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Abstract Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological 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 after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and 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 encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.

BackgroundPost-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD.MethodsThe Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables.ResultsAt baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated.ConclusionPTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Abstract The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

Abstract Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant’s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms.

OBJECTIVES/GOALS: This study examined patient perceptions on the benefits, barriers, and facilitators of conventional and complementary/behavioral pain strategies that can be offered in the ED setting including physical therapy, mindfulness, acupuncture, and yoga. METHODS/STUDY POPULATION: We conducted and recorded semi-structured interviews with 30 patients who presented to the ED with musculoskeletal pain. Interviews focused on patients’ perceptions of NP pain treatments, barriers/facilitators to utilization, and recommendations that would promote engagement. A hierarchical coding system was developed and refined using the interview guide, the Theory of Planned Behavior, and preliminary review of the transcripts. The iterative process of developing the coding system allowed us to identify preliminary themes. RESULTS/ANTICIPATED RESULTS: Patients believe education on pain and the mind-body connection would give a sense of pain control. Likely barriers to engaging at the ED include lights, noise, interruptions, and uncertainty of their medical status. Post-discharge NP treatment barriers are financial and logistical. Engagement can be facilitated by a desire to avoid opioids, familiarity with meditation practices, and consistent positive communication with the health care team. Patients desire evidence on effectiveness, including testimonials, and suggested NP techniques should be introduced early, with written materials used for post-discharge referral. Patients prefer in-person treatment but would appreciate a virtual option. The initial session should occur in-person to build trust and facilitate virtual session engagement. DISCUSSION/SIGNIFICANCE: Patients are willing to engage in nonpharmacological pain treatment, however the unpredictable ED environment, uncertainty of their medical status, and financial and time constraints are significant barriers.

Abstract Aims This study aimed to assess short‐term outcomes among emergency department (ED) patients with acute heart failure (AHF) by preserved (≥50%) vs. reduced (

Abstract 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.

Abstract Background Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management. Objective Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED. Methods This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED‐HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional troponin not due to acute coronary syndrome (ACS) were included. Our primary outcome was a composite endpoint: time to 30‐day cardiovascular death and/or heart failure‐related events. Results Of the 491 subjects included in the GUIDED‐HF trial, 418 had troponin measured during the ED evaluation and 66 (16%) had troponin values above the 99th percentile. Median age was 63 years (interquartile range, 54‐70), 62% (n = 261) were male, 63% (n = 265) were Black, and 16% (n = 67) experienced our primary outcome. There were no differences in our primary outcome between those with and without troponin elevation (12/66, 18.1% vs 55/352, 15.6%; P = 0.60). This effect was maintained regardless of assignment to usual care or the intervention arm. In multivariable regression analysis, there was no association between our primary outcome and elevated troponin (hazard ratio, 1.00; 95% confidence interval, 0.49–2.01, P = 0.994) Conclusion If confirmed in a larger cohort, these findings may facilitate safe ED discharge for a group of patients with AHF without ACS when an elevated troponin is the primary reason for admission.

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.

Abstract 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.

Abstract Background Loop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them. Methods To qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio

Background Timely diagnosis of ST‐segment elevation myocardial infarction (STEMI) in the emergency department (ED) is made solely by ECG. Obtaining this test within 10 minutes of ED arrival is critical to achieving the best outcomes. We investigated variability in the timely identification of STEMI across institutions and whether performance variation was associated with the ED characteristics, the comprehensiveness of screening criteria, and the STEMI screening processes. Methods and Results We examined STEMI screening performance in 7 EDs, with the missed case rate (MCR) as our primary end point. The MCR is the proportion of primarily screened ED patients diagnosed with STEMI who did not receive an ECG within 15 minutes of ED arrival. STEMI was defined by hospital discharge diagnosis. Relationships between the MCR and ED characteristics, screening criteria, and STEMI screening processes were assessed, along with differences in door‐to‐ECG times for captured versus missed patients. The overall MCR for all 7 EDs was 12.8%. The lowest and highest MCRs were 3.4% and 32.6%, respectively. The mean difference in door‐to‐ECG times for captured and missed patients was 31 minutes, with a range of 14 to 80 minutes of additional myocardial ischemia time for missed cases. The prevalence of primarily screened ED STEMIs was 0.09%. EDs with the greatest informedness (sensitivity+specificity−1) demonstrated superior performance across all other screening measures. Conclusions The 29.2% difference in MCRs between the highest and lowest performing EDs demonstrates room for improving timely STEMI identification among primarily screened ED patients. The MCR and informedness can be used to compare screening across EDs and to understand variable performance.

Background More than 30% of patients hospitalized for heart failure are rehospitalized or die within 90 days of discharge. Lower health literacy is associated with mortality among outpatients with chronic heart failure; little is known about this relationship after hospitalization for acute heart failure. Methods and Results Patients hospitalized for acute heart failure and discharged home between November 2010 and June 2013 were followed through December 31, 2013. Nurses administered the Brief Health Literacy Screen at admission; low health literacy was defined as Brief Health Literacy Screen ≤9. The primary outcome was all‐cause mortality. Secondary outcomes were time to first rehospitalization and, separately, time to first emergency department visit within 90 days of discharge. Cox proportional hazards models determined their relationships with health literacy, adjusting for age, gender, race, insurance, education, comorbidity, and hospital length of stay. For the 1379 patients, average age was 63.1 years, 566 (41.0%) were female, and 324 (23.5%) had low health literacy. Median follow‐up was 20.7 months (interquartile range 12.8 to 29.6 months), and 403 (29.2%) patients died. Adjusted hazard ratio for death among patients with low health literacy was 1.32 (95% CI 1.05, 1.66, P=0.02) compared to Brief Health Literacy Screen >9. Within 90 days of discharge, there were 415 (30.1%) rehospitalizations and 201 (14.6%) emergency department visits, with no evident association with health literacy. Conclusions Lower health literacy was associated with increased risk of death after hospitalization for acute heart failure. There was no evident relationship between health literacy and 90‐day rehospitalization or emergency department visits.

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.

ObjectiveWhether 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.MethodsParticipants 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.ResultsOf 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).ConclusionsED 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.

Introduction: The purpose of this study was to test if intravenous (IV) fluids warmed to body temperature are associated with greater patient comfort than room temperature IV fluids in adult emergency department (ED) patients.Methods: This was a pilot double-blind, crossover, randomized controlled trial. Enrolled subjects sequentially received boluses of body temperature (36ºC) and room temperature (22 ºC) IV fluid, with the order of boluses randomized. Each subject’s level of discomfort was assessed prior to and after each bolus, using a 10 cm visual analog scale (Discomfort VAS), with higher scores indicating greater discomfort. We calculated the change in Discomfort VAS score associated with body temperature IV fluid (ΔVASbody) and room temperature IV fluid (ΔVASroom) by subtracting the score reported before the bolus from the score reported after that bolus. We compared changes in Discomfort VAS score with body temperature and room temperature IV fluid using the Wilcoxon matched-pairs signed-rank test.Results: Twenty-seven subjects were included. Treatment with body temperature IV fluid was associated with a significant decrease in discomfort (median ΔVASbody: -0.7 cm; interquartile range (IQR): -4.5 cm to +0.4 cm) compared to room temperature IV fluid (median ΔVASroom: +1.2 cm; interquartile range: -0.1 cm to + 3.6 cm) (P = 0.001).Conclusion: In this small trial of adult ED patients, infusing IV fluids warmed to body temperature was associated with improved comfort compared to standard, room temperature IV fluids. [West J Emerg Med. 2013;14(5):542–546.]