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Introduction: To assist the state of Ohio in addressing the opioid epidemic, the Ohio Attorney General appointed experts in a variety of academic disciplines to the Scientific Committee on Opioid Prevention and Education (SCOPE). The focus of SCOPE is the application of scientific principles to the development of prevention and educational strategies for reducing substance use disorder and related harms (e.g., promoting naloxone awareness). Naloxone awareness is a step in the naloxone cascade, which is a useful model for understanding the sequential steps laypeople must take to prepare themselves to intervene using naloxone; other steps include training and previous administration experience. Prior work has explored correlates of these steps among individuals with risky substance use, but fewer studies have focused on broader populations containing potential bystanders (e.g., family and community members)., Methods: This study was a secondary data analysis of patients from three urban emergency departments. Subsamples differed across five models (n = 479-1208) and included opioid-exposed and -naïve participants. Logistic regression characterized clinically useful sociodemographic predictors (e.g., race, ethnicity, education, employment, housing status) of naloxone awareness, self-efficacy (which relates to training), and previous-overdose administration. Two additional logistic regressions tested associations between risk factors for witnessing an opioid overdose and two cascade steps (awareness and self-efficacy)., Results: Non-White race, Hispanic ethnicity, and lower education predicted not being aware of naloxone; non-White race also predicted lower naloxone self-efficacy, and older age predicted lack of previous-overdose administration. Having family members with risky opioid use was heavily associated with awareness, while personal substance-use behaviors and previous overdose witnessing were associated with both awareness and higher naloxone self-efficacy., Conclusions: Characteristics associated with lower likelihood of completing each cascade step highlight opportunities for targeted interventions. Specifically, findings indicated the importance of expanding naloxone education and training programs to more diverse populations and to family members of individuals with risky opioid use. Further, these findings demonstrate how a state-funded program such as SCOPE can have a positive impact on identifying strategies that may assist in reducing mortality associated with opioid overdose., Competing Interests: Declaration of competing interest The following authors received compensation for time spent on the parent study through awards to their institutions from the Ohio Attorney General Office (Grant Number 12545): Rob Braun, Drs. Freiermuth, Brown, Lyons, and Punches. Dr. Littlefield received compensation for the parent study through consultant payments. Authors Petrovitch, Himes, Jump, and Sprague declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In 2023, 3651 Ohioans died because of an opioid overdose. Of those opioid overdoses, 3579 (98%) of which were attributed to fentanyl. We evaluated the association between 180 candidate single nucleotide polymorphisms (SNPs) and self-reported, nonfatal opioid overdose history from a prospective sample of 1301 adult patients (≥18 years of age) seen in three urban emergency departments in Ohio. Candidate SNPs included 120 related to the dopamine reward pathway and 60 related to pharmacokinetics. Of the 821 patients who reported having been exposed to opioids in their lifetime, 95 (11.6%) also reported having experienced an opioid-related overdose. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and opioid overdose, correcting for multiple comparisons. Three SNPs, located in three different genes were associated with opioid overdose: increased odds with CYP3A5 (rs776746) and DRD2 (rs4436578), and decreased odds with NKIR (rs6715729). Homozygotic CYP3A5 (rs776746) had the highest adjusted odds ratio (OR) of 6.96 (95% CI [2.45, 29.23]) and homozygotic NK1R (rs6715729) had the lowest OR of 0.28 (95% CI [0.14, 0.54). Given that CYP3A5 (rs776746) has been associated with increased plasma concentrations of fentanyl, rs776746 could potentially be utilized as a prognostic risk indicator for the potential of an opioid overdose. NK1R regulates the expression of the neurokinin-1 receptor, a regulator of respiration and NK1R (rs6715729) represents a novel genetic marker for a decreased risk of opioid overdose risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the African/Afro-Caribbean BGAG had slightly lower predicted probabilities of OUD. Variant carriers in the European BGAG had slightly higher predicted probabilities of OUD. Relative to sex, all the six variants met evaluation criteria (five subjects for all sex, variant, and OUD status combinations). No statistically significant interactions were found between a given variant, BGAGs and sex. Findings suggest variant testing relative to OUD risk can be applied across BGAGs and sex, however, studies in larger populations are needed., (© 2024. The Author(s).)

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., (© 2024 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Vaso-occlusive crises (VOCs) cause debilitating pain and are a common cause of emergency department (ED) visits, for people with sickle cell disease (SCD). Strategies for achieving optimal pain control vary widely despite evidence-based guidelines. We tested existing guidelines and hypothesized that a patient-specific pain protocol (PSP) written by their SCD provider may be more effective than weight-based (WB) dosing of parenteral opiate medication, in relieving pain., Methods: This study was a prospective, randomized controlled trial comparing a PSP versus WB protocol for patients presenting with VOCs to six EDs. Patients were randomized to a PSP or WB protocol prior to an ED visit. The SCD provider wrote their protocol and placed it in the electronic health record for future ED visits with VOC exclusion criteria that included preexisting PSP excluding parenteral opioid analgesia or outpatient use of buprenorphine or methadone or highly suspected for COVID-19. Pain intensity scores, side effects, and safety were obtained every 30 min for up to 6 h post-ED bed placement. The primary outcome was change in pain intensity score from placement in an ED space to disposition or 6 h., Results: A total of 328 subjects were randomized; 104 participants enrolled (ED visit, target n = 230) with complete data for 96 visits. The study was unable to reach the target sample size and stopped early due to the impact of COVID-19. We found no significant differences between groups in the primary outcome; patients randomized to a PSP had a shorter ED length of stay (p = 0.008), and the prevalence of side effects was low in both groups. Subjects in both groups experienced both a clinically meaningful and a statistically significant decrease in pain (27 mm on a 0- to 100-mm scale)., Conclusions: We found a shorter ED length of stay for patients assigned to a PSP. Patients in both groups experienced good pain relief without significant side effects., (© 2023 Society for Academic Emergency Medicine.)

Objectives: To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time., Methods: Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program., Results: A total of 10,416 cartons were included for analyses, with a total per capita distribution of 1,275 cartons per 100,000 county residents (average annual rate of 588/100,000). Median monthly opioid overdose mortality in the two years before (28 persons, 95% CI 25-31) and during (26, 95% CI 23-28) the program did not differ significantly., Conclusions: Massive and rapid naloxone distribution to lay bystanders is feasible. Even large-scale take-home naloxone distribution may not substantially reduce opioid overdose mortality rates., Competing Interests: Dr. Shawn Ryan serves as the chief science officer for Brightview. He was involved in the study design and the preparation of this manuscript, although he was not involved in the analysis of data. Funding for evaluation was awarded to the University of Cincinnati to fund time for CF, ML, and BP, none of whom received direct payment. Local health systems in the region funded the efforts of Hamilton County Public Health to manage the inventory and distribution efforts. Dr. Ryan was noted as having a potential competing interest, as he serves as the Chief Science Officer for Brightview. This company contributed to funding that allowed for the evaluation of this project. His involvement does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Freiermuth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genetics are presumed to contribute 30-40% to opioid use disorder (OUD), allowing for the possibility that genetic markers could be used to identify personal risk for developing OUD. We aimed to test the potential association among 180 candidate single nucleotide polymorphisms (SNPs), 120 of which were related to the dopamine reward pathway and 60 related to pharmacokinetics. Participants were randomly recruited in 2020-2021 in a cross-sectional genetic association study. Self-reported health history including Diagnostic and Statistical Manual of Mental Disorders (DSM-5) OUD criteria and buccal swabs were collected. A total of 1,301 participants were included in the analyses for this study. Of included participants, 250 met the DSM-5 criteria for ever having OUD. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and DSM-5 criteria consistent with OUD. Six SNPs found in four genes were associated with OUD: increased odds with CYP3A5 (rs15524 and rs776746) and DRD3 (rs324029 and rs2654754), and decreased odds with CYP3A4 (rs2740574) and CYP1A2 (rs2069514). Homozygotic CYP3A5 (rs15524 and rs776746) had the highest adjusted odds ratio of 2.812 (95% confidence interval (CI) 1.737, 4.798) and 2.495 (95% CI 1.670, 3.835), respectively. Variants within the dopamine reward and opioid metabolism pathways have significant positive (DRD3 and CYP3A5) and negative (CYP3A4 and CYP1A2) associations with OUD. Identification of these variants provides promising possibilities for genetic prognostic and therapeutic targets for future investigation., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use., Methods: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months., Results: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5)., Conclusions: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making., Competing Interests: Conflict of Interest: In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor, Amazon Research, the Center for Discovery, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, the Gates Foundation, Google, One Mind Foundation, and Samsung Research. Dr Clifford has financial interest in AliveCor, and receives unrestricted funding from the company. 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. In the past three years, Dr. Germine has served on the Scientific Advisory Board of Sage Bionetworks, for which she received a small honorarium. She also receives grant support from NIH. 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 paid board service, including equity outside the submitted work; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers). Sophia Sheikh 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. Christopher Jones has been an investigator on studies funded by Roche Diagnostics, AstraZeneca, Janssen, and Hologic Inc, for which my department has received research funding. No direct conflicts related to this paper, and no ongoing conflicts. Dr. Joormann receives consulting payments from Janssen Pharmaceuticals. Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, BlackThorn Therapeutics, Boehringer Ingelheim, Compass Pathway, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, and Millennium Pharmaceuticals. In addition, he has received stock options from BlackThorn Therapeutics. J Elliott reports support from the National Institutes of Health (NIH) through Grant Numbers R01HD079076 & R03HD094577: Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Center for Medical Rehabilitation Research. He also reports funding from New South Wales Health, Spinal Cord Injury Award (2020-2025) and consulting fees (< $15,000 per annum) from Orofacial Therapeutics, LLC. In the past 3 years, Dr. Kessler was a consultant for Datastat, Inc., Holmusk, RallyPoint Networks, Inc., and Sage Pharmaceuticals. He has stock options in Mirah, PYM, and Roga Sciences. Dr. Ressler has received consulting income from Alkermes and Takeda, research support from NIH, Alkermes, Genomind and Brainsway, and he has served on advisory boards for Takeda, Resilience Therapeutics, Janssen and Verily/Google.

Background: Legislation, practice recommendations, and the likely link between therapeutic opioid exposure and iatrogenic opioid use disorder (OUD) have led to reduced opioid prescribing. The effects of this change on unrelieved pain and the overdose crisis are not well-characterized., Aim: We explored emergency department (ED) patients' beliefs and experiences involving pain and emergency care to inform the development of future psychosocial interventions that balance the need for acute pain management with risks from opioid exposure., Methods: Qualitative, semi-structured interviews were conducted after discharge from an urban, academic Level 1 trauma center ED from September 2020 to May 2021 with 18 adult patients presenting with acute pain. After transcription of audio recording, common themes were identified using framework analysis. Thematic hierarchy was validated with Pearson correlation coefficients for cluster analysis of word similarity., Results: Of the 18 participants, most were Black (n = 11, 61%) and male (n = 12, 66.7%). Analysis identified one overarching theme: locus of control with an emergency pain encounter. Four themes were identified surrounding internal and external influences on pain management: (1) accessing healthcare for acute pain; (2) managing the pain after discharge; (3) seeking opioids: self-medicating and misuse; and (4) opioid crisis makes people in pain suffer., Conclusions: Patients discharged from the ED reported unrelieved pain, factors that influence their pain management, and an ability to seek opioids from non-medical sources. There is a significant disconnect between patients and providers in terms of priorities in pain management and the importance of individualized care., (Copyright © 2022 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Importance: Although LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority) physicians experience bias in the workplace, there is a paucity of data on the experiences of physicians who identify specifically as transgender and/or gender expansive (TGE; gender expansive is an umbrella term encompassing individuals and gender identities that may exist beyond the binary framework [eg, may include nonbinary, genderqueer, and agender individuals])., Objectives: To explore the professional experiences of TGE physicians, identify barriers to inclusion, and highlight stakeholder-derived strategies that promote an inclusive workplace., Design, Setting, and Participants: This qualitative study informed by semistructured interviews was conducted among 24 TGE physicians in the US from April 1 to December 31, 2021. The sample of TGE physicians was recruited using convenience and snowball sampling. Interviews were recorded and transcribed. Using thematic analysis, at least 2 members of the research team performed blinded coding of each transcript, in an iterative process., Main Outcomes and Measures: Data collection and thematic analysis examining themes of physicians' experiences., Results: Among 24 physicians (mean [SD] age, 39 [1.4] years) interviewed, 8 (33%) self-identified as transgender women, 7 (29%) as transgender men, 4 (17%) as nonbinary, 3 (13%) as transgender and nonbinary, and 2 (8%) as genderqueer. Prominent themes of the interviews included emotional distress as a result of transphobia, dominance of a rigid binary gender paradigm, and structural and institutional factors that are associated with psychological and physical safety and feelings of isolation as a TGE physician. Clear steps of affirmation were identified that could mitigate the emotional stressors, including signs of safety, active allyship, and mentorship by other TGE physicians., Conclusions and Relevance: In this qualitative study, TGE physicians reported facing both overt and subtle biases associated with their identity and gender presentation. Participants also noted several interpersonal and structural factors that mitigate the effect of these biases.

This second Guideline for Reasonable and Appropriate Care in the Emergency Department (GRACE-2) from the Society for Academic Emergency Medicine is on the topic "low-risk, recurrent abdominal pain in the emergency department." The multidisciplinary guideline panel applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding four priority questions for adult emergency department patients with low-risk, recurrent, undifferentiated abdominal pain. The intended population includes adults with multiple similar presentations of abdominal signs and symptoms recurring over a period of months or years. The panel reached the following recommendations: (1) if a prior negative computed tomography of the abdomen and pelvis (CTAP) has been performed within 12 months, there is insufficient evidence to accurately identify populations in whom repeat CTAP imaging can be safely avoided or routinely recommended; (2) if CTAP with IV contrast is negative, we suggest against ultrasound unless there is concern for pelvic or biliary pathology; (3) we suggest that screening for depression and/or anxiety may be performed during the ED evaluation; and (4) we suggest an opioid-minimizing strategy for pain control. EXECUTIVE SUMMARY: The GRACE-2 writing group developed clinically relevant questions to address the care of adult patients with low-risk, recurrent, previously undifferentiated abdominal pain in the emergency department (ED). Four patient-intervention-comparison-outcome-time (PICOT) questions were developed by consensus of the writing group, who performed a systematic review of the literature and then synthesized direct and indirect evidence to formulate recommendations, following GRADE methodology. The writing group found that despite the commonality and relevance of these questions in emergency care, the quantity and quality of evidence were very limited, and even fundamental definitions of the population and outcomes of interest are lacking. Future research opportunities include developing precise and clinically relevant definitions of low-risk, recurrent, undifferentiated abdominal pain and determining the scope of the existing populations in terms of annual national ED visits for this complaint, costs of care, and patient and provider preferences., (© 2022 Society for Academic Emergency Medicine.)

Background: In order to assist the State of Ohio in the United States in addressing the opioid epidemic, the Ohio Attorney General appointed experts in a variety of academic disciplines to the Scientific Committee on Opioid Prevention and Education (SCOPE). The focus of SCOPE is the application of scientific principles in the development of prevention and educational strategies for reducing substance use disorder (SUD). One area of focus for SCOPE was SUD education of healthcare professionals. The objective of the present was to identify the content and extent to which future healthcare professionals are trained in pain management, SUD, and adverse childhood experiences (ACEs)., Methods: In December of 2019, a survey was distributed to 49 healthcare professional schools in Ohio that included the following disciplines: medicine, pharmacy, advanced practice registered nurse (APRN), physician assistant, dentistry, and optometry. The survey included four domains: initial screening of patients, training in SUD, training in care for patients at high risk for SUD, and education in evaluating patients for ACEs. Descriptive statistics were calculated., Results: Thirty one of the forty-nine schools completed the survey. Most disciplines indicated that some form of basic training in the principles of SUD were taught in their core curriculum. The training on ethical issues surrounding SUD were not as widely covered (range 0-62.5%). Medicine, APRN, physician assistant, and pharmacy schools had a "moderate" to "great" extent of pharmacologic therapy curriculum integration. Other pain management strategies were "somewhat" to "moderately" integrated. There were variations seen in training on risk of medication misuse based on various contributors to health. At least 67.7% of medicine, APRN, physician assistant, and pharmacy programs included motivational interviewing training. The extent to which schools integrated education regarding ACEs into their curriculum varied from 0 to 66.7%., Conclusions: The study finding suggests a need for a unified, consistent, and expanded training requirement in the foundations of pain management, SUD, and ACEs in professional healthcare education., (© 2022. The Author(s).)

The opioid crisis is a national health emergency with immense morbidity, mortality, and socioeconomic cost. Emergency department (ED) pain management is tightly linked to the issue of opioid use disorder (OUD), because opioid exposure is necessary for development of OUD. Emergency nurses are on the frontlines of this complex problem, yet little, if any, attention has been paid to the role they play in the prevention and management of either pain or OUD in this unique and important setting. A framework that conceptualizes and optimizes emergency nurses as change agents in the opioid epidemic is urgently needed. While ED pain management and OUD prevention is dependent on the entire care team, this innovative study qualitatively characterizes emergency nurse perceptions of pain management, OUD prevention, and their potential role in each. Content analysis produced 14 categories that were clustered into two themes, "nurses influence ED pain management" and "adjustments in ED pain management", and an overarching message that "pain management depends on the care team." By generating a more comprehensive and nuanced understanding of the role played by emergency nurses, our findings provide essential insights into potential interventions and frameworks., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Efforts to minimize the impact of prescribed opioids on future adverse outcomes are reliant on emergency care providers' ability to screen and detect opioid use disorder (OUD). Many prescriptions are initiated in the emergency department (ED) for acute pain; thus, validated measures are especially needed. Our systematic review describes the available opioid-related screening measures identified through search of the available literature. Measures were categorized by intent and applied clinical setting. We found 44 articles, identifying 15 screening measures. Of these, nine were developed to screen for current opioid misuse and five to screen for risk of future opioid misuse. None were created for use outside of a chronic pain setting. Many measures were applied differently from intended purpose. Although several measures are available, screening for adverse opioid outcomes in the ED is hampered by lack of validated instruments. Development of clarified conceptual models and ED-specific research is necessary to limit OUD., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Genetics play an important role in opioid use disorder (OUD); however, few specific gene variants have been identified. Therefore, there is a need to further understand the pharmacogenomics influences on the pharmacodynamics of opioids. The Pharmacogenomics Knowledgebase (PharmGKB), a database that links genetic variation and drug interaction in the body, was queried to identify polymorphisms associated with heroin dependence in the context of opioid related disorders/OUD. Eight genes with 22 variants were identified as linked to increased risk of heroin dependence, with three genes and variants linked to decreased risk, although the level of evidence was moderate to low. Therefore, continued exploration of biomarker influences on OUD, reward pathways and other contributing circuitries is necessary to understand the true impact of genetics on OUD before integration into clinical guidelines.

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., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Objectives: Painful vaso-occlusive episodes (VOE) are the most common reason for emergency department (ED) visits experienced by patients with sickle cell disease (SCD). The National Heart, Lung and Blood Institute (NHLBI) evidence-based recommendations for VOE treatment are based primarily on expert opinion. In this randomized controlled trial (RCT), we will compare changes in pain scores between patients randomized to a patient-specific analgesic protocol versus those randomized to a weight-based analgesic protocol, as recommended by the NHLBI guidelines., Methods: We report the rationale and design of a multi-site, phase III, single-blinded, RCT to be conducted in six EDs in the United States. Eligible participants will be randomized after providing consent, anticipating 50% of those randomized would have an ED visit during the enrollment period. A total of 230 participants with one VOE ED visit provides sufficient power to detect a clinically significant difference in pain score reductions of 14 between groups with 0.05 type I error. Uniquely, this trial randomizes participants in a larger population than the study population, given the impossibility of consenting and randomizing participants during emergencies. The primary endpoint is the change in pain scores in the ED from time of placement in treatment area to time of disposition (hospitalization, discharged home, or assigned to observation status) or a maximum treatment duration of 6 hours. Additional outcomes include hospitalizations and ED visits seven days post enrollment, side effects, and safety assessments., Conclusions: The COMPARE-VOE study design will provide high-level evidence to support the NHLBI VOE treatment guidelines., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Patients with opioid use disorder (OUD) are at increased risk for overdose and death. Clinical practice guidelines and professional organization policy statements recommend providing naloxone to patients at risk for overdose. We sought to characterize fidelity to naloxone practice recommendations in a cohort of Emergency Department (ED) patients in whom opioid use disorder was suspected by the treating physician., Methods: This single-center cross-sectional study evaluated electronic health records from an urban academic ED with 73,000 annual encounters in a region with a high prevalence of OUD. Patients ≥18 years old with encounters from January 1, 2018 to November 30, 2019 were included if discharged from the ED and either administered buprenorphine in the ED or referred to outpatient substance use treatment. The primary outcome measure was the percentage of included patients provided naloxone (take-home or prescription). We used random effects multivariable logistic regression (accounting for multiple patient encounters) to estimate the odds ratio (OR) for receiving naloxone., Results: Of 1036 eligible patient encounters, 320 resulted in naloxone provision (30.9%, 95% CI: 28.1-33.8). Naloxone provision occurred for 33.6% (95% CI 30.5-36.7) of 900 patients referred to outpatient substance use treatment without ED buprenorphine administration, 10.6% (95% CI 5.0-19.2) of 85 patients administered buprenorphine and not referred to outpatient substance use treatment, and 17.6% (95% CI 8.4-30.9) of 51 patients administered buprenorphine and referred to outpatient treatment. After controlling for age, sex, race, and prior provision of naloxone, the administration of buprenorphine was associated with a 94% lower odds (aOR = 0.06 [95% CI 0.011-0.33]) for naloxone provision compared to those only referred to outpatient treatment., Conclusion: A majority of ED patients who received an intervention targeted at OUD, in an ED where take-home naloxone is freely available, did not receive either take-home naloxone or a prescription for naloxone at discharge. Patients receiving buprenorphine were less likely to receive naloxone than patients only referred to outpatient treatment. These data suggest barriers other than recognition of potential OUD and naloxone availability impact provision of naloxone and argue for a treatment "bundle" as a conceptual model for care of ED patients with suspected OUD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Emergency department encounters are an opportunity to distribute naloxone kits to patients at risk of opioid overdose. Several programs cite mixed uptake and implementation barriers including staff education and burden. Emergency nurses can facilitate many approaches to naloxone distribution (eg, prescription, overdose education, dispensing take-home naloxone). To evaluate acceptance, we investigated nurse perceptions about take-home naloxone, describing potential barriers to program implementation., Methods: This qualitative study enrolled 17 emergency nurses from an urban trauma center emergency department and affiliated community emergency department. During the study period, nurses in both sites could distribute take-home naloxone kits stocked in the medication dispensing system. We conducted 12 individual, in-depth interviews and 3 distinct focus groups involving 12 nurses in aggregate. A semistructured interview guide was used with a range of topics surrounding pain management, addiction, opioid overdose, and emergency care. We employed conventional content analysis to enable thematic analysis of transcripts., Results: Six component themes emerged as part of the overarching theme "mixed feelings about naloxone-morally distressing." One positive theme identified naloxone as an opportunity for discussion. Negative themes included (1) Addiction is a choice, why can't we help other diseases? It's unfair; (2) Providing naloxone enables and condones the behavior; (3) Emergency departments cannot treat social issues; (4) Patients can't give it to themselves; it's wasting money; and (5) Moral distress., Discussion: Perceptions and moral distress may be a barrier to ED-based take-home naloxone programs. Development of interventions targeting naloxone misperceptions and addiction stigma should be a goal of expanded implementation efforts., (Copyright © 2020 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of emergency department (ED) interventions on clinical, utilization, and care experience outcomes for older adults., Design: A conceptual model informed, protocol-based systematic review., Setting: Emergency Department (ED)., Participants: Older adults 65 years of age and older., Methods and Measurement: Medline, Embase, CINAHL, and PsycINFO were searched for English-language studies published through December 2017. Studies evaluating the use of one or more eligible intervention strategies (discharge planning, case management, medication safety or management, and geriatric EDs including those that cited the 2014 Geriatric ED Guidelines) with adults 65 years of age and older were included. Studies were classified by the number of intervention strategies used (ie, single strategy or multi-strategy) and key intervention components present (ie, assessment, referral plus follow-up, and contact both before and after ED discharge ["bridge"]). The effect of ED interventions on clinical (functional status, quality of life [QOL]), patient experience, and utilization (hospitalization, ED return visit) outcomes was evaluated., Results: A total of 2000 citations were identified; 17 articles describing 15 unique studies (9 randomized and 6 nonrandomized) met eligibility criteria and were included in analyses. ED interventions showed a mixed pattern of effects. Overall, there was a small positive effect of ED interventions on functional status but no effects on QOL, patient experience, hospitalization at or after the initial ED index visit, or ED return visit., Conclusion: Studies using two or more intervention strategies may be associated with the greatest effects on clinical and utilization outcomes. More comprehensive interventions, defined as those with all three key intervention components present, may be associated with some positive outcomes., (© 2019 The American Geriatrics Society.)

Introduction: Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use., Methods: We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients' functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids., Results: We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial's predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery., Conclusion: In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The original trial was funded by BTG International Inc. Funding for the statistical analysis for this secondary analysis was also provided by BTG International Inc. Drs Gerardo and Lavonas report receiving grants from BTG during the original trial and outside of the submitted work. Dr. Kleinschmidt and Ms. Anderson report receiving study-related funds from BTG.

Introduction: Substance use disorders, including opioid use disorders, are a major public health concern in the United States. Between 2005 and 2014, the rate of opioid-related emergency department (ED) visits nearly doubled, from 89.1 per 100,000 persons in 2005 to 177.7 per 100,000 persons in 2014. Thus, the ED presents a distinctive opportunity for harm-reduction strategies such as distribution of naloxone to patients who are at risk for an opioid overdose., Methods: We conducted a systematic review of all existing literature related to naloxone distribution from the ED. We included only those articles published in peer-reviewed journals that described results relating to naloxone distribution from the ED., Results: Of the 2,286 articles we identified from the search, five met the inclusion criteria and had direct relevance to naloxone distribution from the ED setting. Across the studies, we found variation in the methods of implementation and evaluation of take-home naloxone programs in the ED. In the three studies that attempted patient follow-up, success was low, limiting the evidence for the programs' effectiveness. Overall, in the included studies there is evidence that distributing take-home naloxone from the ED has the potential for harm reduction; however, the uptake of the practice remained low. Barriers to implementation included time allocated for training hospital staff and the burden on workflow., Conclusion: This systematic review of the best evidence available supports the ED as a potential setting for naloxone distribution for overdose reversal in the community. The variability of the implementation methods across the studies highlights the need for future research to determine the most effective practices., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Introduction: Use of alternative venues to manage uncomplicated vaso-occlusive crisis (VOC), such as a day hospital (DH) or ED observation unit, for patients with sickle cell anemia, may significantly reduce admission rates, which may subsequently reduce 30-day readmission rates., Methods: In the context of a two-institution quality improvement project to implement best practices for management of patients with sickle cell disease (SCD) VOC, we prospectively compared acute care encounters for utilization of 1) emergency department (ED); 2) ED observation unit; 3) DH, and 4) hospital admission, of two different patient cohorts with SCD presenting to our two study sites. Using a representative sample of patients from each institution, we also tabulated SCD patient visits or admissions to outside hospitals within 20 miles of the patients' home institutions., Results: Over 30 months 427 patients (297 at Site 1 and 130 at Site 2) initiated 4,740 institutional visits, totaling 6,627 different acute care encounters, including combinations of encounters. The range of encounters varied from a low of 0 (203 of 500 patients [40.6%] at Site 1; 65 of 195 patients [33.3%] at Site 2), and a high of 152 (5/month) acute care encounters for one patient at Site 2. Patients at Site 2 were more likely to be admitted to the hospital during the study period (88.4% vs. 74.4%, p=0.0011) and have an ED visit (96.9% vs. 85.5%, p=0.0002). DH was used more frequently at Site 1 (1.207 encounters for 297 patients at Site 1, vs. 199 encounters for 130 patients at Site 2), and ED observation was used at Site 1 only. Thirty-five percent of patients visited hospitals outside their home academic center., Conclusion: In this 30-month assessment of two sickle cell cohorts, healthcare utilization varied dramatically between individual patients. One cohort had more hospital admissions and ED encounters, while the other cohort had more day hospital encounters and used a sickle cell disease observation VOC protocol. One-third of patients sampled visited hospitals for acute care outside of their care providers' institutions., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This study was funded by the Agency for Healthcare Research and Quality (AHRQ R18 HS 19646).

Background: Guidelines recommend rapid, aggressive management of vaso-occlusive crisis (VOC) for patients with sickle cell disease (SCD). A large prospective research and quality improvement (QI) project was conducted to measure changes in clinical outcomes in two EDs-academic medical centers with emergency medicine residency programs and Level 1 trauma centers-during a 2.5-year time period (October 2011-March 2014)., Methods: A QI team used a Plan-Do-Study-Act approach to modify and implement changes to opioid analgesic protocols for the emergency department (ED) treatment of VOC. Data were collected quarterly; the team reviewed the results and made modifications to improve outcomes. A structured health record review was conducted to assess clinical outcomes (10 records/quarter/site). Patient interviews were conducted to measure satisfaction with pain management. Outcomes were compared before (T1) and after (T2) implementation of an electronic health record (EHR)., Results: One hundred ninety-six ED health records (118 unique patients, mean age = 32 [standard deviation, 11], 51% male) were analyzed. Before implementation, trends in decreasing time to initial analgesic administration were noted. There was a statistically significant increase in arrival to administration of first analgesic time between T1 and T2 at Site 1 but not at Site 2. Neither site showed significant changes in time between the administration of the first and second opioid doses, total opioid dose administered, or patient satisfaction., Conclusion: While QI efforts initially shortened door-to-analgesic times, these gains were not sustained. The lessons learned can help other EDs improve the timely delivery of analgesics to patients with SCD., (Copyright © 2016 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Patients with sickle cell disease frequently seek care in the emergency department. They have reported experiencing negative attitudes from emergency providers. This study was undertaken to evaluate change in emergency provider attitudes toward patients with sickle cell disease over a 2.5-year time period when several educational efforts were ongoing. The General Perceptions about Sickle Cell Disease Patients Scale was used to measure emergency provider attitudes at 2 emergency departments at baseline, 6 months, and 30 months into the project. Analyses of covariance were used to test for effects of site, time, and provider type, as well as their interactions, on Negative attitudes, Uneasiness With Care, and Positive Attitudes subscale scores, after controlling for years of provider experience. The number of surveys returned at the 3 time points was 216, 182, and 113, respectively. The mean Negative Attitudes subscale scores decreased significantly over time, with significantly higher mean Negative Attitudes subscale scores reported by nurses than by physicians. The mean Uneasiness With Care subscale scores did not differ significantly over time, but the mean score was significantly higher for physicians than for nurses. The mean Positive Attitudes subscale scores significantly improved over time, with physicians tending to have a higher mean Positive Attitudes subscale scores than nurses. During the observation period, there was improvement in attitudes, with a decline in mean Negative Attitudes subscale scores and increase in mean Positive Attitudes subscale scores. Physicians reported better attitudes than nurses.

Background: The use of electronic interventions (e-interventions) may improve treatment of alcohol misuse., Purpose: To characterize treatment intensity and systematically review the evidence for efficacy of e-interventions, relative to controls, for reducing alcohol consumption and alcohol-related impairment in adults and college students., Data Sources: MEDLINE (via PubMed) from January 2000 to March 2015 and the Cochrane Library, EMBASE, and PsycINFO from January 2000 to August 2014., Study Selection: English-language, randomized, controlled trials that involved at least 50 adults who misused alcohol; compared an e-intervention group with a control group; and reported outcomes at 6 months or longer., Data Extraction: Two reviewers abstracted data and independently rated trial quality and strength of evidence., Data Synthesis: In 28 unique trials, the modal e-intervention was brief feedback on alcohol consumption. Available data suggested a small reduction in consumption (approximately 1 drink per week) in adults and college students at 6 months but not at 12 months. There was no statistically significant effect on meeting drinking limit guidelines in adults or on binge-drinking episodes or social consequences of alcohol in college students., Limitations: E-interventions that ranged in intensity were combined in analyses. Quantitative results do not apply to short-term outcomes or alcohol use disorders., Conclusion: Evidence suggests that low-intensity e-inter ventions produce small reductions in alcohol consumption at 6 months, but there is little evidence for longer-term, clinically significant effects, such as meeting drinking limits. Future e-interventions could provide more intensive treatment and possibly human support to assist persons in meeting recommended drinking limits., Primary Funding Source: U.S. Department of Veterans Affairs.

Introduction: Hypertensive emergency has a high mortality risk and the treatment goal is to quickly lower blood pressure with intravenous (IV) medications. Characteristics that are associated with non-response to IV antihypertensives have not been identified. The objective is to identify patient characteristics associated with resistance to IV antihypertensives., Methods: This was a subanalysis of patients enrolled in the previously described comparative effectiveness trial of IV nicardipine vs. labetalol use in the emergency department (CLUE) study, a randomized trial of nicardipine vs. labetalol. Non-responders were defined as those patients who did not achieve target systolic blood pressure (SBP), as set by the treating physician, within thirty minutes of IV antihypertensive medication, +/- 20mmHg. Stepwise logistic regression was used to identify covariates associated with the measurement outcomes., Results: CLUE enrolled 226 patients, 52.7% female, 76.4% black, mean age of 52.6±14.6 years, of whom 110 were treated with nicardipine and 116 with labetalol. The median (IQR) initial systolic blood pressure was 211mmHg (198, 226), 210 (200, 230), and 211mmHg (198, 226), for the total, non-responder, and responder cohorts, respectively (p-value=0.65, 95% CI [-5.8-11.3]). Twenty-nine were non-responders, 9 in the nicardipine and 20 in the labetalol group. In univariate analysis, several symptoms suggestive of end organ damage were associated with non-response. After multiple variable logistic regression (AUC = 0.72), treatment with labetalol (OR 2.7, 95% CI [1.1-6.7]), history of stroke (OR 5.4, 95% CI [1.6-18.5]), and being male (OR 3.3, 95% CI [1.4-8.1]) were associated with failure to achieve target blood pressure., Conclusion: Male gender and history of previous stroke are associated with difficult to control blood pressure.

Patients with sickle cell disease (SCD) often seek care in the emergency department (ED) for pain associated with vaso-occlusive crises. Research has shown that negative provider attitudes serve as a barrier to care in this patient population. Our aim was to validate a survey that measures attitudes toward SCD patients among ED providers (nurses and physicians) and to compare differences in attitude scores between provider types. We administered the general perceptions about Sickle Cell Disease Patients Scale, previously validated among internal medicine providers, and the Medical Condition Regard Scale (MCRS) to ED nurses and physicians from two EDs. A total of 215 surveys were returned (63% response rate, 200 with attitude items completed). Three subscales were identified: Negative Attitudes, Uneasiness With Care, and Positive Attitudes. Cronbach's αs exceeded 0.81 for each subscale. Mean (SD) scores for the Negative, Uneasiness, and Positive subscales and MCRS were 61.5 (20.3), 66.1 (17.1), 41.2 (17.8), and 42.2 (8.9), respectively. Compared with physicians, nurses had significantly higher mean Negative Attitude scores and lower Uneasiness scores. A slightly modified version of the general perceptions about Sickle Cell Disease Patients Scale appears to be a valid measure of ED provider attitudes toward SCD patients. Among ED providers, this scale identified a dimension not observed in research with the original instrument among internal medicine providers. Provider attitudes influence patient-provider interactions and quality of care. The scale we present here has major clinical implications, particularly for advanced practice nurses, who can use the scale not only to assess providers' attitudes toward SCD patients but also to determine the effectiveness of tailored interventions to improve those attitudes.

Introduction: Patients with sickle cell disease (SCD) often seek care in emergency departments (EDs) for severe pain. However, there is evidence that they experience inaccurate assessment, suboptimal care, and inadequate follow-up referrals. The aim of this project was to 1) explore the feasibility of applying a failure modes, effects and criticality analysis (FMECA) in two EDs examining four processes of care (triage, analgesic management, high risk/high users, and referrals made) for patients with SCD, and 2) report the failures of these care processes in each ED., Methods: A FMECA was conducted of ED SCD patient care at two hospitals. A multidisciplinary group examined each step of four processes. Providers identified failures in each step, and then characterized the frequency, impact, and safeguards, resulting in risk categorization., Results: Many "high risk" failures existed in both institutions, including a lack of recognition of high-risk or high-user patients and a lack of emphasis on psychosocial referrals. Specific to SCD analgesic management, one setting inconsistently used existing analgesic policies, while the other setting did not have such policies., Conclusion: FMECA facilitated the identification of failures of ED SCD care and has guided quality improvement activities. Interventions can focus on improvements in these specific areas targeting improvements in the delivery and organization of ED SCD care. Improvements should correspond with the forthcoming National Heart, Lung and Blood-sponsored guidelines for treatment of patients with sickle cell disease.