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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.

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.

Posttraumatic stress (PTS), depressive symptoms (DS), and musculoskeletal pain (MSP) are common sequelae of trauma exposure. Although these adverse posttraumatic neuropsychiatric sequelae (APNS) are often studied separately, clinical comorbidity is high. In a cohort of European American motor vehicle collision (MVC) trauma survivors (n = 781), substantial PTS (≥33, IES-R), DS (≥26, CES-D), and MSP (≥4, 0–10 NRS) were identified via a 6-month survey. Genetic risk was estimated using polygenic risk scores (PRSs) calculated from the largest available GWAS datasets of PTSD, MDD, and back pain. We then assessed comorbidity and genetic risk influence for developing chronic PTS, DS, and MSP after MVC. Secondary analyses explored whether common social determinants of health ameliorate genetic vulnerability. We found that 6 months after MVC, nearly half 357/781 (46%) of the participants had substantial PTS, DS, and/or MSP, and overlap was common (PTS + MSP (23%), DS + MSP (18%), PTS + DS (12%)). Genetic risk predicted post-MVC outcomes. PTSD-PRSs predicted PTS and DS (R2 = 2.21% and 2.77%, padj R2 = 1.89%, padj padj R2 = 1.49%, padj p = 0.048) and 52% (p = 0.04) less risk of developing PTS, and those with high social support had 60% (p = 0.008) less risk of developing DS. Overall, genetic factors influence the risk of APNS after MVC, genetic risk of distinct APNS are overlapping, and specific social determinants greatly augment genetic risk of APNS development after MVC.

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.

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.

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.

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.

Introduction Blacks in the United States experience greater persistent pain than non-Hispanic Whites across a range of medical conditions, but to our knowledge no longitudinal studies have examined the risk factors or incidence of persistent pain among Blacks experiencing common traumatic stress exposures such as after a motor vehicle collision (MVC). We evaluated the incidence and predictors of moderate to severe axial musculoskeletal pain (MSAP) and widespread pain six weeks after a MVC in a large cohort of Black adults presenting to the emergency department (ED) for care. Methods This prospective, multi-center, cohort study enrolled Black adults who presented to one of 13 EDs across the US within 24 hours of a MVC and were discharged home after their evaluation. Data were collected at the ED visit via patient interview and self-report surveys at six weeks after the ED visit via internet-based, self-report survey, or telephone interview. We assessed MSAP pain at ED visit and persistence at six weeks. Multivariable models examined factors associated with MSAP persistence at six weeks post-MVC. Results Among 787 participants, less than 1% reported no pain in the ED after their MVC, while 79.8 (95% confidence interval [CI], 77.1 - 82.2) reported MSAP and 28.3 (95% CI, 25.5 - 31.3) had widespread pain. At six weeks, 67% (95% CI, 64, 70%) had MSAP and 31% (95% CI, 28, 34%) had widespread pain. ED characteristics predicting MSAP at six weeks post-MVC (area under the curve = 0.74; 95% CI, 0.72, 0.74) were older age, peritraumatic dissociation, moderate to severe pain in the ED, feeling uncertain about recovery, and symptoms of depression. Conclusion These data indicate that Blacks presenting to the ED for evaluation after MVCs are at high risk for persistent and widespread musculoskeletal pain. Preventive interventions are needed to improve outcomes for this high-risk group.

Posttraumatic stress disorder (PTSD) is associated with lower gray matter volume (GMV) in brain regions critical for extinction of learned threat. However, relationships among volume, extinction learning, and PTSD symptom development remain unclear. We investigated subcortical brain volumes in regions supporting extinction learning and fear-potentiated startle (FPS) to understand brain-behavior interactions that may impact PTSD symptom development in recently traumatized individuals. Participants (N = 99) completed magnetic resonance imaging and threat conditioning two weeks following trauma exposure as part of a multisite observational study to understand the neuropsychiatric effects of trauma (AURORA Study). Participants completed self-assessments of PTSD (PTSD Checklist for DSM-5; PCL-5), dissociation, and depression symptoms two- and eight-weeks post-trauma. We completed multiple regressions to investigate relationships between FPS during late extinction, GMV, and PTSD symptom development. The interaction between thalamic GMV and FPS during late extinction at two weeks post-trauma predicted PCL-5 scores eight weeks (t (75) = 2.49, β = 0.28, p = 0.015) post-trauma. Higher FPS predicted higher PCL-5 scores in the setting of increased thalamic GMV. Meanwhile, lower FPS also predicted higher PCL-5 scores in the setting of decreased thalamic GMV. Thalamic GMV and FPS interactions also predicted posttraumatic dissociative and depressive symptoms. Amygdala and hippocampus GMV by FPS interactions were not associated with posttraumatic symptom development. Taken together, thalamic GMV and FPS during late extinction interact to contribute to adverse posttraumatic neuropsychiatric outcomes. Multimodal assessments soon after trauma have the potential to distinguish key phenotypes vulnerable to posttraumatic neuropsychiatric outcomes.

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.

BackgroundThis is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(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.MethodsWe focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.ResultsEight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.ConclusionsThese observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

Study Objectives Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes. Methods A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were assessed retrospectively in the ED. The survey assessed acute stress disorder (ASD) and MDE at 2 weeks and at 8 weeks assessed PTSD and MDE (past 30 days). Control variables included demographics, MVC characteristics, and retrospective reports about PTSD and MDE in the 30 days before the MVC. Results Prevalence estimates were 41.0% for 2-week ASD, 42.0% for 8-week PTSD, 30.5% for 2-week MDE, and 27.2% for 8-week MDE. Pre-MVC nightmares and sleep stress reactivity predicted 8-week PTSD (mediated through 2-week ASD) and MDE (mediated through the transition between 2-week and 8-week MDE). Pre-MVC insomnia predicted 8-week PTSD (mediated through 2-week ASD). Estimates of population attributable risk suggest that blocking effects of sleep disturbance might reduce prevalence of 8-week PTSD and MDE by as much as one-third. Conclusions Targeting disturbed sleep in the immediate aftermath of MVC might be one effective way of reducing MVC-related PTSD and MDE.

Objective To characterize risk factors for and consequences of post-traumatic stress disorder (PTSD) among older adults evaluated in the emergency department (ED) following motor vehicle collision (MVC). Design Prospective multicenter longitudinal study (2011–2015). Setting 9 EDs across the United States. Participants Adults aged 65 years and older who presented to an ED after MVC without severe injuries. Measurements PTSD symptoms were assessed 6 months after the ED visit using the Impact of Event Scale-Revised. Results Of 223 patients, clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%–26%). PTSD symptoms were more common in patients who did not have a college degree, had depressive symptoms prior to the MVC, perceived the MVC as life-threatening, had severe ED pain, and expected their physical or emotional recovery time to be greater than 30 days. Three factors (ED pain severity [0–10 scale], perceived life-threatening MVC [0–10 scale], and pre-MVC depressive symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with an area under the curve of 0.76. Compared to patients without PTSD symptoms, those with PTSD symptoms were at higher risk for persistent pain (72% versus 30%), functional decline (67% versus 42%), and new disability (49% versus 18%). Conclusions Among older adults treated in the ED following MVC, clinically significant PTSD symptoms at 6 months were present in 21% of patients and were associated with adverse health outcomes. Increased risk for PTSD development can be identified with moderate accuracy using information readily available in the ED.

This paper diabetic ketoacidosis (DKA). Previous literature describes these two disease states presenting together, but most reports describe the etiology as uncontrolled diabetes leading to thyroid storm. After literary review, we present what we believe to be the first case of thyroid storm and DKA occurring in the same person on multiple occasions with an insulin pump. Additionally, we provide evidence that points to the thyroid storm being caused by DKA versus the traditional teaching of DKA precipitating thyroid storm.

Transfusion-related acute lung injury (TRALI) is a complication of blood product transfusion characterized by respiratory distress with bilateral lung infiltrates and non-cardiogenic pulmonary edema developing within six hours of transfusion. TRALI is believed to result from an immunological response to transfused blood products. TRALI is a clinical diagnosis that requires the exclusion of other etiologies of pulmonary edema and acute lung injury. Here we report a case of a female who presented to the emergency department in acute respiratory distress two days after receiving a transfusion of packed red blood cells for post-operative anemia following a hysterectomy.

Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a 2-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.

OBJECTIVES To determine the influence of epidemiologic factors and the influence of genetic variants affecting FKBP5, a protein known to modulate hypothalamic-pituitary-adrenocortical axis function, on the severity of somatic symptoms commonly termed "postconcussive" 6 and 12 months after motor vehicle collision (MVC). METHODS European Americans 18 to 65 years of age who presented to one of eight emergency departments (EDs) after MVC were enrolled. Exclusion criteria included hospital admission. Blood samples were collected in the ED for genotyping. Participants completed evaluations including an adapted Rivermead Post-Concussive Symptoms Questionnaire in the ED and at 6 weeks, 6 months, and 1 year. Repeated-measures analysis of covariance was used to evaluate the association between epidemiologic factors (sociodemographic, pre-MVC health, collision characteristics, head injury, peritraumatic pain, and stress), FKBP5 genetic variants, and postconcussive symptom severity. RESULTS Among 943 patients recruited in the ED, follow-up was completed on 835 (88%) at 6 months and 857 (90%) at 1 year. Self-reported head impact during collision was not associated with chronic postconcussive symptom severity. After correction for multiple testing, three FKBP5 single-nucleotide polymorphisms (rs3800373, rs7753746, and rs9380526) predicted chronic postconcussive symptom severity, with an average symptom severity of 1.10 (95% confidence interval = 0.96-1.24), 1.36 (1.21-1.51), and 1.55 (1.23-1.88) for one, two, or three copies of minor allele at rs3800373 (p = .001). Similar effect sizes were observed for the minor alleles of rs7753746 and rs9380526. CONCLUSIONS Postconcussive symptoms after minor MVC are not generally related to the severity of mild brain injury. This study shows that neurobiologic stress systems may play a role in the pathogenesis of postconcussive symptoms.

The μ-opioid receptor 1 (OPRM1) binds endogenous opioids. Increasing evidence suggests that endogenous OPRM1 agonists released at the time of trauma may contribute to the development of posttraumatic musculoskeletal pain (MSP). In this prospective observational study, we evaluated the hypothesis that individuals with an AG or GG genotype at the OPRM1 A118 G allele, which results in a reduced response to opioids, would have less severe MSP 6 weeks after motor vehicle collision (MVC). Based on previous evidence, we hypothesized that this effect would be sex-dependent and most pronounced among women with substantial peritraumatic distress. European American men and women ≥18 years of age presenting to the emergency department after MVC and discharged to home after evaluation (N = 948) were enrolled. Assessments included genotyping and 6-week evaluation of overall MSP severity (0–10 numeric rating scale). In linear regression modeling, a significant A118 G Allele × Sex interaction was observed: an AG/GG genotype predicted reduced MSP severity among women with substantial peritraumatic distress (β = –.925, P = .014) but not among all women. In contrast, men with an AG/GG genotype experienced increased MSP severity at 6 weeks (β = .827, P = .019). Further studies are needed to understand the biologic mechanisms mediating observed sex differences in A118 G effects. Perspective These results suggest a sex-dependent mechanism by which an emotional response to trauma (distress) contributes to a biologic mechanism (endogenous opioid release) that increases MSP in the weeks after stress exposure. These results also support the hypothesis that endogenous opioids influence pain outcomes differently in men and women.

Given the discrepancy between men and women’s equal rates of medical school matriculation and their rates of academic promotion and leadership role acquisition, the need to provide mentorship and education to women in academic medicine is becoming increasingly recognized. Numerous large-scale programs have been developed to provide support and resources for women’s enrichment and retention in academic medicine. Analyses of contributory factors to the aforementioned discrepancy commonly cite insufficient mentoring and role modeling as well as challenges with organizational navigation. Since residency training has been shown to be a critical juncture for making the decision to pursue an academic career, there is a need for innovative and tailored educational and mentorship programs targeting residents. Acknowledging residents’ competing demands, we designed a program to provide easily accessible mentorship and contact with role models for our trainees at the departmental and institutional levels. We believe that this is an important step towards encouraging women’s pursuit of academic careers. Our model may be useful to other emergency medicine residencies looking to provide such opportunities for their women residents.

Patients do not start to exist when they arrive at the door of our emergency departments (ED), nor do they stop existing when they leave. Instead, before they fall ill or become injured they live and exist somewhere and when they are discharged from our care they will likely return to that same somewhere. As emergency providers (EPs), our attention must be focused on the patients in front of us, but fundamentally the details of this “somewhere” directly affect our ability to provide safe and effective emergency care. Specifically, both patient-specific factors like homelessness, immigration status, living situation, or insurance coverage, and structural factors arising from broader community and societal forces like food deserts, community violence, and poor housing quality can strongly impact both emergency presentations and our ability to safely and effectively discharge patients. Here, we argue that our duty as EPs extends beyond the four walls of our EDs into life in our communities, and that understanding and addressing the unique strengths and needs of the communities we serve is a crucial component of our ability to provide effective emergency care.

Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function.The primary objective of this study is to compare the presence of hypoglycemia, coagulopathy, and metabolic acidosis with the King's College criteria for predicting a composite endpoint of death or transplant.This study is a retrospective cohort study of adult patients admitted with a discharge diagnosis of acetaminophen-induced liver failure.The patients were admitted at one of six university-affiliated teaching hospitals in the United States.A total of 334 subjects were identified who met inclusion criteria. Fifty-one subjects (15.3%) met the composite endpoint of death or transplant. Ninety-six (28.7%) subjects met the King's College criteria for transplant. The presence of hypoglycemia increased the odds of reaching the composite endpoint by 3.39-fold. This model performed better than the King's College criteria (pseudo RThe combination of hypoglycemia, coagulopathy, and lactic acidosis performed better than the King's College criteria for predicting death or transplant.

Objectives Certain forms of social support have been shown to improve pain-coping behaviors and pain outcomes in older adults with chronic pain, but little is known about the effect of social support on pain outcomes in older adults following trauma exposure. Methods We analyzed data from a prospective longitudinal study of adults aged 65 years and older presenting to an emergency department after a motor vehicle collision (MVC) to characterize the relationship between perceived social support and MVC-related pain after trauma overall and by subgroups based on sex, depressive symptoms, and marital status. Results In our sample (N=176), patients with low perceived social support had higher pain severity 6 weeks after MVC than patients with high perceived social support after adjustment for age, sex, race, and education (4.2 vs. 3.2, P=0.04). The protective effect of social support on pain severity at 6 weeks was more pronounced in men and in married individuals. Patients with low social support were less likely to receive an opioid prescription in the emergency department (15% vs. 32%, P=0.03), but there was no difference in opioid use at 6 weeks (22% vs. 20%, P=0.75). Discussion Among older adults experiencing trauma, low perceived social support was associated with higher levels of pain at 6 weeks.

Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. We evaluated the effect of opioid analgesics vs NSAIDs initiated from the ED on the presence of moderate to severe musculoskeletal pain and ongoing opioid use at 6 weeks in a large cohort of adult ED patients presenting to the ED after MVC (n = 948). The effect of opioids vs NSAIDs was evaluated using an innovative quasi-experimental design method using propensity scores to account for covariate imbalances between the 2 treatment groups. No difference in risk for moderate to severe musculoskeletal pain at 6 weeks was observed between those discharged with opioid analgesics vs NSAIDs (risk difference = 7.2% [95% confidence interval: -5.2% to 19.5%]). However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.

Few residency curricular interventions have focused on improving well-being and promoting humanism. We describe the implementation of a novel curriculum based on small-group reflection rounds—the Emergency Medicine Reflection Rounds (EMRR)—at a 4-year US emergency medicine (EM) residency. During the inaugural year (2010–2011), nine residents volunteered to take part in 1-hour monthly sessions with faculty facilitators. Residents were provided with a confidential environment to discuss difficult ethical and interpersonal encounters from their clinical experiences. Ongoing feedback from participants was solicited, culminating with a four-question survey in which all respondents remarked that the EMRR contributed to improving their own well-being and agreed that it provided an important forum for residents to discuss difficult issues in a safe environment. In this article, we describe our innovation as an example of a wellness initiative that has promoted reflective practice and fostered cooperative learning around the communication, professional, and ethical challenges inherent in EM practice. Our EMRR model may be useful to other EM residences looking to supplement their wellness curriculum.

Objectives The study purpose was to determine the optimal use of lumbar puncture (LP) red blood cell (RBC) counts to identify subarachnoid hemorrhage (SAH) when some blood remains in the final tube. Methods A case series was performed at a tertiary emergency department (ED). Records of 4,496 consecutive adult patients billed for LPs between 2001 and 2009 were reviewed. Inclusion criteria were headache (HA), final tube RBCs ≥ 5, and neurovascular imaging within 2 weeks of the visit. Demographics, relevant history and physical examination components, LP results, and neuroimaging findings were recorded for 280 patients. True-positive (TP) and true-negative (TN) SAH were strictly defined. Primary outcomes were the areas under the receiver operating characteristic curves (AUC) for final tube RBC count, differential RBC count between the final and initial tubes, and absolute differential RBC count between the final and initial tubes divided by the mean RBC count of the two tubes (also called the percent change in RBC count). Results There were 26 TP and 196 TN results; 58 patients were neither. The TP group consisted of 19 patients with visible or possible SAH on imaging (17 on noncontrast head computed tomography [CT; 12 definite and five possible] and two on magnetic resonance imaging), six with xanthochromia and a vascular lesion (aneurysm or arteriovenous malformation [AVM] > 2 mm), and one with xanthochromia and polymerase chain reaction (PCR)-positive meningitis. As a test for SAH, final tube RBC AUC was 0.85 (95% confidence interval [CI] = 0.80 to 0.91). Interval likelihood ratios (LRs) for final tube RBC count were LR 0 (95% CI = 0 to 0.3) for RBCs 10,000. Differential RBC count was not associated with SAH, with AUC 0.45 (95% CI = 0.31 to 0.60). However, the percent change in RBC count between the final and initial tubes had an AUC 0.84 (95% CI = 0.78 to 0.90), and the optimal test threshold for SAH was 0.63, with positive LR 3.6 (95% CI = 2.7 to 4.7) and negative LR 0.10 (95% CI = 0.03 to 0.4) for percent change 63%, respectively. This test added additional independent information to the final tube RBC count based on improved logistic regression model fit and discriminatory ability as measured by the LR test and c statistic, respectively. Conclusions Final LP tube RBC count and the percent change in RBC count, but not the simple differential count between the final and initial tubes, were associated with SAH. In this sample, there were no patients with SAH who had RBCs 10,000 increased the odds of SAH by a factor of 6.

α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH) in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED) with opioid-related emergencies might identify "hot spots" of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address the emergency and longer-term health needs of the communities they are designed to serve.

BACKGROUND: Musculoskeletal pain is common after motor vehicle collision (MVC). The study objective was to evaluate distribution of pain and predictors of widespread musculoskeletal pain in the early aftermath (within 48 h) of collision. METHODS: European American adults aged 18-65 years presenting to the emergency department (ED) after collision who were discharged to home after evaluation were eligible. Evaluation included an assessment of reported pre-collision psychological characteristics, crash characteristics, current pain severity and location, and current psychological symptoms. Adjusted risk ratios were estimated using generalized linear models. RESULTS: Among 890 participants included in the study, 589/890 (66%) had pain in three or more regions, and 192/890 (22%) had widespread musculoskeletal pain (pain in seven or more regions). In adjusted analyses, the presence of widespread pain was strongly associated with depressive and somatic symptoms prior to collision, pain catastrophizing, and acute psychological symptoms, and was not associated with most collision characteristics (road speed limit, extent of vehicle damage, collision type, driver vs. passenger, airbag deployment). The reported number of body regions that struck an object during the collision was associated with both reported pre-collision depressive symptoms and with widespread pain. CONCLUSION: More than one in five individuals presenting to the ED in the hours after MVC have widespread pain. Widespread pain is strongly associated with patient characteristics known to be modulated by supraspinal mechanisms, suggesting that stress-induced hyperalgesia may influence acute widespread pain after collision. Language: en

Posttraumatic stress disorder (PTSD) symptoms and pain after traumatic events such as motor vehicle collision (MVC) have been proposed to be mutually promoting. We performed a prospective multicenter study that enrolled 948 individuals who presented to the emergency department within 24 hours of MVC and were discharged home after evaluation. Follow-up evaluations were completed 6 weeks, 6 months, and 1 year after MVC. Path analysis results supported the hypothesis that axial pain after MVC consistently promotes the maintenance of hyperarousal and intrusive symptoms, from the early weeks after injury through 1 year. In addition, path analysis results supported the hypothesis that one or more PTSD symptom clusters had an influence on axial pain outcomes throughout the year after MVC, with hyperarousal symptoms most influencing axial pain persistence in the initial months after MVC. The influence of hyperarousal symptoms on pain persistence was only present among individuals with genetic vulnerability to stress-induced pain, suggesting specific mechanisms by which hyperarousal symptoms may lead to hyperalgesia and allodynia. Further studies are needed to better understand the specific mechanisms by which pain and PTSD symptoms enhance one another after trauma, and how such mechanisms vary among specific patient subgroups, to better inform the development of secondary preventive interventions.

Background Restricted physical activity commonly occurs following acute musculoskeletal pain in older adults and may influence long-term outcomes. We sought to examine the relationship between restricted physical activity after motor vehicle collision (MVC) and the development of persistent pain. Methods We examined data from a prospective study of adults ≥65 years of age presenting to the emergency department (ED) after MVC without life-threatening injuries. Restricted physical activity 6 weeks after MVC was defined in three different ways: 1) by a ≥25 point decrease in Physical Activity Scale in the Elderly (PASE) score, 2) by the answer “yes” to the question, “during the past two weeks, have you stayed in bed for at least half a day?”, and 3) by the answer “yes” to the question, “during the past two weeks, have you cut down on your usual activities as compared to before the accident?” We examined relationships between each definition of restricted activity and pain severity, pain interference, and functional capacity at 6 months with adjustment for confounders. Results Within the study sample (N = 164), adjusted average pain severity scores at 6 months did not differ between patients with and without restricted physical activity based on decreased PASE score (2.54 vs. 2.07, p = 0.32). In contrast, clinically and statistically important differences in adjusted average pain severity at 6 months were observed for patients who reported spending half a day in bed vs. those who did not (3.56 vs. 1.91, p

Little is known about gender differences in the treatment of pain after motor vehicle collisions (MVCs) in an emergency department (ED). We aimed to describe gender differences in pain experiences and treatment, specifically the use of opioids and benzodiazepines after ED discharge, for MVC-related pain.This was a secondary analysis of previously collected data from the CRASH Injury studies. We included patients who were seen and discharged from an ED after an MVC and who were enrolled in 1 of 2 multicenter longitudinal prospective cohort studies (1 black/non-Hispanic and 1 white/non-Hispanic). First, we compared the experience of pain as defined by self-reported moderate-to-severe axial pain, widespread pain, number of somatic symptoms, pain catastrophizing, and peritraumatic distress between women and men using bivariate analyses. We then determined whether there were gender differences in the receipt of prescription medications for post-MVC pain symptoms (opioids and benzodiazepines) using multivariate logistic regression adjusting for demographic characteristics, pain, and collision characteristics.In total, 1878 patients were included: 61.4% were women. More women reported severe symptoms on the pain catastrophizing scale (36.8% vs 31.0%; P = 0.032) and peritraumatic distress following the MVC (59.7% vs 42.5%; P0.001), and women reported more somatic symptoms than men (median, 3.9; interquartile range, 3.7-4.0 vs median, 3.3; interquartile range, 3.1-3.5; P0.001). Unadjusted, similar proportions of women and men were given opioids (29.2% vs 29.7%; P = 0.84). After adjusting for covariates, women and men remained equally likely to receive a prescription for opioids (relative risk = 0.83; 95% confidence interval, 0.58-1.19). Women were less likely than men to receive a benzodiazepine at discharge from an ED (relative risk = 0.53; 95% confidence interval, 0.32-0.88).In a large, multicenter study of ED patients treated for MVC, there were gender differences in the acute psychological response to MVC with women reporting more psychological and somatic symptoms. Women and men were equally likely to receive opioid prescriptions at discharge. Future research should investigate potential gender-specific interventions to reduce both posttraumatic distress and the risk of developing negative long-term outcomes like chronic pain.

Study objective Motor vehicle crashes are the second most common form of trauma among older adults. We seek to describe the incidence, risk factors, and consequences of persistent pain among older adults evaluated in the emergency department (ED) after a motor vehicle crash. Methods We conducted a prospective longitudinal study of patients aged 65 years or older who presented to one of 8 EDs after motor vehicle crash between June 2011 and June 2014 and were discharged home after evaluation. ED evaluation was done through in-person interview; follow-up data were obtained through mail-in survey or telephone call. Pain severity (0 to 10 scale) overall and for 15 parts of the body were assessed at each follow-up point. Principal component analysis was used to assess the dimensionality of the locations of pain data. Participants reporting pain severity greater than or equal to 4 attributed to the motor vehicle crash at 6 months were defined as having persistent pain. Results Of the 161 participants, 72% reported moderate to severe pain at the ED evaluation. At 6 months, 26% of participants reported moderate to severe motor vehicle crash–related pain. ED characteristics associated with persistent pain included acute pain severity; pain located in the head, neck, and jaw or lower back and legs; poor self-rated health; less formal education; pre–motor vehicle crash depressive symptoms; and patient's expected time to physical recovery more than 30 days. Compared with individuals without persistent pain, those with persistent pain were substantially more likely at 6-month follow-up to have also experienced a decline in their capacity for physical function (73% versus 36%; difference=37%; 95% confidence interval [CI] 19% to 52%), a new difficulty with activities of daily living (42% versus 17%; difference=26%; 95% CI 10% to 43%), a 1-point or more reduction in overall self-rated health on a 5-point scale (54% versus 30%; difference=24%; 95% CI 6% to 41%), and a change in their living situation to obtain additional help (23% versus 8%; difference=15%; 95% CI 2% to 31%). Conclusion Among older adults discharged home from the ED post-evaluation after a motor vehicle crash, persistent pain is common and frequently associated with functional decline and disability.

Musculoskeletal pain (MSP) is a common sequela of traumatic stress exposure. While biological factors contributing to chronic MSP after motor vehicle collision (MVC) have traditionally focused on tissue injury, increasing evidence suggests that neuro/stress/immune processes mediated by stress system activation may play a more dominant role. In a previous study, we found that genetic variants in the hypothalamic-pituitary-adrenal (HPA) axis-related gene FKBP5 influence vulnerability to persistent MSP 6 weeks after MVC. In the present cohort study (n = 855), we evaluated whether genetic variants in several other important HPA axis-related genes, including the glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor R1 (CRHR1), and corticotropin-releasing hormone-binding protein (CRHBP), influence risk of chronic MSP over time after MVC. Genetic polymorphism rs7718461 in the CRHBP gene showed significant association (P = 0.0012) with overall pain severity during the year after MVC in regression models controlling for multiple comparisons. Two additional CRHBP alleles in high linkage disequilibrium with rs7718461 also showed trend-level significance. In secondary analyses, a significant interaction between this CRHBP locus (minor allele frequency = 0.33) and time was observed (P = 0.015), with increasing effect observed over time following trauma. A significant CRHBP × FKBP5 interaction was also observed, with substantially increased MSP after MVC in those with a risk allele in both genes compared with either gene alone. The results of this study indicate that genetic variants in 2 different HPA axis genes predict chronic MSP severity following MVC and support the hypothesis that the HPA axis is involved in chronic post-MVC MSP pathogenesis.

OBJECTIVES Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tested the hypothesis that genetic variants in the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter (SLC6A3) influence acute pain severity after motor vehicle collision. MATERIALS AND METHODS European Americans presenting to the emergency department after motor vehicle collision were recruited. Overall pain intensity in emergency department was assessed using a 0 to 10 numeric rating scale. DNA was extracted from blood samples and genotyping of single-nucleotide polymorphisms (SNPs) in the DRD2 and SLC6A3 gene was performed. RESULTS A total of 948 patients completed evaluation. After correction for multiple comparisons, SNP rs6276 at DRD2 showed significant association with pain scores, with individuals with the A/A genotype reporting lower mean pain scores (5.3; 95% confidence interval [CI], 5.1-5.5) than those with A/G (5.9; 95% CI, 5.6-6.1) or G/G (5.7; 95% CI, 5.2-6.2) genotypes (P=0.0027). Secondary analyses revealed an interaction between sex and DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with 2 minor alleles had increased pain intensity, whereas males with 2 minor alleles had less pain than individuals with a major allele (interaction P=0.0019). DISCUSSION Genetic variants in DRD2 are associated with acute pain after a traumatic stressful event. These results suggest that dopaminergic agents may be useful for the treatment of individuals with acute posttraumatic pain as part of a multimodal opioid-sparing analgesic regimen.

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings.