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.

Criminal Justice System Involvement as a Risk Factor for Detectable Plasma HIV Viral Load in People Who Use Illicit Drugs: A Longitudinal Cohort Study.

Among HIV-positive people who use illicit drugs (PWUD) in our setting, repeated periods of incarceration adversely affect ART adherence in a dose-dependent manner. However, the impact of non-custodial criminal justice involvement on HIV-related outcomes has not been previously investigated. Data were obtained from a longitudinal cohort of HIV-positive PWUD in a setting of universal no-cost ART and complete dispensation records. Multivariate generalized estimating equations were used to calculate the longitudinal odds of having a detectable HIV VL (VL) associated with custodial and non-custodial CJS exposure. Between 2005 and 2014, 716 HIV-positive ART-exposed PWUD were recruited. In multivariate analysis, both custodial [Adjusted odds ratio (AOR) 0.61, 95% CI 0.45-0.82] and noncustodial (AOR 0.78, 95% CI 0.62-0.99) involvement in the criminal justice system was associated with detectable HIV VL. Among HIV-positive PWUD, both custodial and non-custodial criminal justice involvement is associated with worse HIV treatment outcomes. Our findings highlight the need for increased ART adherence support across the full spectrum of the criminal justice system.

Outpatient Rapid Titration of Slow Release Oral Morphine for the Treatment of Opioid Use Disorder in a Canadian Setting: A Case Series.

INTRODUCTION: In the midst of unprecedented opioid overdose deaths, opioid agonist therapy induction strategies that allow for rapid titration to therapeutic doses for individuals at high risk of overdose are needed. Slow release oral morphine (SROM) is an effective treatment for opioid use disorder; however, current guideline-recommended titration strategies require weeks to achieve therapeutic dose for individuals with high opioid tolerance. Individuals may be lost to care or experience overdose due to ongoing use of unregulated opioids during this time. After years of experience titrating SROM doses rapidly in the inpatient setting, we developed a protocol using short-acting morphine (MOS) to allow for rapid SROM titration in the outpatient setting. CASES: Patients (n = 4) were eligible if they met the criteria for opioid use disorder and had evidence of high opioid tolerance. Patients received supervised MOS doses in the outpatient setting, which were consolidated into a 12-hour extended-release morphine dose (to a maximum of 500 mg) on the evening of the titration. The total titration-day MOS and 12-hour extended-release morphine were summed into the post-titration-day SROM dose, to a maximum of 1000 mg. DISCUSSION: In the cases described, substantial reductions in unregulated fentanyl use and social gains, such as obtaining housing, employment, and enrollment in inpatient treatment programs, were observed after rapid SROM titration. No overdoses occurred during rapid SROM titration or during SROM treatment. More research is needed to determine the role for rapid SROM titrations as a stabilization option for outpatients.

Research With Women Who Use Drugs: Applying a Trauma-informed Framework.

Women who use drugs (WWUD) experience high rates of trauma. The complex impacts of trauma can act as a barrier to accessing substance use and harm reduction services, and to participation and representation within substance use research. Trauma-informed practice is an evidence-based approach for improved clinical care among WWUD, the principles of which can be applied to substance use research. Many researchers are integrating trauma-informed approaches across research settings, yet these principles are often not referenced specifically within publications, and there is a lack of comprehensive guidance regarding integration of trauma-informed methods across different research designs and methodologies. This commentary describes and discusses the merits of applying the 4 principles of trauma-informed practice - trauma awareness, safety and trustworthiness, choice collaboration and connection, and strengths-based and skills building - to promote safety and inclusion of WWUD in substance use research.

Case Study: Naltrexone for the Treatment of Nitrous Oxide Use.

BACKGROUND: Using a clinical case example, we describe and discuss the use of oral naltrexone as a novel treatment strategy for nitrous oxide use. Nitrous oxide is an inhalant drug that is readily available and legally obtained. Though frequency of reported cases of substance use disorder for nitrous oxide is low, previous case reports have described severe neurological and psychiatric harms associated with chronic use. Despite this, evidence for pharmacotherapy is currently lacking. Clinical studies have shown variable efficacy for naltrexone across a number of substances including alcohol, nicotine, and stimulants. CASE: We present here a case of a 41-year-old man with a substance use disorder for nitrous oxide who was reportedly using of up to four hundred 8 g canisters of nitrous oxide per day. Oral naltrexone was initiated at 50 mg daily in an attempt to decrease cravings. The dose was subsequently titrated to 100 mg daily, resulting in a decrease in nitrous oxide use to less than sixty 8 g canisters per week over a 1-month timeframe. DISCUSSION: Previous literature surrounding naltrexone provides both a plausible mechanism of action for craving reduction as well as a precedent for its use across a number of substances. To our knowledge, use of naltrexone for nitrous oxide use has not been previously described. While clinical studies are currently lacking, this case highlights naltrexone as a possible treatment strategy for nitrous oxide use, with potential to reduce significant harms associated with chronic use.

Factors Associated With the Use of Supervised Consumption Facilities Among Women Who Inject Drugs in a Canadian Setting.

BACKGROUND: Supervised consumption facilities (SCFs) are evidence-based harm reduction interventions that have been shown to reduce the risk of social and health-related harms associated with injection drug use. Previous qualitative studies have highlighted important motivations for SCF use among women who use drugs. However, factors associated with SCF use among women have not previously been evaluated. METHODS: Data were obtained from 2 longitudinal community-recruited cohorts of people who use drugs in Vancouver, Canada between 2003 and 2017. Multivariable generalized estimating equations were used to calculate the odds of SCF use associated with social and structural risk factors for drug-related harm among women who reported injection drug use in the preceding 6-months. RESULTS: A total of 795 participants were included in the study, contributing to 6302 interviews, with 602 participants (76%) reporting SCF use in at least one interview. Multivariable analysis demonstrated daily heroin and crystal methamphetamine injection (Adjusted Odds Ratio [AOR] = 1.32 and 1.65, respectively), injecting in public (AOR = 1.77), binge injection (AOR = 1.22) and lack of housing (AOR = 1.74) to be associated with SCF use. CONCLUSIONS: The current study demonstrates higher intensity patterns of drug use, including daily heroin and crystal methamphetamine injection, injecting in public and binge injection, as well as homelessness to be associated with SCF use among women. Future research should identify barriers to SCF use among women to minimize the risk of overdose and other drug-related harms.

Association between public injecting and drug-related harm among HIV-positive people who use injection drugs in a Canadian setting: A longitudinal analysis.

BACKGROUND: and Aims Injecting illicit drugs in public settings has been linked to a higher risk of a range of drug-related harms, including overdose and HIV infection. However, the factors associated with public injecting among HIV-positive individuals have not been previously explored. We investigated the links between public drug injecting, drug-related harm, and HIV treatment measures among a cohort of HIV-positive persons who inject drugs (PWID) in a Canadian setting. METHODS: We used data from a prospective cohort of HIV-positive PWID recruited from community settings in Vancouver, Canada, linked to comprehensive clinical monitoring data in the context of an ongoing Treatment-as-Prevention (TasP) initiative to examine harms associated with public injecting. We used generalized linear mixed-effects analyses to identify longitudinal factors associated with self-reported public drug injection. RESULTS: Between 2005 and 2014, 626 HIV-seropositive PWID were recruited, of whom 213 (34%) reported public injection in the preceding 180days. In a longitudinal multivariable model, public injection was positively associated with daily heroin injection (Adjusted Odds Ratio [AOR]=2.63), incarceration (AOR=1.78), and detectable plasma HIV-1 RNA viral load (VL, AOR=1.42). CONCLUSIONS: Public injecting was linked to numerous drug-related harms among HIV-seropositive PWID in this setting. Given its link with detectable VL, an important marker of poor HIV treatment outcomes, our findings support prioritizing individuals engaged in public injecting with harm reduction strategies as well as clinical and social supports as a part of TasP-based efforts to prevent HIV-related morbidity and mortality, and HIV transmission.

Benzodiazepine use as an independent risk factor for HIV infection in a Canadian setting.

BACKGROUND: Although the harms of prescription drug diversion are of growing international concern, the potential impact of prescription drug use on HIV infection has not been well assessed. We evaluated whether benzodiazepine use was associated with HIV seroconversion among a cohort of persons who inject drugs (PWID) in a Canadian setting. METHODS: Between May, 1996 and November, 2013, data were derived through a prospective cohort study of PWID in Vancouver, Canada. A total of 1682 baseline HIV negative participants were followed for a median of 79.5 months (interquartile range: 32.1-119.1), among whom 501 (29.8%) reported benzodiazepine use at baseline, and 176 seroconverted during follow-up, equal to an incidence density of 1.5 (95% Confidence Interval [CI]: 1.3-1.7) cases per 100 person-years. Poisson regression with time-dependent variables was used to assess whether benzodiazepine use was associated with the time to HIV seroconversion. RESULTS: After adjustment for potential confounders, benzodiazepine use (Adjusted Rate Ratio: 1.50; 95% CI: 1.01-2.24) was independently associated with a higher rate of HIV seroconversion. CONCLUSIONS: Benzodiazepine use was an independent risk factor for HIV seroconversion among PWID in this setting. Greater recognition of the safety concerns related to benzodiazepine medications including diversion are needed.