Genome-wide association study of hospitalized patients and acute kidney injury.

Acute kidney injury (AKI) is a common and devastating complication of hospitalization. Here, we identified genetic loci associated with AKI in patients hospitalized between 2002-2019 in the Million Veteran Program and data from Vanderbilt University Medical Center's BioVU. AKI was defined as meeting a modified KDIGO Stage1 or more for two or more consecutive days or kidney replacement therapy. Control individuals were required to have one or more qualifying hospitalizations without AKI and no evidence of AKI during any other observed hospitalizations. Genome-wide association studies (GWAS), stratified by race, adjusting for sex, age, baseline estimated glomerular filtration rate (eGFR), and the top ten principal components of ancestry were conducted. Results were meta-analyzed using fixed effects models. In total, there were 54,488 patients with AKI and 138,051 non-AKI individuals included in the study. Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09)) and rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96)). These loci colocalized with previous studies of kidney function, and genetic correlation indicated significant shared genetic architecture between AKI and eGFR. Notably, the association at the FTO locus was attenuated after adjustment for BMI and diabetes, suggesting that this association may be partially driven by obesity. Both FTO and the SHROOM3 loci showed nominal evidence of replication from diagnostic-code-based summary statistics from UK Biobank, FinnGen, and Biobank Japan. Thus, our large GWA meta-analysis found two loci significantly associated with AKI suggesting genetics may explain some risk for AKI.

Representing Knowledge Consistently Across Health Systems.

Objectives: Electronic health records (EHRs) have increasingly emerged as a powerful source of clinical data that can be leveraged for reuse in research and in modular health apps that integrate into diverse health information technologies. A key challenge to these use cases is representing the knowledge contained within data from different EHR systems in a uniform fashion. Method: We reviewed several recent studies covering the knowledge representation in the common data models for the Observational Medical Outcomes Partnership (OMOP) and its Observational Health Data Sciences and Informatics program, and the United States Patient Centered Outcomes Research Network (PCORNet). We also reviewed the Health Level 7 Fast Healthcare Interoperability Resource standard supporting app-like programs that can be used across multiple EHR and research systems. Results: There has been a recent growth in high-impact efforts to support quality-assured and standardized clinical data sharing across different institutions and EHR systems. We focused on three major efforts as part of a larger landscape moving towards shareable, transportable, and computable clinical data. Conclusion: The growth in approaches to developing common data models to support interoperable knowledge representation portends an increasing availability of high-quality clinical data in support of research. Building on these efforts will allow a future whereby significant portions of the populations in the world may be able to share their data for research.

Creating a Common Data Model for Comparative Effectiveness with the Observational Medical Outcomes Partnership.

BACKGROUND: Adoption of a common data model across health systems is a key infrastructure requirement to allow large scale distributed comparative effectiveness analyses. There are a growing number of common data models (CDM), such as Mini-Sentinel, and the Observational Medical Outcomes Partnership (OMOP) CDMs. OBJECTIVES: In this case study, we describe the challenges and opportunities of a study specific use of the OMOP CDM by two health systems and describe three comparative effectiveness use cases developed from the CDM. METHODS: The project transformed two health system databases (using crosswalks provided) into the OMOP CDM. Cohorts were developed from the transformed CDMs for three comparative effectiveness use case examples. Administrative/billing, demographic, order history, medication, and laboratory were included in the CDM transformation and cohort development rules. RESULTS: Record counts per person month are presented for the eligible cohorts, highlighting differences between the civilian and federal datasets, e.g. the federal data set had more outpatient visits per person month (6.44 vs. 2.05 per person month). The count of medications per person month reflected the fact that one system's medications were extracted from orders while the other system had pharmacy fills and medication administration records. The federal system also had a higher prevalence of the conditions in all three use cases. Both systems required manual coding of some types of data to convert to the CDM. CONCLUSIONS: The data transformation to the CDM was time consuming and resources required were substantial, beyond requirements for collecting native source data. The need to manually code subsets of data limited the conversion. However, once the native data was converted to the CDM, both systems were then able to use the same queries to identify cohorts. Thus, the CDM minimized the effort to develop cohorts and analyze the results across the sites.

Discrimination and calibration of mortality risk prediction models in interventional cardiology.

OBJECTIVES: Using a local percutaneous coronary intervention (PCI) data repository, we sought to compare the performance of a number of local and well-known mortality models with respect to discrimination and calibration. BACKGROUND: Accurate risk prediction is important for a number of reasons including physician decision support, quality of care assessment, and patient education. Current evidence on the value of applying PCI risk models to individual cases drawn from a different population is controversial. METHODS: Data were collected from January 01, 2002 to September 30, 2004 on 5216 consecutive percutaneous coronary interventions at Brigham and Women's Hospital (Boston, MA). Logistic regression was used to create a local risk model for in-hospital mortality in these procedures, and a number of statistical methods were used to compare the discrimination and calibration of this new and old local risk models, as well as the Northern New England Cooperative Group, New York State (1992 and 1997), University of Michigan consortium, American College of Cardiology-National Cardiovascular Data Registry, and The Cleveland Clinic Foundation risk prediction models. Areas under the ROC (AUC) curves were used to evaluate discrimination, and the Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. RESULTS: Multivariate risk factors included in the newly constructed local model were: age, prior intervention, diabetes, unstable angina, salvage versus elective procedure, cardiogenic shock, acute myocardial infarction (AMI), and left anterior descending artery intervention. The area under the ROC curve (AUC) was 0.929 (SE=0.017), and the p value for the Hosmer-Lemeshow (HL) goodness-of-fit was 0.473. This indicates good discrimination and calibration. Bootstrap re-sampling indicated AUC stability. Evaluation of the external models showed an AUC range from 0.82 to 0.90 indicating good discrimination across all models, but poor calibration (HL p value < or = 0.0001). CONCLUSIONS: Validation of AUC values across all models suggests that certain risk factors have remained important over the last decade. However, the lack of calibration suggests that small changes in patient populations and data collection methods quickly reduce the accuracy of patient level estimations over time. Possible solutions to this problem involve either recalibration of models using local data or development of new local models.