Saudi Cultural Missions Theses & Dissertations
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Item Restricted REPURPOSING DRUGS FOR HYPERCOAGULABLE CONDITIONS: A PRECISION MEDICINE APPROACH TO ADVANCE THERAPEUTIC DISCOVERY(Virginia Commonwealth University, 2024-12) Alghubayshi, Ali; Wijesinghe, Dayanjan SBackground: Sickle Cell Disease (SCD) and related hypercoagulable conditions, particularly those associated with elevated von Willebrand factor (vWF) levels, pose significant health challenges globally, with a notable burden in Saudi Arabia. Despite known genetic factors influencing these conditions, effective treatment options remain limited. This dissertation aims to leverage genomic data and bioinformatic techniques to identify novel therapeutic targets and drug repurposing opportunities for SCD and vWF-linked hypercoagulability. Methods: This research comprises three interconnected studies. First, a case-control Genome-Wide Association Study (GWAS) was conducted comparing Saudi SCD patients with healthy controls. The second study utilized bioinformatic pipelines to analyze the druggability of the identified genes that characterize Saudi SCD patients. The interaction of these genes with the currently approved medications was estimated. The third study extended this approach to vWF-linked hypercoagulability, utilizing publicly available GWAS data. These analyses integrated data from various sources, including databases of drug-gene interaction and protein structures, to identify potential drug repurposing candidates and novel drug targets. Results: The initial GWAS identified numerous significant genetic variants characterizing SCD cases in the Saudi population. Building on these findings, the second study revealed several approved medications showing potential for repurposing in SCD. Notably, drugs such as simvastatin, allopurinol, and specific immunomodulators have emerged as promising candidates. The analysis also identified novel drug targets with high druggability scores, in particular, the olfactory receptor gene clusters. The third study, focusing on vWF-linked hypercoagulability, identified additional potential candidates, including nebivolol, pravastatin, riociguat, candesartan, and acetylcysteine. This study also revealed several novel, highly druggable targets implicated in key processes related to blood coagulation and vascular function, such as CLEC4M and SLC44A2. Conclusion: This research provides a comprehensive framework for drug repurposing and novel drug discovery in SCD and related hypercoagulable conditions. The findings underscore the potential of leveraging genetic data to identify targeted therapies, offering a pathway to more personalized and likely effective treatments. While promising, these computational predictions require further validation through conducting clinical studies to be translated into clinical practice.16 0Item Restricted Economic Evaluations of Sickle Cell Disease-Modifying Therapies in Adult Patients(Howard University, 2024-07) Algatan, Razan; Wingate, La'Marcus T.Throughout history, sickle cell disease (SCD) has faced unequal healthcare treatment, impacting African Americans disproportionately due to difficulties in obtaining high-quality medical services. Although advancements in medicine have resulted in longer lifespans, these improvements may not fully meet the complex requirements of the growing number of elderly individuals dealing with the illness. Objectives: The objectives of this study are to (1) to investigate how the type of insurance influences the use of crizanlizumab and voxelotor in adult patients with SCD; (2) to evaluate the financial burden and therapeutic benefits of SCD therapies in mature individuals; and (3) to determine the financial impact and feasibility of using SCD treatments in U.S. Medicaid programs that have the highest rates of SCD. Methods: A comprehensive review of patient records was undertaken at the adult SCD clinic at Howard University Hospital, spanning from 2019 to 2023. The review focused on patients prescribed crizanlizumab and voxelotor, and extracted demographic data and insurance information. Logistic regression used to predict crizanlizumab or voxelotor usage A cost-utility analysis compared the cost-effectiveness of SCD-modifying therapies to automated red blood cell exchange in adult patients, using a lifetime horizon and taking into account societal costs. This model was then used to estimate the total budgetary impact of these therapies versus automated red blood cell exchange over a one-year period, from the perspective of U.S. Medicaid programs with the highest incidence of SCD, and exploring the potential benefits of an annuity payment model. Results: A total of 54 patients with were included, SCD, with an average age of 39.4 years, and the vast majority were single (90.7%). Notably, patients with dual eligibility had a significantly higher average age (43 years) compared to those with only Medicaid coverage(40 years). After controlling for other factors, the results showed that patients with Medicare coverage were nearly 10 times more likely to receive crizanlizumab compared to those with Medicaid coverage. The cost utility analysis indicated that automated red blood cell exchange (aRBCX) may be a cost-effective strategy compared to other SCD-modifying therapies, with a cost per quality-adjusted life-year (QALY) below $100,000, depending on the severity of SCD and the likelihood of death due to vaso-occlusive crisis. The cost-utility model predicted that hydroxyurea had the lowest lifetime costs, approximately $1,039,311, while voxelotor had the highest, approximately $3,252,674. Also, aRBCX resulted in the highest QALY and the fewest acute pain episodes over a lifetime. In terms of cost-effectiveness, l-glutamine had the lowest incremental cost-effectiveness ratio compared to aRBCX. Furthermore, the analysis demonstrated that voxelotor had the largest annualized budget impact, adding approximately $95,702.40 per patient compared to aRBCX, while hydroxyurea offered significant short-term cost savings of approximately $41,519.23 per patient relative to aRBCX. Conclusions: Medicaid serves as a vital safety net for individuals afflicted with SCD, with roughly half of adult sufferers relying on Medicaid or similar programs for their health insurance needs. Despite this, the adoption of interventions that can alter the course of SCD remains surprisingly limited. In stark contrast, aRBCX has consistently shown more favorable results in adult patients compared to these disease-modifying therapies.18 0Item Restricted SAUDI ADULTS IN VASO-OCCLUSIVE CRISIS ACCESSING HEALTHCARE FOR PAIN MANAGEMENT: A PHENOMENOLOGICAL INQUIRY(Alqahtani, Jawhrah Mohammed, 2023-05-18) Alqahtani, Jawhrah; Chin, ClaudetteBackground: Vaso-occlusive crises (VOCs) require frequent utilization of healthcare services by adults with sickle cell disease (SCD). This increases the likelihood of poor care and healthcare disparities. The experiences of SCD patients attempting to access pain management have rarely been examined. An evaluation of these experiences may ease the lifelong suffering of Saudi Arabians affected by SCD. Purpose: This study explored the lived experience of Saudi Arabian adults when accessing the healthcare system for pain management in VOC. Philosophical Underpinnings: A qualitative transcendental phenomenological approach guided by the interpretivist–constructivist paradigm to inductively understand the lived experiences of adults during VOC. Methods: Purposeful and snowball sampling techniques were used to recruit 12 participants. The data analysis was guided by Moustakas’s transcendental phenomenology. Results: Four major themes emerged: enduring, suffering while crying out for understanding, the paradox of accessing the healthcare system, and longing beyond suffering. The essence of the experience was extracted from a synthesis of textural and structural descriptions: longing for their suffering to be recognized while asking for compassionate and informed care. The praxis of suffering theory provided further insights to study’s findings. Conclusions: This study revealed the profound suffering of patients with SCD during VOCs. They long for their pain to be understood and for better treatment when accessing healthcare. Compassionate, informed care, with positive interventions, would help patients to cope with their pain and to move on, beyond their suffering toward a more hopeful future. The results suggested that offering compassionate care may contribute to pain relief, warranting further research.40 0