National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.

Leveraging a Learning Collaborative Model to Develop and Pilot Quality Measures to Improve Opioid Prescribing in the Emergency Department.

The American College of Emergency Physicians (ACEP) Emergency Medicine Quality Network (E-QUAL) Opioid Initiative was launched in 2018 to advance the dissemination of evidence-based resources to promote the care of emergency department (ED) patients with opioid use disorder. This virtual platform-based national learning collaborative includes a low-burden, structured quality improvement project, data benchmarking, tailored educational content, and resources designed to support a nationwide network of EDs with limited administrative and research infrastructure. As a part of this collaboration, we convened a group of experts to identify and design a set of measures to improve opioid prescribing practices to provide safe analgesia while reducing opioid-related harms. We present those measures here, alongside initial performance data on those measures from a sample of 370 nationwide community EDs participating in the 2019 E-QUAL collaborative. Measures include proportion of opioid administration in the ED, proportion of alternatives to opioids as first-line treatment, proportion of opioid prescription, opioid pill count per prescription, and patient medication safety education among ED visits for atraumatic back pain, dental pain, or headache. The proportion of benzodiazepine and opioid coprescribing for ED visits for atraumatic back pain was also evaluated. This project developed and effectively implemented a collection of 6 potential measures to evaluate opioid analgesic prescribing across a national sample of community EDs, representing the first feasibility assessment of opioid prescribing-related measures from rural and community EDs.

Xylazine Adulteration of the Heroin-Fentanyl Drug Supply : A Narrative Review.

Xylazine is an animal sedative, approved by the U.S. Food and Drug Administration, that is commonly used in veterinary medicine and is not approved for human use. Since 2016, xylazine has consistently appeared in the illicitly manufactured fentanyl supply and has significantly increased in prevalence, likely due to its low cost, easy availability, and presumed synergistic psychoactive effect. Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.

Concurrent Alcohol and Opioid Intoxication in Emergency Department Patients Leads to Greater Resource Utilization.

Background: Concurrent alcohol intoxication can complicate emergency department (ED) presentations for opioid-related adverse events. We sought to determine if there was a difference in resource utilization among patients who presented to the ED with concurrent opioid and alcohol intoxication compared to opioid intoxication alone. Methods: Using linked state-wide databases from the Maryland Healthcare Cost and Utilization Project (HCUP), we identified patients with a diagnosis of opioid intoxication treated in the ED from 2016 to 2018. We measured healthcare utilization for each patient in the ED settings for one year after the initial ED visit and estimated direct costs. We performed logistic regression comparing patients presented with co-intoxication to those without. Results: Of 12,295 patients who presented to the ED for opioid intoxication during the study period, 703 (5.7%) had concurrent alcohol intoxication. Patients with co-intoxication had more recurrent ED visits (340 vs 247.4 per 1000 patients, p < 0.05), higher index ED visit admission rates (26.9% vs 19.4%, p < 0.001), but similar overall costs ($3736 vs $2861, p < 0.05) at one year. Co-intoxication was associated with suicidal ideation (OR = 1.58, 95% CI 1.51-1.65), high zip code income (OR = 1.16, 95% CI 1.12-1.21), and higher rates of intoxication with all classes of drugs analyzed (p < 0.001). Conclusion: Our study demonstrated that mental health disorders, socioeconomic status, and increased ED utilization are associated with co-intoxication of opioids and alcohol presenting to the ED. Further research is needed to elucidate factors responsible for the increased resource use in this population.

Opioid and Benzodiazepine Co-Prescribing Trends from the Emergency Department from 2012 to 2019: A National Analysis.

BACKGROUND: In 2016, the U.S. Food and Drug Administration (FDA) issued its strongest safety warning ("Black Box Warning") for concomitant use of prescription opioids and benzodiazepines due to overdose deaths. OBJECTIVE: Our objective was to look at trends of opioid and benzodiazepine co-prescribing in the emergency department (ED) using national data, because recent data are sparse. METHODS: This is a retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey between 2012 and 2019. Our primary outcome was to determine whether there was a trend in ED visits when opioids and benzodiazepines were co-prescribed at discharge. We also compared the rate of visits when co-prescribing occurred before (2012-2015) and after (2017-2019) the 2016 FDA warning. We identified commonly co-prescribed benzodiazepines and opioids, and the rate of naloxone co-prescribing. We used descriptive statistics and bivariate tests to describe data. RESULTS: Between 2012 and 2019, there were 4,489,613 ED visits (0.41% of ED visits) when benzodiazepines and opioids were co-prescribed. There was no trend in the rate of co-prescribing overall, but a decrease in visits after the 2016 FDA Black Box Warning (2012-2015: mean 0.49%; 2017-2019: mean 0.29%; p < 0.0001). There were 7980 ED visits (0.18%) when naloxone was co-prescribed for these visits within this time frame and an increase over time (p < 0.001). CONCLUSIONS: Our study found that between 2012 and 2019, there was no overall reduction in co-prescribing of opioids and benzodiazepines across EDs nationwide, but a decrease after the 2016 Black Box Warning.

Workplace Mistreatment, Career Choice Regret, and Burnout in Emergency Medicine Residency Training in the United States.

STUDY OBJECTIVE: The influence of workplace mistreatment on the well-being and career satisfaction of emergency medicine residents is unknown. This study examined the relationships between burnout, career choice regret, and workplace mistreatment in a national sample of emergency medicine residents. METHODS: This was a secondary analysis of a survey study on the prevalence of workplace mistreatment among emergency residents. Residents who reported emotional exhaustion or depersonalization at least once per week were considered to have burnout. Residents who reported dissatisfaction with their decision to become an emergency physician were considered to have career choice regret. Respondents also reported the type (discrimination, abuse, sexual harassment) and frequency of mistreatment over the academic year. Multivariable logistic regression, adjusting for program characteristics, was used to examine resident characteristics associated with burnout and career choice regret, with the frequency of mistreatment as a covariate. RESULTS: Of the 8,162 eligible residents, 7,680 (94.1 %) participated. About a third of respondents reported burnout (2,188 of 6,902, 31.7%), whereas a minority (224 of 6,923, 3.2%) reported career choice regret. Of the 7,087 responses on mistreatment frequency, 2,117 (29.9%) reported "a few times per year," and 1,296 (18.3%) reported "a few times per month or more." Compared with residents who never experienced mistreatment, residents who reported increasing frequencies of mistreatment were associated with having burnout-from mistreatment a few times per year (OR [odds ratio],1.6; 99% CI [confidence interval], 1.3 to 1.9) to a few times per month or more (OR, 3.3; 99% CI, 2.7 to 4.1). Compared with residents without burnout, residents who reported burnout were associated with having career choice regret (OR, 11.3; 99% CI, 7.0 to 18.1). After adjusting for burnout, there were no significant relationships between the frequency of mistreatment and career choice regret. CONCLUSIONS: Workplace mistreatment is associated with burnout, but not career choice regret, among emergency medicine residents. Efforts to address workplace mistreatment may improve emergency medicine residents' professional well-being.

Impact of the COVID-19 pandemic on emergency department alcohol intoxication presentations and positive screens for problem drinking.

Our aim was to assess the changes in patients presenting with acute alcohol intoxications or positive screens for problem drinking during the COVID-19 pandemic compared to before the pandemic in a seven-hospital health system. A retrospective chart review of emergency department (ED) visits from seven hospitals in the Washington, DC/Baltimore, and MD area from January 2019 to June 2021 is provided. The health system utilizes a validated system for Screening, Brief Intervention, and Referral to Treatment (SBIRT) for ED patients. We evaluated trends in patients who had a positive SBIRT screen for problem drinking (AUDIT-C score ≥ 3 in women, 4 in men), alcohol misuse (≥5), and those presenting with acute alcohol intoxication before March 2020 and during the early COVID pandemic period. There were 510 648 patients who were screened, ranging from ages of 16 to 95 years during the study period. There was an overall increase in patients who screened positive for problem drinking, alcohol misuse, and acute intoxications. While there was an overall decrease in the total number of ED visits during the start of the pandemic, which later increased near prepandemic levels, alcohol-related presentations as a percentage of total visits increased during the early pandemic period. There was an overall decrease in ED visits during the COVID-19 pandemic study period; problem drinking and acute intoxication presentation held steady, leading to an overall increase in proportion compared to pre-COVID-19 levels. Future research should focus on lessons learned during this time and should navigate the postpandemic care of patients with AUD. There was an increase in the proportion of ED visits for alcohol intoxications and positive screens for problem drinking during the COVID-19 pandemic in our seven-hospital system.

Trends in amphetamine prescriptions given at discharge in emergency departments: A national analysis (2012-2019).

OBJECTIVES: In parallel with the opioid epidemic, there has been a resurgence in abuse, medical complications, and deaths related to amphetamines. The opioid epidemic began with increasing rates of prescription products that evolved overtime to include heroin and more recently, fentanyl analogues. Current trends in amphetamine prescriptions are less well described. We sought to determine if there has been a change in amphetamine prescriptions given at discharge in U.S. emergency departments (EDs) in recent years. METHODS: We conducted a retrospective review of data provided by the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 to 2019. We computed total number of visits that were given amphetamine prescriptions (amphetamine salts, methylphenidate derivatives, and dexmethylphenidate) at discharge for each year. We computed the total number and rate of visits (of all ED visits) that had both amphetamines and opioids prescribed at discharge over the years. We computed data normality using Shapiro Wilke's test and used descriptive statistics such as mean to describe the data distribution as applicable. We used spearman's rho (SR) or pearson's correlation (PC) as applicable to describe trends in data. All p-values were one-tailed and were reported at a 0.05 significance level. All analyses were conducted in IBM SPSS version 28. RESULTS/FINDINGS: From 2012 to 2019, there were an estimated 817,895 ED visits where an amphetamine prescription was given at discharge, with an overall strong increase in rate over time (SR = 0.71, p = 0.02). At the beginning of the study period (2012) there were 83,503 (0.06%) visits and in 2019 there were 186,539 (0.12%) visits (123% absolute increase). On average, there were 102,237 (SD: 52,725) visits with discharge amphetamine prescriptions per year. There was a strong, linear increase in number of visits that involved a discharge amphetamine salt prescription (PC = 0.92, p = 0.001). In 2012, there were a total of 23,676 visits and in 2019, a total of 124,773 visits (427% increase). There was no trend in visits where both an amphetamine and opioid were prescribed (PC: 0.61, p = 0.06). CONCLUSION: There have been increases in discharge prescriptions for amphetamines in the ED over time. This was largely driven by prescriptions for amphetamine salts. Future research initiatives should continue to monitor this trend and in prescriptions and associated abuse in the setting of rising amphetamine abuse.

Trends in naloxone prescribed at emergency department discharge: A national analysis (2012-2019).

BACKGROUND: While having access to naloxone is recommended for patients at risk for opioid overdose, little is known about trends in national naloxone prescribing rates in emergency departments (EDs) both for co-prescription with opioids and for patients who presented with opioid abuse or overdose. This study aims to evaluate the change in naloxone prescribing and opioid/naloxone co-prescribing at discharge using national data. METHODS: We conducted an IRB exempt retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey from 2012 to 2019. The primary outcome was trend in rate of naloxone prescribing at discharge from ED visits. We also computed the proportion of visits where naloxone was both administered in the ED and prescribed at discharge, where naloxone and opioids were co-prescribed at discharge, and where an opioid was administered during the ED visit and naloxone was prescribed at discharge. All data were summarized using descriptive statistics and Spearman's Rho (SR) or Pearson's correlation (PR) were used to describe trends. RESULTS: There was an estimated total of 250,365 patient visits where naloxone was prescribed at discharge with an increasing rate over time (0% of all ED visits in 2012 to 0.075% in 2019, p = 0.002). There were also increases in naloxone being both administered in the ED and prescribed at discharge (PC: 0.8, p = 0.02) as well as in naloxone and opioid co-prescribing (SR: 0.76, P = 0.03). There was an increase in utilization of opioids during the ED visit and naloxone prescribing at discharge for the same visit (SR: 0.80, p = 0.02). CONCLUSION: There are increases in naloxone prescribing at discharge, naloxone and opioid co-prescribing, and opioid utilization during the same visit where naloxone is prescribed at discharge. Future studies should be done to confirm such trends, and targeted interventions should be put into place to increase access to this life-saving antidote.

The impact of an emergency department peer navigator (EDPN) program in improving clinical outcomes and healthcare utilization in an urban setting.

INTRODUCTION: Emergency Department Peer Navigator Programs (EDPN) have been shown to increase the prescribing of medications for opioid use disorder (MOUD) and improve linkage to addiction care. However, what is not known is whether it can improve overall clinical outcomes and healthcare utilization in patients with OUD. METHODS: This is a single-center, IRB approved, retrospective cohort study using patients with OUD enrolled in our peer navigator program from 11/7/19 to 2/16/21. On an annual basis, we determined MOUD clinic follow-up rates and clinical outcomes in those patients who utilized our EDPN program. Finally, we also looked at the social determinants of health factors (e.g., race, status of medical insurance, lack of housing, access to phone and/or internet, employment, etc.) that impact our patients clinical outcomes. ED and inpatient provider notes were reviewed to determine causes of ED visits and hospitalizations one year before and after enrollment into the program. The clinical outcomes of interest were number of ED visits from all-causes, number of ED visits from opioid-related causes, number of hospitalizations from all-causes, and number of hospitalizations from opioid-related causes one year after enrollment into our EDPN program, subsequent urine drug screens, and mortality. Demographic and socioeconomic factors (age, gender, race, employment, housing, insurance status, access to phone) were also analyzed to determine if any were independently associated with clinical outcomes. Death and cardiac arrests were noted. Clinical outcomes data were described using descriptive statistics and compared using t-tests. RESULTS: 149 patients with OUD were included in our study. 39.6% had an opioid-related chief complaint at their index ED visit; 51.0% had any recorded history of MOUD and 46.3% had history of buprenorphine use. 31.5% had buprenorphine given in the ED with individual doses ranging from 2 to 16 mg and 46.3% were provided with a buprenorphine prescription. The average number of ED visits 1-year pre vs post enrollment, respectively, for all-causes was 3.09 vs 2.20 (p < 0.01); for opioid related complications 1.80 vs 0.72 (p < 0. 01). The average number of hospitalizations 1-year pre and post enrollment, respectively, for all-causes was 0.83 vs 0.60 (p = 0.05); for opioid related complications 0.39 vs 0.09 (p < 0.01). ED visits from all-causes decreased in 90 (60.40%) patients, had no change in 28 (18.79%) patients, and increased in 31 (20.81%) patients (p < 0.01). ED visits from opioid-related complications decreased in 92 (61.74%) patients, had no change in 40 (26.85%) patients, and increased in 17 (11.41%) (p < 0.01). Hospitalizations from all causes decreased in 45 (30.20%) patients, had no change in 75 patients (50.34%), and increased in 29 (19.46%) patients (p < 0.01). Lastly, hospitalizations from opioid-related complications decreased in 31 (20.81%) patients, had no change in 113 (75.84%) patients, and increased in 5 (3.36%) patients (p < 0.01). There were no socioeconomic factors that had a statistically significant association with clinical outcomes. Two patients (1.2%) died within 1 year after study enrollment. CONCLUSIONS: Our study found that there was an association between implementation of an EDPN program and decreases in ED visits and hospitalizations from both all-causes as well as from opioid-related complications for patients with opioid use disorder.

A national analysis of ED presentations for early pregnancy and complications: Implications for post-Roe America.

BACKGROUND: Most obstetric emergencies are initially managed in the emergency department (ED). The Supreme Court decision of Dobbs v. Jackson Women's Health Organization, overturning Roe v. Wade, in June 2022, eliminated constitutional protection of abortion rights, allowing states to swiftly enact laws that can greatly change reproductive medicine. In this post-Roe landscape, the ambiguity and uncertainty being imposed on clinicians regarding the legality of certain interventions may have catastrophic effects. To understand and plan for the changes that will come and attempt to mitigate adverse outcomes, the authors first assessed the current state of pregnancy-related complication care in the ED setting. This study utilized data obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) to evaluate trends in pregnancy-related ED visits from 2016 to 2020 that could be impacted by restricted abortion access and trigger laws. The authors subsequently analyzed the legislative changes and translated the pertinent ones to dispel misunderstandings and provide a framework for appropriate medical practice. METHODS: The retrospective study utilized data from the NHAMCS database from 2016 to 2020, encompassing an estimated total of 4,556,778 pregnancy-related ED visits. NHAMCS is a multi-stage probabilistic sample collected by the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention (CDC) using an annual survey of EDs in the United States. All data were summarized using descriptive statistics such as proportions and 95% confidence intervals Furthermore, the supreme court decision was analyzed in addition to multiple state laws and legal texts. The findings were summarized and discussed. RESULTS: The majority (79.4%) of all studied visits were for patients between the ages of 18-34 years, capturing those in peak reproductive years. This age group also comprised of the bulk (76.4%) of visits for pathologic pregnancies, including ectopic and molar pregnancies, and 79.8% of visits for a spontaneous miscarriage or threatened miscarriage in early pregnancy. Black patients accounted for 25.7%, white patients 70.1%. Regarding ethnicity, patients were separated into Hispanic and non-Hispanic, with Hispanic patients comprising 27% of all ED visits for included diagnoses between 2016 and 2020. Most visits for complications following an induced abortion occurred in the south (70.8%) and were nearly twice as likely to occur in non-metropolitan areas. Approximately 18% patients presenting with a pathologic pregnancy required admission to the hospital and approximately 50% of those visits for pathologic pregnancies and visits for bleeding in pregnancy had a procedure in the ED (49.8% and 49.5%). There were 111,264 estimated visits in which methotrexate was administered, amounting to approximately 1 in 7 visits for ectopic or molar pregnancy. In this data set, approximately 14,000 miscarriage and early bleeding patients received misoprostol. CONCLUSION: Pregnancy-related ED visits comprise of a significant proportion of emergency care. As it relates to many of the trends previously elucidated on, the true extent of the burden cannot be predicted. It must be emphasized that contrary to popular belief, Dobbs v. Jackson does not prohibit termination of pregnancy in the setting of life-threatening conditions to the mother, including ectopic pregnancy, preeclampsia, and others, but the resultant uncertainty and ambiguity surrounding the constitutional change is leading to an over-compliance of the law, necessarily obstructing reproductive health care. The authors recommend that physicians be mindful of the rapidly-evolving laws in their particular state, and to also practice in accordance with Emergency Medical Treatment and Active Labor Act (EMTALA). Patient safety must be prioritized.

Systematic Review of Naloxone Dosing and Adverse Events in the Emergency Department.

BACKGROUND: Experts recommend using the lowest effective dose of naloxone to balance the reversal of opioid-induced respiratory depression and avoid precipitated opioid withdrawal, however, there is no established dosing standards within the emergency department (ED). OBJECTIVES: The aim of this review was to determine current naloxone dosing practice in the ED and their association with adverse events. METHODS: We conducted a systematic review by searching PubMed, Cochrane, Embase, and EBSCO from 2000-2021. Articles containing patient-level data for initial ED dose and patient outcome had data abstracted by two independent reviewers. Patients were divided into subgroups depending on the initial dose of i.v. naloxone: low dose ([LD], < 0.4 mg), standard dose ([SD], 0.4-2 mg), or high dose ([HD], > 2 mg). Our outcomes were the dose range administered and adverse events per dose. We compared groups using chi-squared difference of proportions or Fisher's exact test. RESULTS: The review included 13 articles with 209 patients in the results analysis: 111 patients in LD (0.04-0.1 mg), 95 in SD (0.4-2 mg), and 3 in HD (4-12 mg). At least one adverse event was reported in 37 SD patients (38.9%), compared with 14 in LD (12.6%, p < 0.0001) and 2 in HD (100.0%, p = 0.16). At least one additional dose was administered to 53 SD patients (55.8%), compared with 55 in LD (49.5%, p < 0.0001), and 3 in HD (100.0%, p = 0.48). CONCLUSIONS: Lower doses of naloxone in the ED may help reduce related adverse events without increasing the need for additional doses. Future studies should evaluate the effectiveness of lower doses of naloxone to reverse opioid-induced respiratory depression without causing precipitated opioid withdrawal.

A Neuropharmacological Model to Explain Buprenorphine Induction Challenges.

Buprenorphine induction for treating opioid use disorder is being implemented in emergency care. During this era of high-potency synthetic opioid use, novel and divergent algorithms for buprenorphine induction are emerging to optimize induction experience, facilitating continued treatment. Specifically, in patients with chronic fentanyl or other drug exposures, some clinicians are using alternative buprenorphine induction strategies, such as quickly maximizing buprenorphine agonist effects (eg, macrodosing) or, conversely, giving smaller initial doses and slowing the rate of buprenorphine dosing to avoid antagonist/withdrawal effects (eg, microdosing). However, there is a lack of foundational theory and empirical data to guide clinicians in evaluating such novel induction strategies. We present data from clinical studies of buprenorphine induction and propose a neuropharmacologic working model, which posits that acute clinical success of buprenorphine induction (achieving a positive agonist-to-withdrawal balance) is a nonlinear outcome of the opioid balance at the time of initial buprenorphine dose and mu-opioid-receptor affinity, lipophilicity, and mu-opioid-receptor intrinsic efficacy (the "ALE value") of the prior opioid. We discuss the rationale for administering smaller or larger doses of buprenorphine to optimize the patient induction experience during common clinical situations.

American Board of Emergency Medicine Report on Residency and Fellowship Training Information (2021-2022).

The American Board of Emergency Medicine gathers extensive background information on the Accreditation Council of Graduate Medical Education-accredited emergency medicine residency and fellowship programs, as well as the residents and fellows training in those programs. We present the 2022 annual report on the status of physicians training in Accreditation Council of Graduate Medical Education-accredited emergency medicine training programs in the United States.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

The Impact of a Peer-Navigator Program on Naloxone Distribution and Buprenorphine Utilization in the Emergency Department.

Objectives: In recent years many emergency departments (EDs) have adopted interventions to help patients with opioid use disorder (OUD), particularly buprenorphine initiation and ED-based peer recovery support. There are limited data on the impact of peer navigators on provider naloxone kit distribution and buprenorphine utilization. We aimed to examine the impact of a peer recovery program on naloxone kit distribution and buprenorphine administration. Methods: This was a retrospective study analyzing the change in naloxone kits distributed as well as buprenorphine administrations. Data on naloxone kit and buprenorphine administrations was generated every month between November 2017 and February 2021. Time periods were as follows: implementation of guidelines for buprenorphine and naloxone kits, initiation of the navigator program, and first wave of COVID-19. Numbers of naloxone kits distributed and buprenorphine administrations per month were computed. Results: Between November 2017 and December 2020, there was a significant increase overtime among the 238 naloxone kits distributed (p < 0.0001). Between implementation of guidelines and introduction of peer navigators, there were 49 kits distributed, compared to an increase overtime among 235 kits when the navigator program began (p = 0.0001). There was also a significant increase overtime among 1797 administrations of buprenorphine (p < 0.0001). Administrations increased by 22.4% after implementation of the navigator program-a total of 787 compared to 643 post guideline (p = 0.007). Conclusion: Peer recovery support programs for patients with OUD can have an impact on administration of naloxone kits and buprenorphine. Future studies should determine whether these programs can cause a long-term culture change in the ED.

Tramadol Use in United States Emergency Departments 2007-2018.

BACKGROUND: Amidst the opioid epidemic, there has been an increasing focus on opioid utilization in U.S. emergency departments (EDs). Compared with other opioids, little is known about the use of tramadol over the past decade. Tramadol has uncertain efficacy and a concerning adverse effect profile compared with traditional opioids. OBJECTIVE: Our aim was to describe trends in tramadol use in U.S. EDs between 2007 and 2018. METHODS: We analyzed the National Hospital Ambulatory Medical Care Survey from 2007 to 2018 to examine ED visits by patients 18 years or older in which tramadol was administered or prescribed. We examined trends in demographics and resource utilization and compared these trends with those of traditional opioids. Survey-weighted analyses were conducted to provide national-level estimates. RESULTS: Between 2007 and 2018, ED visits in which tramadol was used increased 70.6%, from 1.7% of all ED visits in 2007 to 2.9% in 2018. The largest increases were noted among patients aged 55 through 64 years and 65 years and older. Diagnostic resource utilization increased across the study period. Overall opioid utilization during the study period decreased from 28.4% in 2007 to 17.9% in 2018 (p < 0.001). The use of other specific opioids declined or remained stable between 2007 and 2018. CONCLUSIONS: Although the use of traditional opioids decreased from 2007 to 2018, the use of tramadol increased. Increases were largest among older patients, who may be more susceptible to the adverse effects associated with this medication. Further research in the appropriate use of tramadol in the ED setting is warranted.

Levamisole-a Toxic Adulterant in Illicit Drug Preparations: a Review.

ABSTRACT: Discovered in the 1960s, the common anthelminthic levamisole has seen widespread use in veterinary applications. Its use rapidly expanded thereafter to include human medical treatments for a variety of acute and chronic disorders. Because of reports of severe adverse effects, the US Food and Drug Administration withdrew levamisole's approval for human use in 2000; however, medical options outside the United States and illicit options worldwide allow continued accessibility to levamisole. The compound is rapidly metabolized in the body, with at least 2 known active metabolites. Levamisole has a broad range of immunomodulatory effects, including both stimulatory and inhibitory effects on immune responses. It is generally well tolerated at therapeutic concentrations, although a variety of autoimmune-related adverse effects have been reported, including agranulocytosis, leukopenia, purpura, and visible necrotized skin tissue. Individuals with levamisole-compromised immune systems are more susceptible to infections, including COVID-19. Since the early 2000's, levamisole has been frequently used as an adulterating agent in illicit street drugs, especially cocaine, fentanyl, and heroin. Although its prevalence has varied over time and geographically, levamisole has been detected in up to 79% of the street supply of cocaine at levels up to 74% by weight. Its presence in illicit drug markets also raises concern over the potential for exposure of children and neonates, although this is supported by only limited anecdotal evidence. Levamisole is not currently included in routine drug testing panels, although a variety of confirmatory testing techniques exist across a range of antemortem and postmortem specimen options. Because of its varying presence in illicit drug markets, both the medical and forensic communities need to be aware of levamisole and its potential impact on toxicological investigations.

Consensus Recommendations on the Treatment of Opioid Use Disorder in the Emergency Department.

The treatment of opioid use disorder with buprenorphine and methadone reduces morbidity and mortality in patients with opioid use disorder. The initiation of buprenorphine in the emergency department (ED) has been associated with increased rates of outpatient treatment linkage and decreased drug use when compared to patients randomized to receive standard ED referral. As such, the ED has been increasingly recognized as a venue for the identification and initiation of treatment for opioid use disorder, but no formal American College of Emergency Physicians (ACEP) recommendations on the topic have previously been published. The ACEP convened a group of emergency physicians with expertise in clinical research, addiction, toxicology, and administration to review literature and develop consensus recommendations on the treatment of opioid use disorder in the ED. Based on literature review, clinical experience, and expert consensus, the group recommends that emergency physicians offer to initiate opioid use disorder treatment with buprenorphine in appropriate patients and provide direct linkage to ongoing treatment for patients with untreated opioid use disorder. These consensus recommendations include strategies for opioid use disorder treatment initiation and ED program implementation. They were approved by the ACEP board of directors in January 2021.

The impact of adherence to a guideline for minimizing opioid use for treatment of pain in an urban emergency department.

INTRODUCTION: The opioid epidemic has significantly evolved over the last three decades. The initiation and continuation of prescription opioids for pain control were one of the primary contributors, across different medical settings. The emergency department (ED) is typically the first place patients go to for management of acute pain, and often where opioid naïve patients first become exposed to opioids. In 2018, the ED of University Hospital located in Newark, NJ implemented a pain guideline to ensure that patients are not unnecessarily exposed to opioids. The goal of our study was to determine whether provider adherence was successful in reducing opioid administration. METHODS: We conducted a retrospective review of pharmacy records of patients treated for pain in the ED within the time frame January 1, 2017 and December 31, 2019. We analyzed the change in our practice by comparing the amount of opioid and non-opioid medications administered and the number of patients administered each type, as well as the change in our utilization of specific medications. The t-test or the χ2 test were used as applicable. RESULTS: There were decreases in the mean number of opioid doses administered in 2017 (1273) compared to 2019 (498; p = 0.027). There was an increase in non-opioid analgesics administered, (mean 2017: 1817, mean 2019: 2432.5, p = 0.018). There was also an increase in the proportion of patients given non-opioid analgesics (mean 2017: 22%, mean 2019: 28%, p < 0.0001). There were increases in administrations of acetaminophen (40% to 52%) and ibuprofen (30% to 35.1%), and decreases in administrations of hydromorphone (2.5% to 0.03%), morphine (11.5% to 5.6%), oxycodone (10.6% to 5.3%), and tramadol (5.7% to 1.9%) (all p < 0.0001). DISCUSSION: A guideline that emphasizes the use of non-opioid analgesics first line treatment for acute pain can be effective for reducing opioid administration in the ED. Through the use of our guideline, we reduced the number of patients who have received opioid analgesics and, at the same time, increased non-opioid analgesic administration. Future studies should explore readmission rates, duration of pain relief in patients managed with non-opioid versus opioid analgesics, and perception of relief through the use of satisfaction scores.