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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 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.

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 [SO2], ozone and small particulate matter [PM2.5]), 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 SO2 and PM2.5) in this region, as experienced by children in their first year of life, may be contributory.

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.

Key Points Question What are the incidence and outcomes associated with posttransplant Clostridioides difficile infection (CDI) in people who have undergone solid organ transplant? Findings In this cohort study including 10 724 patients, posttransplant CDI was associated with a 90-day mortality incidence of 17%. Late-onset CDI was associated with a greater risk of short- and long-term mortality compared with early-onset CDI. Meaning The findings of this large cohort of organ transplant recipients suggest a trend toward increasing risk of CDI over time., 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., This cohort study examines the incidence and outcomes associated with the development of Clostridioides difficile infection in individuals who have undergone solid organ transplant.

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) 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 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.

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.Retrospective cohort study.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.RAAS inhibitor prescription.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).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.The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 mRetrospective study and residual confounding.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.

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.

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.

Background The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown. Study Design Population-based cohort study. Settings & Participants 694,956 adults in Ontario, Canada, from 2002 to 2012. Factors eGFR and albumin-creatinine ratio (ACR). Outcome VTE. Results 15,180 (2.2%) VTE events occurred during the study period. Both albuminuria and eGFR were independently associated with VTE. The association of albuminuria and VTE differed by level of eGFR (P for ACR × eGFR interaction 90mL/min/1.73m2) and heavy albuminuria (ACR>300mg/g) compared with those with normal eGFRs and no albuminuria (subdistribution HR, 1.61; 95% CI, 1.38-1.89). Among those with reduced kidney function (eGFR, 15-29mL/min/1.73m2), the risk for VTE was only minimally increased, irrespective of albuminuria (subdistribution HRs of 1.23 [95% CI, 1-1.5] and 1.09 [95% CI, 0.82-1.45] for ACR 300mg/g, respectively). Limitations Only single determinations of ACR and eGFR were used. Diagnostic/International Classification of Diseases codes were used to define VTE. Conclusions Albuminuria increases the risk for VTE markedly in patients with normal eGFRs compared with those with lower eGFRs.

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.

BackgroundOlder adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices.MethodsRetrospective cohort study using linked administrative databases. We included patients with an eGFR ≤30 mL/min/1.73 m2 ≥66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction.ResultsThere were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ≥1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction.ConclusionsPotentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial.

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.

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.

IntroductionMany reports which use healthcare databases adjust the results for patient comorbidity. Several different indices were developed in the general population to summarize patient comorbidity. How well these indices predict one-year all-cause mortality in individuals with chronic kidney disease (CKD) is not well known. Objectives and ApproachWe accrued three groups of patients in Ontario, Canada between the years 2004 and 2014, at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an estimated glomerular filtration rate (eGFR) less than 45 mL/min per 1.73 m2. We compared 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. 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 using calibration plots. ResultsWe identified 4,111 kidney transplant recipients, 23,897 individuals receiving maintenance dialysis, and 181,425 individuals with moderate CKD. Within one year, 108 (2.6%), 4,179 (17.5%), and 17,898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate for all five comorbidity indices, with median c-statistics less than 0.7 for all three groups. Calibration was also poor for all models. Conclusion/ImplicationsExisting comorbidity indices do not accurately predict one-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.

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 300, 30–300, or

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.

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 probability of IFI-related hospitalization, and 1-year post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also examined post-IFI death-censored graft failure in renal transplant patients. Results We included 9326 SOT recipients (median follow-up 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years (95% confidence interval [CI]: 7.5–9.1). The 1-year cumulative probability of IFI was 7.4% (95% CI: 5.8–9.3%), 5.4% (95% CI: 3.6–8.1%), 1.8% (95% CI: 1.3–2.5%), 1.2% (95% CI: 0.5–3.2%), and 1.1% (95% CI: 0.9–1.4%) for lung, heart, liver, kidney-pancreas, and kidney-only transplant recipients, respectively. Lung transplant recipients had both the highest incidence rate and the highest 10-year probability of IFI: 43.0 per 1,000 person-years (95% CI: 36.8–50.0) and 26.4% (95% CI: 22.4–30.9%), respectively. Lung transplantation was also associated with the highest 1-year cumulative probability of post-IFI all-cause mortality (40.2%,95% CI: 33.1–48.3%). Among kidney transplant recipients, the 1-year probability of death-censored graft failure after IFI was 9.8% (95% CI: 6.0–15.8%). Conclusion The 1-year 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. The findings of this study considerably improved our understanding of the long-term probability of post-transplant IFI. Disclosures All authors: No reported disclosures.

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.

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.

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.

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.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.Retrospective cohort study.Ontario, Canada from 1998 to 2008 (n = 11,173).All older patients (65 years) who initiated chronic dialysis.Hospitalization with hemorrhage and its subtypes (upper and lower gastrointestinal, intra-cerebral, subarachnoid) and related-gastrointestinal procedures.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.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.Recurrent events were not included.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.Dans les cas de dialyse chronique, connaître la proportion de patients qui souffriront d’hémorragies nécessitant une hospitalisation dans les trois années suivantes fournit un éclaircissement sur le pronostic des patients, les répercussions de la maladie et la planification des essais et des programmes visant à prévenir ces épisodes.Nous avons examiné l’incidence des hémorragies et des procédures gastro-intestinales endoscopiques connexes chez les patients âgés débutant la dialyse, et les avons stratifiés par âge, par période, par modalité de dialyse et selon qu’on leur a récemment prescrit des médicaments antithrombotiques.Étude rétrospective de cohorte.Ontario, Canada, entre 1998 et 2008 (n = 11 173).Tous les patients âgés (65 ans) qui ont entamé une dialyse chronique.L’hospitalisation avec hémorragie et sous-types (hémorragie digestive haute ou basse, intracérébrale, sous-arachnoïdienne), de même que les procédures gastro-intestinales connexes.Les cas d’hémorragies nécessitant l’hospitalisation dans les trois années suivantes sont exprimés en taux d’incidence cumulatif et en taux d’incidence (nombre de cas pour 1 000 patients par année). Les résultats ont été stratifiés par âge du patient (66 à 74, 75 à 84, ≥ 85), par période (1998 à 2001, 2002 à 2005, 2006 à 2008) et par modalités de dialyse. Parmi ceux qui ont souffert d’hémorragie, nous avons examiné les prescriptions de médicaments antithrombotiques (warfarine, clopidogrel) au cours des 120 jours précédents.Le taux d’incidence cumulatif des hémorragies sur trois ans était de 14,4% (environ 1 patient sur 7). Par localisation du saignement, le taux d’incidence cumulatif sur trois ans indiquait une hémorragie digestive basse à 8,9%, intracérébrale à 0,9% et sous-arachnoïdienne à 0,1%. Le taux d’incidence cumulatif des procédures gastro-intestinales endoscopiques était de 14,8%. Le taux d’incidence cumulatif et le taux d’incidence des hémorragies ne variaient pas sensiblement en fonction de l’âge, de la période ou de la modalité de dialyse. Parmi les patients ayant souffert d’hémorragie, 29,5% ont reçu une prescription de warfarine au cours des 120 jours précédents, et 8,4%, de clopidorel.Les cas récurrents n’ont pas été considérés.Plusieurs patients âgés qui entament une dialyse chronique seront hospitalisés pour hémorragie et subiront les procédures connexes au cours des trois années suivantes. Malgré un âge plus avancé et une comorbidité au cours de la dernière décennie, la fréquence n’a pas changé.