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Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model

BACKGROUND: Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Inten...

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Autores principales: Sikora, Andrea, Rafiei, Alireza, Rad, Milad Ghiasi, Keats, Kelli, Smith, Susan E., Devlin, John W., Murphy, David J., Murray, Brian, Kamaleswaran, Rishikesan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155304/
https://www.ncbi.nlm.nih.gov/pubmed/37131200
http://dx.doi.org/10.1186/s13054-023-04437-2
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author Sikora, Andrea
Rafiei, Alireza
Rad, Milad Ghiasi
Keats, Kelli
Smith, Susan E.
Devlin, John W.
Murphy, David J.
Murray, Brian
Kamaleswaran, Rishikesan
author_facet Sikora, Andrea
Rafiei, Alireza
Rad, Milad Ghiasi
Keats, Kelli
Smith, Susan E.
Devlin, John W.
Murphy, David J.
Murray, Brian
Kamaleswaran, Rishikesan
author_sort Sikora, Andrea
collection PubMed
description BACKGROUND: Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Intensive Care Unit (ICU) Medications (CDM-ICURx) may provide important infrastructure to clinicians and researchers to support artificial intelligence analysis of medication-related outcomes and healthcare costs. Using an unsupervised cluster analysis approach in combination with this common data model, the objective of this evaluation was to identify novel patterns of medication clusters (termed ‘pharmacophenotypes’) correlated with ICU adverse events (e.g., fluid overload) and patient-centered outcomes (e.g., mortality). METHODS: This was a retrospective, observational cohort study of 991 critically ill adults. To identify pharmacophenotypes, unsupervised machine learning analysis with automated feature learning using restricted Boltzmann machine and hierarchical clustering was performed on the medication administration records of each patient during the first 24 h of their ICU stay. Hierarchical agglomerative clustering was applied to identify unique patient clusters. Distributions of medications across pharmacophenotypes were described, and differences among patient clusters were compared using signed rank tests and Fisher's exact tests, as appropriate. RESULTS: A total of 30,550 medication orders for the 991 patients were analyzed; five unique patient clusters and six unique pharmacophenotypes were identified. For patient outcomes, compared to patients in Clusters 1 and 3, patients in Cluster 5 had a significantly shorter duration of mechanical ventilation and ICU length of stay (p < 0.05); for medications, Cluster 5 had a higher distribution of Pharmacophenotype 1 and a smaller distribution of Pharmacophenotype 2, compared to Clusters 1 and 3. For outcomes, patients in Cluster 2, despite having the highest severity of illness and greatest medication regimen complexity, had the lowest overall mortality; for medications, Cluster 2 also had a comparably higher distribution of Pharmacophenotype 6. CONCLUSION: The results of this evaluation suggest that patterns among patient clusters and medication regimens may be observed using empiric methods of unsupervised machine learning in combination with a common data model. These results have potential because while phenotyping approaches have been used to classify heterogenous syndromes in critical illness to better define treatment response, the entire medication administration record has not been incorporated in those analyses. Applying knowledge of these patterns at the bedside requires further algorithm development and clinical application but may have the future potential to be leveraged in guiding medication-related decision making to improve treatment outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04437-2.
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spelling pubmed-101553042023-05-04 Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model Sikora, Andrea Rafiei, Alireza Rad, Milad Ghiasi Keats, Kelli Smith, Susan E. Devlin, John W. Murphy, David J. Murray, Brian Kamaleswaran, Rishikesan Crit Care Research BACKGROUND: Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Intensive Care Unit (ICU) Medications (CDM-ICURx) may provide important infrastructure to clinicians and researchers to support artificial intelligence analysis of medication-related outcomes and healthcare costs. Using an unsupervised cluster analysis approach in combination with this common data model, the objective of this evaluation was to identify novel patterns of medication clusters (termed ‘pharmacophenotypes’) correlated with ICU adverse events (e.g., fluid overload) and patient-centered outcomes (e.g., mortality). METHODS: This was a retrospective, observational cohort study of 991 critically ill adults. To identify pharmacophenotypes, unsupervised machine learning analysis with automated feature learning using restricted Boltzmann machine and hierarchical clustering was performed on the medication administration records of each patient during the first 24 h of their ICU stay. Hierarchical agglomerative clustering was applied to identify unique patient clusters. Distributions of medications across pharmacophenotypes were described, and differences among patient clusters were compared using signed rank tests and Fisher's exact tests, as appropriate. RESULTS: A total of 30,550 medication orders for the 991 patients were analyzed; five unique patient clusters and six unique pharmacophenotypes were identified. For patient outcomes, compared to patients in Clusters 1 and 3, patients in Cluster 5 had a significantly shorter duration of mechanical ventilation and ICU length of stay (p < 0.05); for medications, Cluster 5 had a higher distribution of Pharmacophenotype 1 and a smaller distribution of Pharmacophenotype 2, compared to Clusters 1 and 3. For outcomes, patients in Cluster 2, despite having the highest severity of illness and greatest medication regimen complexity, had the lowest overall mortality; for medications, Cluster 2 also had a comparably higher distribution of Pharmacophenotype 6. CONCLUSION: The results of this evaluation suggest that patterns among patient clusters and medication regimens may be observed using empiric methods of unsupervised machine learning in combination with a common data model. These results have potential because while phenotyping approaches have been used to classify heterogenous syndromes in critical illness to better define treatment response, the entire medication administration record has not been incorporated in those analyses. Applying knowledge of these patterns at the bedside requires further algorithm development and clinical application but may have the future potential to be leveraged in guiding medication-related decision making to improve treatment outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04437-2. BioMed Central 2023-05-02 /pmc/articles/PMC10155304/ /pubmed/37131200 http://dx.doi.org/10.1186/s13054-023-04437-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sikora, Andrea
Rafiei, Alireza
Rad, Milad Ghiasi
Keats, Kelli
Smith, Susan E.
Devlin, John W.
Murphy, David J.
Murray, Brian
Kamaleswaran, Rishikesan
Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title_full Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title_fullStr Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title_full_unstemmed Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title_short Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model
title_sort pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the icurx common data model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155304/
https://www.ncbi.nlm.nih.gov/pubmed/37131200
http://dx.doi.org/10.1186/s13054-023-04437-2
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