, MSCI, bioMerieux: Employee|bioMerieux: Stocks/Bonds Ashley Ky, MLS(ASCP), bioMérieux: Employee|bioMérieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Hana Bay, BS, Biomerieux: Employee|Biomerieux: Stocks/Bonds Daria Drobysheva, PhD, bioMerieux: Employee Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.

Background The role of nasopharyngeal bacteria in respiratory syncytial virus (RSV) disease has been underestimated. We measured the frequency and burden of respiratory bacteria in the upper respiratory tract of infants with RSV infection over 7 respiratory seasons, and their impact on clinical outcomes. Methods Children Results S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; P Conclusions Nasopharyngeal codetection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8–16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Background and ObjectivesEpilepsy and seizures represent a frequent cause of emergency department (ED) visits for patients. By implementing quality improvement (QI) methodology, we planned to decrease ED visits for children and adolescents with epilepsy.MethodsIn 2016, a multidisciplinary team was created to implement QI methodology to address ED visits for patients with epilepsy. Based on previous successes, further ED visit reduction was deemed possible. Our aim statement was to decrease the number of ED visits, per 1000 established patients with epilepsy, from 13.03 to 11.6, by December 2019 and sustain for 1 year.ResultsWe successfully decreased ED visits for seizure-related care in patients with epilepsy from 13.03% to 10.2% per 1,000 patients, which resulted in a centerline shift.DiscussionUsing QI methodology, we improved the outcome measure of decreasing ED visits for children with epilepsy. Implementations of these interventions can be considered at other institutions that may lead to similar results.

Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI.

Objectives As mandated reporters of suspected abuse, physicians must consider abuse when a child dies unexpectedly. Subsequently, a coroner or medical examiner determines the manner of death (MOD) and cause of death (COD). Accurate diagnoses and determinations are important for social safety and justice. This study described discrepancies between physicians' and coroners' findings in cases of fatal suspected physical child abuse. Methods This study was a single-institution, retrospective review. All children 6 years or younger who died in a pediatric emergency department from October 2006 to January 2013 with a coroner report were included in this study. Coroner reports, MODs, and CODs were reviewed. Skeletal survey results were compared with coroners' findings. Results One hundred twenty-nine children were included. The MODs included the following: undetermined, 63 (49%); accident, 32 (25%); natural, 31 (24%); and homicide, 3 (2%). Thirty-three (26%) of the 129 patients had abuse suspected at the time of death in the emergency department; in this subset, MODs were as follows: undetermined, 16 (48%); accident, 8 (24%); natural, 6 (18%); and homicide, 3 (9%). Sudden infant death syndrome or sudden unexpected death was the most common COD in all children (68, 55%). Skeletal surveys were positive in 12 children with 29 fractures identified; 8 (28%) of the 29 fractures were corroborated on autopsy findings. Of the 12 children with positive skeletal survey findings, only 1 was ruled a homicide. Conclusions We found discrepancies between coroner determination of homicide and abuse suspected by physicians, especially among children with fractures. Improved communication between agencies in cases of fatal child abuse is needed.

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis.To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results.Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results.Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count4 × 103 cells/mm3 and procalcitonin0.5 ng/mL.Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

Objective The study sought to present normative and psychometric data and reliable change formulas for the Health and Behavior Inventory (HBI), a postconcussive symptom rating scale embedded in the Child Sport Concussion Assessment Tool 5th edition (Child SCAT5). Design Prospective cohort study with longitudinal follow-up. Setting Pediatric emergency departments (EDs). Participants As part of 3 studies conducted in the United States and Canada between 2001 and 2019, 450 children aged 8 to 16 years with mild orthopedic injuries were recruited during ED visits and assessed postacutely (M = 9.38 days, SD = 3.31) and 1 month and 3 months postinjury. Independent variables were rater (child vs parent), sex, and age at injury. Main outcome measure HBI ratings. Methods Children and parents rated children's symptoms at each time point; parents also rated children's preinjury symptoms retrospectively. Normative data (mean, SD, skewness, kurtosis, and percentiles) were computed for child and parent ratings. Internal consistency was assessed using Cronbach alpha (α), and test-retest reliability and interrater agreement were assessed with intraclass correlations (ICCs). Reliable change formulas were computed using linear regression and mixed models. Results HBI ratings were positively skewed. Mean ratings and percentiles were stable over time. Child and parent ratings demonstrated good-to-excellent internal consistency (α 0.76-0.94) and moderate-to-good test-retest reliability (ICC 0.51-0.76 between adjacent assessments). However, parent-child agreement was poor to moderate (ICC 0.31-0.69). Conclusions The HBI demonstrates acceptable normative and psychometric characteristics. Modest parent-child agreement highlights the importance of multiple informants when assessing postconcussive symptoms. The results will facilitate the use of the HBI in research and clinical practice.

Objective To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. Setting Emergency department or concussion clinics. Participants Youth aged 11 to 17 years with physician-confirmed concussion. Design Prospective cohort with repeated measures. Main measures Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. Results A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). Conclusion Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

Objective This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. Methods Children ( N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments Results PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p Conclusions Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Background Ileocolic intussusception requires timely reduction to prevent complications. Reduction can be distressing. Sedation is uncommon due to controversial beliefs surrounding an increased risk of perforation. Analgesia and sedation practices for children undergoing reduction of intussusception remain largely unknown. Objectives To characterize global practice patterns of analgesia and sedation for reduction of intussusception. Design/Methods We conducted a global, cross-sectional study involving 84 centres in 14 countries. We included children 4 to 48 months with a sonographic or radiographic diagnosis of ileocolic intussusception and attempted reduction between January 1, 2017, and December 31, 2019. The primary and secondary outcomes were analgesia and sedation, respectively, prior to reduction. An a priori explanatory analysis was performed to explore the association of sedation with (i) adverse events, (ii) perforation, and (iii) failed reduction. Results We included 3203 children [2054/3203 (64.1%)] males, with median (IQR) age of 17 (9,27) months. Suspected abdominal pain was present in 2283/3187 (71.6%) children. At triage, a pain assessment tool was documented in 1859/3112 (59.7%) and analgesia was administered to 305/3171 (9.6%) children. After triage, pain was reassessed in 1448/3169 (45.7%) and analgesia was administered to 552/3158 (17.5%) children. Prior to reduction, 550/3161 (17.4%) children were sedated. Non-opioid and opioid analgesia were administered to 183/2945 (6.2%) and 560/3134 (17.9%), respectively. Reduction was performed using air enema in 2372/3184 (74.5%) children and 2700/3184 (84.8%) of all reductions were successful. Reduction related adverse events [65/3166 (2.1%)] were reported in 59 patients, most commonly vomiting [31/3166 (1.0%)] and perforation [13/3166 (0.4%)]. In the bivariate analyses, sedation was not associated with an increased odds of adverse events [OR: 1.1; 95% CI: 0.6-2.1; p=0.79] or perforation [OR: 2.1; 95% CI: 0.7-6.9; p=0.21]. Sedation was associated with an increased odds of failed reduction [OR: 1.4; 95% CI: 1.1-1.7; p=0.01], but this became non-significant in the multivariable analysis [OR: 1.1; 95% CI: 0.8-1.6; p=0.53] after adjusting for age and premorbid gastrointestinal anomaly. Conclusion Although more than 2/3 of children with intussusception present with pain, less than 10% were administered analgesia at triage. Prior to reduction, analgesia or sedation was administered to less than 1/5 of children. Adverse events, including perforation were uncommon. Sedation was not associated with adverse events or an increased odds of failed reduction in the adjusted analysis. Our findings suggest that analgesia should be considered in children with suspected abdominal pain and sedation should be routinely considered for children undergoing reduction of intussusception.

Objectives: An increasing number of children are living with complex chronic diseases (CCDs) due to medical advances. Despite a need for code status discussions (CSDs), there is great variability i...

Objective A multidisciplinary quality improvement (QI) team was established to conduct analysis of data for prescribed seizure rescue medication doses from January 2013 to December 2015 to identify and improve inappropriately low dose prescriptions. The QI team identified areas of focus for improvement opportunities and developed the project objective based on the 2017 American Academy of Neurology (AAN) and Child Neurology Society (CNS) quality measure. Methods Within a freestanding children's hospital, the QI team developed key drivers and implemented interventions, such as the midazolam prefilled syringe program with use of standardized dosing, electronic chart tools, monthly pharmacy review of all underdosed prescriptions, and provider and nursing education. The team created an automated monthly report to monitor prescribed seizure rescue medication dosing compliance. The year 2015 was used as the preliminary data baseline period with an average noncompliance rate of 3.5%. Results From January 2016 to December 2019, the team has decreased and sustained the noncompliance rate to an average of 0.38%. The data for the project included 12,975 seizure rescue medication prescribed by a neurology provider from January 2015 to December 2019. Compliance with properly dosed diazepam orders continues to be the largest area of opportunity. The data demonstrated a centerline shift in January 2019, moving the baseline average of 7.2% noncompliance to the current average rate of 0.22%. In comparison, underdosed midazolam orders occurred at an average rate of 0.037% in the same timeframe. Significance Using quality improvement methodologies, the team successfully and substantially decreased provider prescribed and signed underdosed rescue medication orders by an average of 89%. This QI project demonstrates successful implementation and improvement addressing the AAN/CNS quality measure of proper rescue seizure treatment dosing.

STUDY OBJECTIVE: The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network. METHODS: We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years. RESULTS: A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P.05 for both). CONCLUSION: Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.

Studies of brain morphometry may illuminate the effects of pediatric mild traumatic brain injury (TBI; e.g., concussion). However, no published studies have examined cortical thickness in the early injury phases of pediatric mild TBI using an appropriate comparison group. The current study used an automated approach (i.e., FreeSurfer) to determine whether cortical thickness differed in children following a mild TBI or a mild orthopedic injury (OI), and to examine whether post-acute cortical thickness predicted post-acute and chronic post-concussive symptoms (PCS). Children ages 8.00-16.99 years with mild TBI (n = 136) or OI (n = 70) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (3–24 days post-injury) assessment, which included a 3 Tesla MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Cortical thickness was estimated using FreeSurfer. Linear mixed effects and multi-variable negative binomial regression models were used to test study aims, with false discovery rate (FDR) correction for multiple comparisons. Groups differed significantly on left parietal cortical thickness (TBI > OI) after FDR correction. Cortical thickness also varied by brain subregion and age, but not sex. Groups differed significantly on PCS post-acutely (TBI > OI), but not at 3 or 6 months. Right frontal thickness was positively related to post-acute PCS in both groups. Right cingulum thickness predicted chronic PCS in the OI group only. Results highlight the complexity of predicting outcomes of pediatric mild TBI from post-acute neuroimaging biomarkers.

Objective This study was aimed to explore the intersection between organizational environment, workflow, and technology in pediatric emergency departments (EDs) and how these factors impact antibiotic prescribing decisions. Methods Semistructured interviews with 17 providers (1 fellow and 16 attending faculty), and observations of 21 providers (1 physician assistant, 5 residents, 3 fellows, and 12 attendings) were conducted at three EDs in the United States. We analyzed interview transcripts and observation notes using thematic analysis. Results Seven themes relating to antibiotic prescribing decisions emerged as follows: (1) professional judgement, (2) cognition as a critical individual resource, (3) decision support as a critical organizational resource, (4) patient management with imperfect information, (5) information-seeking as a primary task, (6) time management, and (7) broad process boundaries of antibiotic prescribing. Discussion The emerging interrelated themes identified in this study can be used as a blueprint to design, implement, and evaluate clinical decision support (CDS) systems that support antibiotic prescribing in EDs. The process boundaries of antibiotic prescribing are broader than the current boundaries covered by existing CDS systems. Incongruities between process boundaries and CDS can under-support clinicians and lead to suboptimal decisions. We identified two incongruities: (1) the lack of acknowledgment that the process boundaries go beyond the physical boundaries of the ED and (2) the lack of integration of information sources (e.g., accessibility to prior cultures on an individual patient outside of the organization). Conclusion Significant opportunities exist to improve appropriateness of antibiotic prescribing by considering process boundaries in the design, implementation, and evaluation of CDS systems.

Objectives In children with sickle cell disease treated for vasoocclusive episodes (VOEs), it is unknown if the temperature of infused fluids impacts clinical outcomes. We compared infusions of warmed and nonwarmed saline for treatment of VOE. We also assessed the tolerability and feasibility of infusing warmed saline in patients with VOEs. Methods Patients aged 4 to 21 years with sickle cell disease presenting to the emergency department with VOE were randomized to infusions of warmed (37.5°C, experimental arm) versus nonwarmed (22°C-24°C, controls) saline. Intravenous opioids were administered according to previously established guidelines. We compared hospital admission rates, pain scores, disposition times, dosages of opioid, and comfort. Results Eighty of 92 visits were eligible (40 per arm). The mean age of enrollees was 14 years, and 53% were female. Hospital admission rates were comparable (63% experimental arm and 55% control arm, P = 0.5). Pain score reduction (-2.9 and -2.6, P = 0.52), median morphine equivalents (0.23 mg/kg and 0.25 mg/kg, P = 0.58), and mean treatment-to-disposition times (158 minutes and 155 minutes, P = 0.85) were also similar. Global comfort was higher in children who received warmed saline (4 vs 3, P = 0.01). There were no adverse events reported in patients who received warmed saline. Conclusions It is feasible and tolerable to infuse warmed saline for the treatment of VOE, and it is well tolerated. Patient comfort was higher in those patients who received warmed saline, but there was no improvement in admission rates, disposition times, pain scores, and opioid dosages.

Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA.We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018. For pathogen detection, nasopharyngeal swabs were collected from all subjects. Blood and pleural fluid cultures were available per standard of care.We enrolled a convenience sample of 441 patients: 380 hospitalized and 61 outpatients. Tachypnea and radiologic findings of consolidation and pleural effusion were more frequent among inpatients than outpatients. A pathogen was detected in 64.6% of patients: viruses in 55.6%, atypical bacteria in 8.8% and pyogenic bacteria in 4.3%. Eighteen (4.1%) patients had both viruses and bacteria detected. Rhinovirus/enterovirus (RV; 18.6%) and respiratory syncytial virus (RSV; 16.8%) were the viruses most frequently detected, and Mycoplasma pneumoniae (8.2%) and Streptococcus pneumoniae (2.3%) were the most common bacteria. Except for S. pneumoniae, which was identified more frequently in inpatients, there were no significant differences between inpatients and outpatients in the proportions of children with specific pathogens detected.Rhinovirus/enterovirus and RSV among viruses and M. pneumoniae and S. pneumoniae among bacteria were the most common pathogens detected in children with CAP. Tachypnea and chest radiographs with consolidation and/or pleural effusion were associated with hospitalization.

Objectives To determine whether the use of dry-erase boards for communicating the plan of care of children evaluated in the pediatric emergency department (PED) improves the family experience of care. Methods Dry-erase boards were mounted at eye level in patient examination rooms. The study was conducted during a 4-week period during which physicians were instructed to use the boards on alternating weeks. During the 2 intervention weeks, they were instructed to write their name and plan of care in addition to their standard verbal communication. A questionnaire was administered to a convenience sample of caregivers that measured their perceptions of physician listening skills, time spent with the physician, their understanding of the care plan, their willingness to ask questions, likelihood to recommend the PED, and overall physician care. Differences between intervention and nonintervention weeks were analyzed using adjusted multivariable modeling taking into account clustered observations within physician. Results Surveys were completed by 672 caregivers. There were no significant differences in reported experience of care between the intervention and nonintervention weeks. During the intervention weeks, 59% of caregivers recalled use of the dry-erase boards, whereas 10% of caregivers recalled use during nonintervention weeks. Caregivers who recalled the use of dry-erase boards were more likely to report better physician listening skills, better understanding of the plan of care, and higher overall physician ratings. Conclusions Recommending use of dry-erase boards in pediatric emergency department rooms did not increase overall measures of experience of care, although patients who recalled dry-erase board use did report higher performance. Further study could explore how to effectively and efficiently use these boards.

BACKGROUND Alcohol and cannabis use frequently co-occur, which can result in problems from social and academic impairment to dependence (i.e., alcohol use disorder [AUD] and/or cannabis use disorder [CUD]). The Emergency Department (ED) is an excellent site to identify adolescents with alcohol misuse, conduct a brief intervention, and refer to treatment; however, given time constraints, alcohol use may be the only substance assessed due to its common role in unintentional injury. The current study, a secondary data analysis, assessed the relationship between adolescent alcohol and cannabis use by examining the National Institute of Alcohol Abuse and Alcoholism (NIAAA) two question screen's (2QS) ability to predict future CUD at one, two, and three years post-ED visit. Methods: At baseline, data was collected via tablet self-report surveys from medically and behaviorally stable adolescents 12-17 years old (n = 1,689) treated in 16 pediatric EDs for non-life-threatening injury, illness, or mental health condition. Follow-up surveys were completed via telephone or web-based survey. Logistic regression compared CUD diagnosis odds at one, two, or three-year follow-up between levels constituting a single-level change in baseline risk categorization on the NIAAA 2QS (nondrinker versus low-risk, low- versus moderate-risk, moderate- versus high-risk). Receiver operating characteristic curve methods examined the predictive ability of the baseline NIAAA 2QS cut points for CUD at one, two, or three-year follow-up. Results: Adolescents with low alcohol risk had significantly higher rates of CUD versus nondrinkers (OR range: 1.94-2.76, p < .0001). For low and moderate alcohol risk, there was no difference in CUD rates (OR range: 1.00-1.08). CUD rates were higher in adolescents with high alcohol risk versus moderate risk (OR range: 2.39-4.81, p < .05). Conclusions: Even low levels of baseline alcohol use are associated with risk for a later CUD. The NIAAA 2QS is an appropriate assessment measure to gauge risk for future cannabis use.

Vaso-occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four-hundred charts of children age 3-21 years with SCA/VOE receiving parenteral opioids at 20 high-volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin-SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation-to-ED-disposition was smaller in the NSB group (2.2 vs 3.0, P = .03), while admission rates were higher (71% vs 59%, P = .01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to >50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality.

Background To date, there is limited literature exploring the effectiveness of training staff for a clinical trial via high-fidelity simulations. This study was conducted to explore this educational modality for an emergency department (ED)–based clinical trial. Methods ED nurse educator–driven simulations were deployed for a clinical trial to train diverse ED staff and were described. An anonymous survey was then conducted to assess staff knowledge regarding the clinical trial and participation in trial simulations. Results Over 21 months, 13 seizure simulations were run with 97 participants. ED staff who attended a simulation were ∼3 times more likely to correctly answer survey questions about the clinical trial. The vast majority of simulation participants (95.8%) found them to be helpful. Conclusion Simulations provided lessons to improve the knowledge and operations of a clinical trial. Nursing staff was instrumental during simulations and in the development of site-specific processes. Future clinical trials that involve multidisciplinary groups and time-sensitive actions may benefit from this approach.

The pediatric emergency department (PED) represents an opportune time for alcohol and drug screening. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) recommends a two-question alcohol screen for adolescents as a predictor of alcohol and drug misuse.A multi-site PED study was conducted to determine the association between the NIAAA two-question alcohol screen and adolescent cannabis use disorders (CUD), cigarette smoking, and lifetime use of other drugs.Participants included 12-17-year olds (n = 4834) treated in one of 16 participating PEDs. An assessment battery, including the NIAAA two-question screen and other measures of alcohol, tobacco and drug use, was self-administered on a tablet computer.A diagnosis of CUD, lifetime tobacco use or lifetime drug use was predicted by any self-reported alcohol use in the past year, which indicates a classification of moderate risk for middle school ages and low risk for high school ages on the NIAAA two-question screen. Drinking was most strongly predictive of a CUD, somewhat weaker for lifetime tobacco use, and weakest for lifetime drug use. This same pattern held for high school and middle school students and was stronger for high school students over middle school students for all three categories. This association was also found across gender, ethnicity and race. The association was strongest for CUD for high school students, sensitivity 81.7% (95% CI, 77.0, 86.5) and specificity 70.4% (95% CI, 68.6, 72.1). Conclusions/Importance: A single question about past year alcohol use can provide valuable information about other substance use, particularly marijuana.

Background Ileocolic intussusception is a major cause for intestinal obstruction in early childhood. Reduction of intussusception, in the vast majority of institutions, is performed on awake children, without sedation. Objective The aim of this study was to report the course of the first patients who were sedated by emergency physicians for pneumatic reduction of intussusception (PRI). Methods We conducted a case series analysis of prospectively collected data on patients undergoing PRI, using a sedation recording tool. This tool uses standardized definitions from the Quebec guidelines for terminology and reporting adverse events in emergency medicine. Recording of time interval measurements and adverse events was performed by the emergency physician and nurse. Results Between February 2016 and March 2018, 11 males and 3 females, with a median age of 11 months (interquartile range [IQR] 6–20 months), underwent sedation for PRI by five attending pediatric emergency physicians. All of the reductions were successful and without complications. Eight patients received ketamine and propofol, 5 received ketamine, and 1 received ketamine and midazolam. Median times for the presedation phase, procedure, sedation, physiologic recovery and emergency department recovery were: 131 min (IQR 79–104 min), 10.5 min (IQR, 9–12 min), 21 min (IQR, 20–30 min), 25 min (IQR, 23–30 min), and 108 min (IQR, 82–161 min), respectively. Four respiratory adverse events that required intervention were recorded. All were effectively treated with airway repositioning, suctioning, oxygen administration, or bag-mask ventilation. Conclusions The first series of patients sedated for PRI by emergency physicians is reported. Our initial findings suggest the feasibility of emergency physician–administered sedation for PRI.

Background: Urinary tract infections (UTIs) are the most common serious bacterial infection in young febrile infants, and the urinalysis (UA) is an accurate screening test for emergency department (ED) evaluation. Precise estimates of risk of concomitant bacteremia and/or bacterial meningitis (invasive bacterial infections; IBI) in febrile infants ≤ 60 days have been based on presence of UTIs rather than positive UAs, and lack large prospective study. Objective: We sought to determine the prevalence of IBIs in febrile infants 0-28 …

Objective: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. Study design: We reviewed medical records of children 13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. Results: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children 26%. Conclusions: The HUS severity score was able to discriminate between high- and low-risk children

In 2016, the Cyber Grand Challenge (CGC) provided key foundations and motivations for navigating towards an autonomous cybersecurity approach. Since that time, novel strides have been made in the areas of static analysis, vulnerability discovery, patching, and exploit generation. However, a majority of these efforts have been focused on enterprise systems, leaving a gap in the Cyber-Physical System (CPS) domain. With the rise of connected infrastructure and the introduction of 5G communications, CPS are becoming more ingrained within present-day society. Due to a large amount of legacy software, and control of safety-critical actuation, CPS are and will continue to be a huge attack vector for our adversaries to remotely deploy devastating attacks against our country with low economic cost and at scale. To combat this threat, we propose the need to apply the most beneficial concepts from the CGC to create more secure and resilient CPS. In this paper, we introduce a CPS security assessment architecture RUCKUS for autonomously identifying and analyzing CPS firmware, identifying vulnerabilities, and developing exploits. Further, our approach considers how to integrate graph analytics to extrapolate findings to firmware at scale, allowing for measuring the potential widespread impact of attacks. Our architecture is demonstrated using an automotive case study, leveraging firmware from the most popular automotive and router manufacturers to assess the real-world potential impact of CPS attacks.

Objective Few prospective studies have assessed the occurrence of radiographic pneumonia in young febrile infants. We analyzed factors associated with radiographic pneumonias in febrile infants 60 days or younger evaluated in pediatric emergency departments. Study design We conducted a planned secondary analysis of a prospective cohort study within 26 emergency departments in a pediatric research network from 2008 to 2013. Febrile (≥38°C) infants 60 days or younger who received chest radiographs were included. Chest radiograph reports were categorized as "no," "possible," or "definite" pneumonia. We compared demographics, Yale Observation Scale scores (>10 implying ill appearance), laboratory markers, blood cultures, and viral testing among groups. Results Of 4778 infants, 1724 (36.1%) had chest radiographs performed; 2.7% (n = 46) had definite pneumonias, and 3.9% (n = 67) had possible pneumonias. Patients with definite (13/46 [28.3%]) or possible (15/67 [22.7%]) pneumonias more frequently had Yale Observation Scale score >10 compared with those without pneumonias (210/1611 [13.2%], P = 0.002) in univariable and multivariable analyses. Median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in the definite (WBC, 11.5 [interquartile range, 9.8-15.5]; ANC, 5.0 [3.2-7.6]; PCT, 0.4 [0.2-2.1]) versus no pneumonia (WBC, 10.0 [7.6-13.3]; ANC, 3.4 [2.1-5.4]; PCT, 0.2 [0.2-0.3]; WBC, P = 0.006; ANC, P = 0.002; PCT, P = 0.046) groups, but of unclear clinical significance. There were no cases of bacteremia in the definite pneumonia group. Viral infections were more frequent in groups with definite (25/38 [65.8%]) and possible (28/55 [50.9%]) pneumonias than no pneumonias (534/1185 [45.1%], P = 0.02). Conclusions Radiographic pneumonias were uncommon, often had viruses detected, and were associated with ill appearance, but few other predictors, in febrile infants 60 days or younger.

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a "safe and protective" immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children

Summary Background Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. Methods In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group ( 65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov , NCT01960075 . Findings Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged 65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41–62) of children, 44% (33–55) of adults, and 37% (19–59) of older adults; with fosphenytoin in 49% (38–61) of children, 46% (34–59) of adults, and 35% (17–59) of older adults; and with valproate in 52% (41–63) of children, 46% (34–58) of adults, and 47% (25–70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. Interpretation Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. Funding National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Author(s): Skains, Rachel M; Kuppermann, Nathan; Homme, James L; Kharbanda, Anupam B; Tzimenatos, Leah; Louie, Jeffrey P; Cohen, Daniel M; Nigrovic, Lise E; Westphal, Jessica J; Shah, Nilay D; Inselman, Jonathan; Ferrara, Michael J; Herrin, Jeph; Montori, Victor M; Hess, Erik P | Abstract: ObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint ] = 0.14) or physician trust more in parents with low health literacy (Pint = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; Pint = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; Pint = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.

Neutralizing antibodies to adeno-associated virus (AAV) vectors are highly prevalent in humans1,2, and block liver transduction3–5 and vector readministration6; thus, they represent a major limitation to in vivo gene therapy. Strategies aimed at overcoming anti-AAV antibodies are being studied7, which often involve immunosuppression and are not efficient in removing pre-existing antibodies. Imlifidase (IdeS) is an endopeptidase able to degrade circulating IgG that is currently being tested in transplant patients8. Here, we studied if IdeS could eliminate anti-AAV antibodies in the context of gene therapy. We showed efficient cleavage of pooled human IgG (intravenous Ig) in vitro upon endopeptidase treatment. In mice passively immunized with intravenous Ig, IdeS administration decreased anti-AAV antibodies and enabled efficient liver gene transfer. The approach was scaled up to nonhuman primates, a natural host for wild-type AAV. IdeS treatment before AAV vector infusion was safe and resulted in enhanced liver transduction, even in the setting of vector readministration. Finally, IdeS reduced anti-AAV antibody levels from human plasma samples in vitro, including plasma from prospective gene therapy trial participants. These results provide a potential solution to overcome pre-existing antibodies to AAV-based gene therapy. An IgG-cleaving endopeptidase can degrade circulating anti-adeno-associated virus antibodies in mice and nonhuman primates in vivo, as well as in human plasma in vitro, offering a potential solution for a major hurdle in gene therapy.

Introduction: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). Materials and methods: Children aged 8–16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8–15 years with mTBI or mild orthopedic injuries (OI). Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using AFQ (Automated Fiber Quantification), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although, there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy (FA) and decreases of axial, radial, and mean diffusivity (AD, RD, and MD, respectively) with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.

OBJECTIVES: In preparation for a clinical trial of therapeutic agents for children with moderate-to-severe blunt traumatic brain injuries (TBIs) in emergency departments (EDs), we conducted this feasibility study to 1) determine the number and clinical characteristics of eligible children, 2) determine the timing of patient and guardian arrival to the ED, and 3) describe the heterogeneity of TBIs on computed tomography (CT) scans. METHODS: We conducted a prospective observational study at 16 EDs of children ≤ 18 years of age presenting with blunt head trauma and Glasgow Coma Scale (GCS) scores of 3-12. We documented the number of potentially eligible patients, timing of patient and guardian arrival, patient demographics and clinical characteristics, severity of injuries, and cranial CT findings. RESULTS: We enrolled 295 eligible children at the 16 sites over 6 consecutive months. Cardiac arrest and non-survivable injuries were the most common characteristics that would exclude patients from a future trial. Most children arrived within 2 hours of injury, but most guardians did not arrive until 2-3 hours after the injury. There was a substantial range in types of TBIs, with subdural hemorrhages being the most common. CONCLUSION: Enrolling children with moderate-to-severe TBI into time sensitive clinical trials will require large numbers of sites, meticulous preparation and coordination, and will prove challenging to obtain informed consent given the timing of patient and guardian arrival. The Federal Exception from Informed Consent for Emergency Research will be an important consideration for enrolling these children. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved. Language: en

Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children < 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) < 3 months, (B) between 3 and 6 months, and (C) > 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children < 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-< 3, 3-6, and >6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (>3 months) than in inpatients (p< 0.01), while fever was more common in inpatients that outpatients (p< 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants >3 months, and higher RSV loads in children >6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

Shortage of personal protective equipment (PPE) for frontline healthcare workers managing the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a major, global challenge. In this pilot study, we describe a simulation-based method for evaluating the suitability and acceptability of an alternative biological isolation garment (BIG, a gown or a suit) for clinical use by emergency department (ED) personnel. Using a high-fidelity simulator, participants provided airway management according to the SARS-CoV-2 protocol. A nonvisible fluorescent marker was used as a surrogate marker of contamination. We assessed ultraviolet light visualization of the fluorescent marker after doffing and satisfaction with donning, use during simulation, and doffing. We found that after doffing, markers were not visualized on any of the participants and that the median satisfaction scores of the alternative and standard BIG (sBIG) were 4 [interquartile range (IQR) = 1-5] and 4 (IQR = 2-4), respectively. The results suggest the suitability and acceptability of the alternative BIG (aBIG) for use by ED personnel.