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.

Breast Density and Risk of Interval Cancers: The Effect of Annual Versus Biennial Screening Mammography Policies in Canada.

Regular screening mammography reduces breast cancer mortality. However, in women with dense breasts, the performance of screening mammography is reduced, which is reflected in higher interval cancer rates (ICR). In Canada, population-based screening mammography programs generally screen women biennially; however, some provinces and territories offer annual mammography for women with dense breast tissue routinely and/or on recommendation of the radiologist. This study compared the ICRs in those breast screening programs with a policy of annual vs. those with biennial screening for women with dense breasts. Among 148,575 women with dense breasts screened between 2008 to 2010, there were 288 invasive interval breast cancers; screening programs with policies offering annual screening for women with dense breasts had fewer interval cancers 63/70,814 (ICR 0.89/1000, 95% CI: 0.67-1.11) compared with those with policies of usual biennial screening 225/77,761 (ICR 1.45 /1000 (annualized), 95% CI: 1.19-1.72) i.e. 63% higher (p = 0.0016). In screening programs where radiologists' screening recommendations were able to be analyzed, a total of 76,103 women were screened, with 87 interval cancers; the ICR was lower for recommended annual (65/69,650, ICR 0.93/1000, 95% CI: 0.71, 1.16) versus recommended biennial screening (22/6,453, ICR 1.70/1000 (annualized), 95%CI: 0.70, 2.71)(p = 0.0605). Screening program policies of annual as compared with biennial screening in women with dense breasts had the greatest impact on reducing interval cancer rates. We review our results in the context of current dense breast notification in Canada.

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.

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

BACKGROUND: The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. STUDY DESIGN: Population-based retrospective cohort study from Ontario, Canada. SETTING & PARTICIPANTS: 1,422,978 adult residents with eGFRs < 90mL/min/1.73m2 from April 1, 2006, through March 31, 2015. FACTOR: A diagnosis of AF at hospitalization. OUTCOMES: Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. RESULTS: All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). LIMITATIONS: Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. CONCLUSIONS: Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m2. Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes.

Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short Form for clinical levels of fear of cancer recurrence.

OBJECTIVE: Fear of cancer recurrence (FCR) is a common concern among cancer survivors. Identifying survivors with clinically significant FCR requires validated screening measures and clinical cut-offs. We evaluated the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) clinical cut-off in 2 samples. METHODS: Level of FCR in study 1 participants (from an Australian randomized controlled trial: ConquerFear) was compared with FCRI-SF scores. Based on a biopsychosocial interview, clinicians rated participants as having nonclinical, subclinical, or clinical FCR. Study 2 participants (from a Canadian FCRI-English validation study) were classified as having clinical or nonclinical FCR by using the semistructured clinical interview for FCR (SIFCR). Receiver operating characteristic analyses evaluated the screening ability of the FCRI-SF against clinician ratings (study 1) and the SIFCR (study 2). RESULTS: In study 1, 167 cancer survivors (mean age: 53 years, SD = 10.1) participated. Clinicians rated 43% as having clinical FCR. In study 2, 40 cancer survivors (mean age: 68 years, SD = 7.0) participated; 25% met criteria for clinical FCR according to the SIFCR. For both studies 1 and 2, receiver operating characteristic analyses suggested a cut-off ≥22 on the FCRI-SF identified cancer survivors with clinical levels of FCR with adequate sensitivity and specificity. CONCLUSIONS: Establishing clinical cut-offs on FCR screening measures is crucial to tailoring individual care and conducting rigorous research. Our results suggest using a higher cut-off on the FCRI-SF than previously reported to identify clinically significant FCR. Continued evaluation and validation of the FCRI-SF cut-off is required across diverse cancer populations.

The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation.

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/1.73m2) 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.

Risk of Venous Thromboembolism in Patients by Albuminuria and Estimated GFR.

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 < 0.001). After considering the competing risk for death, there was a 61% higher rate of VTE in patients with normal eGFRs (eGFRs>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<30 and >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.

Filling in the gaps: Sociodemographic and medical predictors of sexual health and other supportive care needs, and desire for help in gynecological cancer survivors.

PURPOSE: The goal of the present study was to evaluate predictors of unmet supportive care needs and readiness for help among gynecological cancer patients. METHODS: A sample of 113 gynecological cancer survivors completed a measure of needs and desire for help. Regression analyses identified sociodemographic and medical predictors of patient needs and desire for help. RESULTS: Younger age and shorter time since treatment were the strongest predictors of many unmet needs. Younger age and chemotherapy predicted greater unmet sexual health needs. Shorter time since treatment predicted readiness for help with informational needs. CONCLUSIONS: Post-treatment unmet needs are diverse and may be greater in younger and recently treated survivors. Chemotherapy treatment may contribute to greater sexual health needs.

Empirical validation of the English version of the Fear of Cancer Recurrence Inventory.

PURPOSE: Cancer patients report that help in managing fear of cancer recurrence (FCR) is one of their greatest unmet needs. Research on FCR has been limited by the very few validated, multi-dimensional measures of this construct. One exception is the Fear of Cancer Recurrence Inventory (FCRI), originally developed and empirically validated in French. The present study validated the English version of the FCRI. METHODS: The FCRI was translated into English using a forward-backward translation procedure and pilot-tested with 17 English-speaking cancer patients. Cross-cultural equivalency of the French and English versions was established by administering both forms to 42 bilingual cancer patients. Last, 350 English-speaking breast, colon, prostate, or lung cancer patients were asked to complete the FCRI. A subsample (n = 135) was mailed the FCRI again one month later to evaluate test-retest reliability. RESULTS: The English translation of the FCRI was well accepted by participants. There was no item-bias when comparing bilingual participants' answers on both versions. A confirmatory factor analysis supported the hypothesized seven-factor structure. The English version has high internal consistency (α = .96 for the total scale and .71-.94 for the subscales) and test-retest reliability (r = .88 for the total scale and 56-.87 for the subscales). CONCLUSIONS: The English version of the FCRI is a reliable and valid measure of FCR applicable to breast, colon, prostate, and lung cancer patients. Its multi-dimensional nature makes it an attractive research and clinical tool to further our knowledge of FCR.

A fluorescence-based high throughput assay for the determination of small molecule-human serum albumin protein binding.

Herein, we describe the development of a fluorescence-based high throughput assay to determine the small molecule binding towards human serum albumin (HSA). This innovative competition assay is based on the use of a novel fluorescent small molecule Red Mega 500 with unique spectroscopic and binding properties. The commercially available probe displays a large fluorescence intensity difference between the protein-bound and protein-unbound state. The competition of small molecules for HSA binding in the presence of probe resulted in low fluorescence intensities. The assay was evaluated with the library of pharmacological active compounds (LOPAC) small molecule library of 1,280 compounds identifying known high protein binders. The small molecule competition of HSA-Red Mega 500 binding was saturable at higher compound concentrations and exhibited IC50 values between 3 and 24 µM. The compound affinity toward HSA was confirmed by isothermal titration calorimetry indicating that the new protein binding assay is a valid high throughput assay to determine plasma protein binding.

Peroxisome proliferation-activated receptor δ agonist GW0742 interacts weakly with multiple nuclear receptors, including the vitamin D receptor.

A high-throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes for modulating gene regulation mediated by VDR. Peroxisome proliferator-activated receptor (PPAR) δ agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations of > 12.1 µM. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor. Surprisingly, GW0742 behaved as a PPAR agonist and antagonist, activating transcription at lower concentrations and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742 increased the fluorescence intensity and level of fluorescence polarization at an excitation wavelength of 595 nm and an emission wavelength of 615 nm in a dose-dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced level of expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3, and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.

Does fear of cancer recurrence predict cancer survivors' health care use?

INTRODUCTION: Fear of cancer recurrence (FCR) is the most frequently cited unmet need among cancer survivors. Theoretical models of FCR suggest that patients with elevated levels of FCR will more frequently consult health care professionals for reassurance about their health. However, the relationship between FCR and health care utilization has not yet been firmly established. We examined the relationship between FCR and quantity of medications, number of emergency room (ER) visits, outpatient visits, specialist visits, allied health visits, and hospital overnight visits. METHODS: A total of 231 participants diagnosed with breast, colon, prostate, or lung cancer in the past 10 years were recruited from a cancer survivor registry. Participants were sent a survey package that included demographic and medical characteristics, a health care utilization questionnaire, and the Fear of Cancer Recurrence Inventory. RESULTS: A multiple regression analysis indicated that higher FCR significantly predicted greater number of outpatient visits in the past 6 months (ß = .016, F(1, 193) = 5.08, p = .025). A hierarchical multiple regression indicated that higher FCR significantly predicted greater number of ER visits in the past 6 months when controlling for relationship status and education level (F(1, 179) = 4.00, p = .047). CONCLUSIONS: The relationship between FCR and health care use has been understudied. Results indicate that patients with elevated FCR may indeed use more health care services. We recommend that clinicians monitor health care use in patients who are struggling with FCR.

Factors contributing to a coronavirus disease 2019 (COVID-19) outbreak on a mixed medical-surgical unit in a Canadian acute-care hospital.

Objective: To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities. Design: A case-control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit. Setting: This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021. Patients: Patients hospitalized on the unit for at least 12 hours and healthcare workers (HCW) working on the unit within 2 weeks of outbreak declaration were included. Methods: Risk factors for SARS-CoV-2 infection were analyzed using simple and multiple logistic regression. Whole-genome sequencing (WGS) was performed to identify SARS-CoV-2 strain relatedness. Network analysis was used to describe patient accommodation. Results: SARS-CoV-2 infections were identified in 21 patients (29.6%) and 11 HCWs (6.6%). WGS data revealed 4 distinct clades of related sequences. Several factors likely contributed to the outbreak, including failure to identify SARS-CoV-2, a largely incomplete or unvaccinated population, and patient wandering behaviors. The most significant risk factor for SARS-CoV-2 infection was room sharing with an infectious patient, which was the only factor that remained statistically significant following multivariate analysis (odds ratio [OR], 9.2l; 95% confidence interval [CI], 2.04-41.67; P = .004). Conclusions: This outbreak likely resulted from admission of 2 patients with COVID-19, with subsequent transmissions to 17 patients and 11 staff. WGS and bioinformatics analyses were critical to identifying previously unrecognized nosocomial transmissions of SARS-CoV-2. This study supports strategies to reduce nosocomial transmissions of SARS-CoV-2, such as single-patient rooms, promotion of COVID-19 vaccination, and infection prevention and control measures including management of wandering behaviors.

Evaluation of the first Ergocalciferol-derived, non hypercalcemic anti-cancer agent MT19c in ovarian cancer SKOV-3 cell lines.

OBJECTIVE: In human trials calcitriol and its analogs displayed unacceptable systemic toxicities including hypercalcemia. This study was designed to evaluate a novel non-hypercalcemic vitamin-D derivative (MT19c) and its anticancer effects in cultured ovarian cancer cell model. METHODS: We modified the Ergocalciferol structure to generate MT19c, a heterocyclic vitamin-D derivative. Hypercalcemic liabilities of MT19c were assessed by estimating the blood calcium levels in drug treated animals. VDR agonistic or antagonistic properties of MT19c were determined via a VDR-coactivator binding assay. The anticancer effects of MT19c were evaluated by (i) cytotoxicity studies in cancer cell lines and the National Cancer Institute (NCI(60)) cell lines, (ii) identification of apoptosis markers by microscopy and western blots, (iii) cell cycle analysis, and (iv) by studying the insulin receptor substrate-1/2 (IRS1/2) signaling in ovarian cancer cells (SKOV-3) by western blotting. RESULTS: MT19c treatment did not cause hypercalcemia in mice and showed minor VDR antagonistic activity. In a NCI(60) screen MT19c revealed cell-type specific growth inhibition. MT19c displayed superior cytotoxicity to cisplatin, calcitriol, EB1089 and Iressa in SKOV-3 cell-lines and was comparable to Taxol in our in vitro assays. In SKOV-3 cells MT19c showed caspase dependent apoptosis, DNA fragmentation and cell cycle arrest. MT19c did not alter VDR but downregulated the IGFR/IRS-1/2-MEK-ras-ERK1/2-pathway via activated TNFα-receptor/SAPK/JNK component. CONCLUSION: Our results demonstrate how structural optimization of the vitamin-D scaffold leads to identification of a non-hypercalcemic compound MT19c which exerts cytotoxicity in vitro based on a VDR-independent signaling pathway and displays potent anti-cancer activity in ovarian cancer cell models.

Comparison of All-Cause Mortality Between Canadian Kidney Transplant Recipients and Patients With Cancer: A Population-Based Cohort Study.

BACKGROUND: Understanding rates of mortality in kidney transplant recipients relative to other common diseases can enhance our understanding of the mortality burden in kidney transplant recipients. OBJECTIVE: To compare the survival probability in Canadian female and male kidney transplant recipients with patients with common cancers (female: breast, colorectal, lung, or pancreas; male: prostate, colorectal, lung, or pancreas) in a contemporary population. DESIGN: Population-based cohort study using linked administrative health care databases. SETTING: Ontario, Canada. PATIENTS: A total of 6888 incident kidney transplant recipients (median age was 50 and 51 years in females and males, respectively) and a total of 532 452 incident patients with cancer (median age range 60 to 72 years across cancer types) from 1997 to 2015. MEASUREMENTS: All-cause mortality. METHODS: The survival of study participants was described using the Kaplan-Meier product limit estimator. The rate of survival was compared between kidney transplant recipients and patients with cancer using extended Cox regression with a Heaviside function. RESULTS: Kidney transplant recipients had a higher survival probability compared with all cancer types. For example, male kidney transplant recipients had a 5-year survival probability of 89.6% (95% confidence interval [CI]: 88.6%-90.5%) compared with 83.3% (95% CI: 83.1%-83.5%) in patients with prostate cancer, and 14.0% (95% CI: 13.7%-14.3%), 56.1% (95% CI: 55.7%-56.5%), and 9.1% (95% CI: 8.5%-9.7%) in patients with lung, colorectal, and pancreas cancer, respectively. After presenting survival probabilities by age at cohort entry and after adjusting for clinical characteristics, similar results were found with a few exceptions. Unlike the unadjusted analysis, in the adjusted analysis males with prostate cancer had a significantly higher survival compared with kidney transplant recipients and females with breast cancer had higher survival compared with kidney transplant recipients at 2+ years of follow-up. In a subpopulation of the cohort who had information available on cancer stage (ie, stages 1-4), we generally found similar results to our primary analysis with kidney transplant recipients having a higher survival probability compared with each cancer stage. However, female kidney transplant recipients had a lower survival probability compared with females with stage 1 breast cancer, whereas male kidney transplant recipients had a lower survival probability compared with males with stage 1 to 3 prostate cancer. LIMITATIONS: External generalizability, residual confounding, and cancer stage could only be provided for a subpopulation. CONCLUSION: Mortality in kidney transplant recipients is lower than in patients with several cancer types. These results improve our understanding of the mortality burden in this population and reaffirm kidney transplantation as a good treatment option for end-stage kidney disease but also highlight the continuing need to improve posttransplant survival. TRIAL REGISTRATION: This is not applicable as this is a population-based cohort study and not a clinical trial.

CONTEXTE: La comparaison du taux de mortalité des receveurs d'une greffe rénale par rapport à celui des patients atteints d'autres maladies courantes pourrait améliorer notre compréhension du fardeau que cela représente chez les transplantés rénaux. OBJECTIFS: Comparer la probabilité de survie des transplantés rénaux canadiens, femmes et hommes, à celle de patients atteints de cancers fréquents (femmes : sein, colorectal poumons ou pancréas; hommes : prostate, colorectal, poumons ou pancréas) dans une population contemporaine. TYPE D'ÉTUDE: Étude de cohorte représentative d'une population réalisée à partir des données administratives en santé. CADRE: Ontario, Canada. SUJETS: L'étude porte sur 6 888 transplantés du rein incidents (âge médian : 50 ans [femmes] et 51 ans [hommes]) et un total de 532 452 patients atteints d'un cancer (âge médian : 60 à 72 ans pour tous les types de cancers) répertoriés entre 1997 et 2015. MESURES: Mortalité toutes causes confondues. MÉTHODOLOGIE: La survie des patients a été décrite à l'aide de l'estimateur produit-limite de Kaplan-Meier. Une régression étendue de Cox avec une distribution de Heaviside a servi à comparer les taux survie des transplantés rénaux et des patients atteints d'un cancer. RÉSULTATS: La probabilité de survie des transplantés Renaud s'est avérée plus élevée que celle observée pour tous les types de cancer. À titre d'exemple, la probabilité de survie des hommes transplantés était de 89,6 % (IC à 95 % : 88,6-56,9 %) après 5 ans alors qu'elle s'établissait à 83,3 % (IC 95 % : 83,1-83,5 %) chez les patients atteints d'un cancer de la prostate et à 14,0 % (IC à 95 % : 13,7-14,3 %), 56,1 % (IC 95 % : 55,7-56,5 %) et 9,1 % (IC 95 % : 8,5-9,7 %) chez les patients atteints respectivement d'un cancer du poumon, colorectal et du pancréas. Des résultats similaires, à quelques exceptions près, ont été observés après une présentation des probabilités de survie selon l'âge à l'inclusion dans la cohorte et après correction en fonction des caractéristiques cliniques. Dans l'analyse corrigée, contrairement à l'analyse non corrigée, la probabilité de survie des hommes atteints d'un cancer de la prostate et celle des femmes atteintes d'un cancer du sein étaient significativement plus élevées que celle des receveurs d'une greffe rénale après plus de deux ans de suivi. Une sous-population issue de la cohorte de patients disposant d'informations sur le stade du cancer (stades 1 à 4) a montré des résultats généralement similaires à ceux de notre analyse primaire; les transplantés rénaux montrant une probabilité de survie plus élevée comparativement à chaque stade de cancer. Cependant, les receveuses d'une greffe rénale présentaient une probabilité de survie plus faible que les femmes atteintes d'un cancer du sein de stade 1; un résultat similaire a été observé chez les receveurs d'un rein comparativement aux hommes atteints d'un cancer de la prostate de stade 1 à 3. LIMITES: Généralisabilité externe; facteurs de confusion résiduels; stade du cancer connu pour une sous-population uniquement. CONCLUSION: Le taux de mortalité chez les receveurs d'un greffe rénale est inférieur à celui des patients atteints de plusieurs types de cancer. Ces résultats permettent de mieux comprendre le fardeau que représente la mortalité dans cette population et de réaffirmer la transplantation rénale comme option de traitement valide pour l'insuffisance rénale terminale. Ces résultats rappellent également qu'il demeure indispensable d'améliorer les taux de survie post-transplantation. ENREGISTREMENT DE L'ESSAI: Sans objet. Il s'agit d'une étude de cohorte basée sur une population et non d'un essai clinique.

Risk Factors and Outcomes of Early Hospital Readmission in Canadian Kidney Transplant Recipients: A Population-Based Multi-Center Cohort Study.

BACKGROUND: Early hospital readmissions (EHRs) occur commonly in kidney transplant recipients. Conflicting evidence exists regarding risk factors and outcomes of EHRs. OBJECTIVE: To determine risk factors and outcomes associated with EHRs (ie, hospitalization within 30 days of discharge from transplant hospitalization) in kidney transplant recipients. DESIGN: Population-based cohort study using linked, administrative health care databases. SETTING: Ontario, Canada. PATIENTS: We included 5437 kidney transplant recipients from 2002 to 2015. MEASUREMENTS: Risk factors and outcomes associated with EHRs. We assessed donor, recipient, and transplant risk factors. We also assessed the following outcomes: total graft failure, death-censored graft failure, death with a functioning graft, mortality, and late hospital readmission. METHODS: We used multivariable logistic regression to examine the association of each risk factor and the odds of EHR. To examine the relationship between EHR status (yes vs no [reference]) and the outcomes associated with EHR (eg, total graft failure), we used a multivariable Cox proportional hazards model. RESULTS: In all, 1128 kidney transplant recipients (20.7%) experienced an EHR. We found the following risk factors were associated with an increased risk of EHR: older recipient age, lower income quintile, several comorbidities, longer hospitalization for initial kidney transplant, and older donor age. After adjusting for clinical characteristics, compared to recipients without an EHR, recipients with an EHR had an increased risk of total graft failure (adjusted hazard ratio [aHR]: 1.46, 95% CI: 1.29, 1.65), death-censored graft failure (aHR: 1.62, 95% CI: 1.36, 1.94), death with graft function (aHR: 1.34, 95% CI: 1.13, 1.59), mortality (aHR: 1.41, 95% CI: 1.22, 1.63), and late hospital readmission in the first 0.5 years of follow-up (eg, 0 to <0.25 years: aHR: 2.11, 95% CI: 1.85, 2.40). LIMITATIONS: We were not able to identify which readmissions could have been preventable and there is a potential for residual confounding. CONCLUSIONS: Results can be used to identify kidney transplant recipients at risk of EHR and emphasize the need for interventions to reduce the risk of EHRs. TRIAL REGISTRATION: This is not applicable as this is a population-based cohort study and not a clinical trial.

CONTEXTE: Les réadmissions précoces à l'hôpital (RPH) sont fréquentes chez les receveurs d'une greffe rénale. Les données sur les facteurs de risque d'une RPH et sur les résultats qui y sont associés restent toutefois contradictoires. OBJECTIF: Définir les facteurs de risque et les effets associés à une RPH (soit une hospitalization dans les 30 jours suivant la sortie de l'hôpital après la transplantation) chez les receveurs de greffe rénale. TYPE D'ÉTUDE: Étude de cohorte représentative d'une population, réalisée à partir des bases de données administratives en santé. CADRE: Ontario, Canada. SUJETS: Ont été inclus 5 437 adultes receveurs d'une greffe rénale entre 2002 et 2015. MESURES: Les facteurs de risque et les résultats associés à une RPH. Nous avons évalué les facteurs de risque du donneur, du receveur et de la transplantation. Nous avons également évalué les résultats suivants : l'échec du greffon, l'échec du greffon censuré par le décès, le décès avec un greffon fonctionnel, la mortalité et les réadmissions tardives. MÉTHODOLOGIE: Nous avons utilisé la régression logistique multivariée pour examiner l'association de chaque facteur de risque et les probabilités de RPH. Un modèle multivarié des risques proportionnels de Cox a par ailleurs servi à examiner la relation entre le statut des RPH (oui vs non [référence]) et les résultats associés à celles-ci (p. ex., l'échec de la greffe). RÉSULTATS: Dans la cohorte étudiée, 1 128 receveurs d'une greffe rénale (20,7 %) ont été réadmis précocement à l'hôpital. Les facteurs de risque suivants ont été associés à un risque accru de RPH : âge plus avancé du receveur, provenance d'un quartier au quintile de revenu inférieur, présence de plusieurs comorbidités, hospitalization initiale plus longue pour la transplantation rénale et âge plus avancé du donneur. Après ajustement pour les caractéristiques cliniques, par rapport aux receveurs de greffe qui n'avaient pas été réadmis précocement, les patients avec une RPH présentaient un risque accru d'échec du greffon (risque relatif corrigé [RRc] : 1,46; IC 95 % : 1,29-1,65), d'échec du greffon censuré par le décès (RRc: 1,62; IC 95 % : 1,36-1,94), de décès avec un greffon fonctionnel (RRc: 1,34; IC 95 % : 1,13-1,59), de mortalité (RRc: 1,41; IC 95 % : 1,22-1,63) et de réadmission tardive au cours des premiers six mois de suivi (p. ex., entre 0 et moins de 0,25 an de suivi, le RRc était de 2,11; [IC 95 % : 1,85-2,40]). LIMITES: Nous n'avons pas été en mesure d'identifier les réadmissions qui auraient pu être prévenues et il existe un risque de facteurs de confusion résiduels. CONCLUSION: Ces résultats peuvent être employés pour identifier les receveurs d'une greffe rénale susceptibles d'être réadmis rapidement à l'hôpital. Ces résultats soulignent en outre la nécessité d'interventions pour réduire le risque de RPH. ENREGISTREMENT DE L'ESSAI: Sans objet puisqu'il s'agit d'une étude de cohorte basée sur la population et non d'un essai clinique.

Population coverage of the Canadian Chronic Disease Surveillance System: a survey of the contents of health insurance registries across Canada. / Couverture de la population dans le Système canadien de surveillance des maladies chroniques : enquête sur le contenu des registres d'assurance-maladie au Canada.

INTRODUCTION: Health insurance registries, which capture insurance coverage and demographic information for entire populations, are a critical component of population health surveillance and research when using administrative data. Lack of standardization of registry information across Canada's provinces and territories could affect the comparability of surveillance measures. We assessed the contents of health insurance registries across Canada to describe the populations covered and document registry similarities and differences. METHODS: A survey about the data and population identifiers in health insurance registries was developed by the study team and representatives from the Public Health Agency of Canada. The survey was completed by key informants from most provinces and territories and then descriptively analyzed. RESULTS: Responses were received from all provinces; partial responses were received from the Northwest Territories. Demographic information in health insurance registries, such as primary address, date of birth and sex, were captured in all jurisdictions. Data captured on familial relationships, ethnicity and socioeconomic status varied among jurisdictions, as did start and end dates of coverage and frequency of registry updates. Identifiers for specific populations, such as First Nations individuals, were captured in some, but not all jurisdictions. CONCLUSION: Health insurance registries are a rich source of information about the insured populations of the provinces and territories. However, data heterogeneity may affect who is included and excluded in population surveillance estimates produced using administrative health data. Development of a harmonized data framework could support timely and comparable population health research and surveillance results from multi-jurisdiction studies.

A Propensity Score-weighted Comparison of Outcomes Between Living and Standard Criteria Deceased Donor Kidney Transplant Recipients.

BACKGROUND: Consider a theoretical situation in which 2 patients with similar baseline characteristics receive a kidney transplant on the same day: 1 from a standard criteria deceased donor, the other from a living donor. Which kidney transplant will last longer? METHODS: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, from January 1, 2005, to March 31, 2014, to evaluate several posttransplant outcomes in individuals who received a kidney transplant from a standard criteria deceased donor (n = 1523) or from a living donor (n = 1373). We used PS weighting using overlap weights, a novel weighting method that emphasizes the population of recipients with the most overlap in baseline characteristics. RESULTS: Compared with recipients of a living donor, the rate of all-cause graft failure was not statistically higher for recipients of a standard criteria deceased donor (hazard ratio, 1.1; 95% confidence interval [CI], 0.8-1.6). Recipients of a standard criteria deceased donor, compared with recipients of a living donor had a higher rate of delayed graft function (23.6% versus 18.7%; odds ratio, 1.3; 95% CI, 1.0-1.6) and a longer length of stay for the kidney transplant surgery (mean difference, 1.7 d; 95% CI, 0.5-3.0). CONCLUSIONS: After accounting for many important donor and recipient factors, we failed to observe a large difference in the risk of all-cause graft failure for recipients of a standard criteria deceased versus living donor. Some estimates were imprecise, which meant we could not rule out the presence of smaller clinically important effects.