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1.  Crystal methamphetamine initiation among street-involved youth 
Background
Although many settings have recently documented a substantial increase in the use of methamphetamine-type stimulants, recent reviews have underscored the dearth of prospective studies that have examined risk factors associated with the initiation of crystal methamphetamine use.
Objectives
Our objectives were to examine rates and risk factors for the initiation of crystal methamphetamine use in a cohort of street-involved youth.
Methods
Street-involved youth in Vancouver, Canada, were enrolled in a prospective cohort known as the At-Risk Youth Study (ARYS). A total of 205 crystal methamphetamine-naïve participants were assessed semi-annually and Cox regression analyses were used to identify factors independently associated with the initiation of crystal methamphetamine use.
Results
Among 205 youth prospectively followed from 2005 to 2012, the incidence density of crystal methamphetamine initiation was 12.2 per 100 person years. In Cox regression analyses, initiation of crystal methamphetamine use was independently associated with previous crack cocaine use (adjusted relative hazard [ARH] = 2.24 [95% CI: 1.20–4.20]) and recent drug dealing (ARH = 1.98 [95% CI: 1.05–3.71]). Those initiating methamphetamine were also more likely to report a recent nonfatal overdose (ARH = 3.63 [95% CI: 1.65–7.98]) and to be male (ARH = 2.12 [95% CI: 1.06–4.25]).
Conclusions
We identified high rates of crystal methamphetamine initiation among this population. Males those involved in the drug trade, and those who used crack cocaine were more likely to initiate crystal methamphetamine use. Evidence-based strategies to prevent and treat crystal methamphetamine use are urgently needed.
doi:10.3109/00952990.2013.836531
PMCID: PMC3934747  PMID: 24191637
Crystal methamphetamine; social harm; youth
2.  EMPLOYMENT PREDICTS DECREASED MORTALITY AMONG HIV-SEROPOSITIVE ILLICIT DRUG USERS IN A SETTING OF UNIVERSAL HIV CARE 
Objective
Given the link between employment and mortality in the general population, we sought to assess this relationship among HIV-positive people who use illicit drugs in Vancouver, Canada.
Methods
Data were derived from a prospective cohort study of HIV seropositive people who use illicit drugs (n=666) during the period of May 1996–June 2010 linked to comprehensive clinical data in Vancouver, Canada, a setting where HIV care is delivered without charge. We estimated the relationship between employment and mortality using proportional hazards survival analysis, adjusting for relevant behavioural, clinical, social and socioeconomic factors.
Results
In a multivariate survival model, a time-updated measure of full time, temporary or self-employment compared with no employment was significantly associated with a lower risk of death (adjusted HR=0.44, 95% CI 0.22 to 0.91). Results were robust to adjustment for relevant confounders, including age, injection and non-injection drug use, plasma viral load and baseline CD4 T-cell count.
Conclusions
These findings suggest that employment may be an important dimension of mortality risk of HIV-seropositive illicit drug users. The potentially health-promoting impacts of labour market involvement warrant further exploration given the widespread barriers to employment and persistently elevated levels of preventable mortality among this highly marginalised population.
doi:10.1136/jech-2013-202918
PMCID: PMC4060796  PMID: 24153247
3.  The Effect of History of Injection Drug Use and Alcoholism on HIV Disease Progression 
AIDS care  2013;26(1):10.1080/09540121.2013.804900.
The effectiveness of highly active antiretroviral therapy (HAART) in preventing disease progression can be negatively influenced by the high prevalence of substance use among patients. Here, we quantify the effect of history of injection drug use and alcoholism on virologic and immunologic response to HAART. Clinical and survey data, collected at the start of HAART and at the interview date, were based on the study Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) in British Columbia, Canada. Substance use was a three-level categorical variable, combining information on history of alcohol dependence and of injection drug use, defined as: no history of alcohol and injection drug use, history of alcohol or injection drug use and history of both alcohol and injection drug use. Virologic response (pVL) was defined by ≥2 log10 copy/mL drop in viral load. Immunologic response was defined as an increase in CD4 cell count percent of ≥100%. We used cumulative logit modeling for ordinal responses to address our objective. Of the 537 HIV-infected patients, 112 (21%) were characterized as having history of both alcohol and injection drug use, 173 (32%) were non adherent (<95%), 196 (36%) had CD4+/pVL+ (Best) response, 180 (34%) a CD4+/pVL− or a CD4−/pVL+ (Incomplete) response, and 161 (30%) a CD4−/pVL− (Worst) response. For individuals with history of both alcohol and injection drug use, the estimated probability of of Best, Incomplete and Worse responses, respectively. Screening and detection of substance dependence will identify individuals at high-risk for non-adherence and ideally prevent their HIV disease from progressing to advanced stages where HIV disease can become difficult to manage.
doi:10.1080/09540121.2013.804900
PMCID: PMC3795995  PMID: 23767757
Alcohol; Injection drug use; Adherence; HAART; HIV; Disease progression
4.  Risk Factors for Progression to Regular Injection Drug Use among Street-Involved Youth in a Canadian Setting 
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.07.008.
Background
Street-involved youth are at high risk for experimenting with injection drug use; however, little attention has been given to identifying the factors that predict progression to on-going injecting.
Methods
Logistic regression was used to identify factors associated with progression to injecting weekly on a regular basis among a Canadian cohort of street-involved youth.
Results
Among our sample of 405 youth who had initiated injecting at baseline or during study observation, the median age was 22 years (interquartile range [IQR] = 21 – 24), and 72% (293) reported becoming a regular injector at some point after their first injection experience. Of these, the majority (n=186, 63%) reported doing so within a month of initiating injection drug use. In multivariate analysis, the drug used at the first injection initiation event (opiates vs. cocaine vs. methamphetamine vs. other; all p > 0.05) was not associated with progression; however, younger age at first injection (adjusted odds ratio [AOR] =1.13), a history of childhood physical abuse (AOR =1.81), prior regular use of the drug first injected (AOR =1.77), and having a sexual partner present at the first injection event (AOR =2.65) independently predicted progression to regular injecting.
Conclusion
These data highlight how quickly youth progress to become regular injectors after experimentation. Findings indicate that addressing childhood trauma and interventions such as evidence-based youth focused addiction treatment that could prevent or delay regular non-injection drug use, may reduce progression to regular injection drug use among this population.
doi:10.1016/j.drugalcdep.2013.07.008
PMCID: PMC3818386  PMID: 23910434
injection drug use; injection initiation; street-involved youth; injection prevention; physical abuse
5.  Predictors of liver-related death among people who inject drugs in Vancouver, Canada: a 15-year prospective cohort study 
Introduction
While HIV/AIDS remains an important cause of death among people who inject drugs (PWID), the potential mortality burden attributable to hepatitis C virus (HCV) infection among this population is of increasing concern. Therefore, we sought to identify trends in and predictors of liver-related mortality among PWID.
Methods
Data were derived from prospective cohorts of PWID in Vancouver, Canada, between 1996 and 2011. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. Multivariate Cox proportional hazards regression was used to examine the relationship between HCV infection and time to liver-related death. A sub-analysis examined the effect of HIV/HCV co-infection.
Results and discussion
In total, 2,279 PWID participated in this study, with 1,921 (84.3%) having seroconverted to anti-HCV prior to baseline assessments and 124 (5.4%) during follow-up. The liver-related mortality rate was 2.1 (95% confidence interval [CI]: 1.5–3.0) deaths per 1,000 person-years and was stable over time. In multivariate analyses, HCV seropositivity was not significantly associated with liver-related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15–1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27–5.63). In sub-analysis, HIV/HCV co-infection had a 2.53 (95% CI: 1.18–5.46) times hazard of liver-related death compared with HCV mono-infection.
Conclusions
In this study, HCV seropositivity did not predict liver-related mortality while HIV seropositivity did. The findings highlight the critical role of HIV mono- and co-infection rather than HCV infection in contributing to liver-related mortality among PWID in this setting.
doi:10.7448/IAS.17.1.19296
PMCID: PMC4228046  PMID: 25391765
injection drug use; hepatitis C virus infection; mortality; Canada
6.  The impact of drug use patterns on mortality among polysubstance users in a Canadian setting: a prospective cohort study 
BMC Public Health  2014;14(1):1153.
Background
Illicit drug use is a well-established risk factor for morbidity and mortality. However, few studies have examined the impact of different drug use patterns on mortality among polysubstance using populations. This study aimed to identify drug-specific patterns of mortality among a cohort of polysubstance using persons who inject drugs (PWIDs).
Methods
PWIDs in Vancouver, Canada were prospectively followed between May 1996 and December 2011. Participants were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to investigate the relationships between drug use patterns (daily alcohol use, heroin injection and non-injection use, cocaine injection, amphetamine injection and non-injection use, crack smoking and speedball injecting) and time to all-cause mortality.
Results
2330 individuals were followed for a median of 61 months (inter-quartile range: 33 – 112). In total, 466 (19.1%) individuals died for an incidence density of 3.1 (95% confidence interval [CI]: 2.8 – 3.4) deaths per 100 person-years. In multivariate analyses, after adjusting for HIV infection and other potential confounders, only daily cocaine injection remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.36, 95% CI: 1.06 – 1.76).
Conclusions
Although heroin injecting is traditionally viewed as carrying the highest risk of mortality, in this setting, only daily cocaine injecting was associated with all-cause mortality. These findings highlight the urgent need to identify novel treatments and harm reduction strategies for cocaine injectors.
doi:10.1186/1471-2458-14-1153
PMCID: PMC4246520  PMID: 25377274
Mortality; Injection drug use; Cocaine; Vancouver; Cohort study
7.  Self-management of pain among people who inject drugs in Vancouver 
Pain management  2014;4(1):27-35.
SUMMARY
Aims
To evaluate factors and methods associated with self-management of pain among people who inject drugs (IDUs) in Vancouver (Canada).
Patients & methods
This cross-sectional study used bivariate statistics and multivariate logistic regression to analyze self-reported responses among 483 IDUs reporting moderate-to-extreme pain in two prospective cohort studies from 1 December 2012 to 31 May 2013.
Results
Median age was 49.6 years (interquartile range: 43.9–54.6 years), 33.1% of IDUs were female and 97.5% reported self-management of pain. Variables independently and positively associated with self-managed pain included having been refused a prescription for pain medication (adjusted odds ratio: 7.83; 95% CI: 1.64–37.3) and having ever been homeless (adjusted odds ratio: 3.70; 95% CI: 1.00–13.7). Common methods of self-management of pain included injecting heroin (52.7%) and obtaining diverted prescription pain medication from the street (65.0%).
Conclusion
Self-management of pain was common among IDUs who reported moderate-to-extreme pain in this setting, particularly among those who had been refused a prescription for pain medication and those who had ever been homeless. These data highlight the challenges of adequate pain management among IDUs.
doi:10.2217/pmt.13.62
PMCID: PMC3962749  PMID: 24641341
8.  Self-reported changes in drug use behaviors and syringe disposal methods following the opening of a supervised injecting facility in Copenhagen, Denmark 
Harm Reduction Journal  2014;11(1):29.
Background
In Denmark, the first standalone supervised injecting facility (SIF) opened in Copenhagen’s Vesterbro neighborhood on October 1, 2012. The purpose of this study was to assess whether use of services provided by the recently opened SIF was associated with changes in injecting behavior and syringe disposal practices among people who inject drugs (PWID). We hypothesized that risk behaviors (e.g., syringe sharing), and unsafe syringe disposal (e.g., dropping used equipment on the ground) had decreased among PWID utilizing the SIF.
Methods
Between February and August of 2013, we conducted interviews using a survey (in English and Danish) with forty-one people who reported injecting drugs at the SIF. We used descriptive statistics and McNemar’s test to examine sociodemographic characteristics of the sample, current drugs used, sites of syringe disposal before and after opening of the SIF, and perceived behavior change since using the SIF.
Results
Of the interviewed participants, 90.2% were male and the majority were younger than 40 years old (60.9%). Three-quarters (75.6%) of participants reported reductions in injection risk behaviors since the opening of the SIF, such as injecting in a less rushed manner (63.4%), fewer outdoor injections (56.1%), no longer syringe sharing (53.7%), and cleaning injecting site(s) more often (43.9%). Approximately two-thirds (65.9%) of participants did not feel that their frequency of injecting had changed; five participants (12.2%) reported a decrease in injecting frequency, and only two participants (4.9%) reported an increase in injecting frequency. Twenty-four (58.5%) individuals reported changing their syringe disposal practices since the opening of the SIF; of those, twenty-three (95.8%) reported changing from not always disposing safely to always disposing safely (McNemar’s test p-value < 0.001).
Conclusions
Our findings suggest that use of the Copenhagen SIF is associated with adoption of safer behaviors that reduce harm and promote health among PWID, as well as practices that benefit the Vesterbro neighborhood (i.e., safer syringe disposal). As a public health intervention, Copenhagen’s SIF has successfully reached PWID engaging in risk behavior. To fully characterize the impacts of this and other Danish SIFs, further research should replicate this study with a larger sample size and prospective follow-up.
doi:10.1186/1477-7517-11-29
PMCID: PMC4226898  PMID: 25352296
Supervised injecting facility; Drug consumption room; People who inject drugs; Injection drug users; Harm reduction; Risk behaviors; Syringe disposal; Denmark
10.  The role of depression and social support in non-fatal drug overdose among a cohort of injection drug users in a Canadian setting 
Drug and alcohol dependence  2013;132(3):603-609.
Objectives
Non-fatal overdose remains a significant source of morbidity among people who inject drugs (IDU). Although depression and social support are important in shaping the health of IDU, little is known about the relationship between these factors and overdose. Therefore, we sought to determine whether depressive symptoms and social support predicted non-fatal overdose among IDU in a Canadian setting.
Methods
Data were derived from three prospective cohorts of people who use drugs: the Vancouver Injection Drug Users Study (VIDUS), the ACCESS Cohort, and the At-Risk Youth Study (ARYS). Multilevel modeling was used to determine if depression and social support were significant predictors of non-fatal overdose across time. Analyses were stratified by sex.
Results
There were 1,931 participants included in this analysis, including 653 (33.8%) females and 69 (3.6%) youth 20 years old or younger. Depressed men (Adjusted odds ratio [AOR] =1.53, 95% confidence intervals [CI] =1.25, 1.87) and women (Adjusted odds ratio [AOR] =2.23, 95% confidence intervals [CI] =1.65, 3.00) were more likely to experience a non-fatal overdose. Further, among women, those who reported having 3 or more persons they could rely upon for social support were less likely to experience a non-fatal overdose (AOR=0.54, 95% 0.31, 0.93).
Conclusion
Although depression was a significant predictor of non-fatal drug overdose, social support was a significant predictor among women only. Possible strategies to prevent non-fatal overdose may include identifying IDU experiencing severe depressive symptoms and providing targeted mental health treatments and mobilizing interpersonal social support among IDU, especially among women.
doi:10.1016/j.drugalcdep.2013.04.007
PMCID: PMC3770831  PMID: 23647731
Depression; social epidemiology; substance use; longitudinal data analysis; social support
11.  Neighborhood of residence and risk of initiation into injection drug use among street-involved youth in a Canadian setting 
Drug and alcohol dependence  2013;132(3):486-490.
Background
While research has suggested that exposure to environments where drug use is prevalent may be a key determinant of drug-related risk, little is known regarding the impact of such exposure on the initiation of illicit injection drug use. We assessed whether neighborhood of residence predicted rates of injecting initiation among a cohort of street-involved youth in Vancouver, British Columbia.
Methods
We followed street-involved injecting naïve youth aged 14–26 and compared rates of injecting initiation between youth residing in Vancouver’s Downtown Eastside (DTES) neighborhood (the site of a large street-based illicit drug market) to those living in other parts of the city. Univariate and multivariate Cox regression analyses were employed to determine whether residence in the DTES was independently associated with increased risk of initiation of injection drug use.
Results
Between September, 2005 and November, 2011, 422 injection-naïve individuals were followed, among whom 77 initiated injecting for an incidence density of injecting of 10.3 (95% Confidence Interval [CI] 5.0–18.8) per 100 person years. In a multivariate model, residence in the DTES was independently associated with initiating injection drug use (Adjusted Hazard Ratio [AHR] = 2.16, 95% CI: 1.33 – 3.52, p = 0.002).
Conclusions
These results suggest neighborhood of residence affects the risk of initiation into injection drug use among street-involved youth. The development of prevention interventions should target high-risk neighborhoods where risk of initiating into injecting drug use may be greatest.
doi:10.1016/j.drugalcdep.2013.03.011
PMCID: PMC3927649  PMID: 23587537
initiation; injection drug use; HIV; street-involved youth; At Risk Youth Study; ARYS; Vancouver; Downtown Eastside
12.  PATTERNS OF INJECTION DRUG USE CESSATION DURING AN EXPANSION OF SYRINGE EXCHANGE SERVICES IN A CANADIAN SETTING 
Drug and alcohol dependence  2013;132(3):535-540.
Background
Needle and syringe programmes (NSPs) have been shown to reduce HIV risk among people who inject drugs (IDU). However, concerns remain that NSPs delay injecting cessation.
Methods
Individuals reporting injection drug use in the past six months in the greater Vancouver area were enrolled in the Vancouver Injection Drug Users Study (VIDUS). Annual estimates of the proportion of IDU reporting injecting cessation were generated. Generalized estimating equation (GEE) analysis was used to assess factors associated with injecting cessation during a period of NSP expansion.
Results
Between May 1996 and December 2010, the number of NSP sites in Vancouver increased from 1 to 29 (P < 0.001). The estimated proportion of participants (n = 2,710) reporting cessation increased from 2.4% (95% Confidence Interval [CI]: 0.0% – 7.0%) in 1996 to 47.9% (95% CI: 46.8% – 48.9%) in 2010 (P < 0.001). In a multivariate GEE analysis, the authors observed an association between increasing calendar year and increased likelihood of injecting cessation (Adjusted Odds Ratio = 1.17, 95% CI: 1.15, 1.19, P < 0.001).
Conclusion
The proportion of IDU reporting injecting cessation increased during a period of NSP expansion, implying that increased NSP availability did not delay injection cessation. These results should help inform community decisions on whether to implement NSPs.
doi:10.1016/j.drugalcdep.2013.03.024
PMCID: PMC3762907  PMID: 23642315
injection drug use; cessation; needle exchange programme; Vancouver
13.  Factors associated with healthcare avoidance among transgender women in Argentina 
Introduction
Transgender (TG) women in many settings continue to contend with barriers to healthcare, including experiences of stigma and discrimination. Argentina has a universal health care system and laws designed to promote healthcare access among TG women. However, little is known about barriers to healthcare access among TG women in this setting. The aim of this study was to explore individual, social-structural and environmental factors associated with healthcare avoidance among TG women in Argentina.
Methods
Data were derived from a 2013 nation-wide, cross-sectional study involving TG women in Argentina. We assessed the prevalence and factors associated with avoiding healthcare using multivariable logistic regression.
Results
Among 452 TG women included in the study, 184 (40.7%) reported that they avoided seeking healthcare because of their transgender identity. In multivariable analysis, factors positively associated with avoiding seeking healthcare were: having been exposed to police violence (adjusted odd ratio [aOR] = 2.20; 95% CI: 1.26 – 3.83), internalized stigma (aOR = 1.60, 95% CI: 1.02–2.51), having experienced discrimination by healthcare workers (aOR = 3.36: 95% CI: 1.25 – 5.70) or patients (aOR = 2.57; 95% CI: 1.58 – 4.17), and currently living in the Buenos Aires metropolitan area (aOR = 2.32; 95% CI: 1.44 – 3.76). In contrast, TG women with extended health insurance were less likely to report avoiding healthcare (aOR = 0.49; 95% CI: 0.26 – 0.93).
Conclusions
A high proportion of TG women in our sample reported avoiding healthcare. Avoiding healthcare was associated with stigma and discrimination in healthcare settings, as well as police violence experiences. Although further research is warranted, these finding suggests that socio-structural interventions tailored TG women needs are needed to improve access to healthcare among this population.
doi:10.1186/s12939-014-0081-7
PMCID: PMC4220051  PMID: 25261275
Transgender women; Argentina; Healthcare access; Police violence; Discrimination; Stigma
14.  TRANSITIONS INTO AND OUT OF HOMELESSNESS AMONG STREET-INVOLVED YOUTH IN A CANADIAN SETTING 
Health & place  2013;23:122-127.
The impact of transitions in housing status among street youth have not been well explored. This study uses a generalized linear mixed effects model to identify factors associated with transitions into and out of homelessness among a prospective cohort of 685 drug-using street-involved youth aged 14–26. In multivariate analysis, high intensity substance use, difficulty accessing addiction treatment, incarceration, sex work, and difficulty accessing housing (all p < 0.05) either significantly facilitated or hindered housing transitions. Findings highlight the importance of external structural factors in shaping youth’s housing status and point to opportunities to improve the housing stability of vulnerable youth.
doi:10.1016/j.healthplace.2013.06.003
PMCID: PMC3758414  PMID: 23838565
Homelessness; drug use; street-youth; addiction treatment; risk behavior; incarceration
15.  Injection drug users’ involvement in drug dealing in the downtown eastside of Vancouver: Social organization and systemic violence 
Background
Illicit drug markets are a key component of the risk environment surrounding injection drug use. However, relatively few studies have explored how injection drug users’ (IDUs) involvement in drug dealing shapes their experiences of drug market-related harm. This exploratory qualitative study aims to understand IDUs’ dealing activities and roles, as well as the perceived benefits and risks related to participation in illicit drug markets, including experiences of drug market violence.
Methods
Ten IDUs with extensive involvement in drug dealing activities were recruited from the Vancouver Injection Drug User Study (VIDUS) and participated in semi-structured qualitative interviews, which elicited discussion of experiences dealing drugs, perceived benefits and hazards related to dealing, and understandings of drug market violence.
Results
Participant's involvement in drug market activities included corporate sales, freelance or independent sales, and opportunistic sales termed “middling” as well as drug market-related hustles entailing selling bogus drugs and robbing dealers. Participants primarily dealt drugs to support their own illicit drug use, and we found that arrest and criminal justice involvement, hazards stemming from drug debts, and drug market-related violence were key risks related to dealing activities.
Conclusion
The challenges of managing personal consumption while selling drugs exacerbates the hazards associated with drug dealing. Efforts to address drug dealing among IDUs should consider both drug dependency and the material conditions that propel drug users towards dealing activities. Interventions should explore the potential of combining enhanced drug treatment programs with low threshold employment and alternative income generation opportunities.
doi:10.1016/j.drugpo.2013.03.006
PMCID: PMC3911907  PMID: 23664788
injection drug use; drug dealing; risk environment; violence
16.  Towards Full Citizenship: Correlates of Engagement with the Gender Identity Law among Transwomen in Argentina 
PLoS ONE  2014;9(8):e105402.
Introduction
In May 2012, Argentina passed its “Gender Identity” Law, which aimed to address the legal invisibility, discrimination and marginalization that transgender individuals have historically faced. The aim of this study was to explore factors associated with engagement with the Gender Identity Law among transwomen living in Argentina.
Methods
Data were derived from a 2013 nationwide, cross-sectional study involving transwomen in Argentina. Using multivariate logistic regression, we assessed the prevalence and factors associated with acquiring a gender-congruent identity card within the first 18 months of enactment of the Gender Identity Law.
Results
Among 452 transwomen, 260 (57.5%) reported that they had obtained a new gender-congruent identity card. In multivariate analysis, factors positively associated with acquiring a new ID were: previously experiencing discrimination by healthcare workers (adjusted odd ratio [aOR] = 2.01, 95% CI: 1.27–3.20); having engaged in transition procedures (aOR = 3.06, 95% CI: 1.58–5.93); and having a job other than sex work (aOR = 1.81, 95% CI: 1.06–3.10). Foreign born transwomen were less likely to have obtained a new ID (aOR = 0.14, 95% CI: 0.06–0.33).
Conclusions
More than half of transwomen in our sample acquired a new gender-congruent ID within the first 18 months of enactment of the Gender Identity Law. However, access to and uptake of this right has been heterogeneous. In particular, our findings suggest that the most empowered transwomen may have been among the first to take advantage of this right. Although educational level, housing conditions, HIV status and sex work were not associated with the outcome, foreign-born status was a strong negative correlate of new ID acquisition. Therefore, additional efforts should be made in order to ensure that benefits of this founding policy reach all transwomen in Argentina.
doi:10.1371/journal.pone.0105402
PMCID: PMC4136870  PMID: 25133547
17.  IDO1 Metabolites Activate β-catenin Signaling to Promote Cancer Cell Proliferation and Colon Tumorigenesis in Mice 
Gastroenterology  2013;145(2):416-425.e4.
BACKGROUND & AIMS
Indoleamine 2,3 dioxygenase-1 (IDO1) catabolizes tryptophan along the kynurenine pathway. Though IDO1 is expressed in inflamed and neoplastic epithelial cells of the colon, its role in colon tumorigenesis is not well understood. We used genetic and pharmacologic approaches to manipulate IDO1 activity in mice with colitis-associated cancer and human colon cancer cell lines.
METHODS
C57Bl6 wild type (control), IDO1−/−, Rag1−/−, Rag1/IDO1 double knockout mice were exposed to azoxymethane and dextran sodium sulfate (DSS) to induce colitis and tumorigenesis. Colitis severity was assessed by measurements of disease activity, cytokine levels and histologic analysis. In vitro experiments were conducted using HCT116 and HT29 human colon cancer cells. 1-methyl tryptophan and small interfering RNA were used to inhibit IDO1. Kynurenine pathway metabolites were used to simulate IDO1 activity.
RESULTS
C57Bl6 mice given pharmacologic inhibitors of IDO1 and IDO1−/− mice had lower tumor burdens and reduced proliferation in the neoplastic epithelium following administration of DSS and azoxymethane than control mice. These reductions were also observed in Rag1/IDO1 double knockout mice compared to Rag1−/− mice (which lack mature adaptive immunity). In human colon cancer cells, blockade of IDO1 activity reduced nuclear and activated β-catenin, transcription of its target genes (cyclin D1 and Axin2), and ultimately proliferation. Exogenous administration of IDO1 pathway metabolites kynurenine and quinolinic acid led to activation of β-catenin and proliferation of human colon cancer cells, and increased tumor growth in mice.
CONCLUSIONS
IDO1, which catabolizes tryptophan, promotes colitis-associated tumorigenesis in mice, independent of its ability to limit T-cell mediated immune surveillance. The epithelial cell-autonomous survival advantage provided by IDO1 to colon epithelial cells indicate its potential as a therapeutic target.
doi:10.1053/j.gastro.2013.05.002
PMCID: PMC3722304  PMID: 23669411
mouse model; metabolism; ulcerative colitis; IBD
18.  Prescription opioid injection and risk of hepatitis C in relation to traditional drugs of misuse in a prospective cohort of street youth 
BMJ Open  2014;4(7):e005419.
Objective
Despite dramatic increases in the misuse of prescription opioids, the extent to which their intravenous injection places drug users at risk of acquiring hepatitis C virus (HCV) remains unclear. We sought to compare risk of HCV acquisition from injection of prescription opioids to that from other street drugs among high-risk street youth.
Design
Prospective cohort study.
Setting
Vancouver, British Columbia, Canada from September 2005 to November 2011.
Participants
The At-Risk Youth Study (ARYS) is a prospective cohort of drug-using adolescents and young adults aged 14–26 years. Participants were recruited through street-based outreach and snowball sampling.
Primary outcome measure
HCV antibody seroconversion, measured every 6 months during follow-up. Risk for seroconversion from injection of prescription opioids was compared with injection of other street drugs of misuse, including heroin, cocaine or crystal methamphetamine, using Cox proportional hazards regression controlling for age, gender and syringe sharing.
Results
Baseline HCV seropositivity was 10.6%. Among 512 HCV-seronegative youth contributing 860.2 person-years of follow-up, 56 (10.9%) seroconverted, resulting in an incidence density of 6.5/100 person-years. In bivariate analyses, prescription opioid injection (HR=3.48; 95% CI 1.57 to 7.70) predicted HCV seroconversion. However, in multivariate modelling, only injection of heroin (adjusted HR=4.56; 95% CI 2.39 to 8.70), cocaine (adjusted HR=1.88; 95% CI 1.00 to 3.54) and crystal methamphetamine (adjusted HR=2.91; 95% CI 1.57 to 5.38) remained independently associated with HCV seroconversion, whereas injection of prescription opioids did not (adjusted HR=0.94; 95% CI 0.40 to 2.21).
Conclusions
Although misuse of prescription opioids is on the rise, traditional street drugs still posed the greatest threat of HCV transmission in this setting. Nonetheless, the high prevalence and incidence of HCV among Canadian street youth underscore the need for evidence-based drug prevention, treatment and harm reduction interventions targeting this vulnerable population.
doi:10.1136/bmjopen-2014-005419
PMCID: PMC4120401  PMID: 25052173
INFECTIOUS DISEASES
19.  Increased hepatitis C virus vaccine clinical trial literacy following a brief intervention among people who inject drugs 
Drug and alcohol review  2012;32(4):419-425.
Background and Aims
While people who inject drugs are at high risk of hepatitis C virus (HCV) infection and will be the target population for future HCV vaccine trials, little is known about clinical trial literacy (CTL) in this group. We assessed the impact of a brief intervention (BI) designed to improve HCV vaccine CTL among people who inject drugs in Sydney, Australia.
Design and Methods
People who inject drugs enrolled in a community-based prospective observational study between November 2008 and September 2010 (n = 102) completed a CTL assessment followed immediately by the BI. Post-test assessment was conducted at 24 weeks.
Results
The median age of the sample was 27 years, 73% were male and 60% had 10 or less years of schooling. The median time since first injection was five years and 20% reported daily or more frequent injecting. The mean number of correct responses increased from 5.3 to 6.3/10 (t = −.4.2; 101df, P < 0.001) 24 weeks post-intervention. Statistically significant differences were observed for three knowledge items with higher proportions of participants correctly answering questions related to randomisation (P = 0.002), blinding (P = 0.005) and vaccine-induced seropositivity (P = 0.003) post-intervention.
Discussion and Conclusions
A significant increase in HCV vaccine CTL was observed, suggesting that new and relatively novel concepts can be learned and recalled in this group. These findings support the feasibility of future trials among this population.
doi:10.1111/dar.12000
PMCID: PMC3567229  PMID: 23113829
hepatitis C virus; injecting drug use; clinical trial literacy; brief intervention; vaccine preparedness study
20.  ‘It’s more about the heroin’: Injection drug users’ response to an overdose warning campaign in a Canadian setting 
Addiction (Abingdon, England)  2013;108(7):1270-1276.
Aims
To assess heroin injectors’ perceptions of and responses to a warning issued by public health officials regarding high-potency heroin and increases in fatal overdoses.
Design
Semi-structured qualitative interviews
Setting
Vancouver, Canada.
Participants
Eighteen active heroin injectors
Measurements
Semi-structured interview guide focussing on heroin injectors’ perceptions of and responses to the overdose warning, including reasons for failing to adhere to risk reduction recommendations.
Findings
Although nearly all participants were aware of the warning, their recollections of the message and the timing of its release were obscured by on-going social interactions within the drug scene focussed on heroin quality. Many injection drug users reported seeking the high potency heroin and nearly all reported no change in overdose risk behaviours. Responses to the warning were shaped by various social, economic and structural forces that interacted with individual behaviour and undermined efforts to promote behavioural change, including sales tactics employed by dealers, poverty, the high cost and shifting quality of available heroin, and risks associated with income-generating activities. Individual-level factors, including emotional suffering, withdrawal, entrenched injecting routines, perceived invincibility and the desire for intense intoxication also undermined risk reduction messages.
Conclusions
Among heroin injectors in British Columbia, a 2011 overdose warning campaign appeared to be of limited effectiveness and also produced unintended negative consequences that exacerbated overdose risk.
doi:10.1111/add.12151
PMCID: PMC3913056  PMID: 23551565
heroin; injection drug use; overdose; public health warning
21.  Did Somebody Say Community? Young People’s Critiques of Conventional Community Narratives in the Context of a Local Drug Scene 
Human organization  2013;72(2):98-110.
The language of community is ubiquitous in academic, public health, and policy discourse about drug using populations. Yet, it has been argued that in some settings, the parameters of “the drug user community” are far from self-evident. We undertook this ethnographic investigation to explore experiences and understandings of a “drug user community” (sometimes referred to more specifically as a “street youth community”) among young people entrenched in Vancouver’s inner city drug scene. Our findings revealed that in this context, conventional notions of community—that is, a social network characterized by commonality, mutual responsibility, solidarity, and/or stability—resonated with some youth. However, most questioned the value of membership within this community, in which what they had in common with other youth were ongoing experiences of poverty, marginalization, and social exclusion. Many felt membership in the drug user community precluded their ability to be responsible and productive citizens within the wider community of “mainstream society.” Experiences of resource deprivation and everyday violence on the streets led many participants to emphasize the limited possibilities for community among their peers. We argue that it is important to critically examine heretofore essentializing assumptions about the nature of inner city drug user or street youth communities in order to better understand young people’s needs and desires in these settings.
PMCID: PMC3947898  PMID: 24634540
drug scene; drug use; street youth; community; violence
22.  Declining Incidence of Hepatitis C Virus Infection among People Who Inject Drugs in a Canadian Setting, 1996-2012 
PLoS ONE  2014;9(6):e97726.
Background
People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection. Trends in HCV incidence and associated risk factors among PWID recruited between 1996 and 2012 in Vancouver, Canada were evaluated.
Methods
Data were derived from a long-term cohort of PWID in Vancouver. Trends in HCV incidence were evaluated. Factors associated with time to HCV infection were assessed using Cox proportional hazards regression.
Results
Among 2,589, 82% (n = 2,121) were HCV antibody-positive at enrollment. Among 364 HCV antibody-negative participants with recent (last 30 days) injecting at enrollment, 126 HCV seroconversions were observed [Overall HCV incidence density: 8.6 cases/100 person-years (py); 95% confidence interval (95% CI): 7.2, 10.1; HCV incidence density among those with injecting during follow-up: 11.5 cases/100 py; 95% CI 9.7, 13.6]. The overall HCV incidence density declined significantly from 25.0/100 py (95% CI: 20.2, 30.3) in 1996–99, as compared to 6.0/100 py (95% CI: 4.1, 8.5) in 2000–2005, and 3.1/100 py (95% CI: 2.0, 4.8) in 2006–2012. Among those with injecting during follow-up, the overall HCV incidence density declined significantly from 27.9/100 py (95% CI: 22.6, 33.6) in 1996–99, as compared to 7.5/100 py (95% CI: 5.1, 10.6) in 2000–2005, and 4.9/100 py (95% CI: 3.1, 7.4) in 2006–2012. Unstable housing, HIV infection, and injecting of cocaine, heroin and methamphetamine were independently associated with HCV seroconversion.
Conclusions
HCV incidence has dramatically declined among PWID in this setting. However, improved public health strategies to prevent and treat HCV are urgently required to reduce HCV-associated morbidity and mortality.
doi:10.1371/journal.pone.0097726
PMCID: PMC4045728  PMID: 24897109
23.  A Mixed Methods Approach to Exploring the Relationship between Norway Rat (Rattus norvegicus) Abundance and Features of the Urban Environment in an Inner-City Neighborhood of Vancouver, Canada 
PLoS ONE  2014;9(5):e97776.
Urban rats (Rattus spp.) are among the most ubiquitous pest species in the world. Previous research has shown that rat abundance is largely determined by features of the environment; however, the specific urban environmental factors that influence rat population density within cities have yet to be clearly identified. Additionally, there are no well described tools or methodologies for conducting an in-depth evaluation of the relationship between urban rat abundance and the environment. In this study, we developed a systematic environmental observation tool using methods borrowed from the field of systematic social observation. This tool, which employed a combination of quantitative and qualitative methodologies, was then used to identify environmental factors associated with the relative abundance of Norway rats (Rattus norvegicus) in an inner-city neighborhood of Vancouver, Canada. Using a multivariate zero-inflated negative binomial model, we found that a variety of factors, including specific land use, building condition, and amount of refuse, were related to rat presence and abundance. Qualitative data largely supported and further clarified observed statistical relationships, but also identified conflicting and unique situations not easily captured through quantitative methods. Overall, the tool helped us to better understand the relationship between features of the urban environment and relative rat abundance within our study area and may useful for studying environmental determinants of zoonotic disease prevalence/distribution among urban rat populations in the future.
doi:10.1371/journal.pone.0097776
PMCID: PMC4022650  PMID: 24830847
24.  Loss of Nuclear Receptor SHP Impairs but Does Not Eliminate Negative Feedback Regulation of Bile Acid Synthesis 
Developmental cell  2002;2(6):713-720.
Summary
The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.
PMCID: PMC4010195  PMID: 12062084
25.  Increases and decreases in drug use attributed to housing status among street-involved youth in a Canadian setting 
Background
Among a cohort of drug-using street-involved youth, we sought to identify the prevalence of reporting increases and decreases in illicit drug use due to their current housing status and to identify factors associated with reporting these changes.
Findings
This longitudinal study was based on data collected between June 2008 and May 2012 from a prospective cohort of street-involved youth aged 14–26 in Vancouver, Canada. At semi-annual study follow-up visits, youth were asked if their drug use was affected by their housing status. Using generalized estimating equations, we identified factors associated with perceived increases and decreases in drug use attributed to housing status. Among our sample of 536 participants at baseline, 164 (31%) youth reported increasing their drug use due to their housing situation and 71 (13%) reported decreasing their drug use. In multivariate analysis, factors that were positively associated with perceived increases in drug use attributed to housing status included the following: being homeless, engaging in sex work and drug dealing. Regular employment was negatively associated with increasing drug use due to housing status. Among those who reported decreasing their drug use, only homelessness was significant in bivariate analysis.
Conclusion
Perceived changes in drug use due to housing status were relatively common in this setting and were associated with being homeless and, among those who increased their drug use, engaging in risky income generation activities. These findings suggest that structural factors, particularly housing and economic opportunities, may be crucial interventions for reducing or limiting drug use among street-involved youth.
doi:10.1186/1477-7517-11-12
PMCID: PMC3999483  PMID: 24721725
Homelessness; Drug use; Street-involved youth; Stable housing; Risk behaviour; Employment

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