Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010-December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15-24), and high-MELD (≥25) groups. We compared outcomes between MELD-stratified LDLT groups and between MELD-stratified LDLT and donation after brain death liver transplantation recipients. We used Kaplan-Meier analysis to compare graft survival rates and multivariable Cox proportional hazards modeling to identify factors associated with graft outcomes. Of 3558 LDLTs, 1605 (45.1%) were low-MELD, 1616 (45.4%) intermediate-MELD, and 337 (9.5%) high-MELD. Over the study period, the annual number of LDLTs increased from 282 to 569, and the proportion of high-MELD LDLTs increased from 3.9% to 7.7%. Graft survival was significantly higher in low-MELD versus high-MELD LDLT recipients (adjusted HR = 1.36, 95% CI: 1.03-1.79); however, 5-year survival exceeded 70.0% in both groups. We observed no significant difference in graft survival between high-MELD LDLT and high-MELD donation after brain death liver transplantation recipients (adjusted HR: 1.25, 95% CI:0.99-1.58), with a 5-year survival of 71.5% and 77.3%, respectively. Low LDLT center volume (<3 LDLTs/year) and recipient life support requirement were both associated with inferior graft outcomes among high-MELD LDLT recipients. While higher MELD scores confer graft failure risk in LDLT, high-MELD LDLT outcomes are acceptable with similar outcomes to MELD-stratified donation after brain death liver transplantation recipients. Future practice guidance should consider the expansion of LDLT recommendations to high-MELD recipients in centers with expertise to help reduce donor shortage.

Patterns of Socioeconomic Marginalization among People Who Use Drugs: A Gender-Stratified Repeated Measures Latent Class Analysis.

Socioeconomic factors are important correlates of drug use behaviors and health-related outcomes in people who use drugs (PWUD) residing in urban areas. However, less is known about the complex overlapping nature of socioeconomic conditions and their association with a range of individual, drug use, and health-related factors in men and women who use drugs. Data were obtained from two community-recruited prospective cohorts of PWUD. Using a gender-stratified approach, we conducted repeated measures latent class analyses (RMLCA) to identify discrete latent socioeconomic subgroups. Multivariable generalized estimating equations were then used to identify correlates of class membership. Between June 2014 and December 2018, RMLCA of 9844 observations from 1654 participants revealed five distinct patterns of socioeconomic status for both men and women. These patterns were primarily distinguished by variations in income, material and housing security, income generation activity, exposure to violence, criminal justice involvement, and police contact. Across gender, progressive increases in exposure to multiple dimensions of socioeconomic disadvantage were found to be associated with frequent use of opioids and stimulants, accessing social services, and being hepatitis C virus antibody-positive. Similar but less congruent trends across gender were observed for age, binge drug use, engagement with opioid agonist therapy, and living with HIV. Gendered patterns of multiple and overlapping dimensions of socioeconomic adversity aligned with patterns of frequent drug use and health-related concerns, highlighting priority areas for gender-inclusive, multilevel responses to mitigate health disparities and meet the diverse socioeconomic needs of urban-dwelling men and women who use drugs.

Characterizing Use of Supervised Consumption Services among Street-involved Youth and Young Adults in the Context of an Overdose Crisis.

In response to an increase in overdose deaths, there was a rapid scale-up of supervised consumption services (SCS), including federally sanctioned SCS and low-barrier SCS known as overdose prevention sites (OPS), in Vancouver, Canada, beginning in December 2016. However, little is known about the use of such services among adolescents and young adults (AYA) in this context. We therefore sought to characterize factors associated with the use of federally sanctioned SCS and OPS among street-involved AYA who inject drugs in Vancouver during an overdose crisis. From December 2016 to March 2020, data were collected from a prospective cohort of street-involved AYA aged 14 to 26 at baseline. Using multivariable generalized estimating equation analyses, we identified factors associated with recent use of federally sanctioned SCS and OPS, respectively. Among 298 AYA who inject drugs, 172 (57.8%) and 149 (50.0%) reported using federally sanctioned SCS and OPS during the study period, respectively. In multivariable analyses, public injecting, negative police interactions, and residing or spending time ≥ weekly in the Downtown Eastside neighborhood were all positively associated with the use of federally sanctioned SCS and OPS, respectively. Additionally, ≥ daily unregulated opioid use and residential eviction were positively associated with federally sanctioned SCS use, while requiring help injecting was inversely associated. Self-identified female or non-binary gender was also positively associated with OPS use (all p < 0.05). Both federally sanctioned SCS and OPS successfully engaged AYA at heightened risk of adverse health outcomes. However, the lack of accommodation of AYA who require manual assistance with injecting at federally sanctioned SCS may be inhibiting service engagement.

Involuntary discharge from drug or alcohol treatment programs in Vancouver, Canada.

BACKGROUND: Retention in substance use treatment is essential to treatment success. While programmatic factors are known to influence retention, less is known about the role of involuntary discharges from drug or alcohol treatment programs. Therefore, we sought to identify the prevalence of and factors associated with involuntary discharge due to ongoing substance use. METHODS: Data were derived from two community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada. Generalized estimating equation (GEE) analyses were used to identify variables associated with involuntary discharge from treatment programs due to ongoing substance use. RESULTS: Between June 2017 and March 2020, 1487 participants who accessed substance use treatment and completed at least one study interview were included in this study. Involuntary discharge from a treatment program due to ongoing substance use was reported by 41 (2.8%) participants throughout the study, with 23 instances reported at baseline and another 18 reported during study follow-up. In a multivariable GEE analysis, involuntary discharge was positively associated with homelessness (Adjusted Odds Ratio [AOR] = 3.22, 95% Confidence Interval [95% CI]: 1.59-6.52), daily injection drug use (AOR = 1.87, 95% CI 1.06-3.32) and recent overdose (AOR = 2.50, 95% CI 1.38-4.53), and negatively associated with age (AOR = 0.93, 95% CI 0.90-0.96). In sub-analyses, participants have most commonly been discharged from in-patient treatment centres (52.2%), recovery houses (28.3%) and detox programs (10.9%), and for using heroin (45.5%) and/or crystal methamphetamine (36.4%). CONCLUSIONS: While involuntary discharge was a relatively rare occurrence, those who were discharged due to active substance use possessed several markers of risk, including high-intensity injection drug use, homelessness, and recent non-fatal overdose. Our findings highlight the need for increased flexibility within treatment programs to account for those who re-initiate or continue to use substances during treatment.

Denial of prescription pain medication among people who use drugs in Vancouver, Canada.

BACKGROUND: People who use drugs experience pain at two to three times the rate of the general population and yet continue to face substantial barriers to accessing appropriate and adequate treatment for pain. In light of the overdose crisis and revised opioid prescribing guidelines, we sought to identify factors associated with being denied pain medication and longitudinally investigate denial rates among people who use drugs. METHODS: We used multivariable generalized estimating equations analyses to investigate factors associated with being denied pain medication among people who use drugs reporting pain in three prospective cohort studies in Vancouver, Canada. Analyses were restricted to study periods in which participants requested a prescription for pain from a healthcare provider. Descriptive statistics detail denial rates and actions taken by participants after being denied. RESULTS: Among 1168 participants who requested a prescription for pain between December 2012 and March 2020, the median age was 47 years and 63.0% were male. Among 4,179 six-month observation periods, 907 (21.7%) included a report of being denied requested pain medication. In multivariable analyses, age was negatively associated with prescription denial (adjusted odds ratio [AOR] = 0.98, 95% confidence interval [CI]:0.97-0.99), while self-managing pain (AOR = 2.48, 95%CI:2.04-3.00), experiencing a non-fatal overdose (AOR = 1.51, 95%CI:1.22-1.88), engagement in opioid agonist therapy (AOR = 1.32, 95%CI:1.09-1.61), and daily use of heroin or other unregulated opioids (AOR = 1.32, 95%CI:1.05-1.66) were positively associated with being denied. Common actions taken (n = 895) after denial were accessing the unregulated drug supply (53.5%), doing nothing (30.6%), and going to a different doctor/emergency room (6.1%). The period following the introduction of new prescribing guidelines was not associated with a change in denial rates. CONCLUSIONS: A substantial proportion of people who use drugs continue to be denied prescriptions for pain, with such denial associated with important substance use-related harms, including non-fatal overdose. Guidelines specific to the pharmaceutical management of pain among people who use drugs are needed.

Biliary atresia and liver transplantation in the United States: A contemporary analysis.

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.

Safer opioid supply via a biometric dispensing machine: a qualitative study of barriers, facilitators and associated outcomes.

BACKGROUND: The MySafe program provides pharmaceutical-grade opioids to participants with opioid use disorder via a biometric dispensing machine. The objectives of this study were to examine facilitators and barriers to safer supply via the MySafe program and the associated outcomes. METHODS: We conducted semistructured interviews with participants who had been enrolled in the MySafe program for at least a month at 1 of 3 sites in Vancouver. We developed the interview guide in consultation with a community advisory board. Interviews focused on context of substance use and overdose risk, enrolment motivations, program access and functionality, and outcomes. We integrated case study and grounded theory methodologies, and used both conventional and directed content analyses to guide inductive and deductive coding processes. RESULTS: We interviewed 46 participants. Characteristics that facilitated use of the program included accessibility and choice, a lack of consequences for missing doses, nonwitnessed dosing, judgment-free services and an ability to accumulate doses. Barriers included technological issues with the dispensing machine, dosing challenges and prescriptions being tied to individual machines. Participant-reported outcomes included reduced use of illicit drugs, decreased overdose risk, positive financial impacts and improvements in health and well-being. INTERPRETATION: Participants perceived that the MySafe program reduced drug-related harms and promoted positive outcomes. This service delivery model may be able to circumvent barriers that exist at other safer opioid supply programs and may enable access to safer supply in settings where programs may otherwise be limited.

The perspectives of street-involved youth who use drugs regarding the acceptability and feasibility of HIV pre-exposure prophylaxis: a qualitative study.

Street-involved youth who use drugs (YWUD) face an elevated risk of HIV acquisition and represent a key population for HIV prevention initiatives, including pre-exposure prophylaxis (PrEP). However, little is known regarding the acceptability and feasibility of PrEP uptake and adherence among this multiply-marginalized population. Semi-structured qualitative interviews were conducted with 24 street-involved YWUD (ages 17-24) to examine their perspectives toward PrEP; youth were recruited through a longitudinal prospective cohort study in Vancouver, Canada. Youth reported high levels of ambivalence toward PrEP despite engagement in HIV-related risk behaviors. This ambivalence was driven by misperceptions regarding HIV transmission, including stigmatizing associations between HIV transmission and personal hygiene. Such misperceptions led participants to enact strategies that were ineffective in preventing HIV transmission. Participants contested their inclusion as a "key population" for PrEP, which limited their enthusiasm for PrEP uptake and adherence. Participants also highlighted that wider social-structural inequities (e.g., housing vulnerability, poverty) that produced HIV-related risks were likely to undermine sustained PrEP use. Findings demonstrate the need for tailored implementation strategies to increase PrEP acceptability, including targeted education and anti-stigma interventions to increase awareness about HIV transmission. Interventions should also target structural inequities in order to fully address HIV risk and PrEP ambivalence.

Experiences of violence during the COVID-19 pandemic among people who use drugs in a Canadian setting: a gender-based cross-sectional study.

OBJECTIVES: People who use drugs (PWUD) experience disproportionately high rates of violent victimization. Emerging research has demonstrated that the COVID-19 pandemic has exacerbated violence against some priority populations (e.g., women), however there is limited research examining the impact of the pandemic on the experiences of violence of PWUD. METHODS: Using data collected between July and November 2020 from three prospective cohort studies of PWUD in Vancouver, Canada, we employed multivariable logistic regression stratified by gender to identify factors associated with recent experiences of violence, including the receipt of COVID-19 emergency income support. RESULTS: In total, 77 (17.3%) of 446 men, and 54 (18.8%) of 288 women experienced violence in the previous six months. Further, 33% of men and 48% of women who experienced violence reported that their experience of violence was intensified since the COVID-19 pandemic began. In the multivariable analyses, sex work (Adjusted Odds Ratio [AOR] = 2.15, 95% confidence interval [CI]: 1.06-4.35) and moderate to severe anxiety or depression (AOR = 3.00, 95% CI: 1.37-6.57) were associated with experiencing violence among women. Among men, drug dealing (AOR = 1.93, 95%CI: 1.10-3.38), street-based income sources (AOR = 1.93, 95%CI: 1.10-3.38), homelessness (AOR = 2.54, 95%CI: 1.40-4.62), and regular employment (AOR = 2.97, 95% CI: 1.75-5.04) were associated with experiencing violence. CONCLUSION: Our study results suggest economic conditions and gender were major factors associated with experiencing violence among our sample of PWUD during COVID-19. These findings highlight criminalization of drug use and widespread socioeconomic challenges as barriers to addressing violence among PWUD during periods of crisis.

Police seizure of drugs without arrest among people who use drugs in Vancouver, Canada, before provincial 'decriminalization' of simple possession: a cohort study.

BACKGROUND: Several jurisdictions in Canada have recently considered decriminalizing possession of illicit drugs for personal use (henceforth, simple possession) as part of their responses to the ongoing drug toxicity/overdose crisis. In this context, we sought to examine an early implementation case of a de facto depenalization policy of simple possession offences in Vancouver, Canada, that was enacted in 2006. Specifically, we characterized experiences of people who use drugs (PWUD) whose drugs were discretionally seized by police without arrest. METHODS: Data were derived from three prospective cohorts of community-recruited PWUD in Vancouver over 16 months in 2019-2021. We conducted multivariable generalized estimating equations analyses to determine the prevalence of and factors associated with drug seizure. Sub-analyses used data collected in 2009-2012 and examined the trends over time. RESULTS: Among 995 participants who were interviewed in 2019-2021, 63 (6.3%) had their drugs seized by police at least once in the past 6 months. In multivariable analyses, factors significantly associated with drug seizure included: homelessness (adjusted odds ratio [AOR]: 1.98; 95% confidence interval [CI] 1.09-3.61), working in the unregulated drug market (AOR: 4.93; 95% CI 2.87-8.49), and naloxone administration (AOR: 2.15; 95% CI 1.23-3.76). In 2009-2012, 67.8% reported having obtained new drugs immediately after having their drugs seized by police. Odds of drug seizure were not significantly different between the two time periods (2019-2021 vs. 2009-2012) (AOR: 0.93; 95% CI: 0.64-1.35). CONCLUSIONS: Despite the depenalization policy, the Vancouver Police Department has continued to seize illicit drugs from PWUD, even in cases where no arrest occurred. This policing practice may create health and safety risks for PWUD as it forces PWUD to increase the engagement with the unregulated illicit drug market. Our findings support calls for abolishing this often-undocumented discretionary policing practice that may exacerbate ongoing health inequities and interfere with peer-based overdose prevention efforts.

Mothers Who Use Drugs: Closing the Gaps in Harm Reduction Response Amidst the Dual Epidemics of Overdose and Violence in a Canadian Urban Setting.

Objectives. To identify key gaps in overdose prevention interventions for mothers who use drugs and the paradoxical impact of institutional practices that can increase overdose risk in the context of punitive drug policies and a toxic drug supply. Methods. Semistructured interviews were conducted with 40 women accessing 2 women-only, low-barrier supervised consumption sites in Greater Vancouver, British Columbia, Canada, between 2017 and 2019. Our analysis drew on intersectional understandings of structural, everyday, and symbolic violence. Results. Participants' substance use and overdose risk (e.g., injecting alone) was shaped by fear of institutional and partner scrutiny and loss (or feared loss) of child custody or reunification. Findings indicate that punitive policies and institutional practices that frame women who use drugs as unfit parents continue to negatively shape the lives of women, most significantly among Indigenous participants. Conclusions. Nonpunitive policies, including access to safe, nontoxic drug supplies, are critical first steps to decreasing women's overdose risk alongside gender-specific and culturally informed harm-reduction responses, including community-based, peer-led initiatives to maintain parent-child relationships. (Am J Public Health. 2022;112(S2):S191-S198. https://doi.org/10.2105/AJPH.2022.306776).

High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). METHODS: We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. RESULTS: Among 1019 HCC patients, baseline NLR was < 5 in 815 (80.0%) and ≥ 5 in 204 (20.0%). Patients with NLR ≥ 5 had a higher proportion of infiltrative tumors (36.2% vs 22.3%), macrovascular invasion (39.6% vs 25.5%), metastatic disease (20.6% vs 11.4%), and AFP > 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41-2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14-1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32-0.95). CONCLUSIONS: In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. IMPACT: NLR is an inexpensive test that may be a useful component of future HCC prognostic models.

The "goldfish bowl": a qualitative study of the effects of heightened surveillance on people who use drugs in a rural and coastal Canadian setting.

BACKGROUND: A growing body of research has focused on contextual factors that shape health and well-being of people who use drugs (PWUD). However, most of this research focuses on large cities and less is known about the effects of social and structural contexts on drug use and associated risks in rural Canadian settings. Therefore, we undertook this study to examine rural-specific contextual factors that affect the day-to-day experiences of PWUD. METHODS: Twenty-seven qualitative semi-structured interviews were conducted with PWUD in a rural and coastal setting in British Columbia, Canada. Participants had to be ≥ 19 years old, used illegal opioids and/or stimulants regularly, and lived in the qathet region. Interview transcripts were coded based on themes identified by the research team. RESULTS: Participants described progressive shifts in politics and culture in the qathet region while also identifying resource scarcity, homelessness, and changes in the drug supply, where illicit drug contents have become highly toxic and unpredictable. Participants discussed the qualities of a small community where everyone knows each other and there is a lack of privacy and confidentiality around drug use, which resulted in experiences of stigma, discrimination, and surveillance. Participants also reported rural-specific policing issues and experiences of surveillance on ferries when traveling to larger cities to purchase drugs. This led to significantly higher drug prices for PWUD due to the time dedication and criminalized risks associated with drug possession and trafficking. CONCLUSIONS: Our findings illustrate the unique experiences faced by PWUD in a rural and coastal setting. The "goldfish bowl" effect in this rural community created heightened social and structural surveillance of PWUD, which led to a variety of negative consequences. There is a clear need for interventions to address the larger contextual drivers affecting people who use drugs in rural settings, including decriminalization and peer-led anti-stigma strategies, in order to improve the lives of PWUD.

Injecting drugs alone during an overdose crisis in Vancouver, Canada.

BACKGROUND: Settings throughout Canada and the USA continue to experience crises of overdose death due to the toxic unregulated drug supply. Injecting drugs alone limits the potential for intervention and has accounted for a significant proportion of overdose deaths, yet the practice remains understudied. We sought to examine the practice of injecting alone among people who inject drugs (PWID) in Vancouver, Canada. METHODS: Data were derived from two prospective cohorts of people who use drugs between June 2016 and November 2018. This analysis was restricted to participants who, in the previous 6 months, reported any injection drug use. Rates of injecting alone were categorized as always, usually, sometimes, or occasionally. We fit a multivariable generalized linear mixed model to identify factors associated with injecting drugs alone. RESULTS: Among 1070 PWID who contributed 3307 observations, 931 (87%) reported injecting alone at least once during the study period. In total, there were 729 (22%) reports of always injecting alone, 722 (21.8%) usually, 471 (14.2%) sometimes, 513 (15.5%) occasionally, and 872 (26.4%) never. In a multivariable model, factors positively associated with injecting drugs alone included male sex (adjusted odds ratio [AOR] 1.69; 95% confidence interval [CI] 1.20-2.37), residence in the Downtown Eastside neighbourhood (AOR 1.43; 95% CI 1.08-1.91), binge drug use (AOR 1.36; 95% CI 1.08-1.72), and experiencing physical or sexual violence or both (AOR 1.43; 95% CI 1.00-2.03). Protective factors included Indigenous ancestry (AOR 0.71; 95% CI 0.52-0.98) and being in a relationship (AOR 0.30; 95% CI 0.23-0.39). CONCLUSION: We observed that injecting alone, a key risk for overdose mortality, was common among PWID in Vancouver. Our findings underline the need for additional overdose prevention measures that are gender-specific, culturally appropriate, violence- and trauma-informed, and available to those who inject alone.

Low awareness of risk mitigation prescribing in response to dual crises of COVID-19 and overdose deaths among people who use unregulated drugs in Vancouver, Canada.

BACKGROUND: When the novel coronavirus pandemic emerged in March 2020, many settings across Canada and the USA were already contending with an existing crisis of drug overdoses due to the toxic unregulated drug supply. In response, the Canadian province of British Columbia (BC) released innovative risk mitigation prescribing (RMP) guidelines for medical professionals to prescribe pharmaceutical alternatives to unregulated drugs in an effort to support the self-isolation of people who use unregulated drugs (PWUD) in preventing both SARS-CoV-2 virus infection and overdoses. We sought to assess the level of awareness of RMP and identify factors associated with this awareness among PWUD in Vancouver, BC. METHODS: Cross-sectional data were derived from participants enrolled in three community-recruited prospective cohort studies of PWUD in Vancouver, interviewed between July and November 2020. Multivariable logistic regression analysis was used to identify factors associated with awareness of RMP. RESULTS: Among 633 participants, 302 (47.7%) had heard of RMP. Of those 302 participants, 199 (65.9%) had never tried to access RMP services, ten (3.3%) made an unsuccessful attempt to access RMP, and 93 (30.8%) received RMP. In the multivariable analysis, participants who had awareness of RMP guidelines were more likely to self-identify as white (adjusted odds ratio [AOR] = 1.47; 95% confidence interval [CI]: 1.01, 2.13), to have completed secondary school education or higher (AOR = 1.67; 95% CI: 1.16, 2.39), to have used drugs at a supervised consumption or overdose prevention site in the past six months (AOR = 1.66; 95% CI: 1.10, 2.52), and to have received opioid agonist therapy as treatment for opioid use disorder in the past six months (AOR = 1.51; 95% CI: 1.02, 2.24). CONCLUSION: At least four months after the release of the guidelines, RMP was known to less than half of our study participants, warranting urgent educational efforts for PWUD, particularly among racialized groups and those who were not accessing other harm reduction services. Furthermore, the majority of participants who were aware of RMP guidelines had never tried to access the service, suggesting the need to improve perceived accessibility and knowledge of eligibility criteria.

Social-Structural Predictors of Fentanyl Exposure among Street Involved Youth.

ObjectiveThe emergence of synthetic fentanyl has been a main contributor to North America's rising overdose death rates. While increasing attention has been given to drug-related harm among youth, little is known about how social-structural conditions influence their risk of fentanyl exposure. Therefore, we evaluated potential relationships between social-structural conditions and fentanyl exposure among youth who use illicit drugs in Vancouver, BC. Methods: Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort study. The ARYS cohort involves street-involved youth, who use illicit substances in Vancouver, Canada. A multivariable logic regression analysis model was used to identify social factors associated with recent fentanyl exposure as determined through urine drug screening. Results: Overall, 423 participants were included in this analysis, with 380 (38.23%) testing positive for recent fentanyl exposure. In a multivariable relative risk analysis, living in Vancouver's Downtown Eastside in the last six months (RR = 1.16, 95% CI: 1.03-1.32) and daily heroin injection drug use (RR = 1.31, 95% CI: 1.15 - 1.50) were positively associated with fentanyl exposure. As a secondary measure, we found that within the encounters who denied using fentanyl (92.25% of total encounters), 321 (35.05%) still tested positive. Conclusions: We found that youth residing in Vancouver's Downtown Eastside was positively associated with being exposed to fentanyl. Our findings highlight the need to support youth in finding secure housing outside of Vancouver's drug use epicenter to reduce fentanyl exposure.

Increasing preference for fentanyl among a cohort of people who use opioids in Vancouver, Canada, 2017-2018.

Background: Despite increasing prevalence of illicit fentanyl use in the US and Canada, preference for fentanyl over other illicit opioids has not been fully characterized. Therefore, we sought to describe changes in illicit opioid preferences over time among people who inject drugs (PWID). Methods: Data were obtained from two prospective cohort studies between 2017 and 2018. Trends in opioid preference over time were examined using bivariable generalized estimating equation (GEE) analysis. Multivariable models were used to identify factors associated with fentanyl preference. Results: Among 732 eligible participants, including 425 (58%) males, the prevalence of preference for fentanyl increased from 4.4% in 2017 to 6.6% in 2018 (Odds Ratio [OR] = 1.27, 95% Confidence Interval [CI]: 1.05-1.52). In a multivariable analysis, younger age (Adjusted Odds Ratio [AOR] = 0.94, 95% CI: 0.92-0.96) and daily crystal methamphetamine injection (AOR = 1.68, 95% CI: 1.01-2.78) were independently associated with preference for fentanyl. The most common reasons for preferring fentanyl included "better high than other opioids" (45%), and "lasts longer than heroin" (27%). Conclusions: The current study has demonstrated that preference for fentanyl has been increasing over time among our sample of PWID who use opioids. Further work is needed to clarify risk factors surrounding transitions to illicit fentanyl.

"It's Helped Me a Lot, Just Like to Stay Alive": a Qualitative Analysis of Outcomes of a Novel Hydromorphone Tablet Distribution Program in Vancouver, Canada.

North America is experiencing an overdose crisis driven by fentanyl, related analogues, and fentanyl-adulterated drugs. In response, there have been increased calls for "safe supply" interventions based on the premise that providing a safer alternative (i.e., pharmaceutical drugs of known quality/quantity, non-adulterated, with user agency in consumption methods) to the street drug supply will limit people's use of fentanyl-adulterated drugs and reduce overdose events. This study examined outcomes of a hydromorphone tablet distribution program intended to prevent overdose events among people who use drugs (PWUD) at high risk of fatal overdose. Semi-structured qualitative interviews were conducted with 42 people enrolled in the hydromorphone distribution program. Additionally, over 100 h of ethnographic observation were undertaken in and around the study site. Transcripts were coded using NVivo and based on categories extracted from the interview guides and those identified during initial interviews and ethnographic fieldwork. Analysis focused on narratives around experiences with the program, focusing on program-related outcomes. Our analysis identified the following positive outcomes of being enrolled in the hydromorphone tablet distribution program: (1) reduced street drug use and overdose risk, (2) improvements to health and well-being, (3) improvements in co-management of pain, and (4) economic improvements. Our findings indicate that the hydromorphone distribution program not only is effective in responding to the current overdose crisis by reducing people's use of illicit drugs but also addresses inequities stemming from the intersection of drug use and social inequality. Safe supply programs should be further implemented and evaluated in both urban and rural setting across North America as a strategy to reduce exposure to the toxic drug supply and fatal overdose.

The effect of depressive symptoms on pain in a substance-using population with persistent pain: a cross-sectional cohort study.

BACKGROUND: In light of the ongoing opioid overdose crisis, there is an urgent need for research on the impacts of mental health among people presenting with concurrent pain and substance use. This study examined the effect of depressive symptoms on pain severity and functional interference among people who use drugs (PWUD) during a community-wide overdose crisis. METHODS: From December 1st 2016 to December 31st 2018, 288 participants in two cohort studies of PWUD in Vancouver, Canada completed interviewer-administered questionnaires that included the Brief Pain Inventory and PROMIS Emotional Distress-Depression instruments. Generalized linear regression modelling (GLM) was used to examine the cross-sectional effect of depressive symptoms and other confounding factors on pain severity and interference. RESULTS: Moderate to severe depressive symptoms were significantly associated with greater pain-related functional interference (adjusted ß = 1.24, 95% confidence interval [CI] = 0.33-2.15), but not significantly associated with greater average pain severity (adjusted ß = 0.22, 95% CI = - 0.3 - 0.82), when controlling for confounding variables. Reported daily heroin use (adjusted ß = 1.26, 95% CI = 0.47-2.05) and non-fatal overdose (adjusted ß = 1.02, 95% CI = 0.08-1.96) were also significantly associated with greater pain-related functional interference. CONCLUSIONS: In a substance-using population, greater pain-related functional interference was positively associated with depressive symptoms as well as overdose and daily heroin use. These findings emphasize the need to address the functional impact of pain, mental health comorbidity, and high-risk substance use that may contribute to overdose and other harms.

Pain and Barriers to Accessing Health Services Among People Who Use Drugs.

BACKGROUND: The opioid overdose crisis underscores the need for health services among people who use drugs (PWUD) with concurrent pain. AIMS: Investigating the effect of pain on barriers to accessing health services among PWUD. DESIGN: Prospective cohort study. SETTINGS: A setting of universal access to no-cost medical care in Vancouver, Canada from June 2014 to May 2016. PARTICIPANTS/SUBJECTS: PWUD who completed at least one study interview. METHODS: Data derived from interviewer-administered questionnaires were used for multivariable generalized linear mixed-effects multiple regression (GLMM) analyses. RESULTS: Among 1,348 PWUD, 469 (34.8%) reported barriers to accessing health services at least once during the study period. The median average pain severity was 3 (IQR: 0-6) out of 10. A dose-response relationship was observed between greater pain and increased odds of reporting barriers to accessing health services (adjusted odds ratio [AOR]: 1.59, 95% confidence interval [CI]: 1.15-2.21, p = .005 for mild versus no pain; AOR: 1.76, 95% CI: 1.30-2.37, p < .001 for moderate versus no pain; AOR: 2.55, 95% CI: 1.92-3.37, p < .001 for severe versus no pain). Common barriers included poor treatment by health professionals, socio-structural barriers such as transportation or mobility, and long wait lists or wait times. CONCLUSIONS: Pain may be a significant risk factor associated with increased barriers to accessing health services among PWUD. Attention to pain management may improve access to health services, and reducing barriers to health services may conversely improve pain management and its related risks and harms.