Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

BACKGROUND AND AIMS: Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. APPROACH AND RESULTS: We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. CONCLUSIONS: Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

The mediating role of SARS-CoV-2 variants between income and hospitalisation due to COVID-19: A period-based mediation analysis.

The mechanisms facilitating the relationship between low income and COVID-19 severity have not been partitioned in the presence of SARS-CoV-2 variants of concern (VOC). To address this, we used causal mediation analysis to quantify the possible mediating role infection with VOC has on the relationship between neighbourhood income (exposure) and hospitalisation due to COVID-19 among cases (outcome). A population-based cohort of 65,629 individuals residing in British Columbia, Canada, was divided into three periods of VOC co-circulation in the 2021 calendar year whereby each period included co-circulation of an emerging and an established VOC. Each cohort was subjected to g-formula mediation techniques to decompose the relationship between exposure and outcome into total, direct and indirect effects. In the mediation analysis, the total effects indicated that low income was associated with increased odds of hospitalisation across all periods. Further decomposition of the effects revealed that income is directly and indirectly associated with hospitalisation. The resulting indirect effect through VOC accounted for approximately between 6 and 13% of the total effect of income on hospitalisation. This study underscores, conditional on the analysis, the importance of addressing underlying inequities to mitigate the disproportionate impact on historically marginalised communities by adopting an equity lens as central to pandemic preparedness and response from the onset.

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.

Health and non-health benefits and equity impacts of individual-level economic relief programs during epidemics/pandemics in high income settings: a scoping review.

BACKGROUND: Economic relief programs are strategies designed to sustain societal welfare and population health during a regional or global scale infectious disease outbreak. While economic relief programmes are considered essential during a regional or global health crisis, there is no clear consensus in the literature about their health and non-health benefits and their impact on promoting equity. METHODS: We conducted a scoping review, searching eight electronic databases from January 01, 2001, to April 3, 2023, using text words and subject headings for recent pathogens (coronavirus (COVID-19), Ebola, Influenza, Middle East Respiratory Syndrome (MERS), severe acute respiratory syndrome (SARS), HIV, West Nile, and Zika), and economic relief programs; but restricted eligibility to high-income countries and selected diseases due to volume. Title and abstract screening were conducted by trained reviewers and Distiller AI software. Data were extracted in duplicates by two trained reviewers using a pretested form, and key findings were charted using a narrative approach. RESULTS: We identified 27,263 de-duplicated records, of which 50 were eligible. Included studies were on COVID-19 and Influenza, published between 2014 and 2023. Zero eligible studies were on MERS, SARS, Zika, Ebola, or West Nile Virus. We identified seven program types of which cash transfer (n = 12) and vaccination or testing incentive (n = 9) were most common. Individual-level economic relief programs were reported to have varying degrees of impact on public health measures, and sometimes affected population health outcomes. Expanding paid sick leave programs had the highest number of studies reporting health-related outcomes and positively impacted public health measures (isolation, vaccination uptake) and health outcomes (case counts and the utilization of healthcare services). Equity impact was most often reported for cash transfer programs and incentive for vaccination programs. Positive effects on general well-being and non-health outcomes included improved mental well-being and quality of life, food security, financial resilience, and job security. CONCLUSIONS: Our findings suggest that individual-level economic relief programs can have significant impacts on public health measures, population health outcomes and equity. As countries prepare for future pandemics, our findings provide evidence to stakeholders to recognize health equity as a fundamental public health goal when designing pandemic preparedness policies.

Differential Patterns by Area-Level Social Determinants of Health in Coronavirus Disease 2019 (COVID-19)-Related Mortality and Non-COVID-19 Mortality: A Population-Based Study of 11.8 Million People in Ontario, Canada.

BACKGROUND: Social determinants of health (SDOH) have been associated with coronavirus disease 2019 (COVID-19) outcomes. We examined patterns in COVID-19-related mortality by SDOH and compared these patterns to those for non-COVID-19 mortality. METHODS: Residents of Ontario, Canada, aged ≥20 years were followed from 1 March 2020 to 2 March 2021. COVID-19-related death was defined as death within 30 days following or 7 days prior to a positive COVID-19 test. Area-level SDOH from the 2016 census included median household income; proportion with diploma or higher educational attainment; proportion essential workers, racially minoritized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19-related mortality, and non-COVID-19 mortality using cause-specific hazard models. RESULTS: Of 11 810 255 individuals, we observed 3880 COVID-19-related deaths and 88 107 non-COVID-19 deaths. After accounting for demographics, baseline health, and other area-level SDOH, the following were associated with increased hazards of COVID-19-related death (hazard ratio [95% confidence interval]: lower income (1.30 [1.04-1.62]), lower educational attainment (1.27 [1.07-1.52]), higher proportions essential workers (1.28 [1.05-1.57]), racially minoritized groups (1.42 [1.08-1.87]), apartment buildings (1.25 [1.07-1.46]), and large vs medium household size (1.30 [1.12-1.50]). Areas with higher proportion racially minoritized groups were associated with a lower hazard of non-COVID-19 mortality (0.88 [0.84-0.92]). CONCLUSIONS: Area-level SDOH are associated with COVID-19-related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non-COVID-19 mortality among racially minoritized groups. Pandemic responses should include strategies to address disproportionate risks and inequitable coverage of preventive interventions associated with SDOH.

Clinical Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Relative to Delta in British Columbia, Canada: A Retrospective Analysis of Whole-Genome Sequenced Cases.

BACKGROUND: In late 2021, the Omicron severe acute respiratory syndrome coronavirus 2 variant emerged and rapidly replaced Delta as the dominant variant. The increased transmissibility of Omicron led to surges in case rates and hospitalizations; however, the true severity of the variant remained unclear. We aimed to provide robust estimates of Omicron severity relative to Delta. METHODS: This retrospective cohort study was conducted with data from the British Columbia COVID-19 Cohort, a large provincial surveillance platform with linkage to administrative datasets. To capture the time of cocirculation with Omicron and Delta, December 2021 was chosen as the study period. Whole-genome sequencing was used to determine Omicron and Delta variants. To assess the severity (hospitalization, intensive care unit [ICU] admission, length of stay), we conducted adjusted Cox proportional hazard models, weighted by inverse probability of treatment weights (IPTW). RESULTS: The cohort was composed of 13 128 individuals (7729 Omicron and 5399 Delta). There were 419 coronavirus disease 2019 hospitalizations, with 118 (22%) among people diagnosed with Omicron (crude rate = 1.5% Omicron, 5.6% Delta). In multivariable IPTW analysis, Omicron was associated with a 50% lower risk of hospitalization compared with Delta (adjusted hazard ratio [aHR] = 0.50, 95% confidence interval [CI] = 0.43 to 0.59), a 73% lower risk of ICU admission (aHR = 0.27, 95% CI = 0.19 to 0.38), and a 5-day shorter hospital stay (aß = -5.03, 95% CI = -8.01 to -2.05). CONCLUSIONS: Our analysis supports findings from other studies that have demonstrated lower risk of severe outcomes in Omicron-infected individuals relative to Delta.

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 population-based study of reported hepatitis C diagnoses from 1998 to 2018 in immigrants and nonimmigrants in Quebec, Canada.

Immigrants living in low hepatitis C (HCV) prevalence countries bear a disproportionate HCV burden, but there are limited HCV population-based studies focussed on this population. We estimated rates and trends of reported HCV diagnoses over a 20-year period in Quebec, Canada, to investigate subgroups with the highest rates and changes over time. A population-based cohort of all reported HCV diagnoses in Quebec (1998-2018) linked to health administrative and immigration databases. HCV rates, rate ratios (RR) and trends overall and stratified by immigrant status and country of birth were estimated using Poisson regression. Among 38,348 HCV diagnoses, 14% occurred in immigrants, a median of 7.5 years after arrival. The average annual HCV rate/100,000 decreased for immigrants and nonimmigrants, but the risk (RR) among immigrants increased over the study period [35.7 vs. 34.5 (RR = 1.03) and 18.4 vs. 12.7 (1.45) between 1998-2008 and 2009-2018]. Immigrants from middle-income Europe & Central Asia [55.8 (RR = 4.39)], sub-Saharan Africa [51.7 (RR = 4.06)] and South Asia [32.8 (RR = 2.58)] had the highest rates between 2009 and 2018. Annual HCV rates decreased more slowly among immigrants vs. nonimmigrants (-5.9% vs. -8.9%, p < 0.001), resulting in a 2.5-fold (9%-21%) increase in the proportion of HCV diagnoses among immigrants (1998-2018). The slower decline in HCV rates among immigrants over the study period highlights the need for targeted screening for this population, particularly those from sub-Saharan Africa, Asia and middle-income Europe. These data can inform micro-elimination efforts in Canada and other low-HCV-prevalence countries.

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.

Clinical severity of Omicron subvariants BA.1, BA.2, and BA.5 in a population-based cohort study in British Columbia, Canada.

The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct subvariants of Omicron, BA.1, BA.2, and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 subvariants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity, and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2, or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between December 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and intensive care unit (ICU) admission (aHRhospital = 1.17; 95% confidence interval [CI] = 1.096-1.252; aHRICU = 1.368; 95% CI = 1.152-1.624), whereas BA.5 infections were associated with an 18% higher risk of hospitalization (aHRhospital = 1.18; 95% CI = 1.133-1.224) after accounting for age, sex, comorbidities, vaccination status, geography, and social determinants of health. Phylogenetic analysis revealed no specific subclades associated with more severe clinical outcomes for any Omicron subvariant. In summary, BA.1, BA.2, and BA.5 subvariants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.

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.

Characterizing the cascade of care for hepatitis C virus infection among Status First Nations peoples in Ontario: a retrospective cohort study.

BACKGROUND: As First Nations Peoples are a priority focus of Canada's commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals' progression from diagnosis to cure can guide prioritization of elimination efforts. We sought to characterize and identify gaps in the HCV care cascade for Status First Nations peoples in Ontario. METHODS: In this retrospective cohort study, a partnership between the Ontario First Nations HIV/AIDS Education Circle and academic researchers, HCV testing records (1999-2018) for Status First Nations peoples in Ontario were linked to health administrative data. We defined the cascade of care as 6 stages, as follows: tested positive for HCV antibody, tested for HCV RNA, tested positive for HCV RNA, HCV genotyped, initiated treatment and achieved sustained viral response (SVR). We mapped the care cascade from 1999 to 2018, and estimated the number and proportion of people at each stage. We stratified analyses by sex, diagnosis date and location of residence. We used Cox regression to analyze the secondary outcomes, namely the associations between undergoing HCV RNA testing and initiating treatment, and demographic and clinical predictors. RESULTS: By Dec. 31, 2018, 4962 people tested positive for HCV antibody. Of those testing positive, 4118 (83.0%) were tested for HCV RNA, with 2480 (60.2%) testing positive. Genotyping was completed in 2374 (95.7%) of those who tested positive for HCV RNA, with 1002 (42.2%) initiating treatment. Nearly 80% (n = 801, 79.9%) of treated people achieved SVR, with 34 (4.2%) experiencing reinfection or relapse. Undergoing testing for HCV RNA was more likely among people in older age categories (within 1 yr of antibody test; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.19-1.41, among people aged 41-60 yr; adjusted HR 1.47, 95% CI 1.18-1.81, among people aged > 60 yr), those living in rural areas (adjusted HR 1.20, 95% CI 1.10-1.30), those with an index date after Dec. 31, 2013 (era of treatment with direct-acting antiviral regimens) (adjusted HR 1.99, 95% CI 1.85-2.15) and those with a record of substance use or addictive disorders (> 1 yr after antibody test; adjusted HR 1.38, 95% CI 1.18-1.60). Treatment initiation was more likely among people in older age categories at index date (adjusted HR 1.32, 95% CI 1.15-1.50, among people aged 41-60 yr; adjusted HR 2.62, 95% CI 1.80-3.82, among people aged > 60 yr) and those with a later diagnosis year (adjusted HR 2.71, 95% CI 2.29-3.22). INTERPRETATION: In comparison with HCV testing and diagnosis, a substantial gap in treatment initiation remains among Status First Nations populations in Ontario. Elimination efforts that prioritize linkage to care and integration with harm reduction and substance use services are needed to close gaps in HCV care among First Nations populations in Ontario.

Moving from intervention management to disease management: a qualitative study exploring a systems approach to health technology assessment in Canada.

OBJECTIVES: Health technology assessment (HTA) traditionally informs decision making for single health technologies, which could lead to ill-informed decisions, suboptimal care, and system inefficiencies. We explored opportunities for conceptualizing the decision space in HTA as a disease management question versus an intervention management question. METHODS: Semistructured interviews were conducted between April 2022 and October 2022 with purposefully selected individuals from national and provincial HTA agencies and related organizations in Canada. We conducted manual line by line coding of data informed by our interview guide and sensitizing concepts from the literature. One author coded the data, and findings were independently verified by a second author who coded a subset of transcripts. RESULTS: Twenty-four invitations were distributed, and eighteen individuals agreed to participate. A disease management approach to HTA was differentiated from traditional approaches as being disease-based, multi-interventional, and dynamic. There was general support for an explicit care pathway approach to HTA by informing discussions around patient choice and suboptimal care, creating a space where decision makers can collaborate on shared objectives, and in setting up a platform for open dialogue about managing high-cost and high-severity diseases. There are opportunities for a care pathway approach to be implemented that build on the strengths of the existing HTA system in Canada. CONCLUSIONS: A disease management approach may enhance the impact of HTA by supporting dynamic decision making that could better inform a proactive, resilient, and sustainable healthcare system in Canada.

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.

Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.

We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.

What Has the Pandemic Revealed about the Shortcomings of Modern Epidemiology? What Can We Fix or Do Better?

In this commentary, we discuss themes that emerged from our symposium about what modern epidemiology as a science may learn from the COVID-19 pandemic. We reflect on the successes and limitations of this discipline from multiple perspectives, including from junior and senior epidemiologists and scientists on the front lines of generating evidence for the COVID-19 pandemic response in Wuhan, China, to Ontario, Canada. These themes include the role of the traditional scientific process in a public health emergency; epidemiologic methods and data that are critical for an effective pandemic response; the interventions that epidemiologists recommended and interventions that we may explore in the future; inequitable impacts of the COVID-19 pandemic contrasted with homogeneity in the epidemiologist workforce; effective and honest communication of uncertainty; trust and collaboration; and the extent to which these themes are currently reflected in our training programs and discipline. We look forward to insights from field epidemiologists directly involved in the ongoing response to the COVID-19 pandemic and further reflection from epidemiologists throughout our discipline.

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.

Prevalence and Mortality Associated with Bloodstream Organisms: a Population-Wide Retrospective Cohort Study.

Bloodstream infections (BSIs) represent a substantial mortality risk, yet most studies are limited to select pathogens or populations. The aim of this study was to describe the population-wide prevalence of BSIs and examine the associated mortality risk for the responsible microorganisms. We conducted a population-wide retrospective cohort study of BSIs in Ontario in 2017. Blood culture data was collected from almost all microbiology laboratories in Ontario and linked to data sets of patient characteristics. For each organism, we determined the prevalence and crude mortality risk, and using logistic regression models, the adjusted odds of 30-day mortality was calculated relative to patients with negative blood cultures and matched patients without blood culture testing. From 531,065 blood cultures, we identified 22,935 positive BSI episodes in 19,326 patients, for an incidence of 150 per 100,000 population. The most frequently isolated organisms were Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella species, and Enterococcus species with 40.2, 22.4, 12.1, 11.1, and 7.1 episodes per 100,000 population respectively. BSI episodes were associated with 17.0% mortality at 30 days. Compared to patients with negative cultures, the adjusted 30-day mortality risk for positive BSIs was 1.47 (95% confidence interval (CI), 1.41 to 1.54) and compared to matched patients without blood culture testing was 2.62 (95% CI, 2.52 to 2.73). Clostridium species were associated with the highest adjusted odds of mortality compared to that of negative cultures (adjusted odds ratio, 5.81; 95% CI, 4.00 to 8.44). Among high incidence pathogens, Staphylococcus aureus had the highest odds ratio of mortality (adjusted odds ratio, 2.14; 95% CI, 1.94 to 2.36). BSIs are associated with increased mortality risk, varying across organisms.

Diagnosis of Chronic Hepatitis B Pericomplication: Risk factors and Trends Over Time.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) is a major cause of chronic liver disease, which can progress to cirrhosis, hepatocellular carcinoma, and death. A timely diagnosis allows for antiviral treatment, which can prevent liver-related complications. Conversely, a late diagnosis signals a missed opportunity for earlier care and treatment. Our objective was to measure the proportion of chronic HBV diagnoses that are made within 6 months of presentation with a liver disease-related complication and examine associated factors and trends over time. APPROACH AND RESULTS: We used provincial laboratory data to identify patients with chronic HBV diagnosed from 2003 to 2014. We measured the proportion who experienced a liver disease complication (decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) within ±6 months of their HBV diagnosis date. A multivariable logistic regression model was used to identify factors associated with HBV diagnosis pericomplication. Of 18,434 patients with chronic HBV, 1,279 (6.9%) developed an HBV-related complication during the follow-up period. Among these, 570 (44.6%) had a first diagnosis pericomplication. HBV diagnosis pericomplication did not decrease over time and was independently associated with older age at HBV diagnosis, rural residence, alcohol use, and moderate to high levels of comorbidity. Female patients, immigrants, and those with more outpatient physician visits were less likely to have an HBV diagnosis pericomplication. CONCLUSIONS: A high proportion of patients with HBV-related complications are first diagnosed with HBV pericomplication. These signal missed opportunities for earlier detection and treatment. Our findings support expansion of HBV screening.

"Bring the Hoses to Where the Fire Is!": Differential Impacts of Marginalization and Socioeconomic Status on COVID-19 Case Counts and Healthcare Costs.

OBJECTIVES: Local health leaders and the Director General of the World Health Organization alike have observed that COVID-19 "does not discriminate." Nevertheless, the disproportionate representation of people of low socioeconomic status among those infected resembles discrimination. This population-based retrospective cohort study examined COVID-19 case counts and publicly funded healthcare costs in Ontario, Canada, with a focus on marginalization. METHODS: Individuals with their first positive severe acute respiratory syndrome coronavirus 2 test from January 1, 2020 to June 30, 2020, were linked to administrative databases and matched to negative/untested controls. Mean net (COVID-19-attributable) costs were estimated for 30 days before and after diagnosis, and differences among strata of age, sex, comorbidity, and measures of marginalization were assessed using analysis of variance tests. RESULTS: We included 28 893 COVID-19 cases (mean age 54 years, 56% female). Most cases remained in the community (20 545, 71.1%) or in long-term care facilities (4478, 15.5%), whereas 944 (3.3%) and 2926 (10.1%) were hospitalized, with and without intensive care unit, respectively. Case counts were skewed across marginalization strata with 2 to 7 times more cases in neighborhoods with low income, high material deprivation, and highest ethnic concentration. Mean net costs after diagnosis were higher for males ($4752 vs $2520 for females) and for cases with higher comorbidity ($1394-$7751) (both P < .001) but were similar across levels of most marginalization dimensions (range $3232-$3737, all P ≥ .19). CONCLUSIONS: This study suggests that allocating resources unequally to marginalized individuals may improve equality in outcomes. It highlights the importance of reducing risk of COVID-19 infection among marginalized individuals to reduce overall costs and increase system capacity.