Context Many studies have shown a high prevalence of sexually transmitted diseases, human immunodeficiency virus (HIV) infection, viral hepatitis, drug dependence, and mental health problems among street youth. However, data on mortality among these youth are sparse.Objectives To estimate mortality rate among street youth in Montreal and to identify causes of death and factors increasing the risk of death.Design, Setting, and Population From street youth 14 to 25 years of age were recruited in a prospective cohort with semiannual follow-ups. Original study objectives were to determine the incidence and risk factors for HIV infection in that population; however, several participants died during the first months of follow-up, prompting investigators to add mortality to the study objectives. Mortality data were obtained from the coroner's office and the Institut de la Statistique du Qué bec. Main Outcome MeasuresMortality rate among participants and factors increasing the risk of death.Results Twenty-six youth died during follow-up for a mortality rate of 921 per 100000 person-years (95% confidence interval [CI], 602-1350); this represented a standardized mortality ratio of 11.4. The observed causes of death were as follows: suicide (13), overdose (8), unintentional injury (2), fulminant hepatitis A (1), heart disease (1); 1 was unidentified. In multivariate Cox regression analyses, HIV infection (adjusted hazard ratio [AHR]=5.6; 95% CI, 1.9-16.8), daily alcohol use in the last month (AHR=3.2; 95% CI, 1.3-7.7), homelessness in the last 6 months (AHR=3.0; 95% CI, 1.1-7.6), drug injection in the last 6 months (AHR=2.7; 95% CI, 1.2-6.2), and male sex (AHR=2.6; 95% CI, 0.9-7.7) were identified as independent predictors of mortality.Conclusions Current heavy substance use and homelessness were factors associated with death among street youth. HIV infection was also identified as an important predictor of mortality; however, its role remains to be clarified. These findings should be taken into account when developing interventions to prevent mortality among street youth.

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SummaryBackgroundPeople who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID.MethodsIn this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity.FindingsWe included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk.InterpretationIncarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID.FundingEngineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health.

Aims: The study objectives were to examine trends in prescription opioid (PO) injection and to assess its association with HCV seroconversion among injection drug users (IDUs), accounting for other risk factors.Design and Setting: A prospective cohort study of IDUs was carried out between 2004 and 2009 in Montreal, Canada.Participants and Measurements: 246 HCV-negative IDUs were included in this analysis. Semiannual visits included HCV antibody testing and an interview-administered questionnaire assessing risk behaviours. HCV incidence rate was calculated using the person-time method.Time-updated Cox regression models were conducted to examine predictors of HCV incidence.Findings: The proportion of IDUs reporting PO injection increased from 21% to 75% between 2004 and 2009 (p < 0.001). Of the 246 participants (81.6% male; mean age 34.5 years; mean follow-up time 23 months), 83 seroconverted to HCV (incidence rate: 17.9 per 100 person-years; 95% CI 14.3, 22.1). PO injectors were more likely to become infected if they did not use injection heroin (Adjusted Hazard Ratio (AHR): 2.9 (95% CI: 1.5, 5.5)), whereas the association was not statistically significant for participants who reported using both drugs (AHR: 1.2 (95%CI: 0.6, 2.3). Other independent predictors of HCV incidence were: cocaine injection, recent incarceration, and > 30 injections per month.Conclusion: PO injection has increased rapidly in recent years, and appears to be an important risk factor for HCV acquisition. Our results suggest that the risks related to PO injection may be conditioned by specific drug practices which differ from those of heroin users.

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Starting in 2007, a 2-year study based on ethnographic methodology was carried out downtown Montréal, Canada. A thematic analysis of observational and interview-based notes was conducted. Illicit prescription opioid (PO) use was widespread among street-based participants. Injection was the main mode of PO administration observed among users. Some injection practices such as “doing a wash” could pose new challenges in terms of prevention of infections. More research is needed to examine the role of illicit PO use in the development of opiate addiction and to better understand drug-using contexts that put PO users at risk of infections. The study’s limitations are noted.

Most street youth used clean needles at first injection, but use of other clean injection materials was less frequent. Factors other than dependence appear to play a significant role in initiation into injection.

By providing access to affected neurons, human induced pluripotent stem cells (iPSc) offer a unique opportunity to model human neurodegenerative diseases. We generated human iPSc from the skin fibroblasts of children with mucopolysaccharidosis type IIIB. In this fatal lysosomal storage disease, defective α-N-acetylglucosaminidase interrupts the degradation of heparan sulfate (HS) proteoglycans and induces cell disorders predominating in the central nervous system, causing relentless progression toward severe mental retardation. Partially digested proteoglycans, which affect fibroblast growth factor signaling, accumulated in patient cells. They impaired isolation of emerging iPSc unless exogenous supply of the missing enzyme cleared storage and restored cell proliferation. After several passages, patient iPSc starved of an exogenous enzyme continued to proliferate in the presence of fibroblast growth factor despite HS accumulation. Survival and neural differentiation of patient iPSc were comparable with unaffected controls. Whereas cell pathology was modest in floating neurosphere cultures, undifferentiated patient iPSc and their neuronal progeny expressed cell disorders consisting of storage vesicles and severe disorganization of Golgi ribbons associated with modified expression of the Golgi matrix protein GM130. Gene expression profiling in neural stem cells pointed to alterations of extracellular matrix constituents and cell-matrix interactions, whereas genes associated with lysosome or Golgi apparatus functions were downregulated. Taken together, these results suggest defective responses of patient undifferentiated stem cells and neurons to environmental cues, which possibly affect Golgi organization, cell migration and neuritogenesis. This could have potential consequences on post-natal neurological development, once HS proteoglycan accumulation becomes prominent in the affected child brain.