Efficacy of a yeast postbiotic on cold/flu symptoms in healthy children: A randomized-controlled trial.

BACKGROUND: Children attending school/daycare are at high risk of acute respiratory tract infections. EpiCorTM postbiotic, derived from yeast fermentate, has been demonstrated to improve immune function in adults, reducing the incidence of cold/flu-like or allergy symptoms. As such, studies are warranted in children as available pharmaceutical options have unwanted side effects. METHODS: Two-hundred and fifty-six children aged 4-12 years attending school/daycare were randomized to either EpiCor or Placebo for 84 days during the 2022-2023 flu season in Ontario, Canada. The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) and study diary assessed the incidence and severity of cold/flu symptoms and the use of cold/flu medications. Adverse events were recorded. RESULTS: Total CARIFS severity scores, 'sore throat' and 'muscle aches or pains' symptom scores in the EpiCor group were significantly lower compared to Placebo during incidences of cold/flu (P ≤ 0.05). Participants taking Placebo were 1.73 times more likely to use cold/flu medication compared to those receiving EpiCor (P = 0.04). The incidence of cold/flu symptoms was not significantly different between groups. EpiCor was found to be safe and well-tolerated. CONCLUSIONS: EpiCor supplementation resulted in significantly lower cold/flu symptom severity and less cold/flu medication usage than Placebo demonstrating a beneficial effect on immune function in children. IMPACT: Children are at high risk of acquiring cold/flu infections and safe and efficacious mitigating regimens are lacking. Children supplemented daily with 500 mg EpiCorTM postbiotic derived from yeast fermentate had significantly lower overall cold/flu symptom severity, and severity of sore throat and muscle aches or pains over the 84-day supplementation period. EpiCor supplementation resulted in decreased use of traditional cold/flu medication. Daily supplementation with 500 mg of EpiCor for 84 days was safe and well tolerated by healthy children aged 4-12 years attending school or daycare.

Reducing the Frequency of Surveillance Blood Work in Patients Treated With Maintenance Hemodialysis: A Local Quality Improvement Initiative.

Introduction: There is little evidence on the ideal frequency of routine blood work in maintenance dialysis patients to manage complications, including anemia, mineral bone disease (MBD), and hyperkalemia. Recent quality improvement studies from Ontario showed no negative impacts when decreasing the frequency from monthly to every 6 weeks in conventional in-center hemodialysis (ICHD) patients. In December 2020, Alberta Kidney Care-South (AKC-S) reduced the frequency of routine blood work from every 6 weeks to every 8 weeks for ICHD patients. Objective: We aimed to assess the impact of reducing blood work frequency on patient outcomes. Methods: We compared prevalent AKC-S ICHD patients in 2 cohorts: (1) retrospective control (October 31, 2019-October 31, 2020) and (2) prospective intervention (December 1, 2020-December 1, 2021). Primary outcomes were true frequency of routine blood work, odds of patients being within target for anemia and MBD, and proportion of lab values of hyperkalemia. Furthermore, we compared hospitalizations and mortality. Results: A total of 972 patients in Calgary's ICHD program were included, 787 in each period (with 602 patients overlapping both cohorts). The frequency of routine blood work decreased from every 39.5 days in the control period to every 54.2 days in the intervention period (P < .01). There was a reduction in the odds of phosphate values in targets (P = .02), and an increase in the odds of labs with hyperkalemia (>6.0 mmol/L) during the intervention period (P = .01). There was no significant change in the odds of being within the accepted targets during the intervention period compared with the control period for hemoglobin, Tsat, calcium, or parathyroid hormone (PTH). Fewer patients were hospitalized during the intervention period and the risk of death decreased as well, although additional factors such as the COVID-19 pandemic may have affected this. A cost-savings of $32 962 occurred from the reduced anemia and MBD blood work during the intervention period. Conclusions: When ICHD units in Calgary reduced routine blood work frequency from every 6 weeks to 8 weeks, there were no negative impacts on hospitalizations or deaths. A slightly lower proportion of phosphate values were within target, and a 0.7% increase in potassium values greater than 6 mmol/L was demonstrated. Our study suggests that blood work frequency in ICHD dialysis patients may be further reduced to every 8 weeks safely. Ultimately, additional pragmatic trials are needed to identify the optimal frequency of routine blood work.

Introduction: Il existe peu de données quant à la fréquence idéale des analyses sanguines chez les patients sous dialyse d'entretien pour gérer les complications comme l'anémie, les troubles liés à la densité osseuse (TDO) et l'hyperkaliémie. De récentes études d'amélioration de la qualité menées en Ontario n'ont montré aucune conséquence négative lorsque la fréquence des analyses des patients traités de façon traditionnelle par hémodialyse en centre (HDC) est passée d'une fois par mois à une fois toutes les 6 semaines. L'Alberta Kidney Care-South (AKC-S) a réduit la fréquence des analyses sanguines de routine; depuis décembre 2020, les analyses des patients traités par HDC sont effectuées toutes les 8 semaines plutôt qu'aux 6 semaines. Objectif: Évaluer les effets d'une réduction de la fréquence des analyses sanguines sur les résultats des patients. Méthodologie: Nous avons comparé des patients de l'AKC-S prévalents pour l'HDC dans deux cohortes: a) période témoin ­ rétrospective (31 octobre 2019 au 31 octobre 2020); b) période d'intervention ­ prospective (1er décembre 2020 au 1er décembre 2021). Les principaux critères d'évaluation étaient la fréquence réelle des analyses sanguines de routine, la probabilité que les patients soient dans la cible pour l'anémie et les TDO, et dans la fourchette cible des valeurs de laboratoire pour l'hyperkaliémie. Les hospitalisations et la mortalité ont également été comparées entre les deux cohortes. Résultats: Au total, 972 patients du programme d'HDC de Calgary ont été inclus, soit deux cohortes de 787 patients (602 patients ont chevauché les deux cohortes). Les analyses sanguines étaient effectuées tous les 39,5 jours pendant la période témoin; cette fréquence est passée aux 54,2 jours pendant la période d'intervention (p<0,01). On a observé une réduction des probabilités que le taux de phosphate soit dans les cibles (p=0,02) et une augmentation des valeurs de laboratoire montrant une hyperkaliémie (>6,0 mmol/L) pendant la période d'intervention (p=0,01). Aucun changement significatif n'a été observé entre les deux périodes en ce qui concerne la probabilité que les valeurs de laboratoire soient dans les cibles acceptées pour l'hémoglobine, le TSAT, le calcium ou la PTH. Pendant la période d'intervention, moins de patients ont été hospitalisés et le risque de décès a diminué, mais d'autres facteurs, notamment la pandémie de COVID-19, ont pu influer sur ce résultat. Enfin, le fait de réduire la fréquence des analyses de suivi pour l'anémie et les TDO a entraîné des économies de 32 962 $. Conclusion: Aucune conséquence négative n'a été observée lorsque la fréquence des analyses sanguines des patients des unités d'hémodialyse en centre de Calgary est passée de 6 à 8 semaines. Une proportion légèrement plus faible des valeurs de phosphate se situait dans la fourchette cible et une augmentation de 0,7 % des valeurs de potassium supérieures à 6 mmol/L a été constatée. Notre étude suggère qu'il est sécuritaire d'effectuer les analyses sanguines des patients hémodialysés en centre toutes les 8 semaines. Des essais pragmatiques sont nécessaires pour déterminer la fréquence optimale de ces analyses.

Risk Factors for Developing Low Estimated Glomerular Filtration Rate and Albuminuria in Living Kidney Donors.

Rationale & Objective: Chronic kidney disease is associated with significant morbidity and mortality in the general population, but little is known about the incidence and risk factors associated with developing low estimated glomerular filtration rate (eGFR) and moderate-severe albuminuria in living kidney donors following nephrectomy. Study Design: Retrospective, population-based cohort study. Setting & Participants: Kidney donors in Alberta, Canada. Exposure: Donor nephrectomy between May 2001 and December 2017. Outcome: Two eGFR measurements <45 mL/min/1.73 m2 or 2 measurements of moderate or severe albuminuria from 1-year postdonation onwards that were at least 90 days apart. Analytical Approach: Associations between potential risk factors and the primary outcome were assessed using Cox proportional hazard regression analyses. Results: Over a median follow-up period of 8.6 years (IQR, 4.7-12.6 years), 47 of 590 donors (8.0%) developed sustained low eGFR or moderate-severe albuminuria with an incidence rate of 9.2 per 1,000 person-years (95% confidence interval, 6.6-11.8). The median time for development of this outcome beyond the first year after nephrectomy was 2.9 years (IQR, 1.4-8.0 years). Within the first 4 years of follow-up, a 5 mL/min/1.73 m2 lower predonation eGFR increased the hazard of developing postdonation low eGFR or moderate-severe albuminuria by 26% (adjusted HR, 1.26; 95% CI, 1.10-1.44). Furthermore, donors were at higher risk of developing low eGFR or albuminuria if they had evidence of predonation hypertension (adjusted HR, 2.52; 95% CI, 1.28-4.96) or postdonation diabetes (adjusted HR, 4.72; 95% CI, 1.54-14.50). Limitations: We lacked data on certain donor characteristics that may affect long-term kidney function, such as race, smoking history, and transplant-related characteristics. Conclusions: A proportion of kidney donors at an incidence rate of 9.2 per 1,000 person-years will develop low eGFR or albuminuria after donation. Donors with lower predonation eGFR, predonation hypertension, and postdonation diabetes are at increased risk of developing this outcome.

The purpose of this study was to understand the risk of developing kidney disease in living kidney donors after donation. We followed 590 donors in Alberta, Canada for almost 9 years. Approximately 8% of donors developed reduced kidney function (low estimated glomerular filtration rate) or increased protein in the urine (albuminuria). Donors with lower kidney function before donation, hypertension before donation, or diabetes after donation had a higher likelihood of experiencing these kidney outcomes. This research provides important insights to patients and health care providers to better support the long-term kidney health of living kidney donors.

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study.

Background: Few studies have assessed outcomes in transplant recipients with failing grafts as most studies have focused on outcomes after graft loss. Objective: To determine whether renal function declines faster in kidney transplant recipients with a failing graft than in people with chronic kidney disease of their native kidneys. Design: Retrospective cohort study. Setting: Alberta, Canada (2002-2019). Patients: We identified kidney transplant recipients with a failing graft (2 estimated glomerular filtration rate [eGFR] measurements 15-30 mL/min/1.73 m2 ≥90 days apart). Measurements: We compared the change in eGFR over time (eGFR with 95% confidence limits, LCLeGFRUCL) and the competing risks of kidney failure and death (cause-specific hazard ratios [HRs], LCLHRUCL). Methods: Recipients (n = 575) were compared with propensity-score-matched, nontransplant controls (n = 575) with a similar degree of kidney dysfunction. Results: The median potential follow-up time was 7.8 years (interquartile range, 3.6-12.1). The hazards for kidney failure (HR1.101.331.60) and death (HR1.211.592.07) were significantly higher for recipients, while the eGFR decline over time was similar (recipients vs controls: -2.60-2.27-1.94 vs -2.52-2.21-1.90 mL/min/1.73 m2 per year). The rate of eGFR decline was associated with kidney failure but not death. Limitations: This was a retrospective, observational study, and there is a risk of bias due to residual confounding. Conclusions: Although eGFR declines at a similar rate in transplant recipients as in nontransplant controls, recipients have a higher risk of kidney failure and death. Studies are needed to identify preventive measures to improve outcomes in transplant recipients with a failing graft.

Contexte: Peu d'études ont évalué les résultats chez les patients transplantés dont le greffon est défaillant; la majorité des études s'étant plutôt concentrées sur les résultats après la perte du greffon. Objectif: Vérifier si la fonction rénale décline plus rapidement chez les patients transplantés dont le greffon est défaillant que chez les personnes souffrant d'une insuffisance chronique sur reins natifs. Conception: Étude de cohorte rétrospective. Cadre: Alberta, Canada (2002 à 2019). Sujets: Nous avons identifié des patients transplantés dont le greffon est défaillant (défini par deux mesures du débit de filtration glomérulaire estimé [DFGe] de 15-30 ml/min/1,73 m2 à au moins 90 jours d'intervalle). Mesures: Nous avons comparé l'évolution du DFGe dans le temps (DFGe avec intervalles de confiance [IC] à 95 % inférieur et supérieur: ICIDFGeICS) et les rapports de risque d'insuffisance rénale et de décès (intervalles de rapport de risque (RR) lié à la cause: ICIRRICS). Méthodologie: Les transplantés dont le greffon est défaillant (n=575) ont été comparés à des témoins non transplantés (n=575) appariés selon le score de propension et présentant un niveau similaire de dysfonctionnement rénal. Résultats: Le temps médian de suivi potentiel était de 7,8 ans (ÉIQ: 3,6 à 12,1). Les risques d'insuffisance rénale (RR: 1,101,331,60) et de décès (RR: 1,211,592,07) étaient significativement plus élevés chez les transplantés dont le greffon est défaillant, mais le déclin du DFGe au fil du temps était similaire dans les deux groupes (receveurs: -2,60-2,27-1,94 ml/min/1,73 m2 par an; témoins: -2,52-2,21-1,90 ml/min/1,73 m2 par an). Le taux de déclin du DFGe a été associé à une insuffisance rénale terminale, mais pas au décès. Limites: Il s'agit d'une étude observationnelle rétrospective et il existe un risque de biais dû à des facteurs de confusion résiduels. Conclusion: Bien que le DFGe décline à un rythme similaire chez les transplantés dont le greffon est défaillant et les témoins non transplantés, le risque d'insuffisance rénale terminale et de décès est plus élevé pour les transplantés. D'autres études sont nécessaires pour identifier les mesures préventives qui pourraient améliorer les résultats des patients transplantés dont le greffon est défaillant.

Calculated versus measured albumin-creatinine ratio to predict kidney failure and death in people with chronic kidney disease.

Albumin-to-creatinine ratio (ACR), the preferred method to quantify proteinuria, can be calculated from urine dipstick protein or protein-to-creatinine ratio (PCR). The performance of calculated vs. measured ACR in predicting kidney failure and death without kidney failure in people with chronic kidney disease (CKD) is unknown. Here, we used population-based data from Alberta, Canada, to identify adults with incident moderate-severe CKD (sustained for more than 90 days) from 2008-04-01 to 2017-03-31, who had same-day measures of ACR and urine dipstick (ACR-dipstick cohort) or PCR (ACR-PCR cohort) in the two years before cohort entry. We followed participants until 2019-03-31 and trained competing risk models of kidney failure and death without kidney failure including age, sex, estimated glomerular filtration rate, diabetes, cardiovascular disease, and either measured or calculated ACR. Model performance was tested in cohorts created using the same algorithm in Manitoba, Canada. The ACR-dipstick and ACR-PCR cohorts included 18,731 and 4,542 people (training cohorts) and 821 and 1,831 people (testing cohorts), respectively. In internal and external testing, there was closer agreement between predictions based on measured vs. PCR-calculated ACR than between those based on measured vs. dipstick-calculated ACR. The dipstick-calculated ACR had higher Brier scores than measured ACR from year three for both outcomes, indicating worsening calibration. Models including measured or calculated ACR had similar discrimination: year one-to-five area under the receiver operating characteristic curve of 83-89% for kidney failure and 69-75% for mortality. Thus, if confirmed in different ethnic groups, calculated ACR can be used for risk predictions when the measured ACR is not available. PCR-calculated ACR may have superior performance to dipstick-calculated ACR.

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer.

Addition of platinums to combination chemotherapy for triple negative breast cancer (TNBC) has shown efficacy and is increasingly accepted in the clinic, yet optimal delivery is unknown. A prospective clinical trial with TNBC patients was conducted to determine the optimal chemotherapy regimen to deliver carboplatin with standard dose dense ACT. Tissue microarray was conducted to isolate markers indicative of response to treatment. 90 TNBC patients were enrolled onto our trial. The most successful version placed the carboplatin on the second and final paclitaxel treatment with liberal hematological parameters. Our final regimen had the lowest grade 3 or 4 toxicities, no delays, no dose reductions of carboplatin, and 32% reduction in paclitaxel doses. Stage I (AJCC7) patients did well with carboplatin-based chemotherapy with zero relapse rate. Reduction in protein levels of androgen receptor and PD-L1 were found to be potential indicators of patient relapse. We have optimized a protocol for the addition of carboplatin to standard of care chemotherapy in TNBC patients. Early data indicates reduced protein levels of androgen receptor and PD-L1 as indicators of response to treatment.Trial registration This trial was registered at Canadian Cancer Trials. http://www.canadiancancertrials.ca/.

Progression and Regression of Chronic Kidney Disease by Age Among Adults in a Population-Based Cohort in Alberta, Canada.

Importance: The burden of chronic kidney disease (CKD) is expected to increase worldwide as the global population ages, potentially increasing the demand for nephrology services. Understanding whether CKD inevitably progresses or may regress can inform clinical decision-making and health policy. Objective: To study CKD progression and regression by age in adults with CKD. Design, Setting, and Participants: This population-based cohort study used linked administrative and laboratory data to assess adults in the province of Alberta, Canada, with incident mild, moderate, or severe CKD, defined by estimated glomerular filtration rate (eGFR) of 45 to 59, 30 to 44, or 15 to 29 mL/min/1.73 m2 for longer than 3 months, from April 1, 2009, to March 31, 2015. Data were analyzed from July 20 to November 30, 2020. Exposures: Age. Main Outcomes and Measures: Time to the earliest of CKD regression or progression (defined as sustained increase or drop in eGFR category for >3 months, respectively, and a ≥25% increase or decrease in eGFR from baseline, respectively), kidney failure (the earlier of kidney replacement initiation or eGFR <15 mL/min/1.73 m2 for >3 months), death, or censoring (outmigration, 5 years of follow-up, or end of study on March 31, 2017). Results: Study participants with CKD (55.2% women and 44.8% men) included 81 320 with mild CKD (mean [SD] age, 72.4 [11.3] years), 35 929 with moderate CKD (mean [SD] age, 77.1 [11.5] years), and 12 237 with severe CKD (mean [SD] age, 76.6 [13.8] years). The annual incidence of CKD increased with advancing age, from 180 per 100 000 population younger than 65 years to 7250 per 100 000 in those 85 years or older. After cohort entry, the 5-year probability of regression was similar to that of progression or kidney failure in mild (14.3% vs 14.6%), moderate (18.9% vs 16.5%), and severe (19.3% vs 20.4%) CKD. As mortality at 5 years increased with advancing age in moderate (from 9.6% for age <65 years to 48.4% for age ≥85 years) and severe (from 10.8% for age <65 years to 60.2% for age ≥85 years) CKD, the risk of progression or kidney failure decreased substantially (for moderate CKD, from 32.3% for <65 years to 9.4% for ≥85 years; for severe CKD, from 55.2% for <65 years to 4.7% for ≥85 years), whereas the probabilities of regression varied to a lesser extent (for moderate CKD, from 22.5% for <65 years to 15.4% for ≥85 years; for severe CKD, from 13.9% for <65 years to 18.7% for ≥85 years). Conclusions and Relevance: This cohort study found that with advancing age, CKD regression and death were more likely than CKD progression or kidney failure. These findings have important implications for patient care and for assessing the potential effect of population aging on the burden of CKD.

Accounting for the Competing Risk of Death to Predict Kidney Failure in Adults With Stage 4 Chronic Kidney Disease.

Importance: Kidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4, [G4]) chronic kidney disease (G4-CKD). Existing prediction tools do not account for the competing risk of death. Objective: To compare predictions of kidney failure (defined as estimated glomerular filtration rate [eGFR] <10 mL/min/1.73 m2 or initiation of kidney replacement therapy) from models that do and do not account for the competing risk of death in adults with G4-CKD. Design, Setting, and Participants: This prognostic study linked population-based laboratory and administrative data (2002-2017) from 2 Canadian provinces (Alberta and Manitoba) to compare 3 kidney risk models: the standard Cox regression, cause-specific Cox regression, and Fine-Gray subdistribution hazard model. Participants were adults with incident G4-CKD (eGFR 15-29 mL/min/1.73 m2). Data analysis occurred between July and December 2020. Main Outcomes and Measures: The performance of kidney risk models at prespecified times and across categories of baseline characteristics, using calibration, reclassification, and discrimination (for competing risks). Predictive characteristics were age, sex, albuminuria, eGFR, diabetes, and cardiovascular disease. Results: The development and validation cohorts included 14 619 (7070 [48.4%] men; mean [SD] age, 74.1 [12.8] years) and 2295 (1152 [50.2] men; mean [SD] age, 71.9 [14.0] years) adults, respectively. The 3 models had comparable calibration up to 2 years from entry. Beyond 2 years, the standard Cox regression overestimated the risk of kidney failure. At 4 years, for example, risks predicted from standard Cox were 40% for people whose observed risks were less than 30%. At 2 years (risk cutoffs 10%-20%) and 5 years (risk cutoffs 15%-30%), 788 (5.4%) and 2162 (14.8%) people in the development cohort were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by standard Cox regression (the opposite was observed in 272 patients [1.9%] and 0 patients, respectively). In the validation cohort, 115 (5.0%) individuals and 389 (16.9%) individuals at 2 and 5 years, respectively, were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by the standard Cox regression; the opposite was observed in 98 (4.3%) individuals and 0 individuals, respectively. Differences in discrimination emerged at 4 to 5 years in the development cohort and at 1 to 2 years in the validation cohort (0.85 vs 0.86 and 0.78 vs 0.8, respectively). Performance differences were minimal during the entire follow-up in people at lower risk of death (ie, aged ≤65 years or without cardiovascular disease or diabetes) and greater in those with a higher risk of death. At 5 years, for example, in people aged 65 years or older, predicted risks from standard Cox were 50% where observed risks were less than 30%. Similar miscalibration was observed at 5 years in people with albuminuria greater than 30 mg/mmol, diabetes, or cardiovascular disease. Conclusions and Relevance: In this study, predictions about the risk of kidney failure were minimally affected by consideration of competing risks during the first 2 years after developing G4-CKD. However, traditional methods increasingly overestimated the risk of kidney failure with longer follow-up time, especially among older patients and those with more comorbidity.

Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease.

BACKGROUND: In people with severe chronic kidney disease (CKD), there is an inverse relationship between age and kidney failure. If this relationship is the same at any age (linear), one effect (hazard ratio) will be sufficient for accurate risk prediction; if it is nonlinear, the effect will vary with age. OBJECTIVE: To investigate the relationship between age and kidney failure in adults with category G4 chronic kidney disease (G4 CKD). METHODS: We performed a population-based study using linked administrative databases in Alberta, Canada, to study adults with G4 CKD (estimated glomerular filtration rate [eGFR] = 15-30 mL/min/1.73 m2) and without previously documented eGFR <15 mL/min/1.73 m2 or renal replacement. We used cause-specific Cox regression to model the relationship between age and the hazard of kidney failure (the earlier of eGFR <10 mL/min/1.73 m2 or receipt of renal replacement) and death, incorporating spline terms to capture any nonlinear effect of age. We included sex, diabetes mellitus, cardiovascular disease, albuminuria, and eGFR in all models. RESULTS: Of the 27 823 participants (97 731 patient-years at risk; mean age = 76 years, ±13), 19% developed kidney failure and 51% died. The decline in the hazard of kidney failure associated with a given increase in age was not constant but became progressively larger as people aged; that is, the hazard ratio became progressively smaller (closer to 0). Assuming an eGFR of 25 mL/min/1.73 m2, for every 10-year increase in age, the hazard ratio declined from 0.76 (95% confidence interval = 0.73-0.79) at age 50 years to 0.43 (95% confidence interval = 34-56) at age 80 years in people without cardiovascular disease, and from 0.75 (95% confidence interval = 0.70-0.79) at age 50 years to 0.36 (95% confidence interval = 0.29-0.45) at age 80 years in people with cardiovascular disease. CONCLUSIONS: The relationship between kidney failure and age varies with age. An age-dependent effect, rather than a constant effect, needs to be specified to accurately predict risk. These findings have implications for risk prediction and advanced care planning.

CONTEXTE: Chez les personnes atteintes d'une forme grave d'insuffisance rénale chronique (IRC), on observe une corrélation inverse entre l'âge et le risque de néphropathie. Si la relation est linéaire (la même à tout âge), un seul effet (risque relatif) suffira pour prédire le risque de façon précise; si elle est non linéaire, l'effet variera avec l'âge. OBJECTIF: Examiner la relation entre l'âge et l'insuffisance rénale terminale chez les adultes atteints d'insuffisance rénale chronique de catégorie G4 (IRC G4). MÉTHODOLOGIE: Nous avons procédé à une étude populationnelle à l'aide des bases de données couplées de l'Alberta (Canada). Nous avons inclus les adultes atteints d'IRC G4 (débit de filtration glomérulaire estimé [DFGe] entre 15 et 30 ml/min/1,73 m2) sans antécédents documentés de DFGe inférieur à 15 ml/min/1,73 m2 ou de thérapie de remplacement rénal. Une régression de Cox par cause spécifique a servi à modéliser la relation entre l'âge et le risque d'insuffisance rénale terminale (la première situation survenant entre un DFGe inférieur à 10 ml/min/1,73 m2 ou un remplacement rénal) et le décès. Les fonctions splines ont été incorporées pour capter tout effet non linéaire lié à l'âge. Nous avons inclus le diabète, les maladies cardiovasculaires, l'albuminurie, le DFGe et le sexe du patient dans tous les modèles. RÉSULTATS: Des 27 823 patients inclus à l'étude (âge médian 76 ans ±13 ans; total de 97 731 années-patients à risque), 19 % ont évolué vers l'insuffisance rénale terminale et 51 % sont décédés. Le déclin du risque d'insuffisance rénale associé à une hausse donnée de l'âge n'était pas constant, mais devenait progressivement plus important à mesure que le patient avançait en âge; en ce sens que le risque relatif était devenu progressivement plus faible (se rapprochait de zéro). Pour chaque tranche de 10 ans d'âge, en supposant un DFGe de 25 ml/min/1,73 m2, le risque relatif est passé de 0,76 à l'âge de 50 ans (intervalle de confiance à 95 % : 0,73-0,79) à 0,43 à 80 ans (IC 95 % : 34-56) pour les personnes sans maladies cardiovasculaires, et de 0,75 à l'âge de 50 ans (IC 95 % : 0,70-0,79) à 0,36 à l'âge de 80 ans (IC 95 % : 0,29-0,45) chez les personnes atteintes de maladies cardiovasculaires. CONCLUSION: La relation entre l'âge et le risque d'insuffisance rénale terminale varie selon l'âge du patient. Un effet dépendant de l'âge, plutôt qu'un effet constant, doit être défini pour prédire le risque plus précisément. Ces résultats ont des implications pour la prévision des risques et la planification de soins avancés.

Association of Age With Risk of Kidney Failure in Adults With Stage IV Chronic Kidney Disease in Canada.

Importance: With population aging, the burden of many age-related chronic conditions, including kidney failure, is increasing globally. Objective: To investigate the risks of kidney failure and death in adults with incident stage IV chronic kidney disease (CKD). Design, Setting, and Participants: This population-based cohort study obtained data recorded between July 30, 2002, and March 31, 2014, from the linked laboratory and administrative data set of Alberta Health in Alberta, Canada. All adults of the province of Alberta with stage IV CKD (estimated glomerular filtration rate [eGFR] of 15-30 mL/min/1.73 m2) were eligible for inclusion. Included individuals were followed up from study entry until the date of kidney failure, death, or censoring, whichever occurred first. Observations were censored at the date of emigration from the province, the study end date (March 31, 2017), or at 10 years after study entry. Data analyses were performed from January 2020 to June 2020. Main Outcomes and Measures: The primary outcome was kidney failure, defined as the earlier of either renal replacement (dialysis or kidney transplant) initiation or severe kidney impairment (eGFR <10 mL/min/1.73 m2). Incidence of stage IV CKD in Alberta was examined over time, along with the association between age at study entry and the competing risks of kidney failure and death. Cumulative incidence functions (95% CIs) were estimated to summarize absolute risks over time across categories of age, accounting for sex, diabetes, cardiovascular disease, eGFR, and albuminuria. Results: The study included 30 801 adults (mean [SD] age, 76.8 [13.3] years; 17 294 women [56.1%]) with stage IV CKD. Of these, 5511 developed kidney failure (17.9%) and 16 285 died (52.9%). The incidence rate of stage IV CKD increased sharply with advancing age; the absolute risk of kidney failure decreased with advancing age, and the risk of death increased, especially in those aged 85 years or older. Compared with the 5-year risk of death, the 5-year risk of kidney failure was higher in people younger than 65 years, similar in people aged 65 to 74 years, and lower for older age groups. For those aged 75 years or older, the risk of death was much higher than the risk of kidney failure: 6-fold higher among those aged 75 to 84 years (0.51 [95% CI, 0.5-0.52] vs 0.09 [95% CI, 0.08-0.09]) and 25-fold higher among those aged 85 years or older (0.75 [95% CI, 0.74-0.76] vs 0.03 [95% CI, 0.02-0.03]). The risk of death was higher than the risk of kidney failure by 24-fold among those aged 85 to 94 years (0.73 [95% CI, 0.72-0.74] vs 0.03 [95% CI, 0.02-0.03]) and by 149-fold among those aged 95 years or older (0.89 [95% CI, 0.87-0.92] vs <0.01 [95% CI, <0.01 to 0.01]). Conclusions and Relevance: This study found that, although the incidence rate of stage IV CKD increased with advancing age, the absolute risk of kidney failure decreased. Unlike other age-related conditions, the expected increase in the burden of kidney failure in the older adults may be less dramatic than expected.

A bivariate autoregressive Poisson model and its application to asthma-related emergency room visits.

There are no gold standard methods that perform well in every situation when it comes to the analysis of multiple time series of counts. In this paper, we consider a positively correlated bivariate time series of counts and propose a parameter-driven Poisson regression model for its analysis. In our proposed model, we employ a latent autoregressive process, AR(p) to accommodate the temporal correlations in the two series. We compute the familiar maximum likelihood estimators of the model parameters and their standard errors via a Bayesian data cloning approach. We apply the model to the analysis of a bivariate time series arising from asthma-related visits to emergency rooms across the Canadian province of Ontario.