Search

Aisha K Lofters,1–3,* Sara JT Guilcher,1,3,4,* Lauren Webster,1 Richard H Glazier,1–3 Susan B Jaglal,1 Ahmed M Bayoumi,1,3 1Institute for Clinical Evaluative Sciences, 2Department of Family and Community Medicine, St Michael’s Hospital, University of Toronto, 3Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St Michael’s Hospital, 4Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada *These authors contributed equally to this work Purpose: Despite more frequent use of health services by people living with disability, the quality of preventive care received may be suboptimal. In this retrospective cohort study, we used administrative data to examine the relationship between cholesterol testing and levels of disability and morbidity among women and men in Ontario, Canada. Methods: We linked multiple provincial-level databases in this study. In stratified analyses for women and men, we used multivariable logistic regression to examine differences in cholesterol testing, and we tested for an interaction effect between disability and morbidity. In a secondary analysis, we tested for a three-way interaction between sex, disability, and morbidity on the entire cohort. Results: There was an interaction between morbidity and disability for both women and men. Women and men with no chronic conditions appeared to be least likely to be up-to-date on cholesterol testing, and among this group, those with moderate disability were more likely to be up-to-date on cholesterol testing than those with no disability (adjusted odds ratio [AOR] =1.51; 95% confidence interval [CI] 1.20–1.90 for women; AOR =1.16; 95% CI 1.00–1.34 for men). Among women and men who had one chronic condition, having severe disability put them at significant disadvantage versus those with no disability. Only 58.5% of men with no disability and no chronic conditions were up-to-date on cholesterol testing. Conclusion: An intermediate level of health care need (reflected in this study as level of disability and level of morbidity) may provide a benefit for cholesterol testing, and conversely, health care needs that are too few or too great may negatively affect testing. Public health and practice-based interventions need to be explored to address these findings. Keywords: primary care, preventative care, cholesterol testing, disability, morbidity

Research in rare lung diseases faces methodologic limitations by virtue of the small number of participants available to be studied. We explored several strategies that may improve researchers' ability to identify and recruit research participants with rare lung diseases. We provide an overview of strategies based on available evidence, previously used approaches, and reasoning. First, disease detection is generally poor and may be improved through strategies targeted at primary care practitioners or directly at patients, thus increasing the pool of patients available for research studies. Next, standardization of case definitions in rare lung diseases is often lacking, hindering research recruitment efforts because of confusion over appropriate recruitment criteria. Expert consensus statements can enhance both clinical care and research recruitment by standardizing definitions. Finally, recruitment strategies using rare lung disease registries, clinical research networks, novel Internet-based direct patient recruitment approaches, and patient organizations may facilitate recruitment of patients with rare lung diseases. In summary, although several strategies for improving the identification and recruitment of research participants with rare lung diseases have been proposed, published examples are few. Objective measurement and reporting of novel recruitment methods and collaboration among researchers facing the same limitations across various rare lung diseases are required. Advancements in this area are vital to the design and performance of much-needed robust clinical studies across the spectrum of rare lung diseases. [ABSTRACT FROM AUTHOR]

Purpose: To elicit neck pain (NP) patients' preference scores for their current health, and investigate the association between their scores and NP disability.Methods: Rating scale scores (RSs) and standard gamble scores (SGs) for current health were elicited from chronic NP patients (n=104) and patients with NP following a motor vehicle accident (n=116). Patients were stratified into Von Korff Pain Grades: Grade I (low-intensity pain, few activity limitations); Grade II (high-intensity pain, few activity limitations); Grade III (pain with high disability levels, moderate activity limitations); and Grade IV (pain with high disability levels, several activity limitations). Multivariable regression quantified the association between preference scores and NP disability.Results: Mean SGs and RSs were as follows: Grade I patients: 0.81, 0.76; Grade II: 0.70, 0.60; Grade III: 0.64, 0.44; Grade IV: 0.57, 0.39. The association between preference scores and NP disability depended on type of NP and preference-elicitation method. Chronic NP patients' scores were more strongly associated with depressive symptoms than with NP disability. In both samples, NP disability explained little more than random variance in SGs, and up to 51% of variance in RSs.Conclusion: Health-related quality-of-life is considerably diminished in NP patients. Depressive symptoms and preference-elicitation methods influence preference scores that NP patients assign to their health. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Inadequate adherence to highly active antiretroviral therapy (HAART) may lead to poor health outcomes and the development of HIV strains that are resistant to HAART. The authors developed a model to evaluate the cost-effectiveness of counseling interventions to improve adherence to HAART among men who have sex with men (MSM). METHODS: The authors developed a dynamic compartmental model that incorporates HIV treatment, adherence to treatment, and infection transmission and progression. All data estimates were obtained from secondary sources. The authors evaluated a counseling intervention given prior to initiation of HAART and before all changes in drug regimens, combined with phone-in support while on HAART. They considered a moderate-prevalence and a high-prevalence population of MSM. RESULTS: If the impact of HIV transmission is ignored, the counseling intervention has a cost-effectiveness ratio of $25,500 per quality-adjusted life year (QALY) gained. When HIV transmission is included, the cost-effectiveness ratio is much lower: $7400 and $8700 per QALY gained in the moderate- and high-prevalence populations, respectively. When the intervention is twice as costly per counseling session and half as effective as estimated in the base case (in terms of the number of individuals who become highly adherent, and who remain highly adherent), then the intervention costs $17,100 and $19,600 per QALY gained in the 2 populations, respectively. CONCLUSIONS: Counseling to improve adherence to HAART increased length of life, modestly reduced HIV transmission, and cost substantially less than $50,000 per QALY gained over a wide range of assumptions but did not reduce the proportion of drug-resistant strains. Such counseling provides only modest benefit as a tool for HIV prevention but can provide significant benefit for individual patients at an affordable cost. [ABSTRACT FROM AUTHOR]

BACKGROUND: Approximately 14% of hemodialysis patients have atrial fibrillation. Hemodialysis patients with atrial fibrillation appear to be at increased risk of both thromboembolic complications and bleeding. Furthermore, there is uncertainty regarding the efficacy of warfarin or acetylsalicylic acid (ASA) therapy for preventing strokes in this subgroup because they were excluded from relevant trials. STUDY DESIGN: We performed a cost-utility analysis. Probabilistic sensitivity analysis was used to incorporate parameter uncertainty into the model. Expected value of perfect information and scenario analyses were performed to identify the important drivers of the decision and focus future research. SETTING & POPULATION: Base case was a 60-year-old male hemodialysis patient in the United States. MODEL, PERSPECTIVE, & TIME FRAME: A Markov Monte Carlo microsimulation model was constructed from the perspective of the health care payer, and patients were followed up during their lifetime. INTERVENTION: We compared 3 alternative treatment strategies for permanent atrial fibrillation in hemodialysis patients: warfarin, ASA, or no treatment. OUTCOMES: Quality-adjusted survival and cost. RESULTS: ASA and warfarin both prolonged survival compared with no treatment (0.06 and 0.15 quality-adjusted life-years [QALYs], respectively). ASA was associated with an incremental cost-effectiveness ratio of $82,100/QALY. Warfarin provided additional benefits at a cost of $88,400 for each QALY gained relative to ASA. At a threshold of $100,000/QALY, the probabilities that no treatment, warfarin, and ASA were the most efficient therapy were 20%, 58%, and 23%, respectively. LIMITATIONS: Parameterization data and costs were taken from US studies and may not be generalizable to other countries. Peritoneal dialysis patients were not included in the analysis. CONCLUSIONS: The high future cost of hemodialysis constrains incremental cost-effectiveness ratios to values greater than commonly cited thresholds ($50,000/QALY). Based on available evidence, warfarin appears to be the optimal therapy to prevent thromboembolic stroke in hemodialysis patients with atrial fibrillation. Additional study is required to determine the efficacy of warfarin and risk of bleeding complications in this population so that patients can make a more informed choice.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Thermal and mechanical properties play a key role in optimizing the performance of nanoelectronic devices. In this study, the lattice thermal conductivity (κL) and elastic constants of Si nanosheets at different sheet thicknesses were determined using recently developed machine learning interatomic potentials (MLIPs). A Si nanosheet with a minimum thickness of 10 atomic layers was used for model training to predict the properties of sheets with greater thicknesses. The training dataset was efficiently constructed using stochastic sampling of the potential energy surface (PES). Density functional theory (DFT) calculations were used to extract
the MLIP, which served as the basis for further analysis. The Moment Tensor Potential (MTP) method was used to obtain the MLIP in this study. The results showed that, at sub-6 nm sheet thickness, the thermal conductivity dropped to ∼ 7 % of its bulk value, whereas some stiffness tensor components dropped to ∼ 3 % of the bulk values. These findings contribute to the understanding of heat transport and mechanical behavior of ultrathin Si nanosheets, which is crucial for designing and optimizing nanoelectronic devices. The technological implications of the extracted parameters on nanosheet field-effect transistor (NS-FET) performance at advanced technology nodes were evaluated using TCAD device simulations., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: A cross-sectional study was conducted to investigate the feasibility of implementing routine collection of the Euro-Qol 5 dimensions (EQ-5D) questionnaire, to inform drug and health technology reimbursement decision making., Methods: Women with breast cancer were recruited during scheduled clinic visits to an academic cancer centre. EQ-5D-5L was self-administered using electronic tablets. Diagnostic and treatment data were abstracted from patient charts. Feasibility was assessed primarily by the proportion of patients who fully completed EQ-5D-5L and by their willingness to complete the instrument at each clinic visit., Results: 588 women were approached for study participation, 341 were enrolled. Fully completed EQ-5D-5L questionnaires were obtained in 323 participants (95% of participants, 95% CI 92-97%). Median time for EQ-5D-5L completion was 1.5 minutes (range:0.35 to 14.7). Mean age of participants was 58 years old. Most women who completed EQ-5D were White, born outside Canada and presented a high education level; one-quarter had metastatic disease. Most participants reported "No problems" in all EQ-5D-5L dimensions. Mean EQ-5D-5L index and mean EQ-5D-5L VAS values for all participants were respectively 0.83 (SD 0.13) and 75.7 (SD 17.45), with patients with metastatic disease scoring the lowest values. Seventy-eight percent of participants were willing to complete EQ-5D-5L at each clinic visit; lower Charlson comorbidity index and higher education level were predictors of willingness to continue to answer EQ-5D-5L., Conclusions: Tablet-based collection of EQ-5D-5L in the context of routine clinical practice proved to be feasible. However, many patients declined study participation or reported being in full health, raising concerns about whether this method of collecting EQ-5D adequately represents the health status of all breast cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada., Study Design and Setting: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT)., Results: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment., Conclusion: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Jordan Feld has received research support from AbbVie Inc and Gilead Sciences for matters unrelated to the current study. Dr Eric Benchimol has acted as a consultant for McKesson Canada, the Dairy Farmers of Ontario and the Canadian Agency for Drugs and Technology in Health (CADTH) for matters unrelated to the topic of this research or to this study. Dr Sofia Bartlett has consulted, participated in advisory boards, and spoken for AbbVie Inc., Gilead Sciences Canada, Inc. and Cepheid Inc. for matters unrelated to the current study, and no personal payments were accepted. Dr Naveed Janjua has participated in advisory boards and has spoken for AbbVie and Gilead, for matters unrelated to the current study. All other coauthors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: The emotional impacts of witnessing and responding to overdose and overdose-related deaths have been largely overlooked during the drug toxicity overdose crisis in North America. Scarce research has analyzed these impacts on the health and well-being of harm reduction workers, and the broader determinants of harm reduction work. Our study investigates the experiences and impacts of witnessing and responding to frequent and escalating rates of overdose on harm reduction workers in Toronto, Canada., Methods: Using semi-structured interviews, 11 harm reduction workers recruited from harm reduction programs with supervised consumption services in Toronto, Canada, explored experiences with and reactions to overdose in both their professional and personal lives. They also provided insights on supports necessary to help people cope with overdose-related loss. We used thematic analysis to develop an initial coding framework, subsequent iterations of codes and emergent themes., Results: Results revealed that harm reductions workers experienced physical, emotional, and social effects from overdose-related loss and grief. While some effects were due to the toll of overdose response and grief from overdose-related losses, they were exacerbated by the lack of political response to the scale of the drug toxicity overdose crisis and the broader socio-economic-political environment of chronic underfunding for harm reduction services. Harm reduction workers described the lack of appropriate workplace supports for trauma from repeated overdose response and overdose-related loss, alongside non-standard work arrangements that resulted in a lack of adequate compensation or access to benefits., Conclusions: Our study highlights opportunities for organizational practices that better support harm reduction workers, including formal emotional supports and community-based supportive care services. Improvement to the socio-economic-political determinants of work such as adequate compensation and access to full benefit packages are also needed in the harm reduction sector for all workers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions., Methods: We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs., Results: We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC., Conclusions: OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies or the US government., (Copyright © 2024. Published by Elsevier Inc.)

Background: Across Canada, the COVID-19 pandemic occurred amidst an ongoing drug toxicity crisis. Although elevated rates of substance-related harms have been observed nationally, it remains unknown if the pandemic state of emergency led to disproportionate increases in opioid toxicities among people with opioid use disorder (OUD) compared to those without., Methods: We conducted a population-based repeated cross-sectional time series analysis of fatal and non-fatal opioid toxicities between January 1, 2014, and December 31, 2021, in Ontario, Canada. We used interventional autoregressive integrated moving average models to examine the impact of the pandemic on monthly rates of opioid toxicities per 100,000 Ontario residents stratified by people with and without OUD., Results: We identified 80,296 opioid toxicities of which 53.5 % occurred among people with OUD. Among 52,052 unique individuals, 60.5 % were male and 46.2 % were 25-44 years old. Between January 2014 and December 2021, the rate of opioid toxicities increased from 2.6 to 10.5 per 100,000 (rate ratio [RR]=4.07). The magnitude of this increase differed among people with OUD (0.8 to 7.4 per 100,000; RR=9.35) and without OUD (1.8 to 3.1 per 100,000; RR=1.74). We observed a significant ramp increase in the overall rate of opioid toxicities following the declaration of the pandemic emergency in March 2020 (+0.19 per 100,000 monthly, 95 % CI: 0.029, 0.36, p = 0.021). In a stratified analysis, we found a similar ramp increase among people with OUD (+0.19 per 100,000 monthly, 95 % CI: 0.10, 0.28, p < 0.001); however, this was not observed among people without OUD (p = 0.95)., Conclusions: The rate of opioid toxicities accelerated across Ontario following the pandemic-related state of emergency, with the majority of this increase among people with OUD. The important differences observed among people with OUD compared with those without, highlights the critical need for improved access to harm reduction and treatment interventions among this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV., Methods: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity)., Results: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed., Conclusions: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV., (© 2024. The Author(s).)

Background: Whereas supervised consumption services (SCSs) are common in many community settings, they are seldomly found in acute care hospitals. As hospitals present unique circumstances that can shape the impacts of an SCS, careful consideration of local implementation contexts and practices is required. We explored the pre-implementation stage of an SCS, to examine how an SCS is made and made differently in relation to the material-discursive context of the hospital., Methods: We conducted 11 focus groups with 83 staff and clinicians at an inner-city hospital in Toronto, Canada. Data analysis followed principles of grounded theory and was informed by an 'evidence making interventions' framework., Results: While most participants indicated they would support the establishment of an SCS at the hospital, multiple enactments of an SCS emerged. An SCS was enacted: as a means to reduce drug-related risks for all people who use drugs, as an opportunity to intervene on patients' drug use, as a means to centralize drug use, and as a transformative intervention for the hospital. In our findings, harm reduction, abstinence, security, and risk mitigation goals existed closely together, yielding overlaying realities., Conclusion: Our findings revealed various enactments of an SCS, some of which are likely to negatively affect people who use drugs and service access. As more hospitals consider the implementation of an SCS, understanding how an SCS is made in practice will be key to building a service that focuses on the needs of people who use drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aims: Calls to prescribe safer supply hydromorphone (SSHM) as an alternative to the toxic drug supply increased during the COVID-19 pandemic but it is unknown whether prescribing behaviour was altered. We aimed to evaluate how the number of new SSHM dispensations changed during the pandemic in Ontario., Methods: We conducted a retrospective interrupted time-series analysis using provincial administrative databases. We counted new SSHM dispensations in successive 28-day periods from March 22, 2016 to August 30, 2021. We used segmented Poisson regression methods to test for both a change in level and trend of new dispensations before and after March 17, 2020, the date Ontario's pandemic-related emergency was declared. We adjusted the models to account for seasonality and assessed for over-dispersion and residual autocorrelation. We used counterfactual analysis methods to estimate the number of new dispensations attributable to the pandemic., Results: We identified 1489 new SSHM dispensations during the study period (434 [mean of 8 per 28-day period] before and 1055 [mean of 56 per 28-day period] during the pandemic). Median age of individuals initiating SSHM was 40 (interquartile interval 33-48) with 61.7% (N = 919) male sex. Before the pandemic, there was a small trend of increased prescribing (incidence rate ratio [IRR] per period 1.002; 95% confidence interval [95CI] 1.001-1.002; p<0.001), with a change in level (immediate increase) at the pandemic date (relative increase in IRR 1.674; 95CI 1.206-2.322; p = 0.002). The trend during the pandemic was not statistically significant (relative increase in IRR 1.000; 95CI 1.000-1.001; p = 0.251). We estimated 511 (95CI 327-695) new dispensations would not have occurred without the pandemic., Conclusion: The pandemic led to an abrupt increase in SSHM prescribing in Ontario, although the rate of increase was similar before and during the pandemic. The absolute number of individuals who accessed SSHM remained low throughout the pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Young et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Emergency department visits and hospital admissions for opioid toxicity are opportunities to initiate opioid agonist therapy (OAT), which reduces morbidity and mortality in patients with opioid use disorder (OUD). The study objectives were to evaluate OAT initiation rates after a hospital encounter for opioid toxicity in Ontario, Canada, and determine whether publication of a 2018 Canadian OUD management guideline was associated with increased initiation., Methods: We conducted a retrospective, population-based serial cross-sectional study of hospital encounters for opioid toxicity among patients with OUD between Jan. 1, 2013, and Mar. 31, 2020, in Ontario, Canada. The primary outcome was OAT initiation (methadone, buprenorphine-naloxone, or slow-release oral morphine) within 7 days of discharge, measured quarterly. We examined the impact of the release of the OUD management guideline on OAT initiation rates using Autoregressive Integrated Moving Average models., Results: Among 20 702 hospital visits for opioid toxicity among patients with OUD, the median age was 35 years, and 65.1% were male. Over the study period, the percentage of visits leading to OAT initiation within 7 days rose from 1.7% or less (Q1 2013) to 5.6% (Q1 2020); however, the publication of the Canadian OUD management guideline was not associated with a significant increase in these rates (0.14% slope change, 95% confidence interval -0.11% to 0.38%; p = 0.3)., Interpretation: Among hospital encounters for opioid toxicity, despite rising prevalence over time, only 1 in 18 patients were dispensed OAT within a week of discharge in early 2020. These findings highlight missed opportunities to initiate therapies proven to reduce mortality in patients with OUD., Competing Interests: Competing interests: David Juurlink reports serving as the principal investigator on a grant from PSI Foundation to study the use of buprenorphine after nonfatal overdose. Dr. Juurlink has received payment for expert testimony from multiple law firms related to individual actions involving opioids, outside the submitted work. Dr. Juurlink is also a volunteer member of Physicians for Responsible Opioid Prescribing (a US organization that advocates for opioid stewardship). Dr. Juurlink holds the view that buprenorphine is an invaluable therapy with a safety profile that is far superior to full opioid agonists; some have perceived this as an intellectual competing interest. Ahmed Bayoumi reports receiving grants from the Canadian Institutes for Health Research in support of this study (paid to institution), and from the Baxter and Alma Ricard Chair in Inner City Health, outside of the submitted work. Dr. Bayoumi has also received consulting fees from the Canadian Centre for Substance Abuse. Pamela Reece reports employment with Public Health Ontario (Ontario for Health Protection and Promotion), as courtesy staff at the Women’s College Hospital, and as a physician at the Kickstart Medical Clinic. Tara Gomes reports receiving a grant from the Canadian Institutes for Health Research in support of this study (paid to institution). Dr. Gomes has also received a grant and contract funding from the Ontario Ministry of Health and Ontario College of Pharmacists to support a research program (paid to institution), outside the submitted work. Dr. Gomes is supported by a Tier 2 Canada Research Chair in Drug Policy Research and Evaluation, which supports salary. Dr. Gomes has also personally received contract funding from the Canadian Agency for Drugs and Technologies in Health for roles as expert reviewer on projects and grant reviewer; fees for consulting on an audit for the British Columbia Auditor General; and support from Indigenous Services Canada for participation on the Drugs and Therapeutics Advisory Committee. Dr. Gomes has also served as a member of the Board of Governors for the Inner City Family Health Team. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: The ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off-label prescriptions of pharmaceutical-grade opioids to high risk individuals with the goal of reducing overdose deaths., Methods: In 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi-structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self-reported impact of these programs on their health and well-being., Results: We interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self-identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self-reported health and well-being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing)., Discussion and Conclusion: Most clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Overdoses are increasing in the province of Ontario, Canada, where northern communities such as Sudbury have witnessed disproportionately elevated rates, with opioid-related deaths double that of the provincial average. To address this issue, governments have implemented supervised consumption services (SCS) where people who use drugs (PWUD) can use their pre-obtained substances onsite under trained supervision. In September 2022, the city of Sudbury opened its first SCS, 'The Spot', but the site's sustainability is contingent on demonstrating benefit to PWUD and the neighboring community. We undertook a qualitative study exploring experiences among clients who used the consumption service inside The Spot. In December 2022, clients of The Spot were invited to participate in a brief survey which collected socio-demographic information and substance use profiles, followed by an in-person semi-structured qualitative interview. Participant survey and interview data were combined with administrative site utilization data provided by site staff of all clients who accessed the consumption service from September 2022 to August 2023 to examine overall service utilization and uptake. Qualitative data were analyzed using iterative thematic analysis techniques, and results were informed by common responses to research questions. The responses were narratively presented. Administrative site utilization data highlighted a relatively stable increase in uptake and utilization of the site since its inception. A total of 20 clients participated in the survey and semi-structured interviews. Participants described the importance of the site in preventing and responding to overdoses, providing a safe and comfortable environment to consume their drugs, and decreasing public drug use, which they suggested may potentially reduce stigmatization in the community. However, clients also suggested challenges, including issues regarding site operational policies that hindered consumption room utilization. Service suggestions made by clients to improve site utilization include the addition of inhalation services, relocating the site to a location in downtown Sudbury where PWUD commonly congregate, and extending operational hours. Positive impacts and recommendations can be drawn on and considered by other northern or rural communities interested in implementing similar harm reduction services., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Highlights: This tutorial provides a user-friendly guide to mathematically formulating constrained optimization problems and implementing them using Python.Two examples are presented to illustrate how constrained optimization is used in health applications, with accompanying Python code provided., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists., Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis., Results: Thirty-three adults living with HIV enrolled in the study ( n  = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural , including weather and the COVID-19 virus; (ii) Societal , including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational , including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human , including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics., Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jiancaro, Bayoumi, Ibáñez-Carrasco, Torres, McDuff, Brown, Chan Carusone, Tang, Loutfy, Cobbing and O'Brien.)

We investigated the association between fentanyl injection frequency and sharing of injection equipment among people who inject drugs. We surveyed 249 people who inject drugs in Toronto in 2019. We estimated predicted probabilities of associations between fentanyl injection frequency and injection risk practices. In prior 6 months, 117 (47.0%) of participants injected fentanyl daily, 49 (19.7%) less than daily, and 78 (31.3%) did not inject fentanyl. Participants who injected fentanyl daily shared syringes more often than those not injecting fentanyl (25.0% vs. 4.9%; χ 2  = 11.54, p = 0.0007). Participants who injected fentanyl daily (42.4% vs. 11.3%; χ 2  = 18.05, p < 0.0001) and less than daily (37.2% vs. 11.3%; χ 2  = 5.88 p = 0.02) shared cookers more often than those not injecting fentanyl. Participants who injected fentanyl daily (30.2% vs. 9.7%; χ 2  = 9.05, p = 0.003) and less than daily (30.3% vs. 9.7%; χ 2  = 4.11, p = 0.04) shared filters more often than those not injecting fentanyl. No differences in probabilities of sharing equipment were detected between participants who injected fentanyl daily and less than daily. People using fentanyl reported injection practices that increased risk for infectious disease transmission., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS., Methods: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored., Results: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology., Conclusion: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV., Methods: We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies., Results: After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV., Discussion: Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication., (© 2023. The Author(s).)

Aims: Although opioid-related harms have reached new heights across North America, the size of the gap in opioid agonist therapy (OAT) delivery for opioid-related health problems is unknown in most jurisdictions. This study sought to characterize the gap in OAT treatment using a cascade of care framework, and determine factors associated with engagement and retention in treatment., Design: A population-based retrospective cohort study., Setting: Ontario, Canada., Participants: Individuals who sought medical care for opioid-related health problems or died from an opioid-related cause between 2005 and 2019., Measurements: Monthly treatment status for buprenorphine/naloxone or methadone OAT between 2013 and 2019 (i.e. 'off OAT', 'retained on OAT < 6 months', 'retained on OAT ≥ 6 months')., Findings: Of 122 811 individuals in the cohort, 97 516 (79.4%) received OAT at least once during the study period. There was decreasing 6-month treatment retention over time. Model results indicated that males had higher odds of being on OAT each month [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.23-1.28] but lower odds of OAT retention (OR = 0.90, 95% CI = 0.88-0.92), while the reverse was observed for older individuals (monthly: OR = 0.76 per 10-year increase, 95% CI = 0.76-0.77; retention: OR = 1.36 per 10-year increase, 95% CI = 1.34-1.38) and individuals with higher neighbourhood income (e.g. highest income quintile, monthly: OR = 0.79, 95% CI = 0.77-0.82; highest income quintile, retention: OR = 1.15, 95% CI = 1.11-1.20). Individuals residing in rural areas and with a history of mental health diagnoses had poorer outcomes overall, including lower odds of being on OAT each month (rural: OR = 0.75, 95% CI = 0.73-0.78; mental health: OR = 0.89, 95% CI = 0.87-0.92) and OAT retention (rural: OR = 0.79, 95% CI = 0.77-0.82; mental health: OR = 0.81, 95% CI = 0.78-0.83), as well as higher risk of starting/stopping OAT [rural, starting OAT: hazard ratio (HR) = 1.07, 95% CI = 1.05-1.10; mental health, starting OAT: HR = 1.20, 95% CI: 1.18-1.23; rural, stopping OAT: HR = 1.24, 95% CI: = 1.22-1.26; mental health, stopping OAT: HR = 1.11, 95% CI = 1.09-1.13]. Individuals with a history of mental health diagnoses also had a higher risk of death, regardless of OAT status (off OAT death: HR = 1.49, 95% CI = 1.33-1.66; on OAT death: HR = 1.20, 95% CI = 1.09-1.31)., Conclusions: Factors influencing engagement and declining retention in treatment with opioid agonist therapy in Ontario's health system include age, sex and neighbourhood income, as well as mental health diagnoses or residing in rural regions., (© 2022 His Majesty the King in Right of Canada. Addiction © 2022 Society for the Study of Addiction. Reproduced with the permission of the Minister of Health.)

Introduction: Our aim is to evaluate the implementation of an online telecoaching community-based exercise (CBE) intervention with the goal of reducing disability and enhancing physical activity and health among adults living with HIV., Methods and Analysis: We will conduct a prospective longitudinal mixed-methods two-phased intervention study to pilot the implementation of an online CBE intervention with ~30 adults (≥18 years) living with HIV who consider themselves safe to participate in exercise. In the intervention phase (0-6 months), participants will take part in an online CBE intervention involving thrice weekly exercise (aerobic, resistance, balance and flexibility), with supervised biweekly personal training sessions with a fitness instructor, YMCA membership providing access to online exercise classes, wireless physical activity monitor to track physical activity and monthly online educational sessions on topics related to HIV, physical activity and health. In the follow-up phase (6-12 months), participants will be encouraged to continue independent exercise thrice weekly. Quantitative assessment: Bimonthly, we will assess cardiopulmonary fitness, strength, weight, body composition and flexibility, followed by administering self-reported questionnaires to assess disability, contextual factor outcomes (mastery, engagement in care, stigma, social support), implementation factors (cost, feasibility, technology), health status and self-reported physical activity. We will conduct a segmented regression analyses to describe the change in level and trend between the intervention and follow-up phases. Qualitative assessment: We will conduct online interviews with a subsample of ~10 participants and 5 CBE stakeholders at baseline (month 0), postintervention (month 6) and end of follow-up (month 12) to explore experiences, impact and implementation factors for online CBE. Interviews will be audiorecorded and analysed using content analytical techniques., Ethics and Dissemination: Protocol approved by the University of Toronto Research Ethics Board (Protocol # 40410). Knowledge translation will occur in the form of presentations and publications in open-access peer-reviewed journals., Trial Registration Number: NCT05006391., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Model-based economic evaluations require conceptualization of the model structure. Our objectives were to identify important health states, events, and patient attributes to be included in a model-based cost-effectiveness analysis of fall prevention interventions, to develop a model structure to examine cost-effectiveness of fall prevention interventions, and to assess the face validity of the model structure., Methods: An expert panel comprising clinicians, health service researchers, health economists, a patient partner, and policy makers completed two rounds of online surveys to gain consensus on health states, events, and patient attributes important for fall prevention interventions. The surveys were informed by a literature search on fall prevention interventions for older adults (≥65 years) including economic evaluations and clinical practice guidelines. The results of the Delphi surveys and subsequent discussions can support the face validity of a state-transition model for an economic evaluation of fall prevention interventions., Results: In total, 11 experts rated 24 health states/events and 41 patient attributes. Consensus was achieved on 14 health states/events and 26 patient characteristics. The proposed model structure incorporated 12 of the 14 selected health states/events. Panelists confirmed the face validity of the model structure during teleconferences., Conclusions: There is a dearth of studies presenting the model conceptualization process; consequently, this study involving multiple end user partners with opportunities for input at several stages adds to the literature as another case study. This process is an example of how a fall prevention economic model was developed using a modified Delphi process and assessed for face validity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Saunders et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Polycystic ovaries (PCO) is a hormonal disorder that is a leading cause of infertility. The formation of multiple persistent cysts and hormonal imbalance are hallmarks of PCO. Recent clinical studies reported a beneficial effect of the ketogenic diet (KD; high-fat, low-carbohydrate) on PCO. The aim of this study was to investigate the effect of the KD alone and in combination with metformin on letrozole-induced PCO in female rats., Methods: Female rats were grouped into control and PCO (letrozole; 1 mg/kg for 21 days). The PCO group was subdivided into PCO (non-treated), PCO-metformin (300 mg/kg), PCO rats fed with KD only, and PCO rats treated with metformin and fed with KD. All groups continued to receive letrozole during the 21-day treatment period. At the end of the experiment, serum and ovaries were collected for further analysis., Results: The untreated-PCO rats showed increased testosterone, LH/FSH ratio, and ovary weights. Disturbed apoptosis and proliferation balance were evident as a low caspase-3 activation and proliferating cell nuclear antigen expression and increased TGF-β expression. The KD improved the letrozole-induced effects, which was comparable to the effect of metformin. Combining the KD with metformin treatment additively enhanced the metformin effect., Conclusion: Our results indicate that the KD has a protective role against PCO in rats, especially when combined with metformin. This study reveals a potential therapeutic role of the KD in PCO, which could prompt valuable future clinical applications., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive alkylating agent. However, cardiac adverse effects of CP interfere with its clinical benefit. Cardio-oncology research is currently an important issue and finding effective cardiopreserving agents is a critical need. For the first time, we aimed to detect if dapagliflozin (DAP) could ameliorate CP-induced cardiac injury and investigated the role of hypoxia inducible factor α (HIF1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway., Methods: Forty male Wistar albino rats were included in the current model. Studied groups are: control group; CP-induced cardiotoxicity group; CP group treated with DAP; CP group treated with DAP and administered a nitric oxide synthase inhibitor; nitro-ω-L-arginine (L-NNA) before DAP to explore the role of eNOS., Results: Our data revealed that CP could induce cardiac damage as manifested by significant increases in cardiac enzymes, blood pressure, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), HIF1α, sodium glucose co-transporter 2 (SGLT2) and cleaved caspase-3 levels with toxic histopathological changes. However, there are significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, and eNOS. On the opposite side, co-administration of DAP showed marked improvement of CP-induced cardiac damage that may be due to its ability to inhibit SGLT2, antioxidant, anti-inflammatory and anti-apoptotic properties. Results showed decreasing the cardioprotective effect of DAP on administration of L-NNA, reflecting the critical effect of eNOS in mediating such protection., Conclusion: DAP could reduce CP cardiotoxicity based upon its ability to modulate SGLT2 and HIF1α/VEGF/eNOS signaling pathway.

Objectives: The Short-Form HIV Disability Questionnaire (SF-HDQ) was developed to measure the presence, severity and episodic nature of health challenges across six domains. Our aim was to assess the sensibility, utility and implementation of the SF-HDQ in clinical practice., Design: Mixed methods study design involving semistructured interviews and questionnaire administration., Participants: We recruited adults living with HIV and HIV clinicians in Canada, Ireland and the USA., Methods: We electronically administered the SF-HDQ followed by a Sensibility Questionnaire (face and content validity, ease of usage, format) and conducted semistructured interviews to explore the utility and implementation of the SF-HDQ in clinical practice. The threshold for sensibility was a median score of > 5/7 (adults living with HIV) and > 4/7 (HIV clinicians) for ≥80% of items. Qualitative interview data were analysed using directed content analysis., Results: Median sensibility scores were > 5 (adults living with HIV; n=29) and > 4 (HIV clinicians; n=16) for 18/19 (95%) items. Interview data indicated that the SF-HDQ represents the health-related challenges of living with HIV and other concurrent health conditions; captures the daily episodic nature of HIV; and is easy to use. Clinical utility included measuring health challenges and change over time, guiding referral to specialists and services, setting goals, facilitating communication and fostering a multidisciplinary approach to care. Considerations for implementation included flexible, person-centred approaches to administration, and communicating scores based on personal preferences., Conclusions: The SF-HDQ possesses sensibility and utility for use in clinical settings with adults living with HIV and HIV clinicians in three countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We investigated the relationship between overdose events and grief and loss responses among people who inject drugs., Methods: We conducted a cross-sectional, tablet-based survey with a convenience sample of people who inject drugs (n = 249) from four community-based harm reduction programs in Toronto in 2019. We examined the association between frequency and types of overdose events (own, witnessed, death of significant person) in the last 6 months with grief and loss responses, identified using latent class analysis., Results: Among respondents, 70 (48.6 %) reported 2 or more personal overdoses, 173 (79.5 %) witnessed 2 or more overdoses, and 69 (41.4 %) experienced overdose deaths of 2 or more significant persons in the last 6 months. We identified 2 latent classes with probability of membership of 38.6 % (95 % confidence interval [CI]=31.0, 46.7) for medium/low intensity of responses to grief/loss and 61.4 % (95 % CI= 53.3, 69.0) for severe responses to grief/loss. In adjusted Poisson regression models with robust standard error estimators, severe responses to grief/loss were associated with exposure to two or more own overdoses (prevalence ratio [PR] = 1.44; 95 % CI=1.12, 1.84, p-value=0.004), and having witnessed one (PR=2.09; 95 % CI=1.05, 4.15, p-value=0.04) or witnessed two or more overdoses (PR=2.25; 95 % CI=1.24, 4.09, p-value=0.008). Severe grief/loss responses were also more common in individuals exposed to all three types of overdose events (PR=2.42; 95 % CI=1.08, 5.41, p-value=0.03)., Conclusions: Cumulative overdose events were associated with severe responses to grief and loss. Bereavement interventions should consider the complex nature of grief and loss following overdoses., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Opioid use among people who inject drugs can lead to serious complications, including infections. We sought to study trends in rates of these complications among people with an opioid use disorder (OUD) and the sequelae of those hospitalizations., Methods: We analyzed all inpatient hospitalizations for serious infections (infective endocarditis [IE], spinal infections, nonvertebral bone infections, and skin or soft tissue infections) among people with OUD in Ontario between 2013 and 2019. We reported the population adjusted rate of hospitalizations for serious infections annually, stratified by type of infection and prevalence of prior opioid agonist therapy and hydromorphone prescribing. We reported characteristics of hospitalizations and 30-day mortality in the most recent 2 years., Results: Among people with OUD there was a 167% increase in rates of IE (7.7-20.6 per million residents; P < 0.01), a 394% increase in rates of spinal infections (3.4-16.8 per million residents; P < 0.01), a 191% increase in rates of nonvertebral bone infections (8.9 to 25.9 per million residents; P < 0.01), and a 147% increase in infections of the skin or soft tissue (32.1-79.4 per million residents; P < 0.01) over 7 years in Ontario. Death in-hospital and within 30 days of discharge was highest among those with IE (11.5% and 15.9%, respectively), and lower among those with other infections (<5%)., Conclusions: Rates of serious infections among people with OUD are rising, placing a significant burden on patients. These findings suggest that early intervention and treatment of infections in this population are needed to prevent downstream harm., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

Introduction: Incarcerated populations represent a vulnerable and marginalised segment of society, with increased health needs and a higher burden of communicable and non-communicable diseases. Traditional population health outcomes do not capture physical, mental, emotional and social well-being. Health-related quality of life (HRQoL) outcomes attempt to measure these important parameters. To date, there has not been a scoping review to summarise the HRQoL literature in the incarcerated population. Thus, we aim to perform such a review to inform health policy decisions in incarcerated populations and support health economic evaluations of interventions in incarcerated populations., Methods and Analysis: We will conduct a scoping review of the literature on the HRQoL in the incarcerated population informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the corresponding PRISMA Extension for Scoping Reviews. The submissions records of six electronic databases with peer-reviewed literature and three health technology assessment agencies will be searched. The search strategy was informed by recommendations for HRQoL reviews. We will include studies that report HRQoL, health state utility values or reference to quality adjusted life years or quality-adjusted life expectancies of incarcerated populations. No assessments of items' quality will be made, as the purpose of this scoping review is to synthesise and describe the coverage of the evidence. We will also identify knowledge gaps on the HRQoL in the incarcerated population., Ethics and Dissemination: Research ethics approval is not required as primary data will not be collected. The findings of this scoping review will be used to inform health economic analyses for the incarcerated population and will be disseminated through peer-reviewed publications and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Opioid-related mortality continues to rise across North America, and mortality rates have been further exacerbated by the COVID-19 pandemic. This study sought to provide an updated picture of trends of opioid-related mortality for Ontario, Canada between January 2003 and December 2020, in relation to age and sex., Methods: Using mortality data from the Office of the Chief Coroner for Ontario, we applied Bayesian Poisson regression to model age/sex mortality per 100,000 person-years, including random walks to flexibly capture age and time effects. Models were also used to explore how trends might continue into 2022, considering both pre- and post-COVID-19 courses., Results: From 2003 to 2020, there were 11,633 opioid-related deaths in Ontario. A shift in the age distribution of mortality was observed, with the greatest mortality rates now among younger individuals. In 2003, mortality rates reached maximums at 5.5 deaths per 100,000 person-years (95% credible interval: 4.0-7.6) for males around age 44 and 2.2 deaths per 100,000 person-years (95% CI: 1.5-3.2) for females around age 51. As of 2020, rates have reached maximums at 67.2 deaths per 100,000 person-years (95% CI: 55.3-81.5) for males around age 35 and 16.8 deaths per 100,000 person-years (95% CI: 12.8-22.0) for females around age 37. Our models estimate that opioid-related mortality among the younger population will continue to grow, and that current conditions could lead to male mortality rates that are more than quadruple those of pre-pandemic estimations., Conclusions: This analysis may inform a refocusing of public health strategy for reducing rising rates of opioid-related mortality, including effectively reaching both older and younger males, as well as young females, with health and social supports such as treatment and harm reduction measures., Competing Interests: The authors have declared that no competing interests exist.

Background: In response to the ongoing overdose crisis, some clinicians in Canada have started prescribing immediate release hydromorphone (IRH) as an alternative to the toxic unregulated drug supply. This practice is often referred to as safer supply. We aimed to identify and characterize patients receiving safer supply IRH and their prescribers in Ontario., Methods: Using provincial administrative health data, we identified individuals with opioid use disorder prescribed safer supply IRH from January 2016 to March 2020 and reported the number of initiations over time. We summarized demographic, health, and medication use characteristics among patients who received safer supply IRH, and examined select clinical outcomes including retention and death. Finally, we characterized prescribers of safer supply IRH and compared frequent and infrequent prescribers., Results: We identified 534 initiations of safer supply IRH (447 distinct individuals) from 155 prescribers. Initiations increased over time with a peak in the third quarter of 2019 (103 initiations). Patients' median age was 42 (interquartile range [IQR] 34-50), and most were male (60.2%), urban residents, (96.2%), and in the lowest neighborhood income quintile (55.7%), with 13.9% having overdosed in the previous one year. The prevalence of HIV was 13.9%. The median duration on IRH was 272 days (IQR 30-1,244) and OAT was co-prescribed in 62.9% of courses. Death while receiving IRH or within 7 days of discontinuation was rare (≤5 courses;≤0.94 per person-year for each)., Conclusions: Clinicians are increasingly prescribing safer supply IRH in Ontario. Patients prescribed safer supply IRH had demographic and clinical characteristics associated with high risk of death from opioid-related overdose. Short-term deaths among people receiving safer supply IRH were rare., Competing Interests: Declarations of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tara Gomes has received grant funding from the Ontario Ministry of Health. No other authors report conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To describe team-based care use among a cohort of people who use drugs (PWUD) and to determine factors associated with receipt of team-based care., Design: A cohort study using survey data collected between March and December 2013. These data were then linked to provincial-level health administrative databases to assess patterns of primary care among PWUD in the 2 years before survey completion., Setting: Ottawa, Ont., Participants: Marginalized PWUD 16 years of age or older., Main Outcome Measures: Patients were assigned to primary care models based on survey responses and then were categorized as attached to team-based medical homes, attached to non-team-based medical homes, not attached to a medical home, and no primary care. Descriptive statistics and multinomial logistic regression were used to determine associations between PWUD and medical home models., Results: Of 663 total participants, only 162 (24.4%) received team-based care, which was associated with high school level of education (adjusted odds ratio [AOR] = 2.18; 95% CI 1.13 to 4.20), receipt of disability benefits (AOR = 2.47; 95% CI 1.22 to 5.02), and HIV infection (AOR = 2.88; 95% CI 1.28 to 6.52), and was inversely associated with recent overdose (AOR = 0.49; 95% CI 0.25 to 0.94). In comparison, 125 (18.8%) received non-team-based medical care, which was associated with university or college education (AOR = 2.31; 95% CI 1.04 to 5.15) and mental health comorbidity (AOR = 4.18; 95% CI 2.33 to 7.50), and was inversely associated with being detained in jail in the previous 12 months (AOR = 0.51; 95% CI 0.28 to 0.90)., Conclusion: Although team-based, integrated models of care will benefit disadvantaged groups the most, few PWUD receive such care. Policy makers should mitigate barriers to physician care and improve integration across health and social services., (Copyright © 2022 the College of Family Physicians of Canada.)

Hepatitis C is a leading cause of liver disease and transplantation and is a significant burden on public health worldwide. This study aimed to apply the Electronic Nose (E-Nose) and quadrupole Mass Spectrometry (MS/MS) technologies for screening blood samples from hepatitis C patients and healthy controls. We analysed volatile organic compounds (VOCs) in the headspace over blood samples to identify those VOCs characteristic for diagnosing hepatitis C patients. The study comprised 150 acute hepatitis C patients with age range: 24-59 years, and mean age ±SD: 41.5 ± 12.8 years and 150 age-matched healthy controls (age range: 24-51 and mean age: 40.11 ± 4.89 years) from the Hospital of the Medical Research Institute, Alexandria University, Alexandria, Egypt. Collected blood samples were analysed qualitatively and quantitatively using the E-Nose and MS/MS techniques, respectively. Principal component analysis of the E-Nose 10-sensor responses accurately classified blood samples from hepatitis C patients and healthy controls. The first two principal components explained over 98.35% of the variance in signals with no false-positive (healthy controls) or false-negative (hepatitis C patients) results. MS/MS showed two fragmentation ions at m/z of 104 and 151 Da with the positive electrospray ionization mode (ESI+) in blood samples for hepatitis C patients, but not for healthy controls or background water samples. We identified the two specific fragmentation ions at m/z 104 and m/z 151 Da as malonic acid (MF: C 3 H 4 O 4 ; MW: 104.06 g/mol) and monosaccharide pentose (MF: C 5 H 10 O 5 ; MW: 150.13 g/mol) in VOCs of the headspace over blood samples for hepatitis C patients. This provides a rationale for developing diagnostic tests for hepatitis C virus based on altered trace VOCs concentrations using the relatively inexpensive, easy-to-use, portable and non-invasive E-Nose technology., (© 2021 John Wiley & Sons Ltd.)