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Introduction: Buprenorphine is a highly effective treatment for opioid use disorder (OUD). However, provider observations and preliminary research suggest that the current standard maintenance dose may be insufficient for suppressing withdrawal and preventing cravings among people who use or have used fentanyl. Buprenorphine dosing guidelines were based on studies among people who use heroin and have not been formally re-evaluated since fentanyl became predominant in the unregulated drug supply. We aim to compare the effectiveness of a high (24 mg) vs standard (16 mg) maintenance daily dose of buprenorphine for improving retention in treatment, decreasing the use of non-prescribed opioids, preventing cravings and reducing opioid overdose risk in patients., Methods and Analysis: Adults who are initiating or continuing buprenorphine for moderate to severe OUD and have a recent history of fentanyl use (n=250) will be recruited at four outpatient substance use treatment clinics in Rhode Island. Patients continuing buprenorphine must be on doses of 16 mg or less and have ongoing fentanyl use to be eligible. Participants will be randomly assigned 1:1 to receive either a high (24 mg) or standard (16 mg) maintenance daily dose, each with usual care, and followed for 12 months to evaluate outcomes. Providers will determine the buprenorphine initiation strategy, with the requirement that participants reach the study maintenance dose within 7 days of randomisation. Providers may adjust the maintenance dose, if clinically needed, for participant safety. The primary study outcome is retention in buprenorphine treatment at 6 months postrandomisation, measured using clinical and statewide administrative data. Other outcomes include non-prescribed opioid use and opioid cravings (secondary), as well as non-fatal or fatal opioid overdose (exploratory)., Ethics and Dissemination: This protocol was approved by the Brown Institutional Review Board (STUDY00000075). Results will be presented at conferences and published in peer-reviewed journals., Trial Registration Number: NCT06316830., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common after traumatic events. We examined whether wrist-wearable devices could provide heart rate variability (HRV) biomarkers for recovery after traumatic stress exposure in a large socioeconomically disadvantaged cohort. Participants were enrolled in the emergency department within 72 hours after a traumatic event as part of the AURORA (Advancing Understanding of RecOvery afteR traumA) multicenter prospective observational cohort study and followed over 6 months. HRV biomarkers were derived and validated for associations with specific APNS symptoms at a point in time and changes in symptom severity over time. Sixty-four HRV characteristics were derived and validated as cross-sectional biomarkers of APNS symptoms, including pain (26), re-experiencing (8), somatic (7), avoidance (7), concentration difficulty (6), hyperarousal (5), nightmares (1), anxiety (1), and sleep disturbance (3). Changes in 22 HRV characteristics were derived and validated as biomarkers identifying changes in APNS symptoms, including reexperiencing (11), somatic (3), avoidance (2), concentration difficulty (1), hyperarousal (1), and sleep disturbance (4). Changes in HRV variables over time predicted symptom improvement (PPV 0.68-0.87) and symptom worsening (NPV 0.71-0.90). HRV biomarkers collected from wrist-wearable devices may have utility as screening tools for APNS symptoms that occur after traumatic stress exposure in high-risk populations., Competing Interests: Declaration of competing interest Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, and the Rett Research Foundation. Dr Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical with significant stock. These relationships are unconnected to the current work. Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. Dr. Rauch reported serving as secretary of the Society of Biological Psychiatry; serving as a board member of Community Psychiatry and Mindpath Health; serving as a board member of National Association of Behavioral Healthcare; serving as secretary and a board member for the Anxiety and Depression Association of America; serving as a board member of the National Network of Depression Centers; receiving royalties from Oxford University Press, American Psychiatric Publishing Inc, and Springer Publishing; and receiving personal fees from the Society of Biological Psychiatry, Community Psychiatry and Mindpath Health, and National Association of Behavioral Healthcare outside the submitted work. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. Dr. Datner serves as a Medical Advisor and on the Board of Directors for Cayaba Care. Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Memorial Sloan Kettering Cancer Center, Indiana University, The Ohio State University, and Dana Farber Cancer Institute. Dr. Ressler has performed scientific consultation for Bioxcel, Bionomics, Acer, and Jazz Pharma; serves on Scientific Advisory Boards for Sage, Boehringer Ingelheim, Senseye, and the Brain Research Foundation, and he has received sponsored research support from Alto Neuroscience. Dr. Koenen's has been a paid scientific consultant for the US Department of Justice and Covington Burling, LLP over the last three years. She receives royalties from Guilford Press and Oxford University Press. In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences. Dr. McLean has served as a consultant for Walter Reed Army Institute for Research, Arbor Medical Innovations, and BioXcel Therapeutics, Inc., (Copyright © 2024. Published by Elsevier B.V.)

Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD)., Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward., Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023., Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC)., Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income)., Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory., Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Background: Although a majority of patients in the U.S. receive post-acute care in skilled nursing facilities (SNFs) following hip fracture, large-sample observational studies of analgesic prescribing and use in SNFs have not been possible due to limitations in available data sources. We conducted a proof-of-concept federated analysis of electronic health records (EHRs) from 11 SNF chains to describe analgesic use during hip fracture post-acute care., Methods: We included residents with a diagnosis of hip fracture between January 1, 2018 and June 30, 2021 who had at least one administration of an analgesic. Use of analgesics was ascertained from EHR medication orders and medication administration records. We quantified the proportion of residents receiving analgesic regimens based on the medications that were administered up to 100 days after hip fracture diagnosis. Plots visualizing trends in analgesic use were stratified by multiple resident characteristics including age and Alzheimer's Disease and Related Dementias (ADRD) diagnosis., Results: The study included 23,706 residents (mean age 80.5 years, 68.6% female, 87.7% White). Most (~ 60%) residents received opioids + APAP. Monotherapy with APAP or opioids was also common. The most prevalent regimens were oxycodone + APAP (20.1%), hydrocodone + APAP (15.8%), APAP only (15.1%), tramadol + APAP (10.4%), and oxycodone only (4.3%). During the study period, use of APAP-only increased, opioids-only decreased, and opioids + APAP remained stable. Use of APAP-only appeared to be more prevalent among individuals aged > 75 years (versus ≤ 75 years) and those with ADRD (versus without)., Conclusions: We successfully leveraged federated SNF EHR data to describe analgesic use among residents receiving hip fracture post-acute care., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Certified peer recovery specialists (CPRS) and licensed clinical social workers (LCSWs) can facilitate substance use disorder (SUD) treatment engagement for emergency department (ED) patients at risk for overdose. Predictors of treatment engagement after such behavioral services are unknown., Methods: This secondary analysis included Rhode Island ED patients at high risk for opioid overdose participating in a randomized controlled trial comparing the effectiveness of CPRS and LCSWs services (2018-2021). SUD treatment engagement within 90 days post-discharge was identified using statewide administrative data. Potential predictors were obtained from baseline questionnaires. Classification and regression trees (CART) were used to identify predictors of treatment engagement., Results: In the ED, 323 and 325 participants received CPRS and LCSWs services, respectively, among whom 141 (43.7 %) and 137 (42.2 %) engaged in SUD treatment within 90 days post-discharge. For the CPRS group, predictors of treatment engagement included unhealthy alcohol use, prescription opioid or benzodiazepine use in past 6 months, and lifetime history of: unstable housing, barriers to treatment, bipolar disorder diagnosis, addiction treatment, and recovery services. In the LCSW group, predictors included health insurance, current pain, opioid overdose in past year, and lifetime history of anxiety disorder diagnosis and mental illness treatment. However, CART had low predictive accuracy (CPRS: 60.9 %, LCSW: 54.8 %)., Conclusions: Among ED patients at high risk of opioid overdose receiving behavioral services, 90-day SUD treatment engagement was high. Sociobehavioral and clinical patient characteristics did not accurately predict treatment engagement. Behavioral services should be offered to all ED patients at high risk of opioid overdose., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brandon Marshall reports financial support was provided by Arnold Ventures LLC. Brandon Marshall reports financial support was provided by Cigna Foundation. Dr. Brandon Marshall was partially supported by the National Institute of General Medical Sciences of the NIH [grant number: P20GM125507] and the National Institute on Allergy and Infectious Disease of the NIH [grant number: 3P30AI042853]. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry post-trauma in humans. Neuroimaging markers may be particularly useful as they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. This study aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure., Methods: Participants were recruited from U.S. emergency departments for the AURORA study (N=286, 178 female). Trauma-related change in alcohol use at 8 weeks post-trauma relative to pre-trauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency Measure. Reward-related neurocircuitry activation and functional connectivity (FC) were assessed 2 weeks post-trauma using fMRI during a monetary reward task using region of interest and whole-brain voxelwise analyses., Results: Greater increase in alcohol use from pre-trauma to 8 weeks post-trauma was predicted by (1) greater ventral tegmental area (VTA) and (2) greater cerebellum activation during Gain>Loss trials measured 2 weeks post-trauma and (3) greater seed-based FC between the VTA and lateral occipital cortex and precuneus., Conclusions: Altered VTA activation and FC early post-trauma may be associated with reward-seeking and processing, contributing to greater alcohol use post-trauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early post-trauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: Chronic posttraumatic pain (CPTP) is common after traumatic stress exposure (TSE) and disproportionately burdens women. We previously showed across 3 independent longitudinal cohort studies that, in women, increased peritraumatic 17β-estradiol (E2) levels were associated with substantially lower CPTP over 1 year. Here, we assessed this relationship in a fourth longitudinal cohort and also assessed the relationship between E2 and CPTP at additional time points post-TSE. Furthermore, we used a well-validated animal model of TSE to determine whether exogenous E2 administration protects against mechanical hypersensitivity. Using nested samples and data from the Advancing Understanding of RecOvery afteR traumA study (n = 543 samples, 389 participants), an emergency department-based prospective study of TSE survivors, we assessed the relationship between circulating E2 levels and CPTP in women and men using multivariate repeated-measures mixed modeling. Male and ovariectomized female Sprague Dawley rats were exposed to TSE and administered E2 either immediately after or 3 days post-TSE. Consistent with previous results, we observed an inverse relationship between peritraumatic E2 and longitudinal CPTP in women only (β = -0.137, P = 0.033). In animals, E2 protected against mechanical hypersensitivity in female ovariectomized rats only if administered immediately post-TSE. In conclusion, peritraumatic E2 levels, but not those at post-TSE time points, predict CPTP in women TSE survivors. Administration of E2 immediately post TSE protects against mechanical hypersensitivity in female rats. Together with previous findings, these data indicate that increased peritraumatic E2 levels in women have protective effects against CPTP development and suggest that immediate post-TSE E2 administration in women could be a promising therapeutic strategy for reducing risk of CPTP., (Copyright © 2024 International Association for the Study of Pain.)

Background: Appropriate pain management can facilitate rehabilitation after a hip fracture as patients transition back to the community setting. Differences in opioid prescribing by race may exist during this critical transition period., Methods: We conducted a retrospective cohort study of older adult U.S. Medicare beneficiaries with a hip fracture to examine whether the receipt and dose of opioids differs between Black and White patients as they transitioned back to the community setting. We stratified beneficiaries by whether they received institutional post-acute care (PAC). Outcomes were (1) receipt of an opioid and (2) opioid doses in the first 90 days in the community in milligram morphine equivalents (MMEs; also presented in mg oxycodone). We estimated relative rates and risk differences of opioid receipt and dose differences using Poisson and linear regression models, respectively, using the parametric g-formula to standardize for age and sex., Results: We identified 164,170 older adults with hip fracture (mean age = 82.7 years; 75% female; 72% with PAC; 46% with opioid use after fracture). Overall use of opioids in the community was similar between Black and white beneficiaries. Black beneficiaries had lower average doses in their first 90 days in both total cumulative doses (PAC group: 165 [95% CI -264 to -69] fewer MMEs [-248 mg oxycodone]; no PAC: 167 [95% CI -274 to -62] fewer MMEs [-251 mg oxycodone]) and average MME per days' supply of medication (PAC: -3.0 [-4.6 to -1.4] fewer MMEs per day [-4.5 mg oxycodone]; no PAC: -4.7 [-4.6 to -1.4] fewer MMEs per day [-7.1 mg oxycodone]). In secondary analyses, Asian beneficiaries experienced the greatest differences (e.g., 617-653 fewer cumulative mg oxycodone)., Conclusion: Racial differences exist in pain management for Medicare beneficiaries after a hip fracture. Future work should examine whether these differences result in disparities in short- and long-term health outcomes., (© 2024 The American Geriatrics Society.)

Background: Overdose remains a pressing public health concern in the United States, particularly with the emergence of fentanyl and other potent synthetic opioids in the drug supply. We evaluated trends in recurrent overdose and opioid use disorder (OUD) treatment initiation following emergency department (ED) visits for opioid overdose to inform response efforts., Methods: This retrospective cohort study used electronic health record and statewide administrative data from Rhode Island residents who visited EDs for opioid overdose between July 1, 2016, and June 30, 2021, a period with fentanyl predominance in the local drug supply. The primary outcome was recurrent overdose in the 365 days following the initial ED visit. OUD treatment initiation within 180 days following the initial ED visit was considered as a secondary outcome. Trends in study outcomes were summarized by year of the initial ED visit., Results: Among 1745 patients attending EDs for opioid overdose, 20 % (n=352) experienced a recurrent overdose within 365 days, and this percentage was similar by year (p=0.12). Among patients who experienced any recurrent overdose, the median time to first recurrent overdose was 88 days (interquartile range=23-208), with 85 % (n=299/352) being non-fatal. Among patients not engaged in OUD treatment at their initial ED visit, 33 % (n=448/1370) initiated treatment within 180 days; this was similar by year (p=0.98)., Conclusions: Following ED visits for opioid overdose in Rhode Island from 2016-2021, the one-year risk of recurrent overdose and six-month treatment initiation rate remained stable over time. Innovative prevention strategies and improved treatment access are needed., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Randomised placebo-controlled trials (RPCTs) are the gold standard for evaluating novel treatments. However, this design is rarely used in the context of orthopaedic interventions where participants are assigned to a real or placebo surgery. The present study examines attitudes towards RPCTs for orthopaedic surgery among 687 orthopaedic surgeons across the USA. When presented with a vignette describing an RPCT for orthopaedic surgery, 52.3% of participants viewed it as 'completely' or 'mostly' unethical. Participants were also asked to rank-order the value of five different types of evidence supporting the efficacy of a surgery, ranging from RPCT to an anecdotal report. Responses regarding RPCTs were polarised with 26.4% viewing it as the least valuable (even less valuable than an anecdote) and 35.7 .% viewing it as the most valuable. Where equipoise exists, if we want to subject orthopaedic surgeries to the highest standard of evidence (RPCTs) before they are implemented in clinical practice, it will be necessary to educate physicians on the value and ethics of placebo surgery control conditions. Otherwise, invasive procedures may be performed without any benefits beyond possible placebo effects., Competing Interests: Competing interests: JS is a Partner Investigator on an Australian Research Council grant LP190100841 which involves industry partnership from Illumina. He does not personally receive any funds from Illumina. JS is a Bioethics Committee consultant for Bayer., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Limited evidence exists on health system characteristics associated with initial and long-term prescribing of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) following total hip and knee arthroplasty (THA/TKA), and if these characteristics differ among individuals based on preoperative NSAID exposure. We identified orthopedic surgeon opioid prescribing practices, hospital characteristics, and regional factors associated with initial and long-term prescribing of opioids and NSAIDs among older adults receiving THA/TKA., Materials and Methods: This observational study included opioid-naïve Medicare beneficiaries aged ≥65 years receiving elective THA/TKA between January 1, 2014 and July 4, 2017. We examined initial (days 1-30 following THA/TKA) and long-term (days 90-180) opioid or NSAID prescribing, stratified by preoperative NSAID exposure. Risk ratios (RRs) for the associations between 10 health system characteristics and case-mix adjusted outcomes were estimated using multivariable Poisson regression models., Results: The study population included 23,351 NSAID-naïve and 10,127 NSAID-prevalent individuals. Increases in standardized measures of orthopedic surgeon opioid prescribing generally decreased the risk of initial NSAID prescribing but increased the risk of long-term opioid prescribing. For example, among NSAID-naïve individuals, the RRs (95% confidence intervals [CIs]) for initial NSAID prescribing were 0.95 (0.93-0.97) for 1-2 orthopedic surgeon opioid prescriptions per THA/TKA procedure, 0.94 (0.92-0.97) for 3-4 prescriptions per procedure, and 0.91 (0.89-0.93) for 5+ opioid prescriptions per procedure (reference: <1 opioid prescription per procedure), while the RRs (95% CIs) for long-term opioid prescribing were 1.06 (1.04-1.08), 1.08 (1.06-1.11), and 1.13 (1.11-1.16), respectively. Variation in postoperative analgesic prescribing was observed across U.S. regions. For example, among NSAID-naïve individuals, the RR (95% CIs) for initial opioid prescribing were 0.98 (0.96-1.00) for Region 2 (New York), 1.09 (1.07-1.11) for Region 3 (Philadelphia), 1.07 (1.05-1.10) for Region 4 (Atlanta), 1.03 (1.01-1.05) for Region 5 (Chicago), 1.16 (1.13-1.18) for Region 6 (Dallas), 1.10 (1.08-1.12) for Region 7 (Kansas City), 1.09 (1.06-1.12) for Region 8 (Denver), 1.09 (1.07-1.12) for Region 9 (San Francisco), and 1.11 (1.08-1.13) for Region 10 (Seattle) (reference: Region 1 [Boston]). Hospital characteristics were not meaningfully associated with postoperative analgesic prescribing. The relationships between health system characteristics and postoperative analgesic prescribing were similar for NSAID-naïve and NSAID-prevalent participants., Discussion: Future efforts aiming to improve the use of multimodal analgesia through increased NSAID prescribing and reduced long-term opioid prescribing following THA/TKA could consider targeting orthopedic surgeons with higher standardized opioid prescribing measures., Conclusions: Orthopedic surgeon opioid prescribing measures and U.S. region were the greatest health system level predictors of initial, and long-term, prescribing of opioids and prescription NSAIDs among older Medicare beneficiaries following THA/TKA. These results can inform future studies that examine why variation in analgesic prescribing exists across geographic regions and levels of orthopedic surgeon opioid prescribing., Competing Interests: F.L.B. works as a Senior Medical Advisor for the Institute for Clinical and Economic Review with funds paid directly to Brown University. S.G. reports grants from Seqirus, Sanofi; and consulting or speaker fees from Sanofi, Seqirus, Merck, and the Gerontological Society of America related to vaccines or nursing home care quality. A.J.S. reports royalties from Wolters-Kluwer and Springer-Nature. V.M. is a paid consultant and Scientific Advisory Board chair to NaviHealth, Inc. Which offers post-acute care management and services to health plans and health systems. A.R.Z. reports prior grants from Sanofi paid directly to Brown University for research on the epidemiology of infections and vaccinations in older nursing home residents as well as respiratory syncytial virus in infants., (© The Author(s) 2024.)

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., Competing Interests: Declaration of competing interest Dr. Neylan reports consultation for Jazz Pharmaceuticals; Dr. Rauch reports royalties from Oxford University Press, the American Psychiatric Publishing Inc., and Springer Publishing royalties; Dr. McLean reports consultation for Walter Reed Army Institute for Research and for Arbor Medical Innovations; Dr. Kessler reports consultation for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, INC Mirah, PYM, and Roga Sciences; Dr. Koenen reports royalties from Guilford Press and Oxford University Press; Dr. Ressler reports consultation for Bioxcel, Bionomics, Acer, and Jazz Pharma; All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In the context of polysubstance use and fentanyl detection in non-opioid drugs supplies (e.g., cocaine, methamphetamine), it is important to re-evaluate and expand our understanding of which populations are at high risk for fatal drug overdoses. The primary objective of this pilot study was to gather data from the ED to characterize the population presenting with drug overdose, including demographics, drug use patterns and comorbidities, to inform upstream overdose prevention efforts., Methods: A consecutive sample of ED patients undergoing treatment for non-fatal overdose were prospectively recruited for study participation at the time of ED visit. Participants reported history of substance use over the past six months, recent and lifetime overdose, and naloxone receipt and administration history., Results: A total of 76 eligible participants were enrolled over the course of seven months. Participants reported high rates of opioid (56%), stimulant (56%), and cannabis use (59%). Self-reported polysubstance use, defined as self-reported use of more than one substance, was 83%. Of enrolled participants, 64% reported at least one overdose and 39% reported three or more lifetime overdoses prior to their index overdose ED visit. Participants with no self-reported intentional opioid use (n = 32) in the past six months had fentanyl positive urine drug screen 84% of the time versus 89% in the overall study population (n = 74). Participants who did not report opioid use in the past six months were less likely to possess (34% vs. 55%) or to know how to acquire (50% vs. 74%) naloxone compared to participants with self-reported history of opioid use., Conclusion: This study demonstrated high rates of fentanyl exposure on toxicology testing at time of overdose across all participants including study participants without self-reported intentional opioid use. Data gathered in the ED at time of overdose can be used to inform upstream naloxone distribution and public health initiatives., Competing Interests: Declaration of competing interest Research reported in this publication is supported by the National Institute of General Medical Sciences of the NIH under grant number P20GM125507. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This data has been presented at the North American Conference of Clinical Toxicology in Montreal, Canada in September 2023., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study examined if emergency department (ED) operational metrics, such as wait time or length of stay, are associated with interest in substance use disorder (SUD) treatment referral among patients at high risk of opioid overdose., Methods: In this observational study, 648 ED patients at high risk of opioid overdose completed a baseline questionnaire. Operational metrics were summarized using electronic health record data. The association between operational metrics and treatment interest was estimated with multivariable logistic regression., Results: Longer time to room (adjusted odds ratio [AOR]=1.12, 95% confidence interval [CI]=1.01-1.25) and length of stay (AOR=1.02, 95% CI=1.00-1.05) were associated with treatment referral interest. Time to provider and number of treating providers showed no significant association., Conclusion: Longer rooming wait times and longer ED visits were associated with increased SUD treatment referral interest. This suggests patients who wait for longer periods may be motivated for treatment and warrant further resource investment.

Background: People with opioid use disorder (OUD) frequently present at the emergency department (ED), a potentially critical point for intervention and treatment linkage. Peer recovery support specialist (PRSS) interventions have expanded in US-based EDs, although evidence supporting such interventions has not been firmly established., Methods: Researchers conducted a pragmatic trial of POINT (Project Planned Outreach, Intervention, Naloxone, and Treatment), an ED-initiated intervention for harm reduction and recovery coaching/treatment linkage in 2 Indiana EDs. Cluster randomization allocated patients to the POINT intervention (n  =  157) versus a control condition (n  =  86). Participants completed a structured interview, and all outcomes were assessed using administrative data from an extensive state health exchange and state systems. Target patients (n  =  243) presented to the ED for a possible opioid-related reason. The primary outcome was overdose-related ED re-presentation. Key secondary outcomes included OUD medication treatment linkage, duration of medication in days, all-cause ED re-presentation, all-cause inpatient re-presentation, and Medicaid enrollment. All outcomes were assessed at 3-, 6-, and 12-months post-enrollment. Ad hoc analyses were performed to assess treatment motivation and readiness., Results: POINT and standard care participants did not differ significantly on any outcomes measured. Participants who presented to the ED for overdose had significantly lower scores (3.5 vs 4.2, P  < .01) regarding readiness to begin treatment compared to those presenting for other opioid-related issues., Conclusions: This is the first randomized trial investigating overdose outcomes for an ED peer recovery support specialist intervention. Though underpowered, results suggest no benefit of PRSS services over standard care. Given the scope of PRSS, future work in this area should assess more recovery- and harm reduction-oriented outcomes, as well as the potential benefits of integrating PRSS within multimodal ED-based interventions for OUD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma., Methods: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months., Results: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus., Conclusions: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

In the United States, 8,000,000 people seek emergency care for traumatic injury annually. Motor vehicle collisions (MVCs) and sexual assault are two common sources of trauma, with evidence that reduced neighborhood-level socioeconomic characteristics increase posttraumatic pain and stress after an MVC. We evaluated whether neighborhood disadvantage was also associated with physical and mental posttrauma outcomes after sexual assault in a sample of adult women (N = 656) who presented for emergency care at facilities in the United States following sexual assault and were followed for 1 year. Neighborhood characteristics were assessed via the Area Deprivation Index, and self-reported pain, anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms were collected at 6 weeks posttrauma. Adjusted log-binomial regression models examined the association between each clinical outcome and neighborhood disadvantage. Women in more disadvantaged neighborhoods were more likely to be non-White and have lower annual incomes. At 6 weeks posttrauma, the prevalence of clinically significant pain, anxiety, and depressive symptoms more than doubled from baseline (41.7% vs. 18.8%, 62.4% vs. 23.9%, and 55.2% vs. 22.7%, respectively); 40.7% of women also reported PTSD symptoms. Black, Hispanic, and lower-income participants were more likely to report pre- and postassault pain, anxiety, and depression. After adjusting for race, ethnicity, and income, no significant association existed between neighborhood disadvantage and any outcome, ps = .197 - .859. Although neighborhood disadvantage was not associated with posttrauma outcomes, these findings highlight the need for continued research in diverse populations at high risk of adverse physical and mental health symptoms following sexual assault., (© 2024 International Society for Traumatic Stress Studies.)

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk., Competing Interests: Declaration of Competing Interest Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, and the Rett Research Foundation. Dr. Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical with significant stock. These relationships are unconnected to the current work. Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. Dr. Rauch reported serving as secretary of the Society of Biological Psychiatry; serving as a board member of Community Psychiatry and Mindpath Health; serving as a board member of National Association of Behavioral Healthcare; serving as secretary and a board member for the Anxiety and Depression Association of America; serving as a board member of the National Network of Depression Centers; receiving royalties from Oxford University Press, American Psychiatric Publishing Inc, and Springer Publishing; and receiving personal fees from the Society of Biological Psychiatry, Community Psychiatry and Mindpath Health, and National Association of Behavioral Healthcare outside the submitted work. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. Dr. Joormann receives consulting payments from Janssen Pharmaceuticals. Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Aptinyx. Dr. Koenen’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, Anonymous Philanthropy, LLC, and Cohen Veterans Bioscience. She has been a paid consultant for the US Department of Justice and Covington Burling, LLP over the last three years. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. Dr. McLean has served as a consultant for Walter Reed Army Institute for Research, Arbor Medical Innovations, and BioXcel Therapeutics, Inc., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture., Methods: Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration., Results: Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day., Conclusions: EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care., (© 2024 John Wiley & Sons Ltd.)

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.

Despite extensive research on sex/gender differences in posttraumatic stress disorder (PTSD), underlying mechanisms are still not fully understood. Here we present a systematic overview of three sex/gender-related risk pathways. We assessed 16 risk factors as well as 3-month PTSD severity in a prospective cohort study (n=2924) of acutely traumatized individuals and investigated potential mediators in the pathway between sex assigned at birth and PTSD severity using multiple mediation analysis with regularization. Six risk factors were more prevalent/severe in women, and none were more pronounced in men. Analyses showed that acute stress disorder, neuroticism, lifetime sexual assault exposure, anxiety sensitivity, and pre-trauma anxiety symptoms fully mediated and uniquely contributed to the relationship between sex assigned at birth and PTSD severity. Our results demonstrate different risk mechanisms for women and men. Such knowledge can inform targeted interventions. Our systematic approach to differential risk pathways can be transferred to other mental disorders to guide sex- and gender-sensitive mental health research., Competing Interests: Competing Interests Statement -Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. - In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation, and Samsung Research. Dr Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. - Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Dr. Germine’s family also has equity in Intelerad Medical Systems, Inc. -Dr. Rauch reports grants from NIH during the conduct of the study; personal fees from SOBP (Society of Biological Psychiatry) paid role as secretary, other from Oxford University Press royalties, other from APP (American Psychiatric Publishing Inc.) royalties, other from VA (Veterans Administration) per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers). - Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. - Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Indiana University and Memorial Sloan Kettering Cancer Center. - Dr. McLean served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations. - In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences. - Dr. Koenen’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, the Anonymous Foundation, and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality, and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. - The remaining authors declare no competing interests.

Objectives: Cannabinoid hyperemesis syndrome (CHS) is a clinical condition of cyclic vomiting, nausea, and abdominal pain associated with chronic cannabis use. Despite increased recognition of CHS, there are limited details on cannabis use practices and symptoms over time. Understanding what happens in the period surrounding the emergency department (ED) visit, including any changes in symptoms and cannabis use practices following the visit, can help inform the development of patient-centered interventions around cannabis use disorder for patients with CHS., Methods: A prospective observational cohort (n = 39) of patients with suspected CHS recruited from the ED at the time of a symptomatic cyclic vomiting episode was followed for 3 months. Disease progression, cannabis use practices, and health care utilization were monitored., Results: Participants reported high rates of persistent CHS symptoms (abdominal pain, nausea, or cyclic vomiting) in the 2-week period immediately following an ED visit with a median duration of 7 days. Cannabis use frequency and quantity were reduced immediately after the ED visit, but most participants returned to pre-ED visit cannabis use patterns within a few days. Recurrent ED visits for cyclic vomiting were reported by 25% of participants who completed follow-up during the 3-month follow-up period., Conclusions: Participants continued to have ongoing symptoms after the ED visit, but most managed symptoms on their own and did not return to the ED. Longitudinal studies beyond 3 months are needed to better understand the clinical course of patients with suspected CHS., (© 2023 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA., Methods: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models., Results: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons., Conclusions: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA., (© 2024. The Author(s).)

Introduction: Chronic pain and serious mental illness increase risk of opioid use, and opioid use can exacerbate both conditions. Substance use disorder (SUD) treatment can be lifesaving, but chronic pain and serious mental illness may make recovery challenging. We evaluated the association between current chronic pain and prior hospitalization for mental illness and 90-day SUD treatment engagement, among emergency department (ED) patients at high risk of opioid overdose., Methods: We conducted a cohort analysis of 648 ED patients enrolled in a randomized controlled trial in Rhode Island. We linked baseline study data on chronic pain and prior hospitalization for mental illness to statewide administrative data on state-licensed treatment programs (including methadone) and buprenorphine treatment via prescription. We defined treatment engagement as initiation of a state-licensed treatment program, transfer between state-licensed programs/providers, or a buprenorphine prescription (re-)fill. We used modified Poisson models to estimate the association between each baseline comorbidity and treatment engagement within 90 days following the ED visit, adjusted for a priori potential confounders. In an exploratory analysis, models were stratified by baseline treatment status., Results: The mean age of participants was 37 years; 439 (68 %) were male, and 446 (69 %) had been recently unhoused. Overall, 278 participants (43 %) engaged in treatment within 90 days of the ED visit. Participants with prior hospitalization for mental illness were more likely to engage in treatment than those without (adjusted risk ratio [ARR] = 1.24, 95 % confidence interval [CI] = 1.01-1.53), although this association was only among those already accessing treatment at baseline (ARR = 1.58, 95 % CI = 1.10-2.27). Chronic pain was not associated with 90-day treatment engagement overall (ARR = 1.12, 95 % CI = 0.91-1.38) or within baseline treatment subgroups., Conclusions: Among ED patients at high risk of opioid overdose and accessing treatment at baseline, those with prior hospitalization for mental illness (but not chronic pain) were more likely to engage in treatment following the ED visit, which may reflect disproportionate initiation of additional treatment programs, transfer between programs/providers, or ongoing buprenorphine treatment. Touchpoints within the medical system should be leveraged to ensure that everyone, including those with serious mental illness, can access high-quality SUD treatment at the desired intensity level., Competing Interests: Declaration of competing interest Dr. Beaudoin received grants from the National Institutes of Health, Centers for Disease Control and Prevention, and Institute for Clinical and Economic Review outside the submitted work. Dr. Marshall received grants from the National Institutes of Health outside of the submitted work. All other authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Amidst increasing opioid-related fatalities in adolescents and young adults (AYA), there is an urgent need to enhance the quality and availability of developmentally appropriate, evidence-based treatments for opioid use disorder (OUD) and improve youth engagement in treatment. Involving families in treatment planning and therapy augments medication-based OUD treatment for AYA by increasing treatment engagement and retention. Yet, uptake of family-involved treatment for OUD remains low. This study examined systems-level barriers and facilitators to integrating families in AYA OUD treatment in Rhode Island., Methods: An online survey was administered to clinic leaders and direct care providers who work with AYA in programs that provide medication and psychosocial treatments for OUD. The survey assessed attitudes towards and experiences with family-based treatment, barriers and facilitators to family-based treatment utilization, as well as other available treatment services for AYA and family members. Findings were summarized using descriptive statistics., Results: A total of 104 respondents from 14 distinct treatment programs completed the survey. Most identified as White (72.5%), female (72.7%), and between 25 and 44 years of age (59.4%). Over half (54.1%) of respondents reported no experience with family based treatment and limited current opportunities to involve families. Barriers perceived as most impactful to adopting family-based treatment were related to limited available resources (i.e. for staff training, program expansion) and lack of prioritization of family-based treatment in staff productivity requirements. Barriers perceived as least impactful were respondent beliefs and attitudes about family-based treatment (e.g., perception of the evidence strength and quality of family-based treatment, interest in implementing family-based treatment) as well as leadership support of family-based treatment approaches. Respondents identified several other gaps in availability of comprehensive treatment services, especially for adolescents (e.g. services that increase social recovery capital)., Conclusions: Family-based treatment opportunities for AYA with OUD in Rhode Island are limited. Affordable and accessible training programs are needed to increase provider familiarity and competency with family-based treatment. Implementation of programming to increase family involvement in treatment (i.e. psychoeducational and skills-based groups for family members) rather than adopting a family-based treatment model may be a more feasible step to better meet the needs of AYA with OUD., Trial Registration: not applicable., (© 2024. The Author(s).)

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD., Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables., Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated., Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata., Competing Interests: KK’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, the Anonymous Foundation, and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality, and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. TN has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years, GDC has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation, and Samsung Research. GDC has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. SR reports grants from NIH during the conduct of the study; personal fees from SOBP Society of Biological Psychiatry paid role as secretary, other from Oxford University Press royalties, other from APP American Psychiatric Publishing Inc. royalties, other from VA Veterans Administration per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, ADAA Anxiety and Depression Association of America, and NNDC National Network of Depression Centers. SS has received funding from the Florida Medical Malpractice Joint Underwriter’s Association Dr. Alvin E. Smith Safety of Healthcare Services Grant; Allergan Foundation; the NIH/NIA-funded Jacksonville Aging Studies Center JAX-ASCENT; R33AG05654; and the Substance Abuse and Mental Health Services Administration 1H79TI083101-01; and the Florida Blue Foundation. CJ has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. JJ receives consulting payments from Janssen Pharmaceuticals. SEH has no competing interests related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Aptinyx, Heron Therapeutics, and Eli Lilly. SM served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor Y-lT declared a shared affiliation with the author(s) GDC., (Copyright © 2024 Garrison-Desany, Meyers, Linnstaedt, House, Beaudoin, An, Zeng, Neylan, Clifford, Jovanovic, Germine, Bollen, Rauch, Haran, Storrow, Lewandowski, Musey, Hendry, Sheikh, Jones, Punches, Swor, Gentile, Hudak, Pascual, Seamon, Harris, Pearson, Peak, Domeier, Rathlev, O’Neil, Sergot, Sanchez, Bruce, Joormann, Harte and McLean, Koenen and Denckla.)

Medications and pharmacy services are critical to post-acute care (PAC) in skilled nursing facilities (SNFs), yet little is known about the long-term care (LTC) pharmacies that provide them. We estimated the market shares of LTC pharmacies and how SNFs differed between pharmacies. This cross-sectional study used data from SNFs that provided PAC services in Rhode Island (RI) in 2019. We applied the parametric g-formula to compare SNF pharmacy-related deficiencies and medication use measures between LTC pharmacies while standardizing for SNF membership in a chain and number of beds. Among 75 SNFs, 68 (91%) were served by either Omnicare ( n  = 32, 43%) or PharMerica ( n  = 36, 48%), and 7 (9%) by other LTC pharmacies. After covariate adjustment, PharMerica SNFs had the lowest prevalences of any pharmacy-related deficiency (PharMerica, 63.2%; Omnicare, 80.2%; other LTC pharmacy, 69.1%) and antianxiety medication use (PharMerica, 9.7%; Omnicare, 13.6%; other LTC pharmacy, 13.5%), but estimates were imprecise. The RI market is highly concentrated between LTC pharmacies. If similarly high LTC pharmacy market concentration exists nationally, there is enormous promise for efficiently delivering interventions to improve medication management in SNFs. However, it may also present a risk of harm if policies do not maintain sufficient competition and innovation is stifled.

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.