No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure.

Importance: Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.

Objective: To determine whether nicotinamide use results in an increase of MACE.

Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes.

Background: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed.

Objectives: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D.

Ascertainment of Infection and Eradication Treatment Using a Nationwide Electronic Health Record Database.

Background And Aims: There are limited contemporary population-based data on epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with testing or treatment using Veterans Health Administration data.

Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for infection (3 algorithms) and treatment status (1 algorithm).

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than (non- CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.

Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes.

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.

Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.

Toward personalized skin cancer care: multiple skin cancer development in five cohorts.

Importance: Many patients will develop more than one skin cancer, however most research to date has examined only case status.

Objective: Describe the frequency and timing of the treatment of multiple skin cancers in individual patients over time.

Design: Longitudinal claims and electronic health record-based cohort study.

Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban.

Importance: Diltiazem, a commonly prescribed ventricular rate-control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.

Objective: To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.

Design, Setting, And Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020.

A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation.

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.

Evaluation of genetic associations with clinical phenotypes of kidney stone disease.

Introduction And Objective: We sought to replicate and discover genetic associations of kidney stone disease within a large-scale electronic health record (EHR) system.

Methods: We performed genome-wide association studies (GWASs) for nephrolithiasis from genotyped samples of 5,571 cases and 83,692 controls. Among the significant risk variants, we performed association analyses of stone composition and first-time 24-hour urine parameters.

X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1.

A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

Background: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD.

Methods: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks.

Understanding Prescribing Practices and Patient Experiences with Renin Angiotensin System Inhibitors Use in Chronic Kidney Disease: A Qualitative Study.

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve outcomes but are underutilized in patients with chronic kidney disease (CKD). Little is known about reasons for discontinuation and lack of reinitiating these medications. We aimed to explore clinicians' and patients' experiences and perceptions of ACEI/ARB use in CKD.

Development of Portable Electronic Health Record Based Algorithms to Identify Individuals with Diabetic Retinopathy.

Objectives: To develop, validate and implement algorithms to identify diabetic retinopathy (DR) cases and controls from electronic health care records (EHR)s. : We developed and validated EHR-based algorithms to identify DR cases and individuals with type I or II diabetes without DR (controls) in three independent EHR systems: Vanderbilt University Medical Center Synthetic Derivative (VUMC), the VA Northeast Ohio Healthcare System (VANEOHS), and Massachusetts General Brigham (MGB). Cases were required to meet one of three criteria: 1) two or more dates with any DR ICD-9/10 code documented in the EHR, or 2) at least one affirmative health-factor or EPIC code for DR along with an ICD9/10 code for DR on a different day, or 3) at least one ICD-9/10 code for any DR occurring within 24 hours of an ophthalmology exam.

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.

Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.

Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.

Design, Setting, And Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics.

Association between risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study.

Background: Two risk variants in the apolipoprotein L1 gene () have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease.

Methods: A retrospective cohort study of 2242 Black patients hospitalized with infections.

Bile Acid Sequestrant Use and Gastric Cancer: A National Retrospective Cohort Analysis.

Introduction: Bile acids have been implicated in gastric carcinogenesis. We hypothesized that bile acid sequestrant medication (BAM) use is associated with a lower gastric cancer (GC) incidence.

Methods: We assembled a cohort of veterans receiving longitudinal care within the Veterans Health Administration between 2000 and 2020 who completed testing for Helicobacterpylori .