Changes in drug use behaviors coinciding with the emergence of illicit fentanyl among people who use drugs in Vancouver, Canada.

Background: With the emergence of illicitly-manufactured fentanyl, drug overdose deaths have risen in unprecedented numbers. In this context, there is an urgent need to characterize potential changes in drug use behaviors among people who use drugs (PWUD). Objective: To examine changes in drug use behaviors following the emergence of illicit fentanyl among people who use drugs (PWUD). Methods: Data for this cross-sectional analysis was derived from three prospective cohorts of PWUD between December 2016 and May 2017 in Vancouver, Canada. Multivariable logistic regression was used to determine factors associated with self-reported behavior changes (binary variable "yes" or "no") following the emergence of illicit fentanyl. Results: Among 999 participants [363 (36.3%) females], 388 (38.8%) reported some behavior change. The remaining 611 (61.2%) reported no change in behavior; 240 (39.3%) of these individuals had recently been exposed to fentanyl. In multivariable analyses, factors independently associated with behavior change included recent non-fatal overdose (Adjusted Odds Ratio [AOR] = 2.28), active injection drug use (AOR = 1.96), being on opioid agonist therapy (AOR = 1.80), and urine drug screen positive for fentanyl (AOR = 1.45), (all p < .05). Conclusion: The majority of PWUD in our sample did not change their drug use behavior despite a high prevalence of fentanyl exposure, indicating a need for targeted behavior change messaging and overdose prevention efforts such as naloxone and addiction treatment for this sub-population of PWUD. Further, the high fentanyl exposure observed in our sample suggests a need to address upstream structural factors shaping the overdose risk in addition to individual behavioral change.

High prevalence of willingness to use direct-acting antiviral-based regimens for hepatitis C virus (HCV) infection among HIV/HCV coinfected people who use drugs.

OBJECTIVES: Despite the high burden of hepatitis C virus (HCV)-related morbidity and mortality among HIV-positive people who use illicit drugs (PWUD), uptake of interferon-based treatments for HCV infection has been negligible among this group. Direct-acting antiviral (DAA) therapies offer an opportunity to expand treatment access among this population. The aim of this study was to explore willingness to use DAA-based regimens among HIV/HCV-coinfected PWUD in Vancouver, Canada. METHODS: Data were drawn from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), a prospective cohort of HIV-positive PWUD. Using logistic regression analyses, we investigated factors associated with willingness to use DAA-based regimens among HIV/HCV-coinfected participants. RESULTS: Of 418 HIV/HCV-coinfected PWUD surveyed between June 2014 and May 2015, 295 (71%) were willing to use DAA-based regimens. In multivariable analysis, participants enrolled in methadone maintenance therapy [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.04-2.51], those with a recent assessment by an HCV specialist (AOR 2.02; 95% CI 1.28-3.19) and those who perceived that HCV infection was affecting their health (AOR 2.49; 95% CI 1.41-4.37) were more likely to be willing to use DAA-based regimens. CONCLUSIONS: Overall, this study found a high prevalence of willingness to use DAA-based regimens among HIV/HCV-coinfected PWUD in Vancouver. Importantly, enrolment in methadone maintenance therapy was positively associated with willingness, suggesting that integrated models of HIV, HCV and addiction care should be explored as a way to address HCV-related morbidity and mortality among HIV/HCV-coinfected PWUD.

The effect of engagement in an HIV/AIDS integrated health programme on plasma HIV-1 RNA suppression among HIV-positive people who use illicit drugs: a marginal structural modelling analysis.

OBJECTIVES: HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load (VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre (DPC; an HIV/AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy (HAART)-exposed HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. METHODS: Data were derived from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a study of a community-recruited cohort of HIV-positive PWUD. A marginal structural model using inverse probability of treatment weights was used to estimate the longitudinal relationship between being a DPC client and exhibiting a VL < 50 HIV-1 RNA copies/mL plasma. RESULTS: Between 2005 and 2014, 746 HAART-exposed participants were included in the study, of whom 269 (36.1%) reported being a DPC client at some time during the study period. A marginal structural model estimated a 1.54 greater odds of achieving VL suppression (95% confidence interval 1.20-1.99) among DPC clients. CONCLUSIONS: Our findings demonstrate that participating in an innovative HIV/AIDS-focused adult integrated health programme that provides a broad range of clinical, harm reduction, and support services may contribute to optimizing the benefits of HAART in terms of morbidity, mortality and viral transmission among PWUD, and as a result help to fulfill the goals of the treatment-as-prevention strategy.

Healthcare avoidance by people who inject drugs in Bangkok, Thailand.

BACKGROUND: Although people who inject drugs (IDU) often contend with various health-related harms, timely access to health care among this population remains low. We sought to identify specific individual, social and structural factors constraining healthcare access among IDU in Bangkok, Thailand. METHODS: Data were derived from a community-recruited sample of IDU participating in the Mitsampan Community Research Project between July and October 2011. We assessed the prevalence and correlates of healthcare avoidance due to one's drug use using multivariate logistic regression. RESULTS: Among 437 participants, 112 (25.6%) reported avoiding health care because they were IDU. In multivariate analyses, factors independently associated with avoiding health care included having ever been drug tested by police [adjusted odds ratio (AOR) = 1.80], experienced verbal abuse (AOR = 3.15), been discouraged from engaging in usual family activities (AOR = 3.27), been refused medical care (AOR = 10.90), experienced any barriers to health care (AOR = 4.87) and received healthcare information and support at a drop-in centre (AOR = 1.92) (all P < 0.05). CONCLUSIONS: These findings highlight the need to address the broader policy environment, which perpetuates the criminalization and stigmatization of IDU, and to expand peer-based interventions to facilitate access to health care for IDU in this setting.

Aboriginal street-involved youth experience elevated risk of incarceration.

OBJECTIVES: Past research has identified risk factors associated with incarceration among adult Aboriginal populations; however, less is known about incarceration among street-involved Aboriginal youth. Therefore, we undertook this study to longitudinally investigate recent reports of incarceration among a prospective cohort of street-involved youth in Vancouver, Canada. STUDY DESIGN: Prospective cohort study. METHODS: Data were collected from a cohort of street-involved, drug-using youth from September 2005 to May 2013. Multivariate generalized estimating equation analyses were employed to examine the potential relationship between Aboriginal ancestry and recent incarceration. RESULTS: Among our sample of 1050 youth, 248 (24%) reported being of aboriginal ancestry, and 378 (36%) reported being incarcerated in the previous six months at some point during the study period. In multivariate analysis controlling for a range of potential confounders including drug use patterns and other risk factors, Aboriginal ancestry remained significantly associated with recent incarceration (adjusted odds ratio [AOR] = 1.44; 95% confidence interval [CI]: 1.12-1.86). CONCLUSIONS: Even after adjusting for drug use patterns and other risk factors associated with incarceration, this study found that Aboriginal street-involved youth were still significantly more likely to be incarcerated than their non-Aboriginal peers. Given the established harms associated with incarceration these findings underscore the pressing need for systematic reform including culturally appropriate interventions to prevent Aboriginal youth from becoming involved with the criminal justice system.

Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

Balloon aortic valvuloplasty as a bridge to liver transplantation in patients with severe aortic stenosis: a case series.

BACKGROUND: Patients with end-stage liver disease and severe aortic stenosis pose a significant perioperative management challenge during liver transplantation (OLT). This patient population is at risk for significant morbidity and mortality and is often denied transplantation. CASE SERIES: We describe the successful use of balloon aortic valvuloplasty as a bridging therapy to facilitate perioperative management during OLT with traditional open aortic valve replacement after recovery from OLT. CONCLUSIONS: Valvuloplasty should be considered as an option to reduce perioperative risk in this patient population.

Criminalisation of clients: reproducing vulnerabilities for violence and poor health among street-based sex workers in Canada-a qualitative study.

OBJECTIVES: To explore how criminalisation and policing of sex buyers (clients) rather than sex workers shapes sex workers' working conditions and sexual transactions including risk of violence and HIV/sexually transmitted infections (STIs). DESIGN: Qualitative and ethnographic study triangulated with sex work-related violence prevalence data and publicly available police statistics. SETTING: Vancouver, Canada, provides a unique opportunity to evaluate the impact of policies that criminalise clients as the local police department adopted a sex work enforcement policy in January 2013 that prioritises sex workers' safety over arrest, while continuing to target clients. PARTICIPANTS: 26 cisgender and 5 transgender women who were street-based sex workers (n=31) participated in semistructured interviews about their working conditions. All had exchanged sex for money in the previous 30 days in Vancouver. OUTCOME MEASURES: Thematic analysis of interview transcripts and ethnographic field notes focused on how police enforcement of clients shaped sex workers' working conditions and sexual transactions, including risk of violence and HIV/STIs, over an 11-month period postpolicy implementation (January-November 2013). RESULTS: Sex workers' narratives and ethnographic observations indicated that while police sustained a high level of visibility, they eased charging or arresting sex workers and showed increased concern for their safety. However, participants' accounts and police statistics indicated continued police enforcement of clients. This profoundly impacted the safety strategies sex workers employed. Sex workers continued to mistrust police, had to rush screening clients and were displaced to outlying areas with increased risks of violence, including being forced to engage in unprotected sex. CONCLUSIONS: These findings suggest that criminalisation and policing strategies that target clients reproduce the harms created by the criminalisation of sex work, in particular, vulnerability to violence and HIV/STIs. The current findings support decriminalisation of sex work to ensure work conditions that support the health and safety of sex workers in Canada and globally.

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users.

AIMS: Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. DESIGN: Pooled analysis of prospective cohort studies. SETTINGS: Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. PARTICIPANTS: We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. MEASUREMENTS: Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. FINDINGS: Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions toward cessation. CONCLUSIONS: PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions.

Methadone maintenance therapy decreases the rate of antiretroviral therapy discontinuation among HIV-positive illicit drug users.

We sought to examine whether methadone maintenance therapy (MMT) decreased rates of antiretroviral therapy (ART) discontinuation and was associated with plasma HIV RNA responses among a cohort of illicit drug users. Cumulative ART discontinuation rates were estimated using Kaplan-Meier methods and factors independently associated with ART discontinuation were identified using Cox proportional hazards regression. Engagement in MMT was negatively and independently associated with ART discontinuation [Adjusted Relative Hazard = 0.67 (95 % CI 0.54-0.83); p < 0.001]. Among participants receiving ART and MMT, 81.6 % of plasma HIV-1 RNA assessments were <500 copies/mL, while 65.81 % of HIV-1 RNA assessments among those prescribed ART without MMT were <500 copies/mL (p < 0.001). These results demonstrate that engagement in MMT conferred a protective benefit against ART discontinuation and was associated with a significant increase in plasma HIV RNA suppression among HIV-infected opioid-dependent drug users.

Low rates of hepatitis C testing among people who inject drugs in Thailand: implications for peer-based interventions.

BACKGROUND: Regular testing for hepatitis C virus (HCV) provides an opportunity for HCV prevention and treatment efforts. In Thailand, the barriers and facilitators of HCV testing among people who inject drugs (IDU) are not known. METHODS: Using data derived from the Mitsampan Community Research Project between July and October 2011, we assessed the prevalence and factors associated with ever having been tested for HCV antibodies using bivariate statistics and multivariate logistic regression. RESULTS: Among 427 participants, 141 (33.0%) reported a history of HCV antibody testing. In multivariate analyses, factors positively associated with receiving an HCV antibody test included higher than secondary education [adjusted odds ratio (AOR) = 2.20; 95% confidence interval (CI): 1.35-3.64], binge drug use (AOR = 1.81; 95% CI: 1.12-2.93), methadone treatment enrollment (AOR = 3.47; 95% CI: 1.85-6.95) and having received peer-based education on HCV (AOR = 4.22; 95% CI: 2.66-6.77). CONCLUSIONS: We found one-third of Thai IDU in our sample reporting a history of HCV testing. The finding that IDU who received peer-based HCV education were more likely to access HCV testing provides evidence for the value of peer-based interventions for this population.

Improved adherence to modern antiretroviral therapy among HIV-infected injecting drug users.

OBJECTIVES: Adherence to antiretroviral therapy (ART) among injecting drug users (IDUs) is often suboptimal, yet little is known about changes in patterns of adherence since the advent of highly active antiretroviral therapy in 1996. We sought to assess levels of optimal adherence to ART among IDUs in a setting of free and universal HIV care. METHODS: Data were collected through a prospective cohort study of HIV-positive IDUs in Vancouver, British Columbia. We calculated the proportion of individuals achieving at least 95% adherence in the year following initiation of ART from 1996 to 2009. RESULTS: Among 682 individuals who initiated ART, the median age was 37 years (interquartile range 31-44 years) and 248 participants (36.4%) were female. The proportion achieving at least 95% adherence increased over time, from 19.3% in 1996 to 65.9% in 2009 (Cochrane-Armitage test for trend: P < 0.001). In a logistic regression model examining factors associated with 95% adherence, initiation year was statistically significant (odds ratio 1.08; 95% confidence interval 1.03-1.13; P < 0.001 per year after 1996) after adjustment for a range of drug use variables and other potential confounders. CONCLUSIONS: The proportion of IDUs achieving at least 95% adherence during the first year of ART has consistently increased over a 13-year period. Although improved tolerability and convenience of modern ART regimens probably explain these positive trends, by the end of the study period a substantial proportion of IDUs still had suboptimal adherence, demonstrating the need for additional adherence support strategies.

Increases in the availability of prescribed opioids in a Canadian setting.

BACKGROUND: The nonmedical use of prescribed opioids (POs) has increased across North America over the past decade. Our objective was to identify changes in the availability of POs and other illicit drugs among drug users in a Canadian setting. METHODS: Information on the availability of illicit drugs was collected in standardized interviews from a large observational research program involving illicit drug users in Vancouver, British Columbia from 2006 to 2010. The primary outcome was the perceived availability of a set of six POs (aspirin/oxycodone, hydromorphone, oxycodone, morphine, acetaminophen/codeine and methadone) among individuals reporting ever using POs. Availability was measured in three levels: not available, delayed availability (available ≥10 min), and immediate availability (available <10 min). Multivariate ordinal logistic regression models were executed to estimate the trend in PO availability, controlling for individual characteristics hypothesized to influence availability. RESULTS: 1871 individuals were followed during the study period (2006-2010), including 583 (31.2%) women. The availability of POs increased over time, regardless of changes in the characteristics of cohort entrants. These increases were observed while the availability of traditional drugs of abuse (e.g., heroin and cocaine) remained constant. The adjusted odds of delayed availability vs. unavailability were between 34% (hydromorphone) and 71% (acetaminophen/codeine) greater in each calendar year. DISCUSSION: The availability of POs among drug users in a Canadian setting increased markedly over a relatively short timeframe, despite persistent and high availability of heroin and cocaine. Further study is required to determine the context of use of POs, associated harms, as well as policy responses to increasing availability.

Dextran sodium sulfate inhibition of real-time polymerase chain reaction amplification: a poly-A purification solution.

BACKGROUND: Dextran sulfate sodium (DSS) induces experimental colitis and promotes colitis-associated cancer in rodents. Here we document potent inhibition of real-time quantitative polymerase chain reaction (qPCR) using cDNA from DSS-exposed mouse tissues, which complicates gene expression analysis. METHODS: We characterize DSS inhibition of qPCR in-vitro and in a wide array of murine tissues following ingestion of DSS. We examine different approaches to RNA purification prior to cDNA synthesis in order to optimize real-time polymerase chain reaction amplification and gene expression analysis. RESULTS: DSS inhibits qPCR amplification of cDNA between 1 and 10 nM. Orally administered DSS interferes with qPCR amplification of cDNA derived from multiple tissues. Poly-A purification of DSS-exposed RNA allows reliable and cost-effective gene expression analysis in DSS-exposed tissue. CONCLUSIONS: DSS is a potent inhibitor of real-time qPCR amplification and interferes with tissue-specific gene expression analysis in DSS-exposed mice. Poly-A purification of tissue-derived RNA results in reliable and cost-effective gene expression analysis in DSS-exposed mice.

Frequent methamphetamine injection predicts emergency department utilization among street-involved youth.

OBJECTIVES: Methamphetamine (MA) use has been associated with health problems that commonly present in the emergency department (ED). This study sought to determine whether frequent MA injection was a risk factor for ED utilization among street-involved youth. STUDY DESIGN: Prospective cohort study. METHODS: Data were derived from a street-involved youth cohort known as the 'At Risk Youth Study'. Behavioural data including MA use were linked to ED records at a major inner-city hospital. Kaplan-Meier and Cox proportional hazards methods were used to determine the risk factors for ED utilization. RESULTS: Between September 2005 and January 2007, 427 eligible participants were enrolled, among whom the median age was 21 (interquartile range 19-23) years and 154 (36.1%) were female. Within 1 year, 163 (38.2%) visited the ED, resulting in an incidence density of 53.7 per 100 person-years. ED utilization was significantly higher among frequent (i.e. ≥daily) MA injectors (log-rank P = 0.004). In multivariate analysis, frequent MA injection was associated with an increased hazard of ED utilization (adjusted hazard ratio = 1.84, 95% confidence interval 1.04-3.25; P = 0.036). CONCLUSIONS: Street-involved youth who frequently inject MA appear to be at increased risk of ED utilization. The integration of MA-specific addiction treatment services within emergency care settings for high-risk youth is recommended.

Screening for methicillin-resistant Staphylococcus aureus (MRSA) in community-recruited injection drug users: are throat swabs necessary?

We examined and described colonization of MRSA in the anterior nares and throat from 184 community-recruited injection drug users. Thirty-seven (20%) were positive for MRSA: most (34, 92%) were carriers in the nares; while only three (8%) were carriers detected by throat swabs alone. The majority (29, 78%) of MRSA isolates were PVL positive.

HIV knowledge and perceptions of risk in a young, urban, drug-using population.

BACKGROUND: Educational programs targeted towards youth to prevent HIV transmission are based on a model that increased knowledge equals reduced risk behaviour. This study explored HIV knowledge among a cohort of young drug users, and their perceptions of HIV risk acquisition. METHODS: Between September 2005 and August 2009, youth who used illegal drugs were recruited into a prospective cohort known as the at-risk youth study (ARYS) in Vancouver, Canada. Participants completed an 18 item HIV Knowledge Questionnaire (HIV-KQ-18) and responses were scored dichotomously (i.e., ≥15 indicating high knowledge and <15 indicating low knowledge). We compared high- and low-scoring youth using Pearson's chi-square test and logistic regression. We also examined youths' perceptions of risk for acquiring HIV compared to their peers. RESULTS: Of 589 youth recruited into ARYS, the mean age was 22 (interquartile range [IQR]: 20-24), 186 (31.6%) were female, and 143 (24.3%) were of Aboriginal ancestry. The median score on the HIV-KQ- 18 was 15 (IQR: 12-16). Internal reliability was high (Cronbach's α=0.82). The analyses demonstrated that youth with higher HIV knowledge were more likely to be older (adjusted odds ratio [AOR]=1.08, per year older p=0.031), completed high school (AOR=1.42, p=0.054), and engage in unprotected intercourse (AOR=1.73, p=0.023). The majority of respondents (77.6%) perceived themselves to be at lower risk for acquiring HIV in comparison to their peers. CONCLUSIONS: HIV knowledge scores of participants were surprisingly low for an urban Canadian setting as was their HIV risk perception. Higher HIV knowledge was not associated with reduced sexual risk behaviour. Results demonstrate that education programs are not reaching or impacting this high-risk population. Given the complex forces that promote HIV risk behaviour, prevention programs should be fully evaluated and must recognize the unique characteristics of drug-using youth and factors that drive risk among this population.