Saudi Cultural Missions Theses & Dissertations
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Item Restricted A Comparative Analysis of CVD and MSK Comorbidities in Usual COPD and AATD-COPD(University of Birmingham, 2024-08) Mousa, Hatim Hammad; Michael, NewnhamBackground: Chronic obstructive pulmonary disease (COPD) and alpha-1 antitrypsin deficiency-related COPD (AATD-COPD) are complex conditions associated with cardiovascular (CVD) and musculoskeletal (MSK) comorbidities, which exacerbate the severity of the disease and impact patient outcomes. Despite their clinical relevance, the prevalence and impact of these comorbidities in AATD-COPD compared to usual COPD have not been thoroughly investigated. This study aims to address this gap by comparing the prevalence of CVD and MSK comorbidities in these two COPD populations to improve treatment approaches and patient care. Methods: This retrospective cohort analysis utilised data from the INTEGR-COPD trial and the Birmingham Alpha-1 cohort to compare the prevalence of CVD and MSK comorbidities in patients with usual COPD and AATD-COPD. Baseline characteristics, comorbidities, and pulmonary exacerbations were analysed. Non-parametric tests, including chi-square and Mann-Whitney U tests, were employed to compare categorical and continuous variables across the cohorts, respectively. Results: The study analysed 1,663 usual COPD and 754 AATD-COPD patients. CVD comorbidities were more prevalent in usual COPD (52.50%) than AATD-COPD (30.11%) (p < 0.001). Similarly, MSK comorbidities were more prevalent in usual COPD (30.07%) compared to AATD-COPD (11.41%) (p < 0.001). AATD-COPD patients were younger, had better lung function, and reported higher dyspnoea scores. Smoking status varied significantly, with higher current smokers in the usual COPD cohort. Pulmonary exacerbations were significantly more frequent in usual COPD patients with CVD than in AATD-COPD patients (p = 0.0011). Conclusion: This study highlights that usual COPD patients exhibit a higher prevalence of CVD and MSK comorbidities. Additionally, they tend to be older and have worse pulmonary outcomes compared to patients with AATD-COPD, who experience more severe dyspnoea. These findings emphasise the need for tailored clinical management approaches for both populations. Further research should explore the mechanisms and interventions to mitigate these comorbidities and improve patient outcomes.5 0Item Restricted Metabolic and Bariatric Surgery: Utilization, Statin Discontinuation, and Cardiovascular Risk Stratification in the Modern Era(University of Cincinnati, 2024) Alsuhibani, Abdulrahman; Hincapie, AnaBackground: Bariatric surgery, as a pivotal intervention to treat obesity, has seen dynamic utilization trends over recent years, and the subsequent pharmacological implications, particularly concerning statin discontinuation, hold significance. With the world grappling with the cardiovascular epidemic and its associated mortality, there's an imperative need to understand the cardiovascular outcomes post-bariatric surgery, especially when linked with discontinuation of critical medications like statins. Aims: This dissertation aimed to delineate the trends in bariatric surgery utilization and the corresponding shifts in surgical techniques in the U.S. Furthermore, it sought to understand the patterns and repercussions of statin discontinuation post-surgery, with an emphasis on discerning the risks associated with discontinuing statin therapy, particularly among patients with a history of Atherosclerotic Cardiovascular Disease (ASCVD). Methods: Comprehensive retrospective analyses were conducted utilizing the TriNetX electronic medical records network, spanning the years 2012 to 2021. The trends in bariatric surgeries were examined alongside their procedural variations. In parallel, patients on statin therapy undergoing bariatric surgery were identified, with their subsequent statin discontinuation patterns being analyzed. The consequences of such discontinuations, especially regarding ASCVD events, were also explored, taking into consideration both primary and secondary prevention cohorts. Results: There was a steady upswing in bariatric surgeries until 2018, which saw a decline during 2020 and 2021, coinciding with the COVID-19 pandemic. The surgical landscape depicted a decline in the Roux-en-Y (RYGB) procedure, substituted by an uptake in the sleeve gastrectomy (SG) procedure. Among statin therapy users, 48% of primary prevention and 34.5% of secondary prevention patients discontinued statin therapy within six months post-bariatric surgery. Alarmingly, within a statin therapy discontinuation post bariatric surgery, secondary prevention patients manifested significantly higher ASCVD event rates compared to their primary prevention counterparts. Distinctly, Hispanic/Latino patients exhibited heightened ASCVD risks post-statin discontinuation, as opposed to non-Hispanic/Latino individuals. Conclusion: The trends in bariatric surgery, amidst their shifting preferences, underscore the importance of understanding the aftermath of such surgeries, especially regarding medication discontinuation. The discontinuation of statins post-bariatric surgery, particularly among those with prior ASCVD, poses discernible risks, accentuating the need for individualized, equitable healthcare strategies. Addressing ethnic disparities and ensuring tailored therapeutic approaches based on comprehensive cardiovascular determinants is crucial. Future research endeavors are essential to further finetune these interventions and recommendations.15 0Item Restricted The Anti-inflammatory Effects of Metformin on Human Pro-inflammatory Macrophages(2023-06-23) Alqurashi, Noor; Rena, GrahamMacrophages are a type of immune cells that have a key role in atherosclerotic plaque development and as such possible target for cardiovascular disease (CVD) therapy. In mouse and human lesions, macrophages adhering to both M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes are present, with M1 being the most common phenotype. The type 2 diabetes drug metformin is thought to reduce inflammation by reducing the polarisation process to M1 macrophages, with AMPK activation likely to be an important mediator of this effect. In this thesis, I have used state-of-the-art data-independent acquisition (DIA) proteomics to perform a systems-wide comparison of the effect of metformin and a selective AMPK agonist A769662 on the polarisation and differentiation processes in THP-1 cells, a human macrophage cell line. This work highlighted the modulation of proteins linked to inflammation, cell adhesion, migration,19 0