Population perinatal substance use and an environmental scan of health services in British Columbia, Canada.

Background: Substance use during pregnancy is underreported globally and there is limited data on its prevalence and the availability of supportive services. This study determined population perinatal substance use in British Columbia (BC) by region and examined the availability of clinical and community-based programs.

Methods: Using linked provincial health administrative data, we conducted a population-based retrospective cohort study including all BC residents accessing care for substance use (alcohol, opioids, stimulants, sedatives, and cannabis) within 12 months of first perinatal care record to delivery during 2016-2021.

Estimating the potential value of MSM-focused evidence-based implementation interventions in three Ending the HIV Epidemic jurisdictions in the United States: a model-based analysis.

Introduction: Improving the delivery of existing evidence-based interventions to prevent and diagnose HIV is key to Ending the HIV Epidemic in the United States. Structural barriers in the access and delivery of related health services require municipal or state-level policy changes; however, suboptimal implementation can be addressed directly through interventions designed to improve the reach, effectiveness, adoption or maintenance of available interventions. Our objective was to estimate the cost-effectiveness and potential epidemiological impact of six real-world implementation interventions designed to address these barriers and increase the scale of delivery of interventions for HIV testing and pre-exposure prophylaxis (PrEP) in three US metropolitan areas.

Translating and disseminating a localised economic model to support implementation of the 'Ending the HIV Epidemic' initiative to public health policymakers.

Background: Despite significant progress in HIV treatment and prevention, the US remains far from its goal of 'Ending the HIV Epidemic' by 2030. Economic models using local data can synthesise the evidence to help policymakers allocate HIV resources efficiently, but persistent research-to-practice gaps remain. Little is known about how to facilitate the use of economic modelling data among local public health policymakers in real-world settings.

Opioid agonist therapy and mortality among First Nations and other residents with concurrent alcohol use disorder in British Columbia, Canada: A population-based cohort study.

Background: Despite the prevalence of alcohol use among people with opioid use disorder (PWOUD) engaged in opioid agonist therapy (OAT), clinical care guidance for concurrent alcohol use disorder (AUD) and OUD is scarce. We assessed the prevalence and risk of mortality for concurrent AUD among PWOUD who accessed OAT in British Columbia (BC).

Methods: Data were obtained from six linked population-level health administrative datasets to identify PWOUD from January 1996 to March 2020.

Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol.

Introduction: Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs-particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency.

Validation and endorsement of health system performance measures for opioid use disorder in British Columbia, Canada: A Delphi panel study.

Background: Limited data exists on the performance of the healthcare system in opioid use disorder (OUD). We evaluated the face validity and potential risks of a set of health system performance measures for OUD collaboratively with clinicians, policymakers and people with lived experience of opioid use (PWLE) in the interest of establishing an endorsed set of measures for public reporting.

Methods: Through a two-stage Delphi-panel approach, a panel of clinical and policy experts validated and considered 102 previously constructed OUD performance measures for endorsement using information on measurement construction, sensitivity analyses, quality of evidence, predictive validity, and feedback from local PWLE.

The Testing Imperative: Why the US Ending the Human Immunodeficiency Virus (HIV) Epidemic Program Needs to Renew Efforts to Expand HIV Testing in Clinical and Community-Based Settings.

Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019.

Incremental expenditures attributable to daily dispensation and witnessed ingestion for opioid agonist treatment in British Columbia: 2014-20.

Background And Aim: While daily witnessed opioid agonist treatment (OAT) ingestion is common in British Columbia (BC), Canada, and elsewhere, sparse evidence supports this resource-intensive practice. Many settings across North America relaxed restrictions for take-home dosing during the COVID-19 pandemic and have reported consistent or improved patient outcomes. This study measured excess expenditures attributed to daily witnessed pharmacy dispensing compared with weekly or biweekly dispensation schedules.

Higher Hospitalization Rates in Children Born HIV-exposed Uninfected in British Columbia, Canada, Between 1990 and 2012.

Background: Compared with children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada.

Methods: This retrospective controlled cohort study used administrative health data from 1990 to 2012.

Opioid Use Disorder and Perinatal Outcomes.

Objectives: Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes.

Preterm Birth and Antiretroviral Exposure in Infants HIV-exposed Uninfected.

Background: Infants HIV-exposed and uninfected (IHEU) who are born to women living with HIV are at an increased risk of preterm birth (PTB). Antenatal exposure to certain maternal antiretroviral therapy (ART) regimens has been associated with PTB, although existing studies in this domain are limited and report discordant findings. We determined odds of PTB among IHEU by antenatal ART regimens and timing of exposure, adjusting for maternal risk factors.

The Potential Epidemiological Impact of Coronavirus Disease 2019 (COVID-19) on the Human Immunodeficiency Virus (HIV) Epidemic and the Cost-effectiveness of Linked, Opt-out HIV Testing: A Modeling Study in 6 US Cities.

Background: Widespread viral and serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a unique opportunity to also test for human immunodeficiency virus (HIV) infection. We estimated the potential impact of adding linked, opt-out HIV testing alongside SARS-CoV-2 testing on the HIV incidence and the cost-effectiveness of this strategy in 6 US cities.

Methods: Using a previously calibrated dynamic HIV transmission model, we constructed 3 sets of scenarios for each city: (1) sustained current levels of HIV-related treatment and prevention services (status quo); (2) temporary disruptions in health services and changes in sexual and injection risk behaviors at discrete levels between 0%-50%; and (3) linked HIV and SARS-CoV-2 testing offered to 10%-90% of the adult population in addition to Scenario 2.

Comparative effectiveness of buprenorphine-naloxone versus methadone for treatment of opioid use disorder: a population-based observational study protocol in British Columbia, Canada.

Introduction: Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics.

"Ending the Epidemic" Will Not Happen Without Addressing Racial/Ethnic Disparities in the United States Human Immunodeficiency Virus Epidemic.

We estimated human immunodeficiency virus incidence and incidence rate ratios (IRRs) for black and Hispanic vs white populations in 6 cities in the United States (2020-2030). Large reductions in incidence are possible, but without elimination of disparities in healthcare access, we found that wide disparities persisted for black compared with white populations in particular (lowest IRR, 1.69 [95% credible interval, 1.

Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study.

Objective: To compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply.

Design: Population based retrospective cohort study.

Setting: Individual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada.

The cascade of care for opioid use disorder: a retrospective study in British Columbia, Canada.

Background And Aims: The 'cascade of care' framework, measuring attrition at various stages of care engagement, has been proposed to guide the public health response to the opioid overdose public health emergency in British Columbia, Canada. We estimated the cascade of care for opioid use disorder and identified factors associated with care engagement for people with opioid use disorder (PWOUD) provincially.

Design: Retrospective study using a provincial-level linkage of four health administrative databases.

Exploring the live birth rates of women living with HIV in British Columbia, Canada.

Objective: To evaluate the birth rates of women living with HIV (WLWH) compared to the general population in British Columbia (BC), Canada.

Methods: We retrospectively reviewed clinical and population level surveillance data from 1997 to 2015. Live birth rates from 1997 to 2015 among WLWH aged 15-49 years were compared with those of all BC women.

Neurodevelopmental outcomes and in-utero antiretroviral exposure in HIV-exposed uninfected children.

Objectives: To assess and compare neurodevelopmental disorders in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children in British Columbia, Canada. To determine associations between these outcomes and in-utero exposure to antiretroviral drugs.

Design: Retrospective controlled cohort study.

Ywhaz/14-3-3ζ Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism.

Multiple signaling pathways mediate the actions of metabolic hormones to control glucose homeostasis, but the proteins that coordinate such networks are poorly understood. We previously identified the molecular scaffold protein, 14-3-3ζ, as a critical regulator of in vitro β-cell survival and adipogenesis, but its metabolic roles in glucose homeostasis have not been studied in depth. Herein, we report that Ywhaz gene knockout mice (14-3-3ζKO) exhibited elevated fasting insulin levels while maintaining normal β-cell responsiveness to glucose when compared with wild-type littermate controls.

Inter-domain tagging implicates caveolin-1 in insulin receptor trafficking and Erk signaling bias in pancreatic beta-cells.

Objective: The role and mechanisms of insulin receptor internalization remain incompletely understood. Previous trafficking studies of insulin receptors involved fluorescent protein tagging at their termini, manipulations that may be expected to result in dysfunctional receptors. Our objective was to determine the trafficking route and molecular mechanisms of functional tagged insulin receptors and endogenous insulin receptors in pancreatic beta-cells.

High-content screening identifies a role for Na(+) channels in insulin production.

Insulin production is the central feature of functionally mature and differentiated pancreatic β-cells. Reduced insulin transcription and dedifferentiation have been implicated in type 2 diabetes, making drugs that could reverse these processes potentially useful. We have previously established ratiometric live-cell imaging tools to identify factors that increase insulin promoter activity and promote β-cell differentiation.