Publications by authors named "Claire Pearson"

50 Publications

Persistent and Widespread Pain Among Blacks Six Weeks after MVC: Emergency Department-based Cohort Study.

West J Emerg Med 2020 Dec 16;22(2):139-147. Epub 2020 Dec 16.

University of North Carolina - Chapel Hill, Department of Anesthesiology and Emergency Medicine, Chapel Hill, North Carolina.

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.
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http://dx.doi.org/10.5811/westjem.2020.8.47450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972399PMC
December 2020

Understanding the Impact of COVID-19 on Physician Moms.

Disaster Med Public Health Prep 2021 Feb 16:1-17. Epub 2021 Feb 16.

Wayne State University,

Objective: This study evaluates the personal and professional experiences of physician mothers during the COVID-19 pandemic and the impact of the pandemic on the lives of physician mothers.

Methods: Using social media to reach a broad range of physicians, a convenience sample of physician mothers completed on-line survey posted between April 27-May 11. Members were encouraged to repost on social media and share with personal contacts resulting in a passive snowball sampling effect.

Results: A total of 2709 physician mothers from 48 states, Puerto Rico and 19 countries representing more than 25 medical specialties completed the survey. Most were between 30-39 years of age, 67% self-identified as white, 17% as Asian, 4% as African American. Most had been working for 11-16 years. 91% had a spouse/partner of the opposite sex. Over half were practicing in an area they identified as high COVID19 density while 50% had personally cared for a person with COVID19. Physician mothers were most concerned about exposing their children to COVID19 and about the morale and safety of their staff.

Conclusions: This is one of the first studies to explore the personal and professional challenges facing physician mothers during a pandemic. Physician mothers were most concerned about exposing their families to COVID-19. Mothers continued to work and at times increased their work despite having domestic, childcare and schooling responsibilities.
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http://dx.doi.org/10.1017/dmp.2021.49DOI Listing
February 2021

Mucosal immune responses in COVID19 - a living review.

Oxf Open Immunol 2021 25;2(1):iqab002. Epub 2021 Jan 25.

Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK.

COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.
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http://dx.doi.org/10.1093/oxfimm/iqab002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871424PMC
January 2021

Accurate identification and quantification of commensal microbiota bound by host immunoglobulins.

Microbiome 2021 01 30;9(1):33. Epub 2021 Jan 30.

Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

Background: Identifying which taxa are targeted by immunoglobulins can uncover important host-microbe interactions. Immunoglobulin binding of commensal taxa can be assayed by sorting bound bacteria from samples and using amplicon sequencing to determine their taxonomy, a technique most widely applied to study Immunoglobulin A (IgA-Seq). Previous experiments have scored taxon binding in IgA-Seq datasets by comparing abundances in the IgA bound and unbound sorted fractions. However, as these are relative abundances, such scores are influenced by the levels of the other taxa present and represent an abstract combination of these effects. Diversity in the practical approaches of prior studies also warrants benchmarking of the individual stages involved. Here, we provide a detailed description of the design strategy for an optimised IgA-Seq protocol. Combined with a novel scoring method for IgA-Seq datasets that accounts for the aforementioned effects, this platform enables accurate identification and quantification of commensal gut microbiota targeted by host immunoglobulins.

Results: Using germ-free and Rag1 mice as negative controls, and a strain-specific IgA antibody as a positive control, we determine optimal reagents and fluorescence-activated cell sorting (FACS) parameters for IgA-Seq. Using simulated IgA-Seq data, we show that existing IgA-Seq scoring methods are influenced by pre-sort relative abundances. This has consequences for the interpretation of case-control studies where there are inherent differences in microbiota composition between groups. We show that these effects can be addressed using a novel scoring approach based on posterior probabilities. Finally, we demonstrate the utility of both the IgA-Seq protocol and probability-based scores by examining both novel and published data from in vivo disease models.

Conclusions: We provide a detailed IgA-Seq protocol to accurately isolate IgA-bound taxa from intestinal samples. Using simulated and experimental data, we demonstrate novel probability-based scores that adjust for the compositional nature of relative abundance data to accurately quantify taxon-level IgA binding. All scoring approaches are made available in the IgAScores R package. These methods should improve the generation and interpretation of IgA-Seq datasets and could be applied to study other immunoglobulins and sample types. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00992-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847592PMC
January 2021

Classification and prediction of post-trauma outcomes related to PTSD using circadian rhythm changes measured via wrist-worn research watch in a large longitudinal cohort.

IEEE J Biomed Health Inform 2021 Jan 22;PP. Epub 2021 Jan 22.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes.

Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models.

Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79.

Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.
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http://dx.doi.org/10.1109/JBHI.2021.3053909DOI Listing
January 2021

Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study.

Neuropsychopharmacology 2021 Jan 21. Epub 2021 Jan 21.

Department of Emergency Medicine, Boston Medical Center, Boston, MA, USA.

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.
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http://dx.doi.org/10.1038/s41386-020-00946-8DOI Listing
January 2021

Lexical Influences on Categorical Speech Perception Are Driven by a Temporoparietal Circuit.

J Cogn Neurosci 2021 Jan 19:1-13. Epub 2021 Jan 19.

University of Memphis, TN.

Categorical judgments of otherwise identical phonemes are biased toward hearing words (i.e., "Ganong effect") suggesting lexical context influences perception of even basic speech primitives. Lexical biasing could manifest via late stage postperceptual mechanisms related to decision or, alternatively, top-down linguistic inference that acts on early perceptual coding. Here, we exploited the temporal sensitivity of EEG to resolve the spatiotemporal dynamics of these context-related influences on speech categorization. Listeners rapidly classified sounds from a /gɪ/-/kɪ/ gradient presented in opposing word-nonword contexts ( vs. ), designed to bias perception toward lexical items. Phonetic perception shifted toward the direction of words, establishing a robust Ganong effect behaviorally. ERPs revealed a neural analog of lexical biasing emerging within ~200 msec. Source analyses uncovered a distributed neural network supporting the Ganong including middle temporal gyrus, inferior parietal lobe, and middle frontal cortex. Yet, among Ganong-sensitive regions, only left middle temporal gyrus and inferior parietal lobe predicted behavioral susceptibility to lexical influence. Our findings confirm lexical status rapidly constrains sublexical categorical representations for speech within several hundred milliseconds but likely does so outside the purview of canonical auditory-sensory brain areas.
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http://dx.doi.org/10.1162/jocn_a_01678DOI Listing
January 2021

Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life.

Cell Rep 2020 11;33(7):108376

Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK. Electronic address:

Follicular mature (FM) and germinal center (GC) B cells underpin humoral immunity, but the dynamics of their generation and maintenance are not clearly defined. Here, we exploited a fate-mapping system in mice that tracks B cells as they develop into peripheral subsets, together with a cell division fate reporter mouse and mathematical models. We find that FM cells are kinetically homogeneous, recirculate freely, are continually replenished from transitional populations, and self-renew rarely. In contrast, GC B cell lineages persist for weeks with rapid turnover and site-specific dynamics. Those in the spleen derive from transitional cells and are kinetically homogeneous, while those in lymph nodes derive from FM B cells and comprise both transient and persistent clones. These differences likely derive from the nature of antigen exposure at the different sites. Our integrative approach also reveals how the host environment drives cell-extrinsic, age-related changes in B cell homeostasis.
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http://dx.doi.org/10.1016/j.celrep.2020.108376DOI Listing
November 2020

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study.

Psychol Med 2020 Oct 29:1-14. Epub 2020 Oct 29.

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: This 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.

Methods: We 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.

Results: Eight-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.

Conclusions: These 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.
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http://dx.doi.org/10.1017/S0033291720003773DOI Listing
October 2020

Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study.

Mol Psychiatry 2020 Oct 19. Epub 2020 Oct 19.

Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.

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.
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http://dx.doi.org/10.1038/s41380-020-00911-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053721PMC
October 2020

Prior sleep problems and adverse post-traumatic neuropsychiatric sequelae of motor vehicle collision in the AURORA study.

Sleep 2021 03;44(3)

Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI.

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.
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http://dx.doi.org/10.1093/sleep/zsaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953217PMC
March 2021

Why Won't Emergency Physicians Discharge Patients With a Low HEART Score From an Observation Unit Without Further Evaluation?

Crit Pathw Cardiol 2020 Dec;19(4):195-199

From the Department of Emergency Medicine, Ascension St. John Hospital, Detroit, MI.

Background: The History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score is a prospectively validated risk stratification tool for patients presenting to the emergency department (ED) with chest pain. Data demonstrate that patients with low HEART scores (0-3) can be safely discharged from the ED. ED physicians, however, may be reluctant to discharge patients based on the score.

Objective: To identify specific factors why ED physicians are reluctant to discharge patients with low-risk HEART scores from an ED observation unit (EDOU) without further evaluation.

Methods: This was a single-center prospective, cross-sectional analysis of ED patients from an urban ED placed in an EDOU for evaluation of chest pain, from July 1, 2016, to August 31, 2016. ED physicians completed a questionnaire that included documentation of patient HEART score and if the patient would or would not be a good candidate for outpatient stress testing or follow-up within 72 hours without further EDOU testing or consultant evaluation. Providers selected reasons why patients were not a good candidate for outpatient stress testing/follow-up.

Results: There were 279 patient questionnaires completed, 42% (117/279) had a HEART score of 0-3. Within this group, 54.7% (64/117) of the patients were identified as not being good candidates for outpatient stress testing/follow-up within 72 hours because of concerns for poor follow-up (n = 14), concerning risk factors (n = 14), concerning symptoms (n = 11), and other (n = 7).

Conclusions: ED physicians in this urban ED felt that over half of patients with a low-risk HEART score were not good candidates for discharge from the EDOU without further evaluation due to poor follow-up, concerning risk factors or symptoms, or coexisting conditions.
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http://dx.doi.org/10.1097/HPC.0000000000000236DOI Listing
December 2020

A 90-second magnetocardiogram using a novel analysis system to assess for coronary artery stenosis in Emergency department observation unit chest pain patients.

Int J Cardiol Heart Vasc 2020 Feb 8;26:100466. Epub 2020 Jan 8.

Ascension St. John Hospital, Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, USA.

Background: Magnetocardiography (MCG) has been shown to non-invasively detect coronary artery stenosis (CAS). Emergency department (ED) patients with possible acute coronary syndrome (ACS) are commonly placed in an observation unit (OU) for further evaluation. Our objective was to compare a novel MCG analysis system with stress testing (ST) and/or coronary angiography (CA) in non-high risk EDOU chest pain patients.

Methods: This is a prospective pilot study of non-high risk EDOU chest pain patients evaluated with ST and/or CA that underwent a resting 90-second MCG scan between August 2017 and February 2018. A positive MCG scan was defined as having current dipole deviations with dispersion or splitting during the repolarization phase. ST, CA and major adverse cardiac events (MACE) 30 days and 6 months post-discharge assessed.

Results: Of 101 study patients, mean age was 56 years and 53.6% were male. MCG scan sensitivity with 95% CI was 27.3% [7.3%, 60.7%], specificity 77.8% [67.5%, 85.6%], PPV 13.0% [3.4%, 34.7%] and NPV 89.7% [80.3%, 95.2%] compared to ST, and 33.3% [7.5%, 70.7%], 78.3% [68.4%, 86.2%], 13% [5.2%, 29.0%] and 92.3% [88.2%, 95.1%] respectively compared to ST and CA. No patients had positive ST, CA or MACE 30 days and 6 months post-discharge.

Conclusion: This pilot study suggests a resting 90-second MCG scan shows promise in evaluating EDOU chest pain patients for CAS and warrants further study as an alternative testing modality to identify patients safe for discharge. Larger studies are needed to assess accuracy of MCG using this novel analysis system.
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http://dx.doi.org/10.1016/j.ijcha.2019.100466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956743PMC
February 2020

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Mol Psychiatry 2020 02 19;25(2):283-296. Epub 2019 Nov 19.

Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion 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 = 5000 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 1 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.
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http://dx.doi.org/10.1038/s41380-019-0581-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981025PMC
February 2020

Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4 T cell memory.

Elife 2019 11 19;8. Epub 2019 Nov 19.

Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, United Kingdom.

Laboratory mice develop populations of circulating memory CD4 T cells in the absence of overt infection. We have previously shown that these populations are replenished from naive precursors at high levels throughout life (Gossel et al., 2017). However, the nature, relative importance and timing of the forces generating these cells remain unclear. Here, we tracked the generation of memory CD4 T cell subsets in mice housed in facilities differing in their 'dirtiness'. We found evidence for sequential naive to central memory to effector memory development, and confirmed that both memory subsets are heterogeneous in their rates of turnover. We also inferred that early exposure to self and environmental antigens establishes persistent memory populations at levels determined largely, although not exclusively, by the dirtiness of the environment. After the first few weeks of life, however, these populations are continuously supplemented by new memory cells at rates that are independent of environment.
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http://dx.doi.org/10.7554/eLife.48901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905650PMC
November 2019

Vitamin D insufficiency increases risk of chronic pain among African Americans experiencing motor vehicle collision.

Pain 2020 02;161(2):274-280

Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina, Chapel Hill, NC, United States.

African Americans experience an increased burden of motor vehicle collision (MVC), post-MVC musculoskeletal pain, and vitamin D insufficiency. In this prospective multicenter study, we tested the hypothesis that African Americans (n = 133) presenting to the emergency department after MVC with low peritraumatic vitamin D levels would have worse chronic musculoskeletal pain outcomes compared to individuals with sufficient vitamin D. Vitamin D levels were assessed in the early aftermath of MVC through enzyme-linked immunosorbent assay, and pain severity was assessed using the 0 to 10 numeric rating scale at 6 weeks, 6 months, and 1 year. In repeated-measures analysis, African American MVC survivors with vitamin D insufficiency experienced more severe chronic pain (β = 1.18, P = 0.031). In secondary analyses, we assessed for evidence that the effect of vitamin D on post-MVC pain outcomes is mediated, at least in part, by the influence of vitamin D on genetic variants in genes involved in immune system regulation (IL-10 and NLRP3). Genotyping was performed using a genome-wide microarray using collected DNA samples. Secondary analyses suggest that the effect of vitamin D on post-MVC pain outcomes may be influenced by genetic variation in IL-10 and NLRP3. Further studies are needed to assess the impact of vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, nonopioid interventions are urgently needed to address chronic pain development after MVC.
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http://dx.doi.org/10.1097/j.pain.0000000000001728DOI Listing
February 2020

MicroRNA-19b predicts widespread pain and posttraumatic stress symptom risk in a sex-dependent manner following trauma exposure.

Pain 2020 01;161(1):47-60

Institute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United States.

Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. Expression of the leading candidate miRNA to target PTWP/PTSS-related genes, miR-19b, has been shown to be influenced by estrogen and stress exposure. We evaluated whether peritraumatic miR-19b blood expression levels predicted PTWP and PTSS development in women and men experiencing trauma of motor vehicle collision (n = 179) and in women experiencing sexual assault trauma (n = 74). A sex-dependent relationship was observed between miR-19b expression levels and both PTWP (β = -2.41, P = 0.034) and PTSS (β = -3.01, P = 0.008) development 6 months after motor vehicle collision. The relationship between miR-19b and PTSS (but not PTWP) was validated in sexual assault survivors (β = -0.91, P = 0.013). Sex-dependent expression of miR-19b was also observed in blood and nervous tissue from 2 relevant animal models. Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.
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http://dx.doi.org/10.1097/j.pain.0000000000001709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923535PMC
January 2020

Time Course for Benefit and Risk of Clopidogrel and Aspirin After Acute Transient Ischemic Attack and Minor Ischemic Stroke.

Circulation 2019 08 26;140(8):658-664. Epub 2019 Jun 26.

Department of Neurology and Neurological Sciences, Stanford Stroke Center, Stanford University, Palo Alto, CA (G.W.A., N.V.).

Background: In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke [POINT] Trial), the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage in comparison to aspirin alone.

Methods: In a secondary analysis of POINT (N=4881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models.

Results: Through 90 days, the rate of major ischemic events was initially high then decreased markedly, whereas the rate of major hemorrhage remained low but relatively constant throughout. With the use of a model-based approach, the optimal change point for major ischemic events was 21 days (0-21 days hazard ratio 0.65 for clopidogrel-aspirin versus aspirin; 95% CI, 0.50-0.85; P=0.0015, in comparison to 22-90 days hazard ratio, 1.38; 95% CI, 0.81-2.35; P=0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.

Conclusions: The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of the CHANCE trial (Clopidogrel in High-Risk Patients With Non-disabling Cerebrovascular Events), a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest that limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk transient ischemic attack or minor ischemic stroke.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040713DOI Listing
August 2019

Community Health Workers in the Emergency Department-Can they Help with Chronic Hypertension Care.

Curr Hypertens Rep 2019 05 21;21(7):49. Epub 2019 May 21.

Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, USA.

Purpose Of Review: To review community health worker (CHW) interventions tailored for hypertension management and to determine if the emergency department (ED) population would benefit from such interventions.

Recent Findings: When working with patients who have one or more chronic diseases, CHW interventions have been very successful in improving health outcomes and are cost-effective. CHWs use a variety of techniques to address social determinants that patients may face that effect how they manage their chronic disease(s). Current CHW interventions in the ED have targeted the "super-user" population. CHW-based interventions help address social determinants of patients in a variety of settings, especially in the ED where the physicians have limited resources and time. There is limited information about how CHWs can improve community health outcomes outside of the ED "super-user" population. Future research needs to determine if creating a data-driven CHW intervention for the ED would be effective.
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http://dx.doi.org/10.1007/s11906-019-0955-6DOI Listing
May 2019

Genes known to escape X chromosome inactivation predict co-morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure.

Am J Med Genet B Neuropsychiatr Genet 2019 09 11;180(6):415-427. Epub 2018 Dec 11.

Institute for Trauma Recovery, University of North Carolina, Chapel Hill, North Carolina.

Co-morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision, are associated with greater disability than either outcome alone, and are more prevalent in women than men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0-10 numeric rating scale) and PTSS (impact of events scale, revised) outcomes were assessed 6 months following motor vehicle collision. Blood RNA were sequenced (n = 101) and the relationship between X chromosome mRNA expression levels and co-morbid CMSP and PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic X chromosome mRNA predicting CMSP and PTSS in women were genes previously found to escape X chromosome inactivation (11/40, z = -2.9, p = .004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of X chromosome inactivation, X-inactive specific transcript (XIST) and Yin Yang 1 (YY1), was different in women developing CMSP and PTSS. Together, these data suggest that X chromosome genes that escape inactivation may contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision.
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http://dx.doi.org/10.1002/ajmg.b.32706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138464PMC
September 2019

Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis.

Nat Commun 2018 09 18;9(1):3797. Epub 2018 Sep 18.

Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, United Kingdom.

Inflammatory bowel disease (IBD) are heterogenous disorders of the gastrointestinal tract caused by a spectrum of genetic and environmental factors. In mice, overlapping regions of chromosome 3 have been associated with susceptibility to IBD-like pathology, including a locus called Hiccs. However, the specific gene that controls disease susceptibility remains unknown. Here we identify a Hiccs locus gene, Alpk1 (encoding alpha kinase 1), as a potent regulator of intestinal inflammation. In response to infection with the commensal pathobiont Helicobacter hepaticus (Hh), Alpk1-deficient mice display exacerbated interleukin (IL)-12/IL-23 dependent colitis characterized by an enhanced Th1/interferon(IFN)-γ response. Alpk1 controls intestinal immunity via the hematopoietic system and is highly expressed by mononuclear phagocytes. In response to Hh, Alpk1 macrophages produce abnormally high amounts of IL-12, but not IL-23. This study demonstrates that Alpk1 promotes intestinal homoeostasis by regulating the balance of type 1/type 17 immunity following microbial challenge.
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http://dx.doi.org/10.1038/s41467-018-06085-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143560PMC
September 2018

A Functional riboSNitch in the 3' Untranslated Region of Alters MicroRNA-320a Binding Efficiency and Mediates Vulnerability to Chronic Post-Traumatic Pain.

J Neurosci 2018 09 27;38(39):8407-8420. Epub 2018 Aug 27.

Institute for Trauma Recovery.

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via , , and analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating expression levels increased as cortisol and glucocorticoid receptor () mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, , and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRNA, miR-320a, to via altering the mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater translation, unchecked by miR-320a. Overall, these results identify an important gene-miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress mRNA expression may constitute useful therapeutic strategies. is a critical regulator of the stress response. Previous studies have shown that dysregulation of the expression of this gene plays a role in the pathogenesis of chronic pain development as well as a number of comorbid neuropsychiatric disorders. In the current study, we identified a functional allele (rs3800373) in the 3'UTR of that influences vulnerability to chronic post-traumatic pain in two ethnic cohorts. Using multiple complementary experimental approaches, we show that the rs3800373 minor allele alters the secondary structure of mRNA, decreasing the binding of a stress- and pain-associated microRNA, miR-320a. This results in relatively greater translation, unchecked by miR-320a, increasing glucocorticoid resistance and increasing vulnerability to post-traumatic pain.
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http://dx.doi.org/10.1523/JNEUROSCI.3458-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158694PMC
September 2018

Outcomes after Concussion Recovery Education: Effects of Litigation and Disability Status on Maintenance of Symptoms.

J Neurotrauma 2019 02 6;36(4):554-558. Epub 2018 Sep 6.

4 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.

This study examined the hypothesis that people who receive concussion recovery education would have better outcomes than those who received usual discharge paperwork from the emergency department (ED) and tested whether participants who were in litigation or seeking disability compensation had more symptoms than individuals not engaged in these activities. Two hundred and fifty-five persons with a diagnosis of concussion were assigned randomly to a brief education group (one-page double-sided document), a longer education group (10-page document), and usual care (standard ED discharge instructions), and were these documents in the ED. A (non-concussion) trauma comparison group was enrolled to determine the symptom rate unrelated to brain injury. The Concussion Symptom Checklist (CSC) and litigation and disability status questions were completed by telephone at one week, three months, and six months. Neither long nor brief information handouts had a significant impact on symptoms over time; the standard form had an average decrease of 1.20 symptoms compared with the brief instructional intervention group (p = 0.031). Litigation status and disability seeking status were significant predictors of symptoms on CSC over time: disability seeking (p = 0.017) and litigation status (p = 0.05). Persons seeking Social Security disability or legal compensation endorsed more symptoms over time than those who were not. Number of symptoms on the CSC for the trauma control group was the same as those who sustained concussion. Type of recovery material was not as important as noting that concussion symptoms resolve over time, and that remaining symptoms are not specific to brain injury. Litigation and disability seeking behavior accounted for maintained symptoms, rather than the concussion itself.
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http://dx.doi.org/10.1089/neu.2018.5873DOI Listing
February 2019

Clinical pharmacy services in the emergency department.

Am J Emerg Med 2018 10 31;36(10):1727-1732. Epub 2018 Jan 31.

Emergency Services Institute, Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic Enterprise Quality, Cleveland, OH, USA.

The emergency department (ED) is a fast-paced, high-risk, and often overburdened work environment. Formal policy statements from several notable organizations, including the American College of Emergency Physicians (ACEP) and the American Society of Health-System Pharmacists (ASHP), have recognized the importance of clinical pharmacists in the emergency medicine (EM) setting. EM clinical pharmacists work alongside emergency physicians and nurses at the bedside to optimize pharmacotherapy, improve patient safety, increase efficiency and cost-effectiveness of care, facilitate antibiotic stewardship, educate patients and clinicians, and contribute to scholarly efforts. This paper examines the history of EM clinical pharmacists and associated training programs, the diverse responsibilities and roles of EM clinical pharmacists, their impact on clinical and financial outcomes, and proposes a conceptual model for EM clinical pharmacist integration into ED patient care. Finally, barriers to implementing EM clinical pharmacy programs and limitations are considered.
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http://dx.doi.org/10.1016/j.ajem.2018.01.056DOI Listing
October 2018

Racial differences in presentations and predictors of acute pain after motor vehicle collision.

Pain 2018 Jun;159(6):1056-1063

Anesthesiology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.

African Americans experience a greater burden of acute pain than non-Hispanic white individuals across of variety of acute medical conditions, but it is unknown whether this is the case after trauma. We evaluated pain, pain-related characteristics (eg, peritraumatic distress), and analgesic treatment in 2 cohorts of individuals (African American [n = 931] and non-Hispanic white [n = 948]) presenting to the emergency department (ED) after a motor vehicle collision. We performed a propensity-matched analysis (n = 796 in each group) to assess racial differences in acute pain in the ED. In multivariable models conducted within the matched sample, race was associated with moderate to severe axial pain (odds ratio [OR] 3.2; 95% confidence interval [CI]: 2.1-5.0, P < 0.001) and higher average numerical rating scale scores (1.3; 95% CI: 1.1-1.6; P < 0.001). After adjustment for pain and other covariates, non-Hispanic white patients were more likely to receive an opioid analgesic in the ED (OR 2.0; 95% CI: 1.4-3.0, P < 0.001) or at discharge (OR 4.9; 95% CI: 3.4-7.1, P < 0.001) and also less likely to receive an NSAID in the ED (OR 0.54; 95% CI: 0.38-0.78; P = 0.001) or at discharge (0.31; 95% CI: 0.43-0.84). Racial differences in the severity of acute posttraumatic pain after a motor vehicle collision are not explained by factors such as socioeconomic status or crash characteristics. Despite a higher burden of acute pain, African Americans were less likely to receive opioid analgesics and more likely to receive NSAIDs. Further work is needed to understand the relationship between pain severity, disparities in analgesic treatment, and longer term outcomes, such as post-motor vehicle collision chronic pain.
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http://dx.doi.org/10.1097/j.pain.0000000000001186DOI Listing
June 2018

Gender Differences in Pain Experience and Treatment after Motor Vehicle Collisions: A Secondary Analysis of the CRASH Injury Study.

Clin Ther 2018 02 20;40(2):204-213.e2. Epub 2018 Jan 20.

Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, Rhode Island; Department of Health Services, Policy, and Practice, Brown University, Providence, Rhode Island.

Purpose: 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.

Methods: 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.

Findings: 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%; P < 0.001), 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; P < 0.001). 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).

Implications: 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.
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http://dx.doi.org/10.1016/j.clinthera.2017.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811333PMC
February 2018

Emergency department visits in patients with low acuity conditions: Factors associated with resource utilization.

Am J Emerg Med 2018 08 13;36(8):1327-1331. Epub 2017 Dec 13.

Department of Emergency Medicine, Wayne State University, 4201 St. Antoine St., Detroit, MI 48201, United States; Department of Emergency Medicine and Cardiovascular Research Institute, Integrated Biosciences Center, Wayne State University School of Medicine, 6135 Woodward Ave., Detroit, MI 48202, United States.

Objectives: To identify health beliefs of emergency department (ED) patients with low acuity conditions and how these affect ambulance (AMB) utilization.

Methods: We performed a prospective, observational study on a convenience sample of patients 18years or older, who presented to the ED of an urban, academic hospital with an Emergency Severity Index (ESI) triage level of 4 or 5. Demographics, treatment, and disposition data were obtained along with self-administered surveys. Characteristics of patients with low acuity conditions who presented to the ED by AMB were compared to the patients who came to the ED by private transportation (PT). Data were analyzed with the chi-square test, t-test, and Mann-Whitney test.

Results: A total of 197 patients (97 AMB and 100 PT) were enrolled. Compared to PT, AMB patients were more likely to: be insured (82% vs. 56%; p=0.000), have a primary care provider (62% vs. 44%; p=0.048), and lack a regular means of transportation (53% vs. 33%; p=0.005). Three surveys were used the SF-8, Short Test of Functional Health Literacy in Adults [STOFHLA], and Health Belief Model [HBM]. Answers to HBM showed patients perceive that their illness required care within one hour of arrival (38% vs. 21%; p=0.04), have used an ambulance in the past year (76% vs. 33%; p=0.001) and to utilize an ambulance in the future for similar concerns (53% vs. 15%; p=0.000). AMB patients were more likely to call an ambulance for any health concern (p=0.035) and felt that there were enough ambulances for all patients in the city (p=0.01). There were no differences in age, employment, level of income and education, nor hospital admission rate between groups.

Conclusions: Ambulance use in low-acuity ED patients is associated with misperceptions regarding severity of illness and resource allocation as well as limited access to private transportation. Understanding patient perceptions of illness and other barriers to receiving care is imperative for the development of interventions aimed at enabling change in health behaviors such as the elective use of limited resources.
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http://dx.doi.org/10.1016/j.ajem.2017.12.033DOI Listing
August 2018

Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG1 GATA3 regulatory T cells in mice.

Immunology 2017 09 19;152(1):74-88. Epub 2017 Jun 19.

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

CD4 Foxp3 regulatory T (Treg) cells include differentiated populations of effector Treg cells characterized by the expression of specific transcription factors. Tumours, including intestinal malignancies, often present with local accumulation of Treg cells that can prevent tumour clearance, but how tumour progression leads to Treg cell accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition and tumour progression, promotes the accumulation of intestinal Treg cells by the specific accumulation of the KLRG1 GATA3 Treg subset. Epithelial E-cadherin ablation activates the β-catenin pathway, and we find that increasing β-catenin signals in intestinal epithelial cells also boosts Treg cell frequencies through local accumulation of KLRG1 GATA3 Treg cells. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of interleukin-33, a cytokine that preferentially expands KLRG1 GATA3 Treg cells. Tumours often present reduced E-cadherin expression and increased β-catenin signalling and interleukin-33 production. Accordingly, Treg cell accumulation in intestinal tumours from APC mice was exclusively due to the increase in KLRG1 GATA3 Treg cells. Our data identify a novel axis through which epithelial cells control local Treg cell subsets, which may be activated during intestinal tumorigenesis.
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http://dx.doi.org/10.1111/imm.12750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543491PMC
September 2017

Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke.

Am J Emerg Med 2017 May 15;35(5):802.e1-802.e5. Epub 2016 Nov 15.

Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, USA; Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, USA.

Background: Rapid and accurate diagnosis of patients presenting with symptoms of stroke is needed to facilitate the timely delivery of proven effective treatment for patients with acute ischemic stroke (AIS). The aim of this study was to determine whether early assessment of platelet reactivity in patients presenting with symptoms of AIS was associated with a diagnosis of AIS, transient ischemic attack (TIA), or stroke mimic.

Methods: This prospective study included patients with symptoms of AIS treated at an inner-city emergency department (ED). Blood samples were obtained and assayed for platelet reactivity (quantified by closure time). Patients were grouped by discharge diagnosis into: AIS, TIA, or stroke mimic. Binary logistic regression model was used to predict the association of closure time with the final diagnosis of 1) either AIS or TIA or, 2) stroke mimic.

Results: Of 114 patients enrolled, 32 were diagnosed with AIS, 33 TIA, and 49 were diagnosed as a stroke mimic. There was no significant difference in closure times among patients with a diagnosis of AIS or TIA versus stroke mimic. A history of migraines and history of seizures were independently associated with lower odds of an AIS or TIA diagnosis (OR 0.31, 95% CI 0.10 to 0.94 and OR 0.08, 95% CI 0.01 to 0.88, respectively).

Conclusion: Closure time was not found to be a clinically reliable differentiator of patients with a diagnosis of AIS, TIA, or stroke mimic in the ED.
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http://dx.doi.org/10.1016/j.ajem.2016.11.036DOI Listing
May 2017