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Background If untreated, Lyme disease can lead to long-term sequelae and post-treatment Lyme disease syndrome (PTLDS), resulting in reduced health-related quality of life. The objective of this study was to develop a microsimulation model to estimate the population-level health burden of Lyme disease in Ontario, Canada. Methods We developed a Lyme disease history model using microsimulation, simulating 100 000 people (mean age 37.6 yr, 51% female) from 2017 in Ontario over a lifetime risk of infection and time horizon. We extracted the sensitivity and specificity of the 2-tier testing recommended by the Canadian Public Health Laboratory Network, probabilities and health state utility values from the published literature and health administrative data. Our reported outcomes from our stochastic analysis include diagnosed cases of Lyme disease (stratified by stage), undiagnosed infections, sequelae, individuals with PTLDS and quality-adjusted life-years (QALYs) lost. Results Our model estimated 333 (95% confidence interval [CI] 329-337) infections over the lifetime of 100 000 simulated people (mean age 37.6 yr, 51% female), with 92% (95% CI 91%-93%) of infections diagnosed. Of those 308 people with Lyme Disease diagnoses, 67 (95% CI 65-69) developed sequelae (e.g., arthritic, cardiac, neurologic sequelae), and 34 (95% CI 33-35) developed PTLDS. Lyme disease resulted in a loss of 84.5 QALYs (95% CI 82.9-86.2) over the lifetime of the simulated cohort. Sensitivity and scenario analysis showed that increasing incidence rates of Lyme disease, potential underreporting, duration of PTLDS and quality of life (health state utility) associated with PTLDS had the greatest impact on health burden. Interpretation Lyme disease contributes considerable health burden in terms of QALYs lost. Our analysis provides evidence to understand the disease burden and lays the foundation to assess the cost-effectiveness of pharmaceutical and nonpharmaceutical interventions.

Background The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. Methods Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. Results We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. Conclusions There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.

Streptococcus pneumoniae infections remain a significant source of morbidity and mortality worldwide. The purpose of this review was to summarize the impact of pneumococcal disease on health state utilities (HSU) in the acute phase of illness. We searched MEDLINE, EMBASE, EconLit, the Health Technology Assessment Database, the National Health Economic Evaluation Database, and Tufts Cost-Effectiveness Registry (up to January 2020) for primary studies. Eligible studies elicited HSU estimates using preference-based instruments for the acute phase of infection of pneumococcal syndromes including acute otitis media, pneumonia/lower respiratory tract infections, bacteremia/sepsis, and meningitis. Two reviewers independently conducted screening, data extraction and quality appraisal. We screened 10,178 studies, of which 26 met our inclusion criteria. Cohort sizes ranged from 8 to 2060 respondents. The most frequently studied syndrome was pneumonia (n = 17), followed by acute otitis media (n = 9), meningitis (n = 7) and bacteremia/sepsis (n = 4). Overall, each syndrome was associated with a substantial impact on HSU. Bacteremia/sepsis (range: − 0.331 to 0.992) and meningitis (range: − 0.330 to 0.977) were generally associated with the lowest HSU, followed by pneumonia (range: − 0.054 to 0.998) and acute otitis media (range: 0.064 to 0.970). HSU estimates varied considerably by treatment setting, elicitation method and type of respondent. The only study to compare pneumococcal infections to non-pneumococcal infections in the same population revealed significantly lower HSU estimates among pneumococcal infections. Pneumococcal syndromes are associated with decreased HSU estimates. Given the considerable heterogeneity in methods and source populations as well as study quality, care should be taken to select the most appropriate estimates.

Background In several countries, the dolutegravir (DTG)-based regimen is generally preferred as first-line antiretroviral therapy (ART) over the efavirenz (EFV)-based regimen, but the evidence in low-income countries is limited. Objective Our study aimed to evaluate the cost effectiveness of DTG- versus EFV-based first-line human immunodeficiency virus (HIV) treatment in Ethiopia. Methods We developed a microsimulation model for the progression of HIV/acquired immune deficiency syndrome (AIDS) to examine the cost effectiveness of DTG-based first-line ART compared with an EFV-based regimen from a healthcare payer perspective. We used a lifetime horizon with a 1-month cycle length and a 3% annual discount rate. The primary outcomes were a lifetime cost in US dollars ($), quality-adjusted life-months (QALMs) that converted to QALYs using the formula QALY = QALM/12, and incremental cost-effectiveness ratio (ICER). Deterministic sensitivity analysis was conducted to account for parameter uncertainty. Results Compared with the EFV-based regimen, the DTG-based regimen was associated with an expected lifetime cost of $12,709 (vs. $12,701) and expected QALYs of 15.3 (vs. 14.7 QALYs) per patient, resulting in an ICER value of $13.33 per QALY. From an alternative analysis with a 5-year time horizon, DTG-based ART was found to be dominant, with expected gains of 0.17 QALYs at a lower cost of $1 per patient. The deterministic sensitivity analysis depicted that the maximum increase in ICER value was $72 per QALY, and all ICER values were below the estimated threshold value. Conclusions The DTG-based first-line regimen appears to be cost effective compared with the EFV-based regimen for the treatment of HIV/AIDS patients in an Ethiopian setting.

Background Upper tract urothelial carcinoma (UTUC) is clinically understudied, and there are no definitive recommendations regarding timing of perioperative chemotherapy. The objective of this study was to compare 3 treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC) using a microsimulation model. Patients and Methods An individual-level state transition model was constructed using TreeAgePro software to compare treatment strategies for patients with newly diagnosed UTUC. The base case was that of a 70-year-old patient with a radiographically localized upper tract tumor. Primary outcome was quality-adjusted life expectancy. Secondary outcomes included crude overall survival, rates of adverse events, and bladder cancer diagnoses. Results A total of 100,000 patients were simulated. NAC was preferred, with an estimated quality-adjusted life expectancy of 7.50 years versus 6.79 years with NU alone and 7.23 years with AC. Median crude overall survival was 123 months with NAC, 96 months with NU only, and 111 months with AC. Overall, 40.0% of patients in the AC group with invasive pathology completed chemotherapy. In the NAC group, 83.3% of patients completed chemotherapy. In the NAC group, 37.5% of patients experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 65.9%, and 67.4% over the patient’s lifetime for the NU, NAC, and AC strategies, respectively. Conclusion This study supports the increased use of NAC in UTUC until robust randomized trials are completed. The ultimate choice should be based on patient and tumor factors.

BACKGROUND: Understanding resource use for coronavirus disease 2019 (COVID-19) is critical. We conducted a descriptive analysis using public health data to describe age- and sex-specific acute care use, length of stay (LOS) and mortality associated with COVID-19. METHODS: We conducted a descriptive analysis using Ontario's Case and Contact Management Plus database of individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ontario from Mar. 1 to Sept. 30, 2020, to determine age- and sex-specific hospital admissions, intensive care unit (ICU) admissions, use of invasive mechanical ventilation, LOS and mortality. We stratified analyses by month of infection to study temporal trends and conducted subgroup analyses by long-term care residency. RESULTS: During the observation period, 56 476 individuals testing positive for SARS-CoV-2 were reported; 41 049 (72.7%) of these were younger than 60 years, and 29 196 (51.7%) were female. Proportion of cases shifted from older populations (> 60 yr) to younger populations (10-39 yr) over time. Overall, 5383 (9.5%) of individuals were admitted to hospital; of these, 1183 (22.0%) were admitted to the ICU, and 712 (60.2%) of these received invasive mechanical ventilation. Mean LOS for individuals in the ward, ICU without invasive mechanical ventilation and ICU with invasive mechanical ventilation was 12.8 (standard deviation [SD] 15.4), 8.5 (SD 7.8) and 20.5 (SD 18.1) days, respectively. Among patients receiving care in the ward, ICU without invasive mechanical ventilation and ICU with invasive mechanical ventilation, 911/3834 (23.8%), 124/418 (29.7%) and 287/635 (45.2%) died, respectively. All outcomes varied by age and decreased over time, overall and within age groups. INTERPRETATION: This descriptive study shows use of acute care and mortality varying by age and decreasing between March and September 2020 in Ontario. Improvements in clinical practice and changing risk distributions among those infected may contribute to fewer severe outcomes.

Background High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. Methods In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. Results We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. Interpretation Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Background Patients’ health-related quality of life (HRQoL) and health state utility values are critical inputs in the clinical and economic evaluation of treatments for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, information on health state utility values is lacking in the context of Ethiopia. Here, we aimed to assess HRQoL and determine health state utility values and factors that influence the values among HIV/AIDS patients in Ethiopia. Methods A cross-sectional study was conducted among 511 HIV/AIDS patients at Tikur Anbessa Specialized Hospital in Ethiopia. Patients aged 18 years or older were eligible for the interview and those who were mentally unstable and with hearing impairment were excluded from the study. We performed face-to-face interviews using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) in combination with EuroQol-Visual Analog Scales (EQ-VAS). Level-specific disutility coefficients obtained from the general population were used for computing utility values. Patients’ health profiles were described using percentages and different statistical analysis were conducted to determine factors associated with the EQ-5D index and EQ-VAS scores. Results A total of 511 patients participated in the study. A higher proportion of patients reported slight or more severe problems on the anxiety/depression (55.2%) and pain/discomfort (51.3%) dimensions. The overall median utility value of HIV/AIDS patients was 0.94 (IQR = 0.87, 1) from the EQ-5D index and 80% (IQR = 70%, 90%) from the EQ-VAS scores. Demographic characteristics including age, occupational status, and household monthly income significantly affected patient’s utility values. Moreover, statistically significant (p p Conclusions The anxiety/depression and pain/ discomfort dimensions were identified to have critical influence in reducing the HRQoL of adult HIV/AIDS patients in the context of Ethiopia. The study is also the first to use the EQ-5D-5L tool to identify health state utility values for Ethiopian adult HIV/AIDS patients. Future economic evaluations of HIV/AIDS interventions are encouraged to employ the identified utility values.

Background & aims Hepatitis C virus (HCV) is a common and treatable cause of cirrhosis and its complications, yet many chronically infected individuals remain undiagnosed until a late stage. We sought to identify the frequency of and risk factors for HCV diagnosis peri-complication, that is within six months of an advanced liver disease complication. Methods This was a retrospective cohort study of Ontario residents diagnosed with chronic HCV infection between 2003 and 2014. HCV diagnosis peri-complication was defined as the occurrence of decompensated cirrhosis, hepatocellular carcinoma or liver transplant within ±6 months of HCV diagnosis. Multivariable logistic regression was used to identify risk factors for peri-complication diagnosis among all those diagnosed with HCV infection. Results Our cohort included 39,515 patients with chronic HCV infection, of whom 4.2% (n = 1645) were diagnosed peri-complication; these represented 31.6% of the 5,202 patients who developed complications in the follow-up period. Peri-complication diagnosis became more common over the study period and was associated with increasing age among baby boomers, alcohol use, diabetes mellitus, chronic HBV co-infection and moderate to high levels of morbidity. Female sex, immigrant status, having more previous outpatient physician visits, a previous emergency department visit, a history of drug use or mental health visits were associated with reduced risk of peri-complication diagnosis. Conclusions Over a quarter of HCV-infected patients with complications were diagnosed peri-complication. This problem increased over time, suggesting a need to further expand HCV screening.

BACKGROUND: Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. METHODS: We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0–11 years who were born in Ontario from 2003 to 2013. RESULTS: From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. INTERPRETATION: Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province’s adolescent vaccination strategy.

BACKGROUND The authors conducted a cost-effectiveness analysis to answer the question: Which motion-preserving surgical strategy, (1) four-corner fusion, (2) proximal row carpectomy, or (3) total wrist arthroplasty, used for the treatment of wrist osteoarthritis, is the most cost-effective? METHODS A simulation model was created to model a hypothetical cohort of wrist osteoarthritis patients (mean age, 45 years) presenting with painful wrist and having failed conservative management. Three initial surgical treatment strategies-(1) four-corner fusion, (2) proximal row carpectomy, or (3) total wrist arthroplasty-were compared from a hospital perspective. Outcomes included clinical outcomes and cost-effectiveness outcomes (quality-adjusted life-years and cost) over a lifetime. RESULTS The highest complication rates were seen in the four-corner fusion cohort: 27.1 percent compared to 20.9 percent for total wrist arthroplasty and 17.4 percent for proximal row carpectomy. Secondary surgery was common for all procedures: 87 percent for four-corner fusion, 57 percent for proximal row carpectomy, and 46 percent for total wrist arthroplasty. Proximal row carpectomy generated the highest quality-adjusted life-years (30.5) over the lifetime time horizon, compared to 30.3 quality-adjusted life-years for total wrist arthroplasty and 30.2 quality-adjusted life-years for four-corner fusion. Proximal row carpectomy was the least costly; the mean expected lifetime cost for patients starting with proximal row carpectomy was $6003, compared to $11,033 for total wrist arthroplasty and $13,632 for four-corner fusion. CONCLUSIONS The authors' analysis suggests that proximal row carpectomy was the most cost-effective strategy, regardless of patient and parameter level uncertainties. These are important findings for policy makers and clinicians working within a universal health care system.

Unstructured Abstract (250 words) In Ontario, on March 16th, 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for three key groups of cardiovascular disease patients; coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across five regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely, data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care., In Ontario, on March 16th, 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential COVID-19 patient surge. This manuscript provides examples of how decision analytic models have helped informed policy decisions and to assess the impact of these policies on incremental waitlist activity for cardiac procedures during the COVID-19 pandemic.

Objectives In this systematic review, we synthesize the current evidence on health-related quality of life (HRQoL) for the two of the most relevant outcomes of Zika virus infection in humans, microcephaly and Guillain-Barre Syndrome (GBS). Methods We searched the following databases: MEDLINE, Embase, CINAHL, LILACS, WHO's ICTRP clinical trials registries database and PROSPERO. Search terms included quality of life, microcephaly, and Guillain-Barre Syndrome. We included primary studies where HRQoL was quantitatively assessed for microcephaly and GBS using validated instruments. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the risk of bias of individual studies. Results From a total of 1,657 abstracts screened and 66 full texts reviewed, 21 studies met the eligibility criteria; one study for microcephaly and 20 for GBS. Adjusted disutilities for microcephaly compared to a normative childhood utility ranged from −0.745 to −0.820. For GBS, time traded-off the expected lifetime ranged from 16 days to 3 years. HRQoL follows the clinical course of GBS, with lower scores in the first months, recovery within the first year post onset, and stabilization after one year. Conclusions Included studies reported a wide range of HRQoL for GBS, due in part to a high level of heterogeneity in methods, inclusion criteria, follow-up and reporting of results. Opportunities exist for primary studies assessing the longitudinal HRQoL over the entire course of the diseases to inform clinical practice, economic evaluations and health policy.

BACKGROUND: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS: We developed an individual-level simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS: We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14–26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION: We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.

Summary Preventing vancomycin-resistant enterococci (VRE) infection is a healthcare priority. However, the cost-effectiveness of VRE control interventions is unclear. The aim of this study was to synthesize evidence on economic evaluation of VRE control practices such as screening, contact precautions, patient cohorting, and others. The literature was searched from January 1985 to June 2018, and included economic evaluations of VRE control practices in hospital settings, published in English. A total of 4711 articles were screened; nine primary studies met our criteria. All studies evaluated some form of VRE screening and contact precautions, in populations ranging from single hospital wards (or select patient groups) to multiple healthcare facilities. There was significant variability in the interventions and comparisons used. Most studies (N = 7) conducted a cost-effectiveness analysis; two studies were cost-consequence studies. All economic evaluations were from the hospital perspective. Four studies found implementing enhanced VRE-specific control practices to be cost-effective/cost-saving and two studies found that discontinuing VRE-specific control practices was not cost-effective. Three studies found decreasing VRE-specific control practices to be cost-effective/cost-saving. The quality of the included studies was generally low according to the Joanna Briggs Institute (JBI) checklist for economic evaluations; major limitations included risks of bias in intervention effect estimates, and a lack of sensitivity analyses. Most studies show that some form of VRE screening and use of Contact Precautions is cost-effective. The low study quality and heterogeneity of interventions and comparators precludes definitive conclusions about the cost effectiveness of specific VRE control interventions. Additional high-quality economic evaluations are needed to strengthen the available evidence.

Background Cancer of the cervix is the most frequent cancer among women in Ethiopia. The disease burden and its treatment adversely affects patients’ health-related quality of life (HRQoL). We aimed to investigate the HRQoL and its predictors among cervical cancer patients in Ethiopia. Methods A hospital-based cross-sectional study was conducted from January to June 2018 at the oncology unit of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A total of 404 cervical cancer patients were interviewed using validated Amharic version of the European Organization for Research and Treatment of Cancer module (EORTC QLQ-C30), cervical cancer module (EORTC QLQ-CX24), and Euro Quality of Life Group’s 5-Domain Questionnaires 5-Levels (EQ-5D) questionnaires. ANOVA test was used to determine the effect of patients’ characteristics on mean scores of the different domains of HRQoL and stepwise multivariable logistic regression was performed to identify predictors of HRQoL. Coefficients of level-specific utility values obtained from a hybrid regression model for the Ethiopian general population were used to compute utility. Results The mean age of patients was 52.1 ± 10.4 years and 379 (93.8%) of the patients were receiving service at the outpatient clinic. About one-third (35%) of patients were diagnosed with stage IV cervical cancer. Mean global health status/QoL, mean utility and visual analog scale scores were 48.3 ± 23.77, 0.77 and 65.7 ± 20.83, respectively. Physical functioning (AOR = 4.98, 95% CI:2.16–11.49), emotional functioning (AOR = 5.25, 95% CI:2.26–12.17), pain (AOR = 5.79, 95% CI:2.30–14.57), and symptom experience (AOR = 4.58, 95% CI:1.95–10.79) were associated with patients’ HRQoL. Conclusions Cervical cancer significantly affects patient’s HRQoL and hence, efforts to improve HRQoL should be commenced especially in terms of physical and emotional functioning, pain, and symptom experience.

Background Jurisdictions worldwide ramped down ophthalmic surgeries to mitigate the effects of COVID-19, creating a global surgical backlog. We sought to predict the long-term impact of COVID-19 on the timely delivery of non-emergent ophthalmology sub-specialty surgical care in Ontario. Methods This is a microsimulation modelling study. We used provincial population-based administrative data from the Wait Time Information System database in Ontario for January 2019 to May 2021 and facility-level data for March 2018 to May 2021 to estimate the backlog size and wait times associated with the COVID-19 pandemic. For the postpandemic recovery phase, we estimated the resources required to clear the backlog of patients accumulated on the wait-list during the pandemic. Outcomes were accrued over a time horizon of 3 years. Results A total of 56 923 patients were on the wait-list in the province of Ontario awaiting non-emergency ophthalmic surgery as of Mar. 15, 2020. The number of non-emergency surgeries performed in the province decreased by 97% in May 2020 and by 80% in May 2021 compared with the same months in 2019. By 2 years and 3 years since the start of the pandemic, the overall estimated number of patients awaiting surgery grew by 129% and 150%, respectively. The estimated mean wait time for patients for all subspecialty surgeries increased to 282 (standard deviation [SD] 91) days in March 2023 compared with 94 (SD 97) days in 2019. The provincial monthly additional resources required to clear the backlog by March 2023 was estimated to be a 34% escalation from the prepandemic volumes (4626 additional surgeries). Interpretation The estimates from this microsimulation modelling study suggest that the magnitude of the ophthalmic surgical backlog from the COVID-19 pandemic has important implications for the recovery phase. This model can be adapted to other jurisdictions to assist with recovery planning for vision-saving surgeries.

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 + 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.

Structured Summary Background Clostridioides difficile infection (CDI) is the leading cause of health care-associated infectious diarrhoea. Several preventative and treatment interventions exist, however, decisions for their use are typically made independent of other interventions along the care pathway. Aim To assess how the scope of the decision problem is defined in economic evaluations of C. difficile interventions. Methods We conducted a scoping review following the Joanna Briggs Institute framework using a comprehensive literature search with C. difficile and economic evaluation as key search concepts. Study selection and extraction was performed independently by two reviewers. We conducted an in-depth analysis of all cost-utility and cost-effectiveness analyses. Care pathway domains (i.e., infection prevention and control, antimicrobial stewardship programs, prevention, diagnostics, treatment) were defined iteratively, and each study was classified according to the scope of the decision problem: a) one intervention, one domain; b) one intervention, multiple domains; c) multiple interventions, one domain; d) multiple interventions, multiple domains. Results A total of 3,886 studies were identified, 116 included in our descriptive overview, and 46 included in our in-depth analysis. Most studies limited the scope of the decision problem to one intervention (43/46; 93%). Only three studies (3/46; 7%) assessed multiple interventions – either as bundled versus standalone interventions for prevention (i.e., a single domain), or as sequences of treatments for initial and recurrent infection (i.e., multiple domains). No study assessed multiple interventions across prevention and treatment domains. Conclusions Economic evaluations for CDI assess narrowly defined decision problems which may have implications for optimal healthcare resource allocation.

BackgroundThe goal of this study was to project the number of COVID-19 cases and demand for acute hospital resources for Fall of 2021 in a representative mid-sized community in southwestern Ontario. We sought to evaluate whether current levels of vaccine coverage and contact reduction could mitigate a potential 4th wave fueled by the Delta variant, or whether the reinstitution of more intense public health measures will be required.MethodsWe developed an age-stratified dynamic transmission model of COVID-19 in a mid-sized city (population 500,000) currently experiencing a relatively low, but increasing, infection rate in Step 3 of Ontario’s Wave 3 recovery. We parameterized the model using the medical literature, grey literature, and government reports. We estimated the current level of contact reduction by model calibration to cases and hospitalizations. We projected the number of infections, number of hospitalizations, and the time to re-instate high intensity public health measures over the fall of 2021 under different levels of vaccine coverage and contact reduction.ResultsMaintaining contact reductions at the current level, estimated to be a 17% reduction compared to pre-pandemic contact levels, results in COVID-related admissions exceeding 20% of pre-pandemic critical care capacity by late October, leading to cancellation of elective surgeries and other non-COVID health services. At high levels of vaccination and relatively high levels of mask wearing, a moderate additional effort to reduce contacts (30% reduction compared to pre-pandemic contact levels), is necessary to avoid re-instating intensive public health measures. Compared to prior waves, the age distribution of both cases and hospitalizations shifts younger and the estimated number of pediatric critical care hospitalizations may substantially exceed 20% of capacity.DiscussionHigh rates of vaccination coverage in people over the age of 12 and mask wearing in public settings will not be sufficient to prevent an overwhelming resurgence of COVID-19 in the Fall of 2021. Our analysis indicates that immediate moderate public health measures can prevent the necessity for more intense and disruptive measures later.

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) is now worldwide recognized as the preferred management strategy for most of low risk prostate cancer (PC) to minimize risks of overtreatment. De...

INTRODUCTION AND OBJECTIVE:The gold standard treatment for muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy. However, response to NAC is unpred...

Background Invasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases. Methods We established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario’s integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models. Results In Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007–2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces. Conclusions IPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.

Introduction: Although many low-risk prostate cancer (PCa) patients worldwide currently receive active surveillance (AS), adherence to clinical guidelines on AS and variations in care at the population level remain poorly understood. We sought to develop system-level quality indicators (QIs) and performance measures for benchmarking the quality of care during AS. Methods: Convenient sampling method was used to identify an expert panel among practicing urologists and radiation oncologists across Canada. QI development involved two phases: 1) proposed QIs were identified through a literature search and published clinical guidelines on AS; and 2) indicators were selected through a modified Delphi process during which each panelist independently rated each indicator based on clinical importance. QI items were chosen as appropriate measures for quality of AS care if they met prespecified criteria (disagreement index

Lyme disease (LD) is the most commonly reported vector-borne disease, but its clinical consequences remain uncertain. We conducted a systematic review of the long-term sequelae and health-related quality of life (HRQoL) associated with LD in North America and Europe. We performed searches in 6 electronic databases up to December 2018 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting long-term sequelae, HRQoL, and prognostic factors. We included 46 studies, published between 1994 and 2019. Based on 21 studies reporting attributable outcomes, higher proportions of sequelae reported from exposed patients were: neck pain, myalgia, arthralgia, paresthesia, sleep disorder, poor appetite, and concentration difficulties. Patients with PTLDS reported impaired HRQoL compared to the general US population. Included studies were highly heterogeneous in terms of study design, settings, patient characteristics, and quality. Patients with LD are more likely to report nonspecific long-term sequelae, especially those experiencing persistent symptoms posttreatment. Opportunities exist for prospective longitudinal studies to better understand LD outcomes.

Background:Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health threat.Objective:To conduct a systematic review of health outcomes and long-term sequelae attributable to CPE infection.Methods:We followed PRISMA reporting guidelines and published our review protocol on PROSPERO (CRD42018097357). We searched Medline, Embase, CINAHL and the Cochrane Library. We included primary studies with a carbapenem-susceptible control group in high-income countries, published in English. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized frequently reported outcomes and conducted a meta-analysis.Results:Our systematic review identified 8,671 studies; 17 met the eligibility criteria for inclusion. All studies reported health outcomes; none reported health-related quality-of-life. Most studies were from Europe (65%), were conducted in teaching or university-affiliated hospitals (76%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections; in-hospital mortality was most often reported (62%). Our meta-analysis (n = 5 studies) estimated an absolute risk difference (ARD) for in-hospital bloodstream infection mortality of 0.25 (95% confidence interval [CI], 0.17–0.32). Duration of antibiotic therapy (range, 4–29.7 vs 1–23.6 days) and length of hospital stay (range, 21–87 vs 15–43 days) were relatively higher for CPE-infected patients than for patients infected with carbapenem-susceptible pathogens. Most studies (82%) met >80% of their respective quality appraisal criteria.Conclusions:The risk of in-hospital mortality due to CPE bloodstream infection is considerably greater than carbapenem-susceptible bloodstream infection (ARD, 0.25; 95% CI, 0.17–0.32). Health outcome studies associated with CPE infection are focused on short-term (eg, in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied.Trial Registration:PROSPERO (CRD42018097357).

Background Vancomycin-resistant enterococci (VRE) are a serious antimicrobial resistant threat in the healthcare setting. We assessed the cost-effectiveness of VRE screening and isolation for patients at high-risk for colonisation on a general medicine ward compared to no VRE screening and isolation from the healthcare payer perspective. Methods We developed a microsimulation model using local data and VRE literature, to simulate a 20-bed general medicine ward at a tertiary-care hospital with up to 1000 admissions, approximating 1 year. Primary outcomes were accrued over the patient’s lifetime, discounted at 1.5%, and included expected health outcomes (VRE colonisations, VRE infections, VRE-related bacteremia, and deaths subsequent to VRE infection), quality-adjusted life years (QALYs), healthcare costs, and incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) and scenario analyses were conducted to assess parameter uncertainty. Results In our base-case analysis, VRE screening and isolation prevented six healthcare-associated VRE colonisations per 1000 admissions (6/1000), 0.6/1000 VRE-related infections, 0.2/1000 VRE-related bacteremia, and 0.1/1000 deaths subsequent to VRE infection. VRE screening and isolation accrued 0.0142 incremental QALYs at an incremental cost of $112, affording an ICER of $7850 per QALY. VRE screening and isolation practice was more likely to be cost-effective (> 50%) at a cost-effectiveness threshold of $50,000/QALY. Stochasticity (randomness) had a significant impact on the cost-effectiveness. Conclusion VRE screening and isolation can be cost-effective in majority of model simulations at commonly used cost-effectiveness thresholds, and is likely economically attractive in general medicine settings. Our findings strengthen the understanding of VRE prevention strategies and are of importance to hospital program planners and infection prevention and control.

Background Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. Methods This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Findings We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. Conclusions The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae., Author summary Interest in Zika virus (ZIKV) has increased in the last decade due to its emergence and rapid spread in the Americas. In this review, we examine ZIKV clinical manifestations and sequelae in adults. Among studies reporting subjects with confirmed ZIKV and critical appraisal scores of at least 70%, symptoms reported include exanthema, fever, arthralgia, conjunctivitis, myalgia, headache, and diarrhea. Neurological sequelae in this group occurred in 0.3% of subjects, of which 75% were Guillain-Barré Syndrome (GBS). Recovery from GBS was variable: some patients returned to health and others endured chronic disability. Mortality was rare (0.1%). Hospitalization (11%) was often associated co-morbidities or GBS; this percentage perhaps reflects studies in which all reported subjects were hospitalized. Synthesizing reported data is challenging given the wide range of case definitions and ZIKV testing practices.

BackgroundDual dose SARS-CoV-2 vaccines demonstrate high efficacy and will be critical in public health efforts to mitigate the COVID-19 pandemic and its health consequences; however, many jurisdictions face very constrained vaccine supply. We examined the impacts of extending the interval between two doses of mRNA vaccines in Canada in order to inform deliberations of Canada’s National Advisory Committee on Immunization.MethodsWe developed an age-stratified, deterministic, compartmental model of SARS-CoV-2 transmission and disease to reproduce the epidemiologic features of the epidemic in Canada. Simulated vaccination comprised mRNA vaccines with explicit examination of effectiveness against disease (67% [first dose], 94% [second dose]), hospitalization (80% [first dose], 96% [second dose]), and death (85% [first dose], 96% [second dose]) in adults aged 20 years and older. Effectiveness against infection was assumed to be 90% relative to the effectiveness against disease. We used a 6-week mRNA dose interval as our base case (consistent with early program rollout across Canadian and international jurisdictions) and compared extended intervals of 12 weeks, 16 weeks, and 24 weeks. We began vaccinations on January 1, 2021 and simulated a third wave beginning on April 1, 2021.ResultsExtending mRNA dose intervals were projected to result in 12.1-18.9% fewer symptomatic cases, 9.5-13.5% fewer hospitalizations, and 7.5-9.7% fewer deaths in the population over a 12-month time horizon. The largest reductions in hospitalizations and deaths were observed in the longest interval of 24 weeks, though benefits were diminishing as intervals extended. Benefits of extended intervals stemmed largely from the ability to accelerate coverage in individuals aged 20-74 years as older individuals were already prioritized for early vaccination. Conditions under which mRNA dose extensions led to worse outcomes included: first-dose effectiveness < 65% against death; or protection following first dose waning to 0% by month three before the scheduled 2nd dose at 24-weeks. Probabilistic simulations from a range of likely vaccine effectiveness values did not result in worse outcomes with extended intervals.ConclusionUnder real-world effectiveness conditions, our results support a strategy of extending mRNA dose intervals across all age groups to minimize symptomatic cases, hospitalizations, and deaths while vaccine supply is constrained.

New variants of concern (VOCs) now account for 67% of all Ontario SARS-CoV-2 infections. Compared with early variants of SARS-CoV-2, VOCs are associated with a 63% increased risk of hospitalization, a 103% increased risk of intensive care unit (ICU) admission and a 56% increased risk of death due to COVID-19. VOCs are having a substantial impact on Ontario’s healthcare system. On March 28, 2021, the daily number of new SARS-CoV-2 infections in Ontario reached the daily number of cases observed near the height of the second wave, at the start of the province-wide lockdown, on December 26, 2020. The number of people hospitalized with COVID-19 is now 21% higher than at the start of the province-wide lockdown, while ICU occupancy is 28% higher (Figure 1). The percentage of COVID-19 patients in ICUs who are younger than 60 years is about 50% higher now than it was prior to the start of the province-wide lockdown. Because the increased risk of COVID-19 hospitalization, ICU admission and death with VOCs is most pronounced 14 to 28 days after diagnosis, there will be significant delays until the full burden to the health care system becomes apparent.

BackgroundLong-term sequelae associated with pneumococcal sepsis (PS) in pediatric patients in existing literature is currently unclear.AimTo review the evidence on sequelae and prognostic factors associated with PS among pediatric patients.MethodWe conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened six databases from their inception to January 15, 2021. Study population were neonates, infants, children and adolescents less than 18 years old with suspected or confirmed PS disease. Outcomes included sequelae types, prognostic factors, pooled death estimate and length of hospital stay (LOS) for survivors and deceased patients. Quality of studies was assessed using Joanna Briggs Institute appraisal checklists.ResultsWe screened 981 abstracts, and 24 full-text articles for final review. Septic shock was the most prevalent physical sequelae reported (13%, n=1492 patients). No functional, cognitive or neurological sequelae were reported in included studies. Meta-analysis of pooled mortality estimate was 14.6% (95%CI: 9.9 −19.4%). Prognostic factors associated with increased risk of PS sequelae and death included pediatric risk of mortality score ≥ 10 and co-infection with meningitis. LOS for survivors and non-survivors ranged between 5-30 days and 1-30 days. Nine included studies met at least 50% of the quality assessment criteria.ConclusionPhysical sequelae and death are the PS sequelae types currently identified in existing literature. Lack of information about other possible sequelae types suggests the long-term consequences of PS disease maybe underreported, especially in resource-limited settings. Future studies should consider exploring reasons for the existing of this knowledge gap.

Key Message Ontario long-term care (LTC) home residents have experienced disproportionately high morbidity and mortality, both from COVID-19 and from the conditions associated with the COVID-19 pandemic. There are several measures that could be effective in preventing COVID-19 outbreaks, hospitalizations, and deaths in Ontario’s LTC homes, if implemented. First, temporary staffing could be minimized by improving staff working conditions. Second, homes could be further decrowded by a continued disallowance of three- and four-resident rooms and additional temporary housing for the most crowded homes. Third, the risk of SARS-CoV-2 infection in staff could be minimized by approaches that reduce the risk of transmission in communities with a high burden of COVID-19. Summary Background The Province of Ontario has 626 licensed LTC homes and 77,257 long-stay beds; 58% of homes are privately owned, 24% are non-profit/charitable, 16% are municipal. LTC homes were strongly affected during Ontario’s first and second waves of the COVID-19 pandemic. Questions What do we know about the first and second waves of COVID-19 in Ontario LTC homes? Which risk factors are associated with COVID-19 outbreaks in Ontario LTC homes and the extent and death rates associated with outbreaks? What has been the impact of the COVID-19 pandemic on the general health and wellbeing of LTC residents? How has the existing Ontario evidence on COVID-19 in LTC settings been used to support public health interventions and policy changes in these settings? What are the further measures that could be effective in preventing COVID-19 outbreaks, hospitalizations, and deaths in Ontario’s LTC homes? Findings As of January 14, 2021, a total of 3,211 Ontario LTC home residents have died of COVID-19, totaling 60.7% of all 5,289 COVID-19 deaths in Ontario to date. There have now been more cumulative LTC home outbreaks during the second wave as compared with the first wave. The infection and death rates among LTC residents have been lower during the second wave, as compared with the first wave, and a greater number of LTC outbreaks have involved only staff infections. The growth rate of SARS-CoV-2 infections among LTC residents was slower during the first two months of the second wave in September and October 2020, as compared with the first wave. However, the growth rate after the two-month mark is comparatively faster during the second wave. The majority of second wave infections and deaths in LTC homes have occurred between December 1, 2020, and January 14, 2021 (most recent date of data extraction prior to publication). This highlights the recent intensification of the COVID-19 pandemic in LTC homes that has mirrored the recent increase in community transmission of SARS-CoV-2 across Ontario. Evidence from Ontario demonstrates that the risk factors for SARS-CoV-2 outbreaks and subsequent deaths in LTC are distinct from the risk factors for outbreaks and deaths in the community (Figure 1). The most important risk factors for whether a LTC home will experience an outbreak is the daily incidence of SARS-CoV-2 infections in the communities surrounding the home and the occurrence of staff infections. The most important risk factors for the magnitude of an outbreak and the number of resulting resident deaths are older design, chain ownership, and crowding. Figure 1. Anatomy of Outbreaks and Spread of COVID-19 in LTC Homes and Among Residents Figure from Peter Hamilton, personal communication. Many Ontario LTC home residents have experienced severe and potentially irreversible physical, cognitive, psychological, and functional declines as a result of precautionary public health interventions imposed on homes, such as limiting access to general visitors and essential caregivers, resident absences, and group activities. There has also been an increase in the prescribing of psychoactive drugs to Ontario LTC residents. The accumulating evidence on COVID-19 in Ontario’s LTC homes has been leveraged in several ways to support public health interventions and policy during the pandemic. Ontario evidence showed that SARS-CoV-2 infections among LTC staff was associated with subsequent COVID-19 deaths among LTC residents, which motivated a public order to restrict LTC staff from working in more than one LTC home in the first wave. Emerging Ontario evidence on risk factors for LTC home outbreaks and deaths has been incorporated into provincial pandemic surveillance tools. Public health directives now attempt to limit crowding in LTC homes by restricting occupancy to two residents per room. The LTC visitor policy was also revised to designate a maximum of two essential caregivers who can visit residents without time limits, including when a home is experiencing an outbreak. Several further measures could be effective in preventing COVID-19 outbreaks, hospitalizations, and deaths in Ontario’s LTC homes. First, temporary staffing could be minimized by improving staff working conditions. Second, the risk of SARS-CoV-2 infection in staff could be minimized by measures that reduce the risk of transmission in communities with a high burden of COVID-19. Third, LTC homes could be further decrowded by a continued disallowance of three- and four-resident rooms and additional temporary housing for the most crowded homes. Other important issues include improved prevention and detection of SARS-CoV-2 infection in LTC staff, enhanced infection prevention and control (IPAC) capacity within the LTC homes, a more balanced and nuanced approach to public health measures and IPAC strategies in LTC homes, strategies to promote vaccine acceptance amongst residents and staff, and further improving data collection on LTC homes, residents, staff, visitors and essential caregivers for the duration of the COVID-19 pandemic. Interpretation Comparisons of the first and second waves of the COVID-19 pandemic in the LTC setting reveal improvement in some but not all epidemiological indicators. Despite this, the second wave is now intensifying within LTC homes and without action we will likely experience a substantial additional loss of life before the widespread administration and time-dependent maximal effectiveness of COVID-19 vaccines. The predictors of outbreaks, the spread of infection, and deaths in Ontario’s LTC homes are well documented and have remained unchanged between the first and the second wave. Some of the evidence on COVID-19 in Ontario’s LTC homes has been effectively leveraged to support public health interventions and policies. Several further measures, if implemented, have the potential to prevent additional LTC home COVID-19 outbreaks and deaths.

ObjectiveTo determine 1-year attributable healthcare costs of bronchiolitis.MethodsUsing a population-based matched cohort and incidence-based cost analysis approach, we identified infants ResultsWe identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148–4,477), with $2,847 (95%CI: $2,712–2,982) spent on hospitalizations, $610 (95%CI: $594–627) on physician services, $562 (95%CI: $556–567)] on ED visits, $259 (95%CI: $222–297) on other healthcare costs and $35 ($27–42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735–2,794) vs $111 (95%CI: $102–121) in the initial 10 days post index date, $4,695 (95%CI: $4,589–4,800) vs $910 (95%CI: $847–973) in the initial 180 days and $1,158 (95%CI: $1,104–1213) vs $639 (95%CI: $599–679) during days 181–360.Mean 1-year bronchiolitis costs were higher in infants ConclusionsCompared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

As the COVID-19 pandemic has progressed, more local data has become available, enabling a more granular modeling approach. In March 2020, we developed a COVID-19 Resource Estimator (CORE) model to estimate the acute care resource use in Ontario, Canada. In this paper, we describe the evolution of CORE2.0 to incorporate age, sex, and time-dependent acute care resource use, length of stay, and mortality to simulate hospital occupancy. Demographics (e.g., age and sex) of infected cases are informed by 4-month averages between March-June, and July-October using 10-year age groups. The probability of hospitalization, ICU admission, and requiring mechanical ventilation are all age and sex-dependent. LOS for each acute care level ranges from 5.7 to 16.15 days in the ward, 6.5 to 10.7 days in the ICU without ventilation, and 14.8 to 21.6 days on the ventilator, depending on month of infection. We calibrated some LOS components to reported ward and ICU occupancy between June 15 and October 31, 2020. Furthermore, we demonstrate the use of CORE2.0 for a regional analysis of Region of Waterloo, Ontario, Canada to simulate the ward bed, ICU bed, and ventilator occupancies for 30 days starting December 2020 for three case trajectory scenarios. Moving forward, this model has become highly flexible and customizable to data updates, and can better inform acute care planning and public measures as the pandemic progresses.

COVID-19 has highlighted the need for credible epidemiological models to inform pandemic policy. Traditional mechanisms of commissioning research are ill-suited to guide policy during a rapidly evolving pandemic. At the same time, contracting with a single centre of expertise has been criticized for failing to reflect challenges inherent in specific modelling approaches.This report describes an alternative approach to mobilizing scientific expertise. Ontario's COVID-19 Modelling Consensus Table (MCT) was created in March 2020 to enable rapid communication of credible estimates of the impact of COVID-19 and to accelerate learning on how the disease is spreading and what could slow its transmission. The MCT is a partnership between the province and academic modellers and consists of multiple groups of experts, health system leaders, and senior decision-makers. Armed with Ministry of Health data, the MCT meets once per week to share results from modelling exercises, generate consensus judgements of the likely future impact of COVID-19, and discuss decision-makers' priorities.The MCT has enabled swift access to data for participants, a structure for developing consensus estimates and communicating these to decision-makers, credible models to inform health system planning, and increased transparency in public reporting of COVID-19 data. It has also facilitated the rapid publication of research findings and its incorporation into government policy.The MCT approach is one way to quickly draw on scientific advice outside of government and public health agencies. Beyond speed, this approach allows for nimbleness as experts from different organizations can be added as needed. It also shows how universities and research institutes have a role to play in crisis situations, and how this expertise can be marshalled to inform policy while respecting academic freedom and confidentiality.RéSUMé: LIEU: La COVID-19 a mis en évidence le besoin de modèles épidémiologiques crédibles pour éclairer la politique pandémique. Les mécanismes habituels pour commander des travaux de recherche sont peu propices à orienter les politiques lors d’une pandémie qui évolue rapidement. En même temps, la passation de contrats avec un seul centre d’expertise est critiquée, car elle ne tient pas compte des difficultés inhérentes de certaines approches de modélisation. INTERVENTION: Le présent rapport décrit une approche de rechange pour mobiliser le savoir scientifique. L’Ontario a créé en mars 2020 une Table de concertation sur la modélisation (TCM) qui permet de communiquer de façon rapide et fiable les estimations des effets de la COVID-19 et d’apprendre plus vite comment la maladie se propage et ce qui pourrait en ralentir la transmission. La TCM, un partenariat entre les modélisateurs de la province et des milieux universitaires, est composée de plusieurs groupes d’experts, de dirigeants du système de santé et de décideurs de haut niveau. Armée des données du ministère de la Santé, la TCM se réunit une fois par semaine pour partager les résultats d’exercices de modélisation, générer des jugements consensuels sur les futurs effets probables de la COVID-19 et discuter des priorités des décideurs. RéSULTATS: La TCM rend possible un accès rapide aux données pour les participants, une structure pour élaborer des estimations consensuelles et les communiquer aux décideurs, des modèles fiables pour éclairer la planification du système de santé, ainsi qu’une transparence accrue dans la communication des données sur la COVID-19 au public. Elle facilite aussi la publication rapide des résultats de recherche et leur intégration dans la politique gouvernementale. CONSéQUENCES: L’approche de la TCM est un moyen d’obtenir rapidement des conseils scientifiques à l’extérieur du gouvernement et des organismes de santé publique. Au-delà de sa rapidité, cette approche offre une grande souplesse, car des experts de différents organismes peuvent être ajoutés au besoin. Elle montre aussi que les universités et les établissements de recherche ont un rôle à jouer dans les situations de crise, et qu’il est possible de mobiliser leurs compétences pour éclairer les politiques tout en respectant la liberté et la confidentialité des milieux de la recherche et de l’enseignement.

BackgroundUnderstanding resource use for COVID-19 is critical. We conducted a population-based cohort study using public health data to describe COVID-19 associated age- and sex-specific acute care use, length of stay (LOS), and mortality.MethodsWe used Ontario’s Case and Contact Management (CCM) Plus database of individuals who tested positive for COVID-19 in Ontario from March 1 to September 30, 2020 to determine age- and sex-specific hospitalizations, intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV) use, LOS, and mortality. We stratified analyses by month of infection to study temporal trends and conducted subgroup analyses by long-term care residency.ResultsDuring the observation period, 56,476 COVID-19 cases were reported (72% < 60 years, 52% female). The proportion of cases shifted from older populations (> 60 years) to younger populations (10-39 years) over time. Overall, 10% of individuals were hospitalized, of those 22% were admitted to ICU, and 60% of those used IMV. Mean LOS for individuals in the ward, ICU without IMV, and ICU with IMV was 12.8, 8.5, 20.5 days, respectively. Mortality for individuals receiving care in the ward, ICU without IMV, and ICU with IMV was 24%, 30%, and 45%, respectively. All outcomes varied by age and decreased over time, overall and within age groups.InterpretationThis descriptive study shows acute care use and mortality varying by age, and decreasing between March and September in Ontario. Improvements in clinical practice and changing risk distributions among those infected may contribute to fewer severe outcomes among those infected with COVID-19.

BackgroundPredicting potential healthcare resource use under different scenarios will help to prepare the healthcare system for a surge in COVID-19 patients. In this study, we aim to predict the effect of COVID-19 on hospital resources in Nigeria.MethodWe adopted a previously published discrete-time, individual-level, health-state transition model of symptomatic COVID-19 patients to the Nigerian healthcare system and COVID-19 epidemiology. We simulated different combined scenarios of epidemic trajectories and acute care capacity. Primary outcomes included expected cumulative number of cases, days until depletion resources, and number of deaths associated with resource constraints. Outcomes were predicted over a 60-day time horizon.ResultsIn our best-case epidemic trajectory, which implies successful implementation of public health measures to control COVID-19 spread, the current number of ventilator resources in Nigeria (conservative resources scenario), were expended within five days, and 901 patients may die while waiting for hospital resources in conservative resource scenario. In our expanded resource scenarios, ventilated ICU beds were depleted in all three epidemic trajectories within 60 days. Acute care resources were only sufficient in the best-case and intermediate epidemic scenarios, combined with a substantial increase in healthcare resources.ConclusionCurrent hospital resources are inadequate to manage the COVID-19 pandemic in Nigeria. Given Nigeria’s limited resources, it is imperative to increase healthcare resources and maintain aggressive public health measures to reduce COVID-19 transmission.KEY QUESTIONSWhat is already known on this subject?While western countries seem to be recovering from the COVID-19 pandemic, there is an increasing community spread of the virus in many African countries.The limited healthcare resources available in the region may not be sufficient to cope with increasing numbers of COVID-19 cases.What this study adds?Using the COVID-19 Resource Estimator (CORE) model, we demonstrate that implementing and maintaining aggressive public health measures to keep the epidemic growth at a low rate, while simultaneously substantially increasing healthcare resources is critical to minimize the impact of COVID-19 on morbidity and mortality.The impact of COVID-19 in low resource settings will likely overwhelm health system capacity if aggressive public health measures are not implemented. To mitigate the impact of COVID-19 in these settings, it is essential to develop strategies to substantially increase health system capacities, including hospital resources, personal protective equipment and trained healthcare personnel and to implement and maintain aggressive public health measures.

Background & 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 & 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 peri-complication. 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 peri-complication. HBV diagnosis peri-complication 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 peri-complication. Conclusions A high proportion of patients with HBV-related complications are first diagnosed with HBV peri-complication. These signal missed opportunities for earlier detection and treatment. Our findings support expansion of HBV screening.

In addition to instituting public health measures for COVID-19, managing healthcare resources is important for outcomes. The experiences in Italy and New York have shown that personal protective equipment (PPE) shortages can cause increased morbidity and mortality. We demonstrate a method to predict PPE demand across a health care system.

BackgroundThe global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing significant strain to healthcare systems. The purpose of our study is to predict the impact of the COVID-19 pandemic on patient outcomes and the healthcare system in Ontario, Canada.MethodsWe developed an individual-level simulation to model the flow of COVID-19 patients through the Ontario healthcare system. We simulated different combined scenarios of epidemic trajectory and healthcare capacity. Outcomes include numbers of patients needing admission to the ward, Intensive Care Unit (ICU), and requiring ventilation; days to resource depletion; and numbers of patients awaiting resources and deaths associated with limited access to resources.FindingsWe demonstrate that with effective early public health measures system resources need not be depleted. For scenarios considering late or ineffective implementation of physical distancing, health system resources would be depleted within 14-26 days. Resource depletion was also avoided or delayed with aggressive measures to rapidly increase ICU, ventilator, and acute care hospital capacity.InterpretationWe found that without aggressive physical distancing measures the Ontario healthcare system would have been inadequately equipped to manage the expected number of patients with COVID-19, despite the rapid capacity increase. This overall lack of resources would have led to an increase in mortality. By slowing the spread of the disease via ongoing public health measures and having increased healthcare capacity, Ontario may have avoided catastrophic stresses to its health care system.

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) is a widely accepted management strategy for low-risk prostate cancer (PC), but limited data exist regarding long-term outcomes after initial AS ...

Background West Nile Virus (WNV) is a mosquito-borne pathogen that has become established in North America. Risk for human infection varies geographically in accordance with climate and population factors. Though often asymptomatic, human WNV infection can cause febrile illness or, rarely, neurologic disease. WNV has become a public health concern in Canada since its introduction in 2001. Methods To identify predictors of human WNV incidence at the public health unit (PHU) level in Ontario, Canada, we combined data on environmental and population characteristics of PHUs with historical mosquito and human surveillance records from 2002 to 2013. We examined the associations between annual WNV incidence and monthly climate indices (e.g. minimum and maximum temperature, average precipitation), land cover (e.g. deciduous forest, water), population structure (e.g. age and sex composition) and the annual percentage of WNV-positive mosquito pools from 2002 to 2013. We then developed a generalized linear mixed model with a Poisson distribution adjusting for spatial autocorrelation and repeat measures. Further to this, to examine potential ‘early season’ predictors of WNV incidence in a given year, we developed a model based on winter and spring monthly climate indices. Results Several climate indices, including mean minimum temperature (o C) in February (RR = 1.58, CI: [1.42, 1.75]), and the annual percentage of WNV-positive mosquito pools (RR = 1.07, CI: [1.04, 1.11]) were significantly associated with human WNV incidence at the PHU level. Higher winter minimum temperatures were also strongly associated with annual WNV incidence in the ‘early season’ model (e.g. February minimum temperature (RR = 1.91, CI: [1.73, 2.12]). Conclusions Our study demonstrates that early season temperature and precipitation indices, in addition to the percentage of WNV-positive mosquito pools in a given area, may assist in predicting the likelihood of a more severe human WNV season in southern regions of Ontario, where WNV epidemics occur sporadically. Electronic supplementary material The online version of this article (10.1186/s12879-018-3052-6) contains supplementary material, which is available to authorized users.

PURPOSE Health technology assessment provides a means to assess the technical properties, safety, efficacy, cost-effectiveness, and ethical/legal/social impact of a novel technology. An important component of health technology assessment is the cost-effectiveness analysis (CEA), which can be performed using model-based CEA. This study used the CEA model to compare the cost-effectiveness of a novel ligament augmentation device with the standard technique for primary repair of complete ulnar collateral ligament (UCL) tears. METHODS A model was developed for complete UCL tear requiring acute surgical repair, comparing the cost-effectiveness of standard technique primary repair and repair using a ligament augmentation device from a societal perspective. Primary outcomes included quality-adjusted life years (QALYs), cost, net monetary benefit (NMB) and incremental NMB. A cost-effectiveness threshold of CAD $50,000/QALY was used to compare the 2 techniques. Sensitivity analyses were conducted to assess the parameter uncertainty, specifically the impact of device cost, time off work, probability of complication, and postoperative outcome. RESULTS The NMB for the standard technique was CAD $42,598, and the NMB for repair using the ligament augmentation device was CAD $41,818. The standard technique was the preferred strategy for primary repair of complete UCL tears. One-way sensitivity analyses demonstrated that the ligament augmentation device became cost-effective if individuals return to work in

Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence.A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection. Eight strategies of postoperative management were evaluated. A lifetime time horizon, an annual discount rate of 5%, a societal perspective, and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed. Deterministic and probabilistic sensitivity analyses were conducted. The model was validated against randomized trials and historical cohorts.Three strategies dominated the others: endoscopy-guided full step-up therapy (14.80 QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY. Probabilistic sensitivity analysis showed that the second strategy has the highest probability of being the optimal alternative in all comparisons at cost-effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided only by clinical recurrence and those using biologics alone were dominated.According to this decision analysis, thiopurines immediately after surgery and addition of biologics guided by endoscopic recurrence is the optimal strategy of postoperative management in patients with Crohn's disease with high risk of recurrence (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B654).

Background In Ontario, Canada, pneumococcal conjugate vaccine (PCV) was approved for infants in 2001 and became part of the publicly funded routine immunization schedule in 2005. We assessed the population-level impact of PCV on pneumonia hospitalizations and related costs. Methods We used the difference-in-differences approach to evaluate the impact of pneumococcal vaccination on pneumonia hospitalizations and related costs, using nonpneumonia hospitalization as the control condition. We extracted monthly hospitalization costs, stratified by age group, from population-based health administrative data between April 1992 and March 2014. The study period was divided into 5 intervals: prevaccine period, availability of 7-valent PCV (PCV7) for private purchase, public funding for PCV7, replacement of PCV7 with 10-valent PCV (PCV10), and replacement of PCV10 with 13-valent PCV (PCV13). Results A total of 1063700 pneumonia hospitalizations were recorded during the study period. In the vaccine-eligible age group, pneumonia hospitalizations declined by 34% (95% confidence interval, 32%-37%), 38% (32%-43%), and 45% (40%-51%) and hospitalization-related costs declined by 38% (25%-51%), 39% (33%-45%), and 46% (41%-52%) after public funding for PCV7, PCV10, and PCV13, respectively. Pneumonia hospitalizations and related costs also declined substantially for PCV-ineligible older children and elderly persons (aged >65 years). Conclusions Our results suggest that the publicly funded PCV immunization program is responsible for substantial reductions in pneumonia hospitalizations and related healthcare costs, among both young children eligible for publicly funded vaccination and other age groups not included in the publicly funded program.

The province of Ontario continues to experience measles virus transmissions despite the elimination of measles in Canada. We describe an unusual outbreak of measles in Ontario, Canada, in early 2015 that involved cases with a unique strain of virus and no known association among primary case-patients. A total of 18 cases of measles were reported from 4 public health units during the outbreak period (January 25–March 23, 2015); none of these cases occurred in persons who had recently traveled. Despite enhancements to case-patient interview methods and epidemiologic analyses, a source patient was not identified. However, the molecular epidemiologic analysis, which included extended sequencing, strongly suggested that all cases derived from a single importation of measles virus genotype D4. The use of timely genotype sequencing, rigorous epidemiologic investigation, and a better understanding of the gaps in surveillance are needed to maintain Ontario’s measles elimination status.