Predicting clopidogrel response using DNA samples linked to an electronic health record.
Ontology highlight
ABSTRACT:
SUBMITTER: Delaney JT
PROVIDER: S-EPMC3621954 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
Publications
Predicting clopidogrel response using DNA samples linked to an electronic health record.
Delaney J T JT Ramirez A H AH Bowton E E Pulley J M JM Basford M A MA Schildcrout J S JS Shi Y Y Zink R R Oetjens M M Xu H H Cleator J H JH Jahangir E E Ritchie M D MD Masys D R DR Roden D M DM Crawford D C DC Denny J C JC
Clinical pharmacology and therapeutics 20111221 2
Variants in ABCB1 and CYP2C19 have been identified as predictors of cardiac events during clopidogrel therapy initiated after myocardial infarction (MI) or percutaneous coronary intervention (PCI). In addition, PON1 has recently been associated with stent thrombosis. The reported effects of these variants have not yet been replicated in a real-world setting. We used BioVU, the Vanderbilt DNA repository linked to de-identified electronic health records (EHRs), to find data on patients who were on ...[more]
Similar Datasets
Project description:AimWarfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European-Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic analysis, but they have not yet been used for this purpose.Patients & methodsWe used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European-Americans (n = 1022) and African-Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose.ResultsAssociations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European-Americans as well as additional variants in CYP2C9 and CALU in African-Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European-Americans (13.5-12.4 and 9.5 mg/week, respectively) but less so in African-Americans (15.2-15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European-Americans and African-Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4-9.6) in European-Americans and 12.4 mg/week (95% CI: 10.0-13.2) in African-Americans. The expanded algorithm explained 41 and 53% of dose variation in African-Americans and European-Americans, respectively, compared with 29 and 50%, respectively, for the IWPC algorithm. Implementing these predictions via dispensable pill regimens similarly reduced dosing error.ConclusionThese results validate EHR-linked DNA biorepositories as real-world resources for pharmacogenomic validation and discovery.
| S-EPMC3361510 | biostudies-literature
Project description:BACKGROUND:Readmissions after hospitalization for pneumonia are common, but the few risk-prediction models have poor to modest predictive ability. Data routinely collected in the electronic health record (EHR) may improve prediction. OBJECTIVE:To develop pneumonia-specific readmission risk-prediction models using EHR data from the first day and from the entire hospital stay ("full stay"). DESIGN:Observational cohort study using stepwise-backward selection and cross-validation. SUBJECTS:Consecutive pneumonia hospitalizations from 6 diverse hospitals in north Texas from 2009-2010. MEASURES:All-cause nonelective 30-day readmissions, ascertained from 75 regional hospitals. RESULTS:Of 1463 patients, 13.6% were readmitted. The first-day pneumonia-specific model included sociodemographic factors, prior hospitalizations, thrombocytosis, and a modified pneumonia severity index; the full-stay model included disposition status, vital sign instabilities on discharge, and an updated pneumonia severity index calculated using values from the day of discharge as additional predictors. The full-stay pneumonia-specific model outperformed the first-day model (C statistic 0.731 vs 0.695; P = 0.02; net reclassification index = 0.08). Compared to a validated multi-condition readmission model, the Centers for Medicare and Medicaid Services pneumonia model, and 2 commonly used pneumonia severity of illness scores, the full-stay pneumonia-specific model had better discrimination (C statistic range 0.604-0.681; P < 0.01 for all comparisons), predicted a broader range of risk, and better reclassified individuals by their true risk (net reclassification index range, 0.09-0.18). CONCLUSIONS:EHR data collected from the entire hospitalization can accurately predict readmission risk among patients hospitalized for pneumonia. This approach outperforms a first-day pneumonia-specific model, the Centers for Medicare and Medicaid Services pneumonia model, and 2 commonly used pneumonia severity of illness scores. Journal of Hospital Medicine 2017;12:209-216.
| S-EPMC6296251 | biostudies-literature
Project description:ImportanceSecondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification.ObjectiveTo develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records.DesignCohort study with patients enrolled between 2003-2016 with follow-up through 2022.SettingPrimary care practices affiliated with two academic medical centers.ParticipantsIndividuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort).ExposuresPredictors of PSCI were ascertained from the electronic health record.Main outcomeThe outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included.ResultsThe analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts.Conclusions and relevanceFive-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.
| S-EPMC10863024 | biostudies-literature
Project description:RationalePatients transferred from the intensive care unit to the wards who are later readmitted to the intensive care unit have increased length of stay, healthcare expenditure, and mortality compared with those who are never readmitted. Improving risk stratification for patients transferred to the wards could have important benefits for critically ill hospitalized patients.ObjectivesWe aimed to use a machine-learning technique to derive and validate an intensive care unit readmission prediction model with variables available in the electronic health record in real time and compare it to previously published algorithms.MethodsThis observational cohort study was conducted at an academic hospital in the United States with approximately 600 inpatient beds. A total of 24,885 intensive care unit transfers to the wards were included, with 14,962 transfers (60%) in the training cohort and 9,923 transfers (40%) in the internal validation cohort. Patient characteristics, nursing assessments, International Classification of Diseases, Ninth Revision codes from prior admissions, medications, intensive care unit interventions, diagnostic tests, vital signs, and laboratory results were extracted from the electronic health record and used as predictor variables in a gradient-boosted machine model. Accuracy for predicting intensive care unit readmission was compared with the Stability and Workload Index for Transfer score and Modified Early Warning Score in the internal validation cohort and also externally using the Medical Information Mart for Intensive Care database (n = 42,303 intensive care unit transfers).ResultsEleven percent (2,834) of discharges to the wards were later readmitted to the intensive care unit. The machine-learning-derived model had significantly better performance (area under the receiver operating curve, 0.76) than either the Stability and Workload Index for Transfer score (area under the receiver operating curve, 0.65), or Modified Early Warning Score (area under the receiver operating curve, 0.58; P value < 0.0001 for all comparisons). At a specificity of 95%, the derived model had a sensitivity of 28% compared with 15% for Stability and Workload Index for Transfer score and 7% for the Modified Early Warning Score. Accuracy improvements with the derived model over Modified Early Warning Score and Stability and Workload Index for Transfer were similar in the Medical Information Mart for Intensive Care-III cohort.ConclusionsA machine learning approach to predicting intensive care unit readmission was significantly more accurate than previously published algorithms in both our internal validation and the Medical Information Mart for Intensive Care-III cohort. Implementation of this approach could target patients who may benefit from additional time in the intensive care unit or more frequent monitoring after transfer to the hospital ward.
| S-EPMC6207111 | biostudies-literature
Project description:BackgroundGuidelines recommend breast and colorectal cancer screening for older adults with a life expectancy >10 years. Most mortality indexes require clinician data entry, presenting a barrier for routine use in care. Electronic health records (EHR) are a rich clinical data source that could be used to create individualized life expectancy predictions to identify patients for cancer screening without data entry.ObjectiveTo develop and internally validate a life expectancy calculator from structured EHR data.DesignRetrospective cohort study using national Veteran's Affairs (VA) EHR databases.PatientsVeterans aged 50+ with a primary care visit during 2005.Main measuresWe assessed demographics, diseases, medications, laboratory results, healthcare utilization, and vital signs 1 year prior to the index visit. Mortality follow-up was complete through 2017. Using the development cohort (80% sample), we used LASSO Cox regression to select ~100 predictors from 913 EHR data elements. In the validation cohort (remaining 20% sample), we calculated the integrated area under the curve (iAUC) and evaluated calibration.Key resultsIn 3,705,122 patients, the mean age was 68 years and the majority were male (97%) and white (85%); nearly half (49%) died. The life expectancy calculator included 93 predictors; age and gender most strongly contributed to discrimination; diseases also contributed significantly while vital signs were negligible. The iAUC was 0.816 (95% confidence interval, 0.815, 0.817) with good calibration.ConclusionsWe developed a life expectancy calculator using VA EHR data with excellent discrimination and calibration. Automated life expectancy prediction using EHR data may improve guideline-concordant breast and colorectal cancer screening by identifying patients with a life expectancy >10 years.
| S-EPMC8858374 | biostudies-literature
Project description:In a general inpatient population, we predicted patient-specific medication orders based on structured information in the electronic health record (EHR). Data on over three million medication orders from an academic medical center were used to train two machine-learning models: A deep learning sequence model and a logistic regression model. Both were compared with a baseline that ranked the most frequently ordered medications based on a patient's discharge hospital service and amount of time since admission. Models were trained to predict from 990 possible medications at the time of order entry. Fifty-five percent of medications ordered by physicians were ranked in the sequence model's top-10 predictions (logistic model: 49%) and 75% ranked in the top-25 (logistic model: 69%). Ninety-three percent of the sequence model's top-10 prediction sets contained at least one medication that physicians ordered within the next day. These findings demonstrate that medication orders can be predicted from information present in the EHR.
| S-EPMC7325318 | biostudies-literature
Project description:Prediction of major adverse kidney events in critically ill patients may help target therapy, allow risk adjustment, and facilitate the conduct of clinical trials. In a cohort comprised of all critically ill adults admitted to five intensive care units at a single tertiary care center over one year, we developed a logistic regression model for the outcome of Major Adverse Kidney Events within 30 days (MAKE30), the composite of persistent renal dysfunction, new renal replacement therapy (RRT), and in-hospital mortality. Proposed risk factors for the MAKE30 outcome were selected a priori and included age, race, gender, University Health System Consortium (UHC) expected mortality, baseline creatinine, volume of isotonic crystalloid fluid received in the prior 24 h, admission service, intensive care unit (ICU), source of admission, mechanical ventilation or receipt of vasopressors within 24 h of ICU admission, renal replacement therapy prior to ICU admission, acute kidney injury, chronic kidney disease as defined by baseline creatinine value, and renal failure as defined by the Elixhauser index. Among 10,983 patients in the study population, 1489 patients (13.6%) met the MAKE30 endpoint. The strongest independent predictors of MAKE30 were UHC expected mortality (OR 2.32 [95%CI 2.06-2.61]) and presence of acute kidney injury at ICU admission (OR 4.98 [95%CI 4.12-6.03]). The model had strong predictive properties including excellent discrimination with a bootstrap-corrected area-under-the-curve (AUC) of 0.903, and high precision of calibration with a mean absolute error prediction of 1.7%. The MAKE30 composite outcome can be reliably predicted from factors present within 24 h of ICU admission using data derived from the electronic health record.
| S-EPMC5821255 | biostudies-literature
Project description:UnlabelledBackgroundThe ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form "biobanks" where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on a large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypotheses generation.ResultsIn this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped for Type 2 Diabetes and Hypothyroidism to discover gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries.ConclusionsThis study demonstrates how Semantic Web technologies can be applied in conjunction with clinical data stored in EHRs to accurately identify subjects with specific diseases and phenotypes, and identify genotype-phenotype associations.
| S-EPMC3554594 | biostudies-literature
Project description:ObjectiveHospital capacity management depends on accurate real-time estimates of hospital-wide discharges. Estimation by a clinician requires an excessively large amount of effort and, even when attempted, accuracy in forecasting next-day patient-level discharge is poor. This study aims to support next-day discharge predictions with machine learning by incorporating electronic health record (EHR) audit log data, a resource that captures EHR users' granular interactions with patients' records by communicating various semantics and has been neglected in outcome predictions.Materials and methodsThis study focused on the EHR data for all adults admitted to Vanderbilt University Medical Center in 2019. We learned multiple advanced models to assess the value that EHR audit log data adds to the daily prediction of discharge likelihood within 24 h and to compare different representation strategies. We applied Shapley additive explanations to identify the most influential types of user-EHR interactions for discharge prediction.ResultsThe data include 26 283 inpatient stays, 133 398 patient-day observations, and 819 types of user-EHR interactions. The model using the count of each type of interaction in the recent 24 h and other commonly used features, including demographics and admission diagnoses, achieved the highest area under the receiver operating characteristics (AUROC) curve of 0.921 (95% CI: 0.919-0.923). By contrast, the model lacking user-EHR interactions achieved a worse AUROC of 0.862 (0.860-0.865). In addition, 10 of the 20 (50%) most influential factors were user-EHR interaction features.ConclusionEHR audit log data contain rich information such that it can improve hospital-wide discharge predictions.
| S-EPMC8633668 | biostudies-literature
Project description:BackgroundPatients with peripheral artery disease (PAD) are at risk of major adverse cardiac and cerebrovascular events. There are no readily available risk scores that can accurately identify which patients are most likely to sustain an event, making it difficult to identify those who might benefit from more aggressive intervention. Thus, we aimed to develop a novel predictive model-using machine learning methods on electronic health record data-to identify which PAD patients are most likely to develop major adverse cardiac and cerebrovascular events.Methods and resultsData were derived from patients diagnosed with PAD at 2 tertiary care institutions. Predictive models were built using a common data model that allowed for utilization of both structured (coded) and unstructured (text) data. Only data from time of entry into the health system up to PAD diagnosis were used for modeling. Models were developed and tested using nested cross-validation. A total of 7686 patients were included in learning our predictive models. Utilizing almost 1000 variables, our best predictive model accurately determined which PAD patients would go on to develop major adverse cardiac and cerebrovascular events with an area under the curve of 0.81 (95% CI, 0.80-0.83).ConclusionsMachine learning algorithms applied to data in the electronic health record can learn models that accurately identify PAD patients at risk of future major adverse cardiac and cerebrovascular events, highlighting the great potential of electronic health records to provide automated risk stratification for cardiovascular diseases. Common data models that can enable cross-institution research and technology development could potentially be an important aspect of widespread adoption of newer risk-stratification models.
| S-EPMC6415677 | biostudies-literature