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Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort

Drug-drug interactions account for up to 30% of adverse drug reactions. Increasing prevalence of electronic health records (EHRs) offers a unique opportunity to build machine learning algorithms to identify drug-drug interactions that drive adverse events. In this study, we investigated hospitalizat...

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Autores principales: Datta, Arghya, Flynn, Noah R., Barnette, Dustyn A., Woeltje, Keith F., Miller, Grover P., Swamidass, S. Joshua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284671/
https://www.ncbi.nlm.nih.gov/pubmed/34228716
http://dx.doi.org/10.1371/journal.pcbi.1009053
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author Datta, Arghya
Flynn, Noah R.
Barnette, Dustyn A.
Woeltje, Keith F.
Miller, Grover P.
Swamidass, S. Joshua
author_facet Datta, Arghya
Flynn, Noah R.
Barnette, Dustyn A.
Woeltje, Keith F.
Miller, Grover P.
Swamidass, S. Joshua
author_sort Datta, Arghya
collection PubMed
description Drug-drug interactions account for up to 30% of adverse drug reactions. Increasing prevalence of electronic health records (EHRs) offers a unique opportunity to build machine learning algorithms to identify drug-drug interactions that drive adverse events. In this study, we investigated hospitalizations’ data to study drug interactions with non-steroidal anti-inflammatory drugs (NSAIDS) that result in drug-induced liver injury (DILI). We propose a logistic regression based machine learning algorithm that unearths several known interactions from an EHR dataset of about 400,000 hospitalization. Our proposed modeling framework is successful in detecting 87.5% of the positive controls, which are defined by drugs known to interact with diclofenac causing an increased risk of DILI, and correctly ranks aggregate risk of DILI for eight commonly prescribed NSAIDs. We found that our modeling framework is particularly successful in inferring associations of drug-drug interactions from relatively small EHR datasets. Furthermore, we have identified a novel and potentially hepatotoxic interaction that might occur during concomitant use of meloxicam and esomeprazole, which are commonly prescribed together to allay NSAID-induced gastrointestinal (GI) bleeding. Empirically, we validate our approach against prior methods for signal detection on EHR datasets, in which our proposed approach outperforms all the compared methods across most metrics, such as area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC).
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spelling pubmed-82846712021-07-28 Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort Datta, Arghya Flynn, Noah R. Barnette, Dustyn A. Woeltje, Keith F. Miller, Grover P. Swamidass, S. Joshua PLoS Comput Biol Research Article Drug-drug interactions account for up to 30% of adverse drug reactions. Increasing prevalence of electronic health records (EHRs) offers a unique opportunity to build machine learning algorithms to identify drug-drug interactions that drive adverse events. In this study, we investigated hospitalizations’ data to study drug interactions with non-steroidal anti-inflammatory drugs (NSAIDS) that result in drug-induced liver injury (DILI). We propose a logistic regression based machine learning algorithm that unearths several known interactions from an EHR dataset of about 400,000 hospitalization. Our proposed modeling framework is successful in detecting 87.5% of the positive controls, which are defined by drugs known to interact with diclofenac causing an increased risk of DILI, and correctly ranks aggregate risk of DILI for eight commonly prescribed NSAIDs. We found that our modeling framework is particularly successful in inferring associations of drug-drug interactions from relatively small EHR datasets. Furthermore, we have identified a novel and potentially hepatotoxic interaction that might occur during concomitant use of meloxicam and esomeprazole, which are commonly prescribed together to allay NSAID-induced gastrointestinal (GI) bleeding. Empirically, we validate our approach against prior methods for signal detection on EHR datasets, in which our proposed approach outperforms all the compared methods across most metrics, such as area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). Public Library of Science 2021-07-06 /pmc/articles/PMC8284671/ /pubmed/34228716 http://dx.doi.org/10.1371/journal.pcbi.1009053 Text en © 2021 Datta et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Datta, Arghya
Flynn, Noah R.
Barnette, Dustyn A.
Woeltje, Keith F.
Miller, Grover P.
Swamidass, S. Joshua
Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title_full Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title_fullStr Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title_full_unstemmed Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title_short Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort
title_sort machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (nsaids) from a retrospective electronic health record (ehr) cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284671/
https://www.ncbi.nlm.nih.gov/pubmed/34228716
http://dx.doi.org/10.1371/journal.pcbi.1009053
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