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It has previously been shown that the encoding of time-dependent signals by feedforward networks (FFNs) of processing units exhibits suprathreshold stochastic resonance (SSR), which is an optimal signal transmission for a finite level of independent, individual stochasticity in the single units. In this study, a recurrent spiking network is simulated to demonstrate that SSR can be also caused by network noise in place of intrinsic noise. The level of autonomously generated fluctuations in the network can be controlled by the strength of synapses, and hence the coding fraction (our measure of information transmission) exhibits a maximum as a function of the synaptic coupling strength. The presence of a coding peak at an optimal coupling strength is robust over a wide range of individual, network, and signal parameters, although the optimal strength and peak magnitude depend on the parameter being varied. We also perform control experiments with an FFN illustrating that the optimized coding fraction is due to the change in noise level and not from other effects entailed when changing the coupling strength. These results also indicate that the non-white (temporally correlated) network noise in general provides an extra boost to encoding performance compared to the FFN driven by intrinsic white noise fluctuations.

Transplantation is the preferred treatment for patients with kidney failure, but the need exceeds the supply of transplantable kidneys, and patients routinely wait >5 years on dialysis for a transplant. Coronary artery disease (CAD) is common in kidney failure and can exclude patients from transplantation or result in death before or after transplantation. Screening asymptomatic patients for CAD using noninvasive tests prior to wait-listing and at regular intervals (ie, annually) after wait-listing until transplantation is the established standard of care and is justified by the need to avoid adverse patient outcomes and loss of organs. Patients with abnormal screening tests undergo coronary angiography, and those with critical stenoses are revascularized. Screening is potentially harmful because patients may be excluded or delayed from transplantation, and complications after revascularization are more frequent in this population. CARSK will test the hypothesis that eliminating screening tests for occult CAD after wait-listing is not inferior to regular screening for the prevention of major adverse cardiac events defined as the composite of cardiovascular death, nonfatal myocardial infarction, urgent revascularization, and hospitalization for unstable angina. Secondary outcomes include the transplant rate, safety measures, and the cost-effectiveness of screening. Enrolment of 3,306 patients over 3 years is required, with patients followed for up to 5 years during wait-listing and for 1 year after transplantation. By validating or refuting the use of screening tests during wait-listing, CARSK will ensure judicious use of health resources and optimal patient outcomes.

The American College of Surgeons Oncology Group Z0011 trial has been lauded as practice changing. We sought to identify its impact on breast cancer surgery in the community hospital setting. A retrospective review was performed from 8 community hospitals identifying patients with invasive breast cancer meeting the Z0011 criteria. The primary outcome measures were the rate of completion axillary lymph node dissection (ALND) and performance of intraoperative sentinel lymph node (SLN) analysis over time. A total of 1,125 lumpectomies with SLN biopsies were performed with 180 subjects meeting inclusion criteria. Performance of ALND (P < .0001) and intraoperative SLN analysis (P < .0001) declined during each time period. Patients more likely to undergo ALND included those with extracapsular extension (odds ratio [OR] 12.8, 95% confidence interval [CI] 2.5 to 67.1) and those who underwent reoperative surgery (OR 10.8, 95% CI 2.6 to 44.4) or intraoperative SLN analysis (OR 5.1, 95% CI 1.2 to 21.9). American College of Surgeons Oncology Group Z0011 trial has been rapidly practice changing in the community hospital setting. •We investigate the effect of ACOSOG Z0011 on breast surgery practice.•We examined factors leading to axillary lymph node dissection.•Intraoperative sentinel lymph node analysis leads to increase in ALND.•ACOSOG Z0011 has been rapidly adopted in community practice.

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.

Background: Due to their history of renal disease and exposure to immunosuppression, kidney transplant recipients with a failing graft may be at higher risk of adverse outcomes compared to nontransplant controls. Understanding the burden of disease in transplant recipients may inform treatment decisions of people whose native kidneys are failing and may be eligible for a transplant. Objective: To compare mortality and morbidity in kidney transplant recipients with a failing graft to matched nontransplant controls. Design: Retrospective cohort study. Setting: Alberta, Canada. Patients: Kidney transplant recipients with a failing graft were identified as having at least 2 estimated glomerular filtration rate (eGFR) measurements between 15-30 mL/min/1.73 m2 (90-365 days apart). We also identified nontransplant controls with a similar degree of kidney dysfunction. Measurements: Mortality and hospitalization. Methods: We propensity-score matched 520 kidney transplant recipients with a failing graft to 520 nontransplant controls. Results: The median age of the matched cohort was 57 years and 40% were women. Compared to matched nontransplant controls, recipients with a failing graft had a higher hazard of death (hazard ratio, 1.54; 95% confidence interval [CI], 1.28-1.85; p < .001) and a higher rate of all-cause hospitalization (rate ratio, 1.67; 95% CI, 1.42-1.97; p < .001). Kidney transplant recipients also had a higher rate of several cause-specific hospitalizations including genitourinary, cardiovascular, and infectious causes. Limitations: Observational design with the risk of residual confounding. Conclusions: A failing kidney transplant is associated with an increased burden of mortality and morbidity beyond chronic kidney disease. This information may assist the discussion of prognosis in kidney transplant recipients with a failing graft and the design of strategies to minimize risks.

Importance Population-based data are needed to inform the safe prescribing of fluoroquinolone antibiotics to patients with advanced chronic kidney disease (CKD). Objective To quantify the 14-day risk of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event in patients with advanced CKD newly prescribed a fluoroquinolone at a higher vs a lower dose. Design, Setting, and Participants This population-based cohort study in Ontario, Canada (January 1, 2008, to March 17, 2020) used linked health care data to identify new users of fluoroquinolone antibiotics. Participants included adults 66 years or older with advanced CKD (an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2but not receiving dialysis). Data analysis was performed from January 1 to April 30, 2021. Exposures A new prescription for a higher-dose fluoroquinolone (ciprofloxacin, 501-1000 mg/d; levofloxacin, 501-750 mg/d; or norfloxacin, 401-800 mg/d) vs a lower-dose fluoroquinolone (ciprofloxacin, 500 mg/d; levofloxacin, 250-500 mg/d; or norfloxacin, 400 mg/d). Main Outcomes and Measure The primary outcome was the 14-day risk of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event. Secondary outcomes included a hospital visit with sepsis, retinal detachment or other tendinopathies, all-cause hospitalization, all-cause mortality, and sudden cardiac death. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on baseline health. Weighted risk ratios and risk differences were obtained using modified Poisson regression and binomial regression, respectively. Results Of 11 917 patients (median age, 83 years [IQR, 77-89 years]; 7438 women [62.4%]; median eGFR, 25 [IQR, 21-28] mL/min/1.73 m2) included in the analysis, 5482 (46.0%) received a higher-dose and 6435 (54.0%) received a lower-dose fluoroquinolone. After weighting, the primary composite outcome—a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event—occurred in 68 of 5482 patients (1.2%) treated with a higher-dose fluoroquinolone and in 47 of 5516 (0.9%) treated with a lower-dose fluoroquinolone (weighted risk ratio, 1.45 [95% CI, 1.01-2.08]; weighted risk difference, 0.39% [95% CI, 0.01%-0.76%]). The risk of sepsis, retinal detachment, all-cause hospitalization, all-cause mortality, and sudden cardiac death did not differ significantly between groups. Conclusions and Relevance These findings suggest that older patients with advanced CKD who were prescribed a fluoroquinolone at a higher-than-recommended dose were significantly more likely to experience the composite outcome of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event, although the absolute risk of these events was less than 2%.

Background: Previous studies conducted in publicly and privately funded health care systems suggest that access to kidney transplants may vary depending on where a patient receives their kidney care. It is poorly understood whether variability exists across the key steps required to receive a kidney transplant in a publicly funded health care system. Objective: To determine whether there is variation across Ontario’s regional renal programs (RRPs) in key steps completed toward receiving a kidney transplant. Design: Population-based cohort study from November 1, 2017, to December 31, 2021, using linked administrative health care databases with a maximum follow-up of March 31, 2023. Setting: This study includes 27 RRPs and independent health facilities in Ontario, Canada. Patients: Patients approaching the need for dialysis and patients receiving maintenance dialysis with no recorded contraindication to kidney transplant. Measurements: Key steps toward receiving a kidney transplant, including (1) referred to a transplant center for an evaluation; (2) had a potential living donor contact a transplant center to be evaluated; (3) deceased donor waitlist activation; and (4) received a transplant from a living or deceased donor. Methods: For each step toward receiving a kidney transplant, we reported a unique incidence rate per 100 person-years with a 95% confidence interval (95% CI), presented by Ontario’s RRPs, including the 27 RRPs and independent health facilities. We also presented results by 5 Ontario geographic regions. In an additional analysis, we examined the time to complete specific transplant steps. Results: We included 8319 individuals approaching the need for dialysis and 4869 individuals receiving maintenance dialysis. During follow-up, 2870 (34.5%) individuals approaching the need for dialysis initiated maintenance dialysis. In individuals approaching the need for dialysis, we found the rate of a potential living kidney donor contacting a transplant center to be evaluated varied more than 17-fold across RRPs from 0.67 (95% CI = 0.1, 4.8) to 11.7 (95% CI = 9.2, 14.9). In the dialysis cohort, the average number of steps completed toward receiving a kidney transplant varied almost 4-fold across RRPs from 11.7 (95% CI = 9.3, 14.8) to 44.0 (95% CI = 38.6, 50.1) steps per 100 person-years. The average rate of each step measured separately also varied widely, with the rate of referral to a transplant center for an evaluation (per 100 person-years) varying across RRPs from 6.0 (95% CI = 4.2, 8.5) to 47.9 (95% CI = 42.6, 53.8), the rate of a potential living kidney donor contacting a transplant center to be evaluated from 1.5 (95% CI = 0.78, 2.9) to 10.7 (95% CI = 7.9, 14.5), the rate of deceased donor waitlisting from 2.9 (95% CI = 1.9, 4.4) to 13.2 (95% CI = 11.0, 15.8), and the rate of kidney transplant from 2.0 (95% CI = 1.1, 3.4) to 12.6 (95% CI = 10.8, 14.8). When examining the results by 5 Ontario geographic regions, we found patients receiving maintenance dialysis in Northern Ontario had substantially lower rates of completing key steps toward receiving a kidney transplant. For example, the rate of transplant referral (per 100 person-years) was almost 3-fold lower in Northern Ontario (10.0, 95% CI = 8.3, 12.0) compared to Toronto (28.7, 95% CI = 25.7, 32.1). Limitations: We did not examine the reason for differences in access to kidney transplant across RRPs (eg, differences in physician practices and staff-to-patient ratio). Conclusions: Despite operating in a publicly funded health care system, there is substantial variability across the 4 key steps required to receive a kidney transplant. Trial registration: Not registered.

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.

Background: Individuals with kidney disease are at a high risk of bleeding and as such tools that identify those at highest risk may aid mitigation strategies. Objective: We set out to develop and validate a prediction equation (BLEED-HD) to identify patients on maintenance hemodialysis at high risk of bleeding. Design: International prospective cohort study (development); retrospective cohort study (validation). Settings: Development: 15 countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018); Validation: Ontario, Canada. Patients: Development: 53 147 patients; Validation: 19 318 patients. Measurements: Hospitalization for a bleeding event. Methods: Cox proportional hazards models. Results: Among the DOPPS cohort (mean age, 63.7 years; female, 39.7%), a bleeding event occurred in 2773 patients (5.2%, event rate 32 per 1000 person-years), with a median follow-up of 1.6 (interquartile range [IQR], 0.9-2.1) years. BLEED-HD included 6 variables: age, sex, country, previous gastrointestinal bleeding, prosthetic heart valve, and vitamin K antagonist use. The observed 3-year probability of bleeding by deciles of risk ranged from 2.2% to 10.8%. Model discrimination was low to moderate (c-statistic = 0.65) with excellent calibration (Brier score range = 0.036-0.095). Discrimination and calibration of BLEED-HD were similar in an external validation of 19 318 patients from Ontario, Canada. Compared to existing bleeding scores, BLEED-HD demonstrated better discrimination and calibration (c-statistic: HEMORRHAGE = 0.59, HAS-BLED = 0.59, and ATRIA = 0.57, c-stat difference, net reclassification index [NRI], and integrated discrimination index [IDI] all P value <.0001). Limitations: Dialysis procedure anticoagulation was not available; validation cohort was considerably older than the development cohort. Conclusion: In patients on maintenance hemodialysis, BLEED-HD is a simple risk equation that may be more applicable than existing risk tools in predicting the risk of bleeding in this high-risk population.

Background: Quality indicators are required to identify gaps in care and to improve equitable access to kidney transplants. Referral to a transplant center for an evaluation is the first step toward receiving a kidney transplant, yet widespread reporting on this metric is lacking. Objective: The objective was to use administrative health care databases to examine multiple ways to define referral for a kidney transplant evaluation by varying clinical inclusion criteria, definitions for end of follow-up, and statistical methodologies. Design: This is a population-based cohort study. Setting: This study linked administrative health care databases in Ontario, Canada. Patients: Adults from Ontario, Canada, with advanced chronic kidney disease (CKD) between April 1, 2017, and March 31, 2018. Measurements: The primary outcome was the 1-year cumulative incidence of kidney transplant referral. Methods: We created several patient cohort definitions, varying patient transplant eligibility by health status (eg, whether patients had a recorded contraindication to transplant). We presented results by advanced CKD status (ie, patients approaching the need for dialysis vs receiving maintenance dialysis) and by method of cohort entry (ie, incident only vs prevalent and incident patients combined), resulting in 12 unique cohorts. Results: Sample size varied substantially from 414 to 4128 depending on the patient cohort definition, with the largest reduction in cohort size occurring when we restricted to a “healthy” (eg, no evidence of cardiovascular disease) group of patients. The 1-year cumulative incidence of transplant referral varied widely across cohorts. For example, in the incident maintenance dialysis population, the cumulative incidence varied more than 2-fold from 16.3% (95% confidence interval [CI] = 15.0%-17.7%) using our most inclusive cohort definition to 40.0% (95% CI = 36.0%-44.5%) using our most restrictive “healthy” cohort of patients. Limitations: Administrative data may have misclassified individuals’ eligibility for kidney transplant. Conclusions: These results can be used by jurisdictions to measure transplant referral, a necessary step in kidney transplantation that is not equitable for all patients. Adoption of these indicators should drive quality improvement efforts that increase the number of patients referred for transplantation and ensure equitable access for all patient groups.