The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs.

Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (<90 mg/day) and daily illicit opioid use, testing for interaction between dose and daily cannabis use. Results: Between December 2005 and December 2018, 1389 participants reported MMT enrolment and were included in the study. We observed a significant interaction (p<0.01) between daily cannabis and lower MMT dose on concurrent daily illicit opioid use: lower MMT doses increased the odds of daily illicit opioid use by 86% (adjusted odds ratio [AOR]=1.86, 95% confidence interval [CI]=1.61-2.16) during periods of no or low-frequency cannabis use and by 30% during periods of daily cannabis use (AOR=1.30, 95% CI=1.01-1.67). Discussion: This study provides preliminary observational evidence that cannabis may mitigate some of the negative effects of subtherapeutic MMT dosing, guiding future clinical investigations into the safety and efficacy of cannabis and cannabinoids as adjunct treatment for MMT.

Latent patterns of polysubstance use among people who use opioids: A systematic review.

BACKGROUND: A mounting body of evidence suggests that polysubstance use (PSU) is common among people who use opioids (PWUO). Measuring PSU, however, is statistically and methodologically challenging. Person-centered analytical approaches (e.g., latent class analysis) provide a holistic understanding of individuals' substance use patterns and help understand PSU heterogeneities among PWUO and their specific needs in an inductive manner. We reviewed person-centered studies that characterized latent patterns of PSU among PWUO. METHODS: We searched MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar from inception, through to June 15, 2020, for empirical peer-reviewed studies or gray literature that reported on latent classes of PSU among PWUO. Two independent reviewers completed the title, abstract, full-text screening, and data extraction. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale, and quality of reporting was evaluated using the Guidelines for Reporting on Latent Trajectory Studies checklist. Studies' findings were summarized and presented in a narrative fashion. RESULTS: Out of the 3372 initial unique studies identified, 30 were included. PSU operationalization varied substantially among the studies. We identified five distinct PSU latent classes frequently observed across the studies: Infrequent/low PSU, PSU primarily involving heroin use, PSU primarily involving heroin and stimulant use, PSU primarily involving stimulant use, and frequent PSU. Belonging to higher frequency or severity PSU classes were associated with frequent injection drug use, sharing needles and paraphernalia, high-risk sexual behaviours, as well as experiences of adversities, such as homelessness, incarceration, and poor mental health. CONCLUSION: PSU patterns vary significantly across different subgroups of PWUO. The substantial heterogeneities among PWUO need to be acknowledged in substance use clinical practices and policy developments. Findings call for comprehensive interventions that recognize these within-group diversities and address the varying needs of PWUO.

Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis.

BACKGROUND: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT. METHODS: Data were drawn from two community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We used generalized linear mixed-effects modeling, adjusted by relevant confounders, to investigate the relationship between cannabis use and recent fentanyl exposure (both assessed by urine drug testing) among participants on OAT between 2016 and 2018. RESULTS: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 - 0.99). CONCLUSIONS: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.

Changes in substance use in relation to opioid agonist therapy among people who use drugs in a Canadian setting.

BACKGROUND: Although previous studies have shown that opioid agonist therapy (OAT) is linked to reductions in illicit opioid use, less is known about how OAT impacts the use of other psychoactive substances. We aimed to examine the changes in use of different substances by comparing patterns before and after initiating OAT. METHODS: Data for this study was derived from three ongoing prospective cohorts involving people who use drugs in Vancouver, Canada from 1996 to 2018. We assessed use patterns for heroin, illicit prescription opioid, cocaine, crack cocaine, crystal methamphetamine, cannabis, daily alcohol use, and benzodiazepines. Segmented regression was conducted to compare the trends of substance use between pre-treatment and post-treatment periods. RESULTS: The study included 1107 participants. After OAT engagement, we observed an immediate decline in the proportion as well as a decreasing trend for heroin (Adjusted Odds Ratio (AOR): 0.80, 95% confidence interval (CI): 0.77, 0.83), illicit prescription opioid (AOR: 0.87, 95% CI: 0.83, 0.90), and benzodiazepines (AOR: 0.73, 95 % CI: 0.67, 0.80). There was no significant difference comparing the pre-treatment and post-treatment trends for cocaine, crack cocaine, crystal methamphetamine, and cannabis. However, higher growth slope was noted during the post-treatment period for daily alcohol use (P = 0.016). CONCLUSIONS: We observed significant reduction in illicit opioids use following OAT initiation, but not for stimulant and cannabis. The increasing problematic use of alcohol may pose challenges to the safety and effectiveness of OAT. Development of comprehensive and tailored treatment strategies is needed for poly-substance users accessing OAT.

Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND: Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS: This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS: We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Interactive Versus Video-Based Training of Police to Communicate Syringe Legality to People Who Inject Drugs: The SHIELD Study, Mexico, 2015-2016.

Objectives. To assess how instructional techniques affect officers' intent to communicate syringe legality during searches in Tijuana, Mexico, where pervasive syringe confiscation potentiates risk of HIV and HCV among people who inject drugs (PWID) and of occupational needle-stick injury among police. Methods. Using the SHIELD (Safety and Health Integration in the Enforcement of Laws on Drugs) model, Tijuana police underwent training to encourage communication of syringe possession legality to PWID. Trainees received either passive video or interactive role-play exercise on safer search techniques. We used logistic regression to assess the training's impact on self-reported intent to communicate syringe legality by training type and gender. Results. Officers (n = 1749) were mostly men (86%) assigned to patrol (84%). After the training, intent to communicate the law improved markedly: from 20% to 39% (video group) and 20% to 58% (interactive group). Gender and training type significantly predicted intent to communicate syringe legality. Male and female officers' adjusted odds ratios in the interactive group were 5.37 (95% confidence interval [CI] = 4.56, 6.33) and 9.16 (95% CI = 5.88, 14.28), respectively, after the training. Conclusions. To more effectively persuade police to endorse harm reduction and occupational safety practices, police trainings should include interactive elements.

Engagement in Maximally-Assisted Therapy and Adherence to Antiretroviral Therapy Among a Cohort of Indigenous People Who Use Illicit Drugs.

Throughout the world, Indigenous populations experience a disproportionate burden of HIV infection. Maximally-assisted therapy (MAT) is an interdisciplinary care intervention that includes ART dispensation to support individuals with a history of addiction and homelessness. This study sought to longitudinally evaluate the relationship between engagement in MAT and achieving optimal adherence using data from an ongoing cohort of HIV-positive individuals who use drugs in Vancouver, Canada, where HIV/AIDS treatment is offered at no cost. Between December 2005 and November 2016, 354 HIV-positive Indigenous participants were enrolled and data were analyzed using generalized mixed-effects (GLMM) and marginal structural modeling. In both multivariable analyses, engagement in MAT was independently associated with optimal adherence to ART (GLMM: AOR = 4.92, 95% CI 3.18-7.62; marginal structural model: AOR = 5.76, 95% CI 3.34-9.96). MAT-based programmes could be a part of a renewed evidence-base to elevated levels of preventable HIV/AIDS-associated morbidity, mortality and viral transmission among Indigenous peoples in Canada.

High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis.

BACKGROUND AND AIMS: Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid-related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use. DESIGN: Data were drawn from two community-recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37-130). SETTING: Vancouver, Canada. PARTICIPANTS: This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV-negative participants, with no other significant differences. MEASUREMENTS: The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6-month period. Confounders assessed included: socio-demographic characteristics, substance use patterns and social-structural exposures. FINDINGS: In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41]. Our secondary analysis showed that compared with non-cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02-1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14). CONCLUSIONS: Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.

Intentional cannabis use to reduce crack cocaine use in a Canadian setting: A longitudinal analysis.

BACKGROUND: No effective pharmacotherapies exist for the treatment of crack cocaine use disorders. Emerging data suggests that cannabinoids may play a role in reducing cocaine-related craving symptoms. This study investigated the intentional use of cannabis to reduce crack use among people who use illicit drugs (PWUD). METHODS: Data were drawn from three prospective cohorts of PWUD in Vancouver, Canada. Using data from participants reporting intentional cannabis use to control crack use, we used generalized linear mixed-effects modeling to estimate the independent effect of three pre-defined intentional cannabis use periods (i.e., before, during and after first reported intentional use to reduce crack use) on frequency of crack use. RESULTS: Between 2012 and 2015, 122 participants reported using cannabis to reduce crack use, contributing a total of 620 observations. In adjusted analyses, compared to before periods, after periods were associated with reduced frequency of crack use (Adjusted Odds Ratio [AOR]=1.89, 95% Confidence Interval [CI]: 1.02-3.45), but not the intentional use periods (AOR=0.85, 95% CI: 0.51-1.41). Frequency of cannabis use in after periods was higher than in before periods (AOR=4.72, 95% CI: 2.47-8.99), and showed a tendency to lower frequency than in intentional cannabis use periods (AOR=0.56, 95% CI: 0.32-1.01). CONCLUSIONS: A period of intentional cannabis use to reduce crack use was associated with decreased frequency of crack use in subsequent periods among PWUD. Further clinical research to assess the potential of cannabinoids for the treatment of crack use disorders is warranted.

High-intensity cannabis use and HIV clinical outcomes among HIV-positive people who use illicit drugs in Vancouver, Canada.

BACKGROUND: Reforms to the legal status of medical and non-medical cannabis are underway in many jurisdictions, including Canada, as are renewed efforts to scale-up HIV treatment-as-prevention (TasP) initiatives. It has been suggested that high-intensity cannabis use may be associated with sub-optimal HIV treatment outcomes. Thus, using data from a setting with a community-wide treatment-as-prevention (TasP) initiative coinciding with increasing access to medical cannabis, we sought to investigate the possible impact of high-intensity cannabis use on HIV clinical outcomes. METHODS: Data was derived from the ACCESS study, a prospective cohort of HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. Cohort data was confidentially linked to comprehensive clinical profiles, including records of all antiretroviral therapy (ART) dispensations and longitudinal plasma HIV-1 RNA viral load (VL) monitoring. We used generalized estimating equations (GEEs) to estimate the longitudinal bivariable and multivariable relationships between at least daily cannabis use and two key clinical outcomes: overall engagement in ART care, and achieving a non-detectable VL among ART-exposed participants. RESULTS: Between December 2005 and June 2015, 874 HIV-positive PWUD (304 [35%] non-male) were included in this study. In total, 788 (90%) were engaged in HIV care at least once over the study period, of whom 670 (85%) achieved non-detectable VL at least once. In multivariable analyses, ≥ daily cannabis use did not predict lower odds of ART care (Adjusted Odds Ratio [AOR]: 1.02, 95% confidence interval [CI]: 0.77-1.36) or VL non-detectability among ART-exposed (AOR: 0.96, 95% CI: 0.75-1.21). Upon testing for potential interactions, ≥ daily cannabis use was found to be negatively associated with ART engagement during periods of binge alcohol use (p<0.05). CONCLUSION: With the exception of frequent cannabis use during periods of binge alcohol use, our results showed no statistically significant impact of daily cannabis use on the likelihood of ART care or VL non-detectability among ART-exposed HIV-positive PWUD. These findings are reassuring in light of the impending legalization of cannabis in Canada and ongoing efforts to expand TasP initiatives.

The impact of an HIV/AIDS adult integrated health program on leaving hospital against medical advice among HIV-positive people who use illicit drugs.

Background: Leaving hospital against medical advice (AMA) is a major source of avoidable morbidity, mortality and healthcare expenditure. The objective of this study was to assess the impact of an innovative HIV/AIDS adult integrated health program on leaving hospital AMA among HIV-positive people who use illicit drugs (PWUD). Methods: Using generalized estimating equations, we examined the relationship between being a participant of the Dr. Peter Centre (DPC), a specialty HIV/AIDS-focused adult integrated health program, and leaving hospital AMA among a cohort of HIV-positive PWUD patients. Results: Between July 2005 and July 2011, 181 HIV-positive PWUD who experienced ≥1 hospitalization were recruited into the study. Of the 406 hospital admissions among these individuals, 73 (39.9%) participants left the hospital AMA. In a multivariable model adjusted for confounders, being a participant of the DPC was independently associated with lower odds of leaving hospital AMA (adjusted odds ratio = 0.42; 95% confidence interval: 0.19-0.89). Conclusions: Our findings suggest that the provision of a broad range of clinical, harm reduction and support services through an innovative HIV/AIDS-focused adult integrated health program operating in proximity to a hospital may curb the rate at which individuals leave hospital prematurely.

The Impact of Enrolment in Methadone Maintenance Therapy on Initiation of Heavy Drinking among People Who Use Heroin.

BACKGROUND: There is equivocal evidence regarding whether people who use heroin substitute heroin for alcohol upon entry to methadone maintenance therapy (MMT). We aimed to examine the impact of MMT enrolment on the onset of heavy drinking among people who use heroin. METHODS: We derived data from prospective, community-based cohorts of people who inject drugs in Vancouver, Canada, between December 1, 2005, and May 31, 2014. Multivariable extended Cox regression analysis examined the effect of MMT enrolment on the onset of heavy drinking among people who used heroin at baseline. RESULTS: In total, 357 people who use heroin were included in this study. Of these, 208 (58%) enrolled in MMT at some point during follow-up, and 115 (32%) reported initiating heavy drinking during follow-up for an incidence density of 7.8 events (95% CI 6.4-9.5) per 100 person-years. The incidence density of heavy drinking was significantly lower among those enrolled in MMT at some point during follow-up compared to those who did not (4.6 vs. 16.2; p < 0.001). MMT enrolment was not significantly associated with time to initiate heavy drinking (adjusted relative hazard (ARH) 1.27; 95% CI 0.78-2.07) after adjustment for relevant demographic and substance-use characteristics. Age and cannabis use were the only variables that were independently associated with the time to onset of heavy drinking (ARH 0.74; 95% CI 0.58-0.94 and ARH 2.06; 95% CI 1.32-3.19, respectively). CONCLUSION: In this study, MMT enrolment did not predict heavy drinking and may even appear to decrease the initiation of heavy drinking. Our findings suggest younger age and cannabis use may predict heavy drinking. These findings could help inform on-going discussions about the effects of opioid agonist therapy on alcohol consumption among people who use heroin.

Prescribing medical cannabis in Canada: Are we being too cautious?

There has been much recent discussion and debate surrounding cannabis in Canada, including the prescribing of medical cannabis for therapeutic purposes. Certain commentators - including the Canadian Medical Association (CMA) - have denounced the prescribing of cannabis for medical purposes due to a perceived lack of evidence related to the drug's efficacy, harms, and mechanism of action. In this commentary, we present arguments in favour of prescribing medical cannabis in Canada. We believe the anti-cannabis position taken by CMA and other commentators is not entirely evidence-based. Using the example of neuropathic pain, we present and summarize the clinical evidence surrounding smoked or vapourized cannabis, including recent evidence pertaining to the effectiveness of cannabis in comparison to existing standard pharmacotherapies for neuropathy. Further, we outline how the concerns expressed regarding cannabis' mechanism of action are inconsistent with current decision-making processes related to the prescribing of many common pharmaceuticals. Finally, we discuss potential secondary public health benefits of prescribing cannabis for pain-related disorders in Canada and North America.

Pain Among High-Risk Patients on Methadone Maintenance Treatment.

The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches.

High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting.

Cannabis is increasingly prescribed clinically and utilized by people living with HIV/AIDS (PLWHA) to address symptoms of HIV disease and to manage side effects of antiretroviral therapy (ART). In light of concerns about the possibly deleterious effect of psychoactive drug use on adherence to ART, we sought to determine the relationship between high-intensity cannabis use and adherence to ART among a community-recruited cohort of HIV-positive illicit drug users. We used data from the ACCESS study, an ongoing prospective cohort study of HIV-seropositive illicit drug users linked to comprehensive ART dispensation records in a setting of universal no-cost HIV care. We estimated the relationship between at least daily cannabis use in the last 6 months, measured longitudinally, and the likelihood of optimal adherence to ART during the same period, using a multivariate linear mixed-effects model accounting for relevant socio-demographic, behavioral, clinical and structural factors. From May 2005 to May 2012, 523 HIV-positive illicit drug users were recruited and contributed 2,430 interviews. At baseline, 121 (23.1 %) participants reported at least daily cannabis use. In bivariate and multivariate analyses we did not observe an association between using cannabis at least daily and optimal adherence to prescribed HAART (Adjusted Odds Ratio = 1.12, 95 % Confidence Interval [95 % CI]: 0.76-1.64, p value = 0.555.) High-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.

Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor and small heterodimer partner in murine hepatic taurine metabolism.

AIM: Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms. METHODS: Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent pathways, we utilized GW4064 (FXR agonist), FGF19 or T-0901317 (liver X receptor [LXR] agonist) and Shp-/- mice. Tissue mRNA was determined by quantitative reverse transcription polymerase chain reaction. Amino acids were measured by high-performance liquid chromatography. RESULTS: Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA while those receiving cholestyramine exhibited increased mRNA. Activation of FXR suppressed CSAD mRNA expression whereas CSAD expression was increased in Shp-/- mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp-/- mice with a corresponding increase in serum taurine conjugated BA. FGF19 administration suppressed hepatic cholesterol 7-α-hydroxylase (CYP7A1) mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. CONCLUSION: BA regulate CSAD mRNA expression in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These findings implicate BA as regulators of CSAD mRNA via mechanisms shared with CYP7A1.

An integrated supervised injecting program within a care facility for HIV-positive individuals: a qualitative evaluation.

While there has been growing interest in comprehensive models of treatment and care for individuals living with HIV/AIDS, little attention has been given to the potential role that supervised injecting programs could play in increasing access to prevention and care services for HIV-positive injection drug users (IDU). We conducted 22 semi-structured interviews with HIV-positive IDU regarding a supervised injection program integrated in an HIV focused care facility known as the Dr. Peter Centre (DPC). We also interviewed seven staff members who supervise injections within the facility. All interviews were audio recorded, transcribed verbatim, and a thematic analysis was conducted. Participant and staff reports indicated that the integrated supervised injection program influenced IDUs' access to care by building more open and trusting relationships with staff, facilitating engagement in safer injection education and improving the management of injection-related infections. Participants and staff viewed the program as facilitating the delivery of care through mediating overdose risks, reducing the need to punitively manage drug use on-site and reducing the risks of encountering used syringes on the premises. For some participants, however, feelings of shame and fear of judgment in relation to their drug use limited initial uptake of the program. Our findings identify mechanisms through which integrated supervised injection programs may serve to better facilitate access and delivery of comprehensive care for HIV-positive IDU and highlight the benefits of addressing HIV-positive IDUs' drug use in the context of comprehensive models of healthcare.

Supervised injection sites: Health Canada approves Vancouver pilot sites, but concerns remain.

The paperwork has been processed, and Health Canada says that two pilot supervised injection sites (SISs) in Vancouver can now proceed, but operational funding for the site to be located in the Downtown Eastside has yet to be secured. Meanwhile, tired of waiting for the sanctioned SISs to open, community groups in Vancouver have begun to operate unsanctioned sites. There are also concerns that even if operational funding for the Downtown Eastside site is obtained, the pilot SIS project is too small in scope to make a major impact on public health in the area.