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K-Means Clustering Analysis To Determine Hormone Aromatization Characterization of Progesterone and Placebo Treated Patients with Traumatic Brain Injuries

Mayrer, Bridget (2024) K-Means Clustering Analysis To Determine Hormone Aromatization Characterization of Progesterone and Placebo Treated Patients with Traumatic Brain Injuries. Master's Thesis, University of Pittsburgh. (Unpublished)

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Per year, traumatic brain injuries (TBIs) cause over 2.4 million emergency department visits, hospitalizations, or deaths. Survivors of severe TBIs are often left with substantial disabilities and require intensive therapy to improve their cognitive function. Additionally, TBIs annually affect 50 to 60 million individuals, and are projected to be one of the top three causes of injury-related fatalities until 2030.
Currently, there is no pharmacologic agent identified to improve survivor outcomes after a severe TBI. Several preclinical trial models targeted progesterone as an approach improve TBI outcomes based off its neurosteroid nature. Progesterone is the initial hormone to enter the aromatization pathway and begins the conversion into additional sex hormones for which clinical data suggests are associated with poor outcomes after TBI. For this study, data from the ProTECT Phase III clinical (N=536) was utilized to assess characterization of the hormone aromatization pathway in progesterone and placebo treated patients with TBIs. The clinical trial assessed the use of progesterone therapy in TBI patients with outcomes of mortality, total non-neurological organ dysfunction (NNOD), and Glasgow Outcome Scale – Extended (GOSE). Serum samples of hormones were collected at enrollment of the clinical trial (baseline), 24 hours after, and 48 hours after enrollment. However, there was not a significant adverse effect of progesterone. K-means clustering analysis was used to identify subgroups of TBI patients based on similar hormone aromatization levels. Analyses were performed to assess association between these subgroups and TBI outcomes. Clustering of 24-hour hormone levels partitioned the dataset into 3 distinct groups with significantly different outcome profiles. The clustering of 118 patients (55% treated, 45% placebo) suggested that those with higher levels of estradiol (pg/mL), testosterone (ng/mL), and androstenedione (pg/mL) and lower levels of estrone (pg/mL) and progesterone (ng/mL) experienced higher proportions of mortality and higher average counts of total non-neurological organ dysfunction. These findings are congruent with previous research on estradiol and estrone association with mortality and GOSE.
The project is relevant to public health as it will improve our understanding of the role of hormone aromatization in patients with TBI and how subgroup characterization may predict survival and recovery outcomes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Mayrer, Bridgetbmm146@pitt.edubmm146
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCarlson, Jennajnc35@pitt.edujnc35
Committee MemberYouk, Ada O.ayouk@pitt.eduayouk
Committee MemberWagner, Amywagnerak@upmc.eduakw4
Date: 16 May 2024
Date Type: Publication
Defense Date: 11 April 2024
Approval Date: 16 May 2024
Submission Date: 24 April 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 53
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: clusters, K-means, traumatic brain injury, hormones, progesterone
Date Deposited: 16 May 2024 19:39
Last Modified: 16 May 2024 19:39


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