Burden and correlates of mental health diagnoses among sex workers in an urban setting

Background: Women involved in both street-level and off-street sex work face disproportionate health and social inequities compared to the general population. While much research has focused on HIV and sexually transmitted infections (STIs) among sex workers, there remains a gap in evidence regarding the broader health issues faced by this population, including mental health. Given limited evidence describing the mental health of women in sex work, our objective was to evaluate the burden and correlates of mental health diagnoses among this population in Vancouver, Canada. Methods: An Evaluation of Sex Workers Health Access (AESHA) is a prospective, community-based cohort of on- and off-street women in sex work in Vancouver, Canada. Participants complete interviewer-administered questionnaires semi-annually. We analyzed the lifetime burden and correlates of self-reported mental health diagnoses using bivariate and multivariable logistic regression. Results: Among 692 sex workers enrolled between January 2010 and February 2013, 338 (48.8%) reported ever being diagnosed with a mental health issue, with the most common diagnoses being depression (35.1%) and anxiety (19.9%). In multivariable analysis, women with mental health diagnoses were more likely to identify as a sexual/gender minority (LGBTQ) [AOR=2.56, 95% CI: 1.72—3.81], to use non-injection drugs [AOR=1.85, 95% CI: 1.12—3.08], to have experienced childhood physical/sexual trauma [AOR=2.90, 95% CI: 1.89—4.45], and work in informal indoor [AOR=1.94, 95% CI: 1.12 – 3.40] or street/public spaces [AOR=1.76, 95% CI: 1.03–2.99]. Conclusions: This analysis highlights the disproportionate mental health burden experienced by women in sex work, particularly among those identifying as a sexual/gender minority, those who use drugs, and those who work in informal indoor venues and street/public spaces. Evidence-informed interventions tailored to sex workers that address intersections between trauma and mental health should be further explored, alongside policies to foster access to safer workspaces and health services.Medicine, Faculty ofOther UBCNon UBCFamily Practice, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult

Gender Influences on Hepatitis C Incidence Among Street Youth in a Canadian Setting

Purpose Few studies have examined gender-based differences in the risk of hepatitis C (HCV) infection among street-involved youth. We compared rates of HCV infection among male and female street-involved youth in a Canadian setting. Methods The At-Risk Youth Study (ARYS) is a prospective cohort of drug-using, street-involved youth. Study recruitment and follow-up occurred in Vancouver, Canada, between September 2005 and November 2011. Eligible participants were illicit drug-using youth aged 14–26 years at enrollment, recruited by street-based outreach. We evaluated rates of HCV antibody seroconversion, measured every six months during study follow-up, and used Cox proportional hazards regression to compare risk factors for HCV incidence between male and female street youth. Results Among 512 HCV-seronegative youth contributing 836 person-years of follow-up, 56 (10.9%) seroconverted to HCV. Among female participants, the incidence density of HCV infection was 10.9 per 100 person-years and in males 5.1 per 100 person-years (p = 0.009). In multivariate analyses, female gender was independently associated with a higher rate of HCV seroconversion (Adjusted Hazard Ratio (AHR) = 2.01; 95% Confidence Interval [CI], 1.18 – 3.44). Risk factors were similar in gender stratified analyses and included injection heroin and injection crystal methamphetamine, although syringe sharing was only associated with HCV incidence among males. Conclusions Among street-involved youth in this setting, females had double the incidence of HCV seroconversion demonstrating the need for gender focused HCV prevention interventions for this population.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofReviewedFacultyResearche

Gender Influences on Hepatitis C Incidence Among Street Youth in a Canadian Setting

PURPOSE: Few studies have examined gender-based differences in the risk of hepatitis C (HCV) infection among street-involved youth. We compared rates of HCV infection among male and female street-involved youth in a Canadian setting. METHODS: The At-Risk Youth Study (ARYS) is a prospective cohort of drug-using, street-involved youth. Study recruitment and follow-up occurred in Vancouver, Canada, between September 2005 and November 2011. Eligible participants were illicit drug-using youth aged 14–26 years at enrollment, recruited by street-based outreach. We evaluated rates of HCV antibody seroconversion, measured every six months during study follow-up, and used Cox proportional hazards regression to compare risk factors for HCV incidence between male and female street youth. RESULTS: Among 512 HCV-seronegative youth contributing 836 person-years of follow-up, 56 (10.9%) seroconverted to HCV. Among female participants, the incidence density of HCV infection was 10.9 per 100 person-years and in males 5.1 per 100 person-years (p = 0.009). In multivariate analyses, female gender was independently associated with a higher rate of HCV seroconversion (Adjusted Hazard Ratio (AHR) = 2.01; 95% Confidence Interval [CI], 1.18 – 3.44). Risk factors were similar in gender stratified analyses and included injection heroin and injection crystal methamphetamine, although syringe sharing was only associated with HCV incidence among males. CONCLUSIONS: Among street-involved youth in this setting, females had double the incidence of HCV seroconversion demonstrating the need for gender focused HCV prevention interventions for this population

Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide

Expansions of a G4C2 repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset neurodegenerative disorders. Using C9-ALS/FTD patient-derived cells and C9ORF72 BAC transgenic mice, we generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of G4C2 repeat-containing transcripts and effectively suppress tissue levels of poly(GP) dipeptides. ASOs with reduced phosphorothioate content showed improved tolerability without sacrificing efficacy. In a single patient harboring mutant C9ORF72 with the G4C2 repeat expansion, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of cerebrospinal fluid poly(GP). This report provides insight into the effect of nucleic acid chemistry on toxicity and, to our knowledge, for the first time demonstrates the feasibility of clinical suppression of the C9ORF72 gene. Additional clinical trials will be required to demonstrate safety and efficacy of this therapy in patients with C9ORF72 gene mutations

Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide

Expansions of a GC repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset neurodegenerative disorders. Using C9-ALS/FTD patient-derived cells and C9ORF72 BAC transgenic mice, we generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of GC repeat-containing transcripts and effectively suppress tissue levels of poly(GP) dipeptides. ASOs with reduced phosphorothioate content showed improved tolerability without sacrificing efficacy. In a single patient harboring mutant C9ORF72 with the GC repeat expansion, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of cerebrospinal fluid poly(GP). This report provides insight into the effect of nucleic acid chemistry on toxicity and, to our knowledge, for the first time demonstrates the feasibility of clinical suppression of the C9ORF72 gene. Additional clinical trials will be required to demonstrate safety and efficacy of this therapy in patients with C9ORF72 gene mutations