PurposeSustained virologic response (SVR) is a validated surrogate marker for successful hepatitis C virus (HCV) treatment. Historically, interferon-based therapies, the standard of care for decades, offered only limited efficacy with respect to SVR. The recent introduction of highly effective direct-acting antivirals (DAAs) revolutionised treatment, expanding treatment eligibility among individuals with advanced liver disease (ALD) and drug/alcohol-related substance use disorder. Given these clinical policy shifts, we assessed the real-world impact of SVR on liver-related death for these key clinical groups for whom treatment had previously been less feasible.MethodsWe conducted a population-based, cohort study of Ontario residents with HCV viremia between January 1st, 1999, and December 31st, 2018, with follow-up to May 31st, 2021 (N = 73,411) and used cause-specific hazard models to explore the association between SVR and liver-related death.ResultsSVR was associated with a significant reduction in liver-related deaths (adjusted hazard ratio [aHR]: 0.22, 95%CI: 0.20-0.24). This benefit was consistent across all levels of liver disease severity, including individuals with (aHR: 0.11, 95%CI: 0.06-0.18) and without (aHR: 0.13, 95%CI: 0.10-0.17) cirrhosis, individuals with ALD (aHR: 0.24, 95%CI: 0.22-0.27) as well as among individuals with (aHR: 0.24, 95%CI: 0.21-0.27) and without (aHR: 0.21, 95%CI: 0.18-0.24) substance use disorder.ConclusionsThis study demonstrates the real-world impact of SVR on liver-related mortality and highlights the value of early treatment and continued support for populations who are marginalised.

BackgroundPatients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec.MethodsWe have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis.ResultsThe results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018.ConclusionsWe estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of ‘HBV’, ‘equity’, ‘social determinants of health’, ‘intervention’, and ‘Organization for Economic Co-operation and Development (OECD) countries’. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV.

Background. Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods. We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results. We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6–3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: −25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions. Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

Background: The World Health Organization (WHO) has set hepatitis C (HCV) elimination targets for 2030. Understanding existing gaps in the “HCV care-cascade” is essential for meeting these targets. We aimed to identify the level of service scale-up needed along the “HCV care-cascade” to achieve the WHO’s HCV elimination targets in Ontario, Canada. Methods: By employing a decision analytic model, we projected the quality-adjusted life years (QALYs) and healthcare costs for individuals with HCV in Ontario. We increased RNA testing and treatment rates to 98%, followed by increasing antibody testing uptake until we achieved the WHO’s mortality target (i.e., a 65% reduction in liver-related mortality by 2030 vs. 2015). Results: Without scaling up by 2030, the expected QALYs and costs per person were 9.156 and CAD 48,996, respectively. Improved RNA testing and treatment rates reduced liver-related deaths to 3.3/100,000, a 57% reduction from 2015. Further doubling the antibody testing rates can achieve the WHO’s mortality target in 2035, but not in 2030. Compared to the status quo, such program would be cost-effective considering a 50,000 CAD/QALY gained threshold if annual implementation costs stayed under 2.3 M CAD/100,000 people. Conclusions: Doubling the antibody testing rates, along with increased RNA testing and treatment rates, showed promise in meeting the WHO’s goals by 2035.

INTRODUCTION: Recently, minimally invasive surgical therapies (MISTs) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH). This study evaluated the cost-utility of water vapor thermal therapy (WVTT) and pros-tatic urethral lift (PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH.METHODS: In this model-based economic evaluation, we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the Canadian healthcare payer perspective) per quality -adjusted life year (QALY), discounted at 1.5% annually. In the model, men could receive up to three lines of therapy: 1) initial pharmacotherapy with MIST as second-line, and TURP or pharmacotherapy as third-line; 2) initial MIST (WVTT or PUL) with MIST again, TURP, or pharmacotherapy as second-line, and TURP as third-line. The model was populated using data from the published literature.RESULTS: The expected lifetime QALYs and costs were 15.50 QALYs and $14 626 for initial treatment with WVTT, 15.35 QALYs and $11 795 for pharmacotherapy followed by WVTT, 15.29 QALYs and $13 582 for pharmacotherapy followed by PUL, and 15.29 QALYs and $19 151 for initial treatment with PUL. Strategies involving PUL procedures were dominated by strategies involving WVTT. The incremental cost per QALY gained was $18 873 for initial WVTT compared to initial pharmacotherapy followed by WVTT.CONCLUSIONS: WVTT appears to be a cost-effective procedure and may be an appropri-ate first-line alternative to pharmacotherapy for patients with BPH and prostate volume less than 80 cm3 who seek faster improvement and no lifelong commitment to daily medications.

Background: HCV elimination requires a thorough understanding of the care cascade. A direct-acting antiviral (DAA)-era description of the care cascade has not been undertaken in Ontario, Canada’s most populous jurisdiction. Our primary objective was to describe the current population-level care cascade in the general Ontario population and among key risk groups ─ baby boomers, immigrants, and individuals experiencing residential instability. The secondary objective was to identify predictors of engagement. Methods: We conducted a population-based cohort study of Ontario residents undergoing HCV testing between January 1, 1999, and December 31, 2018, and mapped the care cascade [antibody-diagnosed, RNA tested, RNA positive, genotyped, treated, achieved sustained virologic response, reinfected/relapsed] as of December 31, 2018. The cascade was stratified by risk groups. Cause-specific hazard modeling was used to identify demographic, and socioeconomic predictors of engagement with key steps of the cascade. Results: Among 108,428 Ontario residents living with an HCV antibody diagnosis, 88% received confirmatory RNA testing; of these, 62% tested positive and 94% of positive tests were genotyped. Of those with confirmed viremia, 53% initiated treatment and 76% of treated individuals achieved sustained virologic response, while ~1% experienced reinfection or relapse. Males, older birth cohorts, long-term residents, those with a history of substance use disorder and social marginalization (eg, material deprivation, residential instability), and those initially diagnosed in the pre-DAA era exhibited lower rates of engagement with almost every step of HCV care. Conclusions: Despite DAA era improvements, treatment initiation remains a major gap. HCV screening and linkage-to-treatment, particularly for those with a history of substance use disorder and social marginalization, will be needed to equitably close gaps in HCV care in the province.

The current study assesses the extent to which government leaders' personality traits are related to divergent policy responses during the pandemic. To do so, we use data from the Oxford COVID-19 Government Response Tracker initiative (OxCGRT) to measure the speed and magnitude of policy responses across countries and NEGex, a dataset that maps the personality traits of current heads of government (presidents or prime ministers) in 61 countries. We find that world leaders scoring high on "plasticity" (extraversion, openness) were quicker to implement travel restrictions and provide financial relief as well as offered a stronger response in general (average overall response). Whereas, leaders scoring high on "stability" (conscientiousness, agreeableness, emotional stability) offered both quicker and stronger financial relief. Our findings underscore the need to account for the personality of decision-makers when exploring decision-making during the pandemic, and during similar crisis situations.

Background Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related mortality. Direct-acting antivirals (DAAs) have revolutionised treatment by offering profound improvements in sustained viral clearance (SVR) and tolerability resulting in rapid expansion of treatment for individuals for whom HCV treatment had previously been less feasible, such as those with advanced liver disease or with drug and/or alcohol-related substance use. Given these clinical policy shifts, the primary objective of this study was to assess the impact of SVR on liver-related death among important clinical groups and the secondary objective was to explore changes in predictors of liver-related death by treatment era using real-world data from a large population-based cohort.Methods We conducted a population-based, linked cohort study of all Ontario residents with HCV viremia between January 1st, 1999, and December 31st, 2018, with follow up to 31st May 2021 (N=73,411). Population-level health administrative, clinical, and demographic data were accessed at ICES. Cause-specific hazard models were used to explore the impact of SVR on liver-related death and to identify factors associated with the rate of liver-related death in the DAA and pre-DAA treatment eras. The moderating effects of liver disease severity and substance-use disorder on the relationship between SVR and liver-related-mortality was explored by stratification.Results Among Ontario residents diagnosed with living with HCV, the achievement of SVR was associated with a significant reduction in liver related mortality (adjusted hazard ratio [aHR] 0.22, 95%CI: 0.20-0.24 vs. no SVR). This was also observed across progressive liver disease severity levels (aHR 0.13, 95%CI: 0.10-0.17 for individuals without cirrhosis; aHR 0.11, 95%CI: 0.06-0.17 for those with compensated cirrhosis, and aHR 0.24, 95%CI: 0.22-0.27 for those with advanced liver disease vs. no SVR) and by substance use status (aHR 0.24, 95%CI: 0.21-0.27 for those with a history of substance use disorder; and aHR 0.21, 95%CI: 0.18-0.24 for those without vs. no SVR). Additionally, factors such as age at diagnosis, sex, liver disease severity, immigration status, birth year, substance use, HBV-coinfection, viral genotype, and markers of social marginalisation were independent predictors of liver-related mortality. However, sex, and viral genotype no longer displayed significant associations with liver-related death in the DAA era as was observed in the earlier treatment era.Conclusions This study provides real-world evidence showing profound impact of SVR on liver-related mortality in a population-based sample of individuals with CHC and highlights the importance of early diagnosis and treatment. This study further demonstrates significant mortality benefits of SVR regardless of substance use status highlighting the importance of supporting marginalised individuals in treatment access.### Competing Interest StatementDr. W. Wong reports a grant from the Canadian Liver Foundation, outside the submitted work.### Funding StatementThis study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). A. Erman is supported by a postdoctoral fellowship from the Canadian Institute of Health Research (CIHR) [FRN:201910MFE-430962-169632]. This research was supported, in part, by a Canada Research Chair in Economics of Infectious Diseases held by Beate Sander [CRC-950-232429]. This study also received funding from CIHR grant [PJT-156066]. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the University Health Network Research Ethics Board. ICES is an independent non-profit research institute with legal status under Ontario health information privacy law to collect and analyze healthcare data for the purposes of healthcare evaluation and improvement without consent. The use of data in this project was authorized under section 45 of the Ontario Personal Health Information Protection Act, which does not require review by a Research Ethics Board.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g., healthcare organizations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at [www.ices.on.ca/DAS][1] (email: das{at}ices.on.ca). The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification. [1]: http://www.ices.on.ca/DAS

BACKGROUND:Recently, minimally invasive therapies (MITs), such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH), offering symptom relief with a favorable safety profile. The objective of this study was to evaluate the cost-utility of MITs (WVTT and PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH.METHODS:In this model-based economic evaluation we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the US public payer perspective) per quality-adjusted life year (QALY), discounted at 3% annually. Various clinical scenarios were evaluated given that most men undergo several lifelong therapies up to surgical intervention and potentially thereafter. As such, in the study model men could receive up to three lines of therapy: (1) initial pharmacotherapy with MIT as second-line, and transurethral resection of the prostate (TURP) or pharmacotherapy as third-line; (2) initial MIT (WVTT or PUL) with MIT again, TURP or pharmacotherapy as second-line, and TURP as third-line. Model was populated using data from the published literature. Probabilistic analyses were performed.RESULTS:Initial treatment with WVTT led to the highest QALYs (13.05) and the lowest cost ($15,461). The cumulative QALYs and lifetime costs were 12.92 QALYs and $20,280 for pharmacotherapy followed by WVTT, 12.87 QALYs and $22,424 for pharmacotherapy followed by PUL, 12.86 QALYs and $20,930 for initial treatment with PUL. In the cost-utility analysis, WVTT as initial treatment dominated all three strategies, i.e., generated more QALYs at a lower cost.CONCLUSION:WVTT is an effective and cost-saving procedure, and may be an appropriate first-line alternative to pharmacotherapy for moderate-to-severe BPH patients who seek faster improvement and no lifelong commitment to daily medications.

Objective The objective of this paper is to conduct a systematic review that summarizes the cost-effectiveness of cleft lip and/or palate (CL/P) care in low- and middle-income countries (LMICs) based on existing literature. Design We searched eleven electronic databases for articles from January 1, 2000 to December 29, 2020. This study is registered in PROSPERO (CRD42020148402). Two reviewers independently conducted primary and secondary screening, and data extraction. Setting All CL/P cost-effectiveness analyses in LMIC settings. Patients, Participants In total, 2883 citations were screened. Eleven articles encompassing 1,001,675 patients from 86 LMICs were included. Main Outcome Measures We used cost-effectiveness thresholds of 1% to 51% of a country's gross domestic product per capita (GDP/capita), a conservative threshold recommended for LMICs. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) checklist. Results Primary CL/P repair was cost-effective at the threshold of 51% of a country's GDP/capita across all studies. However, only 1 study met at least 70% of the JBI criteria. There is a need for context-specific cost and health outcome data for primary CL/P repair, complications, and existing multidisciplinary management in LMICs. Conclusions Existing economic evaluations suggest primary CL/P repair is cost-effective, however context-specific local data will make future cost-effectiveness analyses more relevant to local decision-makers and lead to better-informed resource allocation decisions in LMICs.

You have accessJournal of UrologyCME1 May 2022MP01-12 PHARMACOTHERAPY VS MINIMALLY INVASIVE THERAPIES AS INITIAL THERAPY FOR PATIENTS WITH BENIGN PROSTATE HYPERPLASIA: A MICROSIMULATION MODEL Yeva Sahakyan, Aysegul Erman, Naeem Bhojani, Bilal Chughtai, Kevin C. Zorn, Beate Sander, and Dean Elterman Yeva SahakyanYeva Sahakyan More articles by this author , Aysegul ErmanAysegul Erman More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Bilal ChughtaiBilal Chughtai More articles by this author , Kevin C. ZornKevin C. Zorn More articles by this author , Beate SanderBeate Sander More articles by this author , and Dean EltermanDean Elterman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002513.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study evaluated the effectiveness of MITs (Rezum and Urolift) compared to pharmacotherapy as initial treatment option for patients with moderate-to-severe BPH. METHODS: We developed a simulation model (image_a) to estimate the impact of Rezum and Urolift compared to pharmacotherapy as initial treatment on International Prostate Symptom Score (IPSS) progression, retreatment rates and quality-adjusted life years (QALYs), discounted at a 1.5% rate. We simulated males with a mean age of 65 years and an average IPSS of 16 over their lifetime. BPH progression and treatments effects were modeled through the IPSS score. Patients could receive up to two additional lines of therapy: i) patients who started with pharmacotherapy could receive MIT as a second-line, and TURP or pharmacotherapy as a third-line of therapy; ii) patients who started with MIT (Rezum or UroLift) could receive repeated MIT or TURP or pharmacotherapy as a second-line, and TURP as a third line of therapy. Therapy-specific adverse events were applied. The model was informed by data from the published literature. RESULTS: Simulated health outcomes compared well to the reported trials data (image_b). Over 20 years the proportion of patients who were retreatment free were 49% for Rezum, 39% for Urolift and 50% for pharmacotherapy. Over the patients’ lifetime initial treatment with Rezum was the most effective option (15.18 QALYs), pharmacotherapy followed by Rezum was the second most effective option (15.08 QALY), followed by Urolift (14.99 QALYs) as initial treatment, and, lastly, pharmacotherapy followed by UroLift (14.98 QALY). CONCLUSIONS: MITs are effective treatment options for moderate-to-severe BPH. These findings will be beneficial for clinicians and health policy makers to further define the implementation of MITs in treatment for BPH. Source of Funding: Not applicable © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e5 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yeva Sahakyan More articles by this author Aysegul Erman More articles by this author Naeem Bhojani More articles by this author Bilal Chughtai More articles by this author Kevin C. Zorn More articles by this author Beate Sander More articles by this author Dean Elterman More articles by this author Expand All Advertisement PDF DownloadLoading ...

Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, Ontario, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada ICES, Toronto, Ontario, Canada Public Health Ontario, Toronto, Ontario, Canada CorHealth Ontario, Toronto, Ontario, Canada Division of Vascular Surgery, St Michael’s Hospital, Toronto, Ontario, Canada Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Infections and deaths associated with COVID-19 show a high degree of heterogeneity across different populations. A thorough understanding of population-level predictors of such outcomes is crucial for devising better-targeted and more appropriate public health preparedness measures. While demographic, economic, and health-system capacity have featured prominently in recent work, cultural, and behavioral characteristics have largely been overlooked. However, cultural differences shape both the public policy response and individuals' behavioral responses to the crisis in ways that can impact infection dynamics and key health outcomes. To address this gap, we used meta-analytic methods to explore the global variability of three public health outcomes (i.e., crude test positivity, case/infection fatality, and mortality risk) during the first wave of the pandemic. This set of analyses identified several cultural/behavioral attributes (e.g., uncertainty avoidance and long-term vs. short-term normative orientation) as independent predictors of public health outcomes after adjusting for key demographic, political, economic, and health-system-related predictors; which were robust in sensitivity analyses. In conclusion, this study clearly demonstrates that cultural attributes do in fact account for some of the global disparities in COVID-19-attributed health outcomes. As a consequence, policymakers should more explicitly consider a society's cultural attributes alongside other important parameters such as demographic characteristics and health system constraints in order to develop better tailored and more effective policy responses.

Ontario’s initial mass COVID-19 vaccination strategy in place until April 8, 2021 was based on per-capita regional allocation of vaccines with subsequent distribution – in order of relative priority – by age, chronic health conditions and high-risk congregate care settings, COVID-19 hotspots, and essential worker status. Early analysis of Ontario’s COVID-19 vaccine rollout reveals inequities in vaccine coverage across the province, with residents of higher risk neighbourhoods being least likely get vaccinated. Accelerating the vaccination of COVID-19 hotspots and essential workers will prevent considerably more SARS-CoV-2 infections and COVID-19 hospitalizations, ICU admissions and deaths as compared with Ontario’s initial mass vaccination strategy (Figure 1).

Hepatitis C virus (HCV) affects approximately 250,000 Canadians. Although safe and effective (>95% cure rates) antiviral therapies have become available within the past 5 years, chronic HCV infection still remains a major driver of end-stage liver disease and liver transplantation. Both the Canadian Institute for Health Research and the Public Health Agency of Canada recognize the impact of HCV-related liver diseases and support the Canadian Network for Hepatitis C (CanHepC), a National network for the scientific study of hepatitis C that organizes an annual symposium as part of its knowledge translation mandate. At the 8 th Canadian Symposium on Hepatitis C Virus in May 2019, basic scientists, clinicians, epidemiologists, social scientists, and community members came together to share their work under the theme of “Improving diagnosis and linkage to care”. This symposium also marked the launch of the Blueprint to inform hepatitis C elimination efforts in Canada, a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial and federal organizations developing their own HCV elimination strategies.

Deaths associated with COVID-19 shows a high degree of heterogeneity across different populations. An assessment of the global variability in COVID-19-attributable deaths is essential for predicting the health and economic impact of future outbreaks in different settings. Moreover, a comprehensive understanding of population-level predictors is also crucial for devising better-targeted and more appropriate emergency preparedness measures. While, demographic, economic and health-system capacity have featured prominently in recent work, cultural and behavioural characteristics have largely been overlooked. However, cultural differences likely shape both the public policy response and individuals’ behavioural responses to the crisis in ways that can impact infection dynamics and key health outcomes. To address this gap, we used meta-analytic methods to explore the global variability of COVID-19-attributed deaths during the first-wave of the pandemic and identified cultural/behavioural attributes (e.g., individualism, uncertainty avoidance) as independent predictors of COVID-19 fatalities after adjusting for important demographic, political, economic and health-system-related predictors.

Background & Aims Direct-acting antivirals (DAAs) are highly effective, but expensive treatments for chronic hepatitis C (CHC). To manage costs, drug plans worldwide have rationed access to DAAs in a variety of ways. This study quantifies the health impact of formulary restrictions and presents a clinical decision tool for informing treatment timing decisions. Methods A decision-analytic model was developed to quantify the health impact of delaying DAAs for subpopulations stratified by age, fibrosis level, viral genotype, and injection drug use over their lifetime. The health impact was quantified in terms of quality-adjusted life expectancy (quality-adjusted life years, or QALYs) and life expectancy (years). Results Deferring DAAs for patients with no or mild fibrosis (F0/F1) for 1-5 years is unlikely to result in life expectancy losses and leads only to marginal losses of 0.02-0.06 QALYs per year of delay. However, for 30-50-year-olds with advanced fibrosis (>= F3) delays as short as a year results in a considerable health loss (0.25-1.04 QALYs and 0.19-1.53 years). Reimbursement limits for those with substance use are associated with large health losses. People who actively inject drugs with advanced fibrosis (>= F3) may lose 0.18-1.05 QALYs and 0.13-1.16 years per year of delay, despite the risk of reinfection and competing mortality. Results are robust to parameter uncertainty and key assumptions. Conclusions We present a clinical decision tool for informing treatment timing for various CHC subpopulations. In general, findings suggest that patients with at least moderate fibrosis should be treated promptly regardless of active drug use.

Objectives Mathematical models are increasingly important in planning for the upcoming chronic hepatitis C (CHC) elimination efforts. Such models require reliable natural history inputs to make accurate predictions on health and economic outcomes. Yet, hepatitis C virus disease progression is known to vary widely in the literature and published inputs are currently outdated. The objectives of this study were to obtain updated estimates of fibrosis progression rates (FPR) in treatment-naïve patients with CHC and to explore sources of heterogeneity. Design A systematic review was conducted using Ovid-MEDLINE, Ovid-EMBASE and PubMed databases (January 1990 to January 2018) to identify observational studies of hepatic fibrosis in treatment-naïve patients with CHC. Outcomes Stage-constant FPRs were estimated for each study given the reported fibrosis scores and duration of infection. Stage-specific FPRs (ie, F0→F1; F1→F2; F2→F3; F3→F4) were estimated using Markov maximum likelihood estimation. Estimates were pooled using random-effects meta-analysis and heterogeneity was evaluated by stratification and random-effects meta-regression. Results The review identified 111 studies involving 131 groups of patients (n=42 693). The pooled stage-constant FPR was 0.094 (95% CI 0.088 to 0.100); stage-specific FPRs were F0→F1: 0.107 (95% CI 0.097 to 0.118); F1→F2: 0.082 (95% CI 0.074 to 0.091); F2→F3: 0.117 (95% CI 0.107 to 0.129); F3→F4: 0.116 (95% CI 0.104 to 0.131). Stratified analysis revealed substantial variation in progression by study population. Meta-regression indicated associations between progression and infection age, duration, source, viral genotype and study population. Findings indicate that FPRs display substantial heterogeneity across study populations and pooled values from more homogenous subpopulations should be considered when estimating prognosis. Conclusions This large meta-analysis presents updated prognostic estimates for CHC derived from newer studies using better diagnostic methods and improves estimates for important patient populations in terms of clinical policy (eg, injection drug users, non-clinical populations, liver clinic patients) and should be a valuable resource for patients, clinicians and clinical policymakers.