Medicine and Health Sciences Commons^™

U.S. Army Physician Assistant Retention: A Latent Class Analysis, Robert Greener

Theses & Dissertations

Introduction: Retaining employees is crucial to the success of organizations. While significant effort has been made to model employee retention, models have been unable to significantly predict retention. The purpose of this quantitative, non-experimental, cross-sectional study was to develop an improved employee retention model which could be used as a practical guide to improve employee retention. Materials and Methods: The study analyzed a survey created, implemented, and collected by the Statistical Cell at the U.S. Army Center of Excellence. In September of 2020, all 864 active-duty PAs were sent a link to the survey and 290 completed the survey, …

Chronic Kidney Disease Patients' Experiences In The Decision Making Process: The Relationship Between Personal Characteristics And Decisional Self-Efficacy On Decisional Conflict And The Dialysis Decision In Patients Who Participated In Shared Decision Making, Lincy Jojan

Theses & Dissertations

Patients with End Stage Renal Disease (ESRD) experience a complex and stressful decision making when comes to dialysis modality selection. There are pros and cons to both hemodialysis (HD) and peritoneal dialysis (PD). Patients are often uncertain as to which one is the best modality for them. This decisional conflict increases the likelihood of making a decision that is not based on the patient’s values or preferences and may result in undesirable post-decisional consequences. Purpose The purpose of this study was to explore Chronic Kidney Diseases (CKD) patients' experiences regarding their decision making process in selecting a dialysis modality. The …

Factors Influencing Uptake Of Human Papilloma Virus (Hpv) Vaccine Among Parents Of Adolescent Girls, Irene Nzisa Martin

Theses & Dissertations

Background: Cervical cancer is one of the most common preventable cancers causing morbidity and mortality in women especially in Sub-Saharan Africa. Three HPV vaccines have been approved for vaccination against HPV globally with Cervarix and Gardasil currently available in Kenya. Despite availability of free HPV vaccination and increased media campaigns the proportion of adolescent girls vaccinated against HPV remains low. Understanding the determinants of HPV vaccine uptake will inform strategies to improve the uptake at Aga Khan University Hospital, Nairobi.

Objectives: The aim was to identify the factors influencing HPV vaccine uptake among parents of adolescent girls. The secondary objective …

Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege

Theses & Dissertations

Methodology: This cross-sectional study was carried out at Aga Khan University Hospital, Nairobi between July 1st 2020 and December 31st 2021. Participants were adults aged 18 years and above presenting to the emergency department with signs and symptoms suggesting an acute myocardial infarction. Patients were identified on the hospital management information system (CARE 2000) using test results for baseline high-sensitivity cardiac troponin I. The final diagnosis as well as secondary clinical data was obtained from both physical and electronic patient medical records. The reference standard for the diagnosis of acute myocardial infarction was taken as the final clinical diagnosis made …

The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi

Theses & Dissertations

Introduction: Breast Cancer (BC) is the most diagnosed cancer among women worldwide and in Kenya. It is a highly heterogeneous disease requiring patient specific treatment and strategies to monitor response to therapy, especially in the neoadjuvant (NAC) setting. Currently, there are no reliable markers in use that can predict response to chemotherapy among patients receiving NAC. Tumour Infiltrating Lymphocytes (TILs) and Cell free DNA (cfDNA) are biomarkers that could possibly bridge this gap. However, limited studies have been carried out on the African population. With the increasing mortality rates attributable to BC in Sub-Saharan Africa, coupled with the growing preference …

Knowledge And Practice Of Pediatricians In Kenya Regarding Helicobacter Pylori Infection In Children., Aura Mwende Nzinga

Theses & Dissertations

Background: Helicobacter pylori is one of the most common chronic bacterial infections. It affects more than half of the world’s population and is frequently associated with peptic ulcer disease, gastric carcinoma and other extra gastrointestinal manifestations. Globally, one third of the children are infected with the highest burdens observed in low and middle income countries. In Kenya the prevalence stands at 87% among school going children and 50% in children under three years.

Justification: Studies in high income countries suggest poor knowledge and practice amongst physicians with limited data from Africa. There exists conflicting information regarding the pathogenic role and …

Conversion Of Dissertations To Publications At The Aga Khan University Kenya: An Exploratory Study Of Residents Perceptions And Experiences, Brigette Macharia

Theses & Dissertations

Background: The successful completion and submission of a dissertation is a fundamental milestone for many residency programs worldwide. Publication of a dissertation in a peer-reviewed journal makes it more accessible and is impactful within the scientific context. It contributes to the global outlook of total burden of disease, for which significant geographical variation exists. Publication of residents’ research is a convenient surrogate marker for research training and experience. However, the preparation of a manuscript, successful submission and acceptance in a peerreviewed journal is challenging for both residents and their supervisors.

Justification: Aga Khan University (AKU) invests heavily in infrastructure to …

A Systematic Literature Review Of The Prevalence, Distribution, Exposure, And Human Health Risks Of Tire Microplastics And The Contribution Of Their Physicochemically Diverse Properties, Luke Glastad

Theses & Dissertations

The history of synthetic plastics dates back to their first uses in 1907, continues with their expansion through the middle of the century with a diverse array of new polymers, and are so omnipresent today that many label this age of Earth the Plasticene Era. Tire microplastics (TMPs) have been increasingly identified as one of the environment's most bountiful types of microplastics (MPs). TMPs mainly enter the environment as tire-wear particles (TWPs) and recycled tire crumb (RTC). TWPs, in particular, have a high degree of variability, which impacts their distribution, degradation, and risk for adverse human health effects. This review …

Optimizing Antiretroviral Therapy With Modern Rifapentine Containing Tb Treatment, Anthony T. Podany

Theses & Dissertations

In the past decade there has been a multitude of phase 3 clinical trials targeting treatment shortening for tuberculosis (TB). The synthetic rifamycin derivative rifapentine (RPT) has been at the forefront of many of the treatment shortening approaches. RPT possesses greater potency and a longer pharmacokinetic (PK) half-life (t_1/2) as compared with the long used rifamycin, rifampin (RIF). For TB preventative treatment, a 3-month, once weekly regimen of RPT and isoniazid (INH; 3HP) was shown to be as effective as 9-months of daily INH therapy in the PREVENT TB trial. Similarly, a 4-week course of daily RPT and …

Evaluation Of Medication Optimization In The Setting Of Ecmo Therapy: Assessment Of Therapeutic Effectiveness, Greg Peitz

Theses & Dissertations

A series of studies within the setting of extracorporeal membrane oxygenation (ECMO) was undertaken to specifically answer questions related to medication optimization during this complex therapy. These studies included medication therapies involving optimal anticoagulation, analgesia delivery, fluid resuscitation, and infection related outcomes in the context of ECMO. Each investigation was retrospective in nature and included patients from a single institution. The results of these studies indicated the following: 1.) various anticoagulation goals do not impact severe, life-threatening bleeding events during ECMO therapy; 2.) sepsis is a common occurrence in the setting of ECMO; 3.) the choice of either a crystalloid …

Environmental Exposures And Human Health Challenges: Evidence-Based Insights From Health Surveillance Systems, Jagadeesh Puvvula

Theses & Dissertations

Human exposure to environmental hazards is associated with a variety of preventable adverse health outcomes. As the environmental health risks result from the complex interaction between hazard, exposure, and susceptibility, these exposure-outcome associations are heterogeneous across the population. Improving environmental health literacy by advocating evidence-based environmental risk communication could play a role in reinforcing protective behavior against environmental hazards. The use of public health surveillance systems to assess the exposure-response associations is one of the effective ways to quantify the environmental health risks. However, there are several gaps in effectively quantifying environmental health risks. This dissertation aims to address a …

Agrichemicals (Nitrate And Atrazine) In Drinking Water And Adverse Health Outcomes In Children In Nebraska, Balkissa S. Ouattara

Theses & Dissertations

Objectives: This research was conducted to (1) determine the concentrations of atrazine, and nitrate, in Nebraska watersheds and counties; (2) calculate the incidence of pediatric cancers and prevalence of birth defects in Nebraska counties and watersheds, respectively; (3) assess the relationship between the contaminant levels and the incidence rate of pediatric cancers and birth defects prevalence.

Methods: Pediatric cancers and birth defects data were obtained from the Nebraska Department of Health and Human Services. Water quality data were collected and retrieved from the Water Quality Portal and the Nebraska Groundwater Quality Clearinghouse. Geospatial and statistical analyses were conducted at the …

The Development And In Vivo Immunologic Assessment Of Biodegradable Microparticles Incorporating Cpdi-02 And Mucosal Protein Vaccine, Jacob E. Parriott

Theses & Dissertations

Encapsulation in biodegradable microparticles (MPs) is a promising approach to increase the efficacy of intranasally administered protein vaccines. The generation of long-lived adaptive immune responses against encapsulated protein vaccines, however, requires the incorporation of a suitable mucosal adjuvant. CPDI-02—a complement peptide-derived immunostimulant that selectively activates dendritic cells and macrophages over neutrophils while minimizing the inflammatory side effects of parent C5a—has previously been incorporated into both systemic and mucosal vaccine formulations via direct conjugation to chemical moieties, peptides, proteins, inactivated pathogens, and the surface of biodegradable particles, to enhance Th1-biased cellular immune responses. The effect of CPDI-02 surface conjugation to MPs …

The Effect Of Interproximal Home Regimens Of Inflammatory Biomarkers In Periodontal Maintenance Patients, Grace Moore

Theses & Dissertations

A survey of dental hygienists in general practice (DHGP; n = 74) and periodontal practice (DHPP; n = 62) indicated a difference (p £ 0.04) in preference for interproximal cleaning with oral irrigators (DHGP) and interproximal brushes (DHPP) during periodontal maintenance therapy (PMT). The purpose of the subsequent blinded, randomized controlled clinical trial was to compare the effect of interproximal cleaning aids on reducing inflammation in posterior pockets during PMT. Seventy-six patients on PMT with a 5-7 mm interproximal probing depth were randomly allocated to one of three groups: 1) interproximal brush with tracking device (IB + TD; n=23), 2) …

Applications Of Population Pharmacokinetic Modeling In People Living With Hiv, Michelle M. Pham

Theses & Dissertations

Population pharmacokinetic modeling has become an important tool for the individualization of medicine in HIV care and clinical pharmacology in general. This dissertation explores many applications of population pharmacokinetic modeling to help identify drug exposure, drug-drug interactions, and sources of variability in populations living with HIV. Comprehensive HIV care involves simultaneous treatment of the disease and any co-infection and/or co-conditions.

The first objective was to identify potential drug-drug interactions affecting combination antiretroviral therapy (ART) consisting of efavirenz, tenofovir disoproxil fumarate and emtricitabine, from concomitant use of chemotherapy agents. Three models were developed with sparse sampling to characterize efavirenz, emtricitabine, and …

Prevalence And Factors Associated With Undernutrition Among Children With Congenital Heart Disease At Three Tertiary Hospitals In Nairobi, Kenya., Shamsa Yahya

Theses & Dissertations

Background: Congenital heart disease (CHD) is the commonest birth defect. Children with CHD have a high burden of undernutrition and its consequences. Some of the factors that are associated with undernutrition in children with CHD include the type and complexity of the heart defect, associated pulmonary hypertension, late diagnosis, timing of surgical correction, low socioeconomic status, lack of adequate nutritional support, associated genetic conditions and the presence of other clinical comorbidities.

Justification: Although these factors are well defined, they vary geographically in their distribution and extent to which they influence the level of undernutrition. This limits the extrapolation of findings …

Perceptions And Attitudes Of Physicians And Midwives Towards Patient Safety At The Maternity Department Of A Tertiary Teaching Hospital In Kenya: A Mixed Method Study, Albert Kiretia Gichuki

Theses & Dissertations

Introduction: The maternal mortality ratio (MMR) has declined across the world over the last 17 years. This has been attributed to more women delivering in health facilities with trained birth attendants. Despite this there is still a high maternal mortality rate with over 86% of the mortalities occurring in Sub-Saharan Africa and South East Asia. This has led to increased focus on improving quality of care and patient safety in the health facilities. A positive safety culture, which is the product of individual and group values, attitudes, perceptions and patterns of behaviour that determine the commitment to an organization’s safety …

Prevalence & Factors Associated With Acute Kidney Injury In Patients Undergoing Percutaneous Coronary Intervention At A Tertiary Healthcare Facility In Tanzania, Faisal Hooda

Theses & Dissertations

Background: Acute kidney injury is a potentially fatal but preventable outcome of percutaneous coronary intervention: the most plausible cause being radiocontrast-induced nephropathy; others include: pre-existing renal insufficiency from underlying illnesses and also acute renal insult caused by hypoperfusion from cardiac causes. The prevalence, associated risk factors and outcomes of AKI post-PCI are unclear and unexplored in our setting.

Objectives: The study sought to determine the prevalence of acute kidney injury post-percutaneous coronary intervention at The Aga Khan Hospital, Dar es Salaam, Tanzania. Secondary objectives included: factors associated, with and outcomes of acute kidney injury (AKI) post percutaneous coronary intervention (PCI). …

Comparison Of Two Immunoassays For Detection Of Anti-Sars Cov-2 Antibodies Among Healthcare Workers At A Tertiary Referral Hospital In Nairobi, Kenya, Patrick Muriuki Mugaine

Theses & Dissertations

Background: Tests for antibodies against severe acute respiratory syndrome coronavirus 2, the aetiologic agent of coronavirus disease 2019, provide evidence of past infection or immunization. At the individual level, they are useful as markers of protection against severe disease and in cases where the diagnosis by nucleic acid amplification is inconclusive. At the population level, they are an indirect measure of exposure and may be useful in monitoring changes in viral infection or uptake of immunization over time. The interpretation and optimal use of antibody assays on populations requires an appreciation of the wide variability in individual antibody responses, the …

Single Oral Or Single Intramuscular Dose Of Vitamin D In The Treatment Of Vitamin D Deficiency In Children At Aga Khan University Hospital, Nairobi: A Randomized Controlled Trial, Winfred Mwikali Ndaka

Theses & Dissertations

Background: Vitamin D deficiency is a global health concern and plays an important role in bone health and many chronic non-communicable diseases. Vitamin D deficiency in children is associated with short stature, underdevelopment, respiratory infections and many other features that increase the risk of childhood complications. The prevalence of vitamin D deficiency in Kenya among children is high. Treatment with daily oral vitamin D is associated with poor compliance. While a single high intramuscular dose vitamin D offers an alternative strategy, it is however, associated with injection site pain and its absorption is dependent on the patient’s peripheral circulation. Various …

A Pilot Study Comparing Pre-Analytic Tissue Processes Before And After Implementation Of A Quality Improvement Program For Handling Breast Cancer Specimens, Joseph Gatheru Macharia

Theses & Dissertations

Background: Breast cancer as the most frequently occurring cancer in women is highly heterogeneous in its pathological characteristics. Assessment of tumor biologic characteristics including hormone receptor profile and growth factor receptor activity is important in characterizing the pathologic nature of such cancers. Tumor biomarker activity plays a big role in diagnosis and management of invasive breast cancer (IBC). Biological specimens are the primary sources of this molecular information. Optimal handling of the specimen through the various analytic phases assures of the validity of the final pathologic diagnosis.

Objective: To assess the feasibility of implementing an intervention plan to improve specific …

Biologically-Inspired Nanoparticles For Oncology Applications, Aishwarya Bapat

Theses & Dissertations

Cancer is the leading cause of death in the United States and its high mortality rate can be attributed towards poor diagnosis methods and less effective therapeutic treatments. Many nanotechnology-based diagnostics and therapeutics are being developed to improve cancer patient outcomes. In this work, we have studied nanoparticles for diagnostic and therapeutic applications in cancer treatment.

In the first work, novel fluorescent NPs loaded with indocyanine green (ICG) were developed for bioimaging applications of pancreatic cancer. Targeted fluorescent nanoparticles (NPs) are being developed to image a range of cancer types with the goal to improve patient outcomes by utilizing in …

Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells, Cassie Liu

Theses & Dissertations

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases, and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell …

Tourniquet-Induced Ischemia-Reperfusion Injury, Junliang Qian

Theses & Dissertations

Ischemia-reperfusion (IR) is a pathological condition characterized by an initial restriction of blood supply to an organ followed by subsequent restoration of reperfusion associated with exacerbation of tissue damage. For pre-hospital emergency situations and surgical procedures, tourniquet or femoral artery ligation are widely used to stop extremity hemorrhage or create a bloodless operating field. To fully evaluate the underlying mechanisms in IR pathophysiology and potential therapeutic options, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. We found that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR, including alteration …

Investigation Of Cumulative Genetic Risk And Cc16 In Adult Asthma And Copd Populations, Kelli C. Gribben

Theses & Dissertations

INVESTIGATION OF CUMULATIVE GENETIC RISK AND CC16 IN ADULT ASTHMA AND COPD POPULATIONS

Kelli C. Gribben, Ph.D.

University of Nebraska Medical Center, 2022

Supervisors: Paraskevi A. Farazi and Tricia D. LeVan, Ph.D.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) have complex etiologies and lack biological predictors that can be used for primary prevention, early detection, progression, or monitoring. Genetic risk scores (GRS) aggregate genetic effects from GWAS-identified susceptibility variants associated with a trait. GRS may provide opportunities to improve disease prediction to inform public health and clinical interventions. Asthma GRS studies utilizing multi-ethnic populations are scarce and there is a …

Design, Synthesis, And Biological Investigation Of Pyridine Sulfones As Anti-Chlamydia Trachomatis Agents, Mohamed A. Seleem

Theses & Dissertations

Chlamydia trachomatis is the most prominent cause of sexually transmitted bacterial infections worldwide, with around 128 million reported cases annually. This pathogen can cause severe urogenital and ocular consequences, resulting in infertility and trachoma. In its unique developmental cycle, Chlamydia fluctuates between two distinct forms, elementary bodies (EBs) and reticulate bodies (RBs). We hypothesized that caseinolytic protease P (ClpP), a conserved protease among bacterial species, drives the Chlamydia developmental cycle. Earlier work by the Ouellette group demonstrated that Chlamydia relies on its ClpP2 paralogue (ctClpP2) to differentiate between its developmental forms. Dysregulation of ctClpP2 had a significant …

The Development Of Polymeric Dexamethasone Prodrug Nanomedicines For The Treatment Of Lupus Nephritis, Zhifeng Zhao

Theses & Dissertations

Lupus nephritis (LN) is a significant cause of morbidity and mortality among lupus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GCs’ adverse effects while maintaining their potent therapeutic efficacy, we have developed a micelle-forming polyethylene glycol (PEG)-conjugated dexamethasone prodrug (ZSJ-0228), which could passively target the inflamed kidney in NZB/W F1 lupus-prone mice. It was found that monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. Unlike the dose equivalent daily dexamethasone treatment, long-term …

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

Macromolecular Fluorescent Conjugates For Bioimaging Applications, Paul Lovell

Theses & Dissertations

Bioimaging tools enable the visualization of small anatomical features as well as structures that may be obscured by other tissue. One such group of tools are fluorescent probes, molecules that emit detectable signals when stimulated by an excitation source. Incorporating fluorescent conjugates for clinical purposes would enable direct usage for the diagnosis, detection, or treatment of diseases. The development of specific targeting agents is feasible due to the number of nanomaterials and biological products that contain fluorophores. Specific targeting agents can target a particular region of interest, such as a cancerous tumor for removal or vital nerve structure for avoidance …

Erα As A Modulator Of The Sle1b Lupus Susceptibility Locus And B Cell Receptor Signaling, Jared H. Graham

Theses & Dissertations

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and the production of anti-nuclear autoantibodies. 90% of lupus patients are women, and this sex bias is due to the actions of estrogens, which promote lupus pathogenesis. Our lab has shown that estrogen receptor alpha (ERα) mediates the effect of estrogens in lupus and that ERa acts in a B cell intrinsic manner to promote the development of autoantibodies and SLE. Genetic factors also contribute to lupus. One major lupus susceptibility locus, Sle1, controls loss of tolerance and autoantibody development as well as immune cell …