Hepatitis C infection among pregnant women in British Columbia: reported prevalence and critical appraisal of current prenatal screening methods.

BACKGROUND: Despite the fact that hepatitis C virus (HCV) is a relatively common infection in Canada, particularly in British Columbia (BC), there is a paucity of information on actual HCV prevalence in pregnant women. At present, pregnant women are only screened if they fit risk criteria, which may result in under-identification of HCV in this population. The purpose of this study was to determine the overall prevalence rate, age and geographic distribution of reported HCV infection among pregnant women in BC, and compare results to a previously conducted anonymous seroprevalence survey. METHODS: Reported HCV prevalence was determined through a confidential database linkage of all prenatal screening results at the Canadian Blood Services (CBS) with all HCV test results at the Provincial Laboratory, from May 2000 to Oct 2002. Data were stratified by age group and geographic location, and subsequently compared to an anonymous prenatal seroprevalence survey conducted in 1994. RESULTS: The overall HCV prevalence rate was 50.3/10,000 (95% CI 46.3-54.6), or 0.5% of the cohort. Prevalence was highest in the northern BC region (66.2/10,000, 95% CI 51.4-85.3) and lowest in the populous suburban region southwest of Vancouver (38.0/10,000, 95% CI 32.3-44.8). Of note, the rate of reported HCV among pregnant women was significantly lower than the anonymous seroprevalence rate: 50.3/10,000 vs. 91.3/10,000 (p < 0.0001). CONCLUSION: Rates of reported HCV among pregnant women were approximately 50% lower than the rates determined by the anonymous seroprevalence survey. Further research is needed to determine the relative merits of the current selective screening policy versus universal prenatal HCV screening in pregnancy.

The Cedar Project: correlates of attempted suicide among young Aboriginal people who use injection and non-injection drugs in two Canadian cities.

OBJECTIVES: Aboriginal leadership and families are deeply concerned about the rate of suicide attempt among their young people. The objectives of this study were to (a) describe the prevalence of suicide attempt and (b) to describe correlates of vulnerability to suicide attempts within a cohort of young Aboriginal people who use drugs in 2 Canadian cities. We aimed to situate the findings within the context of historical and lifetime trauma. Study design. The Cedar Project is a prospective cohort study involving 605 young Aboriginal people aged 14-30 who use drugs in Vancouver and Prince George, British Columbia, Canada. METHODS: Multivariable logistic regression modelling identified independent predictors of suicide attempts. Estimates of adjusted odds ratios and 95% confidence intervals were calculated. RESULT: In multivariable analysis, residing in Prince George (Adjusted Odds Ratio [AOR]: 1.80, 95% CI: 1.23, 2.64), ever having been sexually abused (AOR: 2.07, 95% CI: 1.39, 3.08), and ever having overdosed (AOR: 2.29, 95% CI: 1.53, 3.42) independently predicted lifetime attempted suicide. CONCLUSIONS: Suicide prevention and intervention programs must address historical and lifetime trauma among Aboriginal young people who struggle with substance dependence.

The Cedar Project: historical trauma, sexual abuse and HIV risk among young Aboriginal people who use injection and non-injection drugs in two Canadian cities.

Recent Indigenist scholarship has situated high rates of traumatic life experiences, including sexual abuse, among Indigenous peoples of North America within the larger context of their status as colonized peoples. Sexual abuse has been linked to many negative health outcomes including mental, sexual and drug-related vulnerabilities. There is a paucity of research in Canada addressing the relationship between antecedent sexual abuse and negative health outcomes among Aboriginal people including elevated risk of HIV infection. The primary objectives of this study were to determine factors associated with sexual abuse among participants of the Cedar Project, a cohort of young Aboriginal people between the ages of 14 and 30 years who use injection and non-injection drugs in two urban centres in British Columbia, Canada; and to locate findings through a lens of historical and intergenerational trauma. We utilized post-colonial perspectives in research design, problem formulation and the interpretation of results. Multivariate modeling was used to determine the extent to which a history of sexual abuse was predictive of negative health outcomes and vulnerability to HIV infection. Of the 543 eligible participants, 48% reported ever having experienced sexual abuse; 69% of sexually abused participants were female. The median age of first sexual abuse was 6 years for both female and male participants. After adjusting for sociodemographic variables and factors of historical trauma, sexually abused participants were more likely to have ever been on the streets for more than three nights, to have ever self-harmed, to have suicide ideation, to have attempted suicide, to have a diagnosis of mental illness, to have been in the emergency department within the previous 6 months, to have had over 20 lifetime sexual partners, to have ever been paid for sex and to have ever overdosed. The prevalence and consequences of sexual abuse among Cedar Project participants are of grave concern. Sexual trauma will continue to impact individuals, families and communities until unresolved historical trauma is meaningfully addressed in client-driven, culturally safe programming.

Gender differences in HIV and hepatitis C related vulnerabilities among aboriginal young people who use street drugs in two Canadian cities.

OBJECTIVES: Vulnerability to HIV and Hepatitis C virus (HCV) infection for indigenous populations worldwide must be contextualized in experiences of current and past trauma. Aboriginal women entrenched in poverty face further gender-specific harms which place them at increased risk for HIV infection. METHODS: This study was cross-sectional and based on a community-based sample of Aboriginal young people (Metis, Aboriginal, First Nations, Inuit, and non-status Indians) between the ages of 14 and 30 years who used injection or non-injection non-cannabis illegal drugs (street drugs) in the previous month. Between October 2003 and July 2005, 543 participants living in either Vancouver or Prince George, Canada, were recruited by word of mouth, posters, and street outreach. Young people in the study completed a questionnaire administered by Aboriginal interviewers. Female participants (n = 262) were compared to male participants (n = 281) with respect to sociodemographics, trauma, sexual risk variables, and drug use patterns. Trained nurses drew blood samples for HIV and HCV antibodies and provided pre- and post-test counseling. RESULTS: Proportions positive for HIV and HCV were significantly higher among young women. HIV was 13.1% [9.5, 17.7] in women compared to 4.3% [2.5, 7.4] in men, and HCV was 43.6% [37.6, 49.8] in women as compared to 25.4% [20.5, 30.9] in men. When the analysis was restricted to young people who reported injection drug use, the proportions positive for HIV and HCV remained significantly higher among young women. Experiences of forced sex were reported by 70% of young women compared to 29% of young men, p < 0.001, while the median age of first forced sex was 6-years-old for both men and women. DISCUSSION: The results of the final model indicated that HIV had been associated with residing in Vancouver, having injected for longer, and sexual abuse, but not being female. However, this gendered analysis demonstrated that a greater proportion of young women were experiencing sexual abuse, and sexual abuse was associated with HIV positive status. Harm reduction and drug treatment programs are urgently required that target women at a young age and address complex traumatic experiences associated with childhood sexual abuse.

The Cedar Project: a comparison of HIV-related vulnerabilities amongst young Aboriginal women surviving drug use and sex work in two Canadian cities.

BACKGROUND: In Canada, Aboriginal women and youth continue to be overrepresented amongst new cases of HIV, and are considered at increased risk for sex and drug-related harm. Young women involved in sex work are particularly vulnerable. The purpose of this study is to determine HIV-related vulnerabilities associated with sex work amongst young Aboriginal women in two Canadian cities. METHODS: This study is based on a community-based cohort of Aboriginal young people (status and non-status First Nations, Inuit and Métis) between the ages of 14 and 30 who used injection or non-injection illegal drugs (street drugs) in the previous month. Participants lived in Vancouver, Canada, or Prince George, a remote, northern Canadian city. Between October 2003 and July 2005, 543 participants were recruited by word of mouth, posters, and street outreach. A baseline questionnaire was administered by Aboriginal interviewers, and trained nurses drew blood samples for HIV and HCV antibodies and provided pre- and post-test counselling. This study included 262 young women who participated at baseline. Analyses were conducted to compare socio-demographics, drug use patterns, injection practices, sexual experiences, and HIV and HCV prevalence between young women who reported being involved in sex work in the last 6 months (n=154) versus young women who did not (n=108). Logistic regression was used to identify factors independently associated with recent sex work involvement. RESULTS: Both sexual violence and drug using patterns were found to be markedly different for women having recently been involved in sex work. Multivariate analysis revealed daily injection of cocaine (AOR=4.4; 95% CI: 1.9, 10.1 and smoking crack (AOR=2.9; 95% CI: 1.6, 5.2) in the previous 6 months, and lifetime sexual abuse (AOR=2.5; 95% CI: 1.4, 4.4) to be independently associated with sex work. INTERPRETATION: Harm reduction and treatment programs that address historical and lifetime trauma amongst Aboriginal people and prioritize emotional and physical safety for young Aboriginal women involved in sex work are required.

The Cedar project: prevalence and correlates of HIV infection among young Aboriginal people who use drugs in two Canadian cities.

INTRODUCTION: During the past decade, the number of Aboriginal people diagnosed with HIV in Canada has grown more than any other ethnicity. Whereas the majority of infections are related to injection drug use, factors that explain elevated risk and transmission of HIV among Aboriginal young people who use illicit drugs are not well understood. STUDY DESIGN: Observational study. METHODS: The Cedar Project is an observational study of Aboriginal youth living in Vancouver and Prince George, BC. Eligibility criteria include age (14-30 years) and self-reported use of non-injection or injection drugs at least once in the month before enrolment. Between October 2003 and April 2005, 512 participants were recruited and completed a questionnaire administered by an Aboriginal interviewer. Multivariable logistic regression analysis was used to model the independent association of demographic and behavioural variables of individuals with HIV infection. RESULTS: Of the participants, 235 resided in Prince George and 277 in Vancouver. Among the 276 participants that used injection drugs, HIV prevalence was significantly higher in Vancouver (17% vs. 7%) but HCV prevalence was higher in Prince George (62% vs. 57%). In Vancouver, 40% of injectors reported daily heroine use compared with 12% in Prince George. In contrast, Prince George participants were more likely to report daily injection of cocaine compared with those in Vancouver (37% vs. 21%). A higher percentage of Prince George participants reported having difficulty accessing clean syringes (22% vs. 8%). History of non-consensual sex, residing in Vancouver and duration of injection drug use were independent factors associated with increased risk of HIV infection. CONCLUSIONS: HIV and HCV prevalence are elevated in young Aboriginal drug users residing in Vancouver and Prince George. Heterogeneity exists in these locations with respect to drug of choice and access to clean syringes. Prevention and treatment programs are urgently required in this population.

Injury rates, predictors of workplace injuries, and results of an intervention program among community health workers.

BACKGROUND: Few incidence studies of workplace injuries among community health workers exist, and evidence regarding the effectiveness of interventions in this population is lacking. OBJECTIVES: To determine the incidence of workplace injury among community health workers in British Columbia; to identify predictors of injury; and to assess the effectiveness of a multicomponent intervention program in this population. METHODS: Data were collected from an intervention study of 648 community health workers from six agencies to calculate injury rates. Interventions included an education and training module, a risk assessment tool and resource guide, and a lift equipment registry. RESULTS: The majority of injuries were attributed to overexertion and falls. Annual incidence rates were 20.7% for reported injuries, and 8.1% for time-loss injuries. A history of previous injuries and working full time were predictors of time to first injury report. Participants who received an intervention were significantly more likely to report workplace injuries than participants in the comparison group, but were less likely to incur a time-loss injury. CONCLUSIONS: The interventions used in this study led to increased awareness and an increase in reported injuries but resulted in fewer time-loss injuries. The mechanisms that led to these findings need to be explored further.

Health and socioeconomic status differences among antibody hepatitis C positive and negative transfusion recipients, 1986-1990.

OBJECTIVE: To characterize the socioeconomic and health status, disease symptoms of anti-HCV-positive and negative transfusion recipients. METHODS: A cross-sectional interviewer-administered survey of subjects identified through the British Columbia Blood Recipient Program. Study subjects were 18 years and over and had to have had a transfusion between August 1, 1986 and June 30, 1990 and completed an interview of satisfactory quality. Anti-HCV-positive subjects were those seeking monetary compensation from the provincial and Canadian governments and the comparison group was randomly selected from a pool of anti-HCV-negative subjects. The study was designed to detect an assumed difference of 20% in signs and symptoms between the two groups. Statistical comparisons were conducted using bivariate and multivariate logistic regression analyses. RESULTS: A total of 241 and 222 anti-HCV-positive and negative subjects were respectively interviewed and met the study's eligibility criteria. Results from the multivariate analysis indicated that anti-HCV-positive recipients were more likely to have two or more clinical symptoms (OR = 3.53; 95% CI: 1.44, 8.70), to be in worse health status as compared to ten years previous (OR = 1.60; 95% CI: 1.30, 1.96), to have a higher illness intrusiveness rating (OR = 1.35; 95% CI: 1.25, 1.46), and to be younger (OR = 0.97; 95% CI: 0.95, 0.98). CONCLUSION: Our results show that persons exposed to HCV were more likely to have had two or more clinical symptoms, be male, have worse health status as compared to ten years previous, have a higher illness intrusiveness rating, and be younger in age.

Length of ICU stay for chronic obstructive pulmonary disease varies among large community hospitals.

OBJECTIVE: To determine whether differences exist among large community hospitals in length of Intensive Care Unit (ICU) stay, hospital stay or hospital mortality for patients admitted to ICU and whose most responsible diagnosis was chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective cohort study. SETTING: All seven large community hospitals in British Columbia, Canada. PATIENTS. All 296 patients who were admitted to ICUs and whose most responsible diagnosis was COPD during the 3 fiscal years 1994-1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjusting for age, gender, case-mix group, and co-morbidity, we found a significant difference in length of ICU stay for these patients among hospitals ( P <0.03). No differences were found in hospital mortality or length of hospital stay for the same patients among the same hospitals. CONCLUSIONS: There is significant variation in length of ICU stay for patients who are admitted to ICU and whose most responsible diagnosis is COPD, among large community hospitals. These small area variations may point to opportunities to improve efficiency of care. Further prospective, detailed data collection is required to validate these observations and to identify factors responsible for any differences found.

Risk factors for elevated HIV incidence among Aboriginal injection drug users in Vancouver.

BACKGROUND: Because of established links between entrenched poverty and risk of HIV infection, there have long been warnings that HIV/AIDS will disproportionately affect Aboriginal people in Canada. We compared HIV incidence rates among Aboriginal and non-Aboriginal injection drug users (IDUs) in Vancouver and studied factors associated with HIV seroconversion among Aboriginal participants. METHODS: This analysis was based on 941 participants (230 Aboriginal people) recruited between May 1996 and December 2000 who were seronegative at enrollment and had completed at least one follow-up visit. Incidence rates were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to identify independent predictors of time to HIV seroconversion among female and male Aboriginal IDUs. RESULTS: As of May 31, 2001, seroconversion had occurred in 112 (11.9%) of the participants, yielding a cumulative incidence of HIV infection at 42 months of 12.7% (95% confidence interval [CI] 10.3%-15.1%). The cumulative incidence at 42 months was significantly higher among the Aboriginal participants than among the non-Aboriginal participants (21.1% v. 10.7%, p < 0.001). This elevation in risk was present in both female and male Aboriginal IDUs. Among the female Aboriginal IDUs, frequent speedball (combined cocaine and heroin) injection (adjusted relative risk [RR] 3.1; 95% CI 1.4-7.1) and going on binges of injection drug use (adjusted RR 2.3; 95% CI 1.0-5.2) were found to be independent predictors of HIV seroconversion. Among the male Aboriginal IDUs, the independent predictors of seroconversion were frequent speedball injection (adjusted RR 2.9; 95% CI 1.0-8.5) and frequent cocaine injection (adjusted RR 2.5; 95% CI 1.0-6.5). INTERPRETATION: In Vancouver, Aboriginal IDUs are becoming HIV positive at twice the rate of non-Aboriginal IDUs. Our findings emphasize the urgent need for an appropriate and effective public health strategy--planned and implemented in partnership with Aboriginal AIDS service organizations and the Aboriginal community--to reduce the harms of injection drug use in this population.

Age, adherence and injection drug use predict virological suppression among men and women enrolled in a population-based antiretroviral drug treatment programme.

OBJECTIVES: To characterize 1-year virological response to antiretroviral therapy and its determinants by sex. METHODS: This is a population-based analysis of antiretroviral therapy naive HIV-positive adult men and women. Factors associated with sex and with plasma HIV RNA viral load suppression to below 500 copies/ml were examined using non-parametric tests and logistic regression analyses. RESULTS: A total of 739 subjects (92 women and 647 men) were eligible. Female participants were younger (34 vs 37 years; P < 0.001), less likely to have AIDS (6.5 vs 14.4%; P = 0.039), more frequently injection drug users (44.6 vs 25.2%; P = 0.001) and were less likely to be adherent to therapy (34.8 vs 62.9%; P < 0.001) than male participants. There was no difference in baseline median CD4 count (P = 0.424) or HIV RNA levels (P = 0.140), physician experience (P = 0.057), or with respect to antiretroviral regimens containing protease inhibitors or non-nucleoside reverse transcriptase inhibitors (P = 0.911). With treatment, 46.7% (43/92) of women and 64.8% (419/647) of men (P = 0.001) suppressed HIV RNA viral load to below 500 copies/ml at 1 year. In a multivariate analysis, the association of sex with HIV RNA response to antiretroviral therapy fell from statistical significance (odds ratio 1.18; 95% CI: 0.72-1.95) after adjusting for adherence, injection drug use and age. CONCLUSION: Our data indicate that in this population-based setting, sex differences in 1-year virological response to antiretroviral therapy are explained by age, adherence and injection drug use.

Intensive care unit admission has minimal impact on long-term mortality.

OBJECTIVE: To measure the association between intensive care unit (ICU) admission and both hospital and long-term mortality, separate from the effect of hospital admission alone. DESIGN: Retrospective cohort study. SETTING: All hospitals in British Columbia, Canada, during 3 fiscal years, 1994 to 1996. PATIENTS: A total of 27,103 patients admitted to ICU and 41,308 (5% random sample) patients admitted to hospital but not to ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Although ICU admission was an important factor associated with hospital mortality (odds ratio: 9.12; 95% confidence interval: 8.34-9.96), the association between ICU admission and mortality after discharge was relatively minimal (hazard ratio: 1.21; 95% confidence interval: 1.17-1.27) and was completely overshadowed by the effect of age, gender, and diagnosis. CONCLUSIONS: After controlling for the effect of hospital admission, admission to ICU has minimal independent effect on mortality after discharge.

Risk factors for elevated HIV incidence rates among female injection drug users in Vancouver.

BACKGROUND: In 1997, we found a higher prevalence of HIV among female than among male injection drug users in Vancouver. Factors associated with HIV incidence among women in this setting were unknown. In the present study, we sought to compare HIV incidence rates among male and female injection drug users in Vancouver and to compare factors associated with HIV seroconversion. METHODS: This analysis was based on 939 participants recruited between May 1996 and December 2000 who were seronegative at enrolment with at least one follow-up visit completed, and who were studied prospectively until March 2001. Incidence rates were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to identify independent predictors of time to HIV seroconversion. RESULTS: As of March 2001, seroconversion had occurred in 110 of 939 participants (64 men, 46 women), yielding a cumulative incidence rate of HIV at 48 months of 13.4% (95% confidence interval [CI] 11.0%-15.8%). Incidence was higher among women than among men (16.6% v. 11.7%, p = 0.074). Multivariate analysis of the female participants' practices revealed injecting cocaine once or more per day compared with injecting less than once per day (adjusted relative risk [RR] 2.6, 95% CI 1.4-4.8), requiring help injecting compared with not requiring such assistance (adjusted RR 2.1, 95% CI 1.1-3.8), having unsafe sex with a regular partner compared with not having unsafe sex with a regular partner (adjusted RR 2.9, 95% CI 0.9-9.5) and having an HIV-positive sex partner compared with not having an HIV-positive sex partner (adjusted RR 2.7, 95% CI 1.0-7.7) to be independent predictors of time to HIV seroconversion. Among male participants, injecting cocaine once or more per day compared with injecting less than once per day (adjusted RR 3.3, 95% CI 1.9-5.6), self-reporting identification as an Aboriginal compared with not self-reporting identification as an Aboriginal (adjusted RR 2.5, 95% CI 1.4-4.2) and borrowing needles compared with not borrowing needles (adjusted RR 2.0, 95% CI 1.1-3.4) were independent predictors of HIV infection. INTERPRETATION: HIV incidence rates among female injection drug users in Vancouver are about 40% higher than those of male injection drug users. Different risk factors for seroconversion for women as opposed to men suggest that sex-specific prevention initiatives are urgently required.

Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients.

BACKGROUND: Nucleoside analogues can induce toxic effects on mitochondria by inhibiting the human DNA polymerase gamma. The toxic effects can range from increased serum lactate levels to potentially fatal lactic acidosis. We studied changes in mitochondrial DNA relative to nuclear DNA in the peripheral-blood cells of patients with symptomatic, nucleoside-induced hyperlactatemia. METHODS: Total DNA was extracted from blood cells. A nuclear gene and a mitochondrial gene were quantified by real-time polymerase chain reaction. Three groups were studied: 24 controls not infected with the human immunodeficiency virus (HIV), 47 HIV-infected asymptomatic patients who had never been treated with antiretroviral drugs, and 8 HIV-infected patients who were receiving antiretroviral drugs and had symptomatic hyperlactatemia. The patients in the last group were studied longitudinally before, during, and after antiretroviral therapy. RESULTS: Symptomatic hyperlactatemia was associated with marked reductions in the ratios of mitochondrial to nuclear DNA, which, during therapy, averaged 68 percent lower than those of non-HIV-infected controls and 43 percent lower than those of HIV-infected asymptomatic patients never treated with antiretroviral drugs. After the discontinuation of antiretroviral therapy, there was a statistically significant increase in the ratio of mitochondrial to nuclear DNA (P=0.02). In the patients followed longitudinally, the decline in mitochondrial DNA preceded the increase in venous lactate levels. CONCLUSIONS: Mitochondrial DNA levels are significantly decreased in patients with symptomatic, nucleoside-related hyperlactatemia, an effect that resolves on the discontinuation of therapy.

Case series assessing the safety of mycophenolate as part of multidrug rescue treatment regimens.

BACKGROUND: Mycophenolate mofetil (MMF), an inhibitor of lymphocyte proliferation, is emerging as a potential adjunct in the treatment of HIV-1 infection. By potentiating the activity of abacavir, MMF may improve antiviral efficacy. However, it may also lead to myelosuppression, such as was seen in patients taking hydroxyurea-containing regimens. PURPOSE: To assess the safety of MMF as adjunctive therapy for HIV infection. METHOD: Eighteen HIV-positive outpatients, given MMF (500 mg po bid) on a compassionate basis as part of their salvage therapy, were monitored for adverse effects. RESULTS: Five patients discontinued MMF between 26-68 days of follow-up due to adverse effects likely related to other factors. Among the remaining 13 patients, no new clinically significant cytopenias occurred over 107-154 days of follow-up. Three patients exhibited decreases in CD4 counts, despite decreases in plasma HIV-1 RNA. CONCLUSION: Short-term follow-up suggests that MMF (500 mg po bid) does not cause lymphocyte suppression. However, further studies are ongoing to determine its safety and efficacy profile in HIV infection.