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.

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.

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.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

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.

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.

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.

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.

Impact of hepatitis C virus infection on all-cause and liver-related mortality in a large community-based cohort of inner city residents.

The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community-based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause-specific mortality rates and factors associated with all-cause and liver-related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non-injection drug use - 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10.000 person-years; 95% CI: 165, 222), with 21% HIV-related, 20% drug-related and 7% liver-related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs < 40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver-related mortality was associated with age >50 [AHR 18.49 vs < 40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV-infected inner city residents >50 years of age were at significant risk of liver-related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.

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.

The Audio Recorded Cognitive Screen (ARCS) in patients with multiple sclerosis: a practical tool for multiple sclerosis clinics.

BACKGROUND: Cognitive impairment is a common complication of multiple sclerosis, even in early stage disease, with significant impacts on life quality and social interaction. However, its detection is highly test-dependent. OBJECTIVE: To validate a recently described screening tool, the ARCS, for detecting cognitive impairment in a multiple sclerosis population. METHODS: The ARCS administers tests of executive function, memory, visual spatial construction and language via an audio device to unsupervised patients who write their responses for later scoring. Some 127 patients with a wide variety of disease course and severity were assessed by ARCS, of whom 87 also completed the Paced Auditory Serial Addition Test (PASAT) and 45 underwent formal ('gold standard') neuropsychological testing. RESULTS: Compared with PASAT, we found that the ARCS showed better sensitivity (86% versus 68%) at equivalent specificity (71%) for detection of impairment in any cognitive domain, and superiority in the detection of memory and executive impairments. Acceptance and completion rates for the ARCS were as good or better than for the PASAT. CONCLUSIONS: ARCS is sensitive, well-tolerated, easy to administer and facilitates comprehensive cognitive assessment in less than 5 min of clinician time. It has several advantages over the PASAT for detecting cognitive impairment in patients with multiple sclerosis.

Community-associated methicillin-resistant Staphylococcus aureus is prevalent in wounds of community-based injection drug users.

Injection drug users (IDUs) have an elevated risk for carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Cutaneous injection-related infections are common in IDUs but detailed studies are few. Based on a subsample of 218 individuals from a community-recruited cohort of IDUs at a supervised injection facility, we investigated the microbiology and related antibiotic susceptibility profiles of isolates from 59 wounds. Twenty-seven percent of subjects had at least one wound and 25 (43%) were culture positive for S. aureus alone [14 MRSA and 11 (19%) methicillin-susceptible (MSSA) isolates]. Sixteen of 18 MRSA isolates were classified as community associated (CA) by the presence of genes encoding for PVL. MRSA and MSSA occurred in mixed infection with other organisms on three and six occasions, respectively. All CA-MRSA isolates were susceptible to tetracycline, vancomycin and linezolid but only 13% were susceptible to clindamycin compared to 63% of MSSA isolates. The frequency of CA-MRSA is a cause for concern in wound infection in the IDU setting.

Low uptake of treatment for hepatitis C virus infection in a large community-based study of inner city residents.

Despite the availability of effective therapy for hepatitis C virus (HCV) infection, there are little data on the uptake of treatment. We evaluated factors associated with HCV infection and the uptake of HCV treatment in a large community-based inner city cohort in Vancouver, Canada. The Community Health and Safety Evaluation is a cohort study of inner city residents recruited from January 2003 to June 2004. HIV and HCV status and information on prescriptions for HCV treatment were determined through linkage with provincial databases. HCV prevalence was calculated and factors associated with HCV infection were identified. HCV treatment uptake and incidence of HCV infection from January 2000 to December 2004 were expressed in terms of person-years of observation. Among 2913 individuals, HCV antibody testing was performed in 2118 and the HCV seroprevalence was 64.2% (1360 of 2118). In total, 1.1% of HCV antibody-positive individuals (15 of 1360) initiated treatment for HCV infection from January 2000 to December 2004 [0.28 cases per 100 person-years (95% CI, 0.15-0.46)]. Three of 15 (20.0%) treated individuals achieved a sustained virological response. During the same period, the incidence of HCV infection was 7.26 cases (95% CI, 5.72-8.80) per 100 person-years. Overall, the rate of new HCV seroconversions in this cohort in the study period was about 25 times the rate of HCV treatment uptake. There are extremely low rates of HCV treatment initiation and very limited effectiveness, despite a high prevalence of HCV infection in this large community-based cohort of inner city residents with access to universal healthcare.

Condom use among injection drug users accessing a supervised injecting facility.

OBJECTIVES: Although supervised injecting facility (SIF) use has been associated with reductions in injection-related risk behaviours, the impact of SIFs on the sexual behaviour of injection drug users (IDUs) has not been thoroughly investigated. Therefore, we examined the patterns and predictors of condom use among SIF users in Vancouver, Canada. METHODS: We performed a longitudinal analysis of the factors associated with consistent condom use among IDUs recruited from within a SIF. RESULTS: Among 1090 individuals, 650 (59.6%) reported a sexual partner in the past 6 months at baseline. Consistent condom use was reported by 108 (25.3%) and 205 (61.6%) individuals reporting regular or casual partners, respectively. After 2 years of observation, these proportions increased to 32.9% and 69.8%, respectively. In multivariate analysis, predictors of consistent condom use with regular partners included HIV positivity (adjusted odds ratio (AOR) 2.23; 95% CI 1.51 to 3.31), injecting with a sex partner (AOR 0.50; 95% CI 0.37 to 0.68), enrollment in addiction treatment (AOR 0.68, 95% CI 0.52 to 0.89) and time since recruitment (AOR 1.29; 95% CI 1.06 to 1.55 per year). Predictors of consistent condom use with casual partners included HIV positivity (AOR 1.70; 95% CI 1.03 to 2.81), syringe borrowing (AOR 0.54; 95% CI 0.32 to 0.91) and syringe lending (AOR 0.52; 95% CI 0.32 to 0.84). CONCLUSIONS: Our results demonstrate that among SIF users, consistent condom use was more frequent among casual sex partners and among HIV positive individuals. Importantly, while the prevalence of consistent condom use was low at baseline, it increased over time. Our findings suggest a possible beneficial effect of the SIF on safer sexual practices.