Hospital-associated venous thromboembolism prophylaxis use by risk assessment at a large integrated health care network in Northern California.

Background: Hospital-acquired venous thromboembolism (HA VTE) is a preventable complication in hospitalized patients.

Objective: We aimed to examine the use of pharmacologic prophylaxis (pPPX) and compare two risk assessment methods for HA VTE: a retrospective electronic Padua Score (ePaduaKP) and admitting clinician's choice of risk within the admission orderset (low, moderate, or high).

Design, Settings And Participants: We retrospectively analyzed prophylaxis orders for adult medical admissions (2013-2019) at Kaiser Permanente Northern California, excluding surgical and ICU patients.

Predicting stroke risk after sepsis hospitalization with new-onset atrial fibrillation.

Background: New-onset atrial fibrillation (AF) during sepsis is common, but models designed to stratify stroke risk excluded patients with secondary AF. We assessed the predictive validity of CHADSVASc scores among patients with new-onset AF during sepsis and developed a novel stroke prediction model incorporating presepsis and intrasepsis characteristics.

Methods: We included patients ≥40 years old who survived hospitalizations with sepsis and new-onset AF across 21 Kaiser Permanente Northern California hospitals from January 1, 2011 to September 30, 2017.

Development and Validation of a Diabetic Retinopathy Risk Stratification Algorithm.

Objective: Although diabetic retinopathy is a leading cause of blindness worldwide, diabetes-related blindness can be prevented through effective screening, detection, and treatment of disease. The study goal was to develop risk stratification algorithms for the onset of retinal complications of diabetes, including proliferative diabetic retinopathy, referable retinopathy, and macular edema.

Research Design And Methods: Retrospective cohort analysis of patients from the Kaiser Permanente Northern California Diabetes Registry who had no evidence of diabetic retinopathy at a baseline diabetic retinopathy screening during 2008-2020 was performed.

Trends and Risk Factors for Venous Thromboembolism Among Hospitalized Medical Patients.

Importance: While hospital-associated venous thromboembolism (HA-VTE) is a known complication of hospitalization, contemporary incidence and outcomes data are scarce and methodologically contested.

Objective: To define and validate an automated electronic health record (EHR)-based algorithm for retrospective detection of HA-VTE and examine contemporary HA-VTE incidence, previously reported risk factors, and outcomes.

Design, Setting, And Participants: This cohort study was conducted using hospital admissions between January 1, 2013, and June 30, 2021, with follow-up until December 31, 2021.

Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies.

Background: Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored.

Methods: To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls).

Prognostic Accuracy of Presepsis and Intrasepsis Characteristics for Prediction of Cardiovascular Events After a Sepsis Hospitalization.

Objectives: Sepsis survivors face increased risk for cardiovascular complications; however, the contribution of intrasepsis events to cardiovascular risk profiles is unclear.

Setting: Kaiser Permanente Northern California (KPNC) and Intermountain Healthcare (IH) integrated healthcare delivery systems.

Subjects: Sepsis survivors (2011-2017 [KPNC] and 2018-2020 [IH]) greater than or equal to 40 years old without prior cardiovascular disease.

Development of a healthcare system COVID Hotspotting Score in California: an observational study with prospective validation.

Objective: To examine the value of health systems data as indicators of emerging COVID-19 activity.

Design: Observational study of health system indicators for the COVID Hotspotting Score (CHOTS) with prospective validation.

Setting And Participants: An integrated healthcare delivery system in Northern California including 21 hospitals and 4.

Association between Troponin I Levels during Sepsis and Postsepsis Cardiovascular Complications.

Sepsis commonly results in elevated serum troponin levels and increased risk for postsepsis cardiovascular complications; however, the association between troponin levels during sepsis and cardiovascular complications after sepsis is unclear. To evaluate the association between serum troponin levels during sepsis and 1 year after sepsis cardiovascular events. We analyzed adults aged ⩾40 years without preexisting cardiovascular disease within 5 years, admitted with sepsis across 21 hospitals from 2011 to 2017.

Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.

Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types.

Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC).

Pathway Analysis of Renal Cell Carcinoma Genome-Wide Association Studies Identifies Novel Associations.

Background: Much of the heritable risk of renal cell carcinoma (RCC) associated with common genetic variation is unexplained. New analytic approaches have been developed to increase the discovery of risk variants in genome-wide association studies (GWAS), including multi-locus testing through pathway analysis.

Methods: We conducted a pathway analysis using GWAS summary data from six previous scans (10,784 cases and 20,406 controls) and evaluated 3,678 pathways and gene sets drawn from the Molecular Signatures Database.

Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction.

Background: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported.

A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness.

Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95.

Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error.

Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin-Induced Cutaneous Adverse Drug Reactions.

The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin-induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA-B)*15:02 risk allele. In the multi-ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self-identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non-Hispanic.

Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system.

Objective: To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment.

Methods: A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescription between 1996 and 2017. We used laboratory test results, medication dispensing records, and medical notes to identify associations of CYP2C9 genotype with phenytoin blood concentration, neurologic side effects, and medication dispensing patterns reflecting clinician prescribing practice and patient response.

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.

Genetic variation in the locus is associated with erectile dysfunction.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort.

A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss, yet much of the genetic risk remains unaccounted for, especially in African-Americans who have a higher risk for developing POAG. We conduct a multiethnic genome-wide association study (GWAS) of POAG in the GERA cohort, with replication in the UK Biobank (UKB), and vice versa, GWAS in UKB with replication in GERA. We identify 24 loci (P < 5.