Prescription opioid injection and risk of hepatitis C in relation to traditional drugs of misuse in a prospective cohort of street youth

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

Family Talk for substance use prevention

Intervention manual and training module for the Family Talk intervention.Family Talk is an intervention to prevent substance use initiation and progression among teen and young adult children of adults with substance use disorders. It has not yet been piloted or tested. This manual was developed with the input of experts with backgrounds in pediatrics, clinical psychology, prevention, and intervention research design and evaluation

Alcohol Policies and Alcoholic Cirrhosis Mortality in the United States

Introduction Stronger alcohol policies predict decreased alcohol consumption and binge drinking in the United States. We examined the relation- ship between the strength of states’ alcohol policies and alcoholic cirrhosis mortality rates. Methods We used the Alcohol Policy Scale (APS), a validated assessment of policies of the 50 US states and Washington DC, to quantify the efficacy and implementation of 29 policies. State APS scores (the- oretical range, 0–100) for each year from 1999 through 2008 were compared with age-adjusted alcoholic cirrhosis death rates that oc- curred 3 years later. We used Poisson regression accounting for state-level clustering and adjusting for race/ethnicity, college edu- cation, insurance status, household income, religiosity, policing rates, and urbanization. Results Age-adjusted alcoholic cirrhosis mortality rates varied signific- antly across states; they were highest among males, among resid- ents in states in the West census region, and in states with a high proportion of American Indians/Alaska Natives (AI/ANs). Higher APS scores were associated with lower mortality rates among fe- males (adjusted incidence rate ratio [IRR], 0.91 per 10-point in- crease in APS score; 95% confidence interval [95% CI], 0.84–0.99) but not among males (adjusted IRR, 0.97; 95% CI, 0.90–1.04). Among non-AI/AN decedents, higher APS scores were also associated with lower alcoholic cirrhosis mortality rates among both sexes combined (adjusted IRR, 0.89; 95% CI, 0.82–0.97). Policies were more strongly associated with lower mortality rates among those living in the Northeast and West census regions than in other regions. Conclusions Stronger alcohol policy environments are associated with lower al- coholic cirrhosis mortality rates. Future studies should identify un- derlying reasons for racial/ethnic and regional differences in this relationship

Access to substance use treatment among young adults who use prescription opioids non-medically

BACKGROUND: Non-medical prescription opioid (NMPO) use is a substantial public health problem in the United States, with 1.5 million new initiates annually. Only 746,000 people received treatment for NMPO use in 2013, demonstrating substantial disparities in access to treatment. This study aimed to assess correlates of accessing substance use treatment among young adult NMPO users in Rhode Island, a state heavily impacted by NMPO use and opioid overdose. METHODS: This analysis uses data from a study of 200 Rhode Island residents aged 18 to 29 who reported NMPO use in the past 30 days. We compared individuals who had ever successfully enrolled in a substance use treatment program without ever facing barriers, individuals who had ever attempted to enroll but were unable, and individuals who never attempted to enroll. We used multinomial logistic regression to determine the independent correlates of never attempting and unsuccessfully attempting to access substance use treatment. RESULTS: Among 200 participants, the mean age was 24.5, 65.5% were male, and 61.5% were white. Nearly half (45.5%) had never attempted to enroll in substance use treatment, while 35.0% had successfully enrolled without ever facing barriers and 19.5% were unsuccessful in at least one attempt to enroll. In multivariable models, non-white participants were more likely to never have attempted to enroll compared to white participants. Previous incarceration, experiencing drug-related discrimination by the medical community, and a monthly income of $501 -$1500 were associated with a decreased likelihood of never attempting to enroll. A history of overdose and a monthly income of $501 -$1500 were associated with an increased likelihood of unsuccessfully accessing treatment. The most commonly reported barriers to accessing treatment were waiting lists (n = 23), health insurance not approving enrollment (n = 20), and inability to pay (n = 16). CONCLUSIONS: This study demonstrates significant disparities in access to treatment among young adults who report NMPO use. A history of overdose was shown to correlate with experiencing barriers to substance use treatment utilization. Interventions are needed to reduce drug-related discrimination in clinical settings and to provide mechanisms that link young adults (particularly with a history of overdose) to evidence-based treatment

Increased Burden of Suicidality Among Young Street-Involved Sex Workers who Use Drugs in Vancouver, Canada

Abstract: Background: The risks of suicidality among street-involved youth who use drugs and engage in sex work is not well described. This study sought to evaluate if street-involved youth who engage in sex work were at an elevated risk for attempting suicide. Methods: Data were derived from the At-Risk Youth Study, a prospective cohort of street-involved youth who use drugs in Vancouver, Canada. Multivariable generalized estimating equation analyses were employed to examine whether youth who engaged in sex work were at elevated risk of attempting suicide, controlling for possible confounders. Results: Between September 2005 and May 2015, 1210 youth were recruited into the cohort, of whom, 173 (14.3%) reported recently attempting suicide at some point during the study period. In multivariable analysis, youth who engaged in sex work were significantly more likely to report a recent suicide attempt (adjusted odds ratio=1.93; 95% confidence interval: 1.28-2.91). Conclusions: Street-involved youth who engage in sex work were observed to be at a significantly higher risk for suicidality. Systematic discrimination and unaddressed trauma may contribute to the observed increased burden of suicidality among this population. Interventions that support the mental health and well-being of street-involved youth who engage in sex work are urgently needed

NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells

NOTCH signaling is required for the arterial specification and formation of hematopoietic stem cells (HSCs) and lympho-myeloid progenitors in the embryonic aorta-gonad-mesonephros region and extraembryonic vasculature from a distinct lineage of vascular endothelial cells with hemogenic potential. However, the role of NOTCH signaling in hemogenic endothelium (HE) specification from human pluripotent stem cell (hPSC) has not been studied. Here, using a chemically defined hPSC differentiation system combined with the use of DLL1-Fc and DAPT to manipulate NOTCH, we discover that NOTCH activation in hPSC-derived immature HE progenitors leads to formation of CD144+CD43−CD73−DLL4+Runx1 + 23-GFP+ arterial-type HE, which requires NOTCH signaling to undergo endothelial-to-hematopoietic transition and produce definitive lympho-myeloid and erythroid cells. These findings demonstrate that NOTCH-mediated arterialization of HE is an essential prerequisite for establishing definitive lympho-myeloid program and suggest that exploring molecular pathways that lead to arterial specification may aid in vitro approaches to enhance definitive hematopoiesis from hPSCs

State-level prescription drug monitoring program mandates and adolescent injection drug use in the United States, 1995-2017: A difference-in-differences analysis.

BackgroundPrescription opioid misuse is an ongoing crisis and a risk factor for injection drug use (IDU). Few studies have evaluated strategies for preventing opioid or IDU initiation among adolescents. We evaluated changes in the proportion of adolescents reporting IDU before and after prescription drug monitoring program (PDMP) mandates were implemented in 18 states compared to 29 states without such mandates.Methods and findingsThis difference-in-differences analysis used biannual Youth Risk Behavioral Surveillance System (YRBSS) data representative of adolescents 17 to 18 years old across 47 states from 1995 to 2017. We compared changes in adolescent IDU in 18 states with and 29 states without PDMP mandates. Among 331,025 adolescents, 51.7% identified as male, 62.1% as non-Hispanic white, 17.4% as non-Hispanic black, and 14.6% as Hispanic. Overall, 3.5% reported IDU during the 2 years prior to PDMP mandates. In the final multivariable difference-in-differences model, we included individual age, sex, and race/ethnicity, as well as state and year as covariates from the YRBSS. We also included state- and year-specific poverty rates based on US Census Bureau data. Additionally, we controlled for state implementation of (non-mandated) PDMPs before states subsequently implemented mandates and pill mill laws. We conducted several sensitivity analyses, including repeating our main analysis using a logistic, rather than linear, model, and with a lead indicator on PDMP mandate implementation, a lag indicator, and alternative policy implementation dates. PDMP mandates were associated with a 1.5 percentage point reduction (95% CI -2.3 to -0.6 percentage points; p = 0.001) in adolescent IDU, on average over the years following mandate implementation, a relative reduction of 42.9% (95% CI -65.7% to -17.1%). The association of PDMP mandates with this reduction persisted at least 4 years beyond implementation. Sensitivity analyses were consistent with the main results. Limitations include the multi-stepped causal pathway from PDMP mandate implementation to changes in IDU and the potential for omitted state-level time-varying confounders.ConclusionsOur analysis indicated that PDMP mandates were associated with a reduction in adolescent IDU, providing empirical evidence that such mandates may prevent adolescents from initiating IDU. Policymakers might consider PDMP mandates as a potential strategy for preventing adolescent IDU

Stigma associated with medication treatment for young adults with opioid use disorder: a case series.

Abstract Background Opioid-related overdose deaths have risen sharply among young adults. Despite this increase, access to evidence-based medication for opioid agonist treatment (OAT) for youth remains low. Among older adults, barriers to OAT include the paucity of buprenorphine-waivered prescribers and low rates of prescribing among waivered physicians. We have increasingly found in our clinical practice significant stigma related to using OAT to treat addiction for young adults. In this series, we describe three cases of young adults who faced significant stigma related to their treatment. Case presentations The first case is a young male with a history of significant trauma and a severe opioid use disorder. He started buprenorphine and has found a job, stayed abstinent, and began a healthy relationship. At each step in his recovery, he has faced resistance to taking medication from other treatment providers, directors of sober houses, and his parents. The second case is a young woman who presented to a substance use treatment program after a relapse. She was unable to restart buprenorphine despite our calling to ask that it be restarted. Ultimately, she left against medical advice and was stabilized as an outpatient on buprenorphine. The final case is a young woman who stopped buprenorphine after being told she was “not sober” while attending 12-step group but restarted after conversations with her clinical team. In each case, the patient has continued their medication treatment and are stable. Conclusions Opioid-related deaths continue to rise among all age groups, including young adults. Stigma related to medication treatment can be a substantial barrier for many young adult patients but there are concrete steps that providers and communities can take to address this stigma

Cessation of Injecting and Preceding Drug Use Patterns Among a Prospective Cohort of Street-Involved Youth

Purpose: Injection drug use is prevalent among street-involved youth, but patterns of cessation are poorly described. We identified drug use patterns preceding injection cessation among street-involved youth. Methods: From September 2005 to May 2015, we collected data from the At-Risk Youth Study, a prospective cohort of street-involved youth in Vancouver, Canada, and limited the sample to actively injecting youth. The primary outcome was cessation of injecting self-reported at semiannual follow-up visits. We used Cox regression to identify drug use patterns preceding cessation. Results: Among 383 youth, 65% were male, mean age was 22.3 (SD, 2.5; range, 15-30) years, and 171 (45%) ceased injecting for 6 months or more (crude incidence density 22 per 100 person-years; 95% confidence interval [CI], 19-26). Youth who ceased were less likely to have injected daily (adjusted hazard ratio [AHR], 0.40; 95% CI, 0.28-0.56), injected heroin (AHR, 0.40; 95% CI, 0.29-0.56), or injected crystal methamphetamine (AHR, 0.43; 95% CI, 0.31-0.59) prior to cessation. Non-injection heroin use was positively associated with injection cessation (AHR, 1.52; 95 CI, 1.12-2.08). Addiction treatment was not associated with cessation. At the time of cessation, 101 (59%) youth continued to use ‘hard’ non-injection drugs such as heroin and crystal methamphetamine. Conclusions: Periods of injection cessation were common but frequently accompanied by ongoing non-injection drug use. Findings indicate that trajectories of injection drug use among youth are complex and highlight the need to further explore relationships between ongoing non-injection drug use and injection cessation