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

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

Cost-Effectiveness of Preoperative Topical Antibiotic Prophylaxis for Endophthalmitis Following Cataract Surgery.

PURPOSE: To determine the cost-effectiveness of preoperative topical antibiotic prophylaxis for the prevention of endophthalmitis following cataract surgery. DESIGN: Cost-effectiveness analysis using a decision-analytic microsimulation model. METHODS: Preoperative topical antibiotic prophylaxis vs no-prophylaxis costs and effects were projected over a life-time horizon for a simulated cohort of 500 000 adult patients (≥18 years old) requiring cataract surgery in theoretical surgical centers in the United States. Efficacy and cost (2021 US dollars) values were obtained from the literature and discounted at 3% per year. RESULTS: Based on inputted parameters, the mean incidence of endophthalmitis following cataract surgery for preoperative topical antibiotic prophylaxis vs no-prophylaxis was 0.034% (95% CI 0%-0.2%) and 0.042% (95% CI 0%-0.3%), respectively-an absolute risk reduction of 0.008%. The mean life-time costs for cataract surgery with prophylaxis and no-prophylaxis were $2486.67 (95% CI $2193.61-$2802.44) and $2409.03 (95% CI $2129.94-$2706.69), respectively. The quality-adjusted life-years (QALYs) associated with prophylaxis and no-prophylaxis were 10.33495 (95% CI 7.81629-12.38158) and 10.33498 (95% CI 7.81284-12.38316), respectively. Assuming a cost-effectiveness criterion of ≤$50 000 per QALY gained, the threshold analyses indicated that prophylaxis would be cost-effective if the incidence of endophthalmitis after cataract surgery was greater than 5.5% or if the price of the preoperative topical antibiotic prophylaxis was less than $0.75. CONCLUSIONS: General use of preoperative topical antibiotic prophylaxis is not cost-effective compared with no-prophylaxis for the prevention of endophthalmitis following cataract surgery. Preoperative topical antibiotic prophylaxis, however, would be cost-effective at a higher incidence of endophthalmitis and/or a substantially lower price for prophylaxis.

Quantifying the benefits of remission duration in focal and segmental glomerulosclerosis.

BACKGROUND: Although the clinical benefit of obtaining a remission in proteinuria in nephrotic patients with focal segmental glomerulosclerosis (FSGS) is recognized, the long-term value of maintaining it and the impact of relapses on outcome are not well described. METHODS: We examined the impact of remissions and relapses on either a 50% decline in kidney function or end-stage kidney disease (combined event) using time-dependent and landmark analyses in a retrospective study of all patients from the Toronto Glomerulonephritis Registry with biopsy-proven FSGS, established nephrotic-range proteinuria and at least one remission. RESULTS: In the 203 FSGS individuals with a remission, 89 never relapsed and 114 experienced at least one relapse. The first recurrence was often followed by a repeating pattern of remission and relapse. The 10-year survival from a combined event was 15% higher in those with no relapse versus those with any relapse. This smaller than anticipated difference was related to the favourable outcome in individuals whose relapses quickly remitted. Relapsers who ultimately ended in remission (n = 46) versus in relapse (n = 68) experienced a 91% and 32% 7-year event survival (P < .001), respectively. Using time-varying survival analyses that considered all periods of remission and relapse in every patient and adjusting for each period's initial estimated glomerular filtration rate, the state of relapse was associated with a 2.17 (95% confidence interval 1.32-3.58; P = .002) greater risk of experiencing a combined event even in this FSGS remission cohort. CONCLUSION: In FSGS, unless remissions are maintained and relapses avoided, long-term renal survival remains poor. Treatment strategies addressing remission duration remain poorly defined and should be an essential question in future trials.

Development and Validation of Prediction Models of Adverse Kidney Outcomes in the Population With and Without Diabetes.

OBJECTIVE: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS: In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or <60 mL/min/1.73 m2) to predict a composite of ≥40% decline in eGFR or kidney failure (i.e., receipt of kidney replacement therapy) over 2-3 years. RESULTS: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS: Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

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

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

The ophthalmic surgical backlog associated with the COVID-19 pandemic: a population-based and microsimulation modelling study.

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.

The Impact of the COVID-19 Pandemic on Cardiac Procedure Wait List Mortality in Ontario, Canada.

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.

Decision Modeling for Economic Evaluation in Otolaryngology-Head and Neck Surgery: Review of Techniques.

Decision making in health care is complex, and substantial uncertainty can be involved. Structured, systematic approaches to the integration of available evidence, assessment of uncertainty, and determination of choice are of significant benefit in an era of "value-based care." This is especially true for otolaryngology-head and neck surgery, where technological advancements are frequent and applicable to an array of subspecialties. Decision analysis aims to achieve these goals through various modeling techniques, including (1) decision trees, (2) Markov process, (3) microsimulation, and (4) discrete event simulation. While decision models have been used for decades, many clinicians and researchers continue to have difficulty deciphering them. In this review, we present an overview of various decision analysis modeling techniques, their purposes, how they can be interpreted, and commonly used syntax to promote understanding and use of these approaches. Throughout, we provide a sample research question to facilitate discussion of the advantages and disadvantages of each technique.

COVID-19: Adaptation of a model to predicting healthcare resources needs in Valle del Cauca, Colombia / COVID-19: Predicción de las necesidades de recursos sanitarios en el Valle del Cauca, Colombia

Abstract Background: Valle del Cauca is the region with the fourth-highest number of COVID-19 cases in Colombia (>50,000 on September 7, 2020). Due to the lack of anti-COVID-19 therapies, decision-makers require timely and accurate data to estimate the incidence of disease and the availability of hospital resources to contain the pandemic. Methods: We adapted an existing model to the local context to forecast COVID-19 incidence and hospital resource use assuming different scenarios: (1) the implementation of quarantine from September 1st to October 15th (average daily growth rate of 2%); (2-3) partial restrictions (at 4% and 8% growth rates); and (4) no restrictions, assuming a 10% growth rate. Previous scenarios with predictions from June to August were also presented. We estimated the number of new cases, diagnostic tests required, and the number of available hospital and intensive care unit (ICU) beds (with and without ventilators) for each scenario. Results: We estimated 67,700 cases by October 15th when assuming the implementation of a quarantine, 80,400 and 101,500 cases when assuming partial restrictions at 4% and 8% infection rates, respectively, and 208,500 with no restrictions. According to different scenarios, the estimated demand for reverse transcription-polymerase chain reaction tests ranged from 202,000 to 1,610,600 between September 1st and October 15th. The model predicted depletion of hospital and ICU beds by September 20th if all restrictions were to be lifted and the infection growth rate increased to 10%. Conclusion: Slowly lifting social distancing restrictions and reopening the economy is not expected to result in full resource depletion by October if the daily growth rate is maintained below 8%. Increasing the number of available beds provides a safeguard against slightly higher infection rates. Predictive models can be iteratively used to obtain nuanced predictions to aid decision-making

Resumen Introducción: Valle del Cauca es el departamento con el cuarto mayor número de casos de COVID-19 en Colombia (>50,000 en septiembre 7, 2020). Debido a la ausencia de tratamientos efectivos para COVID-19, los tomadores de decisiones requieren de acceso a información actualizada para estimar la incidencia de la enfermedad, y la disponibilidad de recursos hospitalarios para contener la pandemia. Métodos: Adaptamos un modelo existente al contexto local para estimar la incidencia de COVID-19, y la demanda de recursos hospitalarios en los próximos meses. Para ello, modelamos cuatro escenarios hipotéticos: (1) el gobierno local implementa una cuarentena desde el primero de septiembre hasta el 15 de octubre (asumiendo una tasa promedio de infecciones diarias del 2%); (2-3) se implementan restricciones parciales (tasas de infección del 4% y 8%); (4) se levantan todas las restricciones (tasa del 10%). Los mismos escenarios fueron previamente evaluados entre julio y agosto, y los resultados fueron resumidos. Estimamos el número de casos nuevos, el número de pruebas diagnósticas requeridas, y el numero de camas de hospital y de unidad de cuidados intensivos (con y sin ventilación) disponibles, para cada escenario. Resultados: El modelo estimó 67,700 casos a octubre 15 al asumir la implementación de una nueva cuarentena, 80,400 y 101,500 al asumir restricciones parciales al 4 y 8% de infecciones diarias, respectivamente, y 208,500 al asumir ninguna restricción. La demanda por pruebas diagnósticas (de reacción en cadena de la polimerasa) fue estimada entre 202,000 y 1,610,600 entre septiembre 1 y octubre 15, a través de los diferentes escenarios evaluados. El modelo estimó un agotamiento de camas de cuidados intensivos para septiembre 20 al asumir una tasa de infecciones del 10%. Conclusión: Se estima que el levantamiento paulatino de las restricciones de distanciamiento social y la reapertura de la economía no debería causar el agotamiento de recursos hospitalarios si la tasa de infección diaria se mantiene por debajo del 8%. Sin embargo, incrementar la disponibilidad de camas permitiría al sistema de salud ajustarse rápidamente a potenciales picos inesperados de infecciones nuevas. Los modelos de predicción deben ser utilizados de manera iterativa para depurar las predicciones epidemiológicas y para proveer a los tomadores de decisiones con información actualizada.

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.

Impact of Transcatheter Aortic Valve Durability on Life Expectancy in Low-Risk Patients With Severe Aortic Stenosis.

BACKGROUND: Recent clinical trial results showed that transcatheter aortic valve replacement (TAVR) is noninferior and may be superior to surgical aortic valve replacement (SAVR) for mortality, stroke, and rehospitalization. However, the impact of transcatheter valve durability remains uncertain. METHODS: Discrete event simulation was used to model hypothetical scenarios of TAVR versus SAVR durability in which TAVR failure times were varied to determine the impact of TAVR valve durability on life expectancy in a cohort of low-risk patients similar to those in recent trials. Discrete event simulation modeling was used to estimate the tradeoff between a less invasive procedure with unknown valve durability (TAVR) and that of a more invasive procedure with known durability (SAVR). Standardized differences were calculated, and a difference >0.10 was considered clinically significant. In the base-case analysis, patients with structural valve deterioration requiring reoperation were assumed to undergo a valve-in-valve TAVR procedure. A sensitivity analysis was conducted to determine the impact of TAVR valve durability on life expectancy in younger age groups (40, 50, and 60 years). RESULTS: Our cohort consisted of patients with aortic stenosis at low surgical risk with a mean age of 73.4±5.9 years. In the base-case scenario, the standardized difference in life expectancy was <0.10 between TAVR and SAVR until transcatheter valve prosthesis failure time was 70% shorter than that of surgical prostheses. At a transcatheter valve failure time <30% compared with surgical valves, SAVR was the preferred option. In younger patients, life expectancy was reduced when TAVR durability was 30%, 40%, and 50% shorter than that of surgical valves in 40-, 50-, and 60-year-old patients, respectively. CONCLUSIONS: According to our simulation models, the durability of TAVR valves must be 70% shorter than that of surgical valves to result in reduced life expectancy in patients with demographics similar to those of recent trials. However, in younger patients, this threshold for TAVR valve durability was substantially higher. These findings suggest that durability concerns should not influence the initial treatment decision concerning TAVR versus SAVR in older low-risk patients on the basis of current evidence supporting TAVR valve durability. However, in younger low-risk patients, valve durability must be weighed against other patient factors such as life expectancy.

The emergency department as a setting-specific opportunity for population-based hepatitis C screening: An economic evaluation.

BACKGROUND AND AIMS: The World Health Organization's hepatitis C virus (HCV) elimination strategy recognizes the need for interventions that identify populations most affected by infection. The emergency department (ED) has been suggested as a setting for HCV screening. The study objective was to explore the health and economic impact of HCV screening in the ED setting. METHODS: We used a microsimulation model to conduct a cost-utility analysis evaluating two ED setting-specific strategies: no screening, and screening and subsequent treatment. Strategies were examined for two populations: (a) the general ED patient population; and (b) ED patients born between 1945 and 1975. The analysis was conducted from a healthcare payer perspective over a lifetime time horizon. A reference and high ED HCV seroprevalence measure were examined in the Canadian healthcare setting.US costs of chronic infection were used for a scenario analysis of screening in the US healthcare setting. RESULTS: For birth cohort screening, in comparison to no screening, one liver-related death was averted for every 760 and 123 persons screened for the reference and high seroprevalence measures. For general population screening, one liver-related death was averted for every 831 and 147 persons screened for the reference and high seroprevalence measures. In comparison to no screening, birth cohort screening was cost-effective at CAN$25,584/quality-adjusted life year (QALY) and US$42,615/QALY. General population screening was cost-effective at CAN$19,733/QALY and US$32,187/QALY. CONCLUSIONS: ED screening may represent a cost-effective component of population-based strategies to eliminate HCV. Further studies are warranted to explore the feasibility and acceptability of this approach.

Required efficacy for novel therapies in BCG-unresponsive non-muscle invasive bladder cancer: Do current recommendations really reflect clinically meaningful outcomes?

BACKGROUND: Single-arm trials are currently an accepted study design to investigate the efficacy of novel therapies (NT) in non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin (BCG) immunotherapy as randomized controlled trials are either unfeasible (comparator: early radical cystectomy; ERC), or unethical (comparator: placebo). To guide the design of such single-arm trials, expert groups published recommendations for clinically meaningful outcomes. The aim of this study was to quantitatively verify the appropriateness of these recommendations. METHODS: We used a discrete event simulation framework in combination with a supercomputer to find the required efficacy at which a NT can compete with ERC when it comes to quality-adjusted life expectancy (QALE). In total, 24 different efficacy thresholds (including the recommendations) were investigated. RESULTS: After ascertaining face validity with content experts, repeated verification, external validation, and calibration we considered our model valid. Both recommendations rarely showed an incremental benefit of the NT over ERC. In the most optimistic scenario, an increase in the IBCG recommendation by 10% and an increase in the FDA/AUA recommendation by 5% would yield results at which a NT could compete with ERC from a QALE perspective. CONCLUSIONS: This simulation study demonstrated that the current recommendations regarding clinically meaningful outcomes for single-arm trials evaluating the efficacy of NT in BCG-unresponsive NMIBC may be too low. Based on our quantitative approach, we propose increasing these thresholds to at least 45%-55% at 6 months and 35% at 18-24 months (complete response rates/recurrence-free survival) to promote the development of clinically truly meaningful NT.

Using a Health Economic Framework to Prioritize Quality Indicators: An Example With Smoking Cessation in Chronic Obstructive Pulmonary Disease.

Background. Health care performance monitoring is a major focus of the modern quality movement, resulting in widespread development of quality indicators and making prioritizations an increasing focus. Currently, few prioritization methods of performance measurements give serious consideration to the association of performance with expected health benefits and costs. We demonstrate a proof-of-concept application of using a health economic framework to prioritize quality indicators by expected variations in population health and costs, using smoking cessation in chronic obstructive pulmonary disease (COPD) as an example. Methods. We developed a health state transition, microsimulation model to represent smoking cessation practices for adults with COPD from the health care payer perspective in Ontario, Canada. Variations in life years, quality-adjusted life years (QALYs), and lifetime costs were associated with changes in performance. Incremental net health benefit (INHB) was used to represent the joint variation in mortality, morbidity, and costs associated with the performance of each quality indicator. Results. Using a value threshold of $50,000/QALY, the indicators monitoring assessment of smoking status and smoking cessation interventions were associated with the largest INHBs. Combined performance variations among groups of indicators showed that 81% of the maximum potential INHB could be represented by three out of the six process indicators. Conclusions. A health economic framework can be used to bring dimensions of population health and costs into explicit consideration when prioritizing quality indicators. However, this should not preclude policymakers from considering other dimensions of quality that are not part of this framework.

Staphylococcus-Associated Glomerulonephritis Mimicking Henoch-Schönlein Purpura and Cryoglobulinemic Vasculitis in a Patient With an Epidural Abscess: A Case Report and Brief Review of the Literature.

RATIONALE: Staphylococcus-associated glomerulonephritis (SAGN) is a rare immune complex-mediated glomerulonephritis associated with active Staphylococcus infection. We report a case illustrating the importance of clinical history and kidney biopsy findings in establishing the correct diagnosis. PRESENTING CONCERNS OF THE PATIENT: We report the case of a 64-year-old man with alcohol-associated cirrhosis, type 2 diabetes mellitus, and hypertension who presented to hospital with lower back and abdominal pain, rectal bleeding, a purpuric lower extremity rash, and oliguric acute kidney injury with microscopic hematuria and nephrotic-range proteinuria. DIAGNOSES: Skin biopsy revealed IgA leukocytoclastic vasculitis. Serum cryoglobulins were positive and there was hypocomplementemia with a low C3 level. Magnetic resonance imaging of the lumbar spine revealed septic discitis and epidural abscesses caused by a recent Staphylococcus aureus bacteremia. Kidney biopsy showed IgA-dominant and C3-dominant proliferative glomerulonephritis with subepithelial humps in keeping with SAGN. INTERVENTIONS: Urgent hemodialysis was initiated along with a prolonged course of intravenous cefazolin. OUTCOMES: Remarkably, the patient demonstrated a complete recovery of renal function after 2 months of dialysis dependence and successful treatment of the epidural abscesses. LESSONS LEARNED: This case shows that SAGN can closely mimic the clinical, laboratory, and histological presentation of Henoch-Schönlein Purpura or cryoglobulinemic vasculitis. Clinical history and kidney biopsy, particularly electron microscopic analysis, are essential to establishing the correct diagnosis to avoid the unnecessary and potentially harmful administration of immunosuppression. Despite the typically poor prognosis of SAGN, this case report illustrates that full renal recovery remains possible with supportive care and eradication of the underlying infection.

EXPOSITION: La glomérulonéphrite aigüe post-infection à Staphylococcus (GNAS) est une glomérulonéphrite rare, médiée par un complexe immunitaire et associée à une infection active à Staphylococcus aureus. Nous présentons un cas qui illustre l'importance des antécédents médicaux et des résultats de la biopsie rénale dans la pose d'un diagnostic. PRÉSENTATION DU CAS: Nous rapportons le cas d'un homme de 64 ans atteint d'une cirrhose alcoolique, de diabète de type 2 et d'hypertension qui s'est présenté à l'hôpital avec des douleurs lombaires et abdominales, un saignement rectal, une éruption purpurique des extrémités inférieures et une insuffisance rénale aigüe oligurique avec hématurie microscopique et protéinurie néphrotique. DIAGNOSTIC: La biopsie cutanée a révélé une vascularite leucocytoclastique à IgA. Les cryoglobulines sériques étaient positives et une hypocomplémentémie avec un faible taux de C3 a été constatée. L'imagerie par résonnance magnétique du rachis lombal a permis de détecter une discite septique et des abcès périduraux causés par une récente bactériémie à Staphylococcus aureus. La biopsie rénale a quant à elle montré la présence d'une glomérulonéphrite proliférative à IgA et à C3 dominants et de volumineux dépôts sous-épithéliaux en bosse (humps) conformes à une GNAS. TRAITEMENT: On a amorcé une hémodialyse d'urgence et un traitement prolongé à la céfazoline par voie intraveineuse. RÉSULTATS: Fait remarquable, après le traitement des abcès périduraux et deux mois de dépendance à l'hémodialyse, la fonction rénale du patient a été complètement rétablie. CONCLUSION: Ce cas démontre que la GNAS peut simuler la présentation clinique, biologique et histologique du purpura d'Henoch-Schönlein ou celle de la vascularite cryoglobulinémique. La revue des antécédents médicaux et l'analyse d'une biopsie rénale (particulièrement par microscopie électronique) sont essentielles pour établir un diagnostic juste et pour éviter l'administration superflue, voire néfaste, d'immunosuppresseurs. Malgré le pronostic sombre normalement associé à la GNAS, ce cas démontre que le rétablissement complet de la fonction rénale demeure possible, pour autant que l'on procède à un traitement symptomatique et que l'on éradique l'infection sous-jacente.

Nivolumab in the Treatment of Metastatic Renal Cell Carcinoma: A Cost-Utility Analysis.

INTRODUCTION: Nivolumab improves overall survival and health-related quality of life compared with everolimus in metastatic renal cell carcinoma (mRCC). This study assesses the cost-utility of nivolumab from the Canadian health care payer perspective. MATERIALS AND METHODS: To evaluate the cost-utility of nivolumab, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The incremental cost per quality-adjusted life month (QALM) gained for nivolumab was calculated. A lifetime horizon was used in the base-case with costs and outcomes discounted 3% annually. The probabilities of progression and death from cancer and utility values were captured from the CheckMate-025 trial. Expected costs were based on Ontario fees and other sources. Scenario and sensitivity analyses were conducted to assess uncertainty. RESULTS: Compared with everolimus, nivolumab provided an additional 4.2 QALM at an incremental cost of $34,153. The resulting incremental cost-effectiveness ratio was $8138/QALM gained. Assuming a willingness to pay (WTP) threshold of $4167/QALM ($50,000/quality-adjusted life-year [QALY]), nivolumab was not cost-effective. In 1-way sensitivity analyses, nivolumab cost, median overall survival, and median treatment duration were sensitive to changes. Furthermore, the results were sensitive to the WTP threshold and nivolumab became a cost-effective strategy with a WTP of $8333/QALM ($100,000/QALY). CONCLUSIONS: Compared with everolimus, nivolumab is unlikely to be cost-effective for the treatment of mRCC from a Canadian health care perspective with its current price assuming a WTP of $50,000/QALY. Although mRCC patients derive a meaningful clinical benefit from nivolumab, considerations should be given to avoid drug wastage and increase the WTP threshold to render this strategy more affordable.

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

The Role of Desmopressin in the Management of Severe, Hypovolemic Hyponatremia: A Single-Center, Comparative Analysis.

BACKGROUND: The role of desmopressin (DDAVP) to prevent or treat rapid serum sodium concentration ([Na]s) correction during hyponatremia management remains unclear. OBJECTIVE: To assess DDAVP use during the first 48 hours of severe, hypovolemic hyponatremia management. The primary study hypothesis was that the use of DDAVP would slow the rate of [Na]s correction compared with those not receiving DDAVP. DESIGN: A retrospective, observational, comparison study. SETTING: A single, Canadian, tertiary center. PATIENTS: All admitted patients referred to the nephrology service for severe, hypovolemic hyponatremia ([Na]s < 125 mmol/L) over a 12-month period from November 2015. MEASUREMENTS: The primary outcomes measure was the [Na]s after medical management for 48 hours. The length of hospital stay was also measured. METHODS: Patients were grouped based on whether they received DDAVP during the first 48 hours of treatment, and [Na]s correction was compared between groups using linear regression. An exploratory, multivariable, linear regression model was used to adjust for diabetes status, active malignancy, intensive care unit (ICU) admission, and hypertonic saline administration. RESULTS: Twenty-eight patients were identified, with baseline mean [Na]s of 112.7 ± 6.6 mmol/L versus 117 ± 4.3mmol/L (P = .06) in those receiving (n = 16) and not receiving DDAVP (n = 12), respectively. The DDAVP group had a more rapid [Na]s correction on the first day compared with those not receiving DDAVP, 7.7 ± 3.8 mmol/L/d versus 5.1 ± 2.0 mmol/L/d (P = .04). On the second day, there was a similar rate of [Na]s correction between groups: 1.3 ± 4.3 mmol/L/d versus 2.6 ± 3.2 mmol/L/d (P = .39), respectively. Overall, there was no difference in [Na]s correction after 48 hours between those who received DDAVP and those who did not: 121.7 ± 7.5 mmol/L versus 124.8 ± 5.7 mmol/L (P = .24). Patients who had experienced an overcorrection were successfully treated with DDAVP (n = 5), so that no patient had an ongoing overcorrection by 48 hours. LIMITATIONS: The limited sample size and lack of randomization preclude definitive conclusion on the additional benefit of DDAVP to standard care. CONCLUSION: DDAVP appears to be safe and effective in the management of severe, hypovolemic hyponatremia, associated with similar [Na]s correction to those who did not receive DDAVP after 48 hours, despite an initial more rapid correction. A randomized trial should examine what benefit DDAVP confers in addition to standard care in the management of severe, hypovolemic hyponatremia.

CONTEXTE: Dans le contexte du traitement de l'hyponatrémie, le rôle de la desmopressine (DDAVP) pour prévenir et contrer la correction rapide de la concentration de sodium sérique ([Na] s) demeure nébuleux. OBJECTIF DE L'ÉTUDE: Notre objectif était d'étudier l'effet de l'administration de DDAVP au cours des 48 premières heures du traitement de l'hyponatrémie hypovolémique grave. L'hypothèse principale de l'étude était que l'administration de DDAVP ralentit le rythme de correction de la [Na] s chez les patients traités en comparaison des parents non traités. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude comparative observationnelle, menée de façon rétrospective dans un centre de soins tertiaires canadien. PATIENTS: Ont été inclus tous les patients admis et ayant été dirigés vers l'unité de néphrologie en raison d'une hyponatrémie hypovolémique grave ([Na] s inférieure à 125 mmol/l) sur une période de douze mois à partir de novembre 2015. MESURES: La [Na] s après les 48 premières heures de traitement constituait la mesure principale. On a également noté la durée de l'hospitalisation des patients. MÉTHODOLOGIE: Les patients ont été regroupés selon qu'ils avaient reçu ou non de la DDAVP dans les 48 premières heures de traitement, et la comparaison de la correction de la [Na] s entre les groupes a été analysée par régression linéaire. Un modèle de régression linéaire multivariée et exploratoire a été utilisé pour ajuster les résultats en tenant compte de la présence de diabète, d'une affection maligne active, d'une admission à l'unité des soins intensifs et d'une administration de solution saline hypertonique. RÉSULTATS: Un total de 28 patients a été retenu pour l'étude. La [Na] s initiale moyenne était de 112,7 ± 6,6 mmol/l pour les patients ayant reçu de la DDAVP (n = 16) contre 117 ± 4,3 mmol/l pour les douze patients du groupe non traité (P = 0,06). Dans le groupe traité, la correction de la [Na] s a été plus rapide au cours de la première journée comparativement à celle mesurée chez les patients non traités (7,7 ± 3,8 mmol/l/jour contre 5,1 ± 2,0 mmol/l/jour; P = 0,04). Le taux de correction de la [Na] s s'est avéré similaire dans les deux groupes au cours de la deuxième journée de suivi, avec des valeurs de 1,3 ± 4,3 mmol/l/jour pour le groupe ayant reçu de la DDAVP, et de 2,6 ± 3,2 mmol/l/jour pour le groupe non traité. Dans l'ensemble, aucune différence de correction de la [Na] s n'a été observée entre les deux groupes après 48 heures de suivi. Les valeurs se situaient alors à 121,7 ± 7,5 mmol/l pour les patients ayant reçu de la DDAVP et à 124,8 ± 5,7 mmol/l pour les patients non traités (P = 0,24). Cinq patients ont expérimenté une surcorrection et ont dû être traités à la DDAVP; le traitement a bien fonctionné, de sorte qu'aucun patient ne présentait de surcorrection après 48 heures. LIMITES DE L'ÉTUDE: La taille restreinte de l'échantillon et l'absence de répartition aléatoire des cas nous empêchent de tirer une conclusion définitive quant à l'avantage supplémentaire apporté par l'ajout de la DDAVP aux procédures de soins courantes. CONCLUSION: La DDAVP semble efficace et sécuritaire pour traiter l'hyponatrémie hypovolémique grave. Elle est associée à une correction similaire à celle mesurée après 48 heures chez les patients non traités, quoiqu'elle entraîne une correction initiale de la [Na] s plus rapide. Nous sommes d'avis qu'un essai clinique à répartition aléatoire devrait être mené pour étudier les bienfaits offerts par l'ajout de la DDAVP aux procédures de soins courantes contre l'hyponatrémie hypovolémique grave.

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.

Systematic review and network meta-analysis on the relative efficacy of osteoporotic medications: men with prostate cancer on continuous androgen-deprivation therapy to reduce risk of fragility fractures.

Androgen-deprivation therapy (ADT) is an effective treatment for men with advanced prostate cancer, but loss of bone mineral density (BMD) is a major risk factor for fractures. This review compared the efficacy of available treatments to provide prescribing guidance to healthcare professionals. This is the first review to compare the effectiveness of different osteoporotic treatments (bisphosphonates, denosumab, toremifene, and raloxifene) on BMD in patients with non-metastatic prostate cancer on ADT using network meta-analysis. Results suggest that all evaluated treatments are effective in improving BMD compared to placebo. Zoledronic acid (ZA) was found to have a greater improvement in BMD compared to other active treatments at all three studied sites, except for risedronate, which had better BMD improvement compared to ZA at the femoral neck site in one small study. Our study did not identify evidence that one drug is unequivocally more effective than another. All drugs appeared to be effective in reducing the rate of bone loss. Healthcare professionals should also consider patient preference, costs, and local availability as part of the decision process.