Search

In this Letter we report on the first inverse kinematics measurement of key resonances in the Ne22(p,γ)23Na reaction which forms part of the NeNa cycle, and is relevant for 23Na synthesis in asymptotic giant branch (AGB) stars. An anti-correlation in O and Na abundances is seen across all well-studied globular clusters (GC), however, reaction-rate uncertainties limit the precision as to which stellar evolution models can reproduce the observed isotopic abundance patterns. Given the importance of GC observations in testing stellar evolution models and their dependence on NeNa reaction rates, it is critical that the nuclear physics uncertainties on the origin of 23Na be addressed. We present results of direct strengths measurements of four key resonances in Ne22(p,γ)23Na at Ec.m. = 149 keV, 181 keV, 248 keV and 458 keV. The strength of the important Ec.m. = 458 keV reference resonance has been determined independently of other resonance strengths for the first time with an associated strength of ωγ = 0.439(22) eV and with higher precision than previously reported. Our result deviates from the two most recently published results obtained from normal kinematics measurements performed by the LENA and LUNA collaborations but is in agreement with earlier measurements. The impact of our rate on the Na-pocket formation in AGB stars and its relation to the O-Na anti-correlation was assessed via network calculations. Further, the effect on isotopic abundances in CO and ONe novae ejecta with respect to pre-solar grains was investigated.

Quasi-elastic scattering measurements have been performed using 16O and 24Mg projectiles off 90Zr at energies around the Coulomb barrier. Experimental data have been analyzed in the framework of coupled channels (CC) calculations using the code CCFULL. The quasi-elastic scattering excitation function and derived barrier distribution for 16O + 90Zr reaction are well reproduced by the CC calculations using the vibrational coupling strengths for 90Zr reported in the literature. Using these vibrational coupling strengths, a Bayesian analysis is carried out for 24Mg + 90Zr reaction. The β2 and β4 values for 24Mg are determined to be +0.43±0.02 and −0.11±0.02, respectively. The β2 parameter determined in the present work is in good agreement with results obtained using inelastic scattering probes. The hexadecapole deformation of 24Mg has been measured very precisely for the first time. Present results establish that quasi-elastic scattering could provide a useful probe to determine the ground state deformation of atomic nuclei.

Abstract Background Complex social determinants of health may not be easily recognized by health care providers and pose a unique challenge in the vulnerable pediatric population where patients may not be able to advocate for themselves. The goal of this study was to examine the acceptability and feasibility of health care providers using an integrated brief pediatric screening tool in primary care and hospital settings. Methods The framework of the Child and Adolescent Needs and Strengths (CANS) and Pediatric Intermed tools was used to inform the selection of items for the 9-item Child and Adolescent Needs and Strengths-Pediatric Complexity Indicator (CANS-PCI). The tool consisted of three domains: biological, psychological, and social. Semi-structured interviews were conducted with health care providers in pediatric medical facilities in Ottawa, Canada. A low inference and iterative thematic synthesis approach was used to analyze the qualitative interview data specific to acceptability and feasibility. Results Thirteen health care providers participated in interviews. Six overarching themes were identified: acceptability, logistics, feasibility, pros/cons, risk, and privacy. Overall, participants agreed that a routine, trained provider-led pediatric tool for the screening of social determinants of health is important (n = 10, 76.9%), acceptable (n = 11; 84.6%), and feasible (n = 7, 53.8%). Interpretation Though the importance of social determinants of health are widely recognized, there are limited systematic methods of assessing, describing, and communicating amongst health care providers about the biomedical and psychosocial complexities of pediatric patients. Based on this study’s findings, implementation of a brief provider-led screening tool into pediatric care practices may contribute to this gap.

Opioid overdose is a leading cause of death in the United States, and engaging with patients following overdose to provide harm reduction and recovery resources can prove difficult. Quick response models use mobile, multidisciplinary teams to establish a time-sensitive connection between individuals who overdosed and harm reduction and recovery resources that improve outcomes. These quick response models are consistent with the broader field of mobile-integrated health programs that are growing in number and acceptability, though the literature base is sparse and programs vary. We describe the 5-year reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework of the Rapid Response Emergency Addiction and Crisis Team (RREACT), a fire/emergency medical services-led, multidisciplinary (firefighter/paramedic, law enforcement officer, social worker) mobile outreach team. RREACT provides harm reduction, linkage/transportation to care and wrap-around services to individuals following a nonfatal opioid overdose that resulted in an emergency response in Columbus, Franklin County, Ohio, United States. Between 2018 and 2022, RREACT made 22,157 outreach attempts to 11,739 unique patients. RREACT recorded 3,194 direct patient contacts during this time, resulting in 1,200 linkages to care: 799 direct transports to opioid use disorder treatment and 401 warm handoffs to community treatment agencies. Furthermore, RREACT’s staffing increased from 4 full-time equivalent staff in 2018 to 15.5 in 2022 and was supported by the surrounding community through 287 community outreach events and the development of an alumni program. These preliminary results further support the deployment of multidisciplinary mobile outreach teams to increase access to harm reduction and recovery resources following opioid overdose.

Abstract Study objective Earlier intervention for opioid use disorder (OUD) may reduce long‐term health implications. Emergency departments (EDs) in the United States treat millions with OUD annually who may not seek care elsewhere. Our objectives were (1) to compare two screening measures for OUD characterization in the ED and (2) to determine the proportion of ED patients screening positive for OUD and those who endorse other substance use to guide future screening programs. Methods A cross‐sectional study of randomly selected adult patients presenting to three Midwestern US EDs were enrolled, with duplicate patients excluded. Surveys were administered via research assistant and documented on tablet devices. Demographics were self‐reported, and OUD positivity was assessed by the DSM 5 checklist and the WHO ASSIST 3.1. The primary outcome was the concordance between two screening measures for OUD. Our secondary outcome was the proportion of ED patients meeting OUD criteria and endorsed co‐occurring substance use disorder (SUD) criteria. Results We enrolled 1305 participants; median age of participants was 46 years (range 18–84), with 639 (49.0%) Non‐Hispanic, White, and 693 (53.1%) female. Current OUD positivity was identified in 17% (222 out of 1305) of the participants via either DSM‐5 (two or more criteria) or ASSIST (score of 4 or greater). We found moderate agreement between the measures (kappa = 0.56; Phi coefficient = 0.57). Of individuals screening positive for OUD, 182 (82%) endorsed criteria for co‐occurring SUD. Conclusions OUD is remarkably prevalent in ED populations, with one in six ED patients screening positive. We found a high prevalence of persons identified with OUD and co‐occurring SUD, with moderate agreement between measures. Developing and implementing clinically feasible OUD screening in the ED is essential to enable intervention.

IntroductionPatients are stakeholders in their own pain management. Factors motivating individuals to seek or use opioids therapeutically for treatment of acute pain are not well characterized but could be targeted to reduce incident iatrogenic opioid use disorder (OUD). Emergency departments (EDs) commonly encounter patients in acute pain for whom decisions regarding opioid therapy are required. Decision-making is necessarily challenged in episodic, unscheduled care settings given time pressure, limited information, and lack of pre-existing patient provider relationship. Patients may decline to take prescribed opioids or conversely seek opioids from other providers or non-medical sources.MethodsUsing a framework analysis approach, we qualitatively analyzed transcripts from 29 patients after discharge from an ED visit for acute pain at a large, urban, academic hospital in the midwestern United States to describe motivating factors influencing patient decisions regarding opioid use for acute pain. A semi-structured interview guide framed participant discussion in either a focus group or interview transcribed and analyzed with conventional content analysis.ResultsFour major themes emerged from our analysis including a) pain management literacy, b) control preferences, c) risk tolerance, and d) cues to action.DiscussionOur findings suggest targets for future intervention development and a framework to guide the engagement of patients as stakeholders in their own acute pain management.

Abstract Introduction Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. Methods Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. Discussion Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. Conclusion Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine. Graphical Abstract

Objective: To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes. Patients and Methods: Patients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models. Results: Our analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, −0.71; P=.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; P=.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; P=.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; P

Abstract Background There are more than 1 million hospital admissions and 3 million emergency visits for heart failure in the USA annually. Although spouse/partners make substantial contributions to the management of heart failure and experience poor health and high levels of care strain, they are rarely the focus of heart failure interventions. This protocol describes a pilot randomized controlled trial that tests the feasibility, acceptability, and preliminary change in outcomes of a seven-session couple-based intervention called Taking Care of Us© (TCU). The TCU© intervention is grounded in the theory of dyadic illness management and was developed to promote collaborative illness management and better physical and mental health of adults with heart failure and their partners. Methods A two-arm randomized controlled trial will be conducted. Eligible adults with heart failure and their co-residing spouse/partner will be recruited from a clinical site in the USA and community/social media outreach and randomized to either the TCU© intervention or to a control condition (SUPPORT©) that offers education around heart failure management. The target sample is 60 couples (30 per arm). TCU© couples will receive seven sessions over 2 months via Zoom; SUPPORT© couples will receive three sessions over 2 months via Zoom. All participants will complete self-report measures at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3). Acceptability and feasibility of the intervention will be examined using both closed-ended and open-ended questions as well as enrollment, retention, completion, and satisfaction metrics. Preliminary exploration of change in outcomes of TCU© on dyadic health, dyadic appraisal, and collaborative management will also be conducted. Discussion Theoretically driven, evidence-based dyadic interventions are needed to optimize the health of both members of the couple living with heart failure. Results from this study will provide important information about recruitment and retention and benefits and drawbacks of the TCU© program to directly inform any needed refinements of the program and decision to move to a main trial. Trial registration ClinicalTrials.gov (NCT04737759) registered on 27 January 2021.

Abstract Background Hepatitis C (HCV) poses a major public health problem in the USA. While early identification is a critical priority, subsequent linkage to a treatment specialist is a crucial step that bridges diagnosed patients to treatment, cure, and prevention of ongoing transmission. Emergency departments (EDs) serve as an important clinical setting for HCV screening, although optimal methods of linkage-to-care for HCV-diagnosed individuals remain unknown. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial. Methods The DETECT Hep C Linkage-to-Care Trial will be a single-center prospective comparative effectiveness randomized two-arm parallel-group superiority trial to test the effectiveness of linkage navigation and clinician referral among ED patients identified with untreated HCV with a primary hypothesis that linkage navigation plus clinician referral is superior to clinician referral alone when using treatment initiation as the primary outcome. Participants will be enrolled in the ED at Denver Health Medical Center (Denver, CO), an urban, safety-net hospital with approximately 75,000 annual adult ED visits. This trial was designed to enroll a maximum of 280 HCV RNA-positive participants with one planned interim analysis based on methods by O’Brien and Fleming. This trial will further inform the evaluation of cost effectiveness, disparities, and social determinants of health in linkage-to-care, treatment, and disease progression. Discussion When complete, the DETECT Hep C Linkage-to-Care Trial will significantly inform how best to perform linkage-to-care among ED patients identified with HCV. Trial registration ClinicalTrials.gov ID: NCT04026867 Original date: July 1, 2019 URL: https://clinicaltrials.gov/ct2/show/NCT04026867

Abstract Background Multiple lumbar punctures have historically been a strategy to relieve headaches associated with idiopathic intracranial hypertension despite limited clinical evidence of long-term efficacy. Lumbar puncture is typically a straightforward procedure with minimal complications reported, however, serious complications can occur. Lumbar-puncture-related spinal hematomas are rare but can lead to irreversible paralysis. Case presentation We report a case of a 28-year-old Caucasian woman who was treated with multiple lumbar punctures to manage headache, thought to be attributed to idiopathic intracranial hypertension. The patient developed a lumbosacral epidural hematoma following a lumbar puncture, which led to incomplete cauda equina syndrome. Multiple lumbar punctures had been the long-term management for the patient’s chronic headaches associated with her diagnosis of idiopathic intracranial hypertension. She had no risks of an underlying coagulopathy. Following a lumbar puncture, she re-presented with lower back pain and bilateral paresthesia. Over the subsequent 48 hours, this progressed to urinary incontinence and saddle paresthesia. Imaging revealed an epidural hematoma, which was conservatively managed. She continued to report saddle paresthesia and urinary incontinence 7 months following the lumbar puncture. Between 1974 to 2022, our literature search found 41 case reports detailing lumbar-puncture-related spinal hematomas. It is an established but rare complication of lumbar puncture and there are limited studies looking at the incidence of its occurrence. Whilst coagulopathy has been found to be a risk factor, it is unclear if the gauge of the needle is relevant. Case evidence suggests there may be no significant difference in outcomes between surgical and conservative management of spinal hematomas. This case highlights that lumbar punctures can be invasive, with potentially serious complications. A lumbar puncture should therefore only be performed when clinically justified. Conclusions This case highlights a rare complication of lumbar puncture and emphasizes the importance of a risk–benefit discussion for each procedure. Spinal hematoma following lumbar puncture is a rare complication but with potentially devastating consequences. Within the setting of idiopathic intracranial hypertension, the evidence base for the long-term benefit of headache relief by repeat lumbar puncture is low.

Abstract Background Reproductive and sexual health (RSH) concerns are common and distressing for young adults diagnosed with breast and gynecologic cancer and their partners. This study evaluates the efficacy of a virtual couple-based intervention called Opening the Conversation (OC). The OC intervention is grounded in theory and evidence-based practice and was adapted to improve coping and communication specifically in relation to RSH concerns after cancer. Methods This Phase III trial is conducted in a fully remote setting and enrolls young adult couples (current age 18–44 years) with a history of breast or gynecologic cancer (stage 1–4, diagnosed under age 40) within the past 6 months to 5 years. Eligible dyads are recruited from across the USA. The target sample size is 100 couples. Dyads are randomly assigned to receive either the 5-session OC intervention or a 4-session active control intervention (Side by Side). The primary outcomes are change in reproductive distress and sexual distress. Secondary outcomes include communication about reproductive concerns, communication about sexual concerns, depressive symptoms, sexual function, relationship quality, relationship intimacy, sexual satisfaction, self-efficacy to communicate about sex and intimacy, and quality of life. An exploratory aim examines whether dyadic coping and communication quality mediate intervention effects on survivors’ and partners’ reproductive distress or sexual distress. Self-report outcome measures are assessed for both groups at baseline (T1), 2 weeks post-treatment (T2), and 3 months post-treatment (T3). Discussion Despite the importance of RSH for quality of life for young adult cancer survivors and their partners, evidence-based interventions that help couples navigate RSH concerns are lacking. This randomized controlled trial will determine the efficacy of a novel couple-based intervention to reduce distress related to RSH concerns for younger couples after breast or gynecologic cancer, in comparison to an active control intervention. Trial registration ClinicalTrials.gov NCT04806724. Registered on Mar 19, 2021.

Understanding and addressing the impact of adverse life events is an important priority in the design of helping systems. However, creating trauma-informed systems requires efforts to embed effective trauma-informed work in routine practice. This article discusses a model for developing trauma-informed systems using the Transformational Collaborative Outcomes Management (TCOM) framework, a strategy for engineering person-centered care. Person-centered care is naturally congruent with trauma-informed care. We describe the initial stages of implementation of a trauma-informed standardized assessment process to support the sustained evolution of trauma-informed care. Distinguishing between traumatic experiences and traumatic stress is fundamental to an effective trauma-informed system. We describe two sets of analyses—one in a statewide child welfare system and the other in a statewide behavioral health system. These projects found opportunities in the analysis of the detection of traumatic stress based on traumatic experiences to inform practice and policy. Being trauma-informed in child welfare is distinct from being trauma-informed in behavioral health. In child welfare, it appears that a number of children are resilient in the face of traumatic experiences and do not require trauma treatment interventions. However, delayed and missed traumatic stress responses are common. In behavioral health, misses often occur among adolescents, particularly boys, who engage in acting out behavior. Opportunities for the ongoing development of trauma-informed systems using the TCOM framework are discussed.

Abstract Background Early identification of HCV is a critical health priority, especially now that treatment options are available to limit further transmission and provide cure before long-term sequelae develop. Emergency departments (EDs) are important clinical settings for HCV screening given that EDs serve many at-risk patients who do not access other forms of healthcare. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Screening Trial. Methods The DETECT Hep C Screening Trial is a multi-center prospective pragmatic randomized two-arm parallel-group superiority trial to test the comparative effectiveness of nontargeted and targeted HCV screening in the ED with a primary hypothesis that nontargeted screening is superior to targeted screening when identifying newly diagnosed HCV. This trial will be performed in the EDs at Denver Health Medical Center (Denver, CO), Johns Hopkins Hospital (Baltimore, MD), and the University of Mississippi Medical Center (Jackson, MS), sites representing approximately 225,000 annual adult visits, and designed using the PRECIS-2 framework for pragmatic trials. When complete, we will have enrolled a minimum of 125,000 randomized patient visits and have performed 13,965 HCV tests. In Denver, the Screening Trial will serve as a conduit for a distinct randomized comparative effectiveness trial to evaluate linkage-to-HCV care strategies. All sites will further contribute to embedded observational studies to assess cost effectiveness, disparities, and social determinants of health in screening, linkage-to-care, and treatment for HCV. Discussion When complete, The DETECT Hep C Screening Trial will represent the largest ED-based pragmatic clinical trial to date and all studies, in aggregate, will significantly inform how to best perform ED-based HCV screening. Trial registration ClinicalTrials.gov ID: NCT04003454 . Registered on 1 July 2019.

Introduction Opioid-involved overdose deaths continue to surge in many communities, despite numerous evidence-based practices (EBPs) that exist to prevent them. The HEALing Communities Study (HCS) was launched to develop and test an intervention (ie, Communities That HEAL (CTH)) that supports communities in expanding uptake of EBPs to reduce opioid-involved overdose deaths. This paper describes a protocol for a process foundational to the CTH intervention through which community coalitions select strategies to implement EBPs locally.Methods and analysis The CTH is being implemented in 67 communities (randomised to receive the intervention) in four states in partnership with coalitions (one per community). Coalitions must select at least five strategies, including one to implement each of the following EBPs: (a) overdose education and naloxone distribution; expanded (b) access to medications for opioid use disorder (MOUD), (c) linkage to MOUD, (d) retention in MOUD and (e) safer opioid prescribing/dispensing. Facilitated by decision aid tools, the community action planning process includes (1) data-driven goal setting, (2) discussion and prioritisation of EBP strategies, (3) selection of EBP strategies and (4) identification of next steps. Following review of epidemiologic data and information on existing local services, coalitions set goals and discuss, score and/or rank EBP strategies based on feasibility, appropriateness within the community context and potential impact on reducing opioid-involved overdose deaths with a focus on three key sectors (healthcare, behavioural health and criminal justice) and high-risk/vulnerable populations. Coalitions then select EBP strategies through consensus or majority vote and, subsequently, suggest or choose agencies with which to partner for implementation.Ethics and dissemination The HCS protocol was approved by a central Institutional Review Board (Advarra). Results of the action planning process will be disseminated in academic conferences and peer-reviewed journals, online and print media, and in meetings with community stakeholders.Trial registration number NCT04111939.

ObjectiveThe objective of this study was to examine associations between level of depressive symptoms in older adult spouse/partner couples and their physical health and social factors (social activity and number of close friends).MethodsUsing data from 116 community-dwelling couples (age 76.2 ± 8.5), we simultaneously analyzed associations between depressive symptoms (Geriatric Depression Scale, range 0–11) and dyadic physical health, engagement in social activities, and connectedness with close friends.ResultsGreater engagement in social activities was associated with fewer depressive symptoms in men, whereas more close friendships were associated with fewer depressive symptoms in women, controlling for partner effects, age, education, and cognitive function, with good model fit. Additionally, more disparate physical health within the couple (latent incongruence score) was associated with greater depressive symptoms in men.DiscussionLess social activity and fewer close friends were associated with depressive symptoms in older adult couples, but may be distinctly influential depending on gender and in the context of the older adult couple's physical health.

Abstract Background Most cancer survivors are married, and cancer strains the physical and mental health of each partner and their intimate relationship. We created a partnered strength training program, Exercising Together©, where the survivor and his/her partner exercise as a team in order to improve physical and mental health of both members of the couple as well as the quality of their relationship. We have not yet determined if Exercising Together© is similarly effective in couples coping with different types of cancer nor if training as a team has unique and added benefits over those derived from supervised group training and/or shared behavior change. The purpose of this study is to determine the unique benefits of Exercising Together© on physical, mental, and relational health in couples coping with breast, prostate, or colorectal cancer. Methods Survivors of prostate, breast and colorectal cancer (N = 294, 98 per cancer site) and their intimate, co-residing partners are recruited to participate in a single-blind, parallel group, randomized trial comparing three exercise groups that train twice per week for 6 months. Couples are randomized to one of three groups: (1) Exercising Together© where partners train as a team in a supervised group setting; (2) separate supervised group exercise classes for survivors or partners, respectively; (3) unsupervised home exercise program provided to each partner. The primary outcome is relationship quality (dyadic coping by the Dyadic Coping scale, emotional intimacy by the Dyadic Adjustment Scale, physical intimacy by the Physical Intimacy Behavior Scale, and symptom incongruence). Secondary outcomes are physical health (% body fat by DXA, serum fasting lipids (triglycerides, HDL, and LDL cholesterol), insulin resistance (HOMA-IR), resting blood pressure, C-reactive protein, TNF alpha, and physical functioning by the short Physical Performance Battery and SF-36) and mental health (depressive symptoms, anxiety, fear of recurrence) of each partner. Outcomes are collected at baseline, mid (3 months), post-intervention (6 months), and follow-up (12 months). Discussion Exercising Together© could shift the paradigm of survivorship care toward novel couple-based approaches that could optimize outcomes for each partner because their health is interdependent on each other and their relationship. Trial registration ClinicalTrials.gov NCT03630354 . Registered August 14, 2018

ObjectiveWhether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.MethodsParticipants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months.ResultsOf 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5).ConclusionsED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

Abstract Emergency departments (EDs) have played a major role in the science and practice of HIV population screening. After decades of experience, EDs have demonstrated the capacity to provide testing and linkage to care to large volumes of patients, particularly those who do not otherwise engage the healthcare system. Efforts to expand ED HIV screening in the United States have been accelerated by a collaborative national network of emergency physicians and other stakeholders called EMTIDE (Emergency Medicine Transmissible Infectious Diseases and Epidemics). As the COVID‐19 pandemic evolves, EDs nationwide are being tasked with diagnosing and managing COVID‐19 in a myriad of capacities, adopting varied approaches based in part on know‐how, local disease trends, and the supply chain. The objective of this article is to broadly summarize the lessons learned from decades of ED HIV screening and provide guidance for many analogous issues and challenges in population screening for COVID‐19. Over time, and with the accumulated experience from other epidemics, ED screening should develop into an overarching discipline in which the disease in question may vary, but the efficiency of response is increased by prior knowledge and understanding.

Abstract Objective Therapeutic opioid exposure is associated with long‐term use. How much later use is due to opioid use disorder (OUD) and the incidence of OUD without preceding therapeutic exposure are unknown. We preliminarily explored the association between emergency department opioid prescriptions and subsequent OUD. Methods This retrospective cohort study queried electronic health records for discharged adult patients in the year before (2014) and after (2016) their first encounter in 2015 at either of 2 EDs in a Midwestern healthcare system. OUD was defined by diagnosis codes and prescription history. Patients with OUD history before the index encounter were excluded. We report OUD incidence within 1 year, with time to first indicator of OUD among those with a repeat health system encounter post index using a Cox proportional hazards model. Secondary outcomes were sources of therapeutic opioid exposure and frequency of risk factors associated with OUD among those who developed OUD. Results Of the 49,904 unique, adult ED patients without history of OUD, 669 (1.3%; 95% CI, 1.2–1.4) had health records indicating OUD within 12 months. The proportion of ED patients with OUD at 12 months was 1.5% (95% CI, 1.2–1.9) if prescribed an opioid at index and 1.3% (95% CI, 1.2–1.4) if not. Of the 669 who developed OUD, 80 (12.0%) were prescribed an opioid at the index ED visit, 54 (8%) received an opioid prescription at a subsequent ED visit, and median time to OUD was 4.5 months (interquartile range 1.6‐7.6, range 0.0–11.9). When controlling for demographics, mental health, and prior opioid prescriptions, there was no difference in OUD incidence between patients who did or did not receive an initial ED opioid prescription (HR, 1.1; 95% CI, 0.9–1.4). Conclusions A small but meaningful proportion of the ED population will develop OUD within 1 year even without ED opioid prescription. Though we found no association between ED opioid prescription and later OUD, further study is warranted given the complexity factors influencing OUD incidence, ongoing ED opioid exposure, and limitations inherent to this study design.

The downregulation of sclerostin in osteocytes mediates bone formation in response to mechanical cues and parathyroid hormone (PTH). To date, the regulation of sclerostin has been attributed exclusively to the transcriptional downregulation of the Sost gene hours after stimulation. Using mouse models and rodent cell lines, we describe the rapid, minute-scale post-translational degradation of sclerostin protein by the lysosome following mechanical load and PTH. We present a model, integrating both new and established mechanically and hormonally activated effectors into the regulated degradation of sclerostin by lysosomes. Using a mouse forelimb mechanical loading model, we find transient inhibition of lysosomal degradation or the upstream mechano-signaling pathway controlling sclerostin abundance impairs subsequent load-induced bone formation by preventing sclerostin degradation. We also link dysfunctional lysosomes to aberrant sclerostin regulation using human Gaucher disease iPSCs. These results reveal how bone anabolic cues post-translationally regulate sclerostin abundance in osteocytes to regulate bone formation.

The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies.

ABSTRACT IMPACT: This study is designed to address a critical gap in our understanding of how aging patients and caregivers recognize and respond to clinically important changes in heart failure symptoms during vulnerable transitions. OBJECTIVES/GOALS: Research on family involvement in heart failure (HF) symptom response is limited. Our objective is to examine HF symptom monitoring processes in couples after HF hospitalization, and quantify how coupled symptom assessments predict symptom response, patient clinical events, care strain, and dyad health during the high-risk post-discharge period. METHODS/STUDY POPULATION: This is an ongoing T2 translational study that employs an intensive longitudinal design. Adults aged ≥65 years hospitalized for HF and their caregiving spouse/partner are enrolled. The target n is 48 dyads. Over 5 weeks of follow-up, dyads complete daily diaries assessing patient HF symptoms. Clinical biomarkers of HF severity (NTproBNP, ST2) are also collected. Primary study endpoints are dyads’ HF symptom response behaviors and caregiver strain; secondary endpoints are dyads’ health status and patient clinical events. Dyadic dynamics of symptom assessment will first be characterized using dyadic autoregressive time series models. Subsequently, we will extract cross-partner effect parameters from the time series models and test whether dyadic effects predict the trajectories of each of our endpoints. RESULTS/ANTICIPATED RESULTS: This study is currently underway. In line with our study hypotheses, we anticipate that couples who assess patient symptoms similarly (dyadic agreement), and whose symptom assessments accurately reflect clinical severity, will be more likely to respond to symptoms appropriately with lower stress to the caregiving partner, and have better trajectories of health (self-reported and clinical). Characterizing dyadic symptom dynamics will provide important insight into the day-to-day process of symptom recognition in couples. Further, quantifying dyadic symptom dynamics in relation to our endpoints will provide information on the clinical value of dyadic symptom agreement, and whether it might be a target for future interventions to support better symptom response and health outcomes for both dyad members. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project innovates on existing paradigms by applying family-level theory and techniques to better understand and support interventions for couples during post-discharge HF transitions - a vulnerable period for older adults that has traditionally been studied almost exclusively at the patient-level, with marginal success.

BackgroundAlthough current guidelines emphasize the importance of social support to the success of left ventricular assist device (LVAD) therapy, few studies examine the influence of the caregiver on patient outcomes or quantify the impact of LVAD caregiving on caregiver outcomes. The purpose of this analysis was to identify patient and caregiver determinants of patient quality of life (QOL) and caregiver strain in response to LVAD therapy. Methods and ResultsData on patients receiving LVAD therapy and their caregivers (n=50 dyads) were prospectively collected pre‐implantation and 1, 3, and 6 months post‐implantation. Growth curve modeling was used to describe change in patient QOL (Kansas City Cardiomyopathy Questionnaire) and caregiver strain (Multidimensional Caregiver Strain Index). Patient QOL improved most in the first month (β=23.22±3.76, P