Sex Disparities in Chlamydia and Gonorrhea Treatment in US Adult Emergency Departments: A Systematic Review and Meta-analysis.

Importance: In US emergency departments (EDs), empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common due to the unavailability of immediate test results. Evidence suggests sex-based disparities in treatment practices, with females potentially receiving less empiric treatment than males. Objective: To investigate sex differences in empiric antibiotic treatment for GC and CT in EDs, comparing practices to subsequent laboratory-confirmed results. Design Setting and Participants: This systematic review and meta-analysis included studies from US EDs reporting GC/CT testing and empiric antibiotic treatment from January 2010 to February 2021. A total of 1,644 articles were screened, with 17 studies (n = 31,062 patients) meeting inclusion criteria. Main Outcomes and Measures: The primary outcomes were GC/CT test positivity, empiric antibiotic treatment rates, and discordance between treatment and test results, stratified by sex. Data were analyzed using a random-effects model. Results: Overall GC/CT positivity was 14% (95% CI, 11%-16%): 11% (95% CI, 8%-14%) in females and 25% (95% CI, 23%-26%) in males. Empiric antibiotic treatment was administered in 46% (95% CI, 38%-55%) of cases: 31% (95% CI, 24%-37%) in females and 73% (95% CI, 65%-80%) in males. Among patients without a laboratory-confirmed infection, 38% (95% CI, 30%-47%) received treatment: 27% (95% CI, 20%-34%) of females and 64% (95% CI, 55%-73%) of males. Conversely, 39% (95% CI, 31%-48%) of patients with laboratory-confirmed infections were not treated: 52% (95% CI, 46%-57%) of females and 15% (95% CI, 12%-17%) of males. Conclusions and Relevance: There is significant discordance between ED empiric antibiotic treatment and laboratory-confirmed results, with notable sex-based disparities. Females were 3.5 times more likely than males to miss treatment despite confirmed infection. These findings highlight the need for improved strategies to reduce sex-based disparities and enhance empiric treatment accuracy for GC/CT in ED settings. Key Points: Question: Are there sex-based differences in empiric antibiotic treatment for gonorrhea and chlamydia in US emergency departments (EDs), and how do these practices compare to laboratory-confirmed results?Findings: In this systematic review and meta-analysis of 17 studies with 31,062 patients, females were significantly less likely than males to receive empiric antibiotic treatment for gonorrhea and chlamydia. Additionally, 39% of patients with a laboratory-confirmed infection were not empirically treated, with females 3.5 times more likely to miss treatment than males.Meaning: The findings indicate significant sex disparities in ED empiric antibiotic treatment for sexually transmitted infections, underscoring the need for improved strategies to ensure equitable and accurate treatment across sexes.

Emergency Department Screening and Interventions for Adolescents With Substance Use: A Narrative Review.

BACKGROUND: Adolescent substance use is a growing public health concern, particularly given rising mortality rates from drug overdose deaths. The emergency department (ED) provides a unique opportunity to screen adolescents for substance use and provide brief interventions and linkage to care. OBJECTIVE OF THE REVIEW: This article provides a narrative review of the current evidence for ED screening and brief interventions for adolescents with substance use and identifies important opportunities, challenges, and areas for future research. DISCUSSION: There are several validated substance use screening and assessment tools for use with adolescents that can be implemented into ED screening programs. Brief motivational interviewing interventions may reduce alcohol use, but evidence for reductions of other substances is limited due to insufficient research. Both screening and interventions are feasible and acceptable in the ED setting with the appropriate resources. Increased training and the use of emerging technology can provide emergency physicians with opportunities to incorporate these tools into practice to when treating adolescents. Linkage to outpatient care for adolescents with substance use is understudied. The research on adult patient ED interventions and linkage to care is more robust and can provide insights for future ED studies among adolescents. CONCLUSION: ED-based adolescent substance use screening and interventions are necessary, feasible, and acceptable, but understudied. Future studies, focusing on optimizing ED interventions and linkage to care, are important next steps in determining the best care for adolescents with substance use who present to the ED.

Testing a persuasive health communication intervention (PHCI) for emergency department patients who declined rapid HIV/HCV screening: a randomised controlled trial study protocol.

INTRODUCTION: Previous studies have shown that substantial percentages of emergency department (ED) patients in the USA recommended for HIV or hepatitis C (HCV) decline testing. Evidence-based and cost-effective interventions to improve HIV/HCV testing uptake are needed, particularly for people who inject drugs (PWIDs) (currently or formerly), who comprise a group at higher risk for these infections. We developed a brief persuasive health communication intervention (PHCI) designed to convince ED patients who had declined HIV/HCV testing to agree to be tested. In this investigation, we will determine if the PHCI is more efficacious in convincing ED patients to be tested for HIV/HCV when delivered by a video or in person, and whether efficacy is similar among individuals who currently, previously or never injected drugs. METHODS AND ANALYSIS: We will conduct a multisite, randomised controlled trial comparing PHCIs delivered by video versus in person by a health educator to determine which delivery method convinces more ED patients who had declined HIV/HCV testing instead to be tested. We will stratify randomisation by PWID status (current, former or never/non-PWID) to permit analyses comparing the PHCI delivery method by injection-drug use history. We will also perform a cost-effectiveness analysis of the interventions compared with current practice, examining the incremental cost-effectiveness ratio between the two interventions for the ED population overall and within individual strata of PWID. As an exploratory analysis, we will assess if a PHCI video with captions confers increased or decreased acceptance of HIV/HCV testing, as compared with a PHCI video without captions. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of the Icahn School of Medicine. The results will be disseminated at international conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05968573.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.

Emergency department visits in the United States by adults with a complaint of diarrhea (2016-2021).

Objectives: For adults with a complaint of diarrhea presenting to United States emergency departments (EDs) from 2016 to 2021, we examined the: (1) occurrence and temporal trends in these ED visits, (2) frequency with which services were provided (laboratory testing, radiologic imaging, and intravenous fluids (IV fluids) administration) and patients were admitted; and (3) factors associated with service provision and admission. Methods: Data from the National Hospital Ambulatory Medical Care Survey (2016-2021) were analyzed. Multivariable logistic regression modeling was employed to examine factors associated with service provision and admission, according to patient demographic characteristics, healthcare insurance status, and associated clinical symptoms; ED geographic location; and type of ED medical staff who evaluated the patient. Results: From 2016 to 2017, there were 3.3-3.7 million ED visits/year by adults with a complaint of diarrhea (3.1% [95% CI 2.9-3.3] of all adult US ED visits). Services were provided and patients were admitted per these frequencies: complete blood count (80%; 95% CI 76-83); blood culture (8%; 95% CI 6-9); metabolic panel (94%; 95% CI 86-97); ultrasound (8%; 95% CI 7-10); abdominal/pelvic CT (33%; 95% CI 29-35); IV fluids (63%; 95% CI 50-66); and admission (16%; 95% CI 14-18). Factors associated with receipt of these services and admission included other presenting symptoms (abdominal pain, vomiting, and nausea), ED geographic location, ED medical staff member evaluating the patient, race, Hispanic ethnicity, and type of health insurance. Conclusion: For adult patients presenting to US EDs with a complaint of diarrhea, US EDs highly utilized selected laboratory tests and radiologic imaging. Differences in utilization raise concerns about equitable healthcare delivery and call for further investigation into the underlying reasons, as well as the development and adoption of standardized care pathways.

Characterizing opioid overdose hotspots for place-based overdose prevention and treatment interventions: A geo-spatial analysis of Rhode Island, USA.

OBJECTIVE: Examine differences in neighborhood characteristics and services between overdose hotspot and non-hotspot neighborhoods and identify neighborhood-level population factors associated with increased overdose incidence. METHODS: We conducted a population-based retrospective analysis of Rhode Island, USA residents who had a fatal or non-fatal overdose from 2016 to 2020 using an environmental scan and data from Rhode Island emergency medical services, State Unintentional Drug Overdose Reporting System, and the American Community Survey. We conducted a spatial scan via SaTScan to identify non-fatal and fatal overdose hotspots and compared the characteristics of hotspot and non-hotspot neighborhoods. We identified associations between census block group-level characteristics using a Besag-York-Mollié model specification with a conditional autoregressive spatial random effect. RESULTS: We identified 7 non-fatal and 3 fatal overdose hotspots in Rhode Island during the study period. Hotspot neighborhoods had higher proportions of Black and Latino/a residents, renter-occupied housing, vacant housing, unemployment, and cost-burdened households. A higher proportion of hotspot neighborhoods had a religious organization, a health center, or a police station. Non-fatal overdose risk increased in a dose responsive manner with increasing proportions of residents living in poverty. There was increased relative risk of non-fatal and fatal overdoses in neighborhoods with crowded housing above the mean (RR 1.19 [95 % CI 1.05, 1.34]; RR 1.21 [95 % CI 1.18, 1.38], respectively). CONCLUSION: Neighborhoods with increased prevalence of housing instability and poverty are at highest risk of overdose. The high availability of social services in overdose hotspots presents an opportunity to work with established organizations to prevent overdose deaths.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure.

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

Mixed-methods Evaluation of an Expedited Partner Therapy Take-home Medication Program: Pilot Emergency Department Intervention to Improve Sexual Health Equity.

Background: Treatment for partners of patients diagnosed with sexually transmitted infections (STI), referred to as expedited partner therapy (EPT), is infrequently used in the emergency department (ED). This was a pilot program to initiate and evaluate EPT through medication-in-hand ("take-home") kits or paper prescriptions. In this study we aimed to assess the frequency of EPT prescribing, the efficacy of a randomized best practice advisory (BPA) on the uptake, perceptions of emergency clinicians regarding the EPT pilot, and factors associated with EPT prescribing. Methods: We conducted this pilot study at an academic ED in the midwestern US between August-October 2021. The primary outcome of EPT prescription uptake and the BPA impact was measured via chart abstraction and analyzed through summary statistics and the Fisher exact test. We analyzed the secondary outcome of barriers and facilitators to program implementation through ED staff interviews (physicians, physician assistants, and nurses). We used a rapid qualitative assessment method for the analysis of the interviews. Results: During the study period, 52 ED patients were treated for chlamydia/gonorrhea, and EPT was offered to 25% (95% CI 15%-39%) of them. Expedited partner therapy was prescribed significantly more often (42% vs 8%; P < 0.01) when the interruptive pop-up alert BPA was shown compared to not shown. Barriers identified in the interviews included workflow constraints and knowledge of EPT availability. The BPA was viewed positively by the majority of participants. Conclusion: In this pilot EPT program, expedited partner therapy was provided to 25% of ED patients who appeared eligible to receive it. The interruptive pop-up alert BPA significantly increased EPT prescribing. Barriers identified to EPT prescribing should be the subject of future interventions to improve provision of EPT from the emergency department.

Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study.

Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10-7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10-5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10-4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps > .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: -4.41, corrected p < .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma.

Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma.

Importance: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry. Objective: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure. Design, Setting, and Participants: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data analysis was performed from October 25, 2022, to February 15, 2023. Exposure: Neighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address. Main Outcomes and Measures: Participants completed separate threat and reward tasks during functional magnetic resonance imaging. Diffusion-weighted and high-resolution structural images were also collected. Linear models assessed the association of ADI with reactivity, microstructure, and macrostructure of a priori regions of interest after adjusting for income, lifetime trauma, sex at birth, and age. A moderated-mediation model tested whether ADI was associated with neural activity via microstructural changes and if this was modulated by PTSD symptoms. Results: A total of 280 participants (183 females [65.4%]; mean [SD] age, 35.39 [13.29] years) completed the threat task and 244 participants (156 females [63.9%]; mean [SD] age, 35.10 [13.26] years) completed the reward task. Higher ADI (per 1-unit increase) was associated with greater insula (t274 = 3.20; ß = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; ß = 0.16; corrected P = .04) threat-related activity after considering covariates, but ADI was not associated with reward reactivity. Greater disadvantage was also associated with altered microstructure of the cingulum bundle (t274 = 3.48; ß = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = -2.29; ß = -0.13; corrected P = .02; surface area: t273 = 2.53; ß = 0.13; corrected P = .02). The moderated-mediation model revealed that ADI was associated with ACC threat reactivity via cingulum microstructural changes (index of moderated mediation = -0.02). However, this mediation was only present in individuals with greater PTSD symptom severity (at the mean: ß = -0.17; standard error = 0.06, t= -2.28; P = .007; at 1 SD above the mean: ß = -0.28; standard error = 0.08; t = -3.35; P < .001). Conclusions and Relevance: In this study, neighborhood disadvantage was associated with neurobiology that supports threat processing, revealing associations of neighborhood disadvantage with neural susceptibility for PTSD and suggesting how altered structure-function associations may complicate symptoms. Future work should investigate specific components of neighborhood disadvantage that may be associated with these outcomes.

Physician Views of Telehealth for Special Populations of Older Adults: Preliminary Findings.

This study's objective was to determine how frontline physicians perceived telehealth for older adults with sensory impairments, cognitive impairments, mobility challenges, or those receiving end-of-life care. We conducted a multiple-methods study of US emergency, geriatric, and primary care physicians. Phase 1 involved semi-structured interviews with 48 physicians on their experiences using telehealth with older adults. In phase 2, we used those qualitative findings to generate a web-based survey administered to 74 physicians. In phase 3, we reintegrated qualitative data to enrich survey results. We identified 3 key findings: (1) 50% of emergency physicians, 33% of geriatricians, and 18% of primary care physicians considered telehealth to be a poor substitute for providing end-of-life care (p = .68); (2) for hearing, vision, and cognitive impairments, 61%, 58%, and 54%, respectively, saw telehealth as a good or fair substitute for providing care (p = .14); and (3) 98% indicated that telehealth was a good or fair substitute for in-person care for those with mobility impairment (p < .001). Preferences and comfort using telehealth with older adults vary by clinical context, patient population, and physician specialty, requiring tailored adaptations.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

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.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

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.

Use of serial smartphone-based assessments to characterize diverse neuropsychiatric symptom trajectories in a large trauma survivor cohort.

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

MyTPill: study protocol for a cross-over randomised controlled trial comparing novel strategies to monitor antiretroviral adherence among HIV+ prescription opioid users.

INTRODUCTION: Adherence to HIV antiretroviral therapy (ART) remains the cornerstone of HIV treatment. For individuals with suboptimal adherence, electronic adherence monitoring (EAM) technologies have become an important component of multimodal adherence support strategies. Most EAM technologies detect pillbox opening, and therefore, assume but cannot verify actual ingestion of oral medication. In contrast, a digital pill system (ID-capsule manufactured by etectRX, here named My/Treatment/Pill) measures directly ingestion of medications. Identifying the superior method to measure ART adherence would improve virological suppression by enabling the delivery of real-time interventions to support ART adherence, particularly in high-risk populations. METHODS AND ANALYSIS: Cross-over, randomised trial with 1:1 variable block size randomisation comparing two EAM systems in prescription opioid-using HIV+patient on once daily oral bictegravir, emtricitabine and tenofovir alafenamide regimens and detectable viral load >200 copies/mL within 30 days of screening (n=80). The primary outcome is once daily ART adherence measurement efficacy as assessed by comparing the accuracy of each EAM system as measured by concordance of the respective EAM systems to dried blood spot ART concentrations. Secondary outcomes are the identification of multilevel factors that are prevalent in the target population most closely linked to ART non-adherence and EAM non-adherence. ETHICS AND DISSEMINATION: This protocol was approved by the institutional review boards of participating sites (The Ohio State University, The Fenway Institute and the University of Miami). Data will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03978793.

Utility of Wrist-Wearable Data for Assessing Pain, Sleep, and Anxiety Outcomes After Traumatic Stress Exposure.

Importance: Adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure are common and have higher incidence among socioeconomically disadvantaged populations. Pain, depression, avoidance of trauma reminders, reexperiencing trauma, anxiety, hyperarousal, sleep disruption, and nightmares have been reported. Wrist-wearable devices with accelerometers capable of assessing 24-hour rest-activity characteristics are prevalent and may have utility in measuring these outcomes. Objective: To evaluate whether wrist-wearable devices can provide useful biomarkers for recovery after traumatic stress exposure. Design, Setting, and Participants: Data were analyzed from a diverse cohort of individuals seen in the emergency department after experiencing a traumatic stress exposure, as part of the Advancing Understanding of Recovery After Trauma (AURORA) study. Participants recruited from 27 emergency departments wore wrist-wearable devices for 8 weeks, beginning in the emergency department, and completed serial assessments of neuropsychiatric symptoms. A total of 19 019 patients were screened. Of these, 3040 patients met study criteria, provided informed consent, and completed baseline assessments. A total of 2021 provided data from wrist-wearable devices, completed the 8-week assessment, and were included in this analysis. The data were randomly divided into 2 equal parts (n = 1010) for biomarker identification and validation. Data were collected from September 2017 to January 2020, and data were analyzed from May 2020 to November 2022. Exposures: Participants were recruited for the study after experiencing a traumatic stress exposure (most commonly motor vehicle collision). Main Outcomes and Measures: Rest-activity characteristics were derived and validated from wrist-wearable devices associated with specific self-reported symptom domains at a point in time and changes in symptom severity over time. Results: Of 2021 included patients, 1257 (62.2%) were female, and the mean (SD) age was 35.8 (13.0) years. Eight wrist-wearable device biomarkers for symptoms of adverse posttraumatic neuropsychiatric sequelae exceeded significance thresholds in the derivation cohort. One of these, reduced 24-hour activity variance, was associated with greater pain severity (r = -0.14; 95% CI, -0.20 to -0.07). Changes in 6 rest-activity measures were associated with changes in pain over time, and changes in the number of transitions between sleep and wake over time were associated with changes in pain, sleep, and anxiety. Simple cutoffs for these biomarkers identified individuals with good recovery for pain (positive predictive value [PPV], 0.85; 95% CI, 0.82-0.88), sleep (PPV, 0.63; 95% CI, 0.59-0.67, and anxiety (PPV, 0.76; 95% CI, 0.72-0.80) with high predictive value. Conclusions and Relevance: These findings suggest that wrist-wearable device biomarkers may have utility as screening tools for pain, sleep, and anxiety symptom outcomes after trauma exposure in high-risk populations.