Impact of a Medical Fitness Model on Incident Major Adverse Cardiovascular Events: A Prospective Cohort Study of 11 000 Members.

BACKGROUND: Cardiovascular disease remains the leading cause of disease burden and death in the world. The medical fitness model may be an alternative public health strategy to address cardiovascular risk factors with medical integrated programming. METHODS AND RESULTS: We performed a retrospective cohort study between January 1, 2005, and December 31, 2015. Adults (aged ≥18 years) who did not have a prior major adverse cardiovascular event were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of start dates in the medical fitness facility group. Multivariate Cox proportional hazards regression models were adjusted for age, sex, socioeconomic status, comorbidities, and year of index date. We stratified the medical fitness facility group into low-frequency attenders (≤1 weekly visit) and regular-frequency attenders (>1 weekly visit). Our primary outcome was a hospitalization for nonfatal myocardial infarction and stroke, heart failure, or cardiovascular death. We included 11 319 medical fitness facility members and 507 400 controls in our study. Compared with controls, members had a lower hazard risk of a major adverse cardiovascular event-plus (hazard ratio [HR], 0.88 [95% CI, 0.81-0.96]). Higher weekly attendance was associated with a lower hazard risk of a major adverse cardiovascular event-plus compared with controls, but the effect was not significant for lower weekly attendance (low-frequency attenders: HR, 0.94 [95% CI, 0.85-1.04]; regular-frequency attenders: HR, 0.77 [95% CI, 0.67-0.89]). CONCLUSIONS: Medical fitness facility membership and attendance at least once per week may lower the risk of a major adverse cardiovascular event-plus. The medical fitness model should be considered as a public health intervention, especially for individuals at risk for cardiovascular disease.

Association of serum bicarbonate with the development of kidney stones in patients with chronic kidney disease: a retrospective cohort study.

Background: Epidemiological studies demonstrate an association between kidney stones and risk of chronic kidney disease (CKD) and CKD progression. Metabolic acidosis, as a consequence of CKD, results in a reduced urine pH which promotes the formation of some types of kidney stones and inhibits the formation of others. While metabolic acidosis is a risk factor for CKD progression, the association of serum bicarbonate with risk of incident kidney stones is not well understood. Methods: We used an Integrated Claims-Clinical dataset of US patients to generate a cohort of patients with non-dialysis-dependent CKD with two serum bicarbonate values of 12 to <22 mmol/L (metabolic acidosis) or 22 to <30 mmol/L (normal serum bicarbonate). Primary exposure variables were baseline serum bicarbonate and change in serum bicarbonate over time. Cox proportional hazards models evaluated time to first occurrence of kidney stones during a median 3.2-year follow-up. Results: A total of 142 884 patients qualified for the study cohort. Patients with metabolic acidosis experienced post-index date kidney stones at greater frequency than patients with normal serum bicarbonate at the index date (12.0% vs 9.5%, P < .0001). Both lower baseline serum bicarbonate [hazard ratio (HR) 1.047; 95% confidence interval (CI) 1.036-1.057] and decreasing serum bicarbonate over time (HR 1.034; 95% CI 1.026-1.043) were associated with increased risk of kidney stone development. Conclusions: Metabolic acidosis was associated with a higher incidence of kidney stones and shorter time to incident stone formation in patients with CKD. Future studies may investigate the role of correcting metabolic acidosis to prevent stone formation.

Magnitude of the Potential Screening Gap for Fabry Disease in Manitoba: A Population-Based Retrospective Cohort Study.

Background: Fabry disease is a rare disorder caused by the deficient activity of α-galactosidase A (GLA) that often leads to organ damage. Fabry disease can be treated with enzyme replacement or pharmacological therapy, but due to its rarity and nonspecific manifestations, it often goes undiagnosed. Mass screening for Fabry disease is impractical; however, a targeted screening program for high-risk individuals may uncover previously unknown cases. Objective: Our objective was to use population-level administrative health databases to identify patients at high risk of Fabry disease. Design: Retrospective cohort study. Setting: Population-level health administrative databases housed at the Manitoba Centre for Health Policy. Patients: All residents of Manitoba, Canada, between 1998 and 2018. Measurements: We ascertained the evidence of GLA testing in a cohort of patients at high risk of Fabry disease. Methods: Individuals without a hospitalization or prescription indicative of Fabry disease were included if they had evidence of 1 of 4 high-risk conditions for Fabry disease: (1) ischemic stroke <45 years of age, (2) idiopathic hypertrophic cardiomyopathy, (3) proteinuric chronic kidney disease or kidney failure of unknown cause, or (4) peripheral neuropathy. Patients were excluded if they had known contributing factors to these high-risk conditions. Those who remained and had no prior GLA testing were assigned a 0% to 4.2% probability of having Fabry disease depending on their high-risk condition and sex. Results: After applying exclusion criteria, 1386 individuals were identified as having at least 1 high-risk clinical condition for Fabry disease in Manitoba. There were 416 GLA tests conducted during the study period, and of those, 22 were conducted in individuals with at least 1 high-risk condition. This leaves a screening gap of 1364 individuals with a high-risk clinical condition for Fabry disease in Manitoba who have not been tested. At the end of the study period, 932 of those individuals were still alive and residing in Manitoba, and if screened today, we expect between 3 and 18 would test positive for Fabry disease. Limitations: The algorithms we used to identify our patients have not been validated elsewhere. Diagnoses of Fabry disease, idiopathic hypertrophic cardiomyopathy, and peripheral neuropathy were only available via hospitalizations and not physician claims. We were only able to capture GLA testing processed through public laboratories. Patients identified to be at high risk of Fabry disease by the algorithm did not undergo GLA testing due to a clinical rationale that we were unable to capture. Conclusions: Administrative health databases may be a useful tool to identify patients at higher risk of Fabry disease or other rare conditions. Further directions include designing a program to screen high-risk individuals for Fabry disease as identified by our administrative data algorithms.

Contexte: La maladie de Fabry est un trouble rare causé par une activité déficiente de α-galactosidase A (GLA) qui conduit fréquemment à des dommages aux organes. La maladie de Fabry peut être traitée par remplacement enzymatique ou par traitement pharmacologique, mais elle passe souvent inaperçue en raison de sa rareté et de ses manifestations non spécifiques. Le dépistage de masse de la maladie de Fabry est irréalisable, mais un programme de dépistage ciblé pour les personnes présentant un risque élevé pourrait révéler des cas auparavant inconnus. Objectif: Notre objectif était d'utiliser les bases de données administratives sur la santé des populations pour recenser les patients présentant un risque élevé de maladie de Fabry. Conception: Étude de cohorte rétrospective. Cadre: Les bases de données administratives sur la santé des populations hébergées au Manitoba Centre for Health Policy. Sujets: Tous les résidents du Manitoba (Canada) entre 1998 et 2018. Mesures: Nous avons examiné les preuves d'un dosage de la GLA dans une cohorte de patients présentant un risque élevé de maladie de Fabry. Méthodologie: Les individus sans hospitalisation ou ordonnance indicative de la maladie de Fabry ont été inclus s'ils présentaient une des quatre affections suivantes, jugées à haut risque pour la maladie de Fabry: 1) accident vasculaire cérébral ischémique avant 45 ans; 2) cardiomyopathie hypertrophique idiopathique; 3) insuffisance rénale chronique protéinurique ou insuffisance rénale de cause inconnue; 4) neuropathie périphérique. Les patients ont été exclus s'ils présentaient des facteurs de contribution connus à ces maladies à haut risque. Les personnes restantes qui n'avaient pas de preuves d'un dosage antérieur de la GLA ont reçu une probabilité de 0 à 4,2 % d'avoir la maladie de Fabry, selon leur maladie à risque élevé et leur sexe. Résultats: Après l'application des critères d'exclusion, 1 386 personnes ont été identifiées au Manitoba comme ayant au moins une affection clinique présentant un risque élevé pour la maladie de Fabry. Pendant la période de l'étude, 416 dosages de GLA ont été effectués, dont 22 chez des individus présentant au moins une affection à risque élevé; soit un déficit de dépistage pour 1 364 Manitobains présentant un risque élevé de maladie de Fabry à qui aucun dosage n'avait été fait. À la fin de la période de l'étude, 932 de ces personnes étaient encore vivantes et résidaient toujours au Manitoba. Si ces individus étaient dépistés aujourd'hui, on pourrait s'attendre à obtenir entre 3 et 18 dosages positifs pour la maladie de Fabry. Limites: Les algorithmes que nous avons utilisés pour identifier nos sujets n'avaient pas été validés ailleurs. Les diagnostics de maladie de Fabry, de cardiomyopathie hypertrophique idiopathique et de neuropathie périphérique n'étaient disponibles que par une hospitalisation et non par demande d'un médecin. Seuls les dosages de la GLA effectués par des laboratoires publics ont pu être saisis. Les patients répertoriés par l'algorithme comme présentant un risque élevé de maladie de Fabry n'avaient pas subi de dosage de la GLA en raison d'une justification clinique qu'il nous a été impossible de saisir. Conclusion: Les bases de données administratives sur la santé peuvent s'avérer un bon outil pour recenser les patients présentant un risque plus élevé de développer la maladie de Fabry ou d'autres maladies rares. Les orientations futures comprennent la conception d'un programme de dépistage des individus présentant un risque élevé pour la maladie de Fabry, tels que recensés par nos algorithmes de données administratives.

Metabolic acidosis is undertreated and underdiagnosed: a retrospective cohort study.

BACKGROUND: Guidelines recommend treatment of metabolic acidosis (MA) in patients with chronic kidney disease (CKD), but the diagnosis and treatment rates in real-world settings are unknown. We investigated the frequency of MA treatment and diagnosis in patients with CKD. METHODS: In this retrospective cohort study, we examined administrative health data from two US databases [Optum's de-identified Integrated Claims + Clinical Electronic Health Record Database (US EMR cohort; 1 January 2007 to 30 June 2019) and Symphony Health Solutions IDV® (US claims cohort; 1 May 2016 to 30 April 2019)] and population-level databases from Manitoba, Canada (1 April 2006 to 31 March 2018). Patients who met laboratory criteria indicative of CKD and chronic MA were included: two consecutive estimated glomerular filtration results <60 mL/min/1.73 m2 and two serum bicarbonate results 12 to <22 mEq/L over 28-365 days. Outcomes included treatment of MA (defined as a prescription for oral sodium bicarbonate) and a diagnosis of MA (defined using administrative records). Outcomes were assessed over a 3-year period (1 year pre-index, 2 years post-index). RESULTS: A total of 96 184 patients were included: US EMR, 6179; Manitoba, 3223; US Claims, 86 782. Sodium bicarbonate treatment was prescribed for 17.6%, 8.7% and 15.3% of patients, and a diagnosis was found for 44.7%, 20.9% and 20.9% of patients, for the US EMR, Manitoba and US Claims cohorts, respectively. CONCLUSIONS: This analysis of 96 184 patients with laboratory-confirmed MA from three independent cohorts of patients with CKD and MA highlights an important diagnosis and treatment gap for this disease-modifying complication.

Metabolic Acidosis is Associated With Acute Kidney Injury in Patients With CKD.

Introduction: Metabolic acidosis in patients with chronic kidney disease (CKD) results from a loss of kidney function. It has been associated with CKD progression, all-cause mortality, and other adverse outcomes. We aimed to determine whether metabolic acidosis is associated with a higher risk of acute kidney injury (AKI). Methods: This was a retrospective cohort study. Using electronic health records and administrative data, we enrolled 2 North American cohorts of patients with CKD Stages G3-G5 as follows: (i) 136,067 patients in the US electronic medical record (EMR) based cohort; and (ii) 34,957 patients in the Manitoba claims-based cohort. The primary exposure was metabolic acidosis (serum bicarbonate between 12 mEq/l and <22 mEq/l). The primary outcome was the development of AKI (defined using ICD-9 and 10 codes at hospital admission or a laboratory-based definition based on Kidney Disease: Improving Global Outcomes guidelines). We applied Cox proportional hazards regression models adjusting for relevant demographic and clinical characteristics. Results: In both cohorts, metabolic acidosis was associated with AKI: hazard ratio (HR) 1.57 (95% confidence interval [CI] 1.52-1.61) in the US EMR cohort, and HR 1.65 (95% CI 1.58-1.73) in the Manitoba claims cohort. The association was consistent when serum bicarbonate was treated as a continuous variable, and in multiple subgroups, and sensitivity analyses including those adjusting for albuminuria. Conclusion: Metabolic acidosis is associated with a higher risk of AKI in patients with CKD. AKI should be considered as an outcome in studies of treatments for patients with metabolic acidosis.

Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study.

INTRODUCTION: Metformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D. RESEARCH DESIGN AND METHODS: This retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs. RESULTS: Our cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus 'other'). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an 'other' OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs. CONCLUSIONS: Sulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with 'other' OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control.

Percutaneous Versus Surgical Insertion of Peritoneal Dialysis Catheters: A Systematic Review and Meta-Analysis.

BACKGROUND: Home-based peritoneal dialysis (PD) is an alternative to facility-based hemodialysis and has lower costs and greater freedom for patients with kidney failure. For a patient to undergo PD, a safe and reliable method of accessing the peritoneum is needed. However, different catheter insertion techniques may affect patient health outcomes. OBJECTIVE: To compare the risk of infectious and mechanical complications between surgical (open and laparoscopic) PD catheter insertion and percutaneous catheter insertion. DESIGN: Systematic review and meta-analysis. SETTING: We searched for observational studies and randomized controlled trials (RCTs) in CENTRAL, EMBASE, MEDLINE, PubMed, and SCOPUS from inception until June 2018. Data were extracted by 2 independent reviewers based on a preformed template. PATIENTS: Adult (aged 18+) patients with kidney failure who underwent a PD catheter insertion procedure. MEASUREMENTS: We analyzed leak, malfunction, and bleed as early complications (occurring within 1 month of catheter insertion). Infectious complications (exit-site infections, tunnel infections, and peritonitis) were presented as both early complications and with the longest duration of follow-up. METHODS: Random effects meta-analyses with the generic inverse variance method to estimate pooled rate ratios and 95% confidence intervals. We quantified heterogeneity by using the I2 statistic for inconsistency and assessed heterogeneity using the χ2 test. Sensitivity analysis was performed by removing studies at high risk of bias as measured with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. RESULTS: Twenty-four studies (22 observational, 2 RCTs) with 3108 patients and 3777 catheter insertions were selected. Data from 2 studies were unable to be extracted and were qualitatively assessed. In the remaining 22 studies, percutaneous insertion was associated with a lower risk of both exit-site infections (risk ratio [RR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, I2 = 0%) and peritonitis (RR = 0.52, 95% CI = 0.36-0.77, I2 = 3%) within 1 month of the procedure. There was no difference in mechanical complication rates between the 2 techniques. LIMITATIONS: Lack of consistency in the time periods for the various outcomes reported, risk of bias concerns with respect to population comparability, and the inability to analyze individual component causes of primary nonfunction (catheter obstruction, catheter migration, and leak). CONCLUSIONS: Our meta-analysis suggests differences in early infectious complications in favor of percutaneous insertion and no significant differences in mechanical complications compared with surgical insertion. These findings have implications on the direction of PD programs in terms of maximizing operating room resources.

CONTEXTE: La dialyse péritonéale à domicile (DPD) est une alternative plus économique à l'hémodialyse en centre et offre une plus grande liberté aux patients atteints d'insuffisance rénale. Or, pour qu'un patient soit traité par DPD, il est essentiel de recourir à une méthode d'accès au péritoine qui soit fiable et sûre. Les techniques existantes pour l'insertion du cathéter sont toutefois susceptibles d'affecter les résultats de santé du patient. OBJECTIFS: Comparer le risque de complications mécaniques et infectieuses entre l'insertion chirurgicale (incision et laparoscopie) et percutanée d'un cathéter de DP. TYPE D'ÉTUDE: Revue systématique et méta-analyse. CADRE: Nous avons consulté les bases de données CENTRAL, EMBASE, MEDLINE, PubMed et SCOPUS à la recherche d'études observationnelles et d'essais contrôlés à répartition aléatoire (ECRA) de la création à juin 2018. Deux réviseurs indépendants ont procédé à l'extraction des données en suivant un modèle préformé. SUJETS: Des adultes atteints d'insuffisance rénale ayant subi une procédure d'insertion d'un cathéter de DP. MESURES: Nous avons analysé les fuites, le dysfonctionnement et les saignements comme des complications précoces (survenant dans le mois suivant l'insertion du cathéter). Les complications infectieuses (infections au point de sortie, infections des tunnels, péritonite) ont été présentées comme complications précoces et avec la plus longue durée de suivi. MÉTHODOLOGIE: Nous avons procédé à des méta-analyses selon la méthode générique de l'inverse de la variance avec effets aléatoires pour estimer les rapports des taux combinés et les intervalles de confiance à 95 %. L'hétérogénéité a été quantifiée en utilisant la statistique I2 pour l'incohérence et a été évaluée par le test du Chi-Deux. L'analyse de sensibilité a été réalisée en retirant les études présentant un risque élevé de biais, lesquelles ont été définies à l'aide de l'échelle Newcastle-Ottawa et de l'outil Cochrane sur le risque de biais. RÉSULTATS: En tout, 24 études (22 études observationnelles, 2 ECRA) ont été sélectionnées, ce qui représente 3 108 patients et 3 777 insertions de cathéters. Les données de deux études n'ont pu être extraites et ont été évaluées qualitativement. Dans les 22 autres études, l'insertion percutanée a été associée, dans le mois suivant la procédure, à un risque plus faible d'infections au site de sortie (RR = 0,36; IC à 95 %: 0,24-0,53; I2 = 0 %) et de péritonite (RR = 0,52; IC à 95 %: 0,36-0,77; I2 = 3 %). Aucune différence dans les taux de complications mécaniques n'a été observée entre les deux techniques. LIMITES: Les résultats sont limités par le manque de cohérence dans les périodes associées aux divers résultats signalés, le risque de biais quant à la comparabilité des populations et l'incapacité d'analyser les causes individuelles du non-fonctionnement primaire (obstruction du cathéter, migration du cathéter, fuite). CONCLUSION: Notre méta-analyse suggère des différences en faveur de l'insertion percutanée par rapport à l'insertion chirurgicale pour les complications infectieuses précoces, mais aucune différence significative en ce qui concerne les complications mécaniques. Ces résultats ont des implications sur l'orientation des programmes de DP relativement à l'optimisation des ressources du bloc opératoire.

Association of Membership at a Medical Fitness Facility With Adverse Health Outcomes.

INTRODUCTION: Interventions that increase physical activity behavior can reduce morbidity and prolong life, but long-term effects in large populations are unproven. This study investigates the association of medical fitness facility membership and frequency of attendance with all-cause mortality and rate of hospitalization. METHODS: A propensity weighted retrospective cohort study was conducted by linking individuals who attended medical fitness facilities in Winnipeg, Canada to provincial health administrative databases. Members aged ≥18 years who had ≥1 year of provincial health coverage from their index date between January 1, 2005 and December 31, 2015 were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of index dates in the intervention group. Members were stratified into low-frequency attenders (<1 weekly visit), moderate-frequency attenders (1-3 weekly visits), and high-frequency attenders (>3 weekly visits). The primary outcomes were time to all-cause mortality and rate of hospitalizations. Statistical analyses were performed between 2018 and 2020. RESULTS: Among 19,300 adult members and 515,810 controls, members had a 60% lower risk of all-cause mortality during the first 651 days and 48% after 651 days. Membership was associated with a 13% lower risk of hospitalizations. A dose-response effect was apparent because higher weekly attendance was associated with a lower risk of hospitalizations (low frequency: 9%, moderate frequency: 20%, high frequency: 39%). CONCLUSIONS: Membership at a medical fitness facility was associated with a reduced risk of all-cause mortality and hospitalizations. Healthcare systems should consider the medical fitness model as a preventative public health strategy to encourage physical activity participation.

Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKD.

BACKGROUND AND OBJECTIVES: Frailty is common in patients with CKD. Little is known about the prevalence of frailty and its effect on prognosis and decisions surrounding dialysis modalities in patients with advanced CKD (eGFR<30 ml/min per 1.73 m2). Our objective was to determine the agreement between different frailty measures and physical function and their association with dialysis modality choice (home based versus in-center) and all-cause mortality in patients with advanced CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a prospective, multicenter, cohort study. In 603 patients with advanced CKD, we collected demographics, comorbidities, and laboratory results in addition to objective (Fried frailty criteria) and subjective measures of frailty (physician and nurse impressions) and physical function (Short Physical Performance Battery). Logistic regression and Cox proportional hazards models were used to evaluate the association of frailty with dialysis modality choice and all-cause mortality, respectively. RESULTS: The prevalence of frailty varied with assessment tool used (Fried frailty criteria, 34%; Short Physical Performance Battery, 55%; physician impression, 44%; nurse impression, 36%). The agreement between all frailty and physical function measures was poor. We had 227 patients reach kidney failure and decide on a dialysis therapy, and 226 patients died during a mean follow-up of 1455 days. After adjusting for age, sex, and comorbid conditions, the Fried criteria and Short Physical Performance Battery were associated with a two-fold higher risk of all-cause mortality (hazard ratio, 1.96; 95% confidence interval, 1.47 to 2.61 and hazard ratio, 1.96; 95% confidence interval,1.42 to 2.76, respectively). Patients deemed as frail by physician and nurse frailty impressions were three to four times more likely to choose in-center dialysis (odds ratio, 3.41; 95% confidence interval, 1.56 to 7.44; odds ratio, 3.87; 95% confidence interval, 1.76 to 8.51, respectively). CONCLUSIONS: We found that the agreement between objective and subjective measures of frailty and physical function was poor. Objective measures of frailty and physical function were associated with mortality, and subjective measures of frailty were associated with dialysis modality choice.

Cost-Utility of Dialysis in Canada: Hemodialysis, Peritoneal Dialysis, and Nondialysis Treatment of Kidney Failure.

RATIONALE & OBJECTIVE: The kidney failure population is growing, necessitating the expansion of dialysis programs. These programs are costly and require a substantial amount of health care resources. Tools that accurately forecast resource use can aid efficient allocation. The objective of this study is to describe the development of an economic simulation model that incorporates treatment history and detailed modality transitions for patients with kidney disease using real-world data to estimate associated costs, utility, and survival by initiating modality. STUDY DESIGN: Cost-utility model with microsimulation. SETTING & POPULATION: Adult incident maintenance dialysis patients in Canada who initiated facility-based hemodialysis (HD) or home peritoneal dialysis (PD) between 2004 and 2013. INTERVENTION: HD and PD. OUTCOMES: Costs (related to dialysis, transplantation, infections, and hospitalizations), survival, utility, and dialysis modality mix over time. MODEL PERSPECTIVE & TIMEFRAME: The model took the perspective of the health care payer. Patients were followed up for 10 years from initiation of dialysis. Our cost-utility analysis compared the intervention with receiving no treatment. RESULTS: During a 10-year time horizon, the cost-utility ratio for all patients initiating dialysis was $103,779 per quality-adjusted life-year (QALY) in comparison to no treatment. Patients who initiated with facility-based HD were treated at a cost-utility ratio of $104,880/QALY and patients who initiated with home PD were treated at a cost-utility ratio of $83,762/QALY. During this time horizon, the total mean cost and QALYs per patient were estimated at $350,774 ± $204,704 and 3.38 ± 2.05) QALYs respectively. LIMITATIONS: The results do not include costs from the societal perspective. Rare patient trajectories were unable to be assessed. CONCLUSIONS: This model demonstrates that patients who initiated dialysis with PD were treated more cost-effectively than those who initiated with HD during a 10-year time horizon.

A Cost-Minimization Analysis of Nurse-Led Virtual Case Management in Late-Stage CKD.

INTRODUCTION: Interventions are needed to improve early detection of indications for dialysis before development of severe symptoms or complications. This may reduce suboptimal dialysis starts, prevent hospitalizations, and decrease costs. Our objectives were to explore assumptions around a nurse-led virtual case management intervention for patients with late-stage chronic kidney disease (CKD) with a 2-year Kidney Failure Risk Equation (KFRE) estimated risk of kidney failure ≥80% and to estimate how these assumptions affect potential cost savings. METHODS: We performed a cost-minimization analysis by developing a decision analytic microsimulation model constructed from the perspective of the health payer. Our primary outcome was the break-even point, defined as the maximum amount a health payer could spend on the intervention without incurring any net financial loss or gain. The intervention group received remote telemonitoring, including daily measurement of several health metrics (blood pressure, oxygen saturation, and weight), and a validated symptom questionnaire accompanied by nurse-led case management, whereas the comparator group received usual care. We assumed patients received the intervention for a maximum of 2 years. RESULTS: The break-even point was $7339 per late-stage CKD patient enrolled in the intervention. Based on the distribution of time receiving the intervention, we determined a maximum monthly intervention cost of $703.37. In probabilistic sensitivity analyses, we found that 75% of simulations produced break-even points between $3929 and $9460. CONCLUSION: Nurse-led virtual home monitoring interventions in patients with CKD at high risk of kidney failure have the potential for significant cost savings from the perspective of the health payer.

Acute Kidney Injury Events in Patients With Type 2 Diabetes Using SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk for acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared with all other glucose-lowering drugs (oGLDs), is associated with increased rates of AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba, Canada, with type 2 diabetes mellitus followed up from June 2014 until March 2017. EXPOSURES: Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. OUTCOME: The primary outcome was incident AKI, identified either by an increase in serum creatinine level and/or hospital discharge codes for AKI while taking glucose-lowering drugs (on-treatment approach). ANALYTICAL APPROACH: A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of oGLD users. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug treatment (intention-to-treat approach) or incorporated recurrent exposures (new user design). RESULTS: Comparing 4,778 incident users of SGLT2 inhibitors with 4,778 incident users of oGLDs, there were no differences observed in the primary outcome (HR, 0.64; 95% CI, 0.40-1.03; P = 0.06) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with increased risk for AKI. LIMITATIONS: Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the US Food and Drug Administration warning. There were insufficient data to compare individual SGLT2 inhibitors. CONCLUSIONS: Compared with oGLDs, SGLT2 inhibitors were not observed to be associated with increased risk for AKI in a clinical population-based cohort.

A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study.

OBJECTIVE: To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage. PATIENTS AND METHODS: This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m2. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome. RESULTS: The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes. CONCLUSION: Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.

The Fracture Risk Assessment Tool (FRAX®) predicts fracture risk in patients with chronic kidney disease.

The Fracture Risk Assessment Tool (FRAX®) was developed to predict fracture risk in the general population, but its applicability to patients with chronic kidney disease (CKD) is unknown. Using the Manitoba Bone Mineral Density (BMD) Database, we identified adults not receiving dialysis with available serum creatinine measurements and bone densitometry within 1 year. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident major osteoporotic fractures and hip fractures were ascertained from population-based health care databases. The performance of FRAX, derived without and with BMD, was studied in relation to CKD stage. Among 10,099 subjects (mean age 64 ± 13 years, 13.0% male), 2,154 had eGFR 30-60 mL/min/1.73 m2 (CKD stage 3) and 590 had eGFR <30 mL/min/1.73 m2 (CKD stages 4-5). During a 5-year observation period, 772 individuals experienced a major osteoporotic fracture and 226 had a hip fracture. FRAX predicted risk for major osteoporotic fracture and hip fracture in all eGFR strata. For every standard deviation increase in FRAX score derived with BMD, the hazard ratio (HR) for hip fracture was 4.54 (95% confidence interval [CI] 3.57-5.77) in individuals with eGFR ≥ 60 mL/min/1.73m2, 4.52 (95% CI 3.15-6.49) in individuals with eGFR 30-60 mL/min/1.73m2, and 3.10 (95% CI 1.80-5.33) in individuals with eGFR <30 mL/min/1.73m2. The relationship between FRAX and major osteoporotic fracture was stronger in those with CKD compared to those with preserved eGFR. These findings support the use of FRAX to risk stratify patients with non-dialysis CKD for major osteoporotic fractures and hip fractures.

Long term health outcomes in patients with a history of myocardial infarction: A population based cohort study.

BACKGROUND: Myocardial infarction (MI) is associated with high morbidity and mortality, particularly in the first 12 months post-event. Interventions such as dual antiplatelet therapy can reduce the risk of major adverse cardiovascular events (MACE), but the duration of the high-risk time interval and the optimal prescription time frame for these interventions remains unknown. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We performed a retrospective cohort study using data from medical services and hospitalizations in Manitoba, Canada for patients admitted with a MI between April 2006 and March 2010, and followed until Nov 30, 2014. We used survival analysis to determine the cumulative incidence of death, subsequent MI, or stroke, and used Cox proportional hazards models to assess factors associated with these endpoints. RESULTS: There were 8,493 patients in Manitoba admitted to hospital for a MI during the study period. Of those, 6,749 (79.5%) survived for at least 1 year without a recurrent MI or stroke. In the following year, this population remained at high risk, with 372 (5.5%) of the remaining patients dying in the next twelve months (48.1% cardiovascular deaths), 244 (3.6%) having a recurrent MI, and 74 (1.1%) having a stroke. Older age, male sex, diabetes, prior stroke, prior heart failure, prior unstable angina, and absence of revascularization were associated with worse long-term prognosis. CONCLUSIONS: The risk of MACE remains elevated among post-MI patients after the first year. Interventions to more intensively monitor, evaluate, and treat these patients should be considered beyond the first year following myocardial infarction.

Validation of the Kidney Failure Risk Equation in Manitoba.

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk to progress to kidney failure. We previously developed the Kidney Failure Risk Equation (KFRE) to predict progression to kidney failure in patients referred to nephrologists. OBJECTIVE: The objective of this study was to determine the ability of the KFRE to discriminate which patients will progress to kidney failure in an unreferred population. DESIGN: A retrospective cohort study was conducted using administrative databases. SETTING: This study took place in Manitoba, Canada. MEASUREMENTS: Age, sex, estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (ACR) were measured. METHODS: We included patients from the Diagnostic Services of Manitoba database with an eGFR <60 mL/min/1.73 m2 and ACR measured between October 2006 and March 2007. Five-year kidney failure risk was predicted using the 4-variable KFRE and compared with treated kidney failure events from the Manitoba Renal Program database. Sensitivity and specificity for KFRE risk thresholds (3% and 10% over 5 years) were compared with eGFR thresholds (30 and 45 mL/min/1.73 m2). RESULTS: Of 1512 included patients, 151 developed kidney failure over the 5-year follow-up period. The 4-variable KFRE showed a superior prognostic discrimination compared with eGFR alone (area under the receiver operating characteristic curve [AUROC] values, 0.90 [95% confidence interval {CI}: 0.88-0.92] for KFRE vs 0.78 [95% CI: 0.74-0.83] for eGFR). At a 3% threshold over 5 years, the KFRE had a sensitivity of 97% and a specificity of 62%. At 10% risk, sensitivity was 86%, and specificity was 80%. LIMITATIONS: Only 11.7% of stage 3-5 CKD patients had simultaneous ACR measurement. The KFRE does not account for other indications for referral such as suspected glomerulonephritis, polycystic kidney disease, and recurrent stone disease. CONCLUSIONS: The KFRE has been validated in a population with a demographic and referral profile heretofore untested and performs well at predicting 5-year risk of kidney failure in a population-based sample of Manitobans with CKD stages 3 to 5. Thresholds of 3% and 10% over 5 years are sensitive, specific, and can be used in clinical decision making. Further testing of the 4-variable KFRE and these thresholds in clinical practice should be considered.

MISE EN CONTEXTE: Les patients atteints de maladies rénales chroniques courent le risque de voir leur état évoluer vers l'insuffisance rénale. Au cours d'études précédentes, nous avons développé une équation permettant de prédire le risque d'évolution vers l'insuffisance rénale, la Kidney Failure Risk Equation (KFRE), chez les patients référés pour un suivi par un néphrologue. OBJECTIF DE L'ÉTUDE: L'étude visait à évaluer la capacité de la KFRE à cerner les patients à risque de développer de l'insuffisance rénale dans une population de patients non référés à un néphrologue. MODÈLE DE L'ÉTUDE: Une étude de cohorte rétrospective qui a été menée à l'aide de bases de données administratives. CADRE DE L'ÉTUDE: Cette étude a été menée dans la province du Manitoba, au Canada. MESURES: L'âge et le sexe des participants, de même qu'une mesure du débit de filtration glomérulaire estimé (DFGe) et du ratio albumine/créatine (RAC) ont été colligés. MÉTHODOLOGIE: Nous avons inclus les patients inscrits dans la base de données de Services diagnostiques Manitoba qui présentaient un DFGe <60 mL/min/1,73 m2 et une mesure du RAC entre octobre 2006 et mars 2007. Le risque de défaillance rénale à l'intérieur de cinq ans a été prédit à l'aide de la KFRE à quatre variables et comparé aux événements de défaillance rénale répertoriés dans la base de données du programme de santé rénale du Manitoba. La sensibilité et la spécificité des seuils de risque calculés par la KFRE (3% et 10% sur 5 ans) ont été comparées à celles des seuils établis par le DFGe (30 à 45 mL/min/1,73 m2). RÉSULTATS: Des 1512 patients inclus dans l'étude, 151 ont vu leur état évoluer vers l'insuffisance rénale au cours de la période de suivi de 5 ans. Les valeurs de risque calculées avec la KFRE à 4 variables ont montré une discrimination pronostique supérieure par rapport à la capacité de pronostic du DFGe seul (AUROCs 0,90 [IC à 95: 0,88-0,92] pour la KFRE contre 0,78 [IC à 95: 0,74-0,83] pour le DFGe). À un seuil de 3% sur 5 ans, la KFRE avait une sensibilité de 97% et une spécificité de 62%. Au risque de 10%, la sensibilité se situait à 86% et la spécificité à 80%. LIMITES DE L'ÉTUDE: Seulement 11,7% des patients atteints d'insuffisance rénale de stade 3 à 5 présentaient une mesure simultanée du RAC. La KFRE ne tient pas compte des autres indications pour lesquelles des patients sont dirigés en néphrologie tels qu'une glomérulonéphrite suspectée, une polykystose rénale ou des épisodes récurrents de pierres aux reins. CONCLUSIONS: La KFRE a été validée dans une population possédant un profil démographique et de référence non testé jusqu'alors. Cette équation est parvenue à prédire de façon plus que satisfaisante le risque de développer de l'insuffisance rénale dans une période de cinq ans chez un échantillon de patients manitobains en insuffisance rénale chronique de stade 3 à 5. Les seuils de 3% et de 10% sur 5 ans de la KFRE sont suffisamment sensibles et spécifiques, ils peuvent donc être considérés dans la prise de décisions cliniques. Des essais supplémentaires utilisant la KFRE à 4 variables et les seuils de 3% et de 10% sur 5 ans devraient être envisagés en pratique clinique.

A before and after cross-sectional analysis of a public health campaign to increase kidney health awareness in a Canadian province.

BACKGROUND: Chronic kidney disease (CKD) has a major impact on patient health and health system resources. The prevalence of kidney disease is increasing, with Manitoba being one of the provinces in Canada with the highest per capita rate of CKD and end stage renal disease (Anonymous, Canadian organ replacement register annual report: treatment of end-stage organ failure in Canada, 2001-2010, 2011). In 2011, a public health campaign to promote kidney health, by increasing awareness of CKD and its risk factors, was created to target high-risk individuals such as First Nations and those with hypertension and diabetes in urban and rural/remote Manitoba. In this study, we aimed to determine the effectiveness of this public health campaign on increasing the awareness of CKD. METHODS: Our public health campaign ran in March 2011, and employed a multifaceted approach with radio, television, internet, and print advertisements. Campaign awareness and understanding of the public health message were assessed with a telephone omnibus survey of randomly selected individuals with a Manitoba area code during February and April 2011. A before and after cross-sectional analysis was utilized to measure the effect of exposure to the campaign in telephone respondents. RESULTS: 1606 individuals participated in the survey (804 pre and 802 post). Overall awareness of the campaign messaging increased from 7% pre campaign to 25% in the post campaign period. Approximately two-thirds of respondents correctly identified a main theme message of the campaign. Awareness improved across most subgroups surveyed aside from those with lower education and income. CONCLUSIONS: Our study demonstrates the effective reach of our campaign and its relative effectiveness at raising awareness of chronic kidney disease and its risk factors.