Physician Assistant Gender Differences in Research, Professional Goals, and Perceptions of Support.

PURPOSE: The majority of Physician assistant (PA) educators are women, yet men proportionately publish more and advance further in academic rank. This study examined if research interest, promotion goals, and perceptions of institutional support differed between PA educators with different gender identities. METHODS: This is a subset analysis of a previously published cross-sectional study. PA programs were stratified by region and Carnegie classification and were sampled by a stratified random sampling method. PA faculty from selected programs were invited to participate in an anonymous survey. Data were analyzed to account for the stratified sample design. Means and proportions with associated 95% confidence intervals are described. RESULTS: There was a 51% response rate (N = 110). Sixty-three percent of respondents identified as female and 36% as male. Men had a mean of 5.67 (0.17, 11.16) career research articles and women had 1.56 (0.68, 2.44) articles. Fifteen percent (3.7%, 26.3%) of men were full professor compared to 4.3% (0, 9.1%) of women. When transitioning to a faculty role, 72.5% (58.4%, 86.6%) of men and 52.9% (41%, 64.7%) of women felt supported by their institution. Both genders valued promotion, but 80% (67.6%, 92.4%) of men reported having clear 5-year goals compared to 58.8% (46.6%, 71%) of women (P = .034). CONCLUSION: There was no statistical difference in publications between men and women in this study. Women felt less supported when transitioning to a faculty role compared to men. Both men and women valued promotion equally, but men reported working towards that goal more intentionally. This study found few consistent differences in the attitudes and behaviors towards scholarship between men and women.

The Effect of a Flipped Classroom Learning Model Versus Traditional Lecture Model on Resident's Knowledge Acquisition for Atraumatic Back Pain in the Emergency Department.

Objective: The effectiveness of lecture-based (LB) formats for residency education has recently been challenged as the gold standard. Studies suggest a flipped classroom (FC) lecture improves resident satisfaction, but evidence that showing improved knowledge acquisition is lacking. To determine whether the flipped classroom model improves knowledge acquisition compared to traditional LB model. Methods: Emergency medicine resident physicians at 2 academic programs were included in December 2019; at Sinai-Grace Hospital, a traditional lecture was the teaching method and at Detroit Receiving Hospital, FC was utilized. Residents completed prelecture and postlecture content tests. The primary outcome was change in test results (pretest to post-test). A noninferiority design comparing the changes between intervention and control groups was utilized (1-sided t-test, noninferiority margin of -0.5; 1-sided alpha = 0.05). Results: Results were available for 31 residents (17 controls and 14 interventions) out of 83 enrolled. There were 14 postgraduate year 1 (PGY-1), 9 PGY-2, and 8 PGY-3 residents. The mean difference in score was +0.71 (SD 1.38) and +0.77 (SD 1.48) for the FC and LB groups, respectively. This resulted in a mean difference between groups of -0.05 (lower bound of the upper 95% confidence interval -0.93 and therefore crossing the noninferiority margin of -0.05; P = .20). Conclusions: This study of resident education at 2 training programs was unable to demonstrate noninferiority of an FC format compared to standard lecture. Surprisingly, there was little improvement in test results after both teaching formats. Larger studies are needed to power results.

Pediatric hand sanitizer exposures reported to United States poison centers, 2017-2021.

INTRODUCTION: The COVID-19 pandemic increased demand for alcohol-based hand sanitizers. We aimed to describe the epidemiological trends in pediatric alcohol-based hand sanitizer cases reported to United States poison centers. We characterized clinically significant pediatric reports involving alcohol-based hand sanitizer products before and during the pandemic and methanol-containing hand sanitizers during the pandemic. METHODS: We included all single-substance cases involving alcohol-based hand sanitizers reported to the National Poison Data System among children ≤ 19 years from 1 January 2017 to 31 December 2021, and methanol-containing hand sanitizers from 23 June 2020 to 31 December 2021. Multiple product exposures and non-human exposures were excluded. Clinically significant outcomes included moderate or major effects or death. RESULTS: There were 95,718 alcohol-based hand sanitizer pediatric cases during the study period. Most (n = 89,521; 94%) were unintentional, occurred by ingestion (n = 89,879; 93.9%), occurred at home, and were managed at the exposure site (n = 89,774; 93.8%). Common symptoms were vomiting (n = 2,969; 3.1%), coughing (n = 1,102; 1.2%), ocular irritation (n = 1,244; 1.3%), and drowsiness (n = 981; 1.0%). Most children (n = 3,937; 66.2%) managed at a health care facility were treated and released; a minority were admitted (n = 527; 9.0%). Few children (n = 81; 1.4%) were admitted to the intensive care unit. The prevalence of clinically significant cases increased in 2020 and 2021, compared to 2017. Population-adjusted rates, by state, of alcohol-based hand sanitizer cases ranged from 280 to 2,700 per million children. Of the 540 reported cases involving methanol-containing hand sanitizers, the majority (n = 255) occurred in July 2020. Thirteen cases (2.4%) had clinically significant outcomes. The prevalence of clinically significant cases remained similar in 2020 and 2021 and exhibited lower prevalence compared to alcohol-based products. Population-adjusted rates, by state, ranged from fewer than 0.9 to 40 per million children. CONCLUSIONS: Clinically significant pediatric cases involving alcohol-based hand sanitizers increased during the pandemic and remained elevated in 2021. Cases involving methanol-containing products were less frequent. Our findings may inform heightened product quality control and regulatory oversight.

Barriers to Research: A National Survey of Physician Assistant Faculty.

INTRODUCTION: Success in research is a well-known challenge for physician assistant (PA) educators. Multiple barriers to research productivity have been proposed. This study examines potential barriers to PA research productivity. METHODS: Two hundred forty-seven PA programs were stratified by region and Carnegie classification, creating 28 strata. One program was randomly sampled from each stratum, and faculty from sampled programs were invited to participate (N = 214). An electronic survey was deployed via Qualtrics. Data were analyzed, accounting for the stratified survey sample design. Reported are proportions with associated 95% confidence intervals. RESULTS: Survey response rate was 53% (N = 114). The mean age was 46.7 years [44.5, 48.8 years] and 61% [52.4, 70.4] of respondents were female. Most respondents (53.5%; [44.2, 62.8]) were assistant professors and reported being employed as PA faculty for a mean of 12.4 years [11.2, 13.7 years]. Most respondents (68.1%; [59.7, 76.6]) reported 0 peer-reviewed research articles regardless of number of years as faculty. Few reported an interest in research (22.3%; [14.3, 29.9]) or felt internally driven to perform research (35.4%; [26.6, 44.2]). Most pursued a faculty position to teach (78.1%; [70.5, 85.7]) and spent little time pursuing research. Only 15.8% ([9.7, 21.9]) received research mentorship. DISCUSSION: This study identified lack of interest in research by faculty and lack of mentorship engagement as important factors underlying the profession's poor scholarly output. Initiatives to increase scholarship must first focus on fostering individual interest and increasing motivation.

Early echocardiographic assessment of cardiac function may be prognostically informative in unresuscitated patients with sepsis: A prospective observational study.

PURPOSE: The goal of this study was to explore the association cardiac function at Emergency Department (ED) presentation prior to the initiation of resuscitation, and its change at 3-hours, with adverse outcomes in patients with sepsis. METHODS: This was a prospective observational study of patients presenting to an urban ED with suspected sepsis. Patients had a point-of-care echocardiogram performed prior to initiation of resuscitation and again 3 hours later. Left-ventricular (LV) parameters recorded included e', and E/e', and ejection fraction (EF); right-ventricular (RV) function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Logistic and generalized linear regression were used to assess the association of echocardiographic parameters and ≥ 2-point increase in SOFA score at 24 hours (primary outcome) and 24-hours SOFA score and in-hospital mortality (secondary outcomes). RESULTS: For ΔSOFA ≥ 2 and 24-hour SOFA score, declining LVEF was associated with better outcomes in patients with greater baseline SOFA scores, but worse outcomes in patients with lower baseline scores. A similar relationship was found for ΔTAPSE at 3 hours. Reduced LVEF at presentation was associated with increased mortality after adjusting for ED SOFA score (odds-ratio (OR) 0.76 (CI 0.60-0.96). No relationship between diastolic parameters and outcomes was found. IVF administration was similar across ΔLVEF/TAPSE sub-groups. CONCLUSIONS: Our results suggest that early change in LV and RV systolic function are independently prognostic of sepsis illness severity at 24-hours. Further study is needed to determine if this information can be used to guide treatment and improve outcomes.

Increasing illness severity is associated with global myocardial dysfunction in the first 24 hours of sepsis admission.

BACKGROUND: Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission. METHODS: This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models. RESULTS: We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors. CONCLUSIONS: In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.

Multi-institutional intervention to improve patient perception of physician empathy in emergency care.

BACKGROUND: Physician empathy has been linked to increased patient satisfaction, improved patient outcomes and reduced provider burnout. Our objective was to test the effectiveness of an educational intervention to improve physician empathy and trust in the ED setting. METHODS: Physician participants from six emergency medicine residencies in the US were studied from 2018 to 2019 using a pre-post, quasi-experimental non-equivalent control group design with randomisation at the site level. Intervention participants at three hospitals received an educational intervention, guided by acognitivemap (the 'empathy circle'). This intervention was further emphasised by the use of motivational texts delivered to participants throughout the course of the study. The primary outcome was change in E patient perception of resident empathy (Jefferson scale of patient perception of physician empathy (JSPPPE) and Trust in Physicians Scale (Tips)) before (T1) and 3-6 months later (T2). RESULTS: Data were collected for 221 residents (postgraduate year 1-4.) In controls, the mean (SD) JSPPPE scores at T1 and T2 were 29 (3.8) and 29 (4.0), respectively (mean difference 0.8, 95% CI: -0.7 to 2.4, p=0.20, paired t-test). In the intervention group, the JSPPPE scores at T1 and T2 were 28 (4.4) and 30 (4.0), respectively (mean difference 1.4, 95% CI: 0.0 to 2.8, p=0.08). In controls, the TIPS at T1 was 65 (6.3) and T2 was 66 (5.8) (mean difference -0.1, 95% CI: -3.8 to 3.6, p=0.35). In the intervention group, the TIPS at T1 was 63 (6.9) and T2 was 66 (6.3) (mean difference 2.4, 95% CI: 0.2 to 4.5, p=0.007). Hierarchical regression revealed no effect of time×group interaction for JSPPPE (p=0.71) nor TIPS (p=0.16). CONCLUSION: An educational intervention with the addition of text reminders designed to increase empathic behaviour was not associated with a change in patient-perceived empathy, but was associated with a modest improvement in trust in physicians.

Do septic patients with reduced left ventricular ejection fraction require a low-volume resuscitative strategy?

BACKGROUND: Many clinicians are wary of administering 30 cc/kg of intravenous fluid (IVF) to septic patients with reduced left-ventricular ejection fraction (rLVEF), fearing volume overload. Prior studies have used history of heart failure, rather than LVEF measured at presentation, thereby potentially distorting the relationship between rLVEF, IVF, and adverse outcomes. Our goal was to assess the relationship between IVF volume and outcomes in patients with, versus without, rLVEF. METHODS: This was a prospective observational study performed at an urban Emergency Department (ED). Included patients were adults with suspected sepsis, defined as being treated for infection plus either systolic blood pressure <90 mm/Hg or lactate >2 mmol/L. All patients had LVEF assessed by ED echocardiogram, prior to receipt of >1 l IVF. MEASUREMENTS AND MAIN RESULTS: We enrolled 73 patients, of whom 33 had rLVEF, defined as <40%. Patients with rLVEF were older, had greater initial lactate, more ICU admission, and more vasopressor use. IVF volume was similar between LVEF groups at 3-h (2.2 (IQR 0.8) vs 2.0 (IQR 2.4) liters) while patients with rLVEF were more likely to achieve 30 cc/kg (61% (CI 44-75) vs 45% (CI 31-60). In the reduced versus not-reduced LVEF groups, hospital days, ICU days, and ventilator days were similar: 8 (IQR 7) vs 6.5 (8.5) days, 7 (IQR 7) vs 5 (4) days, and 4 (IQR 8) vs. 5 (10) days, respectively. CONCLUSIONS: Septic patients with rLVEF at presentation received similar volume of IVF as those without rLVEF, without an increase in adverse outcomes attributable to volume overload. While validation is needed, our results suggest that limiting IVF administration in the setting of rLVEF is not necessary.

Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury.

OBJECTIVE: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI). METHODS: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury. Plasma concentrations of GFAP and UCH-L1 were measured using i-STAT Alinity and TBI plasma cartridge and compared to acute TII on head CT scan. RESULTS: Of the 2011 subjects enrolled in ALERT-TBI, 1918 had valid CT scans and plasma specimens for testing and 1901 (99.1%) had GCS 13-15 (mTBI), for which the rapid test was intended. Among these subjects, the rapid test had a sensitivity of 0.958 (95% confidence interval [CI] = 0.906 to 0.982), specificity of 0.404 (95% CI = 0.382 to 0.427), negative predictive value of 0.993 (95% CI = 0.985 to 0.997), and positive predictive value of 0.098 (95% CI = 0.082 to 0.116) for acute TII. CONCLUSIONS: A rapid i-STAT-based test had high sensitivity for prediction of acute TII, comparable to lab-based platforms. The speed, portability, and high accuracy of this test may facilitate clinical adoption of brain biomarker testing as an aid to head CT decision making in EDs.

Percutaneous mechanical circulatory support and survival in patients resuscitated from Out of Hospital cardiac arrest: A study from the CARES surveillance group.

INTRODUCTION: Maintenance of cardiac function is required for successful outcome after out-of-hospital cardiac arrest (OHCA). Cardiac function can be augmented using a mechanical circulatory support (MCS) device, most commonly an intra-aortic balloon pump (IABP) or Impella®. OBJECTIVE: Our objective is to assess whether the use of a MCS is associated with improved survival in patients resuscitated from OHCA in Michigan. METHODS: We matched cardiac arrest cases during 2014-2017 from the Cardiac Arrest Registry to Enhance Survival (CARES) in Michigan and the Michigan Inpatient Database (MIDB) using probabilistic linkage. Multilevel logistic regression tested the association between MCS and the primary outcome of survival to hospital discharge. RESULTS: A total of 3790 CARES cases were matched with the MIDB and 1131 (29.8%) survived to hospital discharge. A small number were treated with MCS, an IABP (n = 183) or Impella® (n = 50). IABP use was associated with an improved outcome (unadjusted OR = 2.16, 95%CI [1.59, 2.93]), while use of Impella® approached significance (OR = 1.72, 95% CI [0.96, 3.06]). Use of MCS was associated with improved outcome (unadjusted OR = 2.07, 95% CI [1.55, 2.77]). In a multivariable model, MCS use was no longer independently associated with improved outcome (ORadj = 0.95, 95% CI [0.69, 1.31]). In the subset of subjects with cardiogenic shock (N = 725), MCS was associated with improved survival in univariate (unadjusted OR = 1.84, 95% CI [1.24, 2.73]) but not multi-variable modeling (ORadj = 1.14, 95% CI [0.74, 1.77]). CONCLUSION: Use of MCS was infrequent in patients resuscitated from OHCA and was not independently associated with improvement in post arrest survival after adjusting for covariates.

Substantial variation exists in post-cardiac arrest outcomes across Michigan hospitals.

AIM: Resuscitation from out of hospital cardiac arrest (OHCA) requires success across the entire chain of survival. Using a large state-wide registry, we characterized variation in clinical outcomes at hospital discharge in Michigan hospitals. METHODS: We utilized the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) and included adult OHCA subjects with return of spontaneous circulation (ROSC) from 2014 - 2017 that survived to hospital admission. 39 Michigan hospitals were included which managed >30 cases during the study period. Multilevel logistic regression, controlling for both subject characteristics and clustering of subjects within hospitals, assessed variation across hospitals in survival to hospital discharge and survival with cerebral performance category (CPC 1-2). RESULTS: There were 5,486 CARES subjects that survived to hospital admission, and 4,690 met inclusion for analysis. Of 39 included hospitals, median survival to discharge was 31.3% (range 12.5%-46.7%) and median survival to discharge with CPC 1-2 was 25.0% (range 5.2%-42.2%). We identified 12-fold variation in the utilization of TTM by hospital (median 47.9%, range 6.7%-80.0%) for all admitted subjects. Similarly, there was nearly an eight-fold variation in LHC for all post-arrest subjects (median 22.1%, range 5.4%-42.2%). In multivariable analyses, median adjusted survival to discharge was 26.9% (range 18.1%-42.1%) and median adjusted survival to discharge with CPC 1-2 was 21.3% (range 9.6%-32.1%). CONCLUSION: We observed substantial variation in clinical outcomes at discharge between Michigan hospitals, including a four-fold range of survival and eight-fold range of survival with CPC 1-2. This variation was ameliorated but still persisted in adjusted modeling. Variation in post arrest survival by hospital was not fully explained by available covariates, which suggests the possibility of improving post-arrest clinical outcomes at some hospitals via quality improvement activities.

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

Impact of Type of Healthcare Experience Before Physician Assistant School Admission on PANCE Score.

BACKGROUND: The physician assistant (PA) profession is based on a strong foundation of previous healthcare experience (HCE). It is unclear if HCE requiring more autonomous decision-making equates to a higher likelihood of success as a PA student. The purpose of this study was to determine if there is a correlation between type of pre-PA program HCE and success as determined by Physician Assistant National Certifying Examination (PANCE) scores. METHOD: This retrospective, observational study included PA students (single institution) who took the PANCE (n=188). Self-reported HCE was used to classify students into two broad groups based on locally derived criteria: Group A (less autonomy: such as medical assistant, nursing assistant) and Group B (more autonomy: paramedic, registered nurse, etc.). A linear mixed model was fit to assess the association between the primary outcome, PANCE, and HCE group. RESULTS: Group A (n=124) and Group B (n=64) had similar baseline PANCE scores (mean 497 vs 499; p=0.26). After adjusting for included predictors in the model, Group A was associated with lower PANCE scores but this did not reach statistical significance (p=0.7) and there was no association with number of HCE hours (p=0.77). CONCLUSION: There was no statistically significant association between type of pre-PA program HCE and PANCE.

Biomarkers May Predict Unfavorable Neurological Outcome after Mild Traumatic Brain Injury.

The objective of this study was to determine if initial or repeat measurements of serum concentrations of glial fibrillary acidic protein (GFAP) or ubiquitin C-terminal hydrolase L1 (UCH-L1) are predictive of an acute unfavorable neurological outcome in patients who present to the emergency department (ED) with brain injury and an initial Glasgow Coma Scale Score (GCS) of 14-15. This multi-center observational trial included brain-injured adults presenting to the ED, receiving a head computed tomography (CT) and venipuncture for biomarker concentration measurements within 6 h of injury. Subjects had repeat serum sampling and GCS scores every 4 h for the first 24 h, if available for assessment. We analyzed blood samples using an enzyme-linked immunosorbent assay approved by the Food and Drug Administration (FDA). Wilcoxin two-sample test was used to compare initial and repeat serum concentrations for both biomarkers between CT-positive patients who did not have an acute unfavorable neurological outcome and those patients who did. A total of 145 enrolled subjects had adequate data for analysis; 69 were CT-positive, 74 were CT-negative, and 2 were CT-inconclusive. Five subjects developed an acute unfavorable neurological outcome, defined as need for intracranial pressure monitoring, craniotomy, persistent neurological deficits, or death resulting from brain injury. Initial median serum concentrations of GFAP and UCH-L1 (obtained <6 h from injury) were significantly greater in CT-positive patients who had an acute unfavorable neurological outcome than in CT-positive patients who did not (GFAP: 5237 pg/mL [IQR 4511, 8180] versus 283.5 pg/mL [IQR 107, 1123]; p = 0.026; UCH-L1: 3329 pg/mL [QR 1423, 5010] versus 679.5 pg/mL [IQR 363, 1100] p = 0.014). Repeat serum testing (6- < 12 h from injury) showed that UCH-L1 serum concentration, but not GFAP, was also significantly greater in the acute unfavorable neurological outcome group than in those without an unfavorable outcome: 1088 pg/mL versus 374 pg/mL; p = 0.041.

Predictive Performance of Traumatic Brain Injury Biomarkers in High-Risk Elderly Patients.

BACKGROUND: Serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal esterase L1 (UCH-L1) have recently received US Food and Drug Administration approval for prediction of abnormal computed tomography (CT) in mild traumatic brain injury patients (mTBI). However, their performance in elderly patients has not been characterized. METHODS: We performed a posthoc analysis using the A Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) study data. Previously recorded patient variables and serum values of GFAP and UCH-L1 from mTBI patients were partitioned at 65 years of age (herein referred to as ≥65, high-risk; <65, low-risk). We sought to assess the influence of age on predictive performance, sensitivity, and negative predictive value (NPV) of serum UCH-L1 and GFAP to predict intracranial injury by CT. RESULTS: Elderly mTBI patients constituted 25.7% of the patient cohort (n = 504/1959). Sensitivity and NPV of GFAP/UCH-L1 were 100%, with no significant difference from younger patients (P = 0.5525 and P > 0.9999, respectively). Specificity was significantly lower in elderly patients (0.131 vs 0.442; P < 0.0001) and decreased stepwise with older age. Compared to younger patients, elderly mTBI patients without abnormal (i.e., normal) CT findings also had a significantly higher GFAP (38.6 vs 16.2 pg/mL; P < 0.0001) and UCH-L1 (347.4 vs 232.1 pg/mL; P < 0.0001). CONCLUSIONS: Sensitivity and NPV to predict intracranial injury by CT was nearly identical between younger and elderly mTBI patients. Decrements in specificity and increased serum values suggest that special deference may be warranted for elderly patients.

Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study.

OBJECTIVES: To evaluate the ability of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) to detect concussion in children and adult trauma patients with a normal mental status and assess biomarker concentrations over time as gradients of injury in concussive and non-concussive head and body trauma. DESIGN: Large prospective cohort study. SETTING: Three level I trauma centres in the USA. PARTICIPANTS: Paediatric and adult trauma patients of all ages, with and without head trauma, presenting with a normal mental status (Glasgow Coma Scale score of 15) within 4 hours of injury. Rigorous screening for concussive symptoms was conducted. Of 3462 trauma patients screened, 751 were enrolled and 712 had biomarker data. 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 hours postinjury in adults. MAIN OUTCOMES: Detection of concussion and gradients of injury in children versus adults by comparing three groups of patients: (1) those with concussion; (2) those with head trauma without overt signs of concussion (non-concussive head trauma controls) and (3) those with peripheral (body) trauma without head trauma or concussion (non-concussive body trauma controls). RESULTS: A total of 1904 samples from 712 trauma patients were analysed. Within 4 hours of injury, there were incremental increases in levels of both GFAP and UCH-L1 from non-concussive body trauma (lowest), to mild elevations in non-concussive head trauma, to highest levels in patients with concussion. In concussion patients, GFAP concentrations were significantly higher compared with body trauma controls (p<0.001) and with head trauma controls (p<0.001) in both children and adults, after controlling for multiple comparisons. However, for UCH-L1, there were no significant differences between concussion patients and head trauma controls (p=0.894) and between body trauma and head trauma controls in children. The AUC for initial GFAP levels to detect concussion was 0.80 (0.73-0.87) in children and 0.76 (0.71-0.80) in adults. This differed significantly from UCH-L1 with AUCs of 0.62 (0.53-0.72) in children and 0.69 (0.64-0.74) in adults. CONCLUSIONS: In a cohort of trauma patients with normal mental status, GFAP outperformed UCH-L1 in detecting concussion in both children and adults. Blood levels of GFAP and UCH-L1 showed incremental elevations across three injury groups: from non-concussive body trauma, to non-concussive head trauma, to concussion. However, UCH-L1 was expressed at much higher levels than GFAP in those with non-concussive trauma, particularly in children. Elevations in both biomarkers in patients with non-concussive head trauma may be reflective of a subconcussive brain injury. This will require further study.

Resuscitation Guided by Volume Responsiveness Does Not Reduce Mortality in Sepsis: A Meta-Analysis.

Resuscitation with IV fluids is a critical component in the management of sepsis. Although the optimal volume of IV fluid is unknown, there is evidence that excessive administration can be deleterious. Static measures of volume status have not proven to be meaningful resuscitative endpoints. Determination of volume responsiveness has putative benefits over static measures, but its effect on outcomes is unknown. The goal of this systematic review and meta-analysis was to determine if resuscitation with a volume responsiveness-guided approach leads to improved outcomes in septic patients. DATA SOURCES: We searched PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, and Google Scholar from inception until April 2018. STUDY SELECTION: Prospective studies of patients with sepsis, severe sepsis, or septic shock that compared volume responsiveness-guided fluid resuscitation to standard techniques and reported mortality data. DATA EXTRACTION: We extracted study details, patient characteristics, volume responsiveness assessment method, and mortality data. DATA SYNTHESIS: Of the 1,224 abstracts and 31 full-texts evaluated, four studies (total 365 patients) met inclusion criteria. Using random effects modeling, the pooled odds ratio for mortality at time of longest follow-up with a volume responsiveness-guided strategy was 0.87 (95% CI, 0.49-1.54). Pooling of clinical data was not possibly owing to heterogeneity of reporting in individual studies. CONCLUSIONS: We found no significant difference in mortality between septic patients resuscitated with a volume responsiveness-guided approach compared with standard resuscitative strategies. It remains unclear whether the findings are due to the small sample size or a true lack of efficacy of a volume responsiveness-guided approach.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

BACKGROUND: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI. METHODS: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT. FINDINGS: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative. INTERPRETATION: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted. FUNDING: Banyan Biomarkers and US Army Medical Research and Materiel Command.