Browsing by Subject "Clinical outcomes"
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Item Medication therapy management (MTM): a tool for optimizing clinical and economic outcomes in the management of chronic diseases(2013-04) Soliman, Ahmed Mohamed AhmedMedication Therapy Management (MTM) is an innovative pharmacist-led and delivered pharmacy service that aims to resolve drug therapy problems, improve patient education and increase medication adherence. This dissertation sought to evaluate the impact of receiving MTM services on clinical, economic and behavioral outcomes. The first manuscript showed that diabetes patients exposed to MTM were more likely to meet the glycosylated hemoglobin clinically defined goal compared to a control group of diabetes patients. The second manuscript showed that diabetes patients who took insulin or had diabetes complications were more likely to receive a higher number of MTM visits. The third manuscript showed that patients who took four or more chronic medications had a significant cost reduction seven months after the first MTM encounter compared to a matched cohort of patients who were never exposed to MTM services. Similar results were observed in the fourth manuscript which examined the economic outcomes in diabetes patients who were taking insulin. The last manuscript showed that MTM services resulted in improvement in medication adherence (measured by proportion of days covered (PDC)) across five different classes of chronic disease medications. Taken together, this body of work shows that MTM services is a potential tool that could be used by policy makers and health plan administrators to improve patient outcomes across multiple dimensions of care.Item Single nucleotide polymorphisms in cancer related genes lead to inter-individual response to prognosis, disease risk and environmental agent metabolism in multiple myeloma and lung cancer.(2010-08) Haznadar, MajdaMultiple myeloma is a chronic disease for which there is presently no cure. Because of the significant genetic heterogeneity in this disease and the fact that it is rare, it has been difficult to study genetic variations that contribute to disease risk and clinical outcomes. Nevertheless, there are apoptotic and oncogenic signaling pathways that constitute common themes in genetic deregulation leading to myeloma. Therefore, we biologically guided single nucleotide (SNP) association studies by pre-identifying important pathways. We managed this by designing a targeted SNP chip panel containing genes in functional groups crucial to various cancer processes, especially to myeloma, and applied it to SNP association studies represented in this thesis. Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. Therefore, it is one of the rare diseases for which there is a known environmental exposure. The occurrence of lung cancer is thus attributed to a complex interplay of genetic factors and environmental exposure. Since many polymorphic genetic variations produce proteins with increased, decreased or a complete loss of enzymatic activity, they are relevant factors in the gene--environment interplay. The first part of this thesis explores impact of interindividual variations resulting in variable bone disease, prognosis (progression-free survival) and disease risk in myeloma. In the bone disease association study, we demonstrated that there are genetic variants in genes important in the inflammatory response, Wnt signaling, and in growth factors previously linked to etiology of myeloma. The novelty of this study is in combining gene expression profile of DKK1 with a SNP profile that resulted in a better prediction of bone disease. We then investigated genetic variants in relation to progression-free survival and risk in myeloma. This study resulted in the identification of polymorphisms in genes involved in drug metabolism and detoxification, immunity, DNA repair and signaling cascades important to multiple myeloma (MM) risk and survival. This was done by using novel combinatorial search algorithms that can robustly identify markers that associate with the studied outcomes, and decrease false discovery rates. The second part of this thesis explores impact of interindividual variations on the metabolism of tobacco-smoke carcinogens. Variations in genes involved in tobacco-smoke carcinogen metabolism can result in variable amounts of harmful DNA adducts that can ultimately lead to cancer. We first demonstrated that there is a variation in CYP1B1 gene, previously shown to result in decreased cellular protein levels. This polymorphism appears to function as a protection from lung cancer at low levels of exposure, whereas it loses its protectiveness at high exposure levels. This was important to unraveling gene--environment interactions, especially relevant in the initiation of lung cancer. We then demonstrated that there are SNP-SNP interactions that associate with lung cancer risk by applying a novel data mining combinatorial search algorithm. This approach will serve as a useful tool to more robustly study SNP associations with outcomes of interest, while minimizing the false discovery rate. Our findings will help aid in further understanding etiology of myeloma and lung cancer. The novel computational method we helped to develop and first applied will serve as an important tool in further identifying and validating genetic variability that leads to differential response to disease risk and outcomes.