Guo, Xiaojiang
(2021)
Evaluating the effect of Ondansetron on Reducing ICU Mortality in Patients with Acute Kidney Injury.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Acute kidney injury (AKI) is an abrupt decline in glomerular filtration, which is attributed to various causes, and greatly increased the mortality of patients. The purpose of this study was to identify medications that provide potentially beneficial effects on decreasing mortality of AKI patients. This was a retrospective cohort study using electronic medical record data of AKI patients in intensive care unit (ICU) and the endpoint outcome was patient mortality in ICU. We evaluated the medical records from two ICU databases, MIMIC III and eICU, to find factors with potential effect on reducing ICU mortality. We used logistic regression to investigate associations between medications received and mortality in AKI patients from the MIMIC III database. Drugs associated with lower death rates were validated using the eICU database. We afterwards used acute physiology age chronic health evaluation (APACHE) predicted mortality for matching of the patient’s baseline severity of illness with R package Match It function “matchit”. A chi-square test to calculate the significance of drug use and mortality was followed. Several drugs showed potential beneficial effects on reducing mortality, and most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). Ondansetron, not previously known as a life-saving drug, showed potential beneficial effect on reducing ICU mortality for AKI patients. This association was confirmed in a subsequent analysis using eICU database. Gene Expression Signature was used to explore the molecular mechanism of the drugs on AKI. The therapeutic effect of ondansetron may be elicited through the modulation of NF-KB pathway and JAK-STAT pathway based on the analysis of gene expression signatures. In this study, we identified several drugs associated with lower mortality following AKI and discovered a potential novel indication for an antiemetic drug, ondansetron. Our findings provide real-world evidence to support clinical trials of ondansetron for AKI treatment.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
13 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
23 March 2021 |
| Approval Date: |
13 May 2021 |
| Submission Date: |
5 April 2021 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
66 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Acute kidney injury; Ondansetron; Electronic Medical Records; ICU; Mortality |
| Date Deposited: |
13 May 2021 20:10 |
| Last Modified: |
13 May 2022 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40507 |
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