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Brown, R. P.

Publications and source records attributed to Brown, R. P..

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Preoperative predictions of in-hospital mortality using electronic medical record data

BackgroundPredicting preoperative in-hospital mortality using readily-available electronic medical record (EMR) data can aid clinicians in accurately and rapidly determining surgical risk. While previous work has shown that the American Society of Anesthesiologists (ASA) Physical Status Classification is a useful, though subjective, feature for predicting surgical outcomes, obtaining this classification requires a clinician to review the patients medical records. Our goal here is to create an improved risk score using electronic medical records and demonstrate its utility in predicting in-hospital mortality without requiring clinician-derived ASA scores.\n\nMethodsData from 49,513 surgical patients were used to train logistic regression, random forest, and gradient boosted tree classifiers for predicting in-hospital mortality. The features used are readily available before surgery from EMR databases. A gradient boosted tree regression model was trained to impute the ASA Physical Status Classification, and this new, imputed score was included as an additional feature to preoperatively predict in-hospital post-surgical mortality. The preoperative risk prediction was then used as an input feature to a deep neural network (DNN), along with intraoperative features, to predict postoperative in-hospital mortality risk. Performance was measured using the area under the receiver operating characteristic (ROC) curve (AUC).\n\nResultsWe found that the random forest classifier (AUC 0.921, 95%CI 0.908-0.934) outperforms logistic regression (AUC 0.871, 95%CI 0.841-0.900) and gradient boosted trees (AUC 0.897, 95%CI 0.881-0.912) in predicting in-hospital post-surgical mortality. Using logistic regression, the ASA Physical Status Classification score alone had an AUC of 0.865 (95%CI 0.848-0.882). Adding preoperative features to the ASA Physical Status Classification improved the random forest AUC to 0.929 (95%CI 0.915-0.943). Using only automatically obtained preoperative features with no clinician intervention, we found that the random forest model achieved an AUC of 0.921 (95%CI 0.908-0.934). Integrating the preoperative risk prediction into the DNN for postoperative risk prediction results in an AUC of 0.924 (95%CI 0.905-0.941), and with both a preoperative and postoperative risk score for each patient, we were able to show that the mortality risk changes over time.\n\nConclusionsFeatures easily extracted from EMR data can be used to preoperatively predict the risk of in-hospital post-surgical mortality in a fully automated fashion, with accuracy comparable to models trained on features that require clinical expertise. This preoperative risk score can then be compared to the postoperative risk score to show that the risk changes, and therefore should be monitored longitudinally over time.\n\nAuthor summaryRapid, preoperative identification of those patients at highest risk for medical complications is necessary to ensure that limited infrastructure and human resources are directed towards those most likely to benefit. Existing risk scores either lack specificity at the patient level, or utilize the American Society of Anesthesiologists (ASA) physical status classification, which requires a clinician to review the chart. In this manuscript we report on using machine-learning algorithms, specifically random forest, to create a fully automated score that predicts preoperative in-hospital mortality based solely on structured data available at the time of surgery. This score has a higher AUC than both the ASA physical status score and the Charlson comorbidity score. Additionally, we integrate this score with a previously published postoperative score to demonstrate the extent to which patient risk changes during the perioperative period.

bioinformatics

Haplotype-based eQTL mapping finds evidence for complex gene regulatory regions poorly tagged by marginal SNPs

MotivationExpression quantitative trait loci (eQTLs), variations in the genome that impact gene expression, are identified through eQTL studies that test for a relationship between single nucleotide polymorphisms (SNPs) and gene expression levels. These studies typically assume an underlying additive model. Non-additive tests have been proposed, but are limited due to the increase in the multiple testing burden and are potentially biased by filtering criteria that relies on marginal association data. Here we propose using combinations of short haplotypes instead of SNPs as predictors for gene expression. Essentially, this method looks for genomic regions where haplotypes have different effect sizes. The differences in effect can be due to multiple genetic architectures such as a single SNP, a burden of rare SNPs, multiple SNPs with independent effect or multiple SNPs with an interaction effect occurring on the same haplotype.\n\nResultsSimulations show that when haplotypes, rather than SNPs, are assigned non-zero effect sizes, our method has increased power compared to the marginal SNP method. In the GEUVADIS gene expression data, our method finds 101 more eGenes than the marginal method (5,202 vs. 5,101). The methods do not have full overlap in the eGenes that they find. Of the 5,202 eGenes found by our method, 707 are not found by the marginal method--even though it has a lower significance threshold. This indicates that many genes have regulatory architectures that are not well tagged by marginal SNPs and demonstrates the need to better model alternative archi-tectures.

genetics