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1.  A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases 
PLoS Pathogens  2015;11(5):e1004899.
During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6), a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3’ untranslated region (UTR) that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Here, we pursued how this protective RNA element functions to maintain mRNA stability. Using affinity purification and mass spectrometry, we identified a set of proteins that associate specifically with the protective element. Although multiple proteins contributed to the escape mechanism, depletion of nucleolin (NCL) most severely impacted protection. NCL was re-localized out of the nucleolus during lytic KSHV infection, and its presence in the cytoplasm was required for protection. After loading onto the IL-6 3’ UTR, NCL differentially bound to the translation initiation factor eIF4H. Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the RNA, suggesting that interactions between proteins bound to distant regions of the mRNA are important for escape. Finally, we found that the IL-6 3’ UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX. These findings highlight how a multitude of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA.
Author Summary
During replication of Kaposi’s sarcoma-associated herpesvirus (KSHV), the vast majority of mRNAs in the cytoplasm are cleaved and degraded by the viral nuclease SOX. However, some mRNAs escape this fate, including the transcript encoding the immunoregulatory cytokine IL-6. Here, we discover that this escape is mediated by a group of proteins that associates with a sequence element on the IL-6 mRNA. One of these proteins is nucleolin (NCL), a factor with diverse roles in RNA processing that is frequently co-opted during viral infection. During KSHV replication, a proportion of NCL is redirected from the nucleolar subcompartment of the nucleus into the cytoplasm, where it binds both the IL-6 3’ UTR and a complex of cellular proteins including the translation initiation factor eIF4H. This network of interactions is required for escape from virus-induced degradation. Collectively, these findings reveal novel interplay between the SOX escapees and the cellular mRNA stabilization machinery, and shed light on the complex crosstalk between viruses and hosts over the control of gene expression.
PMCID: PMC4428876  PMID: 25965334
2.  Perception of difficulty and glucose control: Effects on academic performance in youth with type I diabetes 
World Journal of Diabetes  2015;6(3):527-533.
AIM: To investigate whether perceptions of task difficulty on neuropsychological tests predicted academic achievement after controlling for glucose levels and depression.
METHODS: Participants were type 1 diabetic adolescents, with a mean age = 12.5 years (23 females and 16 males), seen at a northwest suburban Chicago hospital. The sample population was free of co-morbid clinical health conditions. Subjects completed a three-part neuropsychological battery including the Digit Symbol Task, Trail Making Test, and Controlled Oral Word Association test. Following each task, individuals rated task difficulty and then completed a depression inventory. Performance on these three tests is reflective of neuropsychological status in relation to glucose control. Blood glucose levels were measured immediately prior to and after completing the neuropsychological battery using a glucose meter. HbA1c levels were obtained from medical records. Academic performance was based on self-reported grades in Math, Science, and English. Data was analyzed using multiple regression models to evaluate the associations between academic performance, perception of task difficulty, and glucose control.
RESULTS: Perceptions of difficulty on a neuropsychological battery significantly predicted academic performance after accounting for glucose control and depression. Perceptions of difficulty on the neuropsychological tests were inversely correlated with academic performance (r = -0.48), while acute (blood glucose) and long-term glucose levels increased along with perceptions of task difficulty (r = 0.47). Additionally, higher depression scores were associated with poorer academic performance (r = -0.43). With the first regression analysis, perception of difficulty on the neuropsychological tasks contributed to 8% of the variance in academic performance after controlling for peripheral blood glucose and depression. In the second regression analysis, perception of difficulty accounted for 11% of the variance after accounting for academic performance and depression. The final regression analysis indicated that perception of difficulty increased with peripheral blood glucose, contributing to 22% of the variance. Most importantly, after controlling for perceptions of task difficulty, academic performance no longer predicted glucose levels. Finally, subjects who found the cognitive battery difficult were likely to have poor academic grades.
CONCLUSION: Perceptions of difficulty on neurological tests exhibited a significant association with academic achievement, indicating that deficits in this skill may lead to academic disadvantage in diabetic patients.
PMCID: PMC4398908  PMID: 25897362
Type 1 diabetes; Adolescents; Perception of difficulty; Academic performance; Glucose control
3.  Harmful microinjecting practices among a cohort of injection drug users in Vancouver Canada 
Substance use & misuse  2010;45(9):1351-1366.
We sought to identify factors associated with harmful microinjecting practices in a longitudinal cohort of IDU.
Using data from the Vancouver Injection Drug Users Study (VIDUS) between January 2004 and December 2005, generalized estimating equations (GEE) logistic regression was performed to examine sociodemographic and behavioral factors associated with four harmful microinjecting practices (frequent rushed injecting, frequent syringe borrowing, frequently injecting with a used water capsule, frequently injecting alone).
In total, 620 participants were included in the present analysis. Our study included 251 (40.5%) women and 203 (32.7%) self-identified Aboriginal participants. The median age was 31.9 (interquartile range: 23.4–39.3). GEE analyses found that each harmful microinjecting practice was associated with a unique profile of sociodemographic and behavioral factors.
We observed high rates of harmful microinjecting practices among IDU. The present study describes the epidemiology of harmful microinjecting practices and points to the need for strategies that target higher risk individuals including the use of peer-driven programs and drug-specific approaches in an effort to promote safer injecting practices.
PMCID: PMC3782079  PMID: 20509739
injection drug use; harmful; Vancouver; microinjecting practices
4.  Incarceration and drug use patterns among a cohort of injection drug users 
Addiction (Abingdon, England)  2009;104(1):69-76.
Drug law enforcement remains the dominant response to drug-related harm. However, the impact of incarceration on deterring drug use remains under-evaluated. We sought to explore the relationship between incarceration and patterns of drug use among people who inject drugs (IDU).
Using generalized estimating equations (GEE), we examined the prevalence and correlates of injection cessation among participants in the Vancouver Injection Drug User Study followed over 9 years. In subanalyses, we used McNemar's tests and linear growth curve analyses to assess changes in drug use patterns before and after a period of incarceration among participants reporting incarceration and those not incarcerated.
Among 1603 IDU, 842 (53%) reported injection cessation for at least 6 months at some point during follow-up. In multivariate GEE analyses, recent incarceration was associated negatively with injection cessation [adjusted odds ratio (AOR) = 0.43, 95% confidence interval (CI) 0.37–0.50], whereas the use of methadone was associated positively with cessation (AOR = 1.38, 95% CI 1.22–1.56). In subanalyses assessing longitudinal patterns of drug use among incarcerated individuals and those not incarcerated over the study period, linear growth curve analyses indicated that there were no statistically significant differences in patterns of drug use between the two groups (all P > 0.05).
These observational data suggest that incarceration does not reduce drug use among IDU. Incarceration may inhibit access to mechanisms that promote injection cessation among IDU. In contrast, results indicate that methadone use is associated positively with injection cessation, independent of previous frequency of drug use.
PMCID: PMC3731940  PMID: 19133890
Addiction treatment; deterrence; drug law enforcement; drug policy; drug use patterns; incarceration; injection cessation; injection drug use
5.  The Burnaby treatment center for mental health and addiction, a novel integrated treatment program for patients with addiction and concurrent disorders: results from a program evaluation 
Patients with addictions and concurrent disorders constitute the most underserved population in the system of care. There are numerous reasons why this population has so much difficulty accessing services, including behavioural issues, criminal engagement, and non-compliance with outpatient services. To improve services to this population which is marked by multiple morbidities, high mortality and insufficient access to health care, the government of British Columbia, Canada developed a program for people with both substance use disorder and one or more mental disorders who have not benefited from previous therapies.
In July 2008, the Burnaby Treatment Centre for Mental Health and Addiction (BCMHA), a specialized and integrated tertiary care facility, was opened. The current article provides a description of the treatment program and a clinical profile of the population.
The target population is being served, at intake clients present with high rates of psychopathology, childhood and adult trauma, and substance use.
While preliminary, these results indicate, that the novel approach of the Burnaby Centre may constitute a new path towards providing effective recovery for this population.
PMCID: PMC3733750  PMID: 23895592
Concurrent disorders; Integrated treatment; Marginalized populations
6.  Global landscape of HIV–human protein complexes 
Nature  2011;481(7381):365-370.
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host’s cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry1-3 to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV–human protein–protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.
PMCID: PMC3310911  PMID: 22190034
7.  Proteomics Analysis Reveals Post-Translational Mechanisms for Cold-Induced Metabolic Changes in Arabidopsis 
Molecular Plant  2011;4(2):361-374.
Cold-induced changes of gene expression and metabolism are critical for plants to survive freezing. Largely by changing gene expression, exposure to a period of non-freezing low temperatures increases plant tolerance to freezing—a phenomenon known as cold acclimation. Cold also induces rapid metabolic changes, which provide instant protection before temperature drops below freezing point. The molecular mechanisms for such rapid metabolic responses to cold remain largely unknown. Here, we use two-dimensional difference gel electrophoresis (2-D DIGE) analysis of sub-cellular fractions of Arabidopsis thaliana proteome coupled with spot identification by tandem mass spectrometry to identify early cold-responsive proteins in Arabidopsis. These proteins include four enzymes involved in starch degradation, three HSP100 proteins, several proteins in the tricarboxylic acid cycle, and sucrose metabolism. Upon cold treatment, the Disproportionating Enzyme 2 (DPE2), a cytosolic transglucosidase metabolizing maltose to glucose, increased rapidly in the centrifugation pellet fraction and decreased in the soluble fraction. Consistent with cold-induced inactivation of DPE2 enzymatic activity, the dpe2 mutant showed increased freezing tolerance without affecting the C-repeat binding transcription factor (CBF) transcriptional pathway. These results support a model that cold-induced inactivation of DPE2 leads to rapid accumulation of maltose, which is a cold-induced compatible solute that protects cells from freezing damage. This study provides evidence for a key role of rapid post-translational regulation of carbohydrate metabolic enzymes in plant protection against sudden temperature drop.
PMCID: PMC3063518  PMID: 21242321
2-D DIGE; Arabidopsis; Cold response; freezing tolerance; heat shock protein; starch metabolism
8.  The male sterility 8 mutation of maize disrupts the temporal progression of the transcriptome and results in mis-regulation of metabolic functions 
Maize anther ontogeny is complex with expression of more than 30,000 genes over four days of cell proliferation, cell fate acquisition, and the start of meiosis. Although many male-sterile mutants disrupt these key steps, few have been investigated in detail. The terminal phenotypes of maize male-sterile 8 (ms8) are small anthers exhibiting meiotic failure. Here we document much earlier defects: ms8 epidermal cells are normal in number but fail to elongate, and there are fewer, larger tapetal cells that retain rather than secrete their contents. ms8 meiocytes separate early, have extra space between them occupied by excess callose, and the meiotic dyads abort. Thousands of transcriptome changes occur in ms8 including ectopic activation of genes not expressed in fertile siblings, failure to express some genes, differential expression compared to fertile siblings and about 40% of the differentially expressed transcripts appear precociously. There is a high correlation between mRNA accumulation assessed by microarray hybridization and qRT-PCR. Sixty-three differentially expressed proteins were identified after 2-D gel electrophoresis followed by LC/MS/MS (liquid chromatography tandem mass spectroscopy), including those involved in metabolism, plasmodesmatal remodeling, and cell division. The majority of these were not identified by differential RNA expression demonstrating the importance of proteomics to define developmental mutants.
PMCID: PMC2974755  PMID: 20626649
maize; ms8; anther; meiosis; microarray; proteomics
9.  Syringe Sharing and HIV Incidence Among Injection Drug Users and Increased Access to Sterile Syringes 
American journal of public health  2010;100(8):1449-1453.
We assessed the effects of syringe exchange program (SEP) policy on rates of HIV risk behavior and HIV incidence among injection drug users.
Using a multivariate generalized estimating equation and Cox regression methods, we examined syringe borrowing, syringe lending, and HIV incidence among a prospective cohort of 1228 injection drug users in Vancouver, British Columbia.
We observed substantial declines in rates of syringe borrowing (from 20.1% in 1998 to 9.2% in 2003) and syringe lending (from 19.1% in 1998 to 6.8% in 2003) following SEP policy change. These declines coincided with a statistically significant increase in the proportion of participants accessing sterile syringes from nontraditional SEP sources (P<.001). In multivariate analyses, the period following the change in SEP policy was independently associated with a greater than 40% reduction in syringe borrowing (adjusted odds ratio [AOR]=0.57; 95% confidence interval [CI]=0.49, 0.65) and lending (AOR=0.52; 95% CI=0.45, 0.60), as well as declining HIV incidence (adjusted hazard ratio=0.13; 95% CI=0.06, 0.31).
Widespread syringe distribution appears to be a more effective SEP policy than do more restrictive SEP policies that limit syringe access. Efforts should be made to ensure that SEP policies and program design serve to maximize rather than hinder syringe access.
PMCID: PMC2901279  PMID: 20558797
10.  Access to Drug and Alcohol Treatment among a Cohort of Street-Involved Youth 
Drug and alcohol dependence  2008;101(1-2):1-7.
A number of options for treatment are available to young drug users, but little is known about the youth who actually attempt to access such services. Here we identify characteristics of a cohort of street-involved youth and highlight commonly encountered barriers.
From September 2005 to July 2007, data were collected from the At-Risk Youth Study (ARYS), a prospective cohort of 529 drug users aged 14–26 living in Vancouver, Canada. Participants who attempted to access any addiction services in the six months prior to enrollment were compared in univariate analyses and multiple logistic regression modeling of sociodemographic and drug-related factors.
Factors positively associated with attempting to access services included Aboriginal ethnicity (adjusted odds ratio [AOR] = 1.66 [1.05 – 2.62]), high school education (AOR = 1.66 [1.09 – 2.55]), mental illness (AOR = 2.25 [1.50 – 3.38]), non-injection crack use (AOR = 2.93 [1.76 – 4.89]), and spending >$50 on drugs per day (AOR = 2.13 [1.41 – 3.22]). Among those who experienced difficulty accessing services, the most commonly identified barrier was excessively long waiting lists. In a subgroup analysis comparing those who tried to access services but were unsuccessful to those who were successful, risk factors positively associated with failure included drug bingeing (odds ratio [OR] = 2.86 [1.22 – 6.76]) and homelessness (OR = 3.86 [1.11 – 13.4]).
In light of accumulating evidence that drug use among street youth is associated with risky health-related behaviors, improving access to treatment and other addiction services should remain an important public health priority.
PMCID: PMC2667152  PMID: 19081203
youth; street youth; adolescents; access; addiction services; methadone maintenance; drug treatment; alcohol treatment; detoxification; Aboriginal
11.  Assisted injection in outdoor venues: an observational study of risks and implications for service delivery and harm reduction programming 
Assisted injection and public injection have both been associated with a variety of individual harms including an increased risk of HIV infection. As a means of informing local IDU-driven interventions that target or seek to address assisted injection, we examined the correlates of receiving assistance with injecting in outdoor settings among a cohort of persons who inject drugs (IDU).
Using data from the Vancouver Injection Drug Users Study (VIDUS), an observational cohort study of IDU, generalized estimating equations (GEE) were performed to examine socio-demographic and behavioural factors associated with reports of receiving assistance with injecting in outdoor settings.
From January 2004 to December 2005, a total of 620 participants were eligible for the present analysis. Our study included 251 (40.5%) women and 203 (32.7%) self-identified Aboriginal participants. The proportion of participants who reported assisted injection outdoors ranged over time between 8% and 15%. Assisted injection outdoors was independently and positively associated with being female (Adjusted Odds Ratio (AOR) = 1.74, 95% Confidence Intervals (CI): 1.21-2.50), daily cocaine injection (AOR = 1.70, 95% CI: 1.29-2.24), and sex trade involvement (AOR = 1.44, 95% CI: 1.00-2.06) and was negatively associated with Aboriginal ethnicity (AOR = 0.58, 95% CI: 0.41-0.82).
Our findings indicate that a substantial proportion of local IDU engage in assisted injecting in outdoor settings and that the practice is associated with other markers of drug-related harm, including being female, daily cocaine injecting and sex trade involvement. These findings suggest that novel interventions are needed to address the needs of this subpopulation of IDU.
PMCID: PMC2856546  PMID: 20302638
12.  Incidence and determinants of initiation into cocaine injection and correlates of frequent cocaine injectors 
Drug and alcohol dependence  2008;99(1-3):176-182.
To investigate the incidence and correlates of cocaine injection initiation and the impacts of daily cocaine injection among a cohort of injection drug users.
Among 1603 participants, from May 1996 and December 2005, risk factors for initiation of cocaine injection among baseline heroin users were determined by Cox proportional hazards regression and correlates of daily cocaine injection by generalized estimating equations.
Of the 238 individuals who had never injected cocaine, 200 (84%) had at least one follow-up visit and 121 (61%) consequently initiated into cocaine injection yielding an incidence density of initiation into cocaine injection of 21.9% (95% Confidence Interval (CI) 17.9 – 25.8) per 100 person years. In a multivariate model, Downtown Eastside (DTES) residence (Adjusted Hazard Ratio (AHR) = 2.46, 95% CI: 1.68-3.60), incarceration (AHR = 1.50, 95% CI: 1.01-2.24), requiring help injecting (AHR = 1.57, 95% CI: 0.99 – 2.49), and binge drug use (AHR = 1.82, 95% CI: 1.22 - 2.73) remained associated with initiation into cocaine injection. DTES residence (adjusted odds ratio (AOR) = 1.99, 95% CI: 1.62 – 2.46), incarceration (AOR = 1.29, 95% CI: 1.04 – 1.60), unstable housing (AOR = 1.28, 95% CI: 1.04 – 1.53), sex trade involvement (AOR = 1.46, 95% CI: 1.15 – 1.85), requiring help injecting (AOR = 2.11, 95% CI: 1.73 – 2.58]), borrowing syringes (AOR = 1.81, 95% CI: 1.35 – 2.43) and binge drug use (AOR = 2.16, 95% CI: 1.81 – 2.58) were independently associated with daily cocaine injection.
The baseline prevalence and subsequent incidence of initiation into cocaine injection was high. Daily cocaine injection was independently associated with a number of health and social harms including elevated HIV risk behavior.
PMCID: PMC2649881  PMID: 18805655
Cocaine; injection drug use; risk factors; HIV
13.  Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs 
Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection.
We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996–Nov. 30, 1999 (period 1), Dec. 1, 1999–Nov. 30, 2002 (period 2), and Dec. 1, 2002–Dec. 30, 2005 (period 3).
Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57–1.85; period 2: HR 1.68, 95% CI 1.01–2.80; and period 3: HR 2.74, 95% CI 1.06–7.11).
Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.
PMCID: PMC2764753  PMID: 19841052
14.  Physical Violence Among a Prospective Cohort of Injection Drug Users: A Gender-Focused Approach 
Drug and alcohol dependence  2008;97(3):237-246.
Although dramatically heightened rates of violence have been observed among injection drug users (IDU), little is known about the gender differences associated with violence among this population. Employing a risk environment framework, we performed an analysis of the factors associated with experiencing violence among participants enrolled in a prospective cohort study of IDU during the years 1996-2005 using generalized estimating equations (GEE). Among 1114 individuals, 291 (66%) of females and 470 (70%) of males reported experiencing violence during the study period. In multivariate analyses, mental illness, frequent alcohol use, frequent crack use, homelessness, Downtown Eastside residency, and requiring help injecting were positively associated with experiencing violence for both sexes (all p < 0.05). For females, binge drug use (AOR = 1.30) and drug dealing (AOR = 1.42) were positively associated with violence, while younger age (AOR = 1.02), frequent heroin injection (AOR = 1.24), and incarceration (AOR = 1.50) were significant for males. Women were more likely to be attacked by acquaintances, partners, and sex trade clients, while men were more likely to experience violence from strangers and the police. These findings indicate that susceptibility to violence among IDU is structured by environmental factors such as homelessness and drug-related factors such as frequent alcohol use and involvement in drug economies. Furthermore, important gender differences with respect to the predictors and characteristics of violent attacks do exist. These findings indicate an urgent need for the development of comprehensive programs and structural interventions that take a gender-focused approach to violence among IDU.
PMCID: PMC2570226  PMID: 18487025
Violence; Gender; Injection Drug Use; HIV; Canada
Drug market policing has been associated with various harms among injection drug users (IDU). However, little is known about instances in which drugs and injecting equipment are confiscated from IDU in the absence of a formal arrest.
We examined factors associated with being stopped, searched, or detained by police among participants in the Vancouver Injection Drug Users Study (VIDUS) using logistic regression. We also examined actions taken by study participants immediately following instances in which drugs or syringes were confiscated by police.
Among 465 active IDU, 130 (28.0%) reported being detained by police in the last six months without being arrested. In multivariate logistic regression analysis, factors associated with being stopped, searched or detained by police included homelessness (Adjusted Odds Ratio [AOR] = 3.96, 95%CI: 1.86 – 8.45), recent incarceration (AOR = 3.52, 95% CI: 1.75 – 7.10), frequent crack use (AOR = 2.24, 95% CI: 1.34 – 3.74), requiring help injecting (AOR = 5.20, 95% CI: 1.21 – 22.39), and lending syringes (AOR = 3.18, 95% CI: 1.09 – 9.30). Of those who reported being detained, 34% participants reported having had drugs confiscated, and 70% of these reported that they immediately acquired more drugs. 51% of participants who reported being detained also reported having had syringes confiscated, and of this group, 6% reported immediately borrowing used syringes.
Our study demonstrates that the IDU most affected by street-level policing tend to possess various characteristics, such as homeless, that place them at heightened risk for various adverse health outcomes. Our findings also suggest that the confiscation of drugs and/or needles and syringes through discretionary policing practices have potential to exacerbate drug market activity or prompt increased syringe borrowing. These findings indicate the need for ongoing evaluation of the public health impacts of discretionary policing approaches.
PMCID: PMC2529170  PMID: 17900888
16.  Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting 
BMC Public Health  2009;9:270.
There has emerged growing recognition of the link between housing and health. Since Vancouver, Canada has had increasing concerns with homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games, we evaluated hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing.
Data were derived from a collaboration between two prospective cohort studies of IDU in Vancouver, Canada. Using Cox Proportional Hazards regression, we compared HCV incidence among participants with and without stable housing, and determined independent predictors of HCV incidence.
Overall, 3074 individuals were recruited between May 1996 and July 2007, among whom 2541 (82.7%) were baseline HCV-infected. Among the 533 (17.3%) individuals who were not HCV-infected at baseline, 147 tested HCV antibody-positive during follow-up, for an incidence density of 16.89 (95% confidence interval: 14.76 – 19.32) per 100 person-years. In a multivariate Cox regression model, unstable housing remained independently associated with HCV infection (relative hazard = 1.47 (1.02 – 2.13).
HCV prevalence and incidence are high in this setting and were associated with unstable housing. Efforts to protect existing low-income housing and improve access to housing may help to reduce HCV incidence.
PMCID: PMC2728719  PMID: 19640297
17.  Elevated HIV risk behaviour among recently incarcerated injection drug users in a Canadian setting: a longitudinal analysis 
BMC Public Health  2009;9:156.
While incarceration has consistently been associated with a higher risk of HIV infection for individuals who use injection drugs (IDU), the effect of incarceration on the post-release risk environment remains poorly described. We sought to assess the impact of incarceration on risk factors for HIV infection after release from prison in a sample of active IDU in Vancouver, Canada.
Using a prospective cohort of community-recruited IDU followed from May 1, 1996 to November 30, 2005, we examined contingency tables and performed linear growth curve analyses to assess changes in the prevalence of independent risk factors for HIV infection from before to after a period of incarceration among participants reporting incarceration and a matched control group.
Of the 1603 participants followed-up over the study period, 147 (9.2%) were eligible for an analysis of post-incarceration risk behaviours and 742 (46.3%) were used as matched controls. Significant differences were found in one or both groups for the prevalence of frequent cocaine injection, requiring help injecting, binge drug use, residence in the HIV outbreak epicentre, sex-trade participation and syringe sharing (all p < 0.05) after incarceration. In linear growth curve adjusted for age, gender and ethnicity, syringe sharing was significantly more common in those recently released from prison (p = 0.03) than in the control group.
In a sample of Canadian IDU, we did not observe any effect of incarceration on the prevalence of several behaviours that are risk factors for HIV infection, including intensity of drug use or participation in the sex trade. However, those recently released from prison were more likely to report syringe sharing that those in a matched control group.
PMCID: PMC2695456  PMID: 19473508
18.  Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study 
Objective To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users.
Design Prospective cohort study.
Setting Inner city community in Vancouver, Canada.
Participants Injecting drug users, with and without HIV, followed up every six months between 1 May 1996 and 30 June 2007.
Main outcome measures Estimated community plasma HIV-1 RNA in the six months before each HIV negative participant’s follow-up visit. Associated HIV incidence.
Results Among 622 injecting drug users with HIV, 12 435 measurements of plasma HIV-1 RNA were obtained. Among 1429 injecting drug users without HIV, there were 155 HIV seroconversions, resulting in an incidence density of 2.49 (95% confidence interval 2.09 to 2.88) per 100 person years. In a Cox model that adjusted for unsafe sexual behaviours and sharing used syringes, the estimated community plasma HIV-1 RNA concentration remained independently associated with the time to HIV seroconversion (hazard ratio 3.32 (1.82 to 6.08, P<0.001), per log10 increase). When the follow-up period was limited to observations after 1 January 1988 (when the median plasma HIV RNA concentration was <20 000 copies/ml), the median viral load was no longer statistically associated with HIV incidence (1.70 (0.79 to 3.67, P=0.175), per log10 increase).
Conclusions A longitudinal measure of community plasma HIV-1 RNA concentration was correlated with the community HIV incidence rate and predicted HIV incidence independent of unsafe sexual behaviours and sharing used syringes. If these findings are confirmed, they could help to inform both HIV prevention and treatment interventions.
PMCID: PMC2675696  PMID: 19406887
19.  High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting 
Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.
PMCID: PMC2607257  PMID: 19019253
20.  A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer Centre – A review of the experience from 1999 to 2005 
Journal of pain research  2008;1:43-48.
Our objective in this study was to review the experience of a one-stop multidisciplinary bone metastases clinic (BMC) that offers a coordinated multidisciplinary approach to the care of cancer patients with bone metastases in a tertiary cancer centre. Patients with symptomatic bone metastases were referred to BMC and assessed by a team of specialists in various disciplines – interventional radiology, orthopedic surgery, palliative medicine, and radiation oncology. At initial consultation, patient demographics, reasons for referral, and case disposition were recorded. From January 1999 to February 2005, a total of 272 patients with bone metastases were referred to the BMC. The median age was 65 years (range 28–95) and median KPS score at consultation was 60 (range 30–90). The majority of patients came from home (74%), while others came from a nursing home or the hospital (9%). Almost a third (28%) of patients had 2 or more reasons of referral, yielding a total of 354 reasons. The most common reason for referral was bone pain (42%), bone metastases (21%), high risk for pathological fracture (12%), and pathological fracture (10%). Of the 272 patients who received consultation, 40% received palliative radiotherapy, 19% received interventional surgery, 7% were referred to other support services such as palliative care, physiotherapy, and 7% had further investigation or imaging. A multidisciplinary clinic is useful for co-coordinating the management of bone metastatic disease in symptomatic patients.
PMCID: PMC3004611  PMID: 21197287
bone metastases; multidisciplinary approach; experience
22.  Income Generating Activities of People Who Inject Drugs 
Drug and alcohol dependence  2007;91(1):50-56.
Injection drug users (IDU) commonly generate income through prohibited activities, such as drug dealing and sex trade work, which carry significant risk. However, little is known about the IDU who engage in such activities and the role of active drug use in perpetuating this behavior.
We evaluated factors associated with prohibited income generation among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS) using logistic and linear regression. We also examined which sources of income respondents would eliminate if they did not require money to pay for drugs.
Among 275 IDU, 145 (53%) reported engaging in prohibited income generating activities in the past 30 days. Sex work and drug dealing accounted for the greatest amount of income generated. Non-aboriginal females were the group most likely to report prohibited income generation. Other variables independently associated with prohibited income generation include daily heroin injection (AOR = 2.3) and daily use of crack cocaine (AOR = 3.5). Among these individuals, 68 (47%) indicated they would forgo these earnings if they did not require money for illegal drugs, with those engaged in sex trade work (62%) being most willing to give up their illegal source of income.
These findings suggest that the costs associated with illicit drugs are compelling IDU, particularly those possessing markers of higher intensity addiction, to engage in prohibited income generating activities. These findings also point to an opportunity to explore interventions that relieve the financial pressure of purchasing illegal drugs and reduce engagement in such activities, such as low threshold employment and expansion of prescription and substitution therapies.
PMCID: PMC2047290  PMID: 17561355
IDU; Income Generation; Sex Trade Work; Drug Dealing
23.  Increasing use and Associated Harms of Crystal Methamphetamine Injection in a Canadian Setting 
Drug and alcohol dependence  2006;88(2-3):313-316.
There is a growing concern surrounding crystal methamphetamine use in Canada despite surprisingly little empirical data to support such claims. We evaluated the trends in crystal methamphetamine injection and factors associated with injection of the drug among a cohort of injection drug users (IDU) in Vancouver.
We conducted a prospective analysis of factors associated with crystal methamphetamine injection among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each individual were available, variables potentially associated with crystal methamphetamine injection were evaluated using generalized estimating equations (GEE) with logit link for binary outcomes.
Overall, 1587 IDU were enrolled into the VIDUS cohort between May 1996 and December 2004. The proportion of IDU who reported injecting crystal methamphetamine during the last six months increased during the study period (Cochran-Armitage trend test, p < 0.001). In multivariate GEE analyses, crystal methamphetamine injection was independently associated with younger age (Adjusted Odds Ratio [AOR]: 4.77, 95% Confidence Interval [CI] = 3.40 - 6.70), Caucasian ethnicity (AOR = 2.21, 95% CI = 1.57 - 3.12), syringe borrowing (AOR = 1.62, 95% CI = 1.22 - 2.13), and syringe lending (AOR = 1.40, 95% CI = 1.02 - 1.86).
There was a significant trend towards increasing crystal methamphetamine injection in this setting and elevated HIV risk behavior and younger age were independently associated with crystal methamphetamine injection. Given that banning precursor chemicals has had a limited effect on reducing methamphetamine supply in other jurisdictions, pragmatic and effective interventions are needed to address the growing use of this drug.
PMCID: PMC1925049  PMID: 17141427
HIV transmission ; Injection drug use ; Crystal methamphetamine
24.  Rate of methadone use among Aboriginal opioid injection drug users 
Previous studies have shown elevated rates of health-related harms among Aboriginal people who use injection drugs such as heroin. Methadone maintenance therapy is one of the most effective interventions to address the harms of heroin injection. We assessed the rate of methadone use in a cohort of opioid injection drug users in Vancouver and investigated whether methadone use was associated with Aboriginal ethnic background.
Using data collected as part of the Vancouver Injection Drug Users Study (May 1996–November 2005), we evaluated whether Aboriginal ethnic background was associated with methadone use using generalized estimating equations and Cox regression analysis. We compared methadone use among Aboriginal and non-Aboriginal injection drug users at the time of enrolment and during the follow-up period, and we evaluated the time to first methadone use among people not using methadone at enrolment.
During the study period, 1603 injection drug users (435 Aboriginal, 1168 non-Aboriginal) were recruited. At enrolment, 54 (12.4%) Aboriginal participants used methadone compared with 247 (21.2%) non-Aboriginal participants (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.73, p < 0.001). Among the 1351 (84.3%) participants who used heroin, Aboriginal people were less likely to use methadone throughout the follow-up period (adjusted OR 0.60, 95% CI 0.45–0.81, p < 0.001). Among people using heroin but who were not taking methadone at enrolment, Aboriginal ethnic background was associated with increased time to first methadone use (adjusted relative hazard 0.60, 95% CI 0.49–0.74, p < 0.001).
Methadone use was lower among Aboriginal than among non-Aboriginal injection drug users. Culturally appropriate interventions with full participation of the affected community are required to address this disparity.
PMCID: PMC1896027  PMID: 17606937
25.  Factors associated with premature mortality among young injection drug users in Vancouver 
Young injection drug users (IDUs) may be at increased risk of premature mortality due to the health risks associated with injection drug use including overdoses and infections. However, there has been little research conducted on mortality causes, rates and associations among this population. We undertook this study to investigate patterns of premature mortality, prior to age 30 years, among young IDUs.
Since 1996, 572 young (≤29 years) IDUs have been enrolled in the Vancouver Injection Drug Users Study (VIDUS). Semi-annually, participants have completed an interviewer-administered questionnaire and have undergone serologic testing for HIV and hepatitis C (HCV). Mortality data have been continually updated through linkages with the Provincial Coroner's Office. Crude and age-specific mortality rates, standardized mortality ratios, and life expectancy measures were calculated using person-time methods. Predictors of mortality were identified using Cox regression analyses.
Twenty-two participants died prior to age 30 years during the follow-up period for an overall crude mortality rate of 1,368 per 100,000 person-years. Overall, young IDUs were 16.4 times (95% confidence interval [CI]; 9.1–27.1) more likely to die; young women IDUs were 54.1 times (95%CI; 29.6–90.8) and young men IDUs were 12.9 times (95%CI; 5.5, 25.3) more likely to die when compared to the Canadian non-IDU population of the same age. The leading observed cause of death among females was: homicide (N = 9); and among males: suicide (N = 3) and overdose (N = 3). In Cox regression analyses, factors associated with mortality were, HIV infection (Hazard Ratio [HR]: 4.55; CI: 1.92–10.80) and sex work (HR: 2.76; CI: 1.16–6.56).
Premature mortality was 13 and 54 times higher among young men and women who use injection drugs in Vancouver than among the general population in Canada. The majority of deaths among the women were attributable to homicide, suggesting that interventions should occur not only through harm reduction services but also through structural interventions at the legal and policy level.
PMCID: PMC1769365  PMID: 17201933

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