Defining pre-emptive living kidney donor transplantation as a quality indicator.

Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems.

Effectiveness of first, second, and third COVID-19 vaccine doses in solid organ transplant recipients: A population-based cohort study from Canada.

Limited data exists on the effectiveness of a third COVID-19 vaccine dose in solid organ transplant recipients. We conducted a population-based cohort study using linked healthcare databases from Ontario, Canada to answer this question. We included solid organ transplant recipients (n = 12,842) as of December 14, 2020, with follow-up until November 28, 2021. We used an extended Cox proportional hazards model with vaccination status, including BNT162b2, mRNA-1273, and ChAdOx1 vaccines, modeled as a time-dependent exposure. Individuals started in the unvaccinated category (reference) and could contribute person-time to first, second, and third doses. Over a median follow-up of 349 days, 12.7% (n = 1632) remained unvaccinated, 54.1% (n = 6953) received 3 doses, and 488 (3.8%) tested positive for SARS-CoV-2 (of which 260 [53.3%] had a clinically important outcome [i.e., hospitalization or death]). Adjusted vaccine effectiveness against infection was 31% (95% CI: 2, 51%), 46% (95% CI: 21, 63%), and 72% (95% CI: 43, 86%) for one, two, and three doses. Vaccine effectiveness against clinically important outcomes was 38% (95% CI: 4, 61%), 54% (95% CI: 23, 73%), and 67% (95% CI: 11, 87%). Vaccine effectiveness in solid organ transplant recipients is lower than the general population, however, vaccine effectiveness improved following a third dose.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1): a pragmatic stepped-wedge, cluster randomized controlled registry trial.

BACKGROUND: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices. METHODS: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention. RESULTS: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery. CONCLUSIONS: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration. TRIAL REGISTRATION: NCT03213171.

Pre-transplant maintenance dialysis duration and outcomes after kidney transplantation: A multicenter population-based cohort study.

The association between pre-transplant dialysis duration and post-transplant outcomes may vary by the population and endpoints studied. We conducted a population-based cohort study using linked healthcare databases from Ontario, Canada including kidney transplant recipients (n = 4461) from 2004 to 2014. Our primary outcome was total graft failure (i.e., death, return to dialysis, or pre-emptive re-transplant). Secondary outcomes included death-censored graft failure, death with graft function, mortality, hospitalization for cardiovascular events, hospitalization for infection, and hospital readmission. We presented results by pre-transplant dialysis duration (pre-emptive transplant, and .01-1.43, 1.44-2.64, 2.65-4.25, 4.26-6.45, and 6.46-36.5 years, for quintiles 1-5). After adjusting for clinical characteristics, pre-emptive transplantation was associated with a lower rate of total graft failure (adjusted hazard ratio [aHR] .68, 95% CI: .46, .99), while quintile 4 was associated with a higher rate (aHR 1.31, 95% CI: 1.01, 1.71), when compared to quintile 1. There was no significant relationship between dialysis duration and death-censored graft failure, cardiovascular events, or hospital readmission. For death with graft function and mortality, quintiles 3-5 had a significantly higher aHR compared to quintile 1, while for infection, quintiles 2-5 had a higher aHR. Longer time on dialysis was associated with an increased rate of several adverse post-transplant outcomes.

Partnering with Patients to Enhance Access to Kidney Transplantation and Living Kidney Donation.

Kidney transplantation gives many patients with kidney failure a longer and healthier life. Unfortunately, some transplant-eligible patients will never receive one. In this paper, we describe how patients and researchers collaborated on new strategies and programs to enhance access to kidney transplantation and living kidney donation. These efforts led to the creation of the Transplant Ambassador Program (TAP). TAP is a patient-led program that helps connect patients who have kidney failure to individuals who have successfully received a kidney transplant or donated a kidney. We also detail barriers, facilitators and lessons learned from engaging patients in research.

Interventions for increasing solid organ donor registration.

BACKGROUND: A solution for increasing the number of available organs for transplantation is to encourage more individuals to register a commitment for deceased organ donation. However, the percentage of the population registered for organ donation remains low in many countries. OBJECTIVES: To evaluate the benefits and harms of various interventions used to increase deceased organ donor registration. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 11 August 2020 through contact with an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs of interventions to promote deceased organ donor registration. We included studies if they measured self-reported or verified donor registration, intention to donate, intention to register a decision or number of individuals signing donor cards as outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed retrieved studies and extracted data from included studies. We assessed studies for risk of bias. We obtained summary estimates of effect using a random-effects model and expressed results as risk ratios (RR) (95% confidence intervals; CI) for dichotomous outcomes and mean difference (MD; 95% CI) or standardised mean difference (SMD; 95% CI) for continuous outcomes. In multi-arm trials, data were pooled to create single pair-wise comparisons. Analyses were stratified by specific intervention setting where available. MAIN RESULTS: Our search strategy identified 46 studies (47 primary articles, including one abstract) comprising 24 parallel RCTs, 19 cluster RCTs and 3 quasi-RCTs. Sample sizes ranged from 138 to 1,085,292 (median = 514). A total of 16 studies measured registration behaviour, 27 measured intention to register/donate and three studies measured both registration behaviour and intention to register. Interventions were delivered in a variety of different settings: schools (14 studies), driver's motor vehicle (DMV) centres (5), mail-outs (4), primary care centres (3), workplaces (1), community settings (7) and general public (12). Interventions were highly varied in terms of their content and included strategies such as educational sessions and videos, leveraging peer leaders, staff training, message framing, and priming. Most studies were rated as having high or unclear risk of bias for random sequence generation and allocation concealment and low risk for the remainder of the domains. Data from 34/46 studies (74%) were available for meta-analysis. Low certainty evidence showed organ donation registration interventions had a small overall effect on improving registration behaviour (16 studies, 1,294,065 participants: RR 1.30, 95% CI 1.19 to 1.43, I2 = 84%), intention to register/donate (dichotomous) (10 studies, 10,838 participants: RR 1.21, 95% CI 1.03 to 1.42, I2 = 91%) and intention to register/donate (continuous) (9 studies, 3572 participants: SMD 0.23, 95% CI 0.11 to 0.36, I2 = 67%). Classroom-based interventions delivered in a lecture format by individuals from the transplant community may be effective at increasing intention to register/donate (3 studies, 675 participants: RR 1.33, 95% CI 1.15 to 1.55, I² = 0%). Community interventions targeting specific ethnic groups were generally effective at increasing registration rates (k = 5, n = 4186; RR 2.14, 95% CI 1.35 to 3.40, I² = 85%), although heterogeneity was high. In particular, interventions delivered in the community by trained peer-leaders appear to be effective (3 studies, 3819 participant: RR 2.09, 95% CI 1.08 to 4.06, I² = 87%), although again, the data lacked robustness. There was some evidence that framing messages (e.g. anticipated regret) and priming individuals (e.g. reciprocity) in a certain way may increase intention to register/donate, however, few studies measured this effect on actual registration. Overall, the studies varied significantly in terms of design, setting, content and delivery. Selection bias was evident and a quarter of the studies could not be included in the meta-analysis due to incomplete outcome data reporting. No adverse events were reported. AUTHORS' CONCLUSIONS: In our review, we identified a variety of approaches used to increase organ donor registration including school-based educational sessions and videos, leveraging peer leaders in the community, DMV staff training, targeted messaging and priming. The variability in outcome measures used and incompleteness in reporting meant that most data could not be combined for analysis. When data were combined, overall effect sizes were small in favour of intervention groups over controls, however, there was significant variability in the data. There was some evidence that leveraging peer-leaders in the community to deliver organ donation education may improve registration rates and classroom-based education from credible individuals (i.e. members of the transplant community) may improve intention to register/donate, however, there is no clear evidence favouring any particular approach. There was mixed evidence for simple, low-intensity interventions utilising message framing and priming. However, it is likely that interest in these strategies will persist due to their reach and scalability. Further research is therefore required to adequately address the question of the most effective interventions for increasing deceased organ donor registration.

Incidence and outcomes of invasive fungal infection among solid organ transplant recipients: A population-based cohort study.

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.

Mortality in Incident Maintenance Dialysis Patients Versus Incident Solid Organ Cancer Patients: A Population-Based Cohort.

RATIONALE & OBJECTIVE: The mortality rate is high among dialysis patients, but how this compares with other diseases such as cancer is poorly understood. We compared the survival of maintenance dialysis patients with that for patients with common cancers to enhance the understanding of the burden of end-stage kidney disease. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 33,500 incident maintenance dialysis patients in Ontario, Canada, and 532,452 incident patients with cancer (women: breast, colorectal, lung, or pancreas; men: prostate, colorectal, lung, or pancreas) from 1997 to 2015 using administrative health care databases. EXPOSURE: Incident kidney failure treated with maintenance dialysis versus incident diagnoses of cancer. OUTCOME: All-cause mortality. ANALYTICAL APPROACH: Kaplan-Meier product limit estimator was used to describe the survival of subgroups of study participants. Extended Cox regression with a Heaviside function was used to compare survival between patients with incident kidney failure treated with maintenance dialysis and individual diagnoses of various incident cancers. RESULTS: In men, dialysis had worse unadjusted 5-year survival (50.8%; 95% CI, 50.1%-51.6%) compared with prostate (83.3%; 95% CI, 83.1%-83.5%) and colorectal (56.1%; 95% CI, 55.7%-56.5%) cancer, but better survival than lung (14.0%; 95% CI, 13.7%-14.3%) and pancreas (9.1%; 95% CI, 8.5%-9.7%) cancer. In women, dialysis had worse unadjusted 5-year survival (49.8%; 95% CI, 48.9%-50.7%) compared with breast (82.1%; 95% CI, 81.9%-82.4%) and colorectal (56.8%; 95% CI, 56.3%-57.2%) cancer, but better survival than lung (19.7%; 95% CI, 19.4%-20.1%) and pancreas (9.4%; 95% CI, 8.9%-10.0%) cancer. After adjusting for clinical characteristics, similar results were found except when examining men and women with lung and pancreas cancer, for which dialysis patients had a higher rate of death 4 or more years after diagnosis. Women and men 70 years and older with incident kidney failure treated with maintenance dialysis had unadjusted 10-year survival probabilities that were comparable to pancreas and lung cancer. LIMITATIONS: Cancer stage could be obtained for only a subpopulation. CONCLUSIONS: Survival in incident dialysis patients was lower than in patients with several different solid-organ cancers. These results highlight the need to develop interventions to improve survival on dialysis therapy and can be used to aid advance care planning for elderly patients beginning treatment with maintenance dialysis.

Venous Thromboembolism and the Risk of Death and Graft Loss in Kidney Transplant Recipients.

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.

Epidemiology of Fracture in Adults from Ontario, Canada, with Chronic Kidney Disease: An Examination of Fracture Burden Using Administrative Health Data.

Fractures are associated with morbidity and mortality. Individuals with chronic kidney disease (CKD) experience bone mineral metabolism changes, which increases fracture risk. Researchers have quantified the epidemiology of fractures in adults with CKD using administrative health databases from Ontario, Canada, held at the Institute for Clinical Evaluative Sciences. Results demonstrated that many individuals with non-transplant CKD sustain fractures, with the risk increasing as kidney function declines. However, fracture risk in kidney transplant recipients was lower than previously described, which suggests recipients may not be a high-risk fracture group. There is a need to test fracture prevention interventions in the CKD population.

Risk of major hemorrhage after kidney transplantation.

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.

Calcium channel blocker-clarithromycin drug interaction did not increase the risk of nonvertebral fracture: a population-based study.

BACKGROUND: Calcium channel blocker (CCB) use in elderly patients lowers blood pressure and can increase the risk of falls and fractures. These drugs are metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme, and blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4, whereas azithromycin is not. OBJECTIVE: In older patients taking a CCB, we investigated whether coprescription of clarithromycin, compared with azithromycin, was associated with a higher risk of fracture. METHODS: This was a population-level retrospective cohort study in Ontario, Canada, from 2003 to 2012 of older adults (mean age = 76 years) newly prescribed clarithromycin (n = 96 226) or azithromycin (n = 94 083) while taking a CCB (amlodipine, nifedipine, felodipine, verapamil, diltiazem). The outcome assessed within 30 days of a new coprescription was a nonvertebral fracture. RESULTS: There were no differences in measured baseline characteristics between the clarithromycin and azithromycin groups. Amlodipine was the most commonly prescribed CCB (more than 50% of patients). Coprescribing clarithromycin, versus azithromycin, was not associated with a higher 30-day risk of nonvertebral fracture (124 patients of 96 226 taking clarithromycin [0.13%] vs 98 patients of 94 083 taking azithromycin [0.10%]; odds ratio = 1.23 [95% CI = 0.94-1.60]; P = 0.134). CONCLUSIONS: Among older adults taking a CCB, concurrent use of clarithromycin, compared with azithromycin, was not associated with a statistically significantly greater 30-day risk of nonvertebral fracture.

The three-year incidence of fracture in chronic kidney disease.

Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2)), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.

Bone health in living kidney donors.

PURPOSE OF REVIEW: Living kidney donors may experience changes in bone mineral metabolism, which adversely affect the skeletal system. In this review, we summarize the literature assessing the relationship between living kidney donation, changes in bone mineral metabolism, and skeletal fracture. RECENT FINDINGS: Living kidney donor nephrectomy may lower the concentration of 1,25-dihydroxyvitamin D and phosphate and raise the concentration of parathyroid hormone, with no appreciable effect on the concentration of calcium. There is conflicting evidence on whether the concentration of fibroblast growth factor 23 rises after kidney donation. Whether these changes in bone mineral metabolism alter skeletal fracture risk in living kidney donors is an open question. To date, a single study of over 2000 living kidney donors (median age 43 years) matched to a segment of the general population selected for good health has found that after a median follow-up of 6.6 years (maximum 17.7 years), the rate of fragility (osteoporotic) fractures is no higher in donors compared to nondonors. SUMMARY: Living kidney donors experience changes in bone mineral metabolism. Long-term studies are needed to determine whether an association between living kidney donation and fracture exists.

Effectiveness of a Fourth COVID-19 mRNA Vaccine Dose Against the Omicron Variant in Solid Organ Transplant Recipients.

BACKGROUND: The effectiveness of booster doses of COVID-19 vaccines in solid organ transplant recipients is unclear. We conducted a population-based matched cohort study using linked administrative healthcare databases from Ontario, Canada to estimate the marginal vaccine effectiveness of a fourth versus third dose of the BNT162b2 and mRNA-1273 vaccines against clinically important outcomes (ie, hospitalization or death) and infection during the era of the Omicron variant. METHODS: We matched 3120 solid organ transplant recipients with a third COVID-19 vaccine dose (reference) to 3120 recipients with a fourth dose. Recipients were matched on the third dose date (±7 d). We used a multivariable Cox proportional hazards model to estimate the marginal vaccine effectiveness with outcomes occurring between December 21, 2021 and April 30, 2022. RESULTS: The cumulative incidence of COVID-19-related hospitalization or death was 2.8% (95% confidence interval [CI], 2.0-3.7) in the third dose group compared with 1.1% (95% CI, 0.59-1.8) in the fourth dose group after 84 d of follow-up (P < 0.001). The adjusted marginal vaccine effectiveness was 70% (95% CI, 47-83) against clinically important outcomes and 39% (95% CI, 21-52) against SARS-CoV-2 infection. CONCLUSIONS: Compared with a third dose, a fourth dose of the COVID-19 vaccine was associated with improved protection against hospitalization, death, and SARS-CoV-2 infection during the Omicron era. Results highlight the importance of a booster COVID-19 vaccine dose in solid organ transplant recipients.

Comparison of COVID-19 Hospitalization and Death Between Solid Organ Transplant Recipients and the General Population in Canada, 2020-2022.

Background: Solid organ transplant recipients have a high risk of severe outcomes from SARS-CoV-2 infection. A comprehensive understanding of the impact of the COVID-19 pandemic across multiple waves in the solid organ transplant population and how this compares to the general population is limited. We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to answer this question. Methods: We included 15 306 solid organ transplant recipients and 12 160 904 individuals from the general population. Our primary outcome was the rate (per 100 person-years) of severe COVID-19 (ie, hospitalization or death with a positive SARS-CoV-2 test) occurring between January 25, 2020, and November 30, 2022. Results: Compared with the general population, solid organ transplant recipients had almost a 6 times higher rate of severe COVID-19 (20.39 versus 3.44 per 100 person-years), with almost 5.5 times as high a rate of death alone (4.19 versus 0.77 per 100 person-years). Transplant recipients with severe COVID-19 were substantially younger (60.1 versus 66.5 y) and had more comorbidities. The rate of severe COVID-19 declined over time in the solid organ transplant population, with an incidence rate of 41.25 per 100 person-years in the first wave (January 25, 2020, to August 31, 2020) and 18.41 in the seventh wave (June 19, 2022, to November 30, 2022, Omicron era). Conclusions: Solid organ transplant recipients remain at high risk of severe outcomes when they are infected with SARS-CoV-2. Resources and strategies to mitigate the impact of SARS-CoV-2 exposure are needed in this vulnerable patient population.

Comparison of Acute Health Care Utilization Between Patients Receiving In-Center Hemodialysis and the General Population: A Population-Based Matched Cohort Study From Ontario, Canada.

Background: Patients receiving maintenance hemodialysis have multiple comorbidities and are at high risk of presenting to the hospital. However, the incidence and cost of acute health care utilization in the in-center hemodialysis population and how this compares with other populations is poorly understood. Objective: To determine the rate, pattern, and cost of emergency department visits and hospitalizations in patients receiving in-center hemodialysis compared with a matched general population. Design: Population-based matched cohort study. Setting: We used linked administrative health care databases from Ontario, Canada. Patients: We included 25 379 patients (incident and prevalent) receiving in-center hemodialysis between January 1, 2010, and December 31, 2018. Patients were matched on birth date (±2 years), sex, and cohort entry date using a 1:4 ratio to 101 516 individuals from the general population. Measurements: Our primary outcomes were emergency department visits (allowing for multiple visits per individual) and hospital admissions from the emergency department. We also assessed all-cause hospitalizations, all-cause readmissions within 30 days of discharge from the original hospitalization, length of stay for hospital admissions (including multiple visits per individual), and the financial cost of these admissions. Methods: We presented the rate, percentage, median (25th, 75th percentiles), and incidence rate per 1000 person-years for emergency department visits and hospitalizations. Individual-level health care costs for emergency department visits and all-cause hospitalization were estimated using resource intensity weights multiplied by the cost per weighted case. Results: Patients receiving in-center hemodialysis had substantially more comorbidities (eg, diabetes) than the matched general population. Eighty percent (n = 20 309) of patients receiving in-center hemodialysis had at least 1 emergency department visit compared with 56% (n = 56 452) of individuals in the matched general population, over a median follow-up of 1.8 years (25th, 75th percentiles: 0.7, 3.6) and 5.2 (2.5, 8.4) years, respectively. The incidence rate of emergency department visits, allowing for multiple visits per individual, was 2274 per 1000 person-years (95% confidence interval [CI]: 2263, 2286) for patients receiving in-center hemodialysis, which was almost 5 times as high as the matched general population (471 per 1000 person-years; 95% CI: 469, 473). The rate of hospital admissions from the emergency department and the rate of all-cause hospital admissions in the in-center hemodialysis population was more than 7 times as high as the matched general population (hospital admissions from the emergency department: 786 vs 101 per 1000 person-years; all-cause hospital admissions: 1056 vs 139 per 1000 person-years). The median number of all-cause hospitalization days per patient year was 4.0 (0, 16.5) in the in-center hemodialysis population compared with 0 (0, 0.5) in the matched general population. The cost per patient-year for emergency department visits in the in-center hemodialysis population was approximately 5.5 times as high as the matched general population while the cost of hospitalizations in the in-center hemodialysis population was approximately 11 times as high as the matched general population (emergency department visits: CAN$ 1153 vs CAN$ 209; hospitalizations: CAN$ 21 151 vs CAN$ 1873 [all costs in 2023 CAN$]). Limitations: External generalizability and we could not determine whether emergency department visits and hospitalizations were preventable. Conclusions: Patients receiving in-center hemodialysis have high acute health care utilization. These results improve our understanding of the burden of disease and the associated costs in the in-center hemodialysis population, highlight the need to improve acute outcomes, and can aid health care capacity planning. Additional research is needed to address the risk of hospitalization after controlling for patient comorbidities. Trial registration: This is not applicable as this is a population-based matched cohort study and not a clinical trial.

Contexte: Les patients qui suivent des traitements d'hémodialyse d'entretien présentent de multiples comorbidités et sont hautement susceptibles de se présenter à l'hôpital. On en sait toutefois peu sur l'incidence de l'utilization des soins de santé aigus chez les patients hémodialysés en center, sur les coûts qui y sont associés, ainsi que sur la manière dont cela se compare à d'autres populations. Objectif: Déterminer, dans une population de patients hémodialysés en center, les taux d'hospitalizations et de visites aux urgences, leurs schémas et les coûts qui y sont associés, puis comparer ces résultats à ceux d'une population générale appariée. Type d'étude: Étudede cohorte populationnelle rétrospective. Cadre: Nous avons utilisé les bases de données couplées du système de santé de l'Ontario (Canada). Sujets: Nous avons inclus 25 379 patients (incidents et prévalents) qui recevaient des traitements d'hémodialyse en center entre le 1er janvier 2010 et le 31 décembre 2018. Les patients inclus ont été appariés,en fonction de leur date de naissance (± 2 ans), de leur sexe et de leur date d'entrée dans la cohorte, à 101 516 individus de la population générale dans un rapport de 1:4. Mesures: Nos principaux critères de jugement étaient les visites aux urgences (en permettant plusieurs visites par personne) et les admissions à l'hôpital à partir de l'urgence. Nous avons également évalué les hospitalizations toutes causes confondues, les réadmissions toutes causes confondues dans les 30 jours suivant le congé initial, la durée du séjour (en comptant les visites multiples par personne) et les coûts associés à ces admissions. Méthodologie: Nous avons présenté le nombre, le pourcentage, la médiane (25e et 75e percentile) et le taux d'incidence par 1000 années-personnes pour les visites aux urgences et les hospitalizations. Les coûts de santé par individu associés aux visites à l'urgence et aux hospitalizations toutes causes confondues ont été estimés en multipliant la pondération du volume des ressources par le coût pondéré par cas. Résultats: Les patients hémodialysés en center présentaient beaucoup plus de comorbidités (p. Ex. diabète) que la population générale appariée. Au cours d'un suivi médian respectif de 1,8 an (25e et 75e percentile: 0,7 et 3,6 ans) et de 5,2 ans (2,5 et 8,4 ans), 80 % (n=20 309) des patients hémodialysés en center ont visité l'urgence au moins une fois, contre 56 % (n= 56 452) des patients de la population générale appariée. Le taux d'incidence des visites aux urgences, en permettant plusieurs visites par personne, était de 2274 pour 1000 années-personnes (intervalle de confiance à 95% [IC 95%]: 2 263 à 2 286) chez les patients hémodialysés en center, soit presque cinq fois plus élevé que la population générale appariée (471 pour 1000 années-personnes; IC95 %: 469 à 473). Les taux d'admissions à partir de l'urgence et d'hospitalizations toutes causes confondues dans la population de patients hémodialysés en center étaient plus de sept fois plus élevés que dans la population générale appariée (admissions à partir de l'urgence: 786 contre 101 pour 1000 années-personnes; hospitalizations toutes causes confondues: 1056 contre 139 pour 1000 années-personnes). La durée médiane des hospitalizations toutes causes confondues par année-patient était de 4,0 jours (0 et 16,5 jours) chez les patients hémodialysés en center et de 0 jour (0 et 0,5 jour) dans la population générale appariée. Le coût par année-patient des visites à l'urgence chez les patients hémodialysés en center était environ 5,5 fois plus élevé que dans la population générale appariée, tandis que celui des hospitalizations était environ 11 fois plus élevé (visites à l'urgence: 1153 CAD contre 209 CAD; hospitalizations: 21 151 CAD contre 1873 CAD [coûts en dollars canadiens de 2023]). Limites: Généralisabilité externe; impossiblede déterminer si les visites aux urgences et les hospitalizations étaient évitables. Conclusion: Les patients hémodialysés en center sont de grands utilisateurs des soins de santé aigus. Ces résultats améliorent notre compréhension du fardeau de la maladie et des coûts associés à cette utilization dans cette population. Ces résultats soulignent également la nécessité d'améliorer les résultats des soins aigus et peuvent aider à la planification des capacités en matière de soins de santé. D'autres études sont nécessaires pour examiner le risque d'hospitalization après la gestion des comorbidités des patients.

Implementation of a One-Day Living Kidney Donor Assessment Clinic to Improve the Efficiency of the Living Kidney Donor Evaluation: Program Report.

Purpose of program: A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day. Sources of information: The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics. Methods: Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions. Key findings: The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic. Limitations: Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward. Implications: This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model.

Objectifs du programme: Devenir donneur de rein vivant est difficile, le principal obstacle étant le processus d'évaluation inefficace auquel les candidats doivent se soumettre. Ce processus comporte plus de 30 examens (p. ex. tests de laboratoire et tests diagnostiques), questionnaires et consultations avec des spécialistes. Les candidats donneurs font plusieurs visites dans les hôpitaux et cliniques, et passent souvent plusieurs mois à attendre des rendez-vous et des résultats de tests. En Ontario (Canada), le délai médian pour l'évaluation d'un candidat au don est de près d'un an. Les temps d'attente plus longs sont associés à de moins bons résultats pour les receveurs d'une greffe rénale, ainsi qu'à des coûts de soins de santé plus élevés. Un processus d'évaluation plus court et plus efficace des donneurs potentiels permettrait à un plus grand nombre de patients atteints d'insuffisance rénale de recevoir une greffe, y compris une greffe préventive (c.-à-d. permettant d'éviter la dialyse). Cet article décrit une intervention d'amélioration de la qualité visant à augmenter l'efficience, l'efficacité et la personnalisation du processus d'évaluation des candidats au don. Nous avons développé une clinique d'un jour pour l'évaluation des donneurs de reins vivants (One-Day Living Kidney Donor Assessment Clinic), soit une clinique condensée où les candidats passent tous les tests et consultent un spécialiste dans la même journée. Sources de l'information: La clinique d'un jour pour l'évaluation des donneurs de reins vivants a été développée à la suite d'un examen approfondi de la littérature, de la consultation des commentaires de patients ayant donné avec succès et de rencontres avec les dirigeants du programme de transplantation du St Joseph's Healthcare d'Hamilton. Une équipe multipartite a été formée; celle-ci réunit du personnel soignant en néphrologie, chirurgie de transplantation, radiologie, cardiologie, travail social et médecine nucléaire, ainsi que des patients ayant une expérience vécue du don de rein. L'équipe s'est réunie régulièrement pendant les étapes de planification pour déterminer les objectifs, les paramètres et le calendrier de la clinique, ainsi que les critères de participation et le flux de patients. Méthodologie: Les donneurs potentiels qui avaient complété les tests de laboratoire initiaux et qui acceptaient de se soumettre à un processus accéléré ont été évalués à la clinique d'un jour. Si des tests supplémentaires étaient nécessaires, ceux-ci étaient effectués un autre jour. Les candidats ont été rencontrés par le néphrologue, le chirurgien de transplantation et le coordonnateur des dons environ deux semaines après leur visite à la clinique pour l'approbation finale. L'équipe multipartite continue de se réunir régulièrement pour examiner les commentaires des donneurs, discuter des défis et trouver des solutions. Principaux résultats: La clinique d'un jour, mise sur pied en mars 2019, est en activité depuis quatre ans et permet des améliorations itératives grâce à la rétroaction continue des patients et des soignants. À ce jour, plus de 150 candidats au don ont été évalués à la clinique. Les commentaires des donneurs sont quasi unanimement positifs (98 % des candidats ont déclaré être très satisfaits de la clinique), la plupart soulignant l'efficacité de la clinique et les conséquences minimes du processus sur les obligations professionnelles et familiales. La direction de l'hôpital, tout comme les professionnels de la santé des services participants, continue d'appuyer la clinique d'un jour et de collaborer à la création d'une expérience fluide pour les donneurs potentiels qui la fréquentent. Limites: Les places à la clinique sont limitées; ainsi, certains candidats au don d'un rein vivant pourraient ne pas pouvoir être admis dans le mois où ils se présentent à la clinique. Conclusion: Cette intervention d'amélioration de la qualité axée sur les patients est conçue pour augmenter l'efficacité du processus d'évaluation et bonifier l'expérience des donneurs de rein vivants. Elle vise également à améliorer les résultats des receveurs d'une greffe rénale et, potentiellement, augmenter le don vivant. La prochaine étape sera une évaluation formelle de la clinique, c'est-à-dire la mesure de la rétroaction qualitative des professionnels de la santé qui y travaillent et des candidats au don qui la fréquentent, et l'analyse des processus clés et des résultats des candidats évalués à la clinique d'un jour par rapport à ceux qui suivent le processus d'évaluation habituel. Cette évaluation du programme fournira des données probantes fiables et propres à la région qui pourront informer les centres de transplantation de tout le pays qui envisagent d'intégrer un processus d'évaluation similaire.

Variation in Kidney Transplant Referral Across Chronic Kidney Disease Programs in Ontario, Canada.

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.

Contexte: Les patients atteints d'insuffisance rénale qui y sont admissibles devraient bénéficier d'un accès égal à la transplantation rénale. L'aiguillage vers un programme de transplantation est la première étape essentielle pour recevoir une greffe de rein. Des études suggèrent cependant qu'il existe des variations substantielles dans les taux d'aiguillage vers une greffe de rein selon les régions. La province de l'Ontario, au Canada, dispose d'un système public de santé à payeur unique comptant 27 programmes régionaux d'insuffisance rénale chronique (IRC). La probabilité d'être aiguillé vers une transplantation rénale n'est pas forcément la même dans tous les programmes d'IRC. Objectif: Déterminer s'il existe une variabilité dans les programmes d'IRC de l'Ontario en ce qui concerne les taux d'aiguillage vers une greffe de rein. Conception: Étude de cohorte représentative d'une population réalisée en Ontario (Canada) entre le 1er janvier 2013 et le 1er novembre 2016 à partir des données administratives en santé. Cadre: Les 27 programmes régionaux d'IRC de la province de l'Ontario (Canada). Sujets: Des patients approchant le besoin de dialyse (IRC de stade avancé) et des patients recevant des traitements de dialyse d'entretien (suivi maximum jusqu'au 1er novembre 2017). Mesures: L'aiguillage vers une greffe de rein. Méthodologie: Nous avons calculé la probabilité cumulative non ajustée d'être aiguillé à l'intérieur d'un an vers une transplantation rénale dans chacun des 27 programmes d'IRC de l'Ontario en utilisant le complément de l'estimateur Kaplan-Meier. Nous avons calculé les ratios d'aiguillage normalisés (SRR­Standardized Reference Ratios) des programmes d'IRC en utilisant les taux d'aiguillge attendus à partir d'un modèle de risques proportionnels de Cox en deux étapes, avec correction en fonction des caractéristiques du patient dans la première étape. Les ratios d'aiguillage normalisés d'une valeur inférieure à 1 étaient inférieurs à la moyenne provinciale (suivi maximum possible de 4 ans et 10 mois). Dans une analyse supplémentaire, nous avons regroupé les programmes d'IRC selon cinq régions géographiques. Résultats: Parmi les 8 641 patients atteints d'IRC de stade avancé, la probabilité cumulative d'aiguillage en un an pour une transplantation rénale variait de 0,9 % (IC 95 %: 0,2-3,7 %) à 21,0 % (IC 95 %: 17,5-25,2 %) pour l'ensemble des 27 programmes d'IRC. Le SRR corrigé variait de 0,2 (IC à 95 %: 0,1-0,4) à 4,2 (IC 95 %: 2,1-7,5). Parmi les 6 852 patients qui recevaient une dialyse d'entretien, la probabilité cumulative d'aiguillage en un an vers la transplantation variait de 6,4 % (IC 95 %: 4,0-10,2 %) à 34,5 % (IC 95 %: 29,5-40,1 %) pour l'ensemble des programmes d'IRC. Le SRR corrigé variait de 0,2 (IC 95 %: 0,1-0,3) à 1,8 (IC 95 %: 1,6-2,1). En regroupant les programmes d'IRC en fonction de la région géographique, nous avons constaté que les patients résidant dans les régions du Nord avaient une probabilité cumulative nettement plus faible d'être aiguillés vers la transplantation en un an. Limites: Nos estimations de la probabilité cumulative n'ont permis de saisir que les aiguillages au cours de la première année d'IRC de stade avancé ou de l'amorce d'une dialyse d'entretien. Conclusion: Il existe une variabilité marquée dans la probabilité d'être aiguillé vers une transplantation rénale dans les programmes d'IRC opérant dans un système de santé financé par l'État.