The Impact of Air Pollution and Long-term Hydroxyurea Use on Health Outcomes in Children with Sickle Cell Disease Öffentlichkeit
George, Paul (Fall 2024)
Abstract
Sickle cell disease (SCD) is a chronic condition characterized by acute, severe pain events, lung disease, and other end-organ damage. Despite being a monogenetic defect, the clinical course of SCD is quite variable and difficult to predict, with some children remaining relatively unaffected in childhood, and others with severe, debilitating disease. Understanding factors that contribute to this phenotypic variability is crucial, as it may unveil modifiable risk factors at the patient level and areas for policy intervention at the population level. For this dissertation, I examine the impact of air pollution exposure on outcomes in children with SCD. I find that air pollution exposure, both short-term and long-term, and at the cohort level and individual level, is associated with significantly worse outcomes in children with SCD. Separately, I examine the long-term, time-varying impact of hydroxyurea, the main disease modifying medication in SCD. Using contemporary difference-in-differences and event study analyses, I find that hydroxyurea has sustained, positive impact on clinical outcomes, whereas its impact on hematologic parameters diminishes over time. In summary, this work contributes to a deeper understanding of the multifaceted influences on SCD outcomes, emphasizing the need for comprehensive and sustained interventions. Lastly, I study the diffusion of a specific cost-saving innovation – outpatient treatment for appendicitis – to better understand why it was widely-adopted.
Table of Contents
Chapter 1 ……………………………………………………………………………………… 1
Abstract ……………………………………………………………………………….. 2
Introduction …………………………………………………………………………… 3
Methods ……………………………………………………………………………….. 5
Results ………………………………………………………………………………… 8
Discussion …………………………………………………………………………….. 9
References ……………………………………………………………………………. 14
Chapter 2 ……………………………………………………………………………………… 33
Abstract ……………………………………………………………………………….. 34
Introduction …………………………………………………………………………… 35
Methods ……………………………………………………………………………….. 36
Results ………………………………………………………………………………… 41
Discussion …………………………………………………………………………….. 42
References ……………………………………………………………………………. 45
Chapter 3 ……………………………………………………………………………………… 63
Abstract ……………………………………………………………………………….. 64
Introduction …………………………………………………………………………… 65
Methods ……………………………………………………………………………….. 66
Results ………………………………………………………………………………… 69
Discussion …………………………………………………………………………….. 71
References ……………………………………………………………………………. 76
Chapter 4 ……………………………………………………………………………………… 91
Abstract ……………………………………………………………………………….. 92
Introduction …………………………………………………………………………… 92
Background …………………………………………………………………………… 95
Methods & Results .…………………………………………………………………… 97
Conclusions …………………………………………………………………………… 109
References …………………………………………………………………………….. 110
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