Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.

Discovery of a Potent and Selective Covalent p300/CBP Inhibitor.

Aberrant gene activation driven by the histone acetyltransferases p300 and CREB binding protein (CBP) has been linked to several diseases, including cancers. Because of this, many efforts have been aimed toward the targeting of the closely related paralogues, p300 and CBP, but these endeavors have been exclusively directed toward noncovalent inhibitors. X-ray crystallography of revealed that both p300 and CBP possess a cysteine (C1450) near the active site, thus rendering covalent inhibition an attractive chemical approach.

Outcomes in Hepatocellular Carcinoma Liver Transplantation before and after the Mandated Six-Month Wait Time.

The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018.

Differences in Risk of Sudden Cardiac Death Between Blacks and Whites.

Background: Prior studies have consistently demonstrated that blacks have an approximate 2-fold higher incidence of sudden cardiac death (SCD) than whites; however, these analyses have lacked individual-level sociodemographic, medical comorbidity, and behavioral health data.

Objectives: The purpose of this study was to evaluate whether racial differences in SCD incidence are attributable to differences in the prevalence of risk factors or rather to underlying susceptibility to fatal arrhythmias.

Methods: The Reasons for Geographic and Racial Differences in Stroke study is a prospective, population-based cohort of adults from across the United States.

Dietary Oxidative Balance Scores and Biomarkers of Inflammation among Individuals with and without Chronic Kidney Disease.

Background: Oxidative stress and inflammation are proposed mechanisms of nonspecific kidney injury and progressive kidney failure. Higher dietary oxidative balance scores (OBS) are associated with lower prevalence of chronic kidney disease (CKD).

Methods: We investigated the association between OBS and biomarkers of inflammation using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

County-level air quality and the prevalence of diagnosed chronic kidney disease in the US Medicare population.

Background: Considerable geographic variation exists in the prevalence of chronic kidney disease across the United States. While some of this variability can be explained by differences in patient-level risk factors, substantial variability still exists. We hypothesize this may be due to understudied environmental exposures such as air pollution.

Serum albumin concentration and risk of end-stage renal disease: the REGARDS study.

Background: Serum albumin concentration is a commonly available biomarker with prognostic value in many disease states. It is uncertain whether serum albumin concentrations are associated with incident end-stage renal disease (ESRD) independently of urine albumin-to-creatinine ratio (ACR).

Methods: A longitudinal evaluation was performed of a population-based community-living cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Older Patients' Perspectives on Managing Complexity in CKD Self-Management.

Background And Objectives: Patients with CKD are asked to perform self-management tasks including dietary changes, adhering to medications, avoiding nephrotoxic drugs, and self-monitoring hypertension and diabetes. Given the effect of aging on functional capacity, self-management may be especially challenging for older patients. However, little is known about the specific challenges older adults face maintaining CKD self-management regimens.

Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.

Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, K = 160 μM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays.

Evaluating Risk Factors for Clostridium difficile Infection In Stem Cell Transplant Recipients: A National Study.

OBJECTIVE Large-scale studies evaluating risk factors for Clostridium difficile infection (CDI), a leading cause of infectious diarrhea among patients undergoing stem cell transplantation (SCT), are lacking. We have evaluated risk factors for CDI among both autologous SCT (auto-SCT), and allogeneic SCT (allo-SCT) recipients using the National Inpatient Sample (NIS) database provided by the Healthcare Cost and Utilization Project (HCUP). METHODS We used patient data obtained from the NIS database for all adult patients admitted for auto- and allo-SCTs from January 2001 to December 2010.

Oxidative Balance Score and the Risk of End-Stage Renal Disease and Cardiovascular Disease.

Background: Oxidative balance score (OBS) is a composite measure of oxidative stress-related exposures. The aim of this study was to investigate the association between OBS, end-stage renal disease (ESRD), and cardiovascular disease (CVD).

Methods: Using data from the Chronic Renal Insufficiency Cohort, we calculated the main exposure OBS by summing up 12 apriori-defined pro- and antioxidant factors obtained from the diet history questionnaire and lifestyle assessment.

Sickle Cell Trait and the Risk of ESRD in Blacks.

Blacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown.

The association between cytomegalovirus infection, obesity, and metabolic syndrome in U.S. adult females.

Objective: The purpose of this analysis was to determine whether cytomegalovirus (CMV) infection is associated with the prevalence of metabolic syndrome (MetS) and whether this relationship differs by BMI.

Methods: Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were pooled (N = 2,532). Logistic regression was used for assessing the association between CMV and MetS, stratified by gender and BMI, categorized as normal weight, overweight, obesity, and extreme obesity, and adjusted for age, race/ethnicity, and poverty level.

Association of Multimorbidity with Mortality and Healthcare Utilization in Chronic Kidney Disease.

Objectives: Chronic kidney disease (CKD) almost universally occurs in individuals with other medical problems. However, few studies have described CKD-related multimorbidity using a framework that identifies chronic conditions as concordant (having overlap in treatment goals) versus discordant (having opposing treatment recommendations) and unrelated (having no overlap, but contributing to complexity via different resource requirements).

Design: Retrospective cohort.

Interdialytic Weight Gain: Trends, Predictors, and Associated Outcomes in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

Background: High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and associations of IDWG with clinical outcomes.

Study Design: Analysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends.

ESRD Databases, Public Policy, and Quality of Care: Translational Medicine and Nephrology.

Efforts to improve care of patients with ESRD and the policies that guide those activities depend on evidence-based best practices derived from clinical trials and carefully conducted observational studies. Our review describes this process in the context of the translational research model (bench to bedside to populations), with a particular emphasis on bedside care. We illustrate some of its accomplishments and describe the limitations of the data and evidence supporting policy and practice.

Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Background: Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed.

Objectives: We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence.

Dietary flavonoid intake and incident coronary heart disease: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Background: Flavonoids are dietary polyphenolic compounds with a variety of proposed beneficial cardiovascular effects, but rigorous prospective studies that examine the association between flavonoid intake and incident coronary heart disease (CHD) in geographically and racially diverse US samples are limited.

Objective: With the use of the new, expanded USDA flavonoid database, we assessed the association between total flavonoid and flavonoid subclass intakes with incident CHD in a biracial and geographically diverse cohort, as well as effect modification by age, sex, race, and region of residence.

Design: Participants were 16,678 black and white men and women enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a national prospective cohort study.

A Randomized Trial to Reduce Disparities in Referral for Transplant Evaluation.

Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral.

Albuminuria, kidney function, and sudden cardiac death: Findings from The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Background: Moderate-to-severe kidney disease increases risk for sudden cardiac death (SCD). Limited studies have evaluated how mild degrees of kidney dysfunction impact SCD risk.

Objective: The purpose of this study was to evaluate the association of albuminuria, which is one of the earliest biomarkers of kidney injury, and SCD.

Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults.

Background And Purpose: In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors.

Methods: Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years.

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults.

Background And Objectives: Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD.

Design, Setting, Participants, & Measurements: We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ≥65 years old with Medicare fee for service coverage.

Pre-ESRD Care and Mortality in Incident ESRD Patients With Multiple Myeloma.

Objectives: The relationship between mortality and pre-ESRD (end-stage renal disease) nephrology care in incident ESRD patients with multiple myeloma (MM) as the primary cause of renal failure has not been examined.

Materials And Methods: Among 439,206 incident US hemodialysis patients with MM as the primary cause of ESRD (June 1, 2005 to May 31, 2009) identified using the US Renal Data System, adjusted odds ratios (OR) for reported pre-ESRD nephrology care for ESRD due to MM (n=4561) versus other causes (n=434,645) were calculated. The association of pre-ESRD nephrology care with subsequent mortality in MM-ESRD patients was examined.

iChoose Kidney: A Clinical Decision Aid for Kidney Transplantation Versus Dialysis Treatment.

Background: Despite a significant survival advantage of kidney transplantation compared with dialysis, nearly one third of end-stage renal disease (ESRD) patients are not educated about kidney transplantation as a treatment option at the time of ESRD diagnosis. Access to individualized, evidence-based prognostic information is needed to facilitate and encourage shared decision making about the clinical implications of whether to pursue transplantation or long-term dialysis.

Methods: We used a national cohort of incident ESRD patients in the US Renal Data System surveillance registry from 2005 to 2011 to develop and validate prediction models for risk of 1- and 3-year mortality among dialysis versus kidney transplantation.

Racial and Ethnic Disparities in Graft and Recipient Survival in Elderly Kidney Transplant Recipients.

Objectives: To investigate racial and ethnic differences in graft and recipient survival in elderly kidney transplant recipients.

Design: Retrospective cohort.

Setting: First-time, kidney-only transplant recipients aged 60 and older of age at transplantation transplanted between July 1996 and October 2010 (N = 44,013).