Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

BACKGROUND: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. OBJECTIVE: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). DESIGN: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. SETTING: Population-based cohort study in Ontario, Canada. PARTICIPANTS: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. MEASUREMENTS: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. RESULTS: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). LIMITATION: Medication use was not available at the population level. CONCLUSION: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

The Kidney Failure Risk Equation: Evaluation of Novel Input Variables including eGFR Estimated Using the CKD-EPI 2021 Equation in 59 Cohorts.

SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.

AIMS: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION: Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

Impact of limited sample size and follow-up on single event survival extrapolation for health technology assessment: a simulation study.

INTRODUCTION: Extrapolation of time-to-event data from clinical trials is commonly used in decision models for health technology assessment (HTA). The objective of this study was to assess performance of standard parametric survival analysis techniques for extrapolation of time-to-event data for a single event from clinical trials with limited data due to small samples or short follow-up. METHODS: Simulated populations with 50,000 individuals were generated with an exponential hazard rate for the event of interest. A scenario consisted of 5000 repetitions with six sample size groups (30-500 patients) artificially censored after every 10% of events observed. Goodness-of-fit statistics (AIC, BIC) were used to determine the best-fitting among standard parametric distributions (exponential, Weibull, log-normal, log-logistic, generalized gamma, Gompertz). Median survival, one-year survival probability, time horizon (1% survival time, or 99th percentile of survival distribution) and restricted mean survival time (RMST) were compared to population values to assess coverage and error (e.g., mean absolute percentage error). RESULTS: The true exponential distribution was correctly identified using goodness-of-fit according to BIC more frequently compared to AIC (average 92% vs 68%). Under-coverage and large errors were observed for all outcomes when distributions were specified by AIC and for time horizon and RMST with BIC. Error in point estimates were found to be strongly associated with sample size and completeness of follow-up. Small samples produced larger average error, even with complete follow-up, than large samples with short follow-up. Correctly specifying the event distribution reduced magnitude of error in larger samples but not in smaller samples. CONCLUSIONS: Limited clinical data from small samples, or short follow-up of large samples, produce large error in estimates relevant to HTA regardless of whether the correct distribution is specified. The associated uncertainty in estimated parameters may not capture the true population values. Decision models that base lifetime time horizon on the model's extrapolated output are not likely to reliably estimate mean survival or its uncertainty. For data with an exponential event distribution, BIC more reliably identified the true distribution than AIC. These findings have important implications for health decision modelling and HTA of novel therapies seeking approval with limited evidence.

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada.

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.

Development of Risk Prediction Equations for Incident Chronic Kidney Disease.

Importance: Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective: To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants: Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures: Demographic and clinical factors. Main Outcomes and Measures: Incident eGFR of less than 60 mL/min/1.73 m2. Results: Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance: Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Approach to asymptomatic paraesophageal hernia: watchful waiting or elective laparoscopic hernia repair?

BACKGROUND: There is no consensus on whether asymptomatic paraesophageal hernia (PEH) should be operated. Some argue that surgery is necessary prophylaxis against potentially catastrophic consequences of acute complications in untreated PEH. Others reason that the acute complications are rare and emergent operations have relatively low mortality. In the laparoscopic era, elective operations have become safer and less morbid. However, recent studies report high incidence of recurrent hernia, some of which affect quality of life and require further interventions. In light of these new findings, we investigated whether asymptomatic PEH should receive elective laparoscopic hernia repair (ELHR) or watchful waiting (WW). METHODS: A Markov Monte Carlo microsimulation decision analysis model followed a hypothetical cohort of asymptomatic PEH patients who have predominantly female gender and normally distributed mean age of 62.5 years for the lifetime. Accrued health benefits expressed in quality-adjusted life months (QALM) were compared between two strategies: WW and ELHR. Two-dimensional simulations were performed to account for uncertainties in the model. Deterministic sensitivity analyses were performed to test key assumptions. RESULTS: After considering both individual- and parameter-level uncertainties in the two-dimensional simulations, WW was the superior strategy in 82% of the simulations, accumulating mean 5 QALM more than ELHR (168 vs. 163). Our model was robust to deterministic sensitivity analyses and was internally validated, which supported the validity of our results. CONCLUSIONS: Patients with asymptomatic PEH are more likely to achieve greater health outcomes if they undergo WW as initial treatment than ELHR.

Past Decline Versus Current eGFR and Subsequent ESRD Risk.

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).

Past Decline Versus Current eGFR and Subsequent Mortality Risk.

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

Cardiovascular disease in chronic kidney disease in 2015.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is strongly linked to premature cardiovascular disease, which is the leading cause of death before end-stage renal disease in these patients. Herein, we review recent literature from 2014 to 2015 that has advanced our understanding of cardiovascular outcomes in patients with advanced and/or progressive CKD. RECENT FINDINGS: We focus on new data describing the mechanisms of cardiac death in patients with CKD as well as the novel associations between cardiac events and the competing risks of end-stage renal disease and pre-end-stage renal disease death. We review new controversies in multivessel revascularization of complex coronary artery disease in CKD and, finally, the treatment of systolic heart failure in advanced CKD, including the use of implantable defibrillator therapy. SUMMARY: Marked advances in the understanding of cardiovascular disease in CKD have occurred in the past year, namely from retrospective and registry data. Although exciting, these recent studies highlight the urgent need for randomized control trials to guide therapeutic decisions.

Progression to Stage 4 chronic kidney disease and death, acute kidney injury and hospitalization risk: a retrospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) Stage 4 is on the path to kidney failure, but there is little information on the risks associated with progression to Stage 4 per se. The objective of this study is to determine how progression from Stage 3 to Stage 4 CKD alters morbidity and mortality in a referred cohort of patients. METHODS: We conducted a retrospective cohort study consisting of 1607 patients with estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m(2) referred to a nephrologist at a tertiary care center in Ontario, Canada, between January 2001 and December 2008. Interim progression from Stage 3 to Stage 4 chronic kidney disease was defined by two independent outpatient eGFR values <30 mL/min/1.73 m(2). Death, acute kidney injury (AKI) and all-cause hospitalizations subsequent to Stage 4 progression, but prior to the development of end-stage renal disease (ESRD), ascertained from administrative databases. RESULTS: The mean (standard deviation) baseline eGFR was 43 (8) mL/min/1.73 m(2). Over 2.66 years (interquartile range: 1.42-4.45), 344 (21%) patients progressed to Stage 4, 47 (3%) developed ESRD, 188 (12%) patients died, 143 (9%) were hospitalized with AKI and 688 (43%) were hospitalized for any reason. Compared with patients who did not progress to Stage 4, those who did progress had significantly higher adjusted risks of death [hazard ratio (HR) = 2.56, 95% confidence interval (95% CI): 1.75-3.75], AKI (HR = 2.32, 95% CI: 1.44-3.74) and all-cause hospitalization (HR = 1.87, 95% CI: 1.45-2.42). CONCLUSIONS: Progression from Stage 3 to Stage 4 CKD is associated with increased risks of death, AKI and hospitalization prior to ESRD.

ESRD and death after heart failure in CKD.

CKD is a risk factor for heart failure, but there is no data on the risk of ESRD and death after recurrent hospitalizations for heart failure. We sought to determine how interim heart failure hospitalizations modify the subsequent risk of ESRD or death before ESRD in patients with CKD. We retrospectively identified 2887 patients with a GFR between 15 and 60 ml/min per 1.73 m2 referred between January of 2001 and December of 2008 to a nephrology clinic in Toronto, Canada. We ascertained interim first, second, and third heart failure hospitalizations as well as ESRD and death before ESRD outcomes from administrative data. Over a median follow-up time of 3.01 (interquartile range=1.56-4.99) years, interim heart failure hospitalizations occurred in 359 (12%) patients, whereas 234 (8%) patients developed ESRD, and 499 (17%) patients died before ESRD. Compared with no heart failure hospitalizations, one, two, or three or more heart failure hospitalizations increased the adjusted hazard ratio of ESRD from 4.89 (95% confidence interval [95% CI], 3.21 to 7.44) to 10.27 (95% CI, 5.54 to 19.04) to 14.16 (95% CI, 8.07 to 24.83), respectively, and the adjusted hazard ratio death before ESRD from 3.30 (95% CI, 2.55 to 4.27) to 4.20 (95% CI, 2.82 to 6.25) to 6.87 (95% CI, 4.96 to 9.51), respectively. We conclude that recurrent interim heart failure is associated with a stepwise increase in the risk of ESRD and death before ESRD in patients with CKD.

Economic Evaluations in the Diagnosis and Management of Traumatic Brain Injury: A Systematic Review and Analysis of Quality.

BACKGROUND: Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. OBJECTIVE: The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. METHODS: Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. RESULTS: Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-consequences analyses. Only six studies were of high quality. Current evidence from high-quality studies suggests the economic attractiveness of the following strategies: a low medical threshold for computed tomography (CT) scanning of asymptomatic infants with possible inflicted TBI, selective CT scanning of adults with mild TBI as per the Canadian CT Head Rule, management of severe TBI according to the Brain Trauma Foundation guidelines, management of TBI in dedicated neurocritical care units, and early transfer of patients with TBI with nonsurgical lesions to neuroscience centers. CONCLUSIONS: Threshold-guided CT scanning, adherence to Brain Trauma Foundation guidelines, and care for patients with TBI, including those with nonsurgical lesions, in specialized settings appear to be economically attractive strategies.

Estimation de l'épuisement des ressources hospitalières attribuable à la COVID-19 en Ontario, au Canada.

CONTEXTE: La propagation à l'échelle planétaire de la maladie à coronavirus 2019 (COVID-2019) se poursuit dans plusieurs pays, mettant à rude épreuve les systèmes de santé. Cette étude avait pour but de prédire les répercussions de la pandémie sur les issues des patients et l'utilisation des ressources hospitalières en Ontario (Canada). MÉTHODES: Nous avons conçu un modèle de simulation axé sur les personnes illustrant le flux de patients atteints de la COVID-19 dans les hôpitaux ontariens. Nous avons simulé diverses combinaisons de trajectoires épidémiques et de capacités de soins hospitaliers. Les paramètres à l'étude étaient le nombre de patients devant être admis au service d'hospitalisation ou à l'unité des soins intensifs (USI) ­avec ou sans respirateur mécanique ­, le nombre de jours jusqu'à l'épuisement des ressources, le nombre de patients en attente de ressources et le nombre de décès. RÉSULTATS: Nous avons constaté que la mise en place rapide de mesures de santé publique efficaces éviterait l'épuisement des ressources hospitalières. Les simulations dans lesquelles les mesures d'éloignement sanitaire étaient inefficaces ou adoptées tardivement ont montré que l'épuisement des ressources prendrait de 14 à 26 jours et qu'il y aurait, dans le pire des cas, 13 321 décès de personnes en attente de ressources. Cet épuisement pourrait être évité ou retardé par la mise en place de mesures rigoureuses visant à améliorer la capacité des hôpitaux en matière de soins intensifs, de respirateurs mécaniques et de soins hospitaliers. INTERPRÉTATION: Sans l'adoption de mesures d'éloignement sanitaire rigoureuses, le système de santé ontarien n'aurait pas eu les ressources nécessaires pour prendre en charge le nombre attendu de patients atteints de la COVID-19, même en cas d'augmentation rapide de sa capacité hospitalière. Les pénuries auraient fait augmenter le taux de mortalité. En ralentissant la transmission de la maladie par la mise en place de mesures de santé publique et l'augmentation de la capacité des hôpitaux, l'Ontario a probablement évité que ces derniers subissent une pression catastrophique.

Economic evaluation of decompressive craniectomy versus barbiturate coma for refractory intracranial hypertension following traumatic brain injury.

OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as second-tier strategies when intracranial hypertension following severe traumatic brain injury is refractory to first-line treatments. Uncertainty surrounds the decision to choose either treatment option. We investigated which strategy is more economically attractive in this context. DESIGN: We performed a cost-utility analysis. A Markov Monte Carlo microsimulation model with a life-long time horizon was created to compare quality-adjusted survival and cost of the two treatment strategies, from the perspective of healthcare payer. Model parameters were estimated from the literature. Two-dimensional simulation was used to incorporate parameter uncertainty into the model. Value of information analysis was conducted to identify major drivers of decision uncertainty and focus future research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a population of patients (mean age = 25 yr) who developed refractory intracranial hypertension following traumatic brain injury. INTERVENTIONS: We compared two treatment strategies: decompressive craniectomy and barbiturate coma. MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an average gain of 1.5 quality-adjusted life years relative to barbiturate coma, with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year gained. Decompressive craniectomy resulted in a greater quality-adjusted life expectancy 86% of the time and was more cost-effective than barbiturate coma in 78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At older age, decompressive craniectomy continued to increase survival but at higher cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive craniectomy for the treatment of refractory intracranial hypertension following traumatic brain injury provides better value in terms of costs and health gains than barbiturate coma. However, decompressive craniectomy might be less economically attractive for older patients. Further research, particularly on natural history of severe traumatic brain injury patients, is needed to make more informed treatment decisions.

CKD stage at nephrology referral and factors influencing the risks of ESRD and death.

BACKGROUND: Patients with chronic kidney disease (CKD) stages 3-5 are at increased risk of progressing to end-stage renal disease (ESRD) or dying prior to the development of ESRD compared with patients with less severe CKD. The magnitude of these risks may vary by stage, which has important implications for therapy. Our objective was to apply a competing risk analysis in order to estimate these risks in a referred cohort of patients with CKD by stage at referral and identify risk factors associated with each outcome. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 3,273 patients with CKD stages 3-5 who were referred to the nephrology clinic at Sunnybrook Health Sciences Centre, Toronto, prior to December 31, 2008, with follow-up data available prior to December 31,2008. PREDICTORS: CKD stage at time of referral; demographic, laboratory, and clinical characteristics. OUTCOMES: ESRD, defined as the initiation of dialysis therapy or pre-emptive kidney transplantation, and death from any cause prior to ESRD. MEASUREMENTS: Baseline laboratory data. RESULTS: Over a median follow-up of 2.98 years, 459 patients (14%) developed ESRD and 540 (16%) died. Rates per 100 patient-years of ESRD versus death prior to ESRD for CKD stage 3A were 0.6 (95% CI, 0.1-1.0) versus 2.2 (95% CI, 1.2-3.1; P<0.001); for CKD stage 3B, 1.4 (95% CI, 0.8-2.1) versus 4.4 (95% CI, 3.3-5.6; P<0.001); for CKD stage 4, 7.7 (95% CI, 5.9-9.4) versus 8.0 (95% CI, 6.2-9.8; P=0.6); and for CKD stage 5, 41.4 (95% CI, 34.4-48.4) versus 9.4 (95% CI, 5.2-13.4; P<0.001). For those with CKD stage 4, we identified 12 variables associated with higher risk of ESRD and 7 variables associated with higher risk of death prior to ESRD. LIMITATIONS: A cohort analyzed retrospectively. CONCLUSIONS: ESRD and death prior to ESRD incidence was most similar in CKD stage 4. We identified variables easily assessed at the time of referral that could discriminate between these risks.

Risk prediction models for patients with chronic kidney disease: a systematic review.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for kidney failure, cardiovascular events, and all-cause mortality. Accurate models are needed to predict the individual risk for these outcomes. PURPOSE: To systematically review risk prediction models for kidney failure, cardiovascular events, and death in patients with CKD. DATA SOURCES: MEDLINE search of English-language articles published from 1966 to November 2012. STUDY SELECTION: Cohort studies that examined adults with any stage of CKD who were not receiving dialysis and had not had a transplant; had at least 1 year of follow-up; and reported on a model that predicted the risk for kidney failure, cardiovascular events, or all-cause mortality. DATA EXTRACTION: Reviewers extracted data on study design, population characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness. DATA SYNTHESIS: Thirteen studies describing 23 models were found. Eight studies (11 models) involved kidney failure, 5 studies (6 models) involved all-cause mortality, and 3 studies (6 models) involved cardiovascular events. Measures of estimated glomerular filtration rate or serum creatinine level were included in 10 studies (17 models), and measures of proteinuria were included in 9 studies (15 models). Only 2 studies (4 models) met the criteria for clinical usefulness, of which 1 study (3 models) presented reclassification indices with clinically useful risk categories. LIMITATION: A validated risk-of-bias tool and comparisons of the performance of different models in the same validation population were lacking. CONCLUSION: Accurate, externally validated models for predicting risk for kidney failure in patients with CKD are available and ready for clinical testing. Further development of models for cardiovascular events and all-cause mortality is needed. PRIMARY FUNDING SOURCE: None.

What Is the Potential Value of a Randomized Trial of Different Thresholds to Initiate Invasive Ventilation? A Health Economic Analysis.

OBJECTIVES: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure. PERSPECTIVE: Publicly funded healthcare payer. SETTING: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice. METHODS: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year. RESULTS: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios. CONCLUSIONS: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.

Validation of the European SCORE2 models in a Canadian primary care cohort.

AIMS: Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort. METHODS AND RESULTS: A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40-69 while the models for older persons (OPs) were applied to 9885 individuals 70-89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men. CONCLUSION: The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions.

In this study, new tools [Systematic Coronary Risk Evaluation Model 2 (SCORE2)] that were developed across Europe to predict heart attack and stroke risk in healthy individuals were tested independently for the first time in a Canadian setting. Key findings are as follows:The accuracy of predictions from SCORE2 in Canadians depends on the age group considered and whether uncalibrated or recalibrated equations are being used.Independent assessment of tools such as SCORE2 remains useful prior to widespread implementation in new jurisdictions.