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We analyze the design constraints of six transistor SRAM cells that arise when using nanoelectromechanical relays. Comparisons are performed between a CMOS 6T conventional SRAM cell and various hybrid memory cells built by replacing a selection of MOSFET transistors with NEM relays. Impact on important memory cell parameters such as various reliability metrics like static noise margin and write noise margin and power consumption are evaluated from circuit simulations using a Verilog-A compact model of the nanomechanical relay. We found that the use of relays involve a new challenge in the design of SRAM hybrid devices as the readability and writeability of the resulting cells manifests a strong dependence with the value of the contact resistance of the NEM relay, a parameter that can experience important variations with the continued operation of the device.

Background: People with HIV are at a greater risk of end-stage kidney disease than the general population. Considering the risk of death after end-stage kidney disease, access to renal transplantation in people with HIV is critically important., Methods: We included all adult patients on chronic dialysis in Ontario, Canada, between 1 April 2007 and 31 December 2020. We determined the probability of kidney transplantation with competing risk of death over time since the initiation of dialysis by calculating the adjusted subdistribution hazard ratios (sdHR; 95% confidence interval [CI]). We also compared long-term renal allograft and posttransplant mortality outcomes between HIV-negative and HIV-positive persons., Results: Of 40 686 people (median age, 68 years; interquartile range, 57-77; 38.4% women), 173 were HIV-positive and 40 513 were HIV-negative. The incidence of kidney transplantation in HIV-negative and HIV-positive patients was 40.5 (95% CI, 39.4-41.6)/1000 person-years and 35.0 (95% CI, 22.8-53.7)/1000 person-years, respectively ( P = .51). Considering the competing risk of death, HIV-positive people had a significantly lower chance of receiving kidney transplants than HIV-negative people (sdHR, 0.46 [95% CI, .30-.70]). The long-term allograft failure risk was not significantly different between HIV-negative and HIV-positive people, considering the competing risk of posttransplant death (sdHR, 1.71 [95% CI, .46-6.35])., Conclusions: Although the incidence and crude probability of kidney transplantation were similar among HIV-negative and HIV-positive persons in this cohort, those with HIV had a significantly lower likelihood of kidney transplantation than those without HIV. Having HIV was not significantly associated with a poor long-term allograft outcome compared with patients without HIV., Competing Interests: Potential conflicts of interest. All authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

For decades, researchers have used linkable administrative health data for evaluating the health care system, subject to local privacy legislation. In Ontario, Canada, the relevant privacy legislation permits some organizations (prescribed entities) to conduct this kind of research but is silent on their ability to identify and contact individuals in those datasets. Following consultation with the Office of the Information and Privacy Commissioner of Ontario, we developed a pilot study to identify and contact by mail a sample of people at high risk for kidney failure within the next 2 years, based on laboratory and administrative data from provincial datasets held by ICES, to ensure they receive needed kidney care. Before proceeding, we conducted six focus groups to understand the acceptability to the public and people living with chronic kidney disease of direct mail outreach to people at high risk of developing kidney failure. While virtually all participants indicated they would likely participate in the study, most felt strongly that the message should come directly from their primary care provider or whoever ordered the laboratory tests, rather than from an unknown organization. If this is not possible, they felt the health care provider should be made aware of the concern related to their kidney health. Most agreed that, if health authorities could identify people at high risk of a treatable life-threatening illness if caught early enough, there is a social responsibility to notify people. While privacy laws allow for free flow of health information among health care providers who provide direct clinical care, the proposed case-finding and outreach falls outside that model. Enabling this kind of information flow will require greater clarity in existing laws or revisions to these laws. This also requires adequate notification and culture change for health care providers and the public around information uses and flows., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Willison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 m 2 , 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 m 2 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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author M.M.S. received speaker fees from, and performed consultancy for, AstraZeneca, Bayer, Otsuka, and GlaxoSmithKline. All other authors have no disclosures., (© The Author(s) 2023.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To determine the incidence of and risk factors for imaging in patients presenting to the emergency department (ED) with renal colic. Subject/Patients and Methods: We conducted a population-based cohort study in the province of Ontario, utilizing linked administrative health data. Patients who presented to an ED with renal colic between April 1, 2010, and June 30, 2020, were included. The rate of initial imaging (CT scans and ultrasound [U/S]) and repeat imaging within 30 days was determined. Generalized linear models were utilized to evaluate patient and institutional-level characteristics associated with imaging, and specifically CT vs U/S. Results: There were 397,491 index renal colic events, of which 67% underwent imaging (CT 68%, U/S 27%, and CT+U/S same day 5%). Repeat imaging was performed in 21% of events (U/S in 12.5%, CT in 8.4%) at a median of 10 days. Of those with an initial U/S, 28% had repeat imaging compared with 18.5% for those with an initial CT. Undergoing an initial CT was associated with being male, urban residence, later year of cohort entry, history of diabetes mellitus and inflammatory bowel disease, and presentation to nonacademic hospitals of larger size, or with a higher volume of ED visits. Conclusion: Two-thirds of renal colic patients underwent imaging, and CT was the most utilized modality. Patients undergoing an initial CT had a lower likelihood of repeat imaging within 30 days. The utilization of CT increased over time and was more common in males and those presenting to nonacademic hospitals of larger size, or with higher ED volumes. Our study highlights the patient- and institution-level factors that need to be targeted with prevention strategies to reduce the utilization of CT scans, when possible, for cost reduction and to minimize patient exposure to ionizing radiation.

Background: Eligible patients with kidney failure should have equal access to kidney transplantation. Transplant referral is the first crucial step toward receiving a kidney transplant; however, studies suggest substantial variation in the rate of kidney transplant referral across regions. The province of Ontario, Canada, has a public, single-payer health care system with 27 regional chronic kidney disease (CKD) programs. The probability of being referred for kidney transplant may not be equal across CKD programs., Objective: To determine whether there is variability in kidney transplant referral rates across Ontario's CKD programs., Design: Population-based cohort study using linked administrative health care databases from January 1, 2013, to November 1, 2016., Setting: Twenty-seven regional CKD programs in the province of Ontario, Canada., Patients: Patients approaching the need for dialysis (advanced CKD) and patients receiving maintenance dialysis (maximum follow-up: November 1, 2017)., Measurements: Kidney transplant referral., Methods: We calculated the 1-year unadjusted cumulative probability of kidney transplant referral for Ontario's 27 CKD programs using the complement of Kaplan-Meier estimator. We calculated standardized referral ratios (SRRs) for each CKD program, using expected referrals from a 2-staged Cox proportional hazards model, adjusting for patient characteristics in the first stage. Standardized referral ratios with a value less than 1 were below the provincial average (maximum possible follow-up of 4 years 10 months). In an additional analysis, we grouped CKD programs according to 5 geographic regions., Results: Among 8641 patients with advanced CKD, the 1-year cumulative probability of kidney transplant referral ranged from 0.9% (95% confidence interval [CI]: 0.2%-3.7%) to 21.0% (95% CI: 17.5%-25.2%) across the 27 CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.4) to 4.2 (95% CI: 2.1-7.5). Among 6852 patients receiving maintenance dialysis, the 1-year cumulative probability of transplant referral ranged from 6.4% (95% CI: 4.0%-10.2%) to 34.5% (95% CI: 29.5%-40.1%) across CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.3) to 1.8 (95% CI: 1.6-2.1). When we grouped CKD programs according to geographic region, we found that patients residing in Northern regions had a substantially lower 1-year cumulative probability of transplant referral., Limitations: Our cumulative probability estimates only captured referrals within the first year of advanced CKD or maintenance dialysis initiation., Conclusions: There is marked variability in the probability of kidney transplant referral across CKD programs operating in a publicly funded health care system., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.X.G. received an investigator-initiated grant from Astellas Pharma Canada, Inc, which featured as a partnership fund in CIHR-funded research. All other authors declare no conflicts of interest., (© The Author(s) 2023.)

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 m 2 . 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 m 2 ) 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 m 2 , 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 m 2 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., (© 2023 The Authors.)

Background: Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD., Methods: This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death., Results: We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing., Conclusions: Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Rationale & Objective: Renin-angiotensin-aldosterone system (RAAS) inhibitors are evidence-based therapies that slow the progression of chronic kidney disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAAS inhibitors after an episode of hyperkalemia and clinical outcomes in patients with CKD., Study Design: Retrospective cohort study., Setting & Participants: Adults in Manitoba (7,200) and Ontario (n = 71,290), Canada, with an episode of de novo RAAS inhibitor-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD., Exposure: RAAS inhibitor prescription., Outcome: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and nonfatal CV events, dialysis initiation, and a negative control outcome (cataract surgery)., Analytical Approach: Cox proportional hazards models examined the association of RAAS inhibitor continuation (vs discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity-matched analyses., Results: The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 m 2 , respectively, in Manitoba; and 5.7 mEq/L and 41 mL/min/1.73 m 2 , respectively, in Ontario. RAAS inhibitor discontinuation was associated with a higher risk of all-cause mortality (Manitoba: HR, 1.32 [95% CI, 1.22-1.41]; Ontario: HR, 1.47 [95% CI, 1.41-1.52]) and CV mortality (Manitoba: HR, 1.28 [95% CI, 1.13-1.44]; and Ontario: HR, 1.32 [95% CI, 1.25-1.39]). RAAS inhibitor discontinuation was associated with an increased risk of dialysis initiation in both cohorts (Manitoba: HR, 1.65 [95% CI, 1.41-1.85]; Ontario: HR, 1.11 [95% CI, 1.08-1.16])., Limitations: Retrospective study and residual confounding., Conclusions: RAAS inhibitor discontinuation is associated with higher mortality and CV events compared with continuation among patients with hyperkalemia and CKD. Strategies to maintain RAAS inhibitor treatment after an episode of hyperkalemia may improve clinical outcomes in the CKD population., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Administrative health care databases can be efficiently analyzed to describe the degree to which patients with end-stage kidney disease (ESKD) have access to kidney transplantation. Measures of access to transplantation are better represented when restricting to only those patients eligible to receive a kidney transplant. The way administrative data can be used to assess kidney transplant eligibility in the absence of clinical data has not been well described., Objective: To demonstrate a method that uses administrative health care databases to identify patients with ESKD who have no recorded contraindication to receiving a kidney transplant., Design and Setting: Population-based cohort study using linked administrative health care databases in Ontario, Canada., Patients: Adult patients with ESKD approaching the need for dialysis (predialysis) or receiving maintenance dialysis between January 1, 2013 and March 31, 2015 in Ontario, Canada., Measurements: Recipient of a kidney-only or kidney-pancreas transplant., Methods: We assessed more than 80 baseline characteristics, including demographic information, comorbidities, kidney-specific characteristics, and referral and listing criteria for kidney transplantation. We compared these characteristics between patients who did and did not receive a kidney transplant., Results: We included 23 642 patients with ESKD (11 195 who were predialysis and 12 447 receiving maintenance dialysis). Over a median follow-up of 3.2 years (25th, 75th percentile: 1.3, 5.6), 3215 (13.6%) received a kidney-only or kidney-pancreas transplant. Of the studied characteristics available in administrative databases, >97% of patients with one or more of these characteristics did not receive a kidney transplant during follow-up: ESKD-modified Charlson Comorbidity Index score ≥7 (a higher score represents greater comorbidity), home oxygen use, age above 75 years, dementia, living in a long-term care facility, receiving at least one physician house call in the past year, and a combination of select malignancies (ie, lung, lymphoma, cervical, colorectal, liver, active multiple myeloma, and bladder cancer). Using these combined criteria reduced the total number of patients from 23 642 to 12 539 with no recorded contraindications to transplant (a 47% reduction), while the proportion who received a kidney transplant changed from 13.6% (denominator of 23 642) to 24.9% (denominator of 12 539)., Limitations: Administrative databases are unable to capture all the complexities of determining transplant eligibility., Conclusion: We identified several criteria available within administrative health care databases that can be used to identify patients with ESKD who have no recorded contraindications to kidney transplant. These criteria could be applied when reporting measures of access to kidney transplantation that require knowledge of transplant eligibility., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Amit Garg received an investigator-initiated grant from Astellas which featured as partnership funds in CIHR-funded research. The other authors declare no conflicts of interest. The results presented in this article have not been published previously in whole or part., (© The Author(s) 2022.)

Importance: Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients., Objective: To estimate the CDI incidence and outcomes in SOT recipients., Design, Setting, and Participants: A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period., Main Outcomes and Measures: The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis., Results: Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality., Conclusions and Relevance: In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Background: Air pollution is a known trigger for exacerbations among individuals with asthma, but its role in the development of new-onset asthma is unclear. We compared the rate of new asthma cases in Sarnia, a city with high pollution levels, with the rates in 2 neighbouring regions in southwestern Ontario, Canada., Methods: Using a population-based birth cohort design and linked health administrative data, we compared the hazard of incident asthma among children 0 to 10 years of age between those born in Lambton (Sarnia) and those born in Windsor and London-Middlesex, for the period Apr. 1, 1993, to Mar. 31, 2009. We used Cox proportional hazards models to adjust for year of birth and exposure to air pollutants (nitrogen dioxide, sulphur dioxide [SO 2 ], ozone and small particulate matter [PM 2.5 ]), as well as maternal, geographic and socioeconomic factors., Results: Among 114 427 children, the highest incidence of asthma was in Lambton, followed by Windsor and London-Middlesex (30.3, 24.4 and 19.8 per 1000 person-years, respectively; p < 0.001). Relative to Lambton, the hazard of asthma, adjusted for socioeconomic and perinatal factors, was lower in Windsor (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77) and London-Middlesex (HR 0.65, 95% CI 0.61-0.69). Inclusion of air pollutants attenuated this relative difference in both Windsor (HR 0.79, 95% CI 0.62-1.01) and London-Middlesex (HR 0.89, 95% CI 0.64-1.24)., Interpretation: We identified a higher incidence of asthma among children born in Lambton (Sarnia) relative to 2 other regions in southwestern Ontario. Higher levels of air pollution (particularly SO 2 and PM 2.5 ) in this region, as experienced by children in their first year of life, may be contributory., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Background and Objective: The optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)-related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia., Design: We performed a population-based, retrospective cohort study of older adults ( n =49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year., Results: Among patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention., Conclusions: Among older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality., (Copyright © 2021 by the American Society of Nephrology.)

Background: Pregnancy-associated venous thromboembolism (VTE) is associated with high morbidity and mortality. Identification of risk factors of VTE may lead to improved maternal and foetal outcomes. Proteinuria confers a pro-thrombotic state, however, its association with VTE in pregnancy remains unknown. We set out to assess the association of proteinuria and VTE during pregnancy., Methods: We conducted a population-based, retrospective cohort study of all pregnant women (≥16 years of age) with a proteinuria measure within 20 weeks of conception ( n  = 306 244; mean age 29.8 years) from Ontario, Canada. Proteinuria was defined by any of the following: urine albumin:creatinine ratio ≥3 mg/mmol, urine protein:creatinine ratio ≥5 mg/mmol or urine dipstick proteinuria ≥1. The main outcome measure was a diagnosis of VTE up to 24-weeks post-partum., Results: A positive proteinuria measurement occurred in 8508 (2.78%) women and was more common with a history of kidney disease, gestational or non-gestational diabetes mellitus and hypertension. VTE events occurred in 625 (0.20%) individuals, with a higher risk among women with positive proteinuria [32 events (0.38%)] compared with women without proteinuria [593 events (0.20%); inverse probability-weighted risk ratio 1.79 (95% confidence interval 1.25-2.57)]. The association was consistent using a more specific VTE definition, in the post-partum period, in high-risk subgroups (hypertension or diabetes) and when the sample was restricted to women with preserved kidney function., Conclusions: The presence of proteinuria in the first 20 weeks of pregnancy is associated with a significantly higher risk of VTE., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objectives: It is uncertain whether primary care physician continuity of care associates with a lower risk of death and hospitalization among patients transitioning to maintenance dialysis., Design, Setting, Participants, & Measurements: Using provincial-linked administrative databases in Ontario, Canada, we conducted a population-based study of incident patients who initiated maintenance dialysis between 2005 and 2014 and survived for at least 90 days. We defined high primary care physician continuity as both a high usual provider of care index (where >75% of primary care physician visits occurred with the same primary care physician) in the 2 years before dialysis (an established measure of primary care physician continuity) and at least one visit with the same primary care physician in the 90 days after dialysis initiation. We used propensity scores to match a group of patients with high and low continuity so that indicators of baseline health were similar. The primary outcome was all-cause mortality, and secondary outcomes included all-cause and disease-specific hospitalizations during the 2 years after maintenance dialysis initiation., Results: We identified 19,099 eligible patients. There were 6612 patients with high primary care physician continuity, of whom 6391 (97%) were matched to 6391 patients with low primary care physician continuity. High primary care physician continuity was not associated with a lower risk of mortality (14.5 deaths per 100 person-years versus 15.2 deaths per 100 person-years; hazard ratio, 0.96; 95% confidence interval, 0.89 to 1.02). There was no difference in the rate of all-cause hospitalizations (hazard ratio, 0.96; 95% confidence interval, 0.92 to 1.01), and high primary care physician continuity was not associated with a lower risk of any disease-specific hospitalization, except for those related to diabetes (hazard ratio, 0.88; 95% confidence interval, 0.80 to 0.97)., Conclusions: High primary care physician continuity before and during the transition to maintenance dialysis was not associated with a lower risk of mortality or all-cause hospitalization., (Copyright © 2020 by the American Society of Nephrology.)

Background: Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood., Methods: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1-, 5-, and 10-year cumulative probabilities of IFI; and post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also determined post-IFI, death-censored renal allograft failure., Results: We included 9326 SOT recipients (median follow-up: 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years. The 1-year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney-pancreas, and 1.1% for kidney-only allograft recipients. Lung transplant recipients had the highest incidence rate and 10-year probability of IFI: 43.0 per 1000 person-years and 26.4%, respectively. The 1-year all-cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow-up period (hazard ratio: 6.50, 95% CI: 5.69-7.42). The 1-year probability of death-censored renal allograft failure after IFI was 9.8%., Conclusion: Long-term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Prior studies reported lower mortality with hemodialysis (HD) compared to peritoneal dialysis (PD) in patients with heart failure (HF). We examined mortality rate by initial dialysis modality in incident dialysis patients with a history of HF using contemporary data and methods that ensure comparable HD and PD groups., Methods: Retrospective cohort study using administrative databases in Ontario, Canada. Adults (age 50-80) with a history of HF who initiated maintenance dialysis between April 1, 2007 and March 31, 2016 were included. We excluded patients typically ineligible for PD as an initial modality (dialysis start in hospital, dementia, long-term care facility residency). We determined the cause-specific hazard ratio (transplant as a competing event) between initial dialysis modality (HD vs. PD) and all-cause mortality using an intention-to-treat approach., Results: We included 2,199 patients with HF who initiated maintenance dialysis (77% HD and 23% PD). There were 1,152 (67.8%) and 340 (68.1%) mortality events over a median follow-up of 2.4 and 2.5 years in the HD and PD groups, respectively. Patients initiating HD versus PD was not associated with the mortality rate (adjusted hazard ratio 1.0, 95% CI 0.9-1.1). Similar results were seen in analyses censoring at modality switches and treating modality as time-varying., Conclusions: We found no difference in mortality by initial dialysis modality. Our data support the current practice of selecting dialysis modality based on patient preference for patients with pre-existing HF., (© 2020 S. Karger AG, Basel.)

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use., Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age., Design, Setting, and Participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level., Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting., Main Outcomes and Measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription., Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury., Conclusions and Relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

Background Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST-segment-elevation myocardial infarction ( STEMI ) and non-ST-segment-elevation myocardial infarction ( NSTEMI ) differ in the chronic kidney disease population is unknown. Methods and Results Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR ) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used. In 248 438 patients with 1.2 million person-years of follow-up, STEMI , NSTEMI , and death occurred in 1436 (0.58%), 4431 (1.78%), and 30 015 (12.08%) patients, respectively. The highest level of albumin-to-creatinine ratio (>30 mg/mmol) was associated with a 2-fold higher adjusted risk of both STEMI and NSTEMI among patients with eGFR ≥60 mL/(min·1.73 m 2 ) compared to albumin-to-creatinine ratio <3 mg/mmol. The lowest level of eGFR (<30 mL/[min·1.73 m 2 ]) was not associated with higher STEMI risk but with a 4-fold higher risk of NSTEMI compared to those with eGFR ≥60 mL/(min·1.73 m 2 ). The lowest eGFR (<30 mL/[min·1.73 m 2 ]) and highest albumin-to-creatinine ratio (>30 mg/mmol) were associated with a greater than 4-fold higher risk of both STEMI and NSTEMI (subdistribution hazard models [95% confidence interval] 4.53 [3.30-6.21] and 4.42 [3.67-5.32], respectively) compared to albumin-to-creatinine ratio <3 mg/mmol and eGFR ≥60 mL/(min·1.73 m 2 ). Conclusions Elevations in albuminuria are associated with a higher risk of both NSTEMI and STEMI , regardless of kidney function, whereas reduced kidney function alone is associated with a higher NSTEMI risk.

Background: Several different indices summarize patient comorbidity using health care data. An accurate index can be used to describe the risk profile of patients, and as an adjustment factor in analyses. How well these indices perform in persons with chronic kidney disease (CKD) is not well known., Objective: Assess the performance of 5 comorbidity indices at predicting mortality in 3 different patient groups with CKD: incident kidney transplant recipients, maintenance dialysis patients, and individuals with low estimated glomerular filtration rate (eGFR)., Design: Population-based retrospective cohort study., Setting: Ontario, Canada, between 2004 and 2014., Patients: Individuals at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an eGFR less than 45 mL/min per 1.73m 2 ., Measurements: Five comorbidity indices: Charlson comorbidity index, end-stage renal disease-modified Charlson comorbidity index, Johns Hopkins' Aggregated Diagnosis Groups score, Elixhauser score, and Wright-Khan index. Our primary outcome was 1-year all-cause mortality., Methods: Comorbidity indices were estimated using information in the prior 2 years. Each group was randomly divided 100 times into derivation and validation samples. Model discrimination was assessed using median c-statistics from logistic regression models, and calibration was evaluated graphically., Results: We identified 4111 kidney transplant recipients, 23 897 individuals receiving maintenance dialysis, and 181 425 individuals with a low eGFR. Within 1 year, 108 (2.6%), 4179 (17.5%), and 17 898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate with median c-statistics less than 0.7 for all 5 comorbidity indices for all 3 groups. Calibration was also poor for all models., Limitations: The study used administrative health care data so there is the potential for misclassification. Indices were modeled as continuous scores as opposed to indicators for individual conditions to limit overfitting., Conclusions: Existing comorbidity indices do not accurately predict 1-year mortality in patients with CKD. Current indices could be modified with additional risk factors to improve their performance in CKD, or a new index could be developed for this population., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Many patients who receive chronic hemodialysis have a limited life expectancy comparable to that of patients with metastatic cancer. However, patterns of home palliative care use among patients receiving hemodialysis are unknown., Objectives: We aimed to undertake a current-state analysis to inform measurement and quality improvement in palliative service use in Ontario., Methods: We conducted a descriptive study of outcomes and home palliative care use by Ontario residents maintained on chronic dialysis using multiple provincial healthcare datasets. The period of study was the final year of life, for those died between January 2010 and December 2014., Results: We identified 9611 patients meeting inclusion criteria. At death, patients were (median [Q1, Q3] or %): 75 (66, 82) years old, on dialysis for 3.0 (1.0-6.0) years, 41% were women, 65% had diabetes, 29.6% had dementia, and 13.9% had high-impact neoplasms, and 19.9% had discontinued dialysis within 30 days of death. During the last year of life, 13.1% received ⩾1 home palliative services. Compared with patients who had no palliative services, those who received home palliative care visits had fewer emergency department and intensive care unit visits in the last 30 days of life, more deaths at home (17.1 vs 1.4%), and a lower frequency of deaths with an associated intensive care unit stay (8.1 vs 37.8%)., Conclusions: Only a small proportion of patients receiving dialysis in Ontario received support through the home palliative care system. There appears to be an opportunity to improve palliative care support in parallel with dialysis care, which may improve patient, family, and health-system outcomes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Contemporary data on venous thromboembolism (VTE) risk in dialysis patients are limited. Our objective was to determine the risk and complications of VTE among incident maintenance dialysis patients., Methods: We performed a retrospective cohort study using administrative databases. We included adult incident dialysis patients from 2004 to 2010 (n = 13 315). Dialysis patients were age- and sex-matched to individuals of the general population using a 1:4 ratio (n = 53 260). We determined the 3-year cumulative incidence and incidence rate (IR) of VTE, pulmonary embolism (PE) and deep venous thrombosis (DVT). We examined outcomes of bleeding and all-cause mortality following a VTE event among matched dialysis patients who did and did not experience a VTE. We used Cox proportional hazards regression models, stratified on matched sets, to calculate the hazard ratios (HRs) for all outcomes of interest., Results: VTE occurred in 1114 (8.4%) dialysis patients compared with 1233 (2.3%) individuals in the general population {IR 37.1 versus 8.1 per 1000 person-years; HR 4.5 [95% confidence interval (CI) 4.1-4.9]; adjusted HR 2.9 (95% CI 2.6-3.4)}. Both components of VTE [PE and DVT; adjusted HR 4.0 (95% CI 2.9-5.6) and HR 2.8 (95% CI 2.4-3.2), respectively] occurred more frequently in dialysis patients. Compared with dialysis patients without a VTE, those with a VTE had a higher risk of bleeding [adjusted HR 2.0 (95% CI 1.3-2.9)] and all-cause mortality [adjusted HR 2.4 (95% CI 2.0-2.8)]., Conclusions: VTE is common in dialysis patients and confers a high risk of major bleeding and all-cause mortality. Thromboprophylaxis and VTE treatment studies in dialysis patients are needed.

The utility of anticoagulants for ischemic stroke prophylaxis in elderly patients with chronic kidney disease (CKD) and atrial fibrillation remains uncertain. In this population-based retrospective cohort study, we determined the association of anticoagulant use with ischemic stroke or hemorrhage in elderly patients (66 years and older) with advanced chronic kidney disease (eGFR under 45 ml/min/1.73m 2 ) and atrial fibrillation. We followed 6,544 patients with CKD and new onset atrial fibrillation, of whom 1,475 filled a prescription for an anticoagulant. We used propensity-score matched Cox proportional hazards and competing risk models to determine the time to first event of ischemic stroke, hemorrhage or mortality. After matching to examine exposure to anticoagulants, 1,417 matched pairs were identified. The crude rate of ischemic stroke and hemorrhage were 41.3 and 61.3 with anticoagulants and 34.4 and 34.3 without anticoagulants per 100 person-years, respectively. The hazard ratios of ischemic stroke, hemorrhage, and mortality for receipt of an anticoagulation prescription were 1.10 (95% confidence interval, 0.78-1.56), 1.42 (1.04-1.93), and 0.74 (0.62-0.88) as compared to non-receipt of anticoagulation. After accounting for the competing risk of death, the hazard ratios for ischemic stroke and hemorrhage were 1.12 (0.90-1.39) and 1.60 (1.31-1.97), respectively. The findings were consistent in a sensitivity analysis accounting for time varying anticoagulant exposure. Thus, in older patients with CKD and atrial fibrillation, receipt of an anticoagulant was not associated with a lower risk of ischemic stroke, but a higher risk of hemorrhage and a lower risk of mortality., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described., Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant., Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE., Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss., (© 2017 S. Karger AG, Basel.)

New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002-2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m(2)) and urine albumin-to-creatinine ratio (ACR; >300, 30-300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m(2) had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted., (Copyright © 2016 by the American Society of Nephrology.)

Background: Major hemorrhagic events are associated with significant morbidity and mortality. We examined the three-year cumulative incidence of hospitalization with major nontraumatic hemorrhage after kidney transplantation., Methods: We performed a retrospective cohort study using healthcare administrative data of all adult-incident kidney-only transplantation recipients in Ontario, Canada from 1994 to 2009. We calculated the three-year cumulative incidence, event rate, and incident rate ratio of hospitalization with major hemorrhage, its subtypes and those undergoing a hemorrhage-related procedure. RESULTS were stratified by patient age and donor type and compared to a random and propensity-score matched sample from the general population., Results: Among 4,958 kidney transplant recipients, the three-year cumulative incidence of hospitalization with nontraumatic major hemorrhage was 3.5% (95% confidence interval [CI] 3.0-4.1%, 12.7 events per 1,000 patient-years) compared to 0.4% (95% CI 0.4-0.5%) in the general population (RR = 8.2, 95% CI 6.9-9.7). The crude risk of hemorrhage was 3-9-fold higher in all subtypes (upper/lower gastrointestinal, intra-cranial) and 15-fold higher for gastrointestinal endoscopic procedures compared to the random sample from the general population. After propensity score matching, the relative risk for major hemorrhage and its subtypes attenuated but remained elevated. The cumulative incidence of hemorrhage was higher for older individuals and those with a deceased donor kidney., Conclusion: Kidney transplantation recipients have a higher risk of hospitalization with hemorrhage compared to the general population, with about 1 in 30 recipients experiencing a major hemorrhage in the three years following transplant., (© 2015 S. Karger AG, Basel.)

Background: For those who initiate chronic dialysis, knowing what proportion will experience 3-year outcomes of hemorrhage with hospitalization informs patient prognosis, disease impact, and the planning of trials and programs to prevent events., Objectives: We examined the incidence of hemorrhage and related gastrointestinal endoscopic procedures in incident older dialysis patients and stratified patients by age, era, dialysis modality and whether recently prescribed anti-thrombotic medication., Design: Retrospective cohort study., Setting: Ontario, Canada from 1998 to 2008 (n = 11,173)., Patients: All older patients (>65 years) who initiated chronic dialysis., Measurements: Hospitalization with hemorrhage and its subtypes (upper and lower gastrointestinal, intra-cerebral, subarachnoid) and related-gastrointestinal procedures., Methods: Three-year outcomes of hospitalization with hemorrhage were expressed as cumulative incidence and incidence rate (number of events per 1,000 patient years). Results were stratified by patient age (66 to 74, 75 to 84, ≥ 85), era (1998 to 2001, 2002 to 2005, 2006 to 2008) and dialysis modality. Among those with hemorrhage, we examined prescriptions for anti-thrombotic medications (warfarin, clopidogrel) in the preceding 120 days., Results: The 3-year cumulative incidence of hemorrhage was 14.4% (roughly 1 in 7 patients). By location, the 3-year cumulative incidence was 8.9% lower gastrointestinal, 6.1% upper gastrointestinal, 0.9% intra-cerebral and 0.1% sub arachnoid hemorrhage. The 3-year cumulative incidence of gastrointestinal endoscopic procedures was 14.8%. The cumulative incidence and rate of hemorrhage were not appreciably different across the 3 age strata, by era or by dialysis modality. Among patients with a hemorrhage, 29.5% were prescribed warfarin in the preceding 120 days, and 8.4% clopidogrel., Limitations: Recurrent events were not included., Conclusions: Many older patients who initiate chronic dialysis will be hospitalized with hemorrhage and receive related procedures over the subsequent three years. Despite greater age and co-morbidity over the last decade this incidence has not changed.