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To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision.Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration.Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort.This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

Emergency department (ED) providers play a critical role in the stabilization and diagnostic evaluation of patients presenting with acute heart failure (AHF), and EDs are key areas for establishing current best practices and future considerations for the disposition of and decision making for patients with AHF. These elements include accurate risk assessment; response to initial treatment and shared decision making concerning optimal venue of care; reframing of physicians' risk perceptions for patients presenting with AHF; exploration of alternative venues of care beyond hospitalization; population-level changes in demographics, management and outcomes of HF patients; development and testing of data-driven pathways to assist with disposition decisions in the ED; and suggested outcomes for measuring success.

Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope.The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies.The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE).Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines.ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.

Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma.All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment.Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms.The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [−0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

BackgroundPatients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biologic mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition at the time of trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether baseline the gut microbiomes of trauma-exposed emergency department patients who later develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms.MethodsWe performed metagenomic analysis on stool samples (n=51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and metabolic pathways.ResultsMicrobial species, includingFlavonifactor plauttiandRuminococcus gnavus,which are associated with inflammation and poor health outcomes, were found to be important in predicting worse APNS outcomes. Notably, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways.ConclusionsPro-inflammatory microbes that are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, which also has been demonstrated in patients with PTSD.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting post-traumatic preventive interventions. METHODS: Data come from 1,306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-week, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative-risk=2.6–7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2-week and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2-weeks and 8-weeks could help target early interventions for psychopathological reactions to MVCs.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N = 69; internal replication cohort: N = 77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Long-term follow-up for clinician-scientist training programs is sparse. We describe the outcomes of clinician-scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 program in emergency care research up to 8.7 years after matriculation in the program.This was a cohort study of faculty clinician-scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow-up 7.7 years (range 5.7-8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations.There were 43 scholars, including 16 (37%) women. Over the follow-up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9-83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log-rank test p = 0.27) or specialty training (emergency medicine versus other specialties, p = 0.59).After 7 years of follow-up for this NHLBI K12 emergency care research training program, three quarters of clinician-scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training.

PurposeIncreases in pediatric firearm-related injuries during the COVID-19 pandemic may be due to changes in where children and adolescents spent their time. This paper examines changes in the frequency of pediatric firearm-related encounters as a function of schooling mode overall and by race/ethnicity and age group at a large trauma center through 2021.MethodsWe use data from a large pediatric and adult trauma center in Tennessee from January 2018 to December 2021 (N=211 encounters) and geographically linked schooling mode data. We use Poisson regressions to estimate smoothed monthly pediatric firearm-related encounters as a function of schooling mode overall and stratified by race and age.ResultsCompared to pre-pandemic, we find a 42% increase in pediatric encounters per month during March 2020 to August 2020, when schools were closed, and a 23% increase in encounters after schools returned to in-person instruction. Effects of schooling mode are heterogeneous by race. Encounters increased among non-Hispanic Black children and adolescents across all periods relative to pre-pandemic. Among non-Hispanic white children and adolescents, encounters increased during the closure period and decreased on return to in-person instruction. Effects of schooling mode are also heterogeneous by age. Relative to pre-pandemic, pediatric firearm-related encounters increased 205% for children aged 5 to 11 and 69% for adolescents aged 12 to 15 during the school closure period.ConclusionCOVID-19-related changes to school instruction mode in 2020 and 2021 are associated with changes in the frequency and composition of pediatric firearm-related encounters at a major trauma center in Tennessee.

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

Pain accounts for up to 78% of emergency department (ED) patient visits and opioids remain a primary method of treatment despite risks of addiction and adverse effects. While prior acupuncture studies are promising as an alternative opioid-sparing approach to pain reduction, successful conduct of a multi-center pilot study is needed to prepare for a future definitive randomized control trial (RCT).Acupuncture in the Emergency Department for Pain Management (ACUITY) is funded by the National Center for Complementary and Integrative Health. The objectives are to: conduct a multi-center feasibility RCT, examine feasibility of data collection, develop/deploy a manualized acupuncture intervention and assess feasibility/implementation (barrier/facilitators) in 3 EDs affiliated with the BraveNet Practice Based Research Network.Adults presenting to a recruiting ED with acute non-emergent pain (e.g., musculoskeletal, back, pelvic, noncardiac chest, abdominal, flank or head) of ≥4 on a 0-10-point Numeric Rating Scale will be eligible. ED participants (n = 165) will be equally randomized to Acupuncture or Usual Care.At pre-, post-, and discharge time-points, patients will self-assess pain and anxiety using the Numeric Rating Scale. Pain, anxiety, post-ED opioid use and adverse events will be assessed at 1 and 4 weeks. Opioid utilization in the ED and discharge prescriptions will be extracted from patients' electronic medical records.Acupuncture recipients will asked to participate in a brief qualitative interview about 3 weeks after their discharge. ED providers and staff will also be interviewed about their general perspectives/experiences related to acupuncture in the ED and implementation of acupuncture in ACUITY.Recruitment began on 5/3/21. As of 12/7/21: 84 patients have enrolled, the responsive acupuncture intervention has been developed and deployed, and 26 qualitative interviews have been conducted.Successful conduct of ACUITY will provide the necessary framework for conducting a future, multi-center, definitive RCT of acupuncture in the ED.NCT04880733 https://clinicaltrials.gov/ct2/show/NCT04880733.

Objective Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. Methods Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. Results Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). Conclusions ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

Younger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.

Background: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department. Methods: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics. We used linear regression to describe changes in KCCQ-12 summary scores and logistic regression to characterize clinically meaningful KCCQ-12 subdomain changes at 30 days. Results: There were 350 patients with both enrollment and 30-day KCCQ summary scores available; 166 allocated to usual care and 184 to the intervention arm. Median age was 64 years (interquartile range, 55–70), 37% were female participants, 63% were Black, median KCCQ-12 summary score at enrollment was 47 (interquartile range, 33–64). Self-care coaching resulted in significantly greater improvement in health status compared with structured usual care (5.4-point greater improvement, 95% CI, 1.12–9.68; P =0.01). Improvements in health status in the intervention arm were driven by improvements within the symptom frequency (adjusted odds ratio, 1.62 [95% CI, 1.01–2.59]) and quality of life (adjusted odds ratio, 2.39 [95% CI, 1.46–3.90]) subdomains. Conclusions: In this secondary analysis, patients with acute heart failure who received a tailored, self-care intervention after emergency department discharge had clinically significant improvements in health status at 30 days compared with structured usual care largely due to improvements within the symptom frequency and quality of life subdomains of the KCCQ-12. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02519283.

Importance A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objectives To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. Design, Setting, and Participants The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. Main Outcomes and Measures The PTSD Checklist forDSM-5was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. Results A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. Conclusions and Relevance The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Ty J. Gluckman, MD, FACC, Chair Niti R. Aggarwal, MD, FACC Nicole M. Bhave, MD, FACC Gregory J. Dehmer, MD, MACC Olivia N. Gilbert, MD, MSc, FACC Dharam J. Kumbhani, MD, SM, FACC Andrea L. Price, MS, CPHQ, RCIS, AACC David E. Winchester, MD, MS, FACC Martha Gulati, MD, MS, FACC— Ex

Study objective The prevalence of pulmonary embolism among patients with syncope is understudied. In accordance with a recent study with an exceptionally high pulmonary embolism prevalence, some advocate evaluating all syncope patients for pulmonary embolism, including those with another clear cause for their syncope. We seek to evaluate the pulmonary embolism prevalence among emergency department (ED) patients with syncope. Methods We combined data from 2 large prospective studies enrolling adults with syncope from 17 EDs in Canada and the United States. Each study collected the results of pulmonary embolism–related investigations (ie, D-dimer, ventilation-perfusion scan, or computed tomography [CT] pulmonary angiography) and 30-day adjudicated outcomes: pulmonary embolism or nonpulmonary embolism outcome (arrhythmia, myocardial infarction, serious hemorrhage, and death). Results Of the 9,374 patients enrolled, 9,091 (97.0%; median age 66 years, 51.9% women) with 30-day follow-up were analyzed: 547 (6.0%) were evaluated for pulmonary embolism (278 [3.1%] had D-dimer, 39 [0.4%] had ventilation-perfusion scan, and 347 [3.8%] had CT pulmonary angiography). Overall, 874 patients (9.6%) experienced 30-day serious outcomes: 818 patients (9.0%) with nonpulmonary embolism serious outcomes and 56 (prevalence 0.6%; 95% confidence interval 0.5% to 0.8%) with pulmonary embolism (including 8 [0.2%] out of 3521 patients diagnosed during the index hospitalization and 7 [0.1%] diagnosed after the index visit). Eighty-six patients (0.9%) died, and 4 deaths (0.04%) were related to pulmonary embolism. Only 11 patients (0.1%) with a nonpulmonary embolism serious condition had a concomitant pulmonary embolism. Conclusion The prevalence of pulmonary embolism is very low among ED patients with syncope, including those hospitalized after syncope. Although an underlying pulmonary embolism may cause syncope, clinicians should be cautious about indiscriminate investigations for pulmonary embolism.

Almost 20% of patients with syncope will experience another event. It is unknown whether recurrent syncope is a marker for a higher or lower risk etiology of syncope. The goal of this study is to determine whether older adults with recurrent syncope have a higher likelihood of 30-day serious clinical events than patients experiencing their first episode. METHODS: This study is a pre-specified secondary analysis of a multicenter prospective, observational study conducted at 11 emergency departments in the US. Adults 60 years or older who presented with syncope or near syncope were enrolled. The primary outcome was occurrence of 30-day serious outcome. The secondary outcome was 30-day serious cardiac arrhythmia. In multivariate analysis, we assessed whether prior syncope was an independent predictor of 30-day serious events. RESULTS: The study cohort included 3580 patients: 1281 (35.8%) had prior syncope and 2299 (64.2%) were presenting with first episode of syncope. 498 (13.9%) patients had 1 prior episode while 771 (21.5%) had more than 1 prior episode. Those with recurrent syncope were more likely to have congestive heart failure, coronary artery disease, previous diagnosis of arrhythmia, and an abnormal ECG. Overall, 657 (18.4%) of the cohort had a serious outcome by 30 days after index ED visit. In multivariate analysis, we found no significant difference in risk of events (adjusted odds ratio 1.09; 95% confidence interval 0.90–1.31; p=0.387). CONCLUSION: In older adults with syncope, a prior history of syncope within the year does not increase the risk for serious 30-day events. TRIAL REGISTRATION NUMBER

Syncope is a common chief complaint in the ED, and the electrocardiogram (ECG) is a routine diagnostic tool in the evaluation of syncope. We assessed whether increasingly prolonged QTc intervals are associated with composite 30-day serious outcomes in older adults presenting to the ED with syncope.This is a secondary analysis of a prospective, observational study at 11 EDs in adults 60 years or older who presented with syncope or near syncope. We excluded patients presenting without an ECG, measurement of QTc, non-sinus rhythm, bundle branch block or those without 30-day follow-up. We categorized QTc cutoffs into values of451; 451-470; 471-500, and500 ms. We determined the rate of composite 30-day serious outcomes including ED serious outcomes and 30-day arrhythmias not identified in ED.The study cohort included 2609 patients. There were 1678 patients (64.3%) that had QTc intervals451 ms; 544 (20.8%) were 451-470 ms; 302 (11.6%) were 471-500 ms, and 85 (3.3%) had intervals500 ms. Composite 30-day serious outcomes was associated with increasingly prolonged QTc intervals (13.0%, 15.3%, 18.2%, 22.4%, p = 0.01), but this association did not persist in multivariate analysis.In a cohort of older patients presenting with syncope, increased QTc interval was a marker of but was not independently predictive of composite 30-day serious outcomes.

Objectives An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope. Methods A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods. Results The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings. Conclusions hscTnT and NT-proBNP are independent predictors of 30-day death and serious outcomes in older ED patients presenting with syncope.

Acute heart failure accounts for over one million hospital discharges annually. Current guidelines suggest treatments for AHF should begin “without delay” but this time interval has not been clearly defined. Data suggest that certain treatments such as earlier treatment with diuretics and vasodilators may improve patient symptom relief, morbidity, and mortality. Secondary analyses of clinical trials of novel treatments under development have not shown similar results. The data are equivocal regarding the impact of early treatment in AHF on in-hospital and long-term morbidity and mortality. Improved clinical trial designs will help answer when and if “early” treatment should begin and whether it impacts short- and long-term outcomes in AHF.

Study Objective: We developed a novel, quick, easy to use electrocardiogram (ECG) screening criterion (Seamens’ Sign) for left ventricular hypertrophy (LVH). This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads. Methods: This study was a retrospective chart review of 2184 patient records. The primary outcome was whether Seamens’ Sign was noninferior in confirming LVH compared to other common criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen’s Kappa. Results: Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens’ Sign. Seamens’ Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens’ Sign was non-inferior to all criteria (p

Background : Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS. Methods : Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (A dvancing U nderstanding of R ec O very afteR traum A ) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception. Results : Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC. Limitations : Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure. Conclusions : Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals.

Background Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. Methods 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. Results 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. Conclusions Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Hippo campal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N = 116, 76 female), we found that PTSD symptoms at 2 weeks were associated with decreased hippocampal responses to threat as assessed with fMRI. Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of fear potentiated startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function because of increases in fear-potentiated arousal. SIGNIFICANCE STATEMENT Alterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on nontrauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Background University students have limited opportunities to gain healthcare clinical exposure within an academic curriculum. Furthermore, traditional pre-medical clinical experiences like shadowing lack active learning components. This may make it difficult for students to make an informed decision about pursuing biomedical professions. An academic university level research course with bedside experience provides students direct clinical participation in the healthcare setting. Methods Described is a research immersion course for senior university students (3rd to 5th year) interested in healthcare and reported study enrollment with final course evaluations. The setting was an adult, academic, urban, level 1 trauma center emergency department (ED) within a tertiary-care, 1000-bed, medical center. Our course, “Immersion in Emergency Care Research”, was offered as a university senior level class delivered consecutively over 16-weeks for students interested in healthcare careers. Faculty and staff from the Department of Emergency Medicine provided a classroom lecture program and extensive bedside, hands-on clinical research experience. Students enrolled patients in a survey study requiring informed consent, interviews, data abstraction and data entry. Additionally, they were required to write and present a mock emergency care research proposal inspired by their clinical experience. The course evaluations from students’ ordinal rankings and blinded text responses report possible career impact. Results Thirty-two students, completed the 16-week, 6–9 h per week, course from August to December in 1 of 4 years (2016 to 2019). Collectively, students enrolled 759 ED patients in the 4 survey studies and reported increased confidence in the clinical research process as each week progressed. Ranked evaluations were extremely positive, with many students describing how the course significantly impacted their career pathways and addressed an unmet need in biomedical education. Six students continued the research experience from the course through independent study using the survey data to develop 3 manuscripts for submission to peer-reviewed journals. Conclusions A bedside emergency care research course for students with pre-healthcare career aspirations can successfully provide early exposure to patients and emergency care, allow direct experience with clinical bedside research, research data collection, and may impact biomedical science career choices.

Objective From the perspective of percutaneous coronary intervention (PCI) centers, locations of ST‐segment elevation myocardial infarction (STEMI) diagnosis can include a referring facility, emergency medical services (EMS) transporting to a PCI center, or the PCI center's emergency department (ED). This challenges the use of door‐to‐balloon‐time as the primary evaluative measure of STEMI treatment pathways. Our objective was to identify opportunities to improve care by quantifying differences in the timeliness of STEMI treatment mobilization based on the location of the diagnostic ECG. Methods This 3‐year, single‐center, retrospective cohort study classified patients by diagnostic ECG location: referring facility, EMS, or PCI center ED. We quantified door‐to‐balloon‐time and diagnosis‐to‐balloon‐time with its care subintervals. Results Of 207 ED STEMI patients, 180 (87%) received PCI. Median diagnosis‐to‐balloon‐times were shortest among the ED‐diagnosed (78 minutes [interquartile range (IQR), 61‐92]), followed by EMS‐identified patients (89 minutes [IQR, 78‐122]), and longest among those referred (140 minutes [IQR, 119‐160]), reflecting time for transport to the PCI center. Conversely, referred patients had the shortest median door‐to‐balloon‐times (38 minutes [IQR, 34‐43]), followed by the EMS‐identified (64 minutes [IQR, 47‐77]), whereas ED‐diagnosed patients had the longest (89 minutes [IQR, 70‐114]), reflecting diagnosis and catheterization lab activation frequently occurring before PCI center ED arrival for referred and EMS‐identified patients. Conclusions Diagnosis‐to‐balloon‐time and its care subintervals are complementary to the traditional door‐to‐balloon‐times as measures of the STEMI treatment process. Together, they highlight opportunities to improve timely identification among ED‐diagnosed patients, use of out‐of‐hospital cath lab activation for EMS‐identified patients, and encourage pathways for referred patients to bypass PCI center EDs.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.