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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., Opioid use disorder (OUD) is a substantial public health problem with an increasing prevalence worldwide. (1) From 2016 to 2021, 26 690 opioid-related deaths occurred in Canada; (1) in Ontario, [...]

In this paper, we present an accelerated Jacobi-gradient-based iterative AJGI algorithm to solve the matrix equation AZ-Z¯B=C, which is based on algorithms presented by Bayoumi (Appl Math Inf Sci, 2021). The iterative solution converges to the exact solution for any initial value under appropriate assumptions. Numerical examples are provided to support the suggested approach and verify its effectiveness and accuracy when compared to a recent one previously described in Bayoumi (Appl Math Inf Sci, 2021).

Since 1997, health care expenditure in Canada has increased much faster than the rate of economic growth. (1) In particular, the proportion of spending from provincial government funds devoted to [...]

In this work, we are concerned with (R, S) – conjugate solutions to coupled Sylvester complex matrix equations with conjugate of two unknowns. When the considered two matrix equations are consistent, it is demonstrated that the solutions can be obtained by utilizing this iterative algorithm for any initial arbitrary – conjugate matrices . A necessary and sufficient condition is established to guarantee that the proposed method converges to the – conjugate solutions. Finally, two numerical examples are provided to demonstrate the efficiency of the described iterative technique.

Abstract Background: The cost-effectiveness of Canada's only supervised injection facility has not been rigorously evaluated. We estimated the impact of the facility on survival, rates of HIV and hepatitis C [...]

Background: Although HIV infection is more prevalent in people younger than age 45 years, a substantial number of infections occur in older persons. Recent guidelines recommend HIV screening in patients age 13 to 64 years. The cost-effectiveness of HIV screening in patients age 55 to 75 years is uncertain. Objective: To examine the costs and benefits of HIV screening in patients age 55 to 75 years. Design: Markov model. Data Sources: Derived from the literature. Target Population: Patients age 55 to 75 years with unknown HIV status. Time Horizon: Lifetime. Perspective: Societal. Intervention: HIV screening program for patients age 55 to 75 years compared with current practice. Outcome Measures: Life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results of Base-Case Analysis: For a 65-year-old patient, HIV screening using traditional counseling costs $55 440 per QALY compared with current practice when the prevalence of HIV was 0.5% and the patient did not have a sexual partner at risk. In sexually active patients, the incremental cost-effectiveness ratio was $30 020 per QALY. At a prevalence of 0.1%, HIV screening cost less than $60000 per QALY for patients younger than age 75 years with a partner at risk if less costly streamlined counseling is used. Results of Sensitivity Analysis: Cost-effectiveness of HIV screening depended on HIV prevalence, age of the patient, counseling costs, and whether the patient was sexually active. Sensitivity analyses with other variables did not change the results substantially. Limitations: The effects of age on the toxicity and efficacy of highly active antiretroviral therapy and death from AIDS were uncertain. Sensitivity analyses exploring these variables did not qualitatively affect the results. Conclusion: If the tested population has an HIV prevalence of 0.1% or greater, HIV screening in persons from age 55 to 75 years reaches conventional levels of cost-effectiveness when counseling is streamlined and if the screened patient has a partner at risk. Screening patients with advanced age for HIV is economically attractive in many circumstances.

ABSTRACTIn this paper, five iterative methods for solving two coupled fuzzy Sylvester matrix equations are considered. The two coupled fuzzy Sylvester matrix equations are expressed by using the generalized inverse of the coefficient matrix, then iterative solutions are constructed by applying the hierarchical identification principle and by using the block-matrix inner product (the star product for short). A proposed modification to this algorithm to solve the first coupled fuzzy Sylvester matrix equations is suggested. This proposed modification is compared with the first algorithm where our modification exhibits fast convergence behavior. Also, we suggested two least-squares iterative algorithm by applying a hierarchical identification principle to solve the two coupled fuzzy Sylvester matrix equations. The proposed methods are illustrated by numerical examples.

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In this paper, two relaxed gradient-based algorithms for solving the linear matrix equation AXB+CXD=Fand finding the Hermitian and skew-Hermitian solutions are presented. We proved that the algorithms converge to the Hermitian and skew-Hermitian solutions. A sufficient condition is given to guarantee that the solutions given by the proposed algorithms converge to the Hermitian and skew-Hermitian solutions for any initial matrix. Two numerical examples are given to test its efficiency and accuracy compared with our proposed modification of the gradient-based iterative algorithm proposed in Ding et al. (Appl Math Comput 197(1):41–50, 2008).

Background The real-world effectiveness of pre-exposure prophylaxis (PrEP) may be influenced by circulating HIV strains resistant to either tenofovir or emtricitabine. Yet, few studies have examined rates of resistance to these drugs in clinical settings.Methods We conducted a retrospective cohort study of antiretroviral-naive participants in the Canadian Observational Cohort collaboration who initiated antiretroviral therapy between 2006 and 2014. In separate analyses, we determined the prevalence of pretherapy resistance and cumulative incidence of follow-up resistance to tenofovir and emtricitabine. We used multivariable proportional hazards models to examine associations between baseline variables and the development of resistance.Results We studied 6,622 antiretroviral-naive participants initiating therapy, of whom 5,428 (82.0%) had a baseline resistance test. Baseline resistance to tenofovir and emtricitabine was observed in 83 (1.5%) and 21 (0.4%) patients, respectively. Among patients without baseline resistance, the cumulative incidence of resistance to tenofovir and emtricitabine 5 years following treatment initiation was 0.0070 (95% CI 0.0046, 0.0095) and 0.033 (95% CI 0.028, 0.038), respectively. Following multivariable analysis, a baseline viral load =100,000 copies/ml was associated with emergence of tenofovir (hazard ratio [HR] 2.88; 95% CI 1.35, 6.15) and emtricitabine (HR 2.27; 95% CI 1.64, 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4+T-cell count below 200 cells/mm3were also associated with resistance to each drug.Conclusions We observed a low prevalence of baseline resistance and a low incidence of emergence of resistance to tenofovir and emtricitabine among antiretroviral-naive patients in routine clinical care.

Background: The costs and side effects of several antiandrogen therapies for advanced prostate cancer differ substantially. We estimated the cost-effectiveness of antiandrogen therapies for advanced prostate cancer. Methods: We performed a cost-effectiveness analysis using a Markov model based on a formal meta-analysis and literature review. The base case was assumed to be a 65-year-old man with a clinically evident, local recurrence of prostate cancer. The model used a societal perspective and a time horizon of 20 years. Six androgen suppression strategies were evaluated: diethylstilbestrol (DES), orchiectomy, a nonsteroidal antiandrogen (NSAA), a luteinizing hormone-releasing hormone (LHRH) agonist, and combinations of an NSAA with an LHRH agonist or orchiectomy. Outcome measures were survival, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. Results: DES, the least expensive therapy, had a discounted lifetime cost of $3600 and the lowest quality-adjusted survival, 4.6 QALYs. At a cost of $7000, orchiectomy was associated with 5.1 QALYs, resulting in an incremental cost-effectiveness ratio of $7500/QALY relative to DES. All other strategies--LHRH agonists, NSAA, and both combined androgen blockade strategies--had higher costs and lower quality-adjusted survival than orchiectomy. These results were sensitive to the quality of life associated with orchiectomy and the efficacy of combined androgen blockade, and they changed little when prostate-specific antigen results were used to guide therapy. Under a wide range of other assumptions, the cost-effectiveness of orchiectomy relative to DES was consistently less than $20000/QALY. Androgen suppression therapies were most cost-effective if initiated after patients became symptomatic from prostate metastases. Conclusions: For men who accept it, orchiectomy is likely to be the most cost-effective androgen suppression strategy. Combined androgen blockade is the least economically attractive option, yielding small health benefits at high relative costs. [J Natl Cancer Inst 2000;92:1731-9]

The article by Ahmed Bayoumi and Peter Kopplin (1) presents an alternative to traditional case presentations. The authors emphasize presentations that produce "logical flow," "present the most salient information early" [...]

How should doctors present case reports? Medical tradition, our mentors and our textbooks teach a standard format that starts with identifying information, followed by the chief complaint, history of present [...]

ObjectivesRates of chlamydia and gonorrhoea have been rising in urban centres in Canada, particularly among HIV-positive men who have sex with men (MSM). Our objective was to identify behavioural risk factors for diagnosis with chlamydia and gonorrhoea in this population, with a focus on the HIV status of sexual partners.MethodsThe OHTN Cohort Study follows people in HIV care across Ontario. We restricted the analysis to 1997 MSM who completed questionnaires in 2010–2013 at one of seven clinics that submit all chlamydia and gonorrhoea tests to the provincial public health laboratory; we obtained test results via record linkage. We estimated cumulative incidences using Kaplan–Meier methods and identified risk factors for diagnosis of a composite outcome (chlamydia or gonorrhoea infection) using Cox regression.ResultsAt follow-up, there were 74 new chlamydia/gonorrhoea diagnoses with a 12-month cumulative incidence of 1.7% (95% CI 1.1% to 2.2%). Risk factors for chlamydia/gonorrhoea diagnosis were: 5+ HIV-positive partners (HR=3.3, 95% CI 1.4 to 7.8; reference=none) and recreational drug use (HR=2.2, 95% CI 1.2 to 3.9).ConclusionsHeightened risks with recreational drug use and multiple HIV-positive partners suggest that chlamydia/gonorrhoea may have achieved high prevalence in certain sexual networks among HIV-positive MSM. Interventions to promote safer sex and timely testing among MSM are needed.

Health in All Policies (HiAP) is a strategy that seeks to integrate health considerations into the development, implementation and evaluation of policies across various non-health sectors of the government. Over the past 15 years, there has been an increase in the uptake of HiAP by local, regional and national governments. Despite the growing popularity of this approach, most existing literature on HiAP implementation remains descriptive rather than explanatory in its orientation. Moreover, prior research has focused on the more technical aspects of the implementation process. Thus, studies that aim to ‘build capacity to promote, implement and evaluate HiAP’ abound. Conversely, there is little emphasis on the political aspects of HiAP implementation. Neglecting the role of politics in shaping the use of HiAP is problematic, since health and the strategies by which it is promoted are partially political.This glossary addresses the politics gap in the existing literature by drawing on theoretical concepts from political, policy, and public health sciences to articulate a framework for studying how political mechanisms influence HiAP implementation. To this end, the glossary forms part of an on-going multiple explanatory case study of HiAP implementation, HARMONICS (HiAP Analysis using Realist Methods on International Case Studies, harmonics-hiap.ca), and is meant to expand on a previously published glossary addressing the topic of HiAP implementation more broadly. Collectively, these glossaries offer a conceptual toolkit for understanding how politics explains implementation outcomes of HiAP.

The optimal timing of biologic agent treatment in polyarticular juvenile idiopathic arthritis (JIA) is unknown. This study evaluated the costs and outcomes of first‐line treatment with etanercept (ETN), an anti–tumor necrosis factor (anti‐TNF) agent, compared with step‐wise therapy in JIA. We compared 2 strategies: methotrexate (MTX) plus ETN as first‐line therapy (ETN‐first) and MTX monotherapy followed by ETN (ETN‐second), using a cohort state‐transition model of newly diagnosed JIA patients. The model's time horizon was 5 years, and the perspective was that of the Canadian health care system. The base case patient was 11 years old, weighed 40 kg, and had 5 or more active joints. Direct costs were calculated and discounted at a rate of 3% per year. Outcomes were expressed as quality‐adjusted life years (QALYs). Scenario analyses varied multiple parameters simultaneously to model more severely and more mildly affected patients. ETN‐first, compared to ETN‐second, yielded a discounted incremental cost of $16,893 (95% confidence interval [95% CI] 9,348–25,310), incremental QALY of 0.19 (95% CI 0.08–0.32), and an incremental cost‐effectiveness ratio of $88,815 per QALY gained. The results were sensitive to the cost of ETN, the time horizon of the model, and estimates of the efficacy of the first‐line therapies. The cost per QALY for treating patients with severe JIA was $33,960. First‐line therapy of ETN and MTX is relatively expensive compared to MTX alone, but may be economically attractive for more severely affected patients. More research is needed regarding the efficacy of first‐line anti‐TNF agents.

Genomic sequencing can generate complex results, including variants of uncertain significance (VUSs). In general, VUSs should not inform clinical decision-making. This study aimed to assess participants’ expected management of VUSs.

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There have been few population-based studies describing the risk of adverse neonatal outcomes among women living with HIV in Canada. Accordingly, we compared the risk of preterm birth (PTB), low birth weight (LBW) and small for gestational age births among Ontario women aged 18 to 49 years living with and without HIV infection.

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.

The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood.

Background Guidelines suggest that clinicians should provide their patients with antiretroviral adherence support, but there is uncertainty about the types of adherence support clinicians think are important, the methods they use to provide adherence support, and the barriers they face in providing such support in clinical practice.Objective To study clinician perspectives on the importance of different antiretroviral adherence support activities and compare these with clinicians' self-reported actual adherence support practices.Methods From March to August 2005, surveys were mailed to physicians, pharmacists, and nurses who provide care to HIV patients in Ontario, Canada. The 84-item survey asked providers to rate how necessary it was to provide 30 types of adherence support activities and how frequently they actually provided each of the types of adherence support. From this, we assessed healthcare provider perceptions of best or ideal practices in supporting medication adherence and actual or usual care in adherence support provision. We also examined whether an adherence support gap existed between the provision of best practice adherence support and actual adherence support in clinical practice.Results One hundred sixty-nine of 300 mailed surveys were returned, for a response rate of 56%. Respondents were highly specialized in HIV care and nearly all practiced in urban settings. Respondents indicated that most of the surveyed adherence support activities should be provided to all patients. However, most clinicians did not actually provide these adherence supports to their patients to the extent that they desired. We calculated an adherence support gap that ranged from 31% to 75% across the different types of adherence support activities.Conclusions We observed important adherence support gaps between ideal best practices in the provision of adherence support and actual provision of adherence support in clinical practice.

Background. Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. Methods. The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities : 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. Results.The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. Conclusion.The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory. Key words:decision analysis; cumulative prospect theory; expected utility theory ; standard gamble. (Med Decis Making 2000;20:404-412)

IntroductionIncidence of syphilis, chlamydia and gonorrhoea continue to rise among HIV-positive men who have sex with men (MSM) in Ontario. We previously observed an elevated risk of sexually transmitted infections (STI) among recreational drug users. Our aim was to determine the effect of a new STI diagnosis and recreational drug use on virologic failure (VF) among MSM successfully treated with antiretroviral therapy (ART). Our hypothesis is that any association between STIs and VF would be confounded by drug use.MethodsThe OHTN Cohort Study follows people receiving HIV care in Ontario. STI results and viral load (VL) data were retrieved via linkage with the provincial laboratory. We restricted analyses to 2610 MSM who completed>=1 annual questionnaire in 2008–2014 and had two consecutive VL<50 within a six-month period on ART. VF was defined as a single VL>=1000 or two consecutive VLs>=200. Periods of STI exposure were set around the diagnosis dates for each STI. We modelled STI diagnosis exposures and drug use as time-varying covariates on risk of VF using Cox regression adjusting for age, region and income as confounders. Our model allowed for repeat STI exposures and repeated VF events using the marginal means/rates model.ResultsThere were 472 VFs with a 24 month cumulative incidence of 12.1% (95%CI 11.1, 13.1). VFs at time of a new chlamydia or gonorrhoea infection were close to nil. We did not observe an increased risk of VF at the time of a new syphilis infection (HR=1.2 95% CI 0.8, 2.0; aHR=1.1 95% CI 0.7, 1.7). Risk was higher among drug users (non-injection aHR=1.4 95% CI 1.1, 1.8; injection aHR=1.8 95% CI 1.1, 2.6). There was no significant interaction but some evidence of positive confounding between syphilis and VF by drug use.ConclusionRegardless of drug use, we did not find an association between a new STI diagnosis and increased risk of VF among men on suppressive ART. Our data are limited by possible misclassification of STI exposures, because not all men were tested, and among those diagnosed, exact dates of acquisition were unknown.