Emergency Department Use Among Adults Receiving Dialysis.

Importance: People with kidney failure receiving maintenance dialysis visit the emergency department (ED) 3 times per year on average, which is 3- to 8-fold more often than the general population. Little is known about the factors that contribute to potentially preventable ED use in this population. Objective: To identify the clinical and sociodemographic factors associated with potentially preventable ED use among patients receiving maintenance dialysis. Design, Setting, and Participants: This cohort study used linked administrative health data within the Alberta Kidney Disease Network to identify adults aged 18 years or older receiving maintenance dialysis (ie, hemodialysis or peritoneal dialysis) between April 1, 2010, and March 31, 2019. Patients who had been receiving dialysis for more than 90 days were followed up from cohort entry (defined as dialysis start date plus 90 days) until death, outmigration from the province, receipt of a kidney transplant, or end of study follow-up. The Andersen behavioral model of health services was used as a conceptual framework to identify variables related to health care need, predisposing factors, and enabling factors. Data were analyzed in March 2024. Main Outcomes and Measures: Rates of all-cause ED encounters and potentially preventable ED use associated with 4 kidney disease-specific ambulatory care-sensitive conditions (hyperkalemia, heart failure, volume overload, and malignant hypertension) were calculated. Multivariable negative binomial regression models were used to examine the association between clinical and sociodemographic factors and rates of potentially preventable ED use. Results: The cohort included 4925 adults (mean [SD] age, 60.8 [15.5] years; 3071 males [62.4%]) with kidney failure receiving maintenance hemodialysis (3183 patients) or peritoneal dialysis (1742 patients) who were followed up for a mean (SD) of 2.5 (2.0) years. In all, 3877 patients had 34 029 all-cause ED encounters (3100 [95% CI, 2996-3206] encounters per 1000 person-years). Of these, 755 patients (19.5%) had 1351 potentially preventable ED encounters (114 [95% CI, 105-124] encounters per 1000 person-years). Compared with patients with a nonpreventable ED encounter, patients with a potentially preventable ED encounter were more likely to be in the lowest income quintile (38.8% vs 30.9%; P < .001); to experience heart failure (46.8% vs 39.9%; P = .001), depression (36.6% vs 32.5%; P = .03), and chronic pain (60.1% vs 54.9%; P = .01); and to have a longer duration of dialysis (3.6 vs 2.6 years; P < .001). In multivariable regression analyses, potentially preventable ED use was higher for younger adults (incidence rate ratio [IRR], 1.69 [95% CI, 1.33-2.15] for those aged 18 to 44 years) and patients with chronic pain (IRR, 1.35 [95% CI, 1.14-1.61]), greater material deprivation (IRR, 1.57 [95% CI, 1.16-2.12]), a history of hyperkalemia (IRR, 1.31 [95% CI, 1.09-1.58]), and historically high ED use (ie, ≥3 ED encounters in the prior year; IRR, 1.46 [95% CI, 1.23-1.73). Conclusions and Relevance: In this study of adults receiving maintenance dialysis in Alberta, Canada, among those with ED use, 1 in 5 had a potentially preventable ED encounter; reasons for such encounters were associated with both psychosocial and medical factors. The findings underscore the need for strategies that address social determinants of health to avert potentially preventable ED use in this population.

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.

Protection against Incidences of Serious Cardiovascular Events Study with daily fish oil supplementation in dialysis patients (PISCES): protocol for a randomised controlled trial.

INTRODUCTION: Patients with kidney failure with replacement therapy (KFRT) suffer premature cardiovascular (CV) mortality and events with few proven pharmacological interventions. Omega-3 polyunsaturated essential fatty acids (n-3 PUFAs) are associated with a reduced risk of CV events and death in non-dialysis patients and in patients with established CV disease but n-3 PUFAs have not been evaluated in the high risk KFRT patient population. METHODS AND ANALYSIS: This multicentre randomised, placebo controlled, parallel pragmatic clinical trial tests the hypothesis that oral supplementation with n-3 PUFA, when added to usual care, leads to a reduction in the rate of serious CV events in haemodialysis patients when compared with usual care plus matching placebo. A target sample size of 1100 KFRT patients will be recruited from 26 dialysis units in Canada and Australia and randomised to n-3 PUFA or matched placebo in a 1:1 ratio with an expected intervention period of at least 3.5 years. The primary outcome to be analysed and compared between intervention groups is the rate of all, not just the first, serious CV events which include sudden and non-sudden cardiac death, fatal and non-fatal myocardial infarction, stroke, and peripheral vascular disease events. ETHICS AND DISSEMINATION: This study has been approved by all institutional ethics review boards involved in the study. Participants could only be enrolled following informed written consent. Results will be published in peer-reviewed journals and presented at scientific and clinical conferences. TRIAL REGISTRATION NUMBER: ISRCTN00691795.

Implementing a Formalized Risk-Based Approach to Determine Candidacy for Multidisciplinary CKD Care: A Descriptive Cohort Study.

Background: The kidney failure risk equation (KFRE) can be used to predict progression to end-stage kidney disease in a clinical setting. Objective: Evaluate implementation of a formalized risk-based approach in nephrologists' outpatient clinics and multidisciplinary chronic kidney disease (CKD) clinics to determine candidacy for multidisciplinary care, and the impact of CKD care selection on clinical outcomes. Design: Population-based descriptive cohort study. Setting: Alberta Kidney Care South. Patients: Adults attending or considered for a multidisciplinary CKD clinic between April 1, 2017, and March 31, 2019. Measurements: Exposure-The course of CKD care assigned by the nephrologist: management at multidisciplinary CKD clinic; management by a nephrologist or primary care physician. Primary Outcome-CKD progression, defined as commencement of kidney replacement therapy (KRT). Secondary Outcomes-Death, emergency department visits, and hospitalizations. Methods: We linked operational data from the clinics (available until March 31, 2019) with administrative health and laboratory data (available until March 31, 2020). Comparisons among patient groups, courses of care, and clinical settings with negative binomial regression count models and calculated unadjusted and fully adjusted incidence rate ratios. For the all-cause death outcome, we used Cox survival models to calculate unadjusted and fully adjusted hazard ratios. Results: Of the 1748 patients for whom a KFRE was completed, 1347 (77%) remained in or were admitted to a multidisciplinary CKD clinic, 310 (18%) were managed by a nephrologist only, and 91 (5%) were referred back for management by their primary care physician. There was a much higher kidney failure risk among patients who remained at or were admitted to a multidisciplinary CKD clinic (median 2-year risk of 34.7% compared with 3.6% and 0.8% who remained with a nephrologist or primary care physician, respectively). None of the people managed by their primary care physician alone commenced KRT, while only 2 (0.6%) managed by a nephrologist without multidisciplinary CKD care commenced KRT. The rates of emergency department visits, hospitalizations, and death were lower in those assigned to management outside the multidisciplinary CKD clinics when compared with those managed in the multidisciplinary care setting. Limitations: The follow-up period may not have been long enough to determine outcomes, and potentially limited generalizability given variability of care in multidisciplinary clinics. Conclusions: Our findings indicate that a portion of patients can be directed to less resource-intensive care without a higher risk of adverse events. Trial registration: Not applicable.

Contexte: L'équation KFRE (Kidney Failure Risk Equation) peut être utilisée en environnement clinique pour prédire le risque d'évolution vers l'insuffisance rénale terminale (IRT). Objectif: Évaluer la mise en œuvre d'une approche structurée fondée sur le risque dans les cliniques multidisciplinaires d'insuffisance rénale chronique (IRC) et les cliniques ambulatoires des néphrologues afin de déterminer l'aptitude des patients à recevoir des soins multidisciplinaires et de mesurer l'incidence des soins d'IRC reçus sur les résultats cliniques. Conception: Étude de cohorte populationnelle descriptive. Cadre: Alberta Kidney Care South. Sujets: Adultes fréquentant ou envisageant de fréquenter une clinique multidisciplinaire d'IRC entre le 1er avril 2017 et le 31 mars 2019. Mesures: Exposition­le parcours de soins d'IRC attribué par le néphrologue ­ prise en charge en clinique multidisciplinaire d'IRC; prise en charge par un néphrologue ou un médecin de premier recours. Principaux résultats­progression de l'IRC, définie comme l'amorce d'une thérapie de remplacement rénal (TRR). Résultats secondaires­décès, visites aux urgences et hospitalisations. Méthodologie: Nous avons couplé les données opérationnelles des cliniques (disponibles jusqu'au 31 mars 2019) aux données administratives de santé et aux données de laboratoire (disponibles jusqu'au 31 mars 2020). Des modèles de régression binomiale négative et des rapports des taux d'incidence non corrigés et entièrement corrigés ont servi aux comparaisons entre les groupes de patients, les parcours de soins et les environnements cliniques. Les risques relatifs non corrigés et entièrement corrigés de décès toutes causes confondues ont été calculés à l'aide de modèles de survie de Cox. Résultats: Des 1 748 patients avec une KFRE calculée, 1 347 (77 %) sont restés ou ont été admis dans une clinique multidisciplinaire d'IRC, 310 (18 %) ont été pris en charge par un néphrologue seulement et 91 (5 %) ont été orientés pour une prise en charge par leur médecin de premier recours. Le risque d'insuffisance rénale terminale était beaucoup plus élevé chez les patients restés ou admis dans une clinique multidisciplinaire d'IRC (risque médian à 2 ans : 34,7 %) que chez ceux pris en charge par un néphrologue (3,6 %) et par un médecin de premier recours (0,8 %). Aucun patient pris en charge par un médecin de premier recours n'avait amorcé une TRR; 2 personnes (0,6 %) prises en charge par un néphrologue sans soins multidisciplinaires d'IRC avaient amorcé une TRR. Les taux de visites aux urgences, d'hospitalisations et de décès étaient plus faibles chez les patients pris en charge à l'extérieur des cliniques multidisciplinaires d'IRC comparativement à ceux pris en charge dans ces cliniques. Limites: La période de suivi n'était peut-être pas été assez longue pour déterminer les résultats. La variabilité des soins dans les cliniques multidisciplinaires pourrait également limiter la généralisation des résultats. Conclusion: Nos résultats suggèrent qu'une partie des patients pourrait être dirigée vers des soins nécessitant moins de ressources sans hausser le risque d'événements indésirables.

Nurse Practitioner Care Compared with Primary Care or Nephrologist Care in Early CKD.

BACKGROUND: Early interventions in CKD have been shown to improve health outcomes; however, gaps in access to nephrology care remain common. Nurse practitioners can improve access to care; however, the quality and outcomes of nurse practitioner care for CKD are uncertain. METHODS: In this propensity score-matched cohort study, patients with CKD meeting criteria for nurse practitioner care were matched 1:1 on their propensity scores for ( 1 ) nurse practitioner care versus primary care alone and ( 2 ) nurse practitioner versus nephrologist care. Processes of care were measured within 1 year after cohort entry, and clinical outcomes were measured over 5 years of follow-up and compared between propensity score-matched groups. RESULTS: A total of 961 (99%) patients from the nurse practitioner clinic were matched on their propensity score to 961 (1%) patients receiving primary care only while 969 (100%) patients from the nurse practitioner clinic were matched to 969 (7%) patients receiving nephrologist care. After matching to patients receiving primary care alone, those receiving nurse practitioner care had greater use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (82% versus 79%; absolute differences [ADs] 3.4% [95% confidence interval, 0.0% to 6.9%]) and statins (75% versus 66%; AD 9.7% [5.8% to 13.6%]), fewer prescriptions of nonsteroidal anti-inflammatory drugs (10% versus 17%; AD -7.2% [-10.4% to -4.2%]), greater eGFR and albuminuria monitoring, and lower rates of all-cause hospitalization (34.1 versus 43.3; rate difference -9.2 [-14.7 to -3.8] per 100 person-years) and all-cause mortality (3.3 versus 6.0; rate difference -2.7 [-3.6 to -1.7] per 100 person-years). When matched to patients receiving nephrologist care, those receiving nurse practitioner care were also more likely to be prescribed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins, with no difference in the risks of experiencing adverse clinical outcomes. CONCLUSIONS: Nurse practitioner care for patients with CKD was associated with better guideline-concordant care than primary care alone or nephrologist care, with clinical outcomes that were better than or equivalent to primary care alone and similar to those with care by nephrologists. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_08_CJN0000000000000305.mp3.

Priorities for peer support delivery among adults living with chronic kidney disease: a patient-oriented consensus workshop.

BACKGROUND: Peer support can address the informational and emotional needs of people living with chronic kidney disease (CKD) and enable self-management. We aimed to identify preferences and priorities for content, format and processes of peer support delivery for patients with non-dialysis CKD and their loved ones. METHODS: Using a patient-oriented research approach, we conducted a half-day, virtual consensus workshop with stakeholder participants from across Canada, including patients, caregivers, peer mentors and clinicians. Using personas (fictional characters), participants discussed and voted on preferences for delivery of peer support across format, content and process categories. We analyzed transcripts from small- and large-group discussions inductively using content analysis. RESULTS: Twenty-one stakeholders, including 9 patients and 4 caregivers, participated in the workshop. In the voting exercise on format, participants prioritized peer mentor matching, programming for both patients and caregivers, and flexible scheduling. For content, participants prioritized informational and emotional support focus, and for process, they prioritized leveraging kidney care programs and alternative sources (e.g., social media) for promotion and referral. Analysis of workshop transcripts complemented prioritization results and emphasized tailoring of peer support delivery to accommodate the diversity of people living with CKD and their support needs. This concept was elaborated in 3 themes, namely alignment of program features with needs, inclusive peer support options and multiple access points. INTERPRETATION: We identified preferences for peer support delivery for people living with CKD and underscore the importance of tailored, flexible programming in this context. Findings could be used to develop, adapt or study CKD-focused peer support interventions.

Frailty and Clinical Outcomes in Patients Treated With Hemodialysis: A Prospective Cohort Study.

Rationale and Objective: Frailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty. Study Design: Prospective cohort study. Setting and Participants: Adults initiating thrice weekly in-center HD in Canada. Exposure: We classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present. Outcomes: All-cause death, hospitalizations, and placement into long-term care. Analytical Approach: We examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders. Results: 985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced ≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87). Limitations: There was missing data on frailty at baseline and during follow-up. Conclusions: Frailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Associations between hearing loss and clinical outcomes: population-based cohort study.

Background: Hearing loss (HL) is a leading cause of disability worldwide, but its clinical consequences and population burden have been incompletely studied. Methods: We did a retrospective population-based cohort study of 4,724,646 adults residing in Alberta between April 1, 2004 and March 31, 2019, of whom 152,766 (3.2%) had HL identified using administrative health data. We used administrative data to identify comorbidity and clinical outcomes, including death, myocardial infarction, stroke/transient ischemic attack, depression, dementia, placement in long-term care (LTC), hospitalization, emergency visits, pressure ulcers, adverse drug events and falls. We used Weibull survival models (binary outcomes) and negative binomial models (rate outcomes) to compare the likelihood of outcomes in those with vs without HL. We calculated population-attributable fractions to estimate the number of binary outcomes associated with HL. Findings: The age-sex-standardized prevalence of all 31 comorbidities at baseline was higher among participants with HL than those without. Over median follow-up of 14.4 y and after adjustment for potential confounders at baseline, participants with HL had higher rates of days in hospital (rate ratio 1.65, 95% CI 1.39, 1.97), falls (RR 1.72, 95% CI 1.59, 1.86), adverse drug events (RR 1.40, 95% CI 1.35, 1.45), and emergency visits (RR 1.21, 95% CI 1.14, 1.28) compared to those without, and higher adjusted hazards of death, myocardial infarction, stroke/transient ischemic attack, depression, heart failure, dementia, pressure ulcers and LTC placement. The estimated number of people with HL who required new LTC placement annually in Canada was 15,631, of which 1023 were attributable to HL. Corresponding estimates for new dementia among people with HL were 14,959 and 4350, and for stroke/TIA the estimates were 11,582 and 2242. Interpretation: HL is common, is often accompanied by substantial comorbidity, and is associated with significant increases in risk for a broad range of adverse clinical outcomes, some of which are potentially preventable. This high population health burden suggests that increased and coordinated investment is needed to improve the care of people with HL. Funding: Canadian Institutes of Health Research; David Freeze chair in health services research.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Comparative Risk of Harm Associated with Zopiclone or Trazodone Use in Nursing Home Residents: a Retrospective Cohort Study in Alberta, Canada.

Background: There is growing evidence of harm associated with trazodone and nonbenzodiazepine sedative hypnotics (e.g., zopiclone); however, their comparative risk of harm is unknown. Methods: We conducted a retrospective cohort study with linked health administrative data, which enrolled older (≥66 years old) nursing home residents living in Alberta, Canada, between December 1, 2009, and December 31, 2018; the last follow-up date was June 30, 2019. We compared the rate of injurious falls and major osteoporotic fractures (primary outcome) and all-cause mortality (secondary outcome) within 180 days of first prescription of zopiclone or trazodone with cause-specific hazard models and inverse probability of treatment weights to control for confounding; primary analysis was intention-to-treat and secondary analysis was per-protocol (i.e., residents censored if dispensed the other exposure drug). Results: Our cohort included 1,403 residents newly dispensed trazodone and 1,599 residents newly dispensed zopiclone. At cohort entry, the mean resident age was 85.7 (standard deviation [SD] 7.4), 61.6% were female, and 81.2% had dementia. New zopiclone use was associated with similar rates of injurious falls and major osteoporotic fractures (intention-to-treat-weighted hazard ratio 1.15, 95% confidence interval [CI] 0.90-1.48; per-protocol-weighted hazard ratio 0.85, 95% CI 0.60-1.21) and all-cause mortality (intention-to-treat-weighted hazard ratio 0.96, 95% CI 0.79-1.16; per-protocol-weighted hazard ratio 0.90, 95% CI 0.66-1.23) compared to trazodone. Conclusions: Zopiclone was associated with a similar rate of injurious falls, major osteoporotic fractures, and all-cause mortality compared to trazodone-suggesting one medication should not be used in lieu of the other. Appropriate prescribing initiatives should also target zopiclone and trazodone.

Prediction of major postoperative events after non-cardiac surgery for people with kidney failure: derivation and internal validation of risk models.

BACKGROUND: People with kidney failure often require surgery and experience worse postoperative outcomes compared to the general population, but existing risk prediction tools have excluded those with kidney failure during development or exhibit poor performance. Our objective was to derive, internally validate, and estimate the clinical utility of risk prediction models for people with kidney failure undergoing non-cardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: This study involved derivation and internal validation of prognostic risk prediction models using a retrospective, population-based cohort. We identified adults from Alberta, Canada with pre-existing kidney failure (estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m2 or receipt of maintenance dialysis) undergoing non-cardiac surgery between 2005-2019. Three nested prognostic risk prediction models were assembled using clinical and logistical rationale. Model 1 included age, sex, dialysis modality, surgery type and setting. Model 2 added comorbidities, and Model 3 added preoperative hemoglobin and albumin. Death or major cardiac events (acute myocardial infarction or nonfatal ventricular arrhythmia) within 30 days after surgery were modelled using logistic regression models. RESULTS: The development cohort included 38,541 surgeries, with 1,204 outcomes (after 3.1% of surgeries); 61% were performed in males, the median age was 64 years (interquartile range [IQR]: 53, 73), and 61% were receiving hemodialysis at the time of surgery. All three internally validated models performed well, with c-statistics ranging from 0.783 (95% Confidence Interval [CI]: 0.770, 0.797) for Model 1 to 0.818 (95%CI: 0.803, 0.826) for Model 3. Calibration slopes and intercepts were excellent for all models, though Models 2 and 3 demonstrated improvement in net reclassification. Decision curve analysis estimated that use of any model to guide perioperative interventions such as cardiac monitoring would result in potential net benefit over default strategies. CONCLUSIONS: We developed and internally validated three novel models to predict major clinical events for people with kidney failure having surgery. Models including comorbidities and laboratory variables showed improved accuracy of risk stratification and provided the greatest potential net benefit for guiding perioperative decisions. Once externally validated, these models may inform perioperative shared decision making and risk-guided strategies for this population.

Long-Term Outcomes for Living Kidney Donors With Early Guideline-Concordant Follow-up Care: A Retrospective Cohort Study.

Background: Current guidelines recommend that living kidney donors receive lifelong annual follow-up care to monitor kidney health. In the United States, the reporting of complete clinical and laboratory data for kidney donors has been mandated for the first 2 years post-donation; however, the long-term impact of early guideline-concordant care remains unclear. Objective: The primary objective of this study was to compare long-term post-donation follow-up care and clinical outcomes of living kidney donors with and without early guideline-concordant follow-up care. Design: Retrospective, population-based cohort study. Setting: Linked health care databases were used to identify kidney donors in Alberta, Canada. Patients: Four hundred sixty living kidney donors who underwent nephrectomy between 2002 and 2013. Measurements: The primary outcome was continued annual follow-up at 5 and 10 years (adjusted odds ratio with 95% confidence interval, LCLaORUCL). Secondary outcomes included mean change in estimated glomerular filtration rate (eGFR) over time and rates of all-cause hospitalization. Methods: We compared long-term follow-up and clinical outcomes for donors with and without early guideline-concordant care, defined as annual physician visit and serum creatinine and albuminuria measurement for the first 2 years post-donation. Results: Of the 460 donors included in this study, 187 (41%) had clinical and laboratory evidence of guideline-concordant follow-up care throughout the first 2 years post-donation. The odds of receiving annual follow-up for donors without early guideline-concordant care were 76% lower at 5 years (aOR 0.180.240.32) and 68% lower at 10 years (aOR 0.230.320.46) compared with donors with early care. The odds of continuing follow-up remained stable over time for both groups. Early guideline-concordant follow-up care did not appear to substantially influence eGFR or hospitalization rates over the longer term. Limitations: We were unable to confirm whether the lack of physician visits or laboratory data in certain donors was due to physician or patient decisions. Conclusions: Although policies directed toward improving early donor follow-up may encourage continued follow-up, additional strategies may be necessary to mitigate long-term donor risks.

Contexte: Les lignes directrices actuelles recommandent que les donneurs de rein vivants soient suivis annuellement, et ce, à vie, afin de surveiller leur santé rénale. Aux États-Unis, la déclaration des données cliniques et des données de laboratoire complètes pour les donneurs de rein est exigée pour les deux premières années suivant le don. On ignore cependant les répercussions à long terme pour ceux qui reçoivent des soins précoces conformes aux lignes directrices. Objectif: Le principal objectif de cette étude était de comparer les soins de suivi post-don à long terme et les résultats cliniques des donneurs de rein vivants, selon qu'ils avaient reçu ou non des soins de suivi précoces conformes aux recommandations. Type d'étude: Étude de cohorte rétrospective basée sur une population. Cadre: Les banques de données couplées du système de santé ont été utilisées pour identifier les donneurs de rein de l'Alberta (Canada). Sujets: L'étude porte sur 460 donneurs de rein vivants ayant subi leur néphrectomie entre 2002 et 2013. Mesures: Le principal critère d'évaluation était un suivi annuel continu à 5 et à 10 ans post-don (rapport de cotes corrigé avec intervalle de confiance de 95 % [LICRRcLSC]). Les résultats secondaires comprenaient la variation moyenne du débit de filtration glomérulaire estimé (DFGe) au fil du temps et les taux d'hospitalisation toutes causes confondues. Méthodologie: Nous avons comparé le suivi à long terme et les résultats cliniques de donneurs qui avaient reçu ou non des soins précoces conformes aux directives, définis par une visite annuelle chez le médecin et des mesures de la créatinine sérique et de l'albuminurie pour les deux premières années post-don. Résultats: Des 460 donneurs inclus à l'étude, 187 (41 %) disposaient de preuves de suivi conformes aux directives, soit de données cliniques et de laboratoire, pour les deux premières années post-don. Les chances d'avoir un suivi annuel pour les donneurs qui n'avaient pas reçu de soins précoces conformes aux directives étaient de 76 % inférieures à 5 ans (RRc: 0,180,240,32) et de 68 % inférieures à 10 ans (RRc: 0,230,320,46) par rapport aux donneurs qui en avaient reçu. Les chances de poursuivre le suivi sont demeurées stables au fil du temps pour les deux groupes. Le fait d'avoir reçu des soins de suivi précoces conformes aux recommandations ne semble pas avoir eu d'incidence importante sur les mesures de DFGe ou les taux d'hospitalisation à long terme. Limites: Nous n'avons pas été en mesure de confirmer si l'absence de visites chez le médecin ou le manque de données de laboratoire chez certains donneurs était dû à des décisions du médecin ou du patient. Conclusion: Bien que les politiques visant à améliorer le suivi précoce des donneurs d'organes puissent encourager la poursuite du suivi, des stratégies supplémentaires pourraient être nécessaires pour atténuer les risques à long terme pour ces personnes.

Self-Management Support Using Advertising Principles for Older Adults With Low Income at High Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: Self-management education and support (SMES) interventions have modest effects on intermediate outcomes for those at risk of cardiovascular disease, but few studies have measured or demonstrated an effect on clinical end points. Advertising for commercial products is known to influence behavior, but advertising principles are not typically incorporated into SMES design. METHODS: This randomized trial studied the effect of a novel tailored SMES program designed by an advertising firm among a population of older adults with low income at high cardiovascular risk in Alberta, Canada. The intervention included health promotion messaging from a fictitious "peer" and facilitated relay of clinical information to patients' primary care provider and pharmacist. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and hospitalizations for cardiovascular-related ambulatory care-sensitive conditions. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (EQ-5D [EuroQoL 5-dimension] index score), medication adherence, and overall health care costs. RESULTS: We randomized 4761 individuals, with a mean age of 74.4 years, of whom 46.8% were female. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. Over a median follow-up time of 36 months, the rate of the primary outcome was lower in the group that received SMES compared with the control group (incidence rate ratio, 0.78 [95% CI, 0.61 to 1.00]; P=0.047). No significant between-group changes in quality of life over time were observed (mean difference, 0.0001 [95% CI, -0.018 to 0.018]; P=0.99). The proportion of participants who were adherent to medications was not different between the 2 groups (P=0.199 for statins and P=0.754 for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Overall adjusted health care costs did not differ between those receiving SMES and the control group ($2015 [95% CI, -$1953 to $5985]; P=0.320). CONCLUSIONS: For older adults with low income, a tailored SMES program using advertising principles reduced the rate of clinical outcomes compared with usual care. The mechanisms of improvement are unclear and further studies are required. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.

Eliminating Medication Copayments for Low-Income Older Adults at High Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: One in eight people with heart disease has poor medication adherence that, in part, is related to copayment costs. This study tested whether eliminating copayments for high-value medications among low-income older adults at high cardiovascular risk would improve clinical outcomes. METHODS: This randomized 2×2 factorial trial studied 2 distinct interventions in Alberta, Canada: eliminating copayments for high-value preventive medications and a self-management education and support program (reported separately). The findings for the first intervention, which waived the usual 30% copayment on 15 medication classes commonly used to reduce cardiovascular events, compared with usual copayment, is reported here. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and cardiovascular-related hospitalizations over a 3-year follow-up. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (Euroqol 5-dimension index score), medication adherence, and overall health care costs. RESULTS: A total of 4761 individuals were randomized and followed for a median of 36 months. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. The rate of the primary outcome was not reduced by copayment elimination, (521 versus 533 events, incidence rate ratio 0.84 [95% CI, 0.66-1.07], P=0.162). The incidence rate ratio for nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (0.97 [95% CI, 0.67-1.39]), death (0.94 [95% CI, 0.80 to 1.11]), and cardiovascular-related hospitalizations (0.78 [95% CI, 0.57 to 1.06]) did not differ between groups. No significant between-group changes in quality of life over time were observed (mean difference, 0.012 [95% CI, -0.006 to 0.030], P=0.19). The proportion of participants who were adherent to statins was 0.72 versus 0.69 for the copayment elimination versus usual copayment groups, respectively (mean difference, 0.03 [95% CI, 0.006-0.06], P=0.016). Overall adjusted health care costs did not differ ($3575 [95% CI, -605 to 7168], P=0.098). CONCLUSIONS: In low-income adults at high cardiovascular risk, eliminating copayments (average, $35/mo) did not improve clinical outcomes or reduce health care costs, despite a modest improvement in adherence to medications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.

Computerised clinical decision support system for the diagnosis of pulmonary thromboembolism: a preclinical pilot study.

BACKGROUND: Recommendations for the diagnosis of pulmonary embolism are available for healthcare providers. Yet, real practice data show existing gaps in the translation of evidence-based recommendations. This is a study to assess the effect of a computerised decision support system (CDSS) with an enhanced design based on best practices in content and reasoning representation for the diagnosis of pulmonary embolism. DESIGN: Randomised preclinical pilot study of paper-based clinical scenarios in the diagnosis of pulmonary embolism. Participants were clinicians (n=30) from three levels of experience: medical students, residents and physicians. Participants were randomised to two interventions for the diagnosis of pulmonary embolism: a didactic lecture versus a decision tree via a CDSS. The primary outcome of diagnostic pathway concordance (derived as a ratio of the number of correct diagnostic decision steps divided by the ideal number of diagnostic decision steps in diagnostic algorithms) was measured at baseline (five clinical scenarios) and after either intervention for a total of 10 clinical scenarios. RESULTS: The mean of diagnostic pathway concordance improved in both study groups: baseline mean=0.73, post mean for the CDSS group=0.90 (p<0.001, 95% CI 0.10-0.24); baseline mean=0.71, post mean for didactic lecture group=0.85 (p<0.001, 95% CI 0.07-0.2). There was no statistically significant difference between the two study groups or between the three levels of participants. INTERPRETATION: A computerised decision support system designed for both content and reasoning visualisation can improve clinicians' diagnostic decision-making.

Association of Kidney Function With Major Postoperative Events After Noncardiac Ambulatory Surgeries: A Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to estimate the association between estimated glomerular filtration rate (eGFR) and acute myocardial infarction (AMI) or death after ambulatory noncardiac surgery. SUMMARY BACKGROUND DATA: People with chronic kidney disease (CKD) commonly undergo surgical procedures. Although most are performed in an ambulatory setting, the risk of major perioperative outcomes after ambulatory surgery for people with CKD is unknown. METHODS: In this retrospective population-based cohort study using administrative health data from Alberta, Canada, we included adults with measured preoperative kidney function undergoing ambulatory noncardiac surgery between April 1, 2005 and February 28, 2017. Participants were categorized into 6 eGFR categories (in mL/min/1.73m 2 )of ≥60 (G1-2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), <15 not receiving dialysis (G5ND), and those receiving chronic dialysis (G5D). The odds of AMI or death within 30 days of surgery were estimated using multivariable generalized estimating equation models. RESULTS: We identified 543,160 procedures in 323,521 people with a median age of 66 years (IQR 56-76); 52% were female. Overall, 2338 people (0.7%) died or had an AMI within 30 days of surgery. Compared with the G1-2 category, the adjusted odds ratio of death or AMI increased from 1.1 (95% confidence interval: 1.0-1.3) for G3a to 3.1 (2.6-3.6) for G5D. Emergency Department and Urgent Care Center visits within 30 days were frequent (17%), though similar across eGFR categories. CONCLUSIONS: Ambulatory surgery was associated with a low risk of major postoperative events. This risk was higher for people with CKD, which may inform their perioperative shared decision-making and management.

Perioperative management for people with kidney failure receiving dialysis: A scoping review.

BACKGROUND: People with kidney failure receiving dialysis (CKD-G5D) are more likely to undergo surgery and experience poorer postoperative outcomes than those without kidney failure. In this scoping review, we aimed to systematically identify and summarize perioperative strategies, protocols, pathways, and interventions that have been studied or implemented for people with CKD-G5D. METHODS: We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials registry (inception to February 2020), in addition to an extensive grey literature search, for sources that reported on a perioperative strategy to guide management for people with CKD-G5D. We summarized the overall study characteristics and perioperative management strategies and identified evidence gaps based on surgery type and perioperative domain. Publication trends over time were assessed, stratified by surgery type and study design. RESULTS: We included 183 studies; the most common study design was a randomized controlled trial (27%), with 67% of publications focused on either kidney transplantation or dialysis vascular access. Transplant-related studies often focused on fluid and volume management strategies and risk stratification, whereas dialysis vascular access studies focused most often on imaging. The number of publications increased over time, across all surgery types, though driven by non-randomized study designs. CONCLUSIONS: Despite many current gaps in perioperative research for patients with CKD-G5D, evidence generation supporting perioperative management is increasing, with recent growth driven primarily by non-randomized studies. Our review may inform organization of evidence-based strategies into perioperative care pathways where evidence is available while also highlighting gaps that future perioperative research can address.

Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.

AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Defining measures of kidney function in observational studies using routine health care data: methodological and reporting considerations.

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.