Decreased patient discharges on weekends part 3: what do the leaders tell us?

BACKGROUND: Emergency department (ED) crowding is a significant challenge to providing safe and quality care to patients. We know that hospital and ED crowding is exacerbated on Mondays because fewer in-patients are discharged on the weekend. We evaluated barriers and potential solutions to improve in-patient flow and diminished weekend discharges, in hopes of decreasing the severe ED crowding observed on Mondays. METHODS: In this observational study, we conducted interviews of (a) leaders at The Ottawa Hospital, a major academic health sciences centre (nursing, allied health, physicians), and (b) leaders of community facilities (long-term care and chronic hospital) that receive patients from the hospital, and (c) home care. Each interview was conducted individually and addressed perceived barriers to the discharge of hospital in-patients on weekends as well as potential solutions. An inductive thematic analysis was conducted whereby themes were organized into a summary table of barriers and solutions. RESULTS: We interviewed 40 leaders including 30 nursing, physician, and allied health leaders from the hospital as well as 10 senior personnel from community facilities and home care. Many barriers to weekend discharges were identified, highlighting that this problem is complex with many interdependent internal and external factors. Fortunately, many specific potential solutions were suggested, in immediate, short-term and long-term time horizons. While many solutions require additional resources, others require a culture change whereby hospital and community stakeholders recognize that services must be provided consistently, seven days a week. INTERPRETATION: We have identified the complex and interdependent barriers to weekend discharges of in-patients. There are numerous specific opportunities for hospital staff and services, physicians, and community facilities to provide the same patient care on weekends as on weekdays. This will lead to improved patient flow and safety, and to decreased ED crowding on Mondays.

ABSTRAIT: CONTEXTE: Le surpeuplement des services d'urgence (SU) est un défi important pour fournir des soins sécuritaires et de qualité aux patients. Nous savons que le surpeuplement des hôpitaux et des urgences est exacerbé le lundi parce que moins de patients hospitalisés reçoivent leur congé le week-end. Nous avons évalué les obstacles et les solutions potentielles pour améliorer le flux de patients hospitalisés et diminuer les congés de fin de semaine, dans l'espoir de réduire le surpeuplement sévère observé le lundi. MéTHODES: Dans cette étude observationnelle, nous avons interviewé (a) des dirigeants de l'Hôpital d'Ottawa, un important centre universitaire des sciences de la santé (soins infirmiers, soins paramédicaux, médecins), et (b) des dirigeants d'établissements communautaires (soins de longue durée et hôpitaux de soins chroniques) qui reçoivent des patients de l'hôpital et (c) des soins à domicile. Chaque entrevue a été menée individuellement et a abordé les obstacles perçus au congé des patients hospitalisés le week-end ainsi que les solutions potentielles. Une analyse thématique inductive a été menée, dans le cadre de laquelle les thèmes ont été organisés en un tableau récapitulatif des obstacles et des solutions RéSULTATS: Nous avons interviewé 40 dirigeants, dont 30 chefs de file des soins infirmiers, des médecins et des professions paramédicales de l'hôpital, ainsi que 10 cadres supérieurs d'établissements communautaires et de soins à domicile. De nombreux obstacles aux congés de fin de semaine ont été cernés, ce qui souligne que ce problème est complexe et qu'il comporte de nombreux facteurs internes et externes interdépendants. Heureusement, de nombreuses solutions potentielles spécifiques ont été proposées, à court terme et à long terme. Bien que de nombreuses solutions exigent des ressources supplémentaires, d'autres exigent un changement de culture par lequel les intervenants hospitaliers et communautaires reconnaissent que les services doivent être fournis de façon uniforme, sept jours par semaine. INTERPRéTATION: Nous avons identifié les obstacles complexes et interdépendants aux sorties de fin de semaine des patients hospitalisés. Il existe de nombreuses possibilités précises pour le personnel et les services hospitaliers, les médecins et les établissements communautaires d'offrir les mêmes soins aux patients les fins de semaine que les jours de semaine. Cela permettra d'améliorer la circulation et la sécurité des patients, et de réduire le surpeuplement des urgences le lundi.

Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.

Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Epidemiology of Cancer in Kidney Transplant Recipients.

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

Implementation of a 1-Day Living Kidney Donor Evaluation Program: A Qualitative Analysis of Donor Candidate and Stakeholder Perspectives.

Introduction: A lengthy donor evaluation process hinders living donor kidney transplantation (LDKT). At The Ottawa Hospital, 1-day evaluation process was recently developed, with a goal to accelerate the determination of donor suitability. The major objective of this study was to solicit feedback from donor candidates and key stakeholders who participated in the 1-day living kidney donor evaluation process, to determine the program's acceptability and factors influencing its implementation elsewhere. Methods: Semi-structured interviews were conducted with donor candidates who participated in the 1-day living kidney donor evaluation process, and with stakeholders who are instrumental to the implementation strategy. Interviews were conducted via videoconference or by telephone from May 2022 to December 2022. Directed content analysis was conducted using 2 unique frameworks for stakeholder and donor candidate interviews. Results: Our study included 13 stakeholders and 18 donor candidates, of whom 16 (89%) were women and 7 (39%) proceeded to kidney donation. Eighteen (100%) perceived the process to be both time-effective and cost-effective, due to reduced travel and missed work time. Thirteen (72%) felt that the 1-day evaluation may accelerate determination of donor suitability. Sequential virtual sessions with a nurse and social worker in advance of the evaluation day were seen as providing critical education and support. Among stakeholders, 11 (85%) emphasized donor candidate care and faster candidacy determinations. Conclusion: The 1-day evaluation process was preferred by most donor candidates, and was perceived as time-effective and cost-effective by most interviewees. An expedited, 1-day evaluation may accelerate determination of donor suitability and improve LDKT rates.

Stroke Subtype Among Individuals With Chronic Kidney Disease.

Background: It is widely accepted that there is a stepwise increase in the risk of acute ischemic stroke with chronic kidney disease (CKD). However, whether the risk of specific ischemic stroke subtypes varies with CKD remains unclear. Objective: To assess the association between ischemic stroke subtypes (cardioembolic, arterial, lacunar, and other) classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and CKD stage. Design: retrospective cohort study. Setting: Ontario, Canada. Patients: A total of 17 434 adults with an acute ischemic stroke in Ontario, Canada between April 1, 2002 and March 31, 2013, with an estimated glomerular filtration rate (eGFR) measurement or receipt of maintenance dialysis captured in a stroke registry were included. Measurements: Kidney function categorized as an eGFR of ≥60, 30-59, <30 mL/min/1.73 m2, or maintenance dialysis. Ischemic stroke classified by TOAST included arterial, cardioembolic, lacunar, and other (dissection, prothrombotic state, cortical vein/sinus thrombosis, and vasculitis) types of strokes. Methods: Adjusted regression models. Results: In our cohort, 58.9% had an eGFR of ≥60, 34.7% an eGFR of 30-59, 6.0% an eGFR of <30 and 0.5% were on maintenance dialysis (mean age of 73 years; 48% women). Cardioembolic stroke was more common in patients with non-dialysis-dependant CKD (eGFR 30-59: 50.4%, adjusted odds ratio [OR] 1.20, 95% confidence interval [CI]: 1.02, 1.44; eGFR<30: 50.6%, OR 1.21, 95% CI: 1.02, 1.44), whereas lacunar stroke was less common (eGFR 30-59: 22.7% OR 0.85, 95% CI: 0.77, 0.93; eGFR <30: 0.73, 95% CI: 0.61, 0.88) compared with those with an eGFR ≥60. In stratified analyses by age and CKD, lacunar strokes were more frequent in those aged less than 65 years, whereas cardioembolic was higher in those aged 65 years and above. Limitations: TOAST classification was not captured for all patients. Conclusion: Non-dialysis CKD was associated with a higher risk of cardioembolic stroke, whereas an eGFR ≥60 mL/min/1.73 m2 was associated with a higher risk of lacunar stroke. Detailed stroke subtyping in CKD may therefore provide mechanistic insights and refocus treatment strategies in this high-risk population.

Contexte: Il est largement admis qu'il y a une augmentation progressive du risque d'accident vasculaire cérébral ischémique aigu en contexte d'insuffisance rénale chronique (IRC). On ignore cependant si le risque de certains sous-types particuliers d'AVC ischémiques varie en présence d'IRC. Objectif: Évaluer le lien entre le stade d'IRC et certains sous-types d'AVC ischémiques (cardioembolique, artériel, lacunaire et autres) classés selon l'essai TOAST (Trial of ORG 10172 in Acute Stroke Treatment). Type d'étude: Étude de cohorte retrospective. Cadre: Ontario (Canada). Sujets: Ont été inclus 17 434 adultes ayant subi un AVC ischémique aigu en Ontario (Canada) entre le 1er avril 2002 et le 31 mars 2013, et pour lesquels le registre d'AVC comportait une mesure du débit de filtration glomérulaire estimé (DFGe) ou une dialyze chronique. Mesures: La fonction rénale a été classée selon le DFGe (≥ 60 ml/min/1,73 m2 ­entre 30 et 59 ml/min/1,73 m2 ­<30 ml/min/1.73 m2) ou une dialyze chronique. Les types d'AVC ischémiques classés par l'essai TOAST comprenaient les AVC artériels, cardioemboliques, lacunaires et autres (dissection, état prothrombotique, thrombose de la veine/sinus cortical, vascularite). Méthodologie: Modèles de régression ajustés. Résultats: Dans notre cohorte (âge moyen de 73 ans; 48% de femmes), 58,9 % des patients avaient un DFGe ≥ 60 ml/min/1,73 m2; 34,7% avaient un DFGe entre 30 et 59 ml/min/1,73 m2; 6,0 % avaient un DFGe < 30 ml/min/1,73 m2 et 0,5 % des patients étaient en dialyze chronique En comparaison des patients ayant un DFGe ≥ 60 ml/min/1,73 m2, les AVC cardioemboliques étaient plus fréquents chez les patients atteints d'IRC sans dialyze (DFGe entre 30 et 59 ml/min/1,73 m2: 50,4%; rapport de cote corrigé [RCc] = 1,20; IC 95 % = 1,02-1,44­DFGe < 30 ml/min/1,73 m2: 50,6 %; RCc = 1,21; IC95% = 1,02-1,44) alors que les AVC lacunaires étaient moins fréquents [DFGe entre 30 et 59 ml/min/1,73 m2: 22,7%; RCc = 0,85; IC 95% = 0,77-0,93­DFGe < 30 ml/min/1,73 m2: RCc = 0,73; IC 95% = 0,61-0,88]. Dans les analyses stratifiées en fonction de l'âge et de l'IRC, les AVC lacunaires étaient plus fréquents chez les moins de 65 ans tandis que les AVC cardioemboliques étaient plus fréquents chez les plus de 65 ans. Limites: La classification TOAST n'était pas enregistrée pour tous les patients. Conclusion: L'IRC sans dialyze a été associée à un risque plus élevé d'AVC cardioembolique alors qu'un DFGe ≥ 60 ml/min/1.73 m2 a été associé à un risque plus élevé d'AVC lacunaire. Le sous-typage détaillé des AVC en contexte d'IRC pourrait donc fournir des informations mécanistiques et recentrer les stratégies de traitement dans cette population à haut risque.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.

Estimated glomerular filtration rate from the renal hypothermia trial: clinical implications.

OBJECTIVE: To assess if estimated glomerular filtration rate (eGFR) can replace measured GFR (mGFR) in partial nephrectomy (PN) trials, using data from a randomised clinical trial. PATIENTS AND METHODS: We conducted a post hoc analysis of the renal hypothermia trial. Patients underwent mGFR with diethylenetriaminepentaacetic acid (DTPA) plasma clearance preoperatively and 1 year after PN. The eGFR was calculated using the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equations incorporating age and sex, with and without race: 2009 eGFRcr(ASR) and 2009 eGFRcr(AS), and the 2021 equation that only incorporates age and sex: 2021 eGFRcr(AS). Performance was evaluated by determining the median bias, precision (interquartile range [IQR] of median bias), and accuracy (percentage of eGFR within 30% of mGFR). RESULTS: Overall, 183 patients were included. Pre- and postoperative median bias and precision were similar between the 2009 eGFRcr(ASR) (-0.2 mL/min/1.73 m2 , 95% confidence interval [CI] -2.2 to 1.7, IQR 18.8; and -2.9, 95% CI -5.1 to -1.5, IQR 15, respectively) and 2009 eGFRcr(AS) (-0.3 mL/min/1.73 m2 , 95% CI -2.4 to 1.5, IQR 18.8; and -3.0, 95% CI -5.7 to -1.7, IQR 15.0, respectively). Bias and precision were worse for the 2021 eGFRcr(AS) (-8.8 mL/min/1.73 m2 , 95% CI -10.9 to -6.3, IQR 24.7; and -12.0, 95% CI -15.8 to -8.9, IQR 23.5, respectively). Similarly, pre- and postoperative accuracy was >90% for the 2009 eGFRcr(ASR) and 2009 eGFRcr(AS) equations. Accuracy was 78.6% preoperatively and 66.5% postoperatively for 2021 eGFRcr(AS). CONCLUSION: The 2009 eGFRcr(AS) can accurately estimate GFR in PN trials and could be used instead of mGFR to reduce cost and patient burden.

Physical Frailty and Functional Status in Patients With Advanced Chronic Kidney Disease: A Systematic Review.

Background: With an aging population and growing number of patients with chronic kidney disease (CKD), integrating the latest risk factors when deciding on a treatment plan can result in better patient care. Frailty remains a prevalent syndrome in CKD resulting in adverse health outcomes. However, measures of frailty and functional status remain excluded from clinical decision making. Objective: To examine the degree to which different measures of frailty and functional status are associated with mortality, hospitalization, and other clinical outcomes in patients with advanced CKD. Design: Systematic review. Setting: Observation studies including cohort study, case-control study, or cross-sectional study examining frailty and functional status on clinical outcomes. There were no restrictions on type of setting or country of origin. Patients: Adults with advanced CKD, including both types of dialysis patients. Measurements: Data including demographic information (e.g., sample size, follow-up time, age, country), assessments of frailty or functional status and their domains, and outcomes including mortality, hospitalization, cardiovascular events, kidney function, and composite outcomes were extracted. Methods: A search was conducted using databases Medline, Embase, and Cochrane Central Register for Controlled Trials. Studies were included from inception to March 17, 2021. The eligibility of studies was screened by 2 independent reviewers. Data were presented by instrument and clinical outcome. Point estimates and 95% confidence intervals from the fully adjusted statistical model were reported or calculated from the raw data. Results: A total of 117 unique instruments were found among 140 studies. The median sample size of studies was 319 (interquartile range, 161-893). Most studies focused on incident and chronic dialysis patient populations, with only 15% of studies examining non-dialysis CKD patients. Frailty and lower functional status were associated with an increased risk for adverse clinical outcomes such as mortality and hospitalization. The 5 individual domains of frailty were also found to be associated with poor health outcomes. Limitations: Meta-analysis could not be performed due to significant heterogeneity between studies and methods used to measure frailty and functional status. Many studies had issues with methodological rigor. Selection bias and the validity of data collection could not be ascertained for some studies. Conclusion: Frailty and functional status measures should be integrated to help guide clinical care decision making for a comprehensive assessment of risk for adverse outcomes among patients with advanced CKD. Registration PROSPERO: CRD42016045251.

Contexte: Compte tenu du vieillissement de la population et du nombre croissant de patients atteints d'insuffisance rénale chronique (IRC), l'intégration des plus récents facteurs de risque dans le processus de prise de décision d'un plan de traitement pourrait améliorer les soins aux patients. La fragilité demeure un syndrome prévalant en contexte d'IRC, qui entraîne des effets néfastes sur la santé. Pourtant, les mesures de la fragilité et de l'état fonctionnel demeurent exclues de la prise de décisions cliniques. Objectif: Déterminer à quel point les différentes mesures de la fragilité et de l'état fonctionnel sont associées à la mortalité, à l'hospitalisation et à d'autres résultats cliniques chez les patients atteints d'IRC avancée. Type d'étude: Examen systématique. Sources: Des études d'observation, y compris des études de cohorte, des études cas-témoins ou des études transversales examinant le rôle de la fragilité et de l'état fonctionnel sur les résultats cliniques. Il n'y avait pas de restrictions quant au cadre ou au pays d'origine de l'étude. Sujets: Des adultes atteints d'IRC avancée, y compris les deux types de patients sous dialyse. Mesures: Les données suivantes ont été extraites : les données démographiques (taille de l'échantillon, temps de suivi, âge des patients, pays), les évaluations de la fragilité ou de l'état fonctionnel et de leurs domaines, et les résultats cliniques (mortalité, hospitalisation, événements cardiovasculaires, fonction rénale et résultats composites). Méthodologie: Une recherche a été effectuée dans les bases de données Medline, embase et Cochrane Central Register for Controlled Trials pour répertorier les études de la création jusqu'au 17 mars 2021. L'admissibilité des études a été déterminée par deux examinateurs indépendants. Les données ont été présentées par instrument et par résultat clinique. Des estimations ponctuelles et des intervalles de confiance à 95 % du modèle statistique ajusté ont été rapportés ou calculés à partir des données brutes. Résultats: Parmi les 140 études répertoriées, 117 instruments uniques ont été trouvés. La taille médiane des échantillons était de 319 patients (ÉIQ : 161 à 893). La plupart des études portaient sur des populations de patients incidents et sous dialyse chronique, seulement 15 % des études portaient sur des patients atteints d'IRC non dialysés. La fragilité et un faible état fonctionnel ont été associés à un risque accru de résultats cliniques défavorables comme une hospitalisation ou le décès. Les cinq domaines individuels de la fragilité ont également été associés à de mauvais résultats de santé. Limites: L'hétérogénéité significative entre les études et les méthodes utilisées pour mesurer la fragilité et l'état fonctionnel ne permettait pas de procéder à une méta-analyse. De nombreuses études n'étaient pas rigoureuses sur le plan méthodologique. Les biais de sélection et la validité de la collecte des données n'ont pas pu être vérifiés pour certaines études. Conclusion: Les mesures de la fragilité et de l'état fonctionnel devraient être intégrées au processus de prise de décision afin d'orienter les soins cliniques et de permettre une évaluation complète du risque d'effets indésirables chez les patients atteints d'IRC avancée. Enregistrement PROSPERO: CRD42016045251.

Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study.

OBJECTIVE: To study age specific associations of modest reductions in estimated glomerular filtration rate (eGFR) with adverse outcomes. DESIGN: Retrospective, population based cohort study. SETTING: Linked healthcare administrative datasets in Ontario, Canada. PARTICIPANTS: Adult residents (18-65 years) with at least one outpatient eGFR value (categorized in 10 unit increments from 50 mL/min/1.73m2 to >120 mL/min/1.73m2), with no history of kidney disease. MAIN OUTCOME MEASURES: eGFRs and hazard ratios of composite adverse outcome (all cause mortality, any cardiovascular event, and kidney failure) stratified by age (18-39 years, 40-49 years, and 50-65 years), and relative to age specific eGFR referents (100-110 mL/min/1.73m2) for ages 18-39 years, 90-100 for 40-49 years, 80-90 for 50-65 years). RESULTS: From 1 January 2008 to 31 March 2021, among 8 703 871 adults (mean age 41.3 (standard deviation 13.6) years; mean index eGFR 104.2 mL/min/1.73m2 (standard deviation 16.1); median follow-up 9.2 years (interquartile range 5.7-11.4)), modestly reduced eGFR measurements specific to age were recorded in 18.0% of those aged 18-39, 18.8% in those aged 40-49, and 17.0% in those aged 50-65. In comparison with age specific referents, adverse outcomes were consistently higher by hazard ratio and incidence for ages 18-39 compared with older groups across all eGFR categories. For modest reductions (eGFR 70-80 mL/min/1.73m2), the hazard ratio for ages 18-39 years was 1.42 (95% confidence interval 1.35 to 1.49), 4.39 per 1000 person years; for ages 40-49 years was 1.13 (1.10 to 1.16), 9.61 per 1000 person years; and for ages 50-65 years was 1.08 (1.07 to 1.09), 23.4 per 1000 person years. Results persisted for each individual outcome and in many sensitivity analyses. CONCLUSIONS: Modest eGFR reductions were consistently associated with higher rates of adverse outcomes. Higher relative hazards were most prominent and occurred as early as eGFR <80 mL/min/1.73m2 in younger adults, compared with older groups. These findings suggest a role for more frequent monitoring of kidney function in younger adults to identify individuals at risk to prevent chronic kidney disease and its complications.

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.

Diagnostic accuracy of ancillary tests for death by neurologic criteria: a systematic review and meta-analysis.

PURPOSE: Ancillary tests are frequently used in death determination by neurologic criteria (DNC), particularly when the clinical neurologic examination is unreliable. Nevertheless, their diagnostic accuracy has not been extensively studied. Our objective was to synthesize the sensitivity and specificity of commonly used ancillary tests for DNC. SOURCE: We performed a systematic review and meta-analysis by searching MEDLINE, EMBASE, Cochrane databases, and CINAHL Ebsco from their inception to 4 February 2022. We selected cohort and case-control studies including patients with 1) clinically diagnosed death by neurologic criteria or 2) clinically suspected death by neurologic criteria who underwent ancillary testing for DNC. We excluded studies without a priori diagnostic criteria and studies conducted solely on pediatric patients. Accepted reference standards were clinical examination, four-vessel conventional angiography, and radionuclide imaging. Data were directly extracted from published reports. We assessed the methodological quality of studies with the QUADAS-2 tool and estimated ancillary test sensitivities and specificities using hierarchical Bayesian models with diffuse priors. PRINCIPAL FINDINGS: Overall, 137 records met the selection criteria. One study (0.7%) had a low risk of bias in all QUADAS-2 domains. Among clinically diagnosed death by neurologic criteria patients (n = 8,891), ancillary tests had similar pooled sensitivities (range, 0.82-0.93). Sensitivity heterogeneity was greater within (σ = 0.10-0.15) than between (σ = 0.04) ancillary test types. Among clinically suspected death by neurologic criteria patients (n = 2,732), pooled ancillary test sensitivities ranged between 0.81 and 1.00 and specificities between 0.87 and 1.00. Most estimates had high statistical uncertainty. CONCLUSION: Studies assessing ancillary test diagnostic accuracy have an unclear or high risk of bias. High-quality studies are required to thoroughly validate ancillary tests for DNC. STUDY REGISTRATION: PROSPERO (CRD42013005907); registered 7 October 2013.

RéSUMé: OBJECTIF: Les examens auxiliaires sont fréquemment utilisés dans la détermination du décès selon des critères neurologiques (DCN), en particulier lorsque l'examen neurologique clinique n'est pas fiable. Néanmoins, leur précision diagnostique n'a pas été étudiée de manière approfondie. Notre objectif était de synthétiser la sensibilité et la spécificité des examens auxiliaires couramment utilisés pour la DCN. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse en effectuant des recherches dans les bases de données MEDLINE, EMBASE, Cochrane et CINAHL Ebsco de leur création jusqu'au 4 février 2022. Nous avons sélectionné des études de cohorte et cas témoins incluant des patients présentant 1) un décès selon des critères neurologiques diagnostiqué cliniquement ou 2) un décès selon des critères neurologiques soupçonné cliniquement qui ont été soumis à des examens auxiliaires pour un DCN. Nous avons exclu les études sans critères diagnostiques a priori et les études menées uniquement auprès de patients pédiatriques. Les normes de référence acceptées étaient l'examen clinique, l'angiographie conventionnelle à quatre vaisseaux et l'imagerie nucléaire. Les données ont été directement extraites de comptes rendus publiés. Nous avons évalué la qualité méthodologique des études avec l'outil QUADAS-2 et estimé les sensibilités et les spécificités des examens auxiliaires à l'aide de modèles hiérarchiques bayésiens avec des distributions préalables diffuses. CONSTATATIONS PRINCIPALES: Au total, 137 études répondaient aux critères de sélection. Une étude (0,7 %) présentait un faible risque de biais dans tous les domaines de QUADAS-2. Parmi les patients ayant reçu un diagnostic clinique de décès selon des critères neurologiques (n = 8891), les examens auxiliaires présentaient des sensibilités combinées similaires (intervalle de 0,82 à 0,93). L'hétérogénéité de sensibilité était plus grande au sein (σ = 0,10-0,15) plutôt qu'entre (σ = 0,04) les types d'examens auxiliaires. Parmi les patients cliniquement soupçonnés de décès selon des critères neurologiques (n = 2732), les sensibilités combinées des examens auxiliaires variaient entre 0,81 et 1,00 et les spécificités entre 0,87 et 1,00. La plupart des estimations comportaient une grande incertitude statistique. CONCLUSION: Les études évaluant la précision diagnostique des examens auxiliaires présentent un risque de biais incertain ou élevé. Des études de haute qualité sont nécessaires pour valider en profondeur les examens auxiliaires pour la DCN. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42013005907); enregistrée le 7 octobre 2013.

Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients.

BACKGROUND: Nirmatrelvir/ritonavir has been shown to reduce the risk of COVID-19 related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program. METHODS: Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on Day 8) based on drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor level monitoring was implemented. Outcomes including tacrolimus level changes, serum creatinine and acute kidney injury (AKI, defined as serum creatinine increase by 30%) and clinical outcomes were described globally and compared between algorithms. RESULTS: Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first timepoint, 7 days after withholding of calcineurin inhibitor and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44(48%) and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 ug/L [4.0, 6.2] versus 4.8 ug/L [4.3, 5.7] p=0.70). There were no acute rejections or other complications. CONCLUSIONS: Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.

Health System-Level Barriers to Living Donor Kidney Transplantation: Protocol for a Comparative Case Study Analysis.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best treatment option for patients with kidney failure and offers significant medical and economic advantages for both patients and health systems. Despite this, rates of LDKT in Canada have stagnated and vary significantly across Canadian provinces, the reasons for which are not well understood. Our prior work has suggested that system-level factors may be contributing to these differences. Identifying these factors can help inform system-level interventions to increase LDKT. OBJECTIVE: Our objective is to generate a systemic interpretation of LDKT delivery across provincial health systems with variable performance. We aim to identify the attributes and processes that facilitate the delivery of LDKT to patients, and those that create barriers and compare these across systems with variable performance. These objectives are contextualized within our broader goal of increasing rates of LDKT in Canada, particularly in lower-performing provinces. METHODS: This research takes the form of a qualitative comparative case study analysis of 3 provincial health systems in Canada that have high, moderate, and low rates of LDKT performance (the percentage of LDKT to all kidney transplantations performed). Our approach is underpinned by an understanding of health systems as complex adaptive systems that are multilevel and interconnected, and involve nonlinear interactions between people and organizations, operating within a loosely bounded network. Data collection will comprise semistructured interviews, document reviews, and focus groups. Individual case studies will be conducted and analyzed using inductive thematic analysis. Following this, our comparative analysis will operationalize resource-based theory to compare case study data and generate explanations for our research question. RESULTS: This project was funded from 2020 to 2023. Individual case studies were carried out between November 2020 and August 2022. The comparative case analysis will begin in December 2022 and is expected to conclude in April 2023. Submission of the publication is projected for June 2023. CONCLUSIONS: By investigating health systems as complex adaptive systems and making comparisons across provinces, this study will identify how health systems can improve the delivery of LDKT to patients with kidney failure. Our resource-based theory framework will provide a granular analysis of the attributes and processes that facilitate or create barriers to LDKT delivery across multiple organizations and levels of practice. Our findings will have practice and policy implications and help inform transferrable competencies and system-level interventions conducive to increasing LDKT. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44172.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

BACKGROUND: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. METHODS: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. RESULTS: The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. CONCLUSIONS: The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low.

Kidney function, cardiovascular outcomes and survival of living kidney donors with hypertension: a systematic review protocol.

INTRODUCTION: Hypertension has been considered a contraindication for living kidney donation in the past. Since transplantation from living kidney donors remains the best modality for kidney failure, there is now an increased acceptance of living kidney donors with hypertension. However, the safety of this practice for the cardiovascular and kidney health of the donor is unclear. We will conduct a systematic review to summarise and synthesise the existing literature on this topic. METHODS AND ANALYSIS: A systematic review of prospective randomised and non-randomised and retrospective studies will be conducted. MEDLINE, EMBASE, Cochrane CENTRAL and EBM reviews published from January 1946 to December 2021 will be reviewed. Primary outcome will be the difference in the survival, major adverse cardiovascular events, estimated glomerular filtration rate of 45 mL/min or less and development of end-stage kidney failure, between living kidney donors with and without hypertension. Study screening, selection, and data extraction will be performed by two independent reviewers. Studies must fulfil all eligibility criteria for inclusion into the systematic review and meta-analysis. The Risk of Bias in Non-Randomised studies tool will be used to assess bias. ETHICS AND DISSEMINATION: No ethical approval is required for this systematic review. The results of this review will be disseminated in a peer-reviewed, open-access journal to ensure access to all stakeholders in kidney transplantation and to inform clinical guidelines on the evaluation and follow-up care of living kidney donor candidates. PROSPERO REGISTRATION NUMBER: CRD42022300119.