Multivariate spatiotemporal functional principal component analysis for modeling hospitalization and mortality rates in the dialysis population.

Dialysis patients experience frequent hospitalizations and a higher mortality rate compared to other Medicare populations, in whom hospitalizations are a major contributor to morbidity, mortality, and healthcare costs. Patients also typically remain on dialysis for the duration of their lives or until kidney transplantation. Hence, there is growing interest in studying the spatiotemporal trends in the correlated outcomes of hospitalization and mortality among dialysis patients as a function of time starting from transition to dialysis across the United States Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multivariate spatiotemporal functional principal component analysis model to study the joint spatiotemporal patterns of hospitalization and mortality rates among dialysis patients. The proposal is based on a multivariate Karhunen-Loéve expansion that describes leading directions of variation across time and induces spatial correlations among region-specific scores. An efficient estimation procedure is proposed using only univariate principal components decompositions and a Markov Chain Monte Carlo framework for targeting the spatial correlations. The finite sample performance of the proposed method is studied through simulations. Novel applications to the USRDS data highlight hot spots across the United States with higher hospitalization and/or mortality rates and time periods of elevated risk.

A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Center Volume and Survival Relationship for Neonates With Congenital Diaphragmatic Hernia Treated With Extracorporeal Life Support.

OBJECTIVES: Literature is emerging regarding the role of center volume as an independent variable contributing to improved outcomes. A higher volume of index procedures may be associated with decreased morbidity and mortality. This association has not been examined for the subgroup of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS). Our study aims to examine the risk-adjusted association between center volume and outcomes in CDH-ECLS neonates, hypothesizing that higher center volume confers a survival advantage. DESIGN: Multicenter, retrospective comparative study using the Extracorporeal Life Support Organization database. SETTING: One hundred twenty international pediatric centers. PATIENTS: Neonates with CDH managed with ECLS from 2000 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort included 4,985 neonates with a mortality rate of 50.6%. For the 120 centers studied, mean center volume was 42.4 ± 34.6 CDH ECLS cases over the 20-year study period. In an adjusted model, higher ECLS volume was associated with lower odds of mortality: odds ratio (OR) 0.995 (95% CI, 0.992-0.999; p = 0.014). For an increase in one sd in volume, that is, 1.75 cases annually, the OR for mortality was lower by 16.7%. Volume was examined as a categorical exposure variable where low-volume centers (fewer than 2 cases/yr) were associated with 54% higher odds of mortality (OR, 1.54; 95% CI, 1.03-2.29) compared with high-volume centers. On-ECLS complications (mechanical, neurologic, cardiac, hematologic metabolic, and renal) were not associated with volume. The likelihood of infectious complications was higher for low- (OR, 1.90; 95% CI, 1.06-3.40) and medium-volume (OR, 1.87; 95% CI, 1.03-3.39) compared with high-volume centers. CONCLUSIONS: In this study, a survival advantage directly proportional to center volume was observed for CDH patients managed with ECLS. There was no significant difference in most complication rates. Future studies should aim to identify factors contributing to the higher mortality and morbidity observed at low-volume centers.

A Bayesian multilevel time-varying framework for joint modeling of hospitalization and survival in patients on dialysis.

Over 782 000 individuals in the United States have end-stage kidney disease with about 72% of patients on dialysis, a life-sustaining treatment. Dialysis patients experience high mortality and frequent hospitalizations, at about twice per year. These poor outcomes are exacerbated at key time periods, such as the fragile period after transition to dialysis. In order to study the time-varying effects of modifiable patient and dialysis facility risk factors on hospitalization and mortality, we propose a novel Bayesian multilevel time-varying joint model. Efficient estimation and inference is achieved within the Bayesian framework using Markov chain Monte Carlo, where multilevel (patient- and dialysis facility-level) varying coefficient functions are targeted via Bayesian P-splines. Applications to the United States Renal Data System, a national database which contains data on nearly all patients on dialysis in the United States, highlight significant time-varying effects of patient- and facility-level risk factors on hospitalization risk and mortality. Finite sample performance of the proposed methodology is studied through simulations.

Inborn Versus Outborn Delivery in Neonates With Congenital Diaphragmatic Hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a morbid and potentially fatal condition that challenges providers. The aim of this study is to compare outcomes in neonates with prenatally diagnosed CDH that are inborn (delivered in the institution where definitive care for CDH is provided) versus outborn. METHODS: Prenatally diagnosed CDH cases were identified from the Congenital Diaphragmatic Hernia Study Group (CDHSG) database between 2007 and 2019. Using risk adjustment based on disease severity, we compared inborn versus outborn status using baseline risk and multivariable logistic regression models. The primary endpoint was mortality and the secondary endpoint was need for extracorporeal life support (ECLS). RESULTS: Of 4195 neonates with prenatally diagnosed CDH, 3087 (73.6%) were inborn and 1108 (26.4%) were outborn. There was no significant difference in birth weight, gestational age, or presence of additional congenital anomalies. There was no difference in mortality between inborn and outborn infants (32.6% versus 33.8%, P = 0.44) or ECLS requirement (30.9% versus 31.5%, P = 0.73). Among neonates requiring ECLS, outborn status was a risk factor for mortality (OR 1.51, 95% CI 1.13-2.01, P = 0.006). After adjusting for post-surgical defect size, which is not known prenatally, outborn status was no longer a risk factor for mortality for infants requiring ECLS. CONCLUSIONS: Risk of mortality and need for ECLS for inborn CDH patients is not different to outborn infants. Future studies should be directed to establishing whether highest risk infants are at risk for worse outcomes based on center of birth.

Multilevel modeling of spatially nested functional data: Spatiotemporal patterns of hospitalization rates in the US dialysis population.

End-stage renal disease patients on dialysis experience frequent hospitalizations. In addition to known temporal patterns of hospitalizations over the life span on dialysis, where poor outcomes are typically exacerbated during the first year on dialysis, variations in hospitalizations among dialysis facilities across the US contribute to spatial variation. Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multilevel spatiotemporal functional model to study spatiotemporal patterns of hospitalization rates among dialysis facilities. Hospitalization rates of dialysis facilities are considered as spatially nested functional data (FD) with longitudinal hospitalizations nested in dialysis facilities and dialysis facilities nested in geographic regions. A multilevel Karhunen-Loéve expansion is utilized to model the two-level (facility and region) FD, where spatial correlations are induced among region-specific principal component scores accounting for regional variation. A new efficient algorithm based on functional principal component analysis and Markov Chain Monte Carlo is proposed for estimation and inference. We report a novel application using USRDS data to characterize spatiotemporal patterns of hospitalization rates for over 400 health service areas across the US and over the posttransition time on dialysis. Finite sample performance of the proposed method is studied through simulations.

Risk Factors for Hemolysis During Extracorporeal Life Support for Congenital Diaphragmatic Hernia.

BACKGROUND: Neonates receiving extracorporeal life support (ECLS) for congenital diaphragmatic hernia (CDH) require prolonged support compared with neonates with other forms of respiratory failure. Hemolysis is a complication that can be seen during ECLS and can lead to renal failure and potentially to worse outcomes. The purpose of this study was to identify risk factors for the development of hemolysis in CDH patients treated with ECLS. METHODS: The Extracorporeal Life Support Organization database was used to identify infants with CDH (2000-2015). The primary outcome was hemolysis (plasma-free hemoglobin >50 mg/dL). Potentially associated variables were identified in the data set. Descriptive statistics and a series of nested multivariable logistic regression models were used to identify associations between hemolysis and demographic, pre-ECLS, and on-ECLS factors. RESULTS: There were 4576 infants with a mortality of 52.5%. The overall mean rate of hemolysis was 10.5% during the study period. In earlier years (2000-2005), the hemolysis rates were 6.3% and 52.7% for roller versus centrifugal pumps, whereas in later years (2010-2015), they were 2.9% and 26.5%, respectively. The fully adjusted model demonstrated that the use of centrifugal pumps was a strong predictor of hemolysis (odds ratio: 6.67, 95% confidence interval: 5.14-8.67). In addition, other risk factors for hemolysis included low 5-min Apgar score, on-ECLS complications (renal, metabolic, and cardiovascular), and duration of ECLS. CONCLUSIONS: In our cohort of CDH patients receiving ECLS over 15 y, the use of centrifugal pumps increased over time, along with the rate of hemolysis. Patient- and treatment-level risk factors were identified contributing to the development of hemolysis.

Continuous glucose monitoring in an end-stage renal disease patient with diabetes receiving hemodialysis.

Diabetes is the leading cause of end-stage renal disease (ESRD) and contributes to heightened morbidity and mortality in dialysis patients. Given that ESRD patients are susceptible to hypoglycemia and hyperglycemia via multiple pathways, adequate glycemic monitoring and control is a cornerstone in diabetic kidney disease management. In ESRD, existing glycemic metrics such as glycated hemoglobin, self-monitored blood glucose, fructosamine, and glycated albumin have limitations in accuracy, convenience, and accessibility. In contrast, continuous glucose monitoring (CGM) provides automated, less invasive glucose measurements and more comprehensive glycemic data versus conventional metrics. Here, we report a 48-year-old male with ESRD due to diabetes receiving thrice-weekly hemodialysis who experienced decreased patient-burden, greater glucose monitoring adherence, improved glycemic parameters, and reduction in hypoglycemia after transitioning to CGM. Through this case, we discuss how CGM is a practical, convenient patient-centered tool that may improve metabolic outcomes and quality of life in ESRD patients with diabetes.

Dietary Potassium Intake and Mortality in a Prospective Hemodialysis Cohort.

OBJECTIVES: Among hemodialysis patients, clinical practice guidelines recommend dietary potassium restriction given concerns about potential hyperkalemia leading to malignant arrhythmias and mortality. However, there are sparse data informing recommendations for dietary potassium intake in this population. We thus sought to examine the relationship between dietary potassium intake and death risk in a prospective cohort of hemodialysis patients. DESIGN AND METHODS: Among 415 hemodialysis patients from the prospective "Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease" cohort recruited across 16 outpatient dialysis clinics, information regarding dietary potassium intake was obtained using Food Frequency Questionnaires administered over October 2011 to March 2015. We first examined associations of baseline dietary potassium intake categorized as tertiles with mortality risk using Cox regression. We then examined clinical characteristics associated with low dietary potassium intake (defined as the lowest tertile) using logistic regression. RESULTS: In expanded case-mix Cox analyses, patients whose dietary potassium intake was in the lowest tertile had higher mortality (ref: highest tertile) (adjusted hazard ratio 1.74, 95% confidence interval 1.14-2.66). These associations had even greater magnitude of risk following adjustment for laboratory and nutritional covariates (adjusted hazard ratio 2.65, 95% confidence interval 1.40-5.04). In expanded case-mix restricted cubic spline analyses, there was a monotonic increase in mortality risk with incrementally lower dietary potassium intake. In expanded case-mix logistic regression models, female sex; higher serum bicarbonate; and lower dietary energy, protein, and fiber intake were associated with low dietary potassium intake. CONCLUSIONS: In a prospective cohort of hemodialysis patients, lower dietary potassium intake was associated with higher mortality risk. These findings suggest that excessive dietary potassium restriction may be deleterious in hemodialysis patients, and further studies are needed to determine the optimal dietary potassium intake in this population.

Conservative vs. preservative management of chronic kidney disease: similarities and distinctions.

PURPOSE OF REVIEW: Dialysis has been the prevailing treatment paradigm in advanced chronic kidney disease (CKD) for patients ineligible for or unlikely to receive kidney transplantation. As dialysis may neither offer survival benefit nor improved quality of life in certain groups, there has been increasing interest in conservative management as an alternative approach. RECENT FINDINGS: Experts and workgroups suggest the main goals of conservative management are to optimize quality of life, treat symptoms of end-stage renal disease without dialysis or transplant, and improve survival and cardiovascular health. Given the implications of preserved kidney function on clinical outcomes, preservative management has been proposed as an integral component of conservative management. Growing evidence suggests the survival benefit of dialysis vs. conservative management without dialysis is marginal or even reversed in certain subpopulations (elderly, multimorbid, cardiovascular disease). Limited data suggest that conservative and preservative management is associated with equivalent to more favorable trajectories of health-related quality of life and symptom burden over time as opposed to dialysis. SUMMARY: Whereas existing data suggest conservative management is a viable patient-centered treatment strategy, further research is needed to determine the comparative effectiveness of preservative kidney management vs. dialysis or palliative management, as well as which patient subgroups will most benefit from these treatment strategies.

Mortality Risk in Chronic Kidney Disease Patients Transitioning to Dialysis: Impact of Opiate and Non-Opiate Use.

BACKGROUND: Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis. METHODS: We examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007-14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models. RESULTS: Among 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05-1.10), 1.07 (1.01-1.13), and 1.00 (0.94-1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use). CONCLUSIONS: In NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality.

A multilevel mixed effects varying coefficient model with multilevel predictors and random effects for modeling hospitalization risk in patients on dialysis.

For patients on dialysis, hospitalizations remain a major risk factor for mortality and morbidity. We use data from a large national database, United States Renal Data System, to model time-varying effects of hospitalization risk factors as functions of time since initiation of dialysis. To account for the three-level hierarchical structure in the data where hospitalizations are nested in patients and patients are nested in dialysis facilities, we propose a multilevel mixed effects varying coefficient model (MME-VCM) where multilevel (patient- and facility-level) random effects are used to model the dependence structure of the data. The proposed MME-VCM also includes multilevel covariates, where baseline demographics and comorbidities are among the patient-level factors, and staffing composition and facility size are among the facility-level risk factors. To address the challenge of high-dimensional integrals due to the hierarchical structure of the random effects, we propose a novel two-step approximate EM algorithm based on the fully exponential Laplace approximation. Inference for the varying coefficient functions and variance components is achieved via derivation of the standard errors using score contributions. The finite sample performance of the proposed estimation procedure is studied through simulations.

Profiling dialysis facilities for adverse recurrent events.

Profiling analysis aims to evaluate health care providers, such as hospitals, nursing homes, or dialysis facilities, with respect to a patient outcome. Previous profiling methods have considered binary outcomes, such as 30-day hospital readmission or mortality. For the unique population of dialysis patients, regular blood works are required to evaluate effectiveness of treatment and avoid adverse events, including dialysis inadequacy, imbalance mineral levels, and anemia among others. For example, anemic events (when hemoglobin levels exceed normative range) are recurrent and common for patients on dialysis. Thus, we propose high-dimensional Poisson and negative binomial regression models for rate/count outcomes and introduce a standardized event ratio measure to compare the event rate at a specific facility relative to a chosen normative standard, typically defined as an "average" national rate across all facilities. Our proposed estimation and inference procedures overcome the challenge of high-dimensional parameters for thousands of dialysis facilities. Also, we investigate how overdispersion affects inference in the context of profiling analysis. The proposed methods are illustrated with profiling dialysis facilities for recurrent anemia events.

Novel Health Information Technology to Aid Provider Recognition and Treatment of Major Depressive Disorder and Posttraumatic Stress Disorder in Primary Care.

BACKGROUND: Millions of traumatized refugees worldwide have resettled in the United States. For one of the largest, the Cambodian community, having their mental health needs met has been a continuing challenge. A multicomponent health information technology screening tool was designed to aid provider recognition and treatment of major depressive disorder and posttraumatic stress disorder (PTSD) in the primary care setting. METHODS: In a clustered randomized controlled trial, 18 primary care providers were randomized to receive access to a multicomponent health information technology mental health screening intervention, or to a minimal intervention control group; 390 Cambodian American patients empaneled to participating providers were assigned to the providers' randomized group. RESULTS: Electronic screening revealed that 65% of patients screened positive for depression and 34% screened positive for PTSD. Multilevel mixed effects logistic models, accounting for clustering structure, indicated that providers in the intervention were more likely to diagnose depression [odds ratio (OR), 6.5; 95% confidence interval (CI), 1.48-28.79; P=0.013] and PTSD (OR, 23.3; 95% CI, 2.99-151.62; P=0.002) among those diagnosed during screening, relative to the control group. Providers in the intervention were more likely to provide evidence-based guideline (OR, 4.02; 95% CI, 1.01-16.06; P=0.049) and trauma-informed (OR, 15.8; 95% CI, 3.47-71.6; P<0.001) care in unadjusted models, relative to the control group. Guideline care, but not trauma-informed care, was associated with decreased depression at 12 weeks in both study groups (P=0.003), and neither was associated with PTSD outcomes at 12 weeks. CONCLUSIONS: This innovative approach offers the potential for training primary care providers to diagnose and treat traumatized patients, the majority of whom seek mental health care in primary care (ClinicalTrials.gov number, NCT03191929).

Association of thyroid status prior to transition to end-stage renal disease with early dialysis mortality.

BACKGROUND: Advanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation. METHODS: Among US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation. RESULTS: Among 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment. CONCLUSIONS: Among new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.

Glycemic Status and Mortality in Chronic Kidney Disease According to Transition Versus Nontransition to Dialysis.

OBJECTIVE: The impact of glycemic control in diabetic patients with chronic kidney disease (CKD) who may or may not transition to dialysis remains uncertain, given recent interest in the conservative management of advanced CKD without dialysis therapy, which may benefit from alternative glycemic control strategies. DESIGN AND METHODS: Among a national cohort of US Veterans, we examined the association of glycemic status, defined by averaged random blood glucose and hemoglobin A1c (HbA1c), with mortality after transitioning to dialysis over 2007-2011 (Transition Cohort) compared with patients in a one-to-one matched cohort of CKD patients with diabetes who did not transition to dialysis (Nontransition Cohort). RESULTS: Among 17,121 patients in the Transition Cohort, averaged random glucose ≥200 mg/dL was associated with higher mortality in expanded case-mix analyses (reference: 100-<120 mg/dL): adjusted hazard ratio (95% confidence interval) 1.26 (1.13-1.40). In the transition cohort, HbA1c 8-<10% and ≥10% were associated with higher mortality (reference: 6-<8%): adjusted hazard ratios (95% confidence interval) 1.21 (1.11-1.33) and 1.43 (1.21-1.69), respectively. Among 8,711 patients in the Nontransition Cohort, averaged random glucose <100 mg/dl and ≥160 mg/dl were associated with higher death risk, whereas HbA1c was not associated with mortality. CONCLUSION: In diabetic CKD patients transitioning to dialysis, higher averaged random glucose and HbA1c were associated with early dialysis mortality, whereas in matched CKD patients who did not transition, both lower and higher glucose levels were associated with higher mortality. These data suggest the need for different glycemic strategies based on whether there are plans to transition to dialysis versus pursue conservative management among diabetic patients with CKD.

Are Electronic and Paper Questionnaires Equivalent to Assess Patients with Overactive Bladder?

PURPOSE: Overactive bladder syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection or another obvious pathological condition. Electronic questionnaires have been used in a few specialties with the hope of improving treatment outcomes and patient satisfaction. However, they have not been widely used in the urological field. When treating overactive bladder, the main outcome is to improve patient quality of life. The primary objective of this study was to evaluate whether electronic questionnaires would be equally accepted as or preferred to paper questionnaires. The secondary objective was to look at the preference in relation to patient age, education and iPad® tablet familiarity. MATERIALS AND METHODS: We prospectively evaluated the iList® electronic questionnaire application using a friendly iPad tablet in patients with overactive bladder who presented to the urology clinic at our institution. Each of the 80 patients who were recruited randomly completed the validated OABSS (Overactive Bladder Symptom Score) and the PPBC (Patient Perception of Bladder Condition) questionnaires in paper and electronic format on the tablet. Variables potentially associated with the outcomes of interest included demographic data, questionnaire method preference, patient response rate and iPad familiarity. We used the 2-sided Z-test to determine whether the proportion of patients who considered the tablet to be the same, better or much better than paper was significantly greater than 50%. The 2-sided chi-square test was applied to assess whether the intervention effect significantly differed among the demographic subgroups. RESULTS: A total of 80 patients 21 to 87 years old were enrolled in the study from November 2015 to August 2016. Of the patients 53% were female and 49% were 65 years or younger. The incidence of those who considered the tablet to be the same or better than paper was 82.5% (95% CI 74.2-90.8, p <0.001). The incidence of patients who considered the tablet to be the same or better than paper ranged from 76% to 97% regardless of age, gender and education subgroup as well as in those with any familiarity with the tablet (each p <0.001). Of the 20 patients who were not familiar with the tablet 45% preferred the electronic questionnaire (p = 0.654). CONCLUSIONS: We found that the proportion of patients who considered electronic questionnaires to be equivalent to or better than paper versions was higher than those who preferred paper questionnaires regardless of age, gender or education level.

Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis.

RATIONALE & OBJECTIVE: Diabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post-end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011. EXPOSURE: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens. OUTCOME: The outcome of post-ESRD all-cause mortality was evaluated relative to pre-ESRD hypoglycemia. The outcome of pre-ESRD hypoglycemia-related hospitalization was evaluated relative to antidiabetic medication regimens. ANALYTIC APPROACH: We examined whether the occurrence and frequency of pre-ESRD hypoglycemia-related hospitalizations are associated with post-ESRD mortality using Cox regression models adjusted for case-mix covariates. In a subcohort of patients prescribed 0 to 2 oral antidiabetic drugs and/or insulin, we examined the 12 most commonly prescribed antidiabetic medication regimens and risk for pre-ESRD hypoglycemia-related hospitalization using logistic regression models adjusted for case-mix covariates. RESULTS: Among 30,156 patients who met eligibility criteria, the occurrence of pre-ESRD hypoglycemia-related hospitalization(s) was associated with higher post-ESRD mortality risk: adjusted HR (aHR), 1.25; 95% CI, 1.17-1.34 (reference group: no hypoglycemia hospitalization). Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: aHRs of 1.21 (95% CI, 1.12-1.30), 1.47 (95% CI, 1.19-1.82), and 2.07 (95% CI, 1.46-2.95) for 1, 2, and 3 or more hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia hospitalization). Compared with patients who were prescribed neither oral antidiabetic drugs nor insulin, medication regimens that included sulfonylureas and/or insulin were associated with higher risk for hypoglycemia. LIMITATIONS: Residual confounding cannot be excluded. CONCLUSIONS: Among incident patients with ESRD with diabetes, a dose-dependent relationship between frequency of pre-ESRD hypoglycemia-related hospitalizations and post-ESRD mortality was observed. Further study of diabetic management strategies that prevent hypoglycemia as patients with chronic kidney disease transition to ESRD are warranted.

Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort.

BACKGROUND: Studies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations. METHODS: We evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models. RESULTS: In baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications. CONCLUSION: Low (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population.

Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients.

Background: Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (Δ) and IDH frequency are incrementally associated with all-cause mortality. Methods: In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP, ΔiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates. Results: We observed that niSBP of <90 and ≥140 mmHg had a 5-year mortality hazard ratio (HR) (95% confidence interval) of 1.57 (1.47-1.67) and 1.25 (1.18-1.33), respectively, compared with niSBP 110 to <120 mmHg. ΔiSBP of <15 and ≥50 compared with 21-30 mmHg had mortality HR of 1.31 (1.26-1.37) and 1.32 (1.24-1.39), respectively. Among patients with >40% IDH frequency, we observed a mortality HR of 1.49 (1.42-1.57) compared with 0% IDH frequency in fully adjusted models. These associations were robust at 1 and 2 years of follow-up. Conclusion: In conclusion, we observed a U-shaped association between niSBP and ΔiSBP and mortality and a direct linear relationship between IDH frequency and mortality. Our findings lend some prognostic insight of HD blood pressure and hemodynamics, and have the potential to guide blood pressure management strategies among the HD population.