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HMS Theses and Dissertations

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  1. A Comparison of Tier 1 and Tier 3 Medical Homes Under Oklahoma Medicaid Program

    Kumar, Jay
    Introduction: The patient-centered medical home (PCMH) is a team-based model of care that seeks to improve quality of care and control costs. The Oklahoma Health Care Authority (OHCA) directs Oklahoma’s Medicaid program and contracts with 861 medical home practices across the state in one of three tiers of operational capacity: Tier 1 (Basic), Tier 2 (Advanced) and Tier 3 (Optimal). Only 13.5% (n=116) homes are at the optimal level; the majority (59%, n=508) at the basic level. In this study, we sought to determine the barriers that prevented Tier 1 homes from advancing to Tier 3 level and the incentives...

  2. Loss of UBE2O Mitigates Beta Thalassemia Through Broad Proteomic Changes

    Nguyen, Anthony Tuan
    UBE2O is a ubiquitin-conjugating enzyme that is upregulated during terminal erythroid differentiation. We previously showed that UBE2O selectively ubiquitinates ribosomal proteins (RPs) and drives the elimination of ribosomes in reticulocytes and non-erythroid cells. Here, we showed that Ube2o-/- reticulocytes have a severe defect in the elimination of RPs by immunoblot analysis. We then used quantitative mass spectrometry to analyze the reticulocyte proteome in a global and unbiased manner. Of the 1235 proteins quantified, we observed significant elevations of 183 proteins, many of which were RPs. Similarly, we quantified the proteomic changes in HEK293-derived cells upon expression of UBE2O. Nearly 10%...

  3. Tissue Architecture Is Required for Chromosome Segregation Fidelity in Epithelia

    Knouse, Kristin
    Chromosome segregation is classically viewed as a cell-intrinsic process. We tested this assumption by comparing chromosome segregation fidelity in various epithelial cells in their native tissue and as dissociated cells in culture and discovered that chromosome segregation fidelity is dependent on the tissue environment. Using organoid culture systems, we show that it is tissue architecture, the cell adhesion and cell polarity patterns that define a tissue, which is responsible for the heightened chromosome segregation fidelity in tissues and that disruption of tissue architecture leads to chromosome instability. Tissue architecture enhances the cell’s ability to correct erroneous microtubule-kinetochore attachments and this...

  4. Determinants of Health-Related Quality of Life in Adolescents With Repaired D-Transposition of the Great Arteries

    Robson, Victoria K.
    Objective: Understanding the determinants of health-related quality of life in adolescents after infant congenital heart surgery is essential to providing life-long care to this patient population. The Boston Circulatory Arrest Study (BCAS) is a randomized clinical trial involving a cohort of patients with dextro-transposition of the great arteries (D-TGA) who underwent the arterial switch operation, and who have since been followed prospectively from infancy through adolescence with in-depth health status and neurodevelopmental evaluations. The objectives of this thesis are to report on 16-year health status in this cohort of patients with repaired D-TGA, to evaluate how health status tracks over...

  5. Investigating the Molecular Mechanisms of Action of Lenalidomide and Other Immunomodulatory Derivatives

    Haldar, Saurav Daniel
    Background: Thalidomide was first released as a sedative and anti-emetic by a German pharmaceutical company in the 1950s. After its withdrawal from the market due to severe teratogenicity, thalidomide and its novel iMiD analogs were repurposed decades later for a variety of new clinical indications, including the treatment of erythema nodosum leprosum, multiple myeloma, and del(5q)-MDS. Recent work has demonstrated that iMiDs act by modulating the substrate specificity of the CRBN-CRL4 E3 ubiquitin ligase. Selective degradation of IKZF1/IKZF3 and CK1α by this complex in the presence of iMiDs leads to therapeutic activity against multiple myeloma and del(5q)-MDS, respectively. In spite...

  6. Readmission Rates Across All Insurance Types After Passage of the Hospital Readmissions Reduction Program: A Nationwide Analysis

    Ferro, Enrico Giuseppe
    Background: Since implementation of the Hospital Readmission Reduction Program (HRRP), readmissions have declined for Medicare patients with target conditions. It is unknown whether similar reductions occurred for other insurance groups. Methods: Readmission rates across all insurance types were analyzed to understand whether readmissions changed in the pre- and post-HRRP periods for target conditions, compared to control. Results: Medicare readmissions declined faster after HRRP implementation, both in aggregate and for individual target conditions. For Medicaid patients, there was a stronger decline for certain target conditions, while readmissions for privately-insured patients were not found to decline after HRRP implementation. Conclusions: The HRRP was...

  7. Expanding the Role of Radiology in the Detection of Physical Elder Abuse

    Lee, Mihan
    Pediatric radiologists play a key role in the detection of child abuse, through the identification of characteristic fracture and injury patterns. Emergency radiologists have the potential to play an equally important role in the detection of elder physical abuse; however, existing literature shows that they currently play little to no part in this effort. We sought to examine the role of radiologists in the detection of physical elder abuse, and potential strategies to expand and optimize this role, by interviewing experienced health care providers who confront abuse at both ends of the age spectrum. Interviews were conducted with attending faculty from...

  8. Methodological Comparison in Analysis of Lesion Burden and Aging in Human Remains From Past Populations

    van Schaik, Katherine Douglas
    Background: Study of disease in the past can help illuminate patterns of human health, disease, and aging in the present and can shed light on human physiology. There are many methods to investigate questions of health and disease in the past, including DNA analysis and examination of human skeletal remains through gross inspection and X-ray imaging. Each method has its own possibilities and limitations for the kinds of information it can provide. Inspection and imaging of bones for evidence of disease is particularly important: such studies provide valuable data about chronic disease, as bones preserve information about malnutrition, longstanding infection,...

  9. Strategies to Improve the Cervical Cancer Screening Experience of LGBTQ Patients: a Film-Based Curriculum

    Berrahou, Iman K.
    Introduction: Reproductive health screenings, such as Papanicolaou (Pap) tests, are an essential aspect of preventative health that enable detection and treatment of precancerous cervical changes (i.e., dysplasia), ultimately resulting in prevention of cervical cancer. Despite being as likely to develop cervical cancer as heterosexual cisgender women, LGBTQ people with a cervix underutilize cervical cancer screening tests. There is a need to educate medical providers and trainees in order to improve the cervical cancer screening experience for LGBTQ patients and, ultimately, to increase rates of cervical cancer screening in this population. Methods: A participatory educational workshop was developed to permit medical trainees...

  10. HIV-Associated Changes in the Human Gut Microbiome and Impact on Disease Progression

    Luévano Jr., Jesús Mario
    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products, enteropathy, and alterations in gut bacterial communities. Whether this is the same in developed and developing nations, and if the status of a human host as an immunological controller affects disease progression remains unknown. We characterized the enteric bacterial microbiome in two geographical cohorts, Boston and Uganda, which included HIV-uninfected controls or HIV-infected subjects on anti-retroviral treated (ART) and individuals with chronic untreated disease that are either immunologically controlled or have progressive disease. In both of the cohorts, serum immune markers were measured as well as...

  11. Better Evidence: Assessing the Utility of an Evidence-Based Clinical Resource in Two African Medical Schools

    Valtis, Yannis K.
    Background: Evidence-based clinical resources (EBCRs) have the potential to improve diagnostic and therapeutic accuracy at the point of care. The majority of U.S. teaching medical institutions have integrated them into clinical training and practice. Many EBCRs are subscription-based, and their cost is prohibitive for clinicians and trainees in low-income countries (LICs). The current use of EBCRs by medical students in sub-Saharan Africa, as well as their utility and impact on students’ educational performance, is not known. Methods: We conducted the first prospective cohort study of African medical students and faculty. Participants were offered free 5-year subscriptions to UpToDate, a leading...

  12. Early Results of Surgical Treatment of Triangular Fibrocartilage Complex (TFCC) Tears in Children and Adolescents

    Wu, Mark
    Purpose: To investigate the clinical results and patient-reported functional outcomes following surgical treatment for TFCC tears in the pediatric and adolescent population. Methods: We reviewed 149 patients with 153 arthroscopy-confirmed TFCC tears. Mean age at surgery was 15.5 years (range,7-19). There were 86 females. Plain radiographs and magnetic resonance imaging (MRI) were used to characterize bony and soft-tissue pathology. Mayo Modified Wrist Score (MMWS) and PROMIS® Upper Extremity Short Form assessed functional outcomes. Median follow-up was 21.8 months (IQR:5.9-55.4). Results: Pre-operatively, all patients had wrist pain or instability with activities. Median pre-operative MMWS was 80(IQR:65-90). Forty-nine(32%) presented with positive ulnar variance. Concomitant pathology...

  13. A Conceptual Model for the Evaluation of Surgical Missions

    Bido, Jennifer
    Background: Medical missions to low and middle-income countries are increasingly frequent, with an estimated 6,000 trips accounting for ~ 200,000 surgical cases and over $250 million in costs annually. However, these missions have received little critical evaluation, which has prompted questions about their sustainability, cost-effectiveness, and quality of care. In response to these critiques, a few proposed frameworks for the evaluation of missions have been published. While these publications offer theoretical frameworks that detail topics for evaluation, they do not agree on which aspects should be assessed and they have not been shown to quantify or change the practices of...

  14. EZH2 Inhibition Induces Endogenous Retroviral Elements and Primes Immunogenicity in Mesenchymal Small Cell Lung Cancer

    Thummalapalli, Rohit
    Small cell lung cancer (SCLC) is characterized by heterogeneous mesenchymal and neuroendocrine cell states. In particular, aggressive mesenchymal subclones in SCLC harbor characteristic cytokine profiles and activation of innate immune signaling pathways. Recent work has shown that exposure of mesenchymal SCLC tumor cells to IFN-γ leads to production of double-stranded RNA (dsRNA) through transcription of a novel subclass of endogenous retroviruses (ERVs) located in the 3’ UTR of IFN-γ-inducible genes, with this subclass being termed SPARCS (Stimulated 3 Prime Antisense Retroviral Coding Sequences). However, the mechanism of SPARCS de-repression or the consequences of SPARCS dsRNA production for immune signaling and...

  15. Deciphering Multi-Dimensional Proteomics From Resected Lung Adenocarcinomas

    Lee, Charlotte
    Lung adenocarcinomas often display a high degree of intratumoral heterogeneity as manifested both by histology and by dynamic changes in protein expression. Clinically, this underlying heterogeneity can drive tumor progression towards a more aggressive neoplastic state and is associated with a worse prognosis. Furthermore, the presence of individual tumor sub-populations may differ in their sensitivity to anti-neoplastic agents, limiting the effectiveness of treatment. Therefore, understanding the diverse composition of a tumor both for risk stratification and for designing novel therapies is of critical importance. To explore whether intratumoral heterogeneity could be used to construct a differentiation-based intracellular hierarchy in a...

  16. The Cost-Effectiveness of Surgical Fixation of Distal Radius Fractures: A Computer Model-Based Evaluation of Three Operative Modalities

    Rajan, Prashant Vaidnath
    Background: There is no consensus on the optimal fixation method for patients who require surgical management for distal radius fractures. We used a cost-effectiveness analysis to determine which of three modalities: closed reduction and percutaneous pinning (CRPP), external fixation (EF), or open reduction internal fixation (ORIF), offers the best value. Methods: We developed a state-transition computerized Markov model that simulates cohorts of patients undergoing surgery for distal radius fracture, projecting short- and long-term health outcomes and costs. Simulations began at age 50 and were run over lifetime. The model inputs were transition probabilities, quality of life values, and costs. Transition probabilities...

  17. Non-Operative Management of Spinal Epidural Abscess: Development of a Predictive Algorithm for Failure

    Shah, Akash A.
    Background context: Prompt diagnosis and treatment is key in spinal epidural abscess (SEA), as delay can lead to paralysis or death. The initial management decision for SEA is not always clear, with the literature showing conflicting results. When considering non-operative management, it is crucial to avoid failure of treatment, given the significant neurologic compromise incurred through failure. Unfortunately, data regarding risk factors associated with failure are scarce. Purpose: The purpose of this study is to identify independent predictors of failure of non-operative management. Furthermore, we aim to develop a predictive algorithm that generates a probability of treatment failure based on the...

  18. Establishing the Clinical Feasibility of a Transparent Computed-Tomography Based Fractional Flow Reserve (CT-FFR) Algorithm

    Tang, Anji
    Coronary artery disease, a condition where plaque buildup in a coronary artery restricts blood flow to the myocardium, is a leading cause of heart disease, which is responsible for a high mortality rate in the US each year. While stress testing and echocardiography have traditionally been the gatekeepers for referrals to invasive coronary angiography (ICA) with possible revascularization, the inclusion of coronary computed tomography angiography (CTA) in risk assessment has been shown to reduce the number of normal coronary arteries found at ICA, i.e. false positives. Coronary CTA, however, provides only anatomic information. An important physiologic metric that has grown...

  19. Dermatologic Involvement Improves the Diagnosis and Treatment of Patients With Presumed Cellulitis: A Randomized Clinical Trial

    Ko, Lauren
    Background: Each year, cellulitis leads to 650,000 hospital admissions and is estimated to cost $3.7 billion in the United States. Previous literature has demonstrated a high misdiagnosis rate for cellulitis, leading to unnecessary antibiotic use and health care cost. Purpose: In this study, we had three objectives – to determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis (Part I), to evaluate the cost and clinical utility of diagnostic imaging and blood cultures for cellulitis (Part II), and to assess whether thermal imaging is a viable way to streamline cellulitis diagnosis moving...

  20. The Ethics of Organ Donation: First, Do No Harm?

    Segal, J. Bradley
    The dead donor rule (DDR) stipulates that donors must be dead before life-sustaining organs are removed. Its normative basis is to protect organ donors from suffering unacceptable harm. The central ethical consideration should not be whether or not a donor is dead: it should be whether the harm of vital-organ retrieval is justified. In this thesis, I argue that under certain circumstances living donors should be granted an exemption from the DDR on ethical grounds, specifically when the retrieval of vital organs would do no wrongful harm.

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