Introduction The initiation of buprenorphine for patients with opioid use disorder (OUD) in the emergency department (ED) has been associated with improved outcomes including reduced ED visits and increased treatment engagement. Though both standard-dose (8 mg buprenorphine equivalent) and high-dose (24 mg buprenorphine equivalent) strategies to initiate buprenorphine have been used in the ED, no prospective trials comparing outcomes among patients receiving these treatments have been reported.Methods and analysis This multisite randomised clinical trial is a multisite double-blind, double-dummy, randomised clinical trial enrolling 360 emergency department patients with moderate-to-severe OUD. Enrolled patients will be randomised to one of two study arms: standard-dose induction or high-dose induction, both provided in the ED. This study will engage, train and provide resources to five EDs throughout the US to recruit patients with untreated OUD into a randomised clinical trial. The primary aim is to evaluate the effects of the standard-dose induction and high-dose induction on rates of OUD treatment participation within 10 days post-randomisation. The secondary aims are to evaluate differences between standard-dose induction and high-dose induction on the outcomes of opioid craving, opioid withdrawal symptoms and illicit drug use assessed during 10 days post randomisation and evaluate the effects between treatment arms on rates of OUD treatment participation within 30 days post randomisation.Ethics and dissemination This study is funded by the National Institute on Drug Abuse and has been approved by the WCG Instutitional Review Board. It has been registered at clinicaltrials.gov. This study will inform the strategy for treatment initiation with buprenorphine among diverse ED settings and will provide ongoing evidence to support the safety and efficacy of initiating treatment for OUD in the ED.Trial registration number NCT06494904.

ABSTRACT:Appropriate short-term use of opioids in opioid-naive adults can result in unintended prolonged opioid use (UPOU) which is associated with significant morbidity and mortality. The objective of this prospective case-control study was to identify incident cases of UPOU and to compare their characteristics with patients who did not progress to UPOU. Opioid-naive adults receiving an initial opioid prescription for surgical or nonsurgical indications were recruited at 3 clinical sites. Patients progressing to UPOU (cases) were identified 90 days after the initial prescription and compared with patients who did not progress to UPOU (controls). The status of opioid use was verified using urine drug tests. The cohort included 513 cases and 517 controls. The mean (SD) patient age was 49.6 (15.3) years and 694 (67.4%) were female. In an adjusted logistic regression analysis, several patient characteristics significantly associated with UPOU included ≥2 emergency department evaluations in the past year; prior spine, joint replacement, or cataract surgery; status as a current or former smoker; daily use of over-the-counter pain medications; opioid craving; and greater pain interference. Conversely, characteristics negatively associated with UPOU included postsurgical pain as the indication for the initial opioid prescription, prior pregnancy, greater widespread body pain, and lower levels of general activity. The findings of this study offer novel insights into the behavioral pain responses and patient characteristics associated with UPOU. These results will be used to promote strategies to identify at-risk patients and to deploy interventions targeting the modifiable risk factors for UPOU.

BackgroundMisuse of prescription opioids remains a public health problem. Appropriate short-term use of these medications in opioid-naive patients is indicated in selected settings but can result in unintended prolonged opioid use (UPOU), defined as the continuation of opioid therapy beyond the period by which acute pain would have been expected to resolve. Clinical strategies aimed at preventing UPOU are lacking due to the absence of information about how this poorly understood clinical phenomenon actually develops. ObjectiveIn this research project, 3 Clinical and Translational Science Awards (CTSA) programs (Mayo Clinic, University of Michigan, and Yale University) leveraged the conceptual framework for UPOU to investigate how patient characteristics, practice environment characteristics, and opioid prescriber characteristics facilitate or impede UPOU. All data management and analyses were conducted at a fourth CTSA program (University of Minnesota). This work was accomplished by pursuing 3 specific aims. MethodsIn aim 1, opioid-naive adults receiving an initial opioid prescription were recruited for study participation. Opioid prescriptions were identified longitudinally, and patterns of use were categorized as short-term, episodic, or long-term use using established criteria. Using a prospective case-control design, patients progressing to UPOU were matched 1:1 with patients who did not develop UPOU, and differences in patient characteristics were assessed. In aim 2, clinicians who prescribed opioids to patients in aim 1 were identified and recruited for prospective assessments. Institutional and individual practice environments were assessed using a validated self-report survey. In aim 3, structural equation modeling was used to evaluate data collected in aims 1 and 2, and identified interactions were further evaluated in a large national administrative claims database. ResultsPatient recruitment began on August 1, 2019. However, due to the COVID-19 pandemic, patient recruitment was slowed and intermittently interrupted over the ensuing 3-year period. As a result of regional variations in the impact of the COVID-19 pandemic on research activities, the majority of patient and clinician recruitment occurred at the Mayo Clinic site. ConclusionsFollowing complete data analyses, it is anticipated that electronic health record systems will be leveraged to help clinicians identify at risk patients and to develop direct-to-patient educational materials to raise awareness of the risk factors for developing UPOU. Trial RegistrationClinicalTrials.gov NCT04024397; https://clinicaltrials.gov/study/NCT04024397 International Registered Report Identifier (IRRID)DERR1-10.2196/72032

BACKGROUND: Risky alcohol use and alcohol dependence are common among patients with opioid dependence during remission; however, therapeutic options for co-occurring addictions remain limited. AIM: This work aimed to conduct a preliminary evaluation of the efficacy and safety of nalmefene in combination with behavioral counseling in patients with opioid dependence in remission and active alcohol dependence. METHODS: A pilot open-label clinical study (August 31, 2017–September 13, 2018; Saint Petersburg) included eight patients with opioid dependence in remission and active alcohol dependence. The intervention comprised daily use of oral nalmefene (36 mg) and weekly individual sessions of structured behavioral counseling based on motivational interviewing and cognitive behavioral therapy, aimed at maintaining remission and preventing relapse. Efficacy was assessed by opioid abstinence (according to urinalysis and self-reports), abstinence from alcohol and other psychoactive substances (self-reports), and retention in the program over 24 weeks. RESULTS: This study was terminated early due to multiple withdrawals of consent caused by adverse events or relapse in opioid dependence. Adverse effects (insomnia, fatigue, anxiety, irritability, agitation, nausea, tremor, muscle pain, increased blood pressure, and opioid craving) were observed in six participants, suggesting a possible withdrawal-like reaction triggered by nalmefene in this population, despite the fact that all participants had abstained from opioid use for at least two months prior to enrollment. CONCLUSION: The findings presented in this study reveal challenges in the use of nalmefene among patients with opioid dependence in remission and alcohol abuse, emphasizing the importance of further research to evaluate the potential of nalmefene use in individuals with combined dependence on different psychoactive substances.

Importance:There are racial and ethnic disparities in opioid use disorder (OUD) treatment engagement during and after emergency department (ED) encounters. Objective:To identify patterns of barriers and facilitators to treatment engagement after an ED visit among Black, Hispanic, and White individuals with OUD. Design, Setting, and Participants:This qualitative study was conducted from June 2023 to May 2024 using in-depth semistructured individual telephone interviews. Participants with OUD were previously enrolled in a multisite study comparing 2 formulations of buprenorphine in ED patients with untreated OUD on treatment engagement. Exposures:A diagnosis of moderate-to-severe OUD and a visit to an ED. Main Outcomes and Measures:The primary outcome was identification of key themes at both the behavioral and health system levels associated with treatment engagement, identified through thematic analysis of interview data. Results:A total of 57 individuals (20 female [35.1%]; mean [SD] age, 41.7 [12.8] years; 20 Black [35.1%]; 17 Hispanic [29.8%]; 20 White [35.1%]) participated in the study. Although racial and ethnic group-specific factors existed, common barriers to treatment engagement included stigma, structural factors (eg, transportation and insurance), uncertainty navigating the health system, and mental health issues. Black participants specifically described how previous trauma and daily stress contributed to a lack of treatment engagement. Black and Hispanic participants expressed experiences of racism and mistrust within the health system. Hispanic and White participants expressed concerns about the adverse effects and taste of sublingual buprenorphine. Common facilitators included positive attitudes toward treatment and patient experiences with ED staff and stable health care access. Hispanic participants described family support as a crucial factor toward treatment engagement. Black participants expressed the importance of connecting with individuals who were abstinent. Conclusions and Relevance:In this qualitative study of 57 individuals with OUD previously treated in the ED, common themes emerged across racial and ethnic groups. However, Black, Hispanic, and White individuals with OUD encountered distinct barriers and facilitators to treatment engagement after an ED visit, such as the importance of family support among Hispanic individuals as a facilitator and experiences of racism within the health system among both Black and Hispanic individuals as a barrier. Future ED-based interventions should address disparities by reducing barriers and enhancing facilitators to improve equitable treatment access.

This qualitative analysis surveys barriers and facilitators of readiness to initiate buprenorphine administration in the emergency department and identifies opportunities to promote readiness among clinicians to treat patients with opioid use disorder. Question What are the key barriers and facilitators for clinician initiation of buprenorphine in the ED with referral for the treatment of opioid use disorder? Findings A mixed-methods evaluation of 268 attending physicians, resident physicians, and advanced practice clinicians in academic emergency departments found that 9 of 258 (3.5%) reported completion of Drug Addiction Treatment Act of 2000 training, and 56 of 268 (20.9%) had high levels of readiness to prescribe buprenorphine in the emergency department. Key barriers included lack of training and experience in treating opioid use disorder, concerns about ability to link to ongoing care, and competing needs for time and resources in a busy emergency department. Meaning Although few emergency department clinicians in this study had high levels of readiness to initiate buprenorphine with referral for ongoing treatment, many expressed a willingness to learn with sufficient support, indicating the importance of clinician and system-level changes. Importance Treatment of opioid use disorder (OUD) with buprenorphine decreases opioid use and prevents morbidity and mortality. Emergency departments (EDs) are an important setting for buprenorphine initiation for patients with untreated OUD; however, readiness varies among ED clinicians. Objective To characterize barriers and facilitators of readiness to initiate buprenorphine for the treatment of OUD in the ED and identify opportunities to promote readiness across multiple clinician types. Design, Setting, and Participants Using data collected from April 1, 2018, to January 11, 2019, this mixed-methods formative evaluation grounded in the Promoting Action on Research Implementation in Health Services framework included 4 geographically diverse academic EDs. Attending physicians (n = 113), residents (n = 107), and advanced practice clinicians (APCs) (n = 48) completed surveys electronically distributed to all ED clinicians (n = 396). A subset of participants (n = 74) also participated in 1 of 11 focus group discussions. Data were analyzed from June 1, 2018, to February 22, 2020. Main Outcomes and Measures Clinician readiness to initiate buprenorphine and provide referral for ongoing treatment for patients with OUD treated in the ED was assessed using a visual analog scale. Responders (268 of 396 [67.7%]) were dichotomized as less ready (scores 0-6) or most ready (scores 7-10). An ED-adapted Organizational Readiness to Change Assessment (ORCA) and 11 focus groups were used to assess ratings and perspectives on evidence and context-related factors to promote ED-initiated buprenorphine with referral for ongoing treatment, respectively. Results Among the 268 survey respondents (153 of 260 were men [58.8%], with a mean [SD] of 7.1 [9.8] years since completing formal training), 56 (20.9%) indicated readiness to initiate buprenorphine for ED patients with OUD. Nine of 258 (3.5%) reported Drug Addiction Treatment Act of 2000 training completion. Compared with those who were less ready, clinicians who were most ready to initiate buprenorphine had higher mean scores across all ORCA Evidence subscales (3.50 [95% CI, 3.35-3.65] to 4.33 [95% CI, 4.13-4.53] vs 3.11 [95% CI, 3.03-3.20] to 3.60 [95% CI, 3.49-3.70]; P < .001) and on the Slack Resources of the ORCA Context subscales (3.32 [95% CI, 3.08-3.55] vs 3.0 [95% CI, 2.87-3.12]; P = .02). Barriers to ED-initiated buprenorphine included lack of training and experience in treating OUD with buprenorphine, concerns about ability to link to ongoing care, and competing needs and priorities for ED time and resources. Facilitators to ED-initiated buprenorphine included receiving education and training, development of local departmental protocols, and receiving feedback on patient experiences and gaps in quality of care. Conclusions and Relevance Only a few ED clinicians had a high level of readiness to initiate buprenorphine; however, many expressed a willingness to learn with sufficient supports. Efforts to promote adoption of ED-initiated buprenorphine will require clinician and system-level changes.

Mitragyna speciosa, also known as kratom, has been reported to have a broad range of pharmacological properties. Freshly harvested leaves and their water extracts are consumed in Southeast Asia while preparations made from dried leaf material are consumed in Western countries. Our study evaluated the phytochemical composition of freshly harvested kratom leaves using LCMS/MS analysis of water and ethanol liquid extracts. Mitragynine and its congeners, including 7-hydroxymitragynine, speciocilliatine, speciogynine, paynantheine, as well as bioactive phenolics including chlorogenic acid, o-coumaric acid, quercitrin, and rutin were identified. However, 7-hydroxymitragynine was detected solely in the water-liquid extract. Currently, unknown compounds were also present in the chromatograms and mass spectra. The study results support that 7-hydroxymitragynine is a post-harvest oxidative derivative or metabolite of mitragynine. Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.

PURPOSE OF REVIEW:Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West. RECENT FINDINGS:Our review of the Scopus database identified a total of 55 publications, including clinical case reports and case series reports, surveys, studies enrolling human participants, and publications based on large-scale national surveys or large-scale national or international health system database records. SUMMARY:Overall, there is dearth of reliable data on key epidemiological factors, including the prevalence rates, and on objective and reliable indices of the risk/safety profiles. Rigorous and systematic studies including improved epidemiological surveillance, human laboratory, and controlled clinical studies are urgently needed to advance our understanding of public health consequences of consuming kratom and kratom-derived products and to improve our understanding of their risk/safety profile and additional analytical studies to better inform development of needed regulatory oversight.

INTRODUCTION:Clinical pharmacists are well positioned to enhance efforts to promote emergency department (ED)-initiated buprenorphine to treat opioid use disorder (OUD). Among clinical pharmacists in urban EDs, we sought to characterize barriers and facilitators for ED-initiated buprenorphine to inform future implementation efforts and enhance access to this highly effective OUD treatment. METHODS:This study was conducted as a part of Project ED Health (CTN-0069, NCT03023930), a multisite effectiveness-implementation study aimed at promoting ED-initiated buprenorphine that was conducted between April 2017 and July 2020. Data collection and analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) framework to assess perspectives on the relationship between 3 elements: evidence for buprenorphine, the ED context, and facilitation needs to promote ED-initiated buprenorphine. The study used an iterative coding process to identify overlapping themes within these 3 domains. RESULTS:The study conducted eight focus groups/interviews across four geographically disparate EDs with 15 pharmacist participants. We identified six themes. Themes related to evidence included (1) varied levels of comfort and experience among pharmacists with ED-initiated buprenorphine that increased over time and (2) a perception that patients with OUD have unique challenges that require guidance to optimize ED care. With regards to context, clinical pharmacists identified: (3) their ability to clarify scope of ED care in the context of unique pharmacology, formulations, and regulations of buprenorphine to ED staff, and that (4) their presence promotes successful program implementation and quality improvement. Participants identified facilitation needs including: (5) training to promote practice change and (6) ways to leverage already existing pharmacy resources outside of the ED. CONCLUSION:Clinical pharmacists play a unique and critical role in the efforts to promote ED-initiated buprenorphine. We identified 6 themes that can inform pharmacist-specific interventions that could aid in the successful implementation of this practice.

Importance:An increasing number of emergency departments (EDs) are initiating buprenorphine for opioid use disorder (OUD) and linking patients to ongoing community-based treatment, yet community-based clinician and staff perspectives regarding this practice have not been characterized.Objective:To explore perspectives and experiences regarding ED-initiated buprenorphine among community-based clinicians and staff in geographically distinct regions.Design, Setting, and Participants:This qualitative study reports findings from Project ED Health, a hybrid type 3 effectiveness-implementation study designed to evaluate the impact of implementation facilitation on ED-initiated buprenorphine with referral to ongoing medication treatment. Clinicians and staff from community-based treatment programs were identified by urban academic EDs as potential referral sites for ongoing OUD treatment in 4 cities across the US in a formative evaluation as having the capability to continue medication treatment. Focus groups were held from April 1, 2018, to January 11, 2019, to examine community OUD treatment clinician and staff perspectives on accepting patients who have received ED-initiated buprenorphine. Data were analyzed from August 2020 to August 2022.Main Outcomes and Measures:Data collection and analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) implementation science framework, focusing on domains including evidence, context, and facilitation.Results:A total of 103 individuals (mean [SD] age, 45.3 [12.0] years; 76 female and 64 White) participated in 14 focus groups (groups ranged from 3-22 participants). Participants shared negative attitudes toward buprenorphine and variable attitudes toward ED-initiated buprenorphine. Prominent barriers included the community site treatment capacity and structure as well as payment and regulatory barriers. Perceived factors that could facilitate this model included additional substance use disorder training for ED staff, referrals and communication, greater inclusion of peer navigators, and addressing sociostructural marginalization that patients faced.Conclusions and Relevance:In this study of community-based clinicians and staff positioned to deliver OUD treatment, participants reported many barriers to successful linkages for patients who received ED-initiated buprenorphine. Strategies to improve these linkages included educating communities and programs, modeling low-barrier philosophies, and using additional staff trained in addiction as resources to improve transitions from EDs to community partners.

Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.

Objective We assessed the frequency of emergency department (ED) HIV and hepatitis C (HCV) screening in a high-risk cohort of ED patients with untreated opioid use disorder (OUD). Methods This analysis used data from a prospective, observational study of English-speaking adults with untreated OUD enrolled from April 2017 to December 2018 in 4 urban, academic EDs. Two cohorts were defined for this analysis by self-reported negative/unknown status for HIV (cohort 1) and HCV (cohort 2). Sites featured structured screening programs throughout the entire enrollment period for HIV and during at least part of the enrollment period for HCV. We calculated the proportion tested for HIV and HCV during the study enrollment ED visit. Results Among 394 evaluated ED patients, 328 of 394 (83.2%) were not tested for HIV or HCV and 244 of 393 (62.1%) lacked a usual medical care provider. In cohort 1, 375 reported negative or unknown HIV status; 59/375 (15.7%) overall and 33/218 (15.1%) of those reporting recent injection drug use were tested for HIV. In cohort 2, 231 reported negative of unknown HCV status; 22/231 (9.5%) overall and 9/98 (9.2%) of those reporting recent injection drug use were tested for HCV. The proportion tested by the ED ranged from 3% to 25% for HIV and 4% to 32% for HCV across study sites. Conclusions Emergency department HIV and HCV screening remains infrequent among patients with untreated OUD, including those who inject drugs, even in EDs committed to screening. Targeted HIV/HCV screening should be considered as an adjunct strategy until the ideal of universal screening is more fully achieved.

Importance:Emergency departments (EDs) are increasingly initiating treatment for patients with untreated opioid use disorder (OUD) and linking them to ongoing addiction care. To our knowledge, patient perspectives related to their ED visit have not been characterized and may influence their access to and interest in OUD treatment.Objective:To assess the experiences and perspectives regarding ED-initiated health care and OUD treatment among US patients with untreated OUD seen in the ED.Design, Setting, and Participants:This qualitative study, conducted as part of 2 studies (Project ED Health and ED-CONNECT), included individuals with untreated OUD who were recruited during an ED visit in EDs at 4 urban academic centers, 1 public safety net hospital, and 1 rural critical access hospital in 5 disparate US regions. Focus groups were conducted between June 2018 and January 2019.Main Outcomes and Measures:Data collection and thematic analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) implementation science framework with evidence (perspectives on ED care), context (ED), and facilitation (what is needed to promote change) elements.Results:A total of 31 individuals (mean [SD] age, 43.4 [11.0] years) participated in 6 focus groups. Twenty participants (64.5%) identified as male and most 13 (41.9%) as White; 17 (54.8%) reported being unemployed. Themes related to evidence included patients' experience of stigma and perceived minimization of their pain and medical problems by ED staff. Themes about context included the ED not being seen as a source of OUD treatment initiation and patient readiness to initiate treatment being multifaceted, time sensitive, and related to internal and external patient factors. Themes related to facilitation of improved care of patients with OUD seen in the ED included a need for on-demand treatment and ED staff training.Conclusions and Relevance:In this qualitative study, patients with OUD reported feeling stigmatized and minimized when accessing care in the ED and identified several opportunities to improve care. The findings suggest that strategies to address stigma, acknowledge and treat pain, and provide ED staff training should be implemented to improve ED care for patients with OUD and enhance access to life-saving treatment.