Common mental disorders (CMDs) are prevalent among people living with HIV (PWH) and cause morbidity, jeopardize HIV care engagement, and worsen HIV outcomes. In Vietnam, PWH who inject drugs are at high risk for poor HIV and CMD outcomes. However, few evidence-based interventions are available to address this population. We conducted a three-arm individually randomized pilot trial assigning 75 PWH with opiate use disorder and a CMD from methadone maintenance treatment clinics to either FB by a professional counselor, FB by a peer counselor, or enhanced usual care. Primary outcomes were feasibility, acceptability, and fidelity of FB; we also assessed preliminary indicators of CMD improvement and HIV care engagement. Feasibility was high, with 99% retention at 6 weeks and 96% retention at 6 months. 100% of patients receiving FB attended all 6 weekly sessions. Acceptability of FB was high for participants in both the professional and peer counselor groups. Providers were highly satisfied with the FB experience. Fidelity was adequate: 72% of professional counselors met or exceeded fidelity expectations, while 44% of peer counselors did. Preliminary indicators of effectiveness for CMDs were promising. Participants in the professional counselor arm had the greatest improvement as measured by CMD symptom improvement and CMD response rates at most follow-up visits. The adapted FB intervention should be scaled up and evaluated in a larger, fully powered randomized controlled trial to evaluate its efficacy in improving CMDs and HIV engagement for PWH and CMDs at greatest risk of poor HIV and CMD outcomes.Clinical Trial Number: NCT04790201 registered 3/10/2021.

Governments are increasingly identifying priority populations on which to focus health policy and to measure health and wellbeing outcomes. Prioritising populations that are considered to be higher risk or to have particular needs that may not be captured within the parameters of health policy developed for the general population, is essential to health equity and efficient resource allocation. However, the criteria that governments use for prioritising populations is often vague or unspecified. To date, people who use drugs are almost never identified as a priority population in health policy, despite poor health and wellbeing outcomes.

We developed three-pronged criteria-disadvantage, prevalence/accessibility and amenability to change-for prioritising populations in government health policy. We used these criteria to compare people who access alcohol, tobacco and other drug (ATOD) services with populations which are prioritised within the Australian Capital Territory Government's Wellbeing Framework.

Use of the criteria indicates that health policy prioritisation of people who access ATOD services is warranted. People who access ATOD services experienced worse health and wellbeing outcomes across all measures.

Given increasingly explicit prioritisation of populations in health policy, there is an opportunity to advance health equity and embed policy efficiency through formal and transparent consideration of which populations to prioritise. Using set criteria for prioritising populations in health policy is possible, and could help identify populations often overlooked for prioritisation, such as people who access ATOD services.

Supervised injecting facilities (SIFs) are designed to reduce the harms associated with injecting drug use and improve access to health and support services for people who need them. The Supervised Injecting Room Cohort Study (SIRX) aims to provide evidence of the effects, including cost-effectiveness, of a SIF embedded within a community health service, the Melbourne Medically Supervised Injecting Room (MSIR), which has a range of integrated harm reduction, health and social support services on-site.

The SIRX study design involves two prospective cohort studies that collect behavioural data and retrospectively and prospectively linked administrative data for primary and tertiary health services, criminal justice records, and mortality. The two cohorts are: (1) participants drawn from the existing Melbourne Injecting Drug User Cohort Study (SuperMIX; established in 2008-ongoing) through which participants consent to annual behavioural surveys (including serological testing for HIV and hepatitis B and C viruses) and linkage to administrative data; and (2) the SIRX-Registration Cohort (SIRX-R; established in 2024) comprising registered MSIR clients who consent to a baseline behavioural survey and administrative data linkage including the frequency of SIF use, and the uptake of on-site services. Primary outcomes are aligned to the legislated aims of the Melbourne MSIR, including ambulance-attended non-fatal overdoses and all-cause and drug-related mortality. Using causal inference methods, analyses will estimate the effect of MSIR exposure (frequent use/infrequent use/no use) on these primary outcomes. The SIRX study also has a secondary focus on the effect of MSIR exposure on health service use and related outcomes.

SuperMIX Study (599/21) and SIRX-R Study (71/23) ethics approvals were obtained from Alfred Hospital Research Ethics Committee. Participants will be assessed for capacity to provide informed consent following a detailed explanation of the study. Participants are informed of their right to withdraw from the study at any time and that withdrawing does not impact their access to services. Aggregated research results will be disseminated via presentations at national and international scientific conferences and publications in peer-reviewed journals. Local-level reports and outputs will be distributed to key study stakeholders and policymakers. Summary findings via accessible outputs (eg, short infographic summaries) for participants will be displayed in relevant services including the Melbourne MSIR and the study van, and distributed via Harm Reduction Victoria.

Our aim was to examine mortality trends in the era of antiretroviral therapy, among people who inject drugs (PWID) who are living with HIV. The study objectives were to assess and quantify mortality among PWID diagnosed with HIV over time in Scotland, in the context of a recent outbreak of HIV and rise in drug-related mortality.

This was a retrospective cohort study of those diagnosed with HIV in Scotland between January 2000 and February 2020, with acquisition related to injecting drug use, linked to mortality data. Factors associated with all-cause mortality were examined using Cox proportional hazards regression.

Among 430 individuals with 3143 person-years (py) of follow-up, 88 (20.5%) died. Drug-related deaths accounted for 45.5% of all deaths, rising to 60% among those diagnosed in 2015-2020. The crude all-cause mortality was 28.00 per 1000 py overall and 37.62 per 1000 py within 5 years of diagnosis. Mortality risk was markedly higher among PWID diagnosed in 2015-2020 [adjusted hazard ratio (aHR) = 3.53], relative to those diagnosed in 2000-2004. Among those diagnosed in 2015-2020 (as part of the HIV outbreak), the mortality risk was higher among those not on, compared with those on, opioid agonist therapy (aHR = 3.87).

Mortality among PWID living with HIV in Scotland has risen substantially in the 21st century. Our findings highlight the important role of opioid-agonist therapy, alongside other prevention and treatment measures to address high levels of drug-related mortality for PWID living with HIV, including within HIV outbreaks in this population group.

The World Health Organization (WHO) has established objectives for eradicating the hepatitis C virus (HCV). People who inject drugs (PWID), a major driver of HCV transmission, are an essential part of China's hepatitis C elimination program. This study aimed to estimate the requisite screening and antiviral treatment levels to achieve these goals among people who inject drugs in China and identify the most cost-effective strategy.

This study utilized models based on dynamic social networks to simulate HCV transmission and disease progression among people who inject drugs in China, incorporating a cost-effectiveness analysis from a healthcare perspective.

To achieve the WHO targets, a minimum screening and treatment rate of 10% is required to meet the mortality goal, while a 25% rate is necessary for the incidence goal. The most cost-effective strategy includes a 25% screening rate and a 95% treatment rate. Compared to no intervention, this approach significantly reduces costs by - $85,873.38 (95% CI  - $94,311.16 to  - $77,435.59) and adds 24.66 (95% CI 23.68 to - 25.64) quality-adjusted life years. The intervention is dominant, with a cost-effectiveness ratio of - $3482.29 (95% CI  - $3982.73 to  - $3020.11) per quality-adjusted life year.

Achieving the WHO's hepatitis C virus elimination targets among people who inject drugs in China is feasible and cost-saving.

Understanding violent criminality and its impact on health and eventually the risk of premature mortality is important for efficient future interventions. This study aimed to explore the effect violent criminality had on premature mortality (i.e., death before the age of 65) among individuals with substance use disorders (SUDs).

The cohort was created by identifying all Swedish patients diagnosed with SUD between the first of January 2013 and 31st of December 2014. The individuals were split into three age categories.

There were significant differences in standard mortality rates (SMR) in the cohort compared to the general Swedish population across the three age categories. We found differences between the SMRs for individuals convicted of violent and nonviolent crimes in the two younger age categories [age 15-29: violent crime (42.4) vs. non-violent crime (36.6), age 30-44: violent crime (28.0) vs. non-violent crime (23.0)]. A Cox regression analysis showed that each conviction of a violent crime increased the hazard ratio (HR) of premature mortality significantly [age 15-29; HR = 1.10 (95% CI: 1.04-1.17), age 30-44; HR =1.06 (95% CI: 1.03-1.09)]. After correcting for non-violent crimes, the increased risk only remained for the youngest group [HR = 1.06 (95% CI: 1.00-1.13)].

This study suggests that criminal behavior constitutes a proxy for the risk behaviors that increase the risk of premature mortality among young individuals with SUD even after controlling for confounders. Longitudinal studies, examining time-dependent risks and protective influences, are needed to explain the different pathways and processes leading to the amplified premature mortality in the groups.

To measure all-cause mortality risk after an ambulance-attended non-fatal opioid overdose and associations with number of days following attendance, and individual and clinical characteristics.

A prospective observational study.

Oslo, Norway.

Patients treated with naloxone for opioid overdose by Oslo Emergency Services between 1 June 2014 and 31 December 2018.

Medical records were linked to the national Cause of Death Registry (1 June 2014-31 December 2019). Crude mortality rates (CMR) and incidence risk ratios (IRR) with 95% confidence intervals (CI) were estimated for the time periods (0-7 days, 8-31 days, 32-91 days, 92-183 days, >183 days) using multivariate Poisson regression analysis. IRR were estimated for sex, age, Glasgow Coma Scale (GCS), respiration rate, place of attendance and non-transportation following treatment. Robust variance estimates applied due to multiple risk periods. Standardized Mortality Rates (SMR) were estimated.

Overall, 890 patients treated for 1764 overdoses contributed to a total time at risk of 3142 person-years (PY). Median number of attendances was 1 (range 1-27). The majority were male (75.5%) and the mean age was 37.7 years. In total, 112 (12.6%) died; 5.2% within 183 days and 2.2% between 184 and 365 days. Acute poisoning was the most common single cause of death (52.7%). The CMR was 3.6 (95% CI = 3.0-4.2) per 100-PY. The women had a SMR of 32 (95% CI = 15.8-57.9) and the men 24.9 (95% CI = 17.7-34.2). The CMR (22.2, 95% CI = 10.6-46.8) was particularly high in the first 7 days, and significantly higher than in the following periods. However, this finding was only valid for those with severe overdose symptoms (GCS score = 3/15 and/or respiratory rate ≤6/min). Except for increasing age, no other indicators were associated with the mortality risk.

Patients treated by Oslo Emergency Services between June 2014 and December 2018 for a non-fatal opioid overdose with severe overdose symptoms at attendance had an overall high mortality risk compared with the general population, but particularly during the first 7 days after attendance.

Inadequate sleep is associated with all-cause mortality in the general population. Substance use has adverse effects on sleep, and insomnia symptoms are common among people with HIV. Therefore, persons who inject drugs may face a heightened risk of adverse outcomes from inadequate sleep. We evaluated the association of inadequate sleep with mortality among persons who inject drugs in a long-standing community cohort.

Participants were from the AIDS Linked to the IntraVenous Experience (ALIVE) study, a cohort of persons who inject drugs in Baltimore, Maryland, USA. From 2005-2020, perceived sleep adequacy and duration were assessed semiannually using survey. Mortality data were obtained through linkage to the National Death Index-Plus. Cause of death was independently characterized and validated by three physicians. Hazards of all-cause and cause-specific mortality were evaluated using Cox regression accounting for repeated measurements.

A total of 2633 participants were included, with a median age at entry of 45.8years; 32.5% were female, and 75% were Black. After adjustment for demographics, mental health, and comorbidities, inadequate sleep was associated with a 32% greater hazard of all-cause mortality (hazard ratio: 1.32, 95% confidence interval: 1.12-1.55) and a 67% greater hazard of HIV/infectious disease-related deaths (hazard ratio: 1.67, 95% confidence interval: 1.15-2.42). Short (<6 hours) and long (≥8 hours) duration of sleep were both associated with higher hazard of all-cause and chronic disease-related mortality (all p < .05).

Sleep plays a critical role in longevity in persons who inject drugs. Research is needed to determine whether interventions targeting sleep improve health and longevity in persons who inject drugs.

This study introduces the DUS Topp-Leone family of distributions, a novel extension of the Topp-Leone distribution enhanced by the DUS transformer. We derive the cumulative distribution function (CDF) and probability density function (PDF), demonstrating the distribution's flexibility in modeling various lifetime phenomena. The DUS-TL exponential distribution was studied as a sub-model, with analytical and graphical evidence revealing that it exhibits a unique unimodal shape, along with fat-tail characteristics, making it suitable for time-to-event data analysis. We evaluate parameter estimation methods, revealing that non-Bayesian approaches, particularly Maximum Likelihood and Least Squares, outperform Bayesian techniques in terms of bias and root mean square error. Additionally, the distribution effectively models datasets with varying skewness and kurtosis values, as illustrated by its application to total factor productivity data across African countries and the mortality rate of people who injected drugs. Overall, the DUS Topp-Leone family represents a significant advancement in statistical modeling, offering robust tools for researchers in diverse fields.

In response to the opioid epidemic, federal agencies have stressed the importance of targeted naloxone distribution through avenues such as Opioid Overdose Education and Naloxone Distribution (OEND). OEND effectively reduces mortality by training laypersons to respond to overdose situations. Despite demonstrated effectiveness, OEND remains underutilized. This project aimed to characterize those who illicitly use opioids to determine avenues for future tailoring of OEND programs.

Individuals who illicitly used opioids within the past 6 months were recruited via online social media. Participants completed an online questionnaire that assessed history of opioid use and were given the option to receive opioid overdose and naloxone administration training. Those who elected training (n = 111) and those who declined (n = 193) were compared on opioid use, severity of use, and overdose experiences.

Participants (N = 304) were 47% male and 83% White. Tests of between group differences with measures of effect size were used for analyses. Those who elected training endorsed greater intravenous administration (χ2 = 4.18, P = 0.041, Cramer's V = 0.12). Individuals who declined training reported more frequent nonprescribed methadone use (χ2 = 7.51, P = 0.006, Cramer's V = 0.16), overdose hospitalizations (t(298) = 2.13, P = 0.034, Cohen's d = 0.26), and observed overdoses (t(300) = 3.01, P = 0.003, Cohen's d = 0.36). After adjusting for multiple comparisons, only the differences in nonprescribed methadone use and observed overdoses remained statistically significant.

Individuals who declined training were more likely to report ever use of nonprescribed methadone and having witnessed others overdose. They may have had greater exposure to naloxone, hence decreasing perceived need for training. Understanding characteristics of those who elect and refuse training could inform structuring of programs and recruitment approaches.

More knowledge is needed to identify and reach those at overdose risk with preventive measures. We examined past 12-month health service utilization, identified the most frequently utilized service, explored this utilization in more detail, and examined correlates of overdose death.

A population-based nested case-control registry study including all drug overdose deaths (1 January 2010 to 31 December 2018) in Norway through the Cause of Death Registry (n = 2388). The year-, age- and gender-matched controls included through a population registry (n = 21,465). Data cross-linked with population and patient registries. Multivariable conditional logistic regression analyses estimated the likelihood of overdose death.

The cases (vs. controls) attended a higher median number of services (3 vs. 1). The General Practitioner (GP) was the most utilized service. The majority (55.7%) of cases had 11-50 encounters, while the majority (60.7%) of the controls had 1-5 encounters. No high school diploma, no employment, urban living, social welfare benefits/disability pension, single-person household, recent incarceration, multiple health service utilization and frequent GP encounters, as well psychological and certain physical diagnoses were correlates of overdose death among the GP attenders.

The cases had utilized more services than the controls and the GP was the most frequently utilized service. In addition to low socioeconomic status, psychological and certain physical diagnoses were correlates of overdose death.

This is the first national case-control registry study to document the high utilization of multiple primary and secondary health care services before drug overdose death, as well as reasons for attendance and correlates of overdose death.

Harm reduction, when applied to drug use, prioritizes improving patient-centered health outcomes and reducing drug-related harm. In order for harm reduction strategies to be adopted by people who inject drugs (PWID), they need to be promoted, accessible, and accepted in that population and the community-at-large. While PWID face stigma at multiple levels, less is known about how stigma influences uptake and acceptance of harm reduction services and strategies among PWID.

We aim to characterize the stigmatizing experiences PWID have had related to harm reduction and the role of stigma in influencing their acceptance and adoption of harm reduction services and strategies.

A qualitative study using in-person, semi-structured interviews.

We recruited hospitalized participants, age 18 and over, with a history of injection drug use.

We developed an interview guide asking about various aspects of stigma and participants' experiences with naloxone, syringe service programs, fentanyl test strips, HIV and hepatitis C testing, and any other harm reduction strategies. Key themes were generated using a thematic analysis. We reached thematic saturation at 16 participants.

PWID reported multi-level stigma related to harm reduction from themselves, the public, the healthcare system, and the legal and carceral systems. Themes were grouped into four main categories: internalized, interpersonal, intervention, and structural stigma. Stigma across all of these domains negatively impacted the ability of PWID to access harm reduction resources. Positive, non-stigmatizing experiences from others, such as syringe service programs and peer navigators, countered historically negative experiences and promoted greater education and comfort about using harm reduction resources among PWID.

To expand the reach of harm reduction services, it is critical to develop interventions that can reduce the stigma against PWID and harm reduction.

Supervised consumption sites (SCS) have been shown to reduce receptive syringe sharing among people who inject drugs (PWID) in the United States and elsewhere, which can prevent HIV and hepatitis C virus (HCV) transmission. PWID are at risk of disease transmission and may benefit from SCS, however legislation has yet to support their implementation. This study aims to determine the potential impact of SCS implementation on HIV and HCV incidence among PWID in three California counties.

A dynamic HIV and HCV joint transmission model among PWID (sexual and injecting transmission of HIV, injecting transmission of HCV) was calibrated to epidemiological data for three counties: San Francisco, Los Angeles, and San Diego. The model incorporated HIV and HCV disease stages and HIV and HCV treatment. Based on United States data, we assumed access to SCS reduced receptive syringe sharing by a relative risk of 0.17 (95 % CI: 0.04-1.03). This model examined scaling-up SCS coverage from 0 % to 20 % of the PWID population within the respective counties and assessed its impact on HIV and HCV incidence rates after 10 years.

By increasing SCS from 0 % to 20 % coverage among PWID, 21.8 % (95 % CI: -1.2-32.9 %) of new HIV infections and 28.3 % (95 % CI: -2.0-34.5 %) of new HCV infections among PWID in San Francisco County, 17.7 % (95 % CI: -1.0-30.8 %) of new HIV infections and 29.8 % (95 % CI: -2.1-36.1 %) of new HCV infections in Los Angeles County, and 32.1 % (95 % CI: -2.8-41.5 %) of new HIV infections and 24.3 % (95 % CI: -1.6-29.0 %) of new HCV infections in San Diego County could be prevented over ten years.

Our models suggest that SCS is an important intervention to enable HCV elimination and could help end the HIV epidemic among PWID in California. It could also have additional benefits such facilitating pathways into drug treatment programs and preventing fatal overdose.

Vaccine hesitancy is increasingly recognized as a health challenge affecting populations worldwide. Given the biological vulnerabilities and structural barriers people who use substances and/or have behavioral addictions face, this systematic review aims to evaluate whether this subpopulation is less prone to adhere to vaccination recommendations.

Electronic searches of published original research were conducted in PubMed, EMBASE, Scopus, and PsycINFO from database inception to December 2022. Our strategy encompassed retrievals regardless of languages and date of publication. Animal studies, abstracts without a full manuscript, and studies which were considered to have lower robustness of scientific evidence were excluded. Outcomes measured were vaccine acceptance, uptake, and adherence. Results were interpreted through a narrative synthesis.

The search yielded 103 retrievals encompassing data collected on 5 576 374 persons who were predominantly residents of Europe (n = 39) and North America (n = 27). Tobacco use, the substance for which many studies were found (n = 91), was significantly associated with poorer vaccine acceptance, uptake and adherence for influenza, COVID-19, human papillomavirus (HPV), and maternal and childhood vaccines. Peri-natal and parental substance use was identified as a risk factor for suboptimal vaccine-related outcomes concerning maternal COVID-19 and childhood vaccines. Finally, people identified as 'using', 'abusing', or 'misusing' drugs or substances may be at decreased odds of all outcomes in various vaccines.

Collectively, the studies identified several groups with statistically significant greater vaccine hesitancy and decreased engagement among whom targeted measures could be beneficial. Timely evidence, especially on behavioral addictions and substances besides tobacco, is lacking, and warrants urgent attention.

Between June and November 2017, four supervised consumption sites (SCS) began operating in Montreal, Quebec. Earlier studies on SCS focused on examining their effects on blood-borne viral infections and overdose mortality. Our objective was to examine the effect of Montreal's SCS on the incidence, health service use and outcomes of injection-related infections (IRI) in people who inject drugs.

We used Quebec's provincial administrative health data to identify people who inject drugs in Montreal and calculated the incidence of IRI in this population between December 2014 and December 2019. We conducted a retrospective, population-based interrupted time series to estimate the effect of Montreal's four SCS on the monthly incidence rates of IRI-related hospitalizations, emergency department (ED) visits, physician visits, and mortality. We also examined the effects of SCS on average length of IRI-related hospitalizations and incidence of hospitalizations involving surgery.

The average age of Montreal's people who inject drugs was 41.84 years, and 66.41% were male. After the implementation of SCS, there was a positive level change in the incidence of hospitalizations (0.97; 95% confidence interval [CI]: 0.26, 1.68) for IRI. There was also a significant post-intervention decline in hospitalization trends (-0.05; 95% CI: -0.08, -0.02), with modest trend changes in ED visits (-0.02; 95% CI: -0.05, 0.02). However, post-intervention changes in level (0.72; 95% CI: -3.85, 5.29) and trend (0.06; 95% CI: -0.23, 0.34) for physician visits remained limited. SCS had no effect on the average length of hospitalizations, but there was a decreasing post-intervention trend in hospitalizations involving surgery (-0.03; 95% CI: -0.06, 0.00).

Following the opening of the SCS, there was a moderate decline in the rate of hospitalizations to treat IRI, but the impact of the sites on the rate of physician visits remained limited. These findings suggest that SCS may mitigate the incidence of more serious and complicated IRI over time.

Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification.

We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment.

Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

People in homelessness have an increased risk of substance use disorders (SUDs) and poor health outcomes. This cohort study aimed to investigate the association between homelessness and mortality in people with SUDs, adjusting for age, sex, narcotic use, intravenous drug use and inpatient care for SUDs.

Data from the Swedish National Addiction Care Quality Register in the Stockholm region were used to analyse mortality risk in people with SUDs (n=8397), including 637 in homelessness, 1135 in precarious housing and 6625 in stable housing, at baseline. HRs and CIs were calculated using Cox regression.

Mortality was increased for people in homelessness (HR 2.30; 95% CI 1.70 to 3.12) and precarious housing (HR 1.23; 95% CI 0.86 to 1.75) compared with those in stable housing. The association between homelessness and mortality decreased (HR 1.27; 95% CI 0.91 to 1.78) after adjusting for narcotic use (HR 1.28; 95% CI 1.00 to 1.63), intravenous drug use (HR 1.98; 95% CI 1.52 to 2.58) and inpatient care for SUDs (HR 1.96; 95% CI 1.57 to 2.45). Standardised mortality ratios (SMRs) showed that mortality among people in homelessness with SUDs was 13.6 times higher than the general population (SMR=13.6; 95% CI 10.2 to 17.9), and 3.7 times higher in people in stable housing with SUDs (SMR=3.7; 95% CI 3.2 to 4.1).

Homelessness increased mortality, but the risk decreased after adjusting for narcotic use, intravenous drug use and inpatient care for SUDs. Interventions are needed to reduce excess mortality among people in homelessness with SUDs.

Background: HIV and drug overdose continue to be the leading causes of death among people who inject drugs (PWID). Mizoram, a small state in the northeast of India, has the highest prevalence of HIV in India and a high HIV prevalence among PWID. Objective: To estimate the mortality among HIV-positive and HIV-negative PWID and to describe its associated factors. Methods: Cross-sectional datasets from the 2007-2021 Mizoram State AIDS Control Society (MSACS) data comprising 14626 PWID were analyzed. Logistic regression analysis was conducted to examine the factors associated with mortality among HIV-negative and HIV-positive PWID after adjusting for potential confounding factors. Results: Mortality among HIV-negative PWID declined by 59% between 2007 and 2021. The mortality rate among HIV-positive PWID also declined by 41% between 2007 and 2021. The multiple logistic regression analysis revealed that being divorced/separated/widowed (AOR = 1.41, 95% CI 1.03-1.94) remained positively associated with mortality among HIV-positive PWID. Mortality among HIV-negative PWID remained positively associated with ages of 24-34 years (AOR = 1.54, 95% CI 1.29-1.84) and above 35 years (AOR = 2.08, 95% CI 1.52-2.86), being divorced/separated/widowed (AOR = 1.28, 95% CI 1.02-1.61), and the sharing of needles/syringes (AOR = 1.28, 95% CI 1.34-2.00). Mortality among HIV-negative PWID was negatively associated with being married (AOR = 0.72, 95% CI 0.57-0.90), being employed (AOR = 0.77, 95% CI 0.64-0.94), and having a monthly income. Conclusions: The mortality rate among HIV-negative and HIV-positive PWID declined significantly between 2007 and 2021 in Mizoram. To further reduce mortality among PWID, interventions should target those sharing needles/syringes, those above 24 years of age, and unmarried participants.

While research has demonstrated associations between experiencing violence from intimate and non-intimate partners and non-fatal drug overdose among women who inject drugs, existing studies focus predominantly on the Global North and are analytically limited. Guided by syndemics theory, this study examined whether different forms of gender-based violence exert independent and interactive effects on non-fatal drug overdose among women who inject drugs in Indonesia.

We recruited 731 cisgender adult women who injected drugs in the preceding year via respondent-driven sampling. We used multivariate logistic regressions to examine associations between self-reported intimate partner violence (IPV), police sexual violence, and police extortion, and non-fatal drug overdose, with covariance adjustment for factors drawn from the risk environment. We tested for interaction effects among violence measures by calculating metrics for attributable proportion (AP), relative excess risk due to interaction (RERI), and synergy index (S).

Experiencing IPV (AOR 2.5; 95 % CI 1.2, 5.1; p = 0.012), police extortion (AOR 2.2; 95 % CI 1.5, 3.2; p ≤ 0.001), and police sexual violence (AOR 3.7; 95 % CI 1.5, 9.4; p = 0.005) each independently predicted non-fatal overdose, after adjusting for potential confounders. A significant positive interaction was detected between IPV and police sexual violence on drug overdose (AP=0.6, p = 0.001; S = 3.8, p = 0.015) such that the joint effect of these two forms of violence was associated with a nearly fourfold increase in non-fatal overdose risk compared to the main effects of each violence exposure.

This is the first study to show that concurrent IPV and police sexual violence exert an amplifying effect on non-fatal overdose beyond the additive effects of each exposure. Supporting the value of gender-responsive harm reduction services that integrate violence and overdose responses, results suggest that eliminating one form of violence when multiple forms of GBV are present could magnify the expected reduction in overdose.

Needle and syringe programs (NSP) are effective harm-reduction strategies against HIV and hepatitis C. Although skin, soft tissue, and vascular infections (SSTVI) are the most common morbidities in people who inject drugs (PWID), the extent to which NSP are clinically and cost-effective in relation to SSTVI in PWID remains unclear. The objective of this study was to model the clinical- and cost-effectiveness of NSP with respect to treatment of SSTVI in PWID.

We performed a model-based, economic evaluation comparing a scenario with NSP to a scenario without NSP. We developed a microsimulation model to generate two cohorts of 100,000 individuals corresponding to each NSP scenario and estimated quality-adjusted life-years (QALY) and cost (in 2022 Canadian dollars) over a 5-year time horizon (1.5% per annum for costs and outcomes). To assess the clinical effectiveness of NSP, we conducted survival analysis that accounted for the recurrent use of health care services for treating SSTVI and SSTVI mortality in the presence of competing risks.

The incremental cost-effectiveness ratio associated with NSP was $70,278 per QALY, with incremental cost and QALY gains corresponding to $1207 and 0.017 QALY, respectively. Under the scenario with NSP, there were 788 fewer SSTVI deaths per 100,000 PWID, corresponding to 24% lower relative hazard of mortality from SSTVI (hazard ratio [HR] = 0.76; 95% confidence interval [CI] = 0.72-0.80). Health service utilization over the 5-year period remained lower under the scenario with NSP (outpatient: 66,511 vs. 86,879; emergency department: 9920 vs. 12,922; inpatient: 4282 vs. 5596). Relatedly, having NSP was associated with a modest reduction in the relative hazard of recurrent outpatient visits (HR = 0.96; 95% CI = 0.95-0.97) for purulent SSTVI as well as outpatient (HR = 0.88; 95% CI = 0.87-0.88) and emergency department visits (HR = 0.98; 95% CI = 0.97-0.99) for non-purulent SSTVI.

Both the individuals and the healthcare system benefit from NSP through lower risk of SSTVI mortality and prevention of recurrent outpatient and emergency department visits to treat SSTVI. The microsimulation framework provides insights into clinical and economic implications of NSP, which can serve as valuable evidence that can aid decision-making in expansion of NSP services.

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.

A better understanding of global patterns of drug use among people who inject drugs can inform interventions to reduce harms related to different use profiles. This review aimed to comprehensively present the geographical variation in drug consumption patterns among this population.

Systematic searches of peer reviewed (PsycINFO, Medline, Embase) and grey literature published from 2008-2022 were conducted. Data on recent (past year) and lifetime drug use among people who inject drugs were included. Data were extracted on use of heroin, amphetamines, cocaine, benzodiazepines, cannabis, alcohol, and tobacco; where possible, estimates were disaggregated by route of administration (injecting, non-injecting, smoking). National estimates were generated and, where possible, regional, and global estimates were derived through meta-analysis.

Of 40,427 studies screened, 394 were included from 81 countries. Globally, an estimated 78.1 % (95 %CI:70.2-84.2) and 71.8 % (65.7-77.2) of people who inject drugs had recently used (via any route) and injected heroin, while an estimated 52.8 % (47.0-59.0) and 19.8 % (13.8-26.5) had recently used and injected amphetamines, respectively. Over 90 % reported recent tobacco use (93.5 % [90.8-95.3]) and recent alcohol use was 59.1 % (52.6-65.6). In Australasia recent heroin use was lowest (49.4 % [46.8-52.1]) while recent amphetamine injecting (64.0 % [60.8-67.1]) and recent use of cannabis (72.3 % [69.9-74.6]) were higher than in all other regions. Recent heroin use (86.1 % [78.3-91.4]) and non-injecting amphetamine use (43.3 % [38.4-48.3]) were highest in East and Southeast Asia. Recent amphetamine use (75.8 % [72.7-78.8]) and injecting heroin use (84.8 % (81.4-87.8) were highest in North America while non-injecting heroin use was highest in Western Europe (45.0 % [41.3-48.7]).

There is considerable variation in types of drugs and routes of administration used among people who inject drugs. This variation needs to be considered in national and global treatment and harm reduction interventions to target the specific behaviours and harms associated with these regional profiles of use.

Injection-related infections continue to rise, particularly in the South. People who inject drugs are increasingly utilizing hospital services for serious injection-related infections but may be discharged to areas without harm reduction services. We explored the availability and travel time to services for HIV and substance use in Alabama.

Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions.

We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs.

We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC.

OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs.

Excess all-cause mortality is a key indicator for assessing direct and indirect consequences of injection drug use and data are warranted to delineate sub-populations within people who inject drugs at higher risk of death. Our aim was to examine mortality and factors associated with mortality among people who inject drugs in Estonia.

Retrospective cohort study using data from people who inject drugs recruited in the community with linkage to death records. Standardized mortality ratios were used to compare the cohort mortality to the general population and potential predictors of death were examined through survival analysis (Cox regression). The cohort include a total of 1399 people who inject drugs recruited for cross-sectional surveys using respondent driven sampling between 2013 and 2018 in Estonia. A cohort with follow-up through 2019 was formed with linkage to national causes of death registry.

Among 1399 participants with 4684 person-years of follow-up, 10% were deceased by 2019. The all-cause mortality rate in the cohort was 28.9 per 1000 person-years (95% confidence interval 25.3-35.3). Being HIV positive, injecting mainly opioids (fentanyl), living in the capital region and the main source of income other than work were associated with greater mortality risk.

While low-threshold services have been available for a long time for people who inject drugs, there is still a need to widen the availability and integration of services, particularly the integration of HIV and opioid treatment.

Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022.

PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model.

Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death.

Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.

Overdoses involving opioids and stimulants are on the rise, yet few studies have examined longitudinal trends in use of both substances. We sought to describe use and co-use of opioids and stimulants, 2005-2019, in the AIDS Linked to the Intravenous Experience (ALIVE) cohort - a community-based cohort of people with a history of injection drug use living in or near Baltimore, MD.

We included 2083 ALIVE participants, who had at least two visits during the study period. Our outcome was based on self-reported use of opioids and stimulants in the prior 6 months. We estimated prevalence of 4 categories of use (neither stimulants nor opioids, only stimulants, only opioids, stimulants and opioids), using a non-parametric multi-state model, accounting for the competing event of death and weighting for informative loss to follow-up. All analyses were stratified by enrollment cohort, with the main analysis including participants who enrolled prior to 2015 and a sub-analysis including participants who enrolled 2015-2018.

In the main analysis, prevalence of using stimulants and opioids decreased from 38 % in 2005 to 12 % 2013 but stabilized from 2014 onwards (13-19 %). The prevalence of using only stimulants (7-11 %) and only opioids (5-10 %) was stable across time. Participants who reported using both were more likely to report homelessness, depression, and other substance use (e.g., marijuana and heavy alcohol use) than participants in the other use categories. On average, 65 % of visits with use of both were followed by a subsequent visit with use of both; of participants transitioning out of using both, 13% transitioned to using neither.

While use of stimulants and opioids declined in the cohort through 2013, a meaningful proportion of participants persistently used both. More research is needed to understand and develop strategies to mitigate harms associated with persistent use of both stimulants and opioids.

People who inject drugs (PWID) are at high risk for opioid overdose and infectious diseases including HIV. We piloted PARTNER UP, a telemedicine-based program to provide PWID with medication for opioid use disorder (MOUD) with buprenorphine/naloxone (bup/nx) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine through two syringe services programs (SSP) in North Carolina. We present overall results from this project, including participant retention rates and self-reported medication adherence.

Study participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly until program end at month 6. Participants were asked to start both MOUD and PrEP at initiation but could choose to discontinue either at any point during the study. Demographics and health history including substance use, sexual behaviors, and prior use of MOUD/PrEP were collected at baseline. Follow-up surveys were conducted at 3- and 6-months to assess attitudes towards MOUD and PrEP, change in opioid use and sexual behaviors, and for self-reported medication adherence. Participant retention was measured by completion of visits; provider notes were used to assess whether the participant reported continuation of medication.

Overall, 17 persons were enrolled and started on both bup/nx and PrEP; the majority self-identified as white and male. At 3 months, 13 (76%) remained on study; 10 (77%) reported continuing with both MOUD and PrEP, 2 (15%) with bup/nx only, and 1 (8%) with PrEP only. At 6 months, 12 (71%) remained on study; 8 (67%) reported taking both bup/nx and PrEP, and 4 (33%) bup/nx only. Among survey participants, opioid use and HIV risk behaviors decreased. Nearly all reported taking bup/nx daily; however, self-reported daily adherence to PrEP was lower and declined over time. The most common reason for not continuing PrEP was feeling not at risk for acquiring HIV.

Our study results show that MOUD and PrEP can be successfully administered via telemedicine in SSPs. PrEP appears to be a lower priority for participants with decreased continuation and adherence. Low perception of HIV risk was a reason for not continuing PrEP, possibly mitigated by MOUD use. Future studies including helping identify PWID at highest need for PrEP are needed.

Providing Suboxone and PrEP Using Telemedicine, NCT04521920. Registered 18 August 2020. https://clinicaltrials.gov/study/NCT04521920?term=mehri%20mckellar&rank=2 .

Encounter-based datasets like the Treatment Episode Dataset-Admissions (TEDS-A) are used for substance use-related research. Although TEDS-A reports the number of previous treatment admissions, a limitation is this reflects encounters, not people. We sought to quantify the methodologic bias incorporated by using all encounters versus initial encounters and assess if this risk is evenly distributed across all routes of drug administration.

TEDS-A 2000-2020 dataset with nonmissing primary substance data was used. Of the data, 3.17% were missing the usual administration route, and 11.9% were missing prior admission data. Prior admissions are documented as 0 through 4, then binned for 5 or greater (5+). Risk of admission bias was defined as odds ratio (OR RAB ): odds of total admissions relative to the odds of the first admission. Bootstrap confidence intervals were generated (5000 iterations) across administration routes and demographics; however, their widths were <0.0055 and not reported.

There were 38,238,586 admissions over the 21 years, with 13,865,517 (41.2%) first admissions. Of all admissions, 15.7% indicated injection drug use (IDU); 26.3% of encounters reporting IDU were in the 5+ group. This resulted in an OR RAB of 1.77. White enrollees had an elevated OR RAB (1.05), whereas among Latinos, OR RAB was low (0.74).

Using encounter-based datasets can introduce bias when including all admissions versus exclusively initial treatment episodes. This report is the first to quantify this bias and shows that individuals with IDU are at highest risk for returning to treatment, thereby over-representing this method of use when all encounters are used.

The risk of mortality in people with a history of injection drug use (PHID) is high, as is the prevalence of hepatitis C virus (HCV) infection. Although direct-acting antivirals (DAA) are effective in this population in terms of sustained virological response, it is not known whether PHID benefit as much as people with no history of injection drug use from DAA-related HCV cure in terms of reduced all-cause mortality.

Using Cox proportional hazards models based on the ANRS CO22 Hepather cohort data (n = 9735), we identified factors associated with all-cause mortality among HCV-infected people. We tested for interaction effects between drug injection status, HCV cure and other explanatory variables.

DAA-related HCV cure was associated with a 66% (adjusted hazard ratio [95% confidence interval]: 0.34 [0.29-0.39]) lower risk of all-cause mortality, irrespective of drug injection status. Detrimental effects of unhealthy alcohol use on mortality were identified in PHID only.

DAA-related HCV cure led to comparable benefits in terms of reduced mortality in PHID and people with no history of injection drug use. Policies and strategies to enhance DAA uptake among PHID are needed to lower mortality in this population. Clinical trial registration details: ClinicalTrials.gov: NCT01953458.

Recreational drug use is increasingly common in the dermatology patient population and is often associated with both general and specific mucocutaneous manifestations. Signs of substance use disorder may include changes to general appearance, skin, and mucosal findings associated with particular routes of drug administration (injection, insufflation, or inhalation) or findings specific to a particular drug. In this review article, we provide an overview of the mucocutaneous manifestations of illicit drug use including cocaine, methamphetamine, heroin, hallucinogens, marijuana, and common adulterants to facilitate the identification and improved care of these patients with the goal being to connect this patient population with appropriate resources for treatment.

This study aimed to synthetize the evidence on the effectiveness of harm minimization interventions on reducing blood-borne infection transmission and injecting behaviors among people who inject drugs (PWID) through a comprehensive overview of systematic reviews and evidence gap mapping.

A systematic review was conducted with searches in PubMed and Scopus to identify systematic reviews assessing the impact of interventions aimed at reducing the harms associated with injectable drug use. The overall characteristics of the studies were extracted and their methodological quality was assessed using AMSTAR-2. An evidence gap map was constructed, highlighting the most frequently reported outcomes by intervention (CRD42023387713).

Thirty-three systematic reviews were included. Of these, 14 (42.2%) assessed the impact of needle/syringe exchange programs (NSEP) and 11 (33.3%) examined opioid agonist therapy (OAT). These interventions are likely to be associated with reductions of HIV/HCV incidence (10-40% risk reduction for NSEP; 50-60% for OAT) and sharing injecting paraphernalia (50% for NSEP, 25-85% for OAT), particularly when combined (moderate evidence). Behavioral/educational interventions were assessed in 12 reviews (36.4%) with most authors in favor/partially in favor of the use of these approaches (moderate evidence). Take-home naloxone programs and supervised-injection facilities were each assessed in two studies (6.1%), which reported inconclusive results (limited/inconsistent evidence). Most authors reported high levels of heterogeneity and risk of bias. Other interventions and outcomes were inadequately reported. Most systematic reviews presented low or critically low quality.

The evidence is sufficient to support the effectiveness of OAT, NSEP and their combination in reducing blood-borne infection transmission and certain injecting behaviors among PWID. However, evidence of other harm minimizations interventions in different settings and for some outcomes remain insufficient.

Aim: This Norwegian case study examines groups at risk of drug overdose deaths, evidence-based harm reduction interventions, low-threshold services and treatment implemented, as well as trends in drug overdose deaths between 2010 and 2021. We aimed to explore the relevance of interventions for at-risk groups and discuss their potential impact on drug overdose trends. Method/data: Using an ecological approach, we analysed the following: (1) groups identified through latent profile analysis (LPA) among a sample of 413 high-risk drug users collected in 2010-2012, supplemented with other relevant studies up to 2021; (2) published information on harm-reduction interventions, low-threshold services and treatment in Norway; and (3) nationwide drug overdose mortality figures supplemented with published articles on the topic. Results: High-risk drug users in 2010-2012 commonly engaged in frequent illegal drug use, injecting and poly-drug use (including pharmaceutical opioids), which continued into following decade. The interventions implemented between 2010 and 2021 were relevant for at-risk groups identified in the surveys. However, there was no decrease in the trend of drug overdose deaths up to 2021. While relevant interventions may have mitigated a theoretical increase in mortality, new at-risk groups may have contributed to fatal outcomes associated with pharmaceutical opioids. Conclusion: The interventions were relevant to the risk groups identified among high-risk drug users and potentially effective in preventing an increase in drug overdose trends. However, tailored interventions are needed for individuals at risk of death from prescribed opioids. Comprehensive studies encompassing all at-risk populations, including both legal and non-medical users of prescription opioids, are needed.

People who use opioids (PWUO) have an excess mortality from a range of causes. The cumulative effect of behavioral, social, and health risk factors complicates the interpretation of the effects of suitable interventions. This study explores mortality causes among a cohort of PWUO in the take-home naloxone (THN) program.

This was a prospective cohort study of PWUO who received THN between 2015 and 2023. Participant data was linked with death registry data. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all causes, internal causes, and accidental opioid overdoses (AOOs). In addition to age and gender, risk factors like main route of administration, polydrug use, self-experienced overdoses, and using while alone were fitted in a Cox Regression model to explore factors associated with mortality.

The 2194 participants had a considerably higher mortality ratio for all causes investigated when compared to the general population (SMR=10.9, 95 % CI = 9.3,12.6). AOOs were the most prevalent cause of death (49 %). Those who reported frequent opioid use while alone had an elevated risk of dying of 2.6 (95 % CI = 1.1,6.4) compared to those who never used while alone.

Frequent opioid use while alone was associated with elevated mortality risk, supporting the importance of overdose prevention education with naloxone distribution, and additional efforts to improve environmental and social areas for safer drug-use practices among PWUO. The variety of mortality causes found in this study illustrates the need for multifaceted and targeted interventions for people at risk of overdosing.

The drug-overdose crisis in the United States continues to intensify. Fatalities have increased 5-fold since 1999 reaching a record high of 108,000 deaths in 2021. The epidemic has unfolded through distinct waves of different drug types, uniquely impacting various age, gender, race, and ethnic groups in specific geographical areas. One major challenge in designing interventions and efficiently delivering treatment is forecasting age-specific overdose patterns at the local level. To address this need, we develop a forecasting method that assimilates observational data obtained from the CDC WONDER database with an age-structured model of addiction and overdose mortality. We apply our method nationwide and to three select areas: Los Angeles County, Cook County, and the five boroughs of New York City, providing forecasts of drug-overdose mortality and estimates of relevant epidemiological quantities, such as mortality and age-specific addiction rates.

While there are approved therapeutics to treat opioid overdoses, the need for treatments to reverse overdoses due to ultrapotent fentanyls remains unmet. This may be due in part to an adrenergic mechanism of fentanyls in addition to their stereotypical mu-opioid receptor (MOR) effects. Herein, we report our efforts to further understanding of the functions these distinct mechanisms impart. Employing the known MOR neutral antagonist phenylfentanil as a lead, 17 analogues were designed based on the concept of isosteric replacement. To probe mechanisms of action, these analogues were pharmacologically evaluated in vitro and in vivo, while in silico modeling studies were also conducted on phenylfentanil. While it did not indicate MOR involvement in vivo, phenylfentanil yielded respiratory minute volumes similar to those caused by fentanyl. Taken together with molecular modeling studies, these results indicated that respiratory effects of fentanyls may also correlate to inhibition of both α1A- and α1B-adrenergic receptors.

The United States' (US) opioid overdose epidemic has evolved into a combined stimulant/opioid epidemic, a pattern driven in part by mitigating opioid overdose risk, variable substance availability, and personal preferences. This study aimed to investigate the association between self-reported substance preference (heroin or methamphetamine) and behavioral/health outcomes among individuals who used both heroin and methamphetamine in the rural US.

The Rural Opioid Initiative is a consortium of 8 research cohorts from 10 states and 65 rural counties that recruited individuals reporting past 30-day injection of any substance or opioid substance use by any route from 1/2018 to 3/2020. Analyses were restricted to participants ⩾18 years, who self-reported either heroin or methamphetamine as their preferred substance and past 30-day use of both heroin and methamphetamine. We examined cross-sectional associations between preferred substance (heroin versus methamphetamine) and behavioral and health outcomes using random effects meta-analysis with adjusted regression models.

Among 1239 participants, 61% (n = 752) reported heroin as their preferred substance. Adjusting for age, sex, and race/ethnicity, methamphetamine preference was associated with lower prevalence ratios for current naloxone possession (adjusted prevalence ratio [aPR] = 0.68; 95% Confidence Interval [95% CI] = 0.59-0.78; P-value ⩽ .001), of ever being told they had the hepatitis C virus (HCV; aPR = 0.72; 95% CI: 0.61-0.85; P-value ⩽ .001) and a personal history of overdose (aPR = 0.81; 95% CI = 0.73-0.90; P-value ⩽ .001).

In our study analyzing associations between preferred substance and various behavioral and health outcomes amongst people who use both heroin and methamphetamine, a majority of participants preferred heroin. Methamphetamine preference was associated with lower prevalence of naloxone possession, ever being told they had HCV, and prior history of an overdose. This study underscores the need for targeted harm reduction services for people who prefer methamphetamine in rural areas.