The i-gel® supraglottic airway device compared to endotracheal intubation as the initial prehospital advanced airway device: A natural experiment during the COVID-19 pandemic.

Objective: Unlike randomized controlled trials, practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings where there may be reluctance to adopt new practices. We present the results of a natural experiment that was driven by mandated COVID-19 pandemic-driven shift from endotracheal intubation (ETI) to the i-gel® supraglottic airway (SGA) as a primary advanced airway management device in the prehospital setting to reduce emergency medical services (EMS) personnel exposure to potentially infectious secretions. The objective was to compare first-pass success and timing to successful airway placement between ETI and the i-gel® SGA under extenuating circumstances. Methods: This pre/post study compared airway placement metrics in prehospital patients requiring advance airway management for non-trauma-related conditions. Data from EMS records were extracted over 2 years, 12 months pre-pandemic, and 12 months post-pandemic. During the pre-COVID-19 year, the EMS protocols utilized ETI as the primary advanced airway device (ETI group). Post-pandemic paramedics were mandated to utilize i-gel® SGA as the primary advanced airway device to reduce exposure to secretions (SGA group). Results: There were 199 adult patients, 83 (42%) in the ETI group and 116 (58%) in the SGA group. First-pass success was significantly higher with SGA 96% (92%-99%) than ETI 68% (57%-78%) with paramedics citing the inability to visualize the airway in 52% of ETI cases. Time to first-pass success was significantly shorter in the SGA group (5.9 min [5.1-6.7 min]) than in the ETI group (8.3 min [6.9-9.6 min]), as was time to overall successful placement at 6.0 min (5.1-6.8 min) versus 9.6 min (8.2-11.1 min), respectively. Multiple placement attempts were required in 26% of ETI cases and 1% of the SGA cases. There were no statistically significant differences in the number and types of complications between the cohorts. Return of spontaneous circulation (on/before emergency department [ED] arrival), mortality at 28 days, intensive care unit length of stay, or ventilator-free days between the groups were not statistically different between the groups. Conclusion: In this natural experiment, the SGA performed significantly better than ETI in first-pass airway device placement success and was significantly faster in achieving first-pass success, and overall airway placement, thus potentially reducing exposure to respiratory pathogens. Practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings and in systems with a low frequency of tracheal intubations.

Timing and causes of death to 1 year among children presenting to emergency departments.

BACKGROUND AND OBJECTIVES: A better characterization of deaths in children following emergency care is needed to inform timely interventions. This study aimed to describe the timing, location, and causes of death to 1 year among a cohort of injured and medically ill children. METHODS: We conducted a retrospective cohort study of children <18 years requiring emergency care in six states from January 1, 2012, through December 31, 2017, with follow-up through December 31, 2018, for patients who were not discharged from the emergency department (ED). In this cohort, 1-year mortality, time to death within 1 year, and causes of death were assessed from ED, inpatient, and vital status records. RESULTS: There were 546,044 children during the 6-year period. The 1-year mortality rate was 2.2% (n = 1356) for injured children and 1.4% (n = 6687) for medically ill children. Matched death certificates were available for 861 (63.5%) of 1356 deaths in the injury cohort and for 4712 (70.5%) of 6687 deaths in the medical cohort. Among deaths in the injury cohort, 1274 (94.0%) occurred in the ED or hospital. The most common causes of death were motor vehicle collisions, firearm injuries, and pedestrian injuries. Among the 6687 deaths in the medical cohort, 5081 (76.0%) children died in the ED or hospital (primarily in the ED) and 1606 (24.0%) occurred after hospital discharge. The most common causes of death were sudden infant death syndrome, suffocation and drowning, and congenital conditions. CONCLUSIONS: The 1-year mortality of children presenting to an ED is 2.2% for injured children and 1.4% for medically ill children with most deaths occurring in the ED. Future interventional trials, quality improvement efforts, and health policy focused in the ED could have the potential to improve outcomes of pediatric patients.

Emergency Department Pediatric Readiness and Disparities in Mortality Based on Race and Ethnicity.

Importance: Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. Objective: To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. Design, Setting, and Participants: This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. Exposure: Hospitalization for acute medical emergency or traumatic injury. Main Outcomes and Measures: The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. Results: The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. Conclusions and Relevance: In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Sex Differences in Neurological Emergencies Presenting to Multiple Urban Level 1 Trauma Centers.

Previous studies have suggested that there are sex differences in the treatment and outcome of neurological emergencies; however, research identifying the role these sex differences play in the management of neurological emergencies is lacking. More knowledge of the way sex factors into the pathophysiology of neurological emergencies will be helpful in improving outcomes for these patients. The aim of this cross-sectional study was to assess the prevalence and management of neurological emergencies while evaluating sex differences in the diagnosis and treatment of these emergencies. We analyzed a cohort of 530 adult patients from four level 1 trauma centers over a period of 4 weeks who had a chief complaint of a neurological emergency, including seizures, cerebrovascular events, headache disorders, traumatic brain injuries, and central nervous system infections. Among patients with neurological emergencies, a significantly lower proportion of female patients underwent neurosurgery and were admitted to the intensive care unit compared to male patients, but there were no significant differences between sexes in the time of symptom onset, type of hospital transportation, amount of neuroimaging performed, admission rates, hospital length of stay, and disposition from the emergency department. Although female patients were more likely to have a chief complaint of headache compared to traumatic injuries in male patients, this was not statistically significant. A significantly higher proportion of female patients had health insurance coverage than male patients.

Age and sex differences in blood product transfusions and mortality in trauma patients at a level I trauma center.

Objectives: Hemorrhage is a common complication of trauma. We evaluated age and sex differences in treatment with blood product transfusions and massive transfusions as well as in-hospital mortality following trauma at a Level 1 Trauma Center. Methods: This cross-sectional study evaluated trauma data from a Level 1 trauma center registry from January 2013 to December 2017. The primary outcome was amount of blood products (packed red blood cells (PRBCs), plasma, platelets), and massive transfusion (MT) by biological sex and by age group: 16-24 (youth), 25-59 (middle age), and >=60 (older age) The secondary outcome was in-hospital mortality to hospital discharge. Results: There were 13596 trauma patients in the registry, mean age was 48 years, 4589 (34%) female and 9007 (66%) male, and median ISS of 9. Male patients received significantly more PRBC transfusions than female patients within 4-hours 6.6% vs 4.4%, and 24-hours 6.7% vs 4.5% respectively. Older patients received significantly fewer PRBC transfusions within 4-hours and 24-hours than their younger counterparts, with 6.9% in the youth group, 6.8% in the middle age group, and 3.9% in the older group (p<0.001). When adjusted for injury severity, the odds of receiving a blood transfusion within 4 hours of injury was significantly lower in older females. Using multivariate analysis, predictors of mortality included (in order of significance) injury severity, older age, transfusion within 4 hours of injury, penetrating trauma, and male sex. Conclusion: In this large trauma cohort, older female trauma patients were less likely to receive blood products compared to younger females and to their older male counterparts, even after adjusting for injury severity. Predictors of mortality included injury severity, older age, early transfusion, penetrating trauma, and male sex. Following trauma, older women appear vulnerable to undertreatment. Further study is needed to determine the reasons for these differences and their impact on patient outcomes.

Sex differences in time course and diagnostic accuracy of GFAP and UCH-L1 in trauma patients with mild traumatic brain injury.

Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers' diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.

Does a change in end-tidal carbon dioxide level predict high altitude mountain sickness?

Background: It is postulated that lack of hypoxic ventilatory response is a predictor for AMS. End-tidal carbon dioxide (ETCO2) is an accurate, noninvasive surrogate measure of ventilation. Objectives: We sought to determine if changes in baseline ETCO2 predicts the development of AMS. Methods: This prospective cohort study took place in three separate high-altitude hiking treks. Subjects included a convenience sample of hikers. Predictor variable was change in ETCO2 levels and outcome variable was AMS. Measurements of ETCO2 levels were obtained at the base and repeated daily at various elevations and the summit of each hike. Concurrently, hikers were scored for AMS by a trained investigator. We utilized correlation coefficients and developed a linear regression model for analysis. Results: 21 subjects in 3 separate hikes participated: 10 ascended to 19,341 ft over 7 days, 6 ascended to 8900 ft in 1 day, and 4 ascended to 11,006 ft in 1 day. Mean age was 40 years, 67% were males, mean daily elevation gain was 2150 ft, and 5 hikers developed AMS. The correlation coefficients for ETCO2 and development of AMS were -0.46 (95%CI -0.33 to -0.57), and -0.77 (95%CI -0.71 to -0.83) for ETCO2 and altitude. ETCO2 predicted the development of symptoms better than the elevation with AUCs of 0.90 (95%CI 0.81-0.99) versus 0.64 (95%CI 0.45-0.83). An ETCO2 measurement of ≤22 mmHg was 100% sensitive and 60% specific for predicting AMS. Conclusions: ETCO2 was strongly correlated with altitude and moderately correlated with AMS and it was a better predictor than altitude.

End-tidal carbon dioxide measured at emergency department triage outperforms standard triage vital signs in predicting in-hospital mortality and intensive care unit admission.

OBJECTIVES: This study assessed the ability of end-tidal carbon dioxide (ETCO2 ) in predicting in-hospital mortality and intensive care unit (ICU) admission compared to standard vital signs at ED triage as well as comparing to measures of metabolic acidosis. METHODS: This prospective study enrolled adult patients presenting to the ED of a tertiary care Level I trauma center over 30 months. Patients had standard vital signs measured along with exhaled ETCO2 at triage. Outcome measures included in-hospital mortality; ICU admission; and correlations with lactate, sodium bicarbonate (HCO3 ), and anion gap. RESULTS: There were 1136 patients enrolled and 1091 patients with outcome data available. There were 26 (2.4%) patients who did not survive to hospital discharge. Mean ETCO2 levels were 34 (33-34) in survivors and 22 (18-26) nonsurvivors (p < 0.001). The area under the curve (AUC) for predicting in-hospital mortality for ETCO2 was 0.82 (0.72-0.91). In comparison the AUC for temperature was 0.55 (0.42-0.68), respiratory rate (RR) 0.59 (0.46-0.73), systolic blood pressure (SBP) 0.77 (0.67-0.86), diastolic blood pressure (DBP) 0.70 (0.59-0.81), heart rate (HR) 0.76 (0.66-0.85), and oxygen saturation (SpO2 ) 0.53 (0.40-0.67). There were 64 (6%) patients admitted to the ICU, and the ETCO2 AUC for predicting ICU admission was 0.75 (0.67-0.80). In comparison the AUC for temperature was 0.51, RR 0.56, SBP 0.64, DBP 0.63, HR 0.66, and SpO2 0.53. Correlations between expired ETCO2 and serum lactate, anion gap, and HCO3 were rho = -0.25 (p < 0.001), rho = -0.20 (p < 0.001), and rho = 0.330 (p < 0.001), respectively. CONCLUSIONS: ETCO2 was a better predictor of in-hospital mortality and ICU admission than the standard vital signs at ED triage. ETCO2 correlated significantly with measures of metabolic acidosis.

Is Lateral Decubitus or Upright Positioning Optimal for Lumbar Puncture Success in a Teaching Hospital?

BACKGROUND: Lumbar puncture is a common procedure performed by emergency physicians and trainees. The optimal patient positioning for lumbar puncture procedures has not been studied adequately. OBJECTIVES: We performed a prospective randomized study in an urban, level I academic trauma center. Patients of all ages were included. Patients were randomized to either lateral decubitus or upright positioning. Patient demographic characteristics, level of physician training and experience, number of needle insertions and redirections, need for repositioning, alternative operator use, and laboratory results of the cerebrospinal fluid were recorded. We compared the success rate of each position as our primary outcome measure. We also evaluated number of needle insertions and re-directions and success rates based on experience and patient age. RESULTS: A total of 116 patients were enrolled, with 55 patients assigned to lateral decubitus and 61 to upright position for initial lumbar puncture attempt. Spinal fluid was obtained successfully in 47 of the lateral decubitus group (85.5%; 95% CI 73.8-92.4%) vs. 49 (80.3%; 95% CI 68.7-88.4%) in the upright assignment group. Comparable results were also obtained for first-pass success, number of failures, and number of bloody taps. Postgraduate year 2 residents or those with 31-50 previous lumbar punctures had the highest success rates at 94.3% (95% CI 81.2-98.4%) and 90.3% (95% CI 75.1-96.7%), respectively. CONCLUSIONS: Lateral decubitus and upright positioning for emergency lumbar puncture yielded equal success rates in emergency physicians and trainees.

Intranasal Fentanyl to Reduce Pain and Improve Oral Intake in the Management of Children With Painful Infectious Mouth Lesions.

OBJECTIVES: Painful infectious mouth conditions such as herpangina, hand-foot-and-mouth disease, and herpetic gingivostomatitis can cause pain, dehydration, and hospitalization in young children. Treatment for these conditions is generally supportive and directed toward pain relief from ulcerative lesions, thus facilitating oral intake, and preventing dehydration. Attempts at oral therapy at home and in the emergency department are often refused and immediately spit back out. This study evaluated the efficacy of intranasal fentanyl (INF) compared with a commonly used oral (PO) acetaminophen/hydrocodone formulation for the treatment of children with painful infectious mouth conditions. METHODS: This study was a prospective, nonblinded, randomized controlled noninferiority trial conducted in an academic tertiary care pediatric emergency department. The study enrolled children between the ages of 6 months and 18 years with painful infectious mouth lesions and poor oral intake. Patients were randomized to receive either INF (1.5 µg/kg, intervention) or PO acetaminophen/hydrocodone (0.15 mg/kg, control) based on the dose of hydrocodone. The primary outcome was volume of fluid intake per body weight (in milliliters per kilogram) 60 minutes after analgesic administration. Secondary outcomes included pain scores using a validated visual assessment scale (VAS; 1, no pain; 10, worst pain), hydration score (VAS; 1, well hydrated; 4, very dehydrated), admission rate and overall satisfaction score (VAS; 1, worst; 7, best). A priori power analysis indicated that 34 patients would achieve an 81% power with an α value of 0.05. RESULTS: Of the 34 patients enrolled, 17 were randomized to INF and 17 to PO. The demographics between both groups were similar in age, weight, sex, and race. There were no significant differences in parental perception of pain ( P = 0.69) or hydration status ( P = 0.78). Oral fluid intake at 60 minutes was 20 mL/kg for INF versus 18 mL/kg for PO ( P = 0.53). Pain scores at 15 and 30 minutes were 1.7 versus 2.9 ( P = 0.09) and 0.6 versus 1.6 ( P = 0.59). Parental perceptions of pain and hydration status at 60 minutes were 2.2 versus 2.4 ( P = 0.77) and 1.7 versus 1.5 ( P = 0.37). Overall parental satisfaction was 6.4 for INF versus 6.5 for PO ( P = 0.71), and admission rate was 0 vs 12% ( P = 0.49). There were no adverse events such as respiratory, cardiac, or central nervous system depression in either group. CONCLUSIONS: Intranasal fentanyl seems to be a safe and effective alternative to acetaminophen with hydrocodone in reducing pain and improving hydration status in children with painful infectious mouth lesions and poor oral intake.

Concussion severity and functional outcome using biomarkers in children and youth involved in organized sports, recreational activities and non-sport related incidents.

This prospective multicenter study evaluated differences in concussion severity and functional outcome using glial and neuronal biomarkers glial Fibrillary Acidic (GFAP) and Ubiquitin C-terminal Hydrolase (UCH-L1) in children and youth involved in non-sport related trauma, organized sports, and recreational activities. Children and youth presenting to three Level 1 trauma centersfollowing blunt head trauma with a GCS 15 with a verified diagnosis of a concussion were enrolled within 6 hours of injury. Traumatic intracranial lesions on CT scan and functional outcome within 3 months of injury were evaluated. 131 children and youth with concussion were enrolled, 81 in the no sports group, 22 in the organized sports group and 28 in the recreational activities group. Median GFAP levels were 0.18, 0.07, and 0.39 ng/mL in the respective groups (p = 0.014). Median UCH-L1 levels were 0.18, 0.27, and 0.32 ng/mL respectively (p = 0.025). A CT scan of the head was performed in 110 (84%) patients. CT was positive in 5 (7%), 4 (27%), and 5 (20%) patients, respectively. The AUC for GFAP for detecting +CT was 0.84 (95%CI 0.75-0.93) and for UCH-L1 was 0.82 (95%CI 0.71-0.94). In those without CT lesions, elevations in UCH-L1 were significantly associated with unfavorable 3-month outcome. Concussions in the 3 groups were of similar severity and functional outcome. GFAP and UCH-L1 were both associated with severity of concussion and intracranial lesions, with the most elevated concentrations in recreational activities .

A Pilot Study Testing Intranasal Ketamine for the Treatment of Procedural Anxiety in Children Undergoing Laceration Repair.

Identifying non-invasive methods for anxiolysis is becoming increasingly important in the pediatric emergency department (ED). Few studies have examined the use of intranasal (IN) ketamine for procedural anxiolysis. We aim to evaluate if IN ketamine provides satisfactory anxiolysis for patients undergoing laceration repair based on anxiety and sedation scoring. We also evaluated the feasibility of using IN ketamine in future trials based on its tolerability and side-effects. A pilot study evaluating IN ketamine in the treatment of procedural anxiety for patients, 2 years and older, weighing 40 kg or less, presenting to the pediatric ED with lacerations. The need for anxiolysis was defined by an elevated modified-Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) score. Patients received 5 mg/kg of IN ketamine in addition to topical anesthesia, mYPAS-SF scoring before and during the procedure, sedation scoring, adverse events, vital signs, age, weight, laceration size and location, and satisfaction surveys were recorded. Twenty-five patients were enrolled, with mean age of 61 ± 29.2 months and mean weight of 21 ± 6.4 kg. Lacerations were located on the face, extremities, and groin with mean size of 2.1 cm. A decrease in anxiety levels was observed, from median m-YPAS-SF score of 66.7 (62.50-80.2) to 33.3 (27.09-52.00), p < 0.001. Among the patients, 92% (n = 23) were less anxious during the procedure. IN ketamine appears to be safe and well-tolerated with a positive impact on procedural anxiety. A dosage of 5 mg/kg is a reasonable starting point, as 80% of patients had appropriate anxiolysis.

Effect of Player Position on Serum Biomarkers during Participation in a Season of Collegiate Football.

This prospective cohort study examined the relationship between a panel of four serum proteomic biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], total Tau, and neurofilament light chain polypeptide [NF-L]) in 52 players from two different cohorts of male collegiate student football athletes from two different competitive seasons of Division I National Collegiate Athletic Association Football Bowl Subdivision. This study evaluated changes in biomarker concentrations (as indicators of brain injury) over the course of the playing season (pre- and post-season) and also assessed biomarker concentrations by player position using two different published classification systems. Player positions were divided into: 1) speed (quarterbacks, running backs, halfbacks, fullbacks, wide receivers, tight ends, defensive backs, safety, and linebackers) versus non-speed (offensive and defensive linemen), and 2) "Profile 1" (low frequency/high strain magnitudes positions including quarterbacks, wide receivers, and defensive backs), "Profile 2" (mid-range impact frequency and strain positions including linebackers, running backs, and tight ends), and "Profile 3" (high frequency/low strains positions including defensive and offensive linemen). There were significant increases in GFAP 39.3 to 45.6 pg/mL and NF-L 3.5 to 5.4 pg/mL over the course of the season (p < 0.001) despite only five players being diagnosed with concussion. UCH-L1 decreased significantly, and Tau was not significantly different. In both the pre- and post-season blood samples Tau and NF-L concentrations were significantly higher in speed versus non-speed positions. Concentrations of GFAP, Tau, and NF-L increased incrementally from "Profile 3," to "Profile 2" to "Profile 1" in the post-season. UCH-L1 did not. GFAP increased (by Profiles 3, 2, 1) from 42.4 to 49.6 to 78.2, respectively (p = 0.051). Tau increased from 0.37 to 0.61 to 0.67, respectively (p = 0.024). NF-L increased from 3.5 to 4.9 to 8.2, respectively (p < 0.001). Although GFAP and Tau showed similar patterns of elevations by profile in the pre-season samples they were not statistically significant. Only NF-L showed significant differences between profiles 2.7 to 3.1 to 4.2 in the pre-season (p = 0.042). GFAP, Tau, and NF-L concentrations were significantly associated with different playing positions with the highest concentrations in speed and "Profile 1" positions and the lowest concentrations were in non-speed and "Profile 3" positions. Blood-based biomarkers (GFAP, Tau, NF-L) provide an additional layer of injury quantification that could contribute to a better understanding of the risks of playing different positions.

Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2.

BACKGROUND: Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction. METHODS: Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations. RESULTS: The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (ß = 0.488 p = 0.000) as well as reduced cognitive independence (ß = - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (ß = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (ß = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (ß = 0.679, p = 0.010). CONCLUSIONS: Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.

Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality.

Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control ( p S o b e l p e r m ≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.

Association of Emergency Department Pediatric Readiness With Mortality to 1 Year Among Injured Children Treated at Trauma Centers.

IMPORTANCE: There is substantial variability among emergency departments (EDs) in their readiness to care for acutely ill and injured children, including US trauma centers. While high ED pediatric readiness is associated with improved in-hospital survival among children treated at trauma centers, the association between high ED readiness and long-term outcomes is unknown. OBJECTIVE: To evaluate the association between ED pediatric readiness and 1-year survival among injured children presenting to 146 trauma centers. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, injured children younger than 18 years who were residents of 8 states with admission, transfer to, or injury-related death at one of 146 participating trauma centers were included. Children cared for in and outside their state of residence were included. Subgroups included those with an Injury Severity Score (ISS) of 16 or more; any Abbreviated Injury Scale (AIS) score of 3 or more; head AIS score of 3 or more; and need for early critical resources. Data were collected from January 2012 to December 2017, with follow-up to December 2018. Data were analyzed from January to July 2021. EXPOSURES: ED pediatric readiness for the initial ED, measured using the weighted Pediatric Readiness Score (wPRS; range, 0-100) from the 2013 National Pediatric Readiness Project assessment. MAIN OUTCOMES AND MEASURES: Time to death within 365 days. RESULTS: Of 88 071 included children, 30 654 (34.8%) were female; 2114 (2.4%) were Asian, 16 730 (10.0%) were Black, and 49 496 (56.2%) were White; and the median (IQR) age was 11 (5-15) years. A total of 1974 (2.2%) died within 1 year of the initial ED visit, including 1768 (2.0%) during hospitalization and 206 (0.2%) following discharge. Subgroups included 12 752 (14.5%) with an ISS of 16 or more, 28 402 (32.2%) with any AIS score of 3 or more, 13 348 (15.2%) with a head AIS of 3 or more, and 9048 (10.3%) requiring early critical resources. Compared with EDs in the lowest wPRS quartile (32-69), children cared for in the highest wPRS quartile (95-100) had lower hazard of death to 1 year (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.56-0.88). Supplemental analyses removing early deaths had similar results (aHR, 0.75; 95% CI, 0.56-0.996). Findings were consistent across subgroups and multiple sensitivity analyses. CONCLUSIONS AND RELEVANCE: Children treated in high-readiness trauma center EDs after injury had a lower risk of death that persisted to 1 year. High ED readiness is independently associated with long-term survival among injured children.

Metabolomic response to collegiate football participation: Pre- and Post-season analysis.

Contact sports participation has been shown to have both beneficial and detrimental effects on health, however little is known about the metabolic sequelae of these effects. We aimed to identify metabolite alterations across a collegiate American football season. Serum was collected from 23 male collegiate football athletes before the athletic season (Pre) and after the last game (Post). Samples underwent nontargeted metabolomic profiling and 1131 metabolites were included for univariate, pathway enrichment, and multivariate analyses. Significant metabolites were assessed against head acceleration events (HAEs). 200 metabolites changed from Pre to Post (P < 0.05 and Q < 0.05); 160 had known identity and mapped to one of 57 pre-defined biological pathways. There was significant enrichment of metabolites belonging to five pathways (P < 0.05): xanthine, fatty acid (acyl choline), medium chain fatty acid, primary bile acid, and glycolysis, gluconeogenesis, and pyruvate metabolism. A set of 12 metabolites was sufficient to discriminate Pre from Post status, and changes in 64 of the 200 metabolites were also associated with HAEs (P < 0.05). In summary, the identified metabolites, and candidate pathways, argue there are metabolic consequences of both physical training and head impacts with football participation. These findings additionally identify a potential set of objective biomarkers of repetitive head injury.

Patient controlled analgesia for the management of acute pain in the emergency department: A systematic review.

BACKGROUND: The most common presenting complaint to the emergency department (ED) is pain. Several studies have shown that a large proportion of ED patients either receive no or sub-optimal analgesia. Patient-controlled analgesia (PCA) pumps used in the post-operative setting has shown to decrease total opioid consumption and has increased patient and nurse satisfaction. OBJECTIVE: The purpose of this systematic review was to evaluate clinical trials that have used PCAs in the ED setting, to evaluate safety and efficacy as well as patient and healthcare provider experience. METHODS: A search of PubMed, MEDLINE, and the Cochrane Database was conducted using the MESH search terms emergency department, patient-controlled analgesia, and acute pain up to September 2021. These terms were searched in all fields of publication and were limited to the English-language articles, clinical "human" studies, and studies that included the use of patient-controlled analgesia in the setting of the emergency department. RESULTS: The search initially identified 227 potentially relevant articles and a total of 10 studies met criteria for inclusion. ED use of PCA therapy was associated with increased patient satisfaction, decreased pain scores, and an overall increase in opioid consumption. CONCLUSION: The quality, the differences in study methods and outcome measures used, and heterogeneity of the studies performed to date do not provide adequate evidence to support its widespread use in the ED. Well-designed studies conducted in the ED are still needed to evaluate the ideal patient population to whom these PCAs may provide the most benefit as well as a robust cost-analysis to ensure feasibility of use in the future.

Decreases in Dorsal Cervical Spinal Cord White Matter Tract Integrity Are Associated with Elevated Levels of Serum MicroRNA Biomarkers in NCAA Division I Collegiate Football Players.

This prospective, controlled, observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers relative to findings on cervical spinal cord magnetic resonance imaging (MRI) in collegiate football players. There were 44 participants included in the study: 30 non-athlete control subjects and 14 male collegiate football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association. Diffuse tensor MRI and blood samples were acquired within the week before the athletic season began and within the week after the last game of the season. All miRNAs were significantly higher in athletes regardless of their fractional anisotropy (FA) values (p < 0.001), even those considered to be in the "normal" range of FA for white and gray matter integrity in the cervical spinal cord. miRNA biomarkers were most significantly correlated with FA of the white matter (WM) tracts of the dorsal (posterior) spinal cord; particularly, the fasciculus gracilis, fasciculus cuneatus, lateral corticospinal tract, rubrospinal tract, lateral reticulospinal tract, spinal lemniscus, and spinothalamic and -reticular tracts. Areas under the curve for miRNA biomarkers predicting lower FA of WM dorsal (posterior) cervical spinal tracts, therefore lower white matter integrity (connectivity), were miR-505* = 0.75 (0.54-0.96), miR-30d = 0.74 (0.52-0.95), and miR-92a = 0.75 (0.53-0.98). Should these findings be replicated in a larger cohort of athletes, these markers could potentially serve as measures of neuroimaging abnormalities in athletes at risk for concussion and subconcussive injuries to the cervical spinal cord.