Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Artificial intelligence and digital pathology: clinical promise and deployment considerations.

Artificial intelligence (AI) presents an opportunity in anatomic pathology to provide quantitative objective support to a traditionally subjective discipline, thereby enhancing clinical workflows and enriching diagnostic capabilities. AI requires access to digitized pathology materials, which, at present, are most commonly generated from the glass slide using whole-slide imaging. Models are developed collaboratively or sourced externally, and best practices suggest validation with internal datasets most closely resembling the data expected in practice. Although an array of AI models that provide operational support for pathology practices or improve diagnostic quality and capabilities has been described, most of them can be categorized into one or more discrete types. However, their function in the pathology workflow can vary, as a single algorithm may be appropriate for screening and triage, diagnostic assistance, virtual second opinion, or other uses depending on how it is implemented and validated. Despite the clinical promise of AI, the barriers to adoption have been numerous, to which inclusion of new stakeholders and expansion of reimbursement opportunities may be among the most impactful solutions.

Dyspnea in patients with stage IV non-small cell lung cancer: a population-based analysis of disease burden and patterns of care.

Background: Patients with metastatic non-small cell lung cancer (NSCLC) experience significant morbidity with dyspnea being a common symptom with a prevalence of 70%. The objective of this study was to determine factors associated with a moderate-to-severe dyspnea score based on the Edmonton Symptom Assessment System (ESAS), as well as resultant patterns of intervention and factors correlated to intervention receipt. Methods: Using health services administrative data, we conducted a population-based study of all patients diagnosed with metastatic NSCLC treated from January 2007 to September 2018 in the province of Ontario. The primary outcomes of interest are the prevalence of moderate-to-severe dyspnea scores, and the receipt of dyspnea-directed intervention. Differences in baseline characteristic between moderate-to-severe dyspnea and low dyspnea score cohorts were assessed by comparative statistics. Predictors of intervention receipt for patients with moderate-to-severe dyspnea scores were estimated using multivariable modified Poisson regression. Results: The initial study cohort included 13,159 patients diagnosed with metastatic NSCLC and of these, 9,434 (71.7%) reported a moderate-to-severe dyspnea score. Compared to patients who did not report moderate-to-severe dyspnea scores, those who reported a moderate-to-severe dyspnea score were more likely to complete a greater number of ESAS surveys, be male, have a higher Elixhauser comorbidity index (ECI) score, and receive subsequent systemic therapy after diagnosis. Most patients with a moderate-to-severe dyspnea score received intervention (96%), of which the most common were palliative care management (87%), thoracic radiotherapy (56%) and thoracentesis (37%). Multivariable regression identified older patients to be less likely to undergo pleurodesis. Thoracentesis was less common for patients living in rural and non-major urban areas, lower income areas, and earlier year of diagnosis. Receipt of thoracic radiotherapy was less common for older patients, females, those with ECI ≥4, patients living in major urban areas, and those with later year of diagnosis. Finally, palliative care referrals were less frequent for patients with ECI ≥4, age 60-69, residence outside of major urban areas, earlier year of diagnosis, and lower income areas. Conclusions: Dyspnea is a prevalent symptom amongst patients with metastatic NSCLC. Subpopulations of patients with moderate-to-severe dyspnea scores were in which inequities may exist in access to care that require further attention and evaluation.

Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.

Ensuring Superior Reporting of Radiation Therapy Noninferiority Trials: A Systematic Review.

Purpose: Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess the reporting quality of radiation therapy noninferiority trials. Methods and Materials: The PubMed, Embase, and Cochrane databases were queried for randomized controlled radiation therapy trials with noninferiority hypotheses published in English between January 2000 and July 2022, and this was performed by an information scientist. Descriptive statistics were used to summarize data. Results: Of 423 records screened, 59 (14%) were included after full-text review. All were published after 2003 and open label. The most common primary cancer type was breast (n = 15, 25%). Altered radiation fractionation (n = 26, 45%) and radiation de-escalation (n = 11, 19%) were the most common types of interventions. The most common primary endpoints were locoregional control (n = 17, 29%) and progression-free survival (n = 14, 24%). Fifty-three (90%) reported the noninferiority margin, and only 9 (17%) provided statistical justification for the margin. The median absolute noninferiority margin was 9% (interquartile range, 5%-10%), and the median relative margin was 1.51 (interquartile range, 1.33-2.04). Sample size calculations and confidence intervals were reported in 54 studies (92%). Both intention-to-treat and per-protocol analyses were reported in 27 studies (46%). In 31 trials (53%), noninferiority of the primary endpoint was reached. Conclusions: There was variability in the reporting of key components of noninferiority trials. We encourage consideration of additional statistical reasoning such as guidelines or previous trials in the selection of the noninferiority margin, reporting both absolute and relative margins, and the avoidance of statistically vague or misleading language in the reporting of future noninferiority trials.

CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance.

Signal transduction induced by chimeric antigen receptors (CARs) is generally believed to rely on the activity of the SRC family kinase (SFK) LCK, as is the case with T cell receptor (TCR) signaling. Here, we show that CAR signaling occurs in the absence of LCK. This LCK-independent signaling requires the related SFK FYN and a CD28 intracellular domain within the CAR. LCK-deficient CAR-T cells are strongly signaled through CAR and have better in vivo efficacy with reduced exhaustion phenotype and enhanced induction of memory and proliferation. These distinctions can be attributed to the fact that FYN signaling tends to promote proliferation and survival, whereas LCK signaling promotes strong signaling that tends to lead to exhaustion. This non-canonical signaling of CAR-T cells provides insight into the initiation of both TCR and CAR signaling and has important clinical implications for improvement of CAR function.

Top Ten Lessons Learned from Trials in Oligometastatic Cancers.

Recent evidence supports the role of aggressive local treatment in the oligometastatic setting. In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed. These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

Improving drug allergy label accuracy by supervised safety- and protocol-driven evaluation.

INTRODUCTION: Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels. METHOD: All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded. RESULTS: A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited. CONCLUSION: Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated.

The state of wound assessment tools in Singapore: an evaluation study.

OBJECTIVE: Variations in wound assessment and documentation remain an issue for clinicians despite efforts to standardise practices using national guidelines such as the Wound Care Assessment Minimum Data Set (WCA-MDS). As little is known about the quality of the wound assessment tools (WATs) used in Singapore, this study aimed to determine whether the existing WATs used meet the WCA-MDS criteria and clinicians' needs. METHOD: The study adopted an action evaluation methodology to evaluate seven well-established WATs, such as the Applied Wound Management (AWM) and National Wound Assessment Form (NWAF), and eight locally-designed WATs against the 34-item WCA-MDS criteria. Two clinicians reviewed the WATs using a self-developed audit form between June and July 2020. RESULTS: The results show that only five WATs met at least 50% of the 34 criteria indicators, with the MEASURE assessment framework achieving the most at 68%, followed by TIME-CDST at 65%, Hospital C WAT at 56%, NWAF at 53%, and AWM form at 50%. The five most common criteria indicators included wound type/classification, date and time of wound, wound size, wound bed tissue type, and exudate information. Most criteria indicators under the 'patient information' and 'specialist's referral' subdomains were omitted, reflecting the lack of focus on these areas in the local WATs. CONCLUSION: Despite advances in WAT development in the literature, the current state of wound assessment and documentation across healthcare institutions remains inconsistent. There is a need to focus on clinician training and establishing a nationally-validated WAT in Singapore.

The Chinese (Mandarin) instructions of the 6-minute walk test: A validation study.

BACKGROUND/OBJECTIVE: To date, a validated Chinese (Mandarin) six-minute walk test (6MWT) translated instruction is not available. Translation of the Chinese 6MWT instruction is done in an ad hoc manner within the Chinese-speaking populations. This study aimed to develop a set of valid and reliable Chinese (Mandarin) instructions of the 6MWT. METHODS: Translation was performed from the original English instruction via the recommended "Process of translation and adaptation of instruments" by the World Health Organization to generate the Chinese instructions. The Chinese instructions were tested with 52 healthy adult participants for its validity. Each participant underwent three 6MWTs and a cardiopulmonary exercise test. Randomization allowed participants to undergo the walk test in both the original English and the new Chinese instructions. Face and content validity, intra-rater and inter-rater reliability of the Chinese instructions of the 6MWT were established through the translation process. Criterion validity was established by analyzing the results of the 6MWT and cardiopulmonary exercise test. RESULTS: Intraclass correlation coefficient for inter-rater reliability was excellent ( ICC = 0 . 999 , 95% confidence interval = 0 . 996 -1.000). Similarly, the intra-rater reliability across the three raters was high (R1: ICC = 0 . 996 , 95% confidence interval ( CI )= 0 . 812 -1.000; R2: ICC = 1 . 000 , 95% CI = 0 . 994 -1.000; R3: ICC = 1 . 000 , 95% CI = 0 . 998 -1.000). The 6-min walk distances collected from the Chinese and English instructed trials correlated positively with the maximal oxygen consumption ( r = 0 . 315 , p = 0 . 023 ; r = 0 . 309 , p = 0 . 026 ). CONCLUSION: This is the first study to develop and validate the Chinese (Mandarin) instructions of the 6MWT, and the translation is as reliable and valid as the original English instructions.

Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection.

The early interactions between the nasal epithelial layer and the innate immune cells during viral infections remains an under-explored area. The significance of innate immunity signaling in viral infections has increased substantially as patients with respiratory infections who exhibit high innate T cell activation show a better disease outcome. Hence, dissecting these early innate immune interactions allows the elucidation of the processes that govern them and may facilitate the development of potential therapeutic targets and strategies for dampening or even preventing early progression of viral infections. This protocol details a versatile model that can be used to study early crosstalk, interactions, and activation of innate immune cells from factors secreted by virally infected airway epithelial cells. Using an H3N2 influenza virus (A/Aichi/2/1968) as the representative virus model, innate cell activation of co-cultured peripheral blood mononuclear cells (PBMCs) has been analyzed using flow cytometry to investigate the subsets of cells that are activated by the soluble factors released from the epithelium in response to the viral infection. The results demonstrate the gating strategy for differentiating the subsets of cells and reveal the clear differences between the activated populations of PBMCs and their crosstalk with the control and infected epithelium. The activated subsets can then be further analyzed to determine their functions as well as molecular changes specific to the cells. Findings from such a crosstalk investigation may uncover factors that are important for the activation of vital innate cell populations, which are beneficial in controlling and suppressing the progression of viral infection. Furthermore, these factors can be universally applied to different viral diseases, especially to newly emerging viruses, to dampen the impact of such viruses when they first circulate in naïve human populations.

Implementing the Clinical Occurrence Reporting and Learning System: A Double-Loop Learning Incident Reporting System in Long-term Care.

BACKGROUND: Most incident reporting systems have been questioned for their effectiveness in improving patient safety as they serve as an administrative reporting system. LOCAL PROBLEM: The long-term-care sector faced unique challenges, such an aging population and resource constraints, and its current incident reporting systems lack contextualization to address its needs. METHODS: This quality improvement project was conducted at a 624-bed nursing home in Singapore from January to September 2019, using the Plan-Do-Study-Act methodology. INTERVENTION: The existing incident reporting system (known as Clinical Occurrence Reporting and Learning System-CORALS) was redesigned to facilitate double-loop learning and workplace improvement initiatives. RESULTS: The results demonstrated significant improvement in nurses' postintervention knowledge and confidence in handling future adverse events and greater staff awareness and information dissemination on patient safety issues. CONCLUSION: A double-looped system could improve nurses' patient safety awareness and their workplace practices, which would ultimately lead to better patient outcomes.

Nursing Home's Measures during the COVID-19 Pandemic: A Critical Reflection.

This study examined the pandemic measures taken by nursing leaders to cope with COVID-19 at a nursing home in Singapore. The pandemic has affected over 215 countries, sparking a series of containment and pandemic measures by governments and healthcare organizations worldwide. Long-term care facilities are especially vulnerable to the pandemic, but little has been reported about the nursing homes' measures in handling the pandemic. The present study used Morley's (2014) three-stage critical reflection method to review meeting minutes, organizational emails, and government advisories on the COVID-19 pandemic measures undertaken by nursing leaders at a nursing home in Singapore between January and June 2020. The pandemic measures were broadly classified into four groups: (1) infection surveillance and containment measures; (2) ensuring continuity in clinical care and operational support; (3) resource and administrative coordination; and (4) staff training and development. Nurses have played a vital role in the fight against COVID-19 by ensuring continuity in patient care and demonstrating clinical leadership in pandemic efforts. This study proposes a useful nursing pandemic structure that outlines a set of functions and measures required for handling a pandemic and that can be applied to various medical emergencies and contingencies.

Molecular characterization of breast cancer needle core biopsy specimens by the 21-gene Breast Recurrence Score test.

BACKGROUND AND OBJECTIVE: Recent COVID-19 pandemic guidelines recommend genomic assessment of core biopsies to help guide treatment decisions in estrogen receptor (ER)-positive early-stage breast cancer. Herein we characterize biopsy and excisional breast cancer specimens submitted for 21-gene testing. METHODS: US samples submitted to Genomic Health for 21-gene testing (01/2004-04/2020) were assessed by pathologists and analyzed by a standardized quantitative reverse transcription-polymerase chain reaction. Predefined cutoffs were: ESR1 (positive ≥6.5), PGR (positive ≥5.5), and ERBB2 (negative <10.7). ER status by immunohistochemistry (IHC) and lymph node status were determined locally. Median and interquartile range were reported for continuous variables, and total and percent for categorical variables. Distributions were assessed overall, by age, and by nodal involvement. RESULTS: Of 919 701 samples analyzed, 13% were biopsies and 87% were excisions. Initial assay success rates were 94.5% (biopsies) and 97.3% (excisions). ER IHC concordance with central ESR1 was 96.8% (biopsies) and 97.6% (excisions). Biopsy and excisional medians were: Recurrence Score results 16 (each); ESR1 10.2 (each); PGR 7.7 and 7.6; ERBB2 9.4 and 9.2, respectively. CONCLUSIONS: Biopsy submissions for 21-gene testing are common and consistently generate results that are very similar to the experience with excisions. The 21-gene test can be performed reliably on core biopsies.

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium.

Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

Delayed Treatment of Retroclival Meningioma in a 70-year-old Female.

We report a case of a 70-year-old female who presented with a four-year history of progressive headaches in the occipital area. MRI revealed a right inferior clival meningioma. Treatment was delayed for over a year due to multiple referrals resulting in the development of new symptoms including decreased balance, generalized weakness, and difficulty swallowing.

Socioeconomic Status and Kidney Transplant Outcomes in a Universal Healthcare System: A Population-based Cohort Study.

BACKGROUND: Conflicting evidence exists regarding the relationship between socioeconomic status (SES) and outcomes after kidney transplantation. METHODS: We conducted a population-based cohort study in a publicly funded healthcare system using linked administrative healthcare databases from Ontario, Canada to assess the relationship between SES and total graft failure (ie, return to chronic dialysis, preemptive retransplantation, or death) in individuals who received their first kidney transplant between 2004 and 2014. Secondary outcomes included death-censored graft failure, death with a functioning graft, all-cause mortality, and all-cause hospitalization (post hoc outcome). RESULTS: Four thousand four hundred-fourteen kidney transplant recipients were included (median age, 53 years; 36.5% female), and the median (25th, 75th percentile) follow-up was 4.3 (2.1-7.1) years. In an unadjusted Cox proportional hazards model, each CAD $10000 increase in neighborhood median income was associated with an 8% decline in the rate of total graft failure (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.97). After adjusting for recipient, donor, and transplant characteristics, SES was not significantly associated with total or death-censored graft failure. However, each CAD $10000 increase in neighborhood median income remained associated with a decline in the rate of death with a functioning graft (adjusted (a)HR, 0.91; 95% CI, 0.83-0.98), all-cause mortality (aHR, 0.92; 95% CI, 0.86-0.99), and all-cause hospitalization (aHR, 0.95; 95% CI, 0.92-0.98). CONCLUSIONS: In conclusion, in a universal healthcare system, SES may not adversely influence graft health, but SES gradients may negatively impact other kidney transplant outcomes and could be used to identify patients at increased risk of death or hospitalization.

Predicting 3-Year Survival in Patients Receiving Maintenance Dialysis: An External Validation of iChoose Kidney in Ontario, Canada.

BACKGROUND: Many patients with end-stage kidney disease (ESKD) do not appreciate how their survival may differ if treated with a kidney transplant compared with dialysis. A risk calculator (iChoose Kidney) developed and validated in the United States provides individualized mortality estimates for different treatment options (dialysis vs living or deceased donor kidney transplantation). The calculator can be used with patients and families to help patients make more educated treatment decisions. OBJECTIVE: To validate the iChoose Kidney risk calculator in Ontario, Canada. DESIGN: External validation study. SETTING: We used several linked administrative health care databases from Ontario, Canada. PATIENTS: We included 22 520 maintenance dialysis patients and 4505 kidney transplant recipients. Patients entered the cohort between 2004 and 2014. MEASUREMENTS: Three-year all-cause mortality. METHODS: We assessed model discrimination using the C-statistic. We assessed model calibration by comparing the observed versus predicted mortality risk and by using smoothed calibration plots. We used multivariable logistic regression modeling to recalibrate model intercepts using a correction factor, when appropriate. RESULTS: In our final version of the iChoose Kidney model, we included the following variables: age (18-80 years), sex (male, female), race (white, black, other), time on dialysis (<6 months, 6-12 months, >12 months), and patient comorbidities (hypertension, diabetes, and/or cardiovascular disease). Over the 3-year follow-up period, 33.3% of dialysis patients and 6.2% of kidney transplant recipients died. The discriminatory ability was moderate (C-statistic for dialysis: 0.70, 95% confidence interval [CI]: 0.69-0.70, and C-statistic for transplant: 0.72, 95% CI: 0.69-0.75). The 3-year observed and predicted mortality estimates were comparable and even more so after we recalibrated the intercepts in 2 of our models (dialysis and deceased donor kidney transplantation). As done in the United States, we developed a Canadian Web site and an iOS application called Dialysis vs. Kidney Transplant- Estimated Survival in Ontario. LIMITATIONS: Missing data in our databases precluded the inclusion of all variables that were in the original iChoose Kidney (ie, patient ethnicity and low albumin). We were unable to perform all preplanned analyses due to the limited sample size. CONCLUSIONS: The original iChoose Kidney risk calculator was able to adequately predict mortality in this Canadian (Ontario) cohort of ESKD patients. After minor modifications, the predictive accuracy improved. The Dialysis vs. Kidney Transplant- Estimated Survival in Ontario risk calculator may be a valuable resource to help ESKD patients make an informed decision on pursuing kidney transplantation.

CONTEXTE: Plusieurs patients atteints d'insuffisance rénale terminale (IRT) ignorent à quel point leurs chances de survie varient selon qu'ils sont traités par dialyse ou par une greffe rénale. Un modèle de prévision des risques (l'outil de calcul iChoose Kidney), développé et validé aux États-Unis, fournit une estimation personnalisée des chances de survie selon les différentes modalités de traitement (dialyse ou greffe d'un rein provenant d'un donneur vivant ou décédé). L'outil de calcul peut être employé par les patients et leurs familles pour les aider à prendre une décision plus éclairée au sujet du traitement. OBJECTIF DE L'ÉTUDE: Valider l'outil de calcul iChoose Kidney dans une cohorte de patients de l'Ontario, au Canada. TYPE D'ÉTUDE: Une étude de validité externe. CADRE DE L'ÉTUDE: Plusieurs bases de données couplées du système de santé ontarien (Canada). PATIENTS: Un total de 22 520 patients dialysés et de 4 505 receveurs d'une greffe de rein ont été inclus entre 2004 et 2014. MESURES: La mortalité toutes causes sur une période de trois (3) ans. MÉTHODOLOGIE: Nous avons évalué le pouvoir discriminant du modèle à l'aide de la statistique C. L'étalonnage du modèle a été établi en comparant les risques de mortalité observé et prédit, et à l'aide de courbes d'étalonnage lissées. Des modèles de régression logistique multivariés ont été employés pour réétalonner les valeurs à l'origine en utilisant au besoin un facteur de correction. RÉSULTATS: Notre version définitive du modèle de prévision inclut les variables suivantes : l'âge du patient (18 à 80 ans), son genre, sa race (blanc, noir, autre), son expérience en dialyse (moins de 6 mois, entre 6 et 12 mois, plus de 12 mois) et ses comorbidités (hypertension, diabète et maladies cardiovasculaires). Au cours des trois ans de suivi, 33,3 % des patients dialysés et 6,2 % des receveurs d'une greffe sont décédés. Le pouvoir discriminant s'est avéré modéré avec une valeur de statistique C de 0,70 (IC 95 % : 0,69-0,70) pour la dialyse et de 0,72 (IC 95 % : 0,69-0,75) pour les greffes. Les taux de mortalité observé et estimé au cours des trois ans étaient comparables, et davantage après le réétalonnage des valeurs à l'origine dans deux de nos modèles (dialyse et receveur d'un rein d'un donneur décédé). Comme aux États-Unis, nous avons développé un site Web et une application iOS canadiens nommés Dialysis vs. Kidney Transplant-Estimated Survival in Ontario. LIMITES: Des informations manquantes dans les bases de données consultées nous ont empêchés de tenir compte de toutes les variables incluses dans le modèle iChoose Kidney original, notamment l'origine ethnique du patient et les valeurs d'albuminurie. De plus, la taille restreinte de l'échantillon ne nous a pas permis de procéder à toutes les analyses prévues. CONCLUSION: La version originale du modèle de prévision des risques iChoose Kidney a prédit adéquatement le risque de mortalité dans une cohorte de patients ontariens atteints d'IRT. La précision du pouvoir prédictif du modèle s'est améliorée à la suite d'ajustements mineurs. L'outil Dialysis vs. Kidney Transplant-Estimated Survival in Ontario pourrait ainsi devenir une ressource précieuse pour les patients ontariens atteints d'IRT, pour les aider à prendre une décision éclairée dans leur choix d'une modalité de traitement.