Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: We 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.

Inclusion of non-medical interventions in model-based economic evaluations for tuberculosis: A scoping review.

BACKGROUND: The economic evaluation of health interventions is important in priority setting. Several guidance documents exist to support the conduct of economic evaluations, however, there is limited guidance for the evaluation of non-medical interventions. For tuberculosis (TB), where equity-deserving groups are disproportionately impacted, assessing interventions aimed at addressing social risk factors is necessary to effectively reduce TB burden. OBJECTIVE: This scoping review seeks to assess the existing literature on model-based economic evaluations of TB interventions to gauge the extent to which non-medical interventions have been evaluated in low-TB-incidence jurisdictions. As a secondary objective, this review aims to characterize key features of existing economic evaluations of medical and non-medical interventions. METHODS: A literature search was conducted in the grey literature and MEDLINE, Embase, EconLit, and PsychINFO databases to September 6, 2022 following the Arksey and O'Malley framework. Eligible articles were those that used decision-analytic modeling for economic evaluation of TB interventions in low-TB-incidence jurisdictions. RESULTS: This review identified 127 studies that met the inclusion criteria; 11 focused on prevention, 73 on detection, and 43 on treatment of TB. Only three studies (2%) evaluated non-medical interventions, including smoking reduction strategies, improving housing conditions, and providing food vouchers. All three non-medical intervention evaluations incorporated TB transmission and robust uncertainty analysis into the evaluation. The remainder of the studies evaluated direct medical interventions, eight of which were focused on specific implementation components (e.g., video observed therapy) which shared similar methodological challenges as the non-medical interventions. The majority of remaining evaluated medical interventions were focused on comparing various screening programs (e.g., immigrant screening program) and treatment regimens. CONCLUSIONS: This scoping review identified a gap in literature in the evaluation of non-medical TB interventions. However, the identified articles provided useful examples of how economic modeling can be used to explore non-traditional interventions using existing economic evaluation methods.

Engagement with the HCV care cascade among high-risk groups: A population-based study.

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.

Applying Quality Indicators to Examine Quality of Care During Active Surveillance in Low-Risk Prostate Cancer: A Population-Based Study.

BACKGROUND: Although a few studies have reported wide variations in quality of care in active surveillance (AS), there is a lack of research using validated quality indicators (QIs). The aim of this study was to apply evidence-based QIs to examine the quality of AS care at the population level. METHODS: QIs were measured using a population-based retrospective cohort of patients with low-risk prostate cancer diagnosed between 2002 and 2014. We developed 20 QIs through a modified Delphi approach with clinicians targeting the quality of AS care at the population level. QIs included structure (n=1), process of care (n=13), and outcome indicators (n=6). Abstracted pathology data were linked to cancer registry and administrative databases in Ontario, Canada. A total of 17 of 20 QIs could be applied based on available information in administrative databases. Variations in QI performance were explored according to patient age, year of diagnosis, and physician volume. RESULTS: The cohort included 33,454 men with low-risk prostate cancer, with a median age of 65 years (IQR, 59-71 years) and a median prostate-specific antigen level of 6.2 ng/mL. Compliance varied widely for 10 process QIs (range, 36.6%-100.0%, with 6 [60%] QIs >80%). Initial AS uptake was 36.6% and increased over time. Among outcome indicators, significant variations were observed by patient age group (10-year metastasis-free survival was 95.0% for age 65-74 years and 97.5% in age <55 years) and physician average annual AS volume (10-year metastasis-free survival was 94.5% for physicians with 1-2 patients with AS and 95.8% for those with ≥6 patients with AS annually). CONCLUSIONS: This study establishes a foundation for quality-of-care assessments and monitoring during AS implementation at a population level. Considerable variations appeared with QIs related to process of care by physician volume and Qis related to outcome by patient age group. These findings may represent areas for targeted quality improvement initiatives.

Cost-effectiveness analysis of genetic tools to predict treatment response in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies show variable efficacy for patients with CF. Patient-derived predictive tools may identify individuals likely to respond to CFTRs, but are not in routine use. We aimed to determine the cost-utility of predictive tool-guided treatment with CFTRs as add-on to standard of care (SoC) for individuals with CF. METHODS: This economic evaluation compared two strategies using an individual level simulation: (i) Treat All, where all patients received CFTRs plus SoC and (ii) Test→Treat, where patients who tested positive on predictive tools received CFTRs plus SoC and those who tested negative received SoC only. We simulated 50,000 individuals over their lifetime, and estimated costs (2020 CAD) per quality-adjusted life year (QALY) from the healthcare payer's perspective, discounted at 1.5% annually. The model was populated using Canadian CF registry data and published literature. Probabilistic and deterministic sensitivity were conducted. RESULTS: The Treat All and Test→Treat and strategies yielded 22.41 and 21.36 QALYs, and cost $4.21 M and $3.15 M respectively. Results of probabilistic sensitivity analysis showed that Test→Treat was highly cost-effective compared to Treat All in 100% of simulations at cost-effectiveness thresholds as high as $500,000 per QALY. Test→Treat may save between $931 K to $1.1 M per QALY lost, depending on sensitivity and specificity of predictive tools. CONCLUSION: The use of predictive tools could optimize the health benefits of CFTR modulators while reducing costs. Our findings support the use of pre-treatment predictive testing and may help inform coverage and reimbursement policies for individuals with CF.

Evaluating the Impact of Ex Vivo Lung Perfusion on Organ Transplantation: A Retrospective Cohort Study.

BACKGROUND: Ex vivo lung perfusion (EVLP) sustains and allows advanced assessment of potentially useable donor lungs before transplantation, potentially relieving resource constraints. OBJECTIVE: We sought to characterize the effect of EVLP on organ utilization and patient outcomes. METHODS: We performed a retrospective, before-after cohort study using linked institutional data sources of adults wait-listed for lung transplant and donor organs transplanted in Ontario, Canada between 2005 and 2019. We regressed the annual number of transplants against year, EVLP use, and organ characteristics. Time-to-transplant, waitlist mortality, primary graft dysfunction, tracheostomy insertion, in-hospital mortality, and chronic lung allograft dysfunction were evaluated using propensity score-weighted regression. RESULTS: EVLP availability ( P =0.01 for interaction) and EVLP use ( P <0.001 for interaction) were both associated with steeper increases in transplantation than expected by historical trends. EVLP was associated with more donation after circulatory death and extended-criteria donors transplanted, while the numbers of standard-criteria donors remained relatively stable. Significantly faster time-to-transplant was observed after EVLP was available (hazard ratio=1.64 [1.41-1.92]; P <0.001). Fewer patients died on the waitlist after EVLP was available, but no difference in the hazard of waitlist mortality was observed (HR=1.19 [0.81-1.74]; P =0.176). We observed no difference in the likelihood of chronic lung allograft dysfunction before versus after EVLP was available. CONCLUSIONS: We observed a significant increase in organ transplantation since EVLP was introduced into practice, predominantly from increased acceptance of donation after circulatory death and extended-criteria lungs. Our findings suggest that EVLP-associated increases in organ availability meaningfully alleviated some barriers to transplant.

A Systematic Review of the Cost-Effectiveness of Cleft Care in Low- and Middle-Income Countries: What is Needed?

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.

Pharmacotherapy vs. minimally invasive therapies as initial therapy for moderate-to-severe benign prostatic hyperplasia: a cost-effectiveness study.

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.

Cost-utility of minimally invasive therapies vs. pharmacotherapy as initial therapy for benign prostatic hyperplasia A Canadian healthcare payer perspective.

INTRODUCTION: Recently, minimally invasive surgical therapies (MIST s) 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 prostatic 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 appropriate 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.

Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

BACKGROUND: Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim's value for money remains unclear. OBJECTIVE: To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020. RESULTS: We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17-97.4%) and mortality rates (5.8-8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit. CONCLUSIONS: Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

Do Health Technology Assessment organisations consider manufacturers' costs in relation to drug price? A study of reimbursement reports.

INTRODUCTION: Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers' costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations. METHOD: An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins. RESULTS: A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer's costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers' costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer's costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs. CONCLUSION: Despite the attention given to manufacturers' costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.

Patient-Proxy and Societal Perspectives of Quality-of-Life Utilities in Children With Cleft Lip and Palate Managed With Surgical Repair vs No Repair in Ethiopia.

Importance: In Ethiopia, more than 70% of infants with cleft lip and/or palate (CL/P) lack access to surgery. Infants who are untreated can experience severe malnutrition and extreme social stigma resulting in abandonment. Utilities are standardized measures of health-related quality of life (HRQOL) that inform health care resource allocation. However, CL/P utilities are missing from low- and middle-income countries (LMICs). Objective: To elicit utilities for untreated and surgically treated children with CL/P with consideration for social determinants of health from patient-proxy and societal participants. Design, Setting, and Participants: This cross-sectional study used patient proxies and societal participants in Addis Ababa, Ethiopia, from July 1, 2019, to January 30, 2020. Eligible patient proxies were caregivers of children younger than 18 years with nonsyndromic CL/P who were untreated or received surgery. Proxies were necessary as most patients were 0 to 4 years old and cannot reliably self-report. Eligible societal participants were 18 years and older with no family history of CL/P. Exposures: Surgical treatment and social determinants of health. Main Outcomes and Measures: Participants measured utilities using the visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG). Results: In this study, 312 patient proxies and 135 societal participants were recruited. Mean (SD) utilities for untreated CL/P ranged from 0.57 (0.23) to 0.70 (0.22) from patient proxies and from 0.35 (0.21) to 0.8 (0.23) from societal participants, depending on utility instrument and cleft type. Surgical treatment was associated with a better HRQOL from the patient-proxy perspective (VAS, 0.17; 95% CI, 0.09 to 0.26; TTO, 0.15; 95% CI, 0.05 to 0.25) from the societal perspective (VAS, 0.21; 95% CI, 0.16 to 0.26; TTO, 0.17; 95% CI, 0.13 to 0.22; SG, 0.11; 95% CI, 0.06 to 0.15). Social determinants of health that were associated with patient-proxy utilities were income above the national mean (VAS, 0.10; 95% CI, 0.02 to 0.17; TTO, 0.11; 95% CI, 0.02 to 0.20), and religion (Christian vs other: TTO, -0.10; 95% CI, -0.17 to -0.03). From the societal perspective, the association between treatment and utilities was smaller in females compared with males (TTO, -0.05; 95% CI, -0.10 to -0.01). Conclusions and Relevance: The findings of this study suggest that CL/P disease severity and surgical impact in Ethiopia were undervalued by previous estimates from high-income countries and were associated with social determinants of health. Utility studies from participants from LMICs are feasible and necessary for representing HRQOL in LMICs and addressing health inequalities.

Feasibility of hepatitis B elimination in high-income countries with ongoing immigration.

BACKGROUND & AIMS: Addressing HBV is vital to meeting the World Health Organization (WHO)'s viral hepatitis elimination goals, as 47% of viral hepatitis complications can be attributed to HBV. The objective of this study is to develop an agent-based model determining which integrated strategies involving vaccination, screening, and treatment would achieve the WHO's goals. METHODS: We developed an agent-based model to characterize the HBV epidemic in a high-income country with ongoing immigration. The spread of HBV was simulated through sexual networks and perinatal transmission. Model parameters were estimated from the literature and calibrated against historical HBV data. Sensitivity analyses were performed to assess the uncertainty. RESULTS: We predict that under the current strategies, the incidence of acute hepatitis B, and HBV-attributable decompensated cirrhosis and hepatocellular carcinoma would decrease by 64.5%, 9.4%, and 10.5% between 2015-2030, respectively. However, the incidence of chronic hepatitis B and liver-related deaths would increase by 26.6% and 1.0% between 2015-2030, respectively. Results were sensitive to the number of immigrants and HBV prevalence in immigrants. CONCLUSIONS: The results suggest that the current vaccination, screening, and treatment strategies will be inadequate to achieve WHO elimination goals. Even with extensive integrated scale-up in vaccination, screening, and treatment, the morbidity and mortality targets may not be reachable, highlighting the need for a re-evaluation of the global strategy for HBV, the importance of developing curative therapy for HBV, and of establishing tailored strategies to prevent long-term sequelae and improve health in immigrants. LAY SUMMARY: We have developed a model that reflects the dynamics of hepatitis B virus (HBV) transmission in a high-income country with ongoing immigration, which enabled us to forecast the epidemiology of HBV for policy-level decision making. Our analysis suggests that current vaccination, screening, and treatment strategies are inadequate to achieve the WHO goals of eliminating chronic hepatitis B. Even with extensive integrated scale-up in vaccination, screening, and treatment, the morbidity and mortality targets may not be reachable.

Diagnostic accuracy of teleretinal screening for detection of diabetic retinopathy and age-related macular degeneration: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of teleretinal screening compared with face-to-face examination for detection of diabetic retinopathy (DR) and age-related macular degeneration (AMD). METHODS AND ANALYSIS: This study adhered to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). A comprehensive search of OVID MEDLINE, EMBASE and Cochrane CENTRAL was performed from January 2010 to July 2021. QUADAS-2 tool was used to assess methodological quality and applicability of the studies. A bivariate random effects model was used to perform the meta-analysis. Referrable DR was defined as any disease severity equal to or worse than moderate non-proliferative DR or diabetic macular oedema (DMO). RESULTS: 28 articles were included. Teleretinal screening achieved a sensitivity of 0.91 (95% CI: 0.82 to 0.96) and specificity of 0.88 (0.74 to 0.95) for any DR (13 studies, n=7207, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) low). Accuracy for referrable DR (10 studies, n=6373, GRADE moderate) was lower with a sensitivity of 0.88 (0.81 to 0.93) and specificity of 0.86 (0.79 to 0.90). After exclusion of ungradable images, the specificity for referrable DR increased to 0.95 (0.90 to 0.98), while the sensitivity remained nearly unchanged at 0.85 (0.76 to 0.91). Teleretinal screening achieved a sensitivity of 0.71 (0.49 to 0.86) and specificity of 0.88 (0.85 to 0.90) for detection of AMD (three studies, n=697, GRADE low). CONCLUSION: Teleretinal screening is highly accurate for detecting any DR and DR warranting referral. Data for AMD screening is promising but warrants further investigation. PROSPERO REGISTRATION NUMBER: CRD42020191994.

Impact of cancer surgery slowdowns on patient survival during the COVID-19 pandemic: a microsimulation modelling study.

BACKGROUND: With the declaration of the global pandemic, surgical slowdowns were instituted to conserve health care resources for anticipated surges in patients with COVID-19. The long-term implications on survival of these slowdowns for patients with cancer in Canada is unknown. METHODS: We constructed a microsimulation model based on real-world population data on cancer care from Ontario, Canada, from 2019 and 2020. Our model estimated wait times for cancer surgery over a 6-month period during the pandemic by simulating a slowdown in operating room capacity (60% operating room resources in month 1, 70% in month 2, 85% in months 3-6), as compared with simulated prepandemic conditions with 100% resources. We used incremental differences in simulated wait times to model survival using per-day hazard ratios for risk of death. Primary outcomes included life-years lost per patient and per cancer population. We conducted scenario analyses to evaluate alternative, hypothetical scenarios of different levels of surgical slowdowns on risk of death. RESULTS: The simulated model population comprised 22 799 patients waiting for cancer surgery before the pandemic and 20 177 patients during the pandemic. Mean wait time to surgery prepandemic was 25 days and during the pandemic was 32 days. Excess wait time led to 0.01-0.07 life-years lost per patient across cancer sites, translating to 843 (95% credible interval 646-950) life-years lost among patients with cancer in Ontario. INTERPRETATION: Pandemic-related slowdowns of cancer surgeries were projected to result in decreased long-term survival for many patients with cancer. Measures to preserve surgical resources and health care capacity for affected patients are critical to mitigate unintended consequences.

Health Care System Costs Associated With Surgery and Medical Therapy for Children With Drug-Resistant Epilepsy in Ontario.

BACKGROUND AND OBJECTIVES: Improvement in seizure control after epilepsy surgery could lead to lower health care resource use and costs, but it is uncertain whether this could offset the high costs related to surgery. This study aimed to evaluate phase-specific and cumulative long-term health care costs of surgery compared to medical therapy in children with drug-resistant epilepsy from the health care payer perspective. METHODS: Children who were evaluated for epilepsy surgery and treated with surgery or medical therapy from 2003 to 2018 at the Hospital for Sick Children in Toronto were identified from chart review and linked to their health administrative databases in Ontario, Canada. Inverse probability of treatment weighting with stabilized weights was used to balance the baseline covariates between the 2 groups. Patients were assigned to presurgery, surgery, short-term (first 2 years), intermediate-term (2-5 years), and long-term (>5 years) postsurgery care phases on the basis of treatment trajectory. Phase-specific and cumulative long-term health care costs were evaluated. Costs were converted from Canadian to US dollars year 2018 value. RESULTS: There were 372 surgical and 258 medical patients. Costs were higher in surgical than medical patients for presurgery (3 and 39 weeks), surgery, and short-term care phase, and the attributable costs of surgery per 7 patient-days were $1,602 (95% CI $1,438-$1,785), $172 (95% CI $147-$185), $19,819 (95% CI $18,822-$20,932), and $28 (95% CI $22-$32), respectively. Costs were lower in surgical patients for intermediate- and long-term care phase, and the attributable costs were -$72 (95% CI -$124 to -$35) and -$94 (95% CI -$129 to -$63), respectively. In surgical patients, costs were highest for surgery followed by presurgery care phase, with hospitalizations accounting for the highest cost component. In medical patients, costs increased gradually from presurgery to long-term care phase. Cumulative costs were higher for surgical than medical patients in the first 7 years after surgery, but from 8 years on, costs were lower for surgical patients. DISCUSSION: This study demonstrated the long-term economic benefits of epilepsy surgery compared to medical therapy for the health care system with the use of real-world data, which would justify the high costs of surgery. The results will support future economic evaluation comparing minimally invasive treatment such as laser therapy to surgery.

A cost-utility analysis of apalutamide for metastatic castrationsensitive prostate cancer.

INTRODUCTION: Earlier application of oral androgen receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer (mCSPC) has established improvements in overall survival, as compared to androgen deprivation therapy (ADT) alone. Recently, the use of apalutamide plus ADT has demonstrated improvement in mCSPC-related mortality vs. ADT alone, with an acceptable toxicity profile. However, the cost-effectiveness of this therapeutic option remains unknown. METHODS: We used a state-transition model with probabilistic analysis to compare apalutamide plus ADT, as compared to ADT alone, for mCSPC patients over a time horizon of 20 years. Primary outcomes included expected life-years (LY), quality-adjusted life-years (QALY), lifetime cost (2020 Canadian dollars), and incremental cost-effectiveness ratio (ICER). Parameter and model uncertainties were assessed through scenario analyses. Health outcomes and cost were discounted at 1.5%, as per Canadian guidelines. RESULTS: For the base-case analysis, expected LY for ADT and apalutamide plus ADT were 4.11 and 5.56, respectively (incremental LY 1.45). Expected QALYs were 3.51 for ADT and 4.84 for apalutamide plus ADT (incremental QALYs 1.33); expected lifetime cost was $36 582 and $255 633, respectively (incremental cost $219 051). ICER for apalutamide plus ADT, as compared to ADT alone, was $164 700/QALY. Through scenario analysis, price reductions ≥50% were required for apalutamide in combination with ADT to be considered cost-effective, at a cost-effectiveness threshold of $100 000/QALY. CONCLUSIONS: Apalutamide plus ADT is unlikely to be cost-effective from the Canadian healthcare perspective unless there are substantial reductions in the price of apalutamide treatment.

The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.