Exploring Xylazine Awareness, Health Impacts, and Harm Reduction Strategies: Findings From a Multimethods Study in Lowell, Massachusetts.

BACKGROUND: Xylazine, an adulterant in local drug supplies, has been detected in approximately 30% of opioid samples submitted for testing in Massachusetts. A better understanding of local risks, harms, and use preferences is needed to combat xylazine-related impacts on local communities. METHODS: Through the STOP-OD Lowell study, we aimed to assess local xylazine awareness through in-depth interviews with local community stakeholders (n = 15) and local people who use drugs (PWUD; n = 15) and surveys with local PWUD (n = 94). The qualitative interviews focused on the current drug landscape and knowledge of adulterants in Lowell, and the results informed subsequent survey design. Through our survey, we examined whether PWUD were aware of xylazine and their willingness to use xylazine test strips. RESULTS: Most community stakeholders and PWUD had limited awareness about the presence and impact of xylazine as an adulterant. Forty-seven (50%) survey respondents were aware of xylazine. When provided with more information about xylazine, 65% of all respondents expressed a willingness to use xylazine test strips. PWUD who had received naloxone training, reported using with others, and using tester shots were more willing to use xylazine test strips. CONCLUSION: Our findings are congruent with existing literature that indicates that there is limited awareness of xylazine among PWUD, and they consider xylazine an unwanted adulterant. We also found that PWUD who use other harm reduction measures are more willing to use xylazine test strips. The increase in xylazine warrants additional community-level interventions such as wound management and local testing infrastructure. Further research is needed to understand better the impacts associated with xylazine use, effective harm reduction techniques, and perceptions of xylazine test strips.

Development of a Patient and Clinician Informed Website on Injection Drug Use Related Infective Endocarditis.

BACKGROUND: Few patient-facing educational materials and interventions exist for the prevention of injection drug use-related infective endocarditis (IDU-IE). We developed a patient and clinician-informed website for patients about IDU-IE to promote education and prevention strategies. METHODS: This mixed-methods study integrated surveys and semi-structured interviews with patients and clinician to develop a patient website about IDU-IE. Patient participants included hospitalized adults with an opioid use disorder, history of injection drug use, and an injection drug use-related infection. Interprofessional healthcare clinicians including trainees participated. A baseline survey and semi-structured interviews were conducted with patients to understand knowledge of IDU-IE and preferences in educational materials content and format. Interviews were analyzed using rapid qualitative analysis. Results informed development of the patient website. Finally, patients and clinicians provided 2 rounds of survey feedback after reviewing the website, assessing the likelihood of using and recommending it to others, helpfulness of information in the website sections, and content satisfaction. RESULTS: Patient participants (n = 15) reported low baseline understanding of injection practice and risk of IDU-IE. After reviewing the website (n = 17), patients reported they were very likely to recommend the website as a reference for themselves (mean of 4.3; 4 = very likely) and for others (mean = 4.3). They found the following sections, on average, to be very helpful (4 = very helpful): complications from injection drug use (4.4), safer injection practice (4.4), and information about infective endocarditis (4.4). Patients on average were satisfied with the website content overall (4.8). Clinicians (n = 27) reported, on average, being very likely to recommend this website to a patient (4.4) and to use the website to counsel patients (4.1). CONCLUSIONS: A patient and clinician-informed website on IDU-IE is acceptable for patients and clinicians to use as a patient education resource to help prevent IDU-IE-related harms.

Understanding Clinician Knowledge, Attitudes, and Practices Relating to Nonpharmaceutical Fentanyl and Harm Reduction.

BACKGROUND: Nonpharmaceutical fentanyl (NPF) is driving the national epidemic of opioid overdose deaths. Clinicians can play a role in fostering awareness of this growing risk and delivering interventions to reduce mortality. However, there is limited research assessing clinician knowledge, attitudes, and practices relating to NPF and harm reduction strategies. METHODS: A 34-question survey was designed to assess knowledge, attitudes, and practices related to NPF and harm reduction strategies of adult and pediatric hospital-based and emergency clinicians at a single academic medical center. Results were summarized using descriptive statistics. Chi square and Fishers exact tests were used to compare groups. RESULTS: There were 136 survey responses. The majority (88%) of respondents correctly answered a question on NPF potency. Most respondents were aware that NPF exposure was very (84%) or somewhat likely (10%) for someone using illicit opioids and very (44%) or somewhat likely (46%) for nonopioid drugs. Respondents viewed overdose prevention as highly important for patients using illicit opioids (93%) and nonopioid drugs (86%) but few (21%) were very/extremely familiar with overdose prevention strategies and just over half (57%) were comfortable/very comfortable counseling about overdose prevention. There was wide variability in utilization of harm reduction/treatment strategies (7.3% frequently providing fentanyl test kits to 70% frequently prescribing naloxone). Higher levels of comfort and familiarity with overdose prevention were associated with more frequent counseling on harm reduction strategies. Pediatric-only clinicians had less familiarity (5% very/extremely familiar) and comfort (35% comfortable/very comfortable) with overdose prevention, and limited use of harm reduction strategies (0%-31% using each strategy frequently). CONCLUSIONS: While clinicians had knowledge and awareness of NPF and rated overdose prevention as highly important, utilization of harm reduction and treatment strategies was variable. This study highlights opportunities for education and system-based support to improve clinician-driven harm reduction practices for patients at risk of overdose.

Modeling the population health impact of accurate and inaccurate perceptions of harm from nicotine.

BACKGROUND: Scientific evidence clearly demonstrates that inhaling the smoke from the combustion of cigarettes is responsible for most of the harm caused by smoking, and not the nicotine. However, a majority of U.S. adults who smoke inaccurately believe that nicotine causes cancer which may be a significant barrier, preventing switching to potentially reduced risk, non-combustible products like electronic nicotine delivery systems (ENDS) and smokeless tobacco (ST). We assessed the population health impact associated with nicotine perceptions. METHODS: Using a previously validated agent-based model to the U.S. population, we analyzed nationally representative data from the Population Assessment of Tobacco and Health (PATH) study to estimate base case rates of sustained (maintained over four waves) cessation and switching to non-combustible product use, by sex. Nicotine perception scenarios were determined from PATH data. The overall switch rate from smoking in Wave 4 to non-combustible product use in Wave 5 (3.94%) was stratified based on responses to the nicotine perception question "Do you believe nicotine is the chemical that causes most of the cancer caused by smoking cigarettes?", (four-item scale from "Definitely not" to "Definitely yes"). The relative percent change between the overall and stratified rates, corresponding to each item, was used to adjust the base case rates of switching, to determine the impact, if all adults who smoke exhibited switching behaviors based on responses to the nicotine perceptions question. The public health impact of nicotine perceptions was estimated as the difference in all-cause mortality between the base case and the four nicotine perception scenarios. RESULTS: Switch rates associated with those who responded, "Definitely not" (8.39%) resulted in a net benefit of preventing nearly 800,000 premature deaths over an 85-year period. Conversely switch rates reflective of those who responded, "Definitely yes" (2.59%) resulted in a net harm of nearly 300,000 additional premature deaths over the same period. CONCLUSIONS: Accurate knowledge regarding the role of nicotine is associated with higher switch rates and prevention of premature deaths. Our findings suggest that promoting public education to correct perceptions of harm from nicotine has the potential to benefit public health.

An Automated Text Messaging Intervention to Reduce Substance Use Self-Stigma (Project RESTART): Protocol for a Feasibility and Acceptability Pilot Study.

BACKGROUND: Stigma is a barrier to treatment and harm reduction seeking in people who use drugs. Most stigma reduction interventions offer psychotherapy or psychoeducation in group-based clinical settings, failing to reach people who are not in treatment. SMS text messaging is an effective and acceptable modality for delivering health information to people who use drugs and may be a suitable conduit for providing information and advice to understand and cope with stigma. OBJECTIVE: This paper presents the protocol for a study that aims to determine the feasibility, acceptability, and preliminary effectiveness of a 4-week automated SMS text message intervention to increase stigma resistance and reduce self-stigma in people who use drugs. METHODS: We designed a novel automated SMS text message intervention to address the four personal-level constructs of stigma resistance: (1) not believing stigma and catching and challenging stigmatizing thoughts, (2) empowering oneself through learning about substance use and one's recovery, (3) maintaining one's recovery and proving stigma wrong, and (4) developing a meaningful identity and purpose apart from one's substance use. Theory-based messages were developed and pilot-tested in qualitative elicitation interviews with 22 people who use drugs, resulting in a library of 56 messages. In a single-group, within-subjects, community-based pilot trial, we will enroll 30 participants in the Resisting Stigma and Revaluating Your Thoughts (RESTART) intervention. Participants will receive 2 daily SMS text messages for 4 weeks. Implementation feasibility will be assessed through recruitment, enrollment, retention, and message delivery statistics. User feasibility and acceptability will be assessed at follow-up using 23 survey items informed by the Theoretical Framework of Acceptability. Primary effectiveness outcomes are changes in self-stigma (Substance Abuse Self-Stigma Scale) and stigma resistance (Stigma Resistance Scale) from baseline to follow-up measured via a self-administered survey. Secondary outcomes are changes in hope (Adult Dispositional Hope Scale) and self-esteem (Rosenberg Self-Esteem Scale). Feasibility and acceptability will be assessed with descriptive statistics; effectiveness outcomes will be assessed with paired 2-tailed t tests, and group differences will be explored using ANOVA. Overall, 12 participants will also be selected to complete acceptability interviews. RESULTS: This pilot study was funded by the National Institute on Drug Abuse in April 2023 and received regulatory approval in January 2024 by the University of North Carolina-Chapel Hill Institutional Review Board. Recruitment and enrollment began in March 2024. Follow-up visits are expected to conclude by May 2024. Results will be disseminated in relevant peer-reviewed journals. CONCLUSIONS: To the best of our knowledge, this is the first study to address substance use stigma via a self-help SMS text messaging program. Results will add to the nascent literature on stigma reduction in people who use drugs. This protocol may interest researchers who are considering text messaging to address psychosocial needs in hard-to-reach populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT06281548; https://clinicaltrials.gov/ct2/show/NCT06281548. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59224.

The ethics of enhancement among image and performance enhancing drug coaches.

This research examines image and performance-enhancing drug (IPED) use, specifically focusing on the emerging role of IPED coaches. Situating drug use within broader assemblage theory, we investigated how these coaches, often operating in an online context, function as enabling environments, influencing practices, and contributing to harm reduction in a broader social context within and for IPED communities. Ten IPED coaches were interviewed, with this work focusing on their legal, ethical, and moral considerations, risk assessment, and harm reduction strategies of their practices. We employed a critical realist approach, following flexible coding to identify and develop themes which were further framed an enabling environments framework. Coaches operated along an ethical tightrope, emphasising the conscious regulation of conduct within established norms and the nuanced assessment of risks aligned with individual goals and motivations. Power dynamics and responsibility concerns unfolded through the lens of collaborative decision-making, where trust emerged as an essential element of these relations within contextual risk assessments. IPED coaches play a role in harm reduction by fostering trust and informed decision-making, balancing clients' goals with health considerations. These findings emphasise the potential for collaboration between IPED coaches and the health workforce to enhance health promotion and support within IPED communities.

Direct health implications of e-cigarette use: a systematic scoping review with evidence assessment.

Background: E-cigarettes are often marketed as a less harmful alternative to traditional tobacco cigarettes. Despite their popularity, the evidence regarding their effects on human health remains unclear and is filled with complexities. Objectives: This systematic review aims to elucidate the direct effects of electronic cigarette use on human health, carefully distinguishing between the specific characteristics of the populations studied. Methodology: Adhering to the PRISMA guidelines, we conducted a comprehensive search in PubMed/Medline, Web of Science, Scopus, and Google Scholar databases without date restrictions, including articles in both Spanish and English. This approach enabled the identification and analysis of primary studies to understand the direct effect of electronic cigarettes on human health. Results: A total of 33 studies were included that evaluated cardiovascular, pulmonary, renal, weight and fertility effects. Only five studies analyzed e-cigarettes in healthy populations and seven studies compared healthy individuals against smokers. The effects evaluated on smokers or former tobacco smokers were apparently positive, however, among healthy individuals, increased heart rate, mean arterial pressure, oxidative stress, alteration of respiratory epithelial cells and increased airflow resistance were found. Conclusion: Smokers or former smokers who switch to e-cigarettes may reduce their exposure to carcinogens and lower their risk of developing severe health issues associated with conventional smoking. However, in healthy individuals who have never smoked traditional cigarettes, the use of e-cigarettes introduces several cardiovascular and respiratory adverse effects. These findings suggest that while e-cigarettes can be a strategic harm reduction tool for smokers, they are not a safe option for non-smokers.

Providers' knowledge and perception of xylazine in the unregulated drug supply: a sequential explanatory mixed-methods study.

BACKGROUND: Xylazine is increasingly prevalent in the unregulated opioid supply in the United States. Exposure to this adulterant can lead to significant harm, including prolonged sedation and necrotic wounds. In the absence of literature describing healthcare providers' experiences with treating patients who have been exposed to xylazine, we aimed to explore what gaps must be addressed to improve healthcare education and best practices. METHODS: From October 2023 to February 2024, we conducted a sequential explanatory mixed-methods study, with (1) a quantitative survey phase utilizing convenience sampling of healthcare providers treating patients in Connecticut and (2) a qualitative semi-structured interview phase utilizing purposive sampling of providers with experience treating patients with xylazine exposure. Summary statistics from the survey were tabulated; interview transcripts were analyzed using thematic analysis. RESULTS: Seventy-eight eligible healthcare providers participated in our survey. Most participants had heard of xylazine (n = 69, 95.8%) and had some knowledge about this adulterant; however, fewer reported seeing one or more patients exposed to xylazine (n = 46, 59.8%). After sampling from this subgroup, we conducted fifteen in-depth interviews. This qualitative phase revealed five themes: (1) while xylazine is novel and of concern, this is not necessarily exceptional (i.e., there are other emerging issues for patients who use drugs); (2) participants perceived that xylazine was increasingly prevalent in the drug supply, even if they were not necessarily seeing more patients with xylazine-related outcomes (XROs); (3) patients primarily presented with non-XROs, making it difficult to know when conversations about xylazine were appropriate; (4) patients with XROs may experience issues accessing healthcare; (5) providers and their patients are learning together about how to minimize XROs and reduce the sense of helplessness in the face of a novel adulterant. CONCLUSIONS: Xylazine-specific education for healthcare providers is currently insufficient. Improving this education, as well as resources (e.g., drug checking technologies) and data (e.g., research on prevention and treatment of XROs), is crucial to improve care for patients who use drugs.

Non-injection drug use among incarcerated people in Iran: Findings from three consecutive national bio-behavioral surveys.

BACKGROUND: Prisons often serve as high-risk environments for drug use, and incarcerated people are at a high risk for substance use-related mental and physical harms. This study aimed to determine the prevalence of non-injection drug use inside the prison and its related factors among incarcerated people in Iran. METHODS: We utilized data from three national bio-behavioral surveillance surveys conducted among incarcerated people in Iran in 2009, 2013, and 2017. Eligibility criteria were being ≥ 18 years old, providing informed consent, and being incarcerated for over a week. Overall, 17,228 participants across all surveys were recruited through a multi-stage random sampling approach. Each participant underwent a face-to-face interview and HIV test. The primary objective of the study was to assess self-reported non-injection drug use within the prison environment within the last month. A multivariable logistic regression model was built to determine associated covariates with drug use inside prison and an adjusted odds ratio (aOR) with 95% confidence intervals (CI) were reported. RESULT: The prevalence of non-injection drug use inside the prison was 24.1% (95% CI 23.5, 24.7) with a significant decreasing trend (39.7% in 2009, 17.8% in 2013, 14.0% in 2017; p-value < 0.001). Overall, 44.0% of those who used drugs were also receiving opioid agonist therapy (OAT) and we noted that in 2017, 75.1% of those on OAT used stimulants. In the multivariable logistic regression model, the year of interview (2013: aOR = 1.43 and 2009: aOR = 5.60), younger age (19-29: aOR = 1.14 and 30-40: aOR = 1.37), male sex (aOR = 3.35), < high school education (aOR = 1.31), having a history of previous incarceration (aOR = 1.26), and having a history of lifetime HIV testing (aOR = 1.76) were significantly and positively associated with recent non-injection drug use inside the prison. CONCLUSIONS: Approximately one in four incarcerated people in Iran reported drug use within the last month inside prisons. While a declining trend in non-injection drug use was noted, substantial gaps persist in harm reduction programs within Iranian prisons. In particular, there is a pressing need for improvements in drug treatment programs, focusing on the integration of initiatives specifically designed for people who use stimulants.

An individual-based dynamic model to assess interventions to mitigate opioid overdose risk.

BACKGROUND: Illicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto. METHODS: An individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events. RESULTS: Model simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses. CONCLUSIONS: Within a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction.

Fentanyl harm reduction strategies among Latinx communities in the United States: a scoping review.

PURPOSE: Fueled by the prescription opioid overdose crisis and increased influx of illicitly manufactured fentanyl, fentanyl overdoses continue to be a public health crisis that has cost the US economy over $1 trillion in reduced productivity, health care, family assistance, criminal justice, and accounted for over 74,000 deaths in 2023. A recent demographic shift in the opioid crisis has led to a rise in overdose deaths among the Latinx population. Harm reduction interventions, including the use of naloxone and fentanyl test strips, have been shown to be effective measures at reducing the number of opioid overdose deaths. The aim of this scoping review is to summarize naloxone and fentanyl test strip interventions and public health policies targeted to Latinx communities. METHODS: PubMed, CINHAL, Web of Science, Embase, and PsycINFO research databases using the keywords "fentanyl," "Latinx," "Harm Reduction," "Naloxone," and "Fentanyl Test Strips'' to identify studies published between January 1, 2013 and December 31, 2023. Endnote and Covidence software were used to catalog and manage citations for review of studies. Subsequently, studies that met inclusion criteria were then summarized using resulting themes. RESULTS: Twenty-seven articles met the inclusion criteria and were further abstracted for the scoping review. Of these articles, 77.7% (n = 21) included a naloxone intervention, while only 11.1% (n = 3) included a fentanyl test strip intervention. Furthermore, 30.1% (n = 8) of these studies were Latinx targeted, and 7.7% (n = 2) of the studies were adapted for Latinx populations. Four themes, including an overall lack of knowledge and awareness, a lack of access to harm reduction or opioid overdose prevention resources, an overall lack of culturally adapted and/or targeted interventions, and restrictive and punitive policies that limit the effectiveness of protective factors were highlighted in this scoping review. CONCLUSION: Limited published research exists on the use of emerging harm reduction behaviors, such as the use of naloxone and fentanyl test strips as community intervention strategies to prevent opioid overdose deaths. Even fewer publications exist on the targeting and cultural adaptation of harm reduction interventions responsive to Latinx communities, especially those using theoretical approaches or frameworks to support these interventions. Future research is needed to assess the unique needs of Latinx populations and to develop culturally responsive programs to prevent opioid-related overdose deaths among this population.

Exploring the harm reduction paradigm: the role of Board-Certified Psychiatric Pharmacists.

Deaths related to opioid overdoses continue to climb, and there remains a need for innovative strategies to address this ongoing crisis. Harm reduction (HR), a nonjudgmental philosophy aimed at reducing consequences associated with drug use and other potentially unsafe behavior, has emerged as a compassionate and effective approach. Harm reduction further emphasizes overdose prevention and fosters a shift in perspective that recognizes substance use disorder as a disease and not a moral failing. The tenets of HR collectively advocate for the well-being of individuals who use substances and support any positive change as defined by the individual. Given the high rate of morbidity and mortality associated with substance misuse and barriers or ambivalence to receiving treatment, awareness of and advocacy for HR practice is essential. This manuscript aims to describe evidence-based HR interventions, provide a foundation for the implementation of services, and further promote the importance of providing humanistic care without judgment. As valued members of the multidisciplinary treatment team, Board-Certified Psychiatric Pharmacists should implement and engage in HR services in the settings where people with substance use disorders receive care.

Special considerations in managing pain and psychosocial distress in patients with opioid use disorder and cancer: the role of the supportive care and psycho-oncology interdisciplinary team.

People with a substance use disorder (SUD) have shortened lifespans due to complications from their substance use and challenges engaging with traditional health care settings and institutions. This impact on life expectancy is especially prominent in patients with co-occurring SUDs and cancer, and often has a much worse prognosis from the cancer than a similar patient without a SUD. Palliative care teams are experts in serious illness communication and symptom management and have become increasingly embedded in the routine care of patients with cancer. We argue that the skill set of palliative care teams is uniquely suited for addressing the needs of this oft marginalized group. We provide a comprehensive review of tools for addressing these needs, including medications that can both treat pain and opioid use disorder (OUD), and highlight psychosocial approaches to treating patients with OUD and cancer in a way that is respectful and effective. Using a trauma informed framework, we focus on the application of harm reduction principles from addiction medicine and the principles of clear communication, accompaniment, and emotional presence from palliative care to maximize support. We also focus on ways to reduce stigma in the delivery of care, by providing language that reduces barriers and increases patient engagement. Finally, we describe a clinic embedded within our institution's cancer center which aims to serve patients with cancer and SUDs, built on the framework of harm reduction, accompaniment and trauma informed care (TIC). Overall, we aim to provide context for addressing the common challenges that arise with patients with cancer and OUD, including the direct impact of psychosocial stress on substance use and cancer treatment, delays in disease directed treatment that can potentially impact further treatment options and outcomes, challenging pain management due to greater opioid debt, and potential loss of primary coping mechanism through substance use in the face of potential terminal diagnosis.

Xylazine in the Unregulated Drug Market: An Integrative Review of Its Prevalence, Health Impacts, and Detection and Intervention Challenges in the United States.

Xylazine, a veterinary sedative, has emerged as a concerning element in the landscape of substance use in the United States. This integrative review synthesizes evidence from a systematic examination of 14 selected studies conducted between 2008 and 2023. The primary objective is to comprehensively understand the epidemiology and prevalence of xylazine use, particularly its involvement in drug-related deaths, regional variations, national impact, co-occurrence with opioids, and challenges associated with detection and intervention. The results underscore stark regional disparities in xylazine prevalence. West Virginia and Miami-Dade County have experienced alarming surges in xylazine-involved drug-related deaths. Nationally, its influence extends beyond regional boundaries, predominantly affecting white males in the Northeast. The co-occurrence of xylazine with opioids, especially fentanyl and heroin, significantly amplifies the risks of fatal overdoses. Detecting xylazine presents formidable challenges due to its frequent presence alongside other substances, necessitating enhanced surveillance and more effective detection methods. User perspectives emerge as pivotal, emphasizing the importance of user-informed harm reduction strategies. In conclusion, this review has significant policy implications. Tailored, region-specific strategies are imperative to address the diverse prevalence of xylazine use. A nationwide response is indispensable, prioritizing harm reduction initiatives, enhanced detection methods, and active user engagement. The multifaceted nature of the xylazine issue requires comprehensive approaches to mitigate its profound risks effectively. Policymakers are urged to consider regional disparities and the co-occurrence of xylazine with opioids when crafting targeted interventions. Immediate, user-informed harm reduction is vital to address the evolving landscape of xylazine use in the United States.

Overdose prevention centres as spaces of safety, trust and inclusion: A causal pathway based on a realist review.

ISSUES: Overdose prevention centres (OPC) are non-residential spaces where people can use illicit drugs (that they have obtained elsewhere) in the presence of staff who can intervene to prevent and manage any overdoses that occur. Many reviews of OPCs exist but they do not explain how OPCs work. APPROACH: We carried out a realist review, using the RAMESES reporting standards. We systematically searched for and then thematically analysed 391 documents that provide information on the contexts, mechanisms and outcomes of OPCs. KEY FINDINGS: Our retroductive analysis identified a causal pathway that highlights the feeling of safety - and the immediate outcome of not dying - as conditions of possibility for the people who use OPCs to build trust and experience social inclusion. The combination of safety, trust and social inclusion that is triggered by OPCs can - depending on the contexts in which they operate - generate other positive outcomes, which may include less risky drug use practices, reductions in blood borne viruses and injection-related infections and wounds, and access to housing. These outcomes are contingent on relevant contexts, including political and legal environments, which differ for women and people from racialised minorities. CONCLUSIONS: OPCs can enable people who live with structural violence and vulnerability to develop feelings of safety and trust that help them stay alive and to build longer term trajectories of social inclusion, with potential to improve other aspects of their health and living conditions.

Use of Syringe Service Programs in Rural vs Urban Maine: A Harm-Reduction Study.

Introduction: Syringe service programs (SSPs) reduce HIV and viral hepatitis transmission, as well as the prevalence of improperly disposed needles and needle stick injuries among first responders. Infections associated with injection drug use are rising in rural areas, including Maine, leading to concerns that SSP services are difficult to access for rural residents. Methods: A cross-sectional survey of 101 participants hospitalized with infections associated with injection drug use at 4 hospitals in Maine was collected over a 15-month period. Descriptive analyses were performed. Statistical analyses were completed using Fisher's exact tests, Pearson's chi-squared tests, and Student's t tests. Results: Of 101 participants, 66 (65%) lived in urban areas, and 35 (35%) lived rurally. Participants living in rural areas reported less SSP use in the past 3 months (76% urban vs 43% rural). Rural participants also had a higher prevalence of injecting buprenorphine than urban participants (6% urban vs 12% rural). Rural participants were also more likely to obtain needles from pharmacies than urban participants (40% urban vs 71% rural). Discussion: SSP programs are underrepresented and accessed less in rural areas of Maine. Rural populations of people who inject drugs have unique health characteristics and syringe-use practices. Conclusions: These findings highlight the need to develop rural SSP programs that address the unique needs of rural populations.

Effectively engaging faith-based leaders on syringe services programs: U.S. pastors' knowledge, perceptions, and questions.

OBJECTIVE: To identify faith-based leaders' (FBLs') knowledge, perceptions, and questions about syringe services programs (SSPs). METHODS: We conducted a one-time, national online survey of 461 Christian FBLs August-September 2022. RESULTS: 56% of FBLs agreed they support having SSPs in their communities; only 7% strongly disagreed. We identified 15 main questions FBLs have about SSPs. We found statistically significant differences based on FBL Protestant affiliations. Mainline FBLs are more knowledgeable about SSPs, likely to believe a larger number of SSP services would benefit their community, supportive of SSPs, interested in data related to SSPs, and likely to look to local public health officials to shape their opinions on SSPs compared with non-mainline FBLs. CONCLUSIONS: SSP advocates can address questions that FBLs have about SSPs before beginning outreach. By understanding common Protestant denominational affiliations, advocates can focus initial engagement efforts on FBLs in their communities who are more likely to support SSPs. Our findings suggest that local public health officials can influence FBLs' opinions about SSPs.

Detecting univariate, bivariate, and overall effects of drug mixtures using Bayesian kernel machine regression.

Background: Innovative analytic approaches to drug studies are needed to understand better the co-use of opioids with non-opioids among people using illicit drugs. One approach is the Bayesian kernel machine regression (BKMR), widely applied in environmental epidemiology to study exposure mixtures but has received far less attention in substance use research.Objective: To describe the utility of the BKMR approach to study the effects of drug substance mixtures on health outcomes.Methods: We simulated data for 200 individuals. Using the Vale and Maurelli method, we simulated multivariate non-normal drug exposure data: xylazine (mean = 300 ng/mL, SD = 100 ng/mL), fentanyl (mean = 200 ng/mL, SD = 71 ng/mL), benzodiazepine (mean = 300 ng/mL, SD = 55 ng/mL), and nitazene (mean = 200 ng/mL, SD = 141 ng/mL) concentrations. We performed 10,000 MCMC sampling iterations with three Markov chains. Model diagnostics included trace plots, r-hat values, and effective sample sizes. We also provided visual relationships of the univariate and bivariate exposure-response and the overall mixture effect.Results: Higher levels of fentanyl and nitazene concentrations were associated with higher levels of the simulated health outcome, controlling for age. Trace plots, r-hat values, and effective sample size statistics demonstrated BKMR stability across multiple Markov chains.Conclusions: Our understanding of drug mixtures tends to be limited to studies of single-drug models. BKMR offers an innovative way to discern which substances pose a greater health risk than other substances and can be applied to assess univariate, bivariate, and cumulative drug effects on health outcomes.