Remote gate control of topological transitions in moiré superlattices via cavity vacuum fields.

Placed in cavity resonators with three-dimensionally confined electromagnetic wave, the interaction between quasiparticles in solids can be induced by exchanging virtual cavity photons, which can have a nonlocal characteristic. Here, we investigate the possibility of utilizing this nonlocality to realize the remote control of the topological transition in mesoscopic moiré superlattices at full filling (one electron/hole per supercell) embedded in a split-ring terahertz electromagnetic resonator. We show that gate tuning one moiré superlattice can remotely drive a topological band inversion in another moiré superlattice not in contact but embedded in the same cavity. Our study of remote on/off switching of a topological transition provides a paradigm for the control of material properties via cavity vacuum fields.

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.

Electron-Photon Chern Number in Cavity-Embedded 2D Moiré Materials.

We explore theoretically how the topological properties of 2D materials can be manipulated by cavity quantum electromagnetic fields for both resonant and off-resonant electron-photon coupling, with a focus on van der Waals moiré superlattices. We investigate an electron-photon topological Chern number for the cavity-dressed energy minibands that is well defined for any degree of hybridization and entanglement of the electron and photon states. While an off-resonant cavity mode can renormalize electronic topological phases that exist without cavity coupling, we show that when the cavity mode is resonant to electronic miniband transitions, new and higher electron-photon Chern numbers can emerge.

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.

Emergence of amoxicillin resistance and identification of novel mutations of the pbp1A gene in Helicobacter pylori in Vietnam.

BACKGROUND: Amoxicillin-resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients. MATERIALS AND METHODS: Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbor-joining tree building method. RESULTS: There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 µg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310-596, with the proportion varying from 0.4 to 100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (AmoxS) and amoxicillin-resistant (AmoxR) samples, including Phe366 to Leu (p <  0.001), Ser414 to Arg (p <  0.001), Glu/Asn464-465 (p = 0.009), Val469 to Met (p = 0.021), Phe473 to Val (p <  0.001), Asp479 to Glu (p = 0.044), and Ser/Ala/Gly595-596 (p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A. CONCLUSIONS: We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.

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.

Progressive Left Ventricular Hypertrophy After Ozaki Procedure: A Case Report.

We describe a 57-year-old man with symptomatic severe aortic stenosis who underwent aortic valve reconstruction with glutaraldehyde-treated autologous pericardium with the Ozaki technique (Ozaki procedure). Seven months later, he rapidly developed progressive left ventricular hypertrophy with a left ventricular outflow tract obstruction. This required a reoperation for septal myectomy.

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.