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Background: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD)., Methods: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs. Using published guidelines, we assessed and compared each IV according to the four assumptions for IVs, employing both empirical assessment and content expertise. We evaluated the robustness of results using sensitivity analyses., Results: The study sample included 35,904 incident users (43.3% on buprenorphine/naloxone) initiated on opioid agonist treatment by 1585 prescribers during the study period. While all candidate IVs were strong (A1) according to conventional criteria, by expert opinion, we found no evidence against assumptions of exclusion (A2), independence (A3), monotonicity (A4a), and homogeneity (A4b) for prescribing preference-based IV. Some criteria were violated for the calendar time-based IV. We determined that preference in provider-level prescribing, measured on a continuous scale, was the most suitable IV for comparative effectiveness of buprenorphine/naloxone and methadone for the treatment of OUD., Conclusions: Our results suggest that prescriber's preference measures are suitable IVs in comparative effectiveness studies of treatment for OUD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Background: In response to the COVID-19 pandemic, the US Substance Abuse and Mental Health Services Administration (SAMHSA) allowed for an increase in methadone take-home doses for the treatment of Opioid Use Disorder (OUD) in March 2020., Objective: To evaluate the effects of the SAMSHA exemption on methadone adherence and OUD-related outcomes., Methods: A convenience sample of 183 clients (58% female) were recruited from a methadone clinic in the fall of 2019 for a cross-sectional survey. Survey data was linked to clinical records, including urine drug testing (UDT) results for methadone and emergency department (ED) visits at the local hospital. Participants were on stable methadone dosing for 9 months prior to and following March 2020. Methadone adherence was assessed by UDTs; OUD-related outcomes were assessed by overdose events and ED visits. Logistic regression was used to assess the association between change in take-home methadone doses and outcomes., Results: Mean take-home doses increased nearly 200% (11.4 doses/30 days pre-COVID-19 vs. 22.3 post-SAMHSA exemption). ED visits dropped from 74 (40.4%) pre-COVID-19 to 56 (30.6%) post-SAMHSA exemption ( p = <0.001). No significant changes were observed in either the number of clients experiencing overdose or those who experienced one or more methadone negative UDTs in the post-SAMHSA exemption period. Adjusted models did not show a significant association between changes in take-home doses and associated outcomes., Conclusions: Despite a near-doubling of take-home methadone doses during the COVID-19 exemption period, the increase in take-home doses was not associated with negative treatment outcomes in methadone-adherent clients.

Background: Active illicit drug use can present a barrier to the medical management of HIV infection by complicating adherence to antiretroviral therapy (ART). Plasma HIV-1 RNA viral load (VL) rebound, defined as a period of detectable HIV VL following ART and VL suppression, can lead to the generation of viral resistance and potential treatment failure. We sought to investigate the contribution of substance use patterns on rates of VL rebound., Methods: We used data from the ACCESS study, a long-running community-recruited prospective cohort of HIV-positive people who use illicit drugs in Vancouver, Canada, a setting of universal no-cost HIV treatment. We analysed time to VL rebound (that is, two consecutive observations ≥1,000 copies/ml) after ART initiation and sustained viral suppression (that is, two consecutive observations <50 copies/ml) using extended Cox regression models with a recurrent events framework., Results: Between May 1996 and November 2013, 564 ART-exposed participants achieved at least one instance of VL suppression and contributed 1,893.8 person-years of observation. Over follow-up, 198 (35.1%) participants experienced ≥ one instance of VL rebound. In adjusted analyses, VL rebound was associated with younger age (adjusted hazard ratio [AHR] =0.97, 95% CI: 0.95, 0.98), heroin injection (≥ daily versus < daily, AHR =1.52, 95% CI: 1.01, 2.30), crack use (≥ daily versus < daily, AHR = 1.73, 95% CI: 1.08, 1.92) and heavy alcohol use (≥ four versus < four drinks/day, AHR =1.97, 95% CI: 1.17, 3.31)., Conclusions: The present study suggests that in addition to heavy alcohol use, high-intensity illicit drug use, particularly ≥ daily heroin injection and ≥ daily crack smoking are risk factors for VL rebound. In addition to the impact of high-intensity drug use on health-care engagement and ART adherence, some evidence exists on the direct impact of psychoactive substances on ART metabolism and the natural progression of HIV disease. At-risk individuals should be provided additional supports to preserve virological control and maintain the benefits of ART.

Background: Hepatitis C virus (HCV) represents a significant cause of morbidity and mortality globally. While sex workers may face elevated HCV risks through both drug and sexual pathways, incidence data among sex workers are severely lacking. HCV incidence and predictors of HCV seroconversion among women sex workers in Vancouver, BC were characterized in this study., Methods: Questionnaire and serological data were drawn from a community-based cohort of women sex workers (2010-2014). Kaplan-Meier methods and Cox regression were used to model HCV incidence and predictors of time to HCV seroconversion., Results: Among 759 sex workers, HCV prevalence was 42.7%. Among 292 baseline-seronegative sex workers, HCV incidence density was 3.84/100 person-years (PY), with higher rates among women using injection drugs (23.30/100 PY) and non-injection crack (6.27/100 PY), and those living with HIV (13.27/100 PY) or acute sexually transmitted infections (STIs) (5.10/100 PY). In Cox analyses adjusted for injection drug use, age (hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.01), acute STI (HR 2.49, 95% CI 1.02-6.06), and non-injection crack use (HR 2.71, 95% CI 1.18-6.25) predicted time to HCV seroconversion., Discussion: While HCV incidence was highest among women who inject drugs, STIs and the use of non-injection stimulants appear to be pathways to HCV infection, suggesting potential dual sexual/drug transmission. Integrated HCV services within sexual health and HIV/STI programs are recommended., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

When bone is exposed to the burial environment it may experience structural changes induced by multiple agents. The study of postmortem alterations is important to differentiate decomposition phenomena from normal physiological processes or pathological lesions, as well as to assess bone tissue quality. Microscopy is of great utility to evaluate the integrity of bone microstructure and it provides significant data on long-term bone decomposition. A total of 18 human bone sections (eight archeological and ten retrieved from an identified skeletal collection) were selected for analysis under plane light and polarized light. The aim of this exploratory study was to analyze the impact of diagenesis and taphonomy on the bone microstructure, as well as on the differential diagnosis of pathological conditions. The results showed that the microscopy approach to bone tissues contributed materially as an aid in the detailed description of the main diagenetic changes observed. It showed that gross inspection does not provide a realistic assessment of bone tissue preservation, which can impact in the characterization of lesions present and subsequent disease diagnosis. Therefore, researchers should continue to consider the application of histological techniques if the aim is to comprehend tissue integrity and its association with decomposition or disease.

Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. Specific stool techniques for the detection of larvae of S. stercoralis, like Baermann's and Koga's agar plate, despite superiority over direct techniques are still suboptimal. New serologies using recombinant antigens and molecular-based techniques offer new hopes in those areas. The use of ivermectin rather than benzimidazoles for its treatment and the need to have curative regimens rather than lowering the parasite burden are also unique for S. stercoralis in comparison to the other STH due to its life cycle, which allows reproduction and amplification of the worm burden within the human host. The potential impact on STH of the benzimidazoles/ivermectin combinations, already used for control/elimination of lymphatic filariasis, should be further evaluated in public health settings. While waiting for more effective single-dose drug regimens and new sensitive diagnostics, the evidence and the tools already available warrant the planning of a common platform for STH and S. stercoralis control.