Medicine and Health Sciences Commons^™

Characterization Of The Macular Choriocapillaris In Dry Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography, Phillip X. Braun

Yale Medicine Thesis Digital Library

The purpose of this study was to characterize further, using swept-source (SS-) optical coherence tomography angiography (OCTA), the relationship between dry age-related macular degeneration (AMD) and the macular choriocapillaris (CC), which may have pathophysiologic and therapeutic implications. It included (1) a topographic analysis to determine if there is a significant relationship between dry AMD stage and macular CC perfusion, and (2) an investigation of the predictive value of macular CC perfusion with respect to geographic atrophy (GA) growth rate.

Study design was retrospective and cross-sectional. A database of 6x6 mm fovea-centered swept-source OCTA images of the CC from eyes with …

The Cost-Effectiveness Of Culture Vs Naat Based Screening Of Pregnant Women For Group B Streptococcus To Reduce Early-Onset Sepsis Of The Newborn, Bertie Geng

Yale Medicine Thesis Digital Library

While great progress has been made to reduce its incidence, group B streptococcus (GBS) is still a leading cause of neonatal disease. Current standard of care recommends antepartum rectovaginal GBS culture of all pregnant women at 36 weeks of gestation in order to identify candidates for intrapartum prophylaxis to reduce vertical transmission. The purpose of the study is to assess three alternative nucleic acid amplification (NAAT) screening strategies for GBS: antepartum NAAT at 36 weeks, intrapartum NAAT, or a combined intrapartum and antepartum approach in which patients with penicillin allergies undergo antepartum culture screening and all other patients undergo intrapartum …

Decline In Medication Affordability Despite Closure Of The Medicare Part D Coverage Gap, Matthew Jordan Klebanoff

Yale Medicine Thesis Digital Library

The original Medicare Part D benefit included a gap in coverage, commonly known as the “doughnut hole,” where beneficiaries were responsible for 100% of drug costs. The Affordable Care Act included provisions to gradually close this gap, beginning in 2011, in order to reduce the financial burden of drug spending for Part D enrollees. Using a nationally representative survey of Medicare beneficiaries, we examined the effect of this policy on out-of-pocket drug spending and medication affordability. We found that the policy was associated with a decrease in out-of-pocket spending. However, this trend was limited to relatively healthy enrollees in stand-alone …

Hair Cortisol As A Retrospective Biomarker Of Stress Among Minorities And Immigrants During The First Year Of The Trump Administration, Dennis Wang

Yale Medicine Thesis Digital Library

Cortisol is an important part of the body’s physiological response to stress. Chronic exposure to race-based discrimination and stress is thought to explain, in part, minority health disparities. Hair cortisol concentration (HCC) can be used as an objective proxy of a participant’s chronic stress prior to recruitment. It has not to our knowledge been used to investigate stress following an unexpected political event. President Trump issued in his first week in office multiple Executive Orders targeting minorities and immigrants. The Gallup-Sharecare Well-Being Index also showed significant declines in Democrats but not in Republicans, and in women but not in men, …

Obstructive Sleep Apnea And Pain Intensity In Young Patients, Wardah Athar

Yale Medicine Thesis Digital Library

Obstructive sleep apnea and pain intensity in young patients

Wardah Athar; Mary E. Card; Antonios Charokopos; Kathleen Akgün; Eric C. DeRycke; Sally G Haskell; Henry K. Yaggi; Lori A. Bastian. Yale University School of Medicine, New Haven, CT.

Objective: This study aims to examine whether young patients who are diagnosed with obstructive sleep apnea (OSA) are more likely to report higher pain intensity when compared to young patients without OSA.

Design/Participants: To do so, we conducted a cross-sectional analysis of a cohort study of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans who had at least one clinical encounter …

Understanding Costs Of Healthcare: Patient Perspectives And Beyond, Edwin Yirong Chan

Yale Medicine Thesis Digital Library

Introduction: Healthcare spending in the US is among the highest in the world and continues to grow year-over-year despite outcomes comparable to or worse than other nations. This spending has translated to extensive patient burden and high out-of-pocket costs for many individuals. Despite high costs to both systems and individuals, patients continue to pursue expensive care options such as emergency department care over other appropriate alternatives. Here, we assess patient understanding of emergency room costs and influences on their decisions to pursue emergency department care.

Methods: Adult patients presenting to the emergency department for conditions not meriting hospital admission or …

Meat Consumption, Cooking Practices, And Blood Harmane Concentrations In Essential Tremor: A Population-Based, Environmental Study In The Faroe Islands, Monica Ferrer Socorro

Yale Medicine Thesis Digital Library

Background: Essential tremor (ET) is among the most prevalent neurological disease, yet potential modifiable environmental factors contributing to its etiology are poorly understood. Harmane [1-methyl-9H-pyrido(3,4-b)indole], is a potent neurotoxin, of which elevated levels may be linked to ET. Possible etiologies for this elevation include increased dietary consumption, impaired metabolism, or increased endogenous production. Harmane is particularly abundant in meats and long cooking times can increase its concentrations. One previous study provided preliminary data of a dietary difference between male ET cases and controls. To clarify the relationship between ET and harmane we conducted a population-based, case-control study, in the Faroe …

Aging With Hiv: Biomarkers Of Inflammation And Incident Rheumatologic Disease, Jennifer Leslie Simon Hanberg

Yale Medicine Thesis Digital Library

Chronic Human Immunodeficiency Virus (HIV) infection results in multimorbidity and shortened lifespan. Inflammation and immune dysfunction contribute to these outcomes. The aim of this thesis is (1) to investigate the utility of two inflammatory biomarkers evaluated in other settings (neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)) for prognostication in patients living with HIV (PLWH) and comorbid inflammatory states; and (2) to compare the frequency and severity with which rheumatologic disease states occur in PLWH to demographically and behaviorally similar uninfected individuals (“controls”).

Three cohorts were created from the Veterans Aging Cohort Study. In each cohort, patients were stratified by presence …

Genetic Investigation Reveals Novel Pathways For Disease Pathogenesis In Inherited And Mosaic Skin Disorders, Shayan Cheraghlou

Yale Medicine Thesis Digital Library

Introduction

Genetic mosaicism underlies many inherited and acquired cutaneous disorders. Despite the barriers to genetic analysis of mosaic disorders, next generation sequencing has led to substantial progress in understanding their pathogenesis, which has significant implications for clinical management and genetic counselling. Advances in paired and deep sequencing technologies in particular have made study of mosaic disorders more feasible. In this study, we aim to utilize next generation sequencing technologies in order to evaluate the genetic cause of three mosaic cutaneous disorders: epidermolytic acanthoma (EA), progressive symmetric erythrokeratodermia (PSEK), and mosaic childhood acantholytic dyskeratosis.

Methods

Using genomic DNA extracted from paraffin-embedded …

Identification Of A Novel Disorder With Cholestasis, Liver Fibrosis And Congenital Diarrhea Due To Organic Solute Transporter Alpha Deficiency, Emily Gao

Yale Medicine Thesis Digital Library

BACKGROUND: Much of our understanding of normal liver pathophysiology comes from studying patients with liver disease who remain undiagnosed after a comprehensive workup. Searching for diagnoses among such cohorts has benefits both for the underserved patients with idiopathic liver disease, but also for science as a whole. Unbiased genomic analysis of patients with undiagnosed disease has yielded remarkable results, including clinically actionable diagnoses in children and adults, as well as the discovery of novel genetic diseases. Thus, we posit that among pediatric patients with undiagnosed liver disease, there may be previously unrecognized Mendelian causes.

METHODS: We report a 2.5 year …

Cbpr 2.0 - A Community-Based Participatory Research Approach To Program Scaling In Maternal Mental Health: Responding To Community Risk Factors For Maternal Depression While Replicating New Haven Moms To Bridgeport And New York City, Sonia Taneja

Yale Medicine Thesis Digital Library

“Community-Based Participatory Research 2.0” refers to a methodologic framework describing the process of scaling the New Haven MOMS Partnership, an existing participatory intervention, to new sites in Bridgeport, Connecticut and New York City.

Following a community-based participatory approach to the process of program differentiation within implementation science, informal team canvassing identified core components of the program: neighborhood hub sites, community mental health workers, and utilization of incentives. Community needs assessments were prepared, distributed, and analyzed to identify flexible program components. Assessments were tailored to specific communities and included the Center for Epidemiologic Studies-Depression Scale (CES-D), the Oslo-3 perceived social support …

Lifestyle Factors Associated With Neoadjuvant Chemotherapy Outcomes In Breast Cancer, Ilana Usiskin

Yale Medicine Thesis Digital Library

Lifestyle factors such as lower BMI, higher levels of physical activity, and increased fruit and vegetable intake, have been shown to benefit breast cancer survival, but the association between these factors and the pathologic complete response (pCR) to chemotherapy, has not been studied. We investigated whether lifestyle factors including BMI, physical activity, diet and alcohol use are associated with pCR from neoadjuvant chemotherapy for breast cancer treatment. Secondarily, we assessed whether the relative dose intensity (RDI) of neoadjuvant chemotherapy is associated with pCR.

We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer between …

Characterization Of Temperature Curves In The Intensive Care Unit, Patricia Lourdes Valda Toro

Yale Medicine Thesis Digital Library

Fevers are extremely common in hospitalized patients, particularly in those admitted to the intensive care unit (ICU). Up to 50% of fevers in the ICU are non-infectious in origin. Yet, the development of a fever commonly prompts extensive, costly and invasive infectious workups. Patients with persistent fevers are usually treated with antimicrobials long after infectious workups prove unrevealing. While this is viewed as a ‘safe’ approach, inappropriate antibiotic use has shown to be harmful to patients – even effecting an increase in mortality – in addition to contributing to the spread of antibiotic resistance. The purpose of this study is …

Maternal Anxiety And Neural Responses To Infant Cues, Emily Vancor

Yale Medicine Thesis Digital Library

Maternal anxiety is highly prevalent during pregnancy and the postpartum period and is associated with disruptions to children’s socioemotional development. These long-term outcomes are thought to be mediated in part by anxiety’s effects on parenting and parental sensitivity to infant cues. Recent event-related potential (ERP) studies have found a positive association between generalized anxiety symptoms during the perinatal time and enhanced sustained processing of neutral infant faces. It has been suggested that for perinatal women with anxiety, the uncertainty of how an infant with a neutral expression may be feeling could be experienced as distressing, leading to enhanced sustained neural …

The Development And Validation Of A Novel Ichthyosis Severity Assessment Instrument, Qisi Sun

Yale Medicine Thesis Digital Library

Abstract: THE DEVELOPMENT AND VALIDATON OF A NOVEL ICHTHYOSIS SEVERITY ASSESSMENT INSTRUMENT. Qisi Sun, Amy Paller, Keith A. Choate. Department of Dermatology, Genetics & Pathology, Yale University School of Medicine, New Haven, CT.

Ichthyosis clinical trials require reliable, validated severity assessments to identify appropriate subjects and quantify treatment outcomes. There is no validated scale to measure ichthyosis severity across the entire body. We aim to create and validate a comprehensive and user-friendly instrument to measure total body ichthyosis severity in adults and children.We divided the body into 10 regions to score special regions of interest. Likert scales (0-4) were established …

How Exposure To Mass Incarceration Is Associated With The Wellbeing Of Individuals And Families, Ram Sundaresh

Yale Medicine Thesis Digital Library

Mass incarceration in America has far-reaching effects on individuals and their families. Although a large body of evidence has described the effects of incarceration on specific physical and social outcomes, there is almost no research on its effects on broader wellbeing, a more holistic measure of lived experience that can more sensitively reflect social welfare and structural vulnerability. The goal of this thesis is to assess the association between exposure to the American system of mass incarceration and wellbeing. We examine individual-level exposure to the broader criminal legal system (CLS), including police stops, arrests, and incarceration, and family-level exposure to …

Immunologic Analysis Of Non-Small Cell Lung Cancer In People Living With Hiv, Ramsey Yusuf

Yale Medicine Thesis Digital Library

Among people living with HIV (PLWH), non-small cell lung cancer (NSCLC) has emerged as the most common non-AIDS defining cancer and a leading cause of death. PLWH with NSCLC are diagnosed at younger ages and demonstrate worse outcomes compared to the general population. Global immune dysregulation in the setting of HIV infection may account for these disparities, however little is known about the immunobiology of HIV-associated NSCLC. The goal of this study was to investigate the clinical and pathology of NSCLC in PLWH. This retrospective cohort study examined HIV-associated and uninfected NSCLC cases within Yale-New Haven Hospital between 2000-2016. Medical …

Context Of Injury Among Abusive And Accidental Injuries In Children, Lindsay Eysenbach

Yale Medicine Thesis Digital Library

Child physical abuse is a significant public health challenge with an incidence of approximately 6.4 hospitalized cases per 100,000 children. Many abused children, however, will go undiagnosed by physicians evaluating these injuries. Assessing whether a child has been abused is a high-stakes decision: a missed case leaves a child vulnerable to future injury, but an inaccurate diagnosis of abuse may be greatly disruptive and stigmatizing to children and their families. Previous research has established key physical examination and radiographic findings that are associated with abusive injury. A gap in the literature, however, is the role of additional injury circumstances and …

Myrf Represses Nodal Signaling Via Furin During Left-Right Patterning And Gastrulation, Sarah Amalraj

Yale Medicine Thesis Digital Library

Congenital heart disease (CHD) is the most common major birth defect in children, affecting nearly 3% of children and is the leading cause of infant mortality. Heterotaxy (Htx) is a disorder of left-right (LR) patterning, in which organs, including the heart, are mispatterned relative to the LR axis. Htx is associated with severe forms of CHD, but its genetic causes remain largely undefined. Exome sequencing studies of large patient cohorts have recently revealed hundreds of CHD/Htx candidate disease genes, which now need to be validated in experimental systems for causality in order to better understand the causes and biological mechanisms …

Meningitis In Infants ≤60 Days Of Age Diagnosis, Parent Experiences And Potential Improvements In Care And Communication, Eduardo Fleischer

Yale Medicine Thesis Digital Library

Objectives: The aims of this body of work are several fold. Aim 1: To describe the cerebrospinal fluid (CSF) profile of infants ≤60 days old with bacterial meningitis and characterize the clinical and laboratory features of infants with bacterial meningitis who present with no CSF abnormalities. Aim 2: To evaluate the performance characteristics of the BioFire® FilmArray® Meningitis/Encephalitis panel (ME panel), the only Food and Drug Administration (FDA)-cleared multiplexed panel for the evaluation of CSF samples. Aim 3: To identify themes to be included in a parent-reported outcome measure for febrile infants ≤60 days old and to describe the process …

Acute And Chronic Liver Disease: Lessons Learned From Retrospective Cohort Studies, Ysabel C. Ilagan-Ying

Yale Medicine Thesis Digital Library

Current trends in liver disease are changing due to increased access to pharmacotherapies and the worsening burden of obesity. Large, observational cohort studies are a common tool in clinical and epidemiological research to determine risk for patients that may have experienced an exposure of interest. Past studies have largely examined risk factors for liver disease in patients with cirrhosis or fatty liver disease. We utilized retrospective cohort studies in a disease-agnostic approach and aimed to characterize risk for two increasingly prevalent populations: patients with severe acute liver injury and those with liver fibrosis progressing to hepatocellular carcinoma (HCC).

First, we …

Impact Of Race, Gender, And Clinical Risk Factors On Outcomes Following Treatment Of Unruptured Intracranial Aneurysms, Andrew Koo

Yale Medicine Thesis Digital Library

INTRODUCTION: In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as surrogate markers for operative success. Length of hospital stay (LOS) and discharge disposition during index admission are two metrics increasingly used. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay and poor discharge disposition remain relatively unknown.

OBJECTIVES: 1) To investigate the influence that patient demographics, such as gender and race, have on post-procedural discharge disposition after treatment of unruptured aneurysms, and 2) To identify the nationwide impact …

Assessing Trends In Industry Payments To Orthopaedic Surgeons: A Sub-Specialty Analysis, Neil Pathak

Yale Medicine Thesis Digital Library

Background: The Open Payments Database (OPD), mandated by the Sunshine Act, is a listing of physician-industry payments. With the growing scrutiny of such transactions, the present study aims to characterize and investigate trends in industry payments to orthopaedic surgeons using four full years of data available. The study assessed payments to four orthopaedic sub-specialties: (1) pediatric surgery, (2) foot and ankle (F&A) surgery, (3) spine surgery, (4) adult reconstructive surgery. As the majority of industry payments were classified as General (other categories are Research and Ownership), the present study primarily focused on General payments.

Methods: Industry payments were characterized by …

Contraception And Sexual Health Counseling In Adolescent And Young Adult Female Cancer Patients, Sarah Hadassah Abelman

Yale Medicine Thesis Digital Library

Introduction:

Adolescent and young adult women undergoing cancer treatment face unique reproductive health risks. The objectives of this study were to assess the prevalence of sexual health counseling and contraception use in the oncology setting, and to identify factors associated with these outcomes.

Methods:

After institutional review board approval, a retrospective chart review was conducted of female patients ages 15-25 receiving cancer treatment at Yale New Haven Hospital from 2013-2018. Univariate and multivariate analyses were used to assess the relationship between patient variables and the outcomes of counseling and contraception use. Additionally, with institutional review board approval, a cross-sectional survey …

The Pharmacokinetics Of A Novel Anti-Renalase Antibody Used For The Treatment Of Melanoma In A Congenic Mouse Species, Oriyomi Alimi

Yale Medicine Thesis Digital Library

The pharmacokinetics of a humanized anti-RNLS monoclonal antibody used for the treatment of melanoma in a congenic mouse species

Authors: Oriyomi Alimi1, Gary Desir1

1Department of Internal Medicine, Yale School of Medicine, New Haven, CT

Cancer cells can overcome signaling that restrains their growth and promotes senescence and cell death. Renalase (RNLS) is a secreted flavoprotein that functions as a survival factor after ischemic and toxic injury, signaling through the plasma calcium channel PMCA4b to activate the PI3K/AKT and MAPK pathways. In addition, recent studies, indicate that dysregulated RNLS signaling promotes survival of melanoma cells due to its capacity to …

Natural History Of Thoracic Aortic Aneurysm Associated With Bicuspid Aortic Valve, Thais Faggion Vinholo

Yale Medicine Thesis Digital Library

Hypothesis: Thoracic aortic aneurysm (TAA) is a silent but virulent disease. Bicuspid aortic valve (BAV) is the most common congenital heart disease. The association between BAV and ascending TAA (ATAA) is well described. However, the guidelines for surgical management to treat patients with thoracic aortic aneurysms associated with bicuspid aortic valve (ATAA-BAV) remains controversial. We hypothesized that the surgical management of patients with ATAA-BAV should not differ from the management of those who have ATAA with a trileaflet aortic valve (TAV). Additionally, we suspected that BAVs that are free of stenosis and regurgitation can be spared in the setting of …

Differential Response To Rituximab In Anti-Achr And Anti-Musk Positive Myasthenia Gravis Patients, Tess Litchman

Yale Medicine Thesis Digital Library

Response to immunomodulatory therapies in myasthenia gravis (MG) can be variable. A subset of MG patients remains refractory to conventional agents. B-cell targeted therapy with rituximab has demonstrated a durable response in treating refractory myasthenia gravis (MG). This study compares the response to rituximab between patients with acetylcholine receptor autoantibody positive (AChR+) and muscle-specific kinase autoantibody positive (MuSK+) MG.

This retrospective study included 33 patients with either AChR+ or MuSK+ MG who were treated with rituximab from 05/31/2003 to 05/31/2017. Pretreatment and post-treatment immunotherapy regimens, clinical symptoms, and examination findings were evaluated.

Median MGFA Class of II at baseline improved …

Human Amniotic Membrane Improves Healing In A Chronic, Massive Rotator Cuff Repair Model, Maarouf Saad

Yale Medicine Thesis Digital Library

Rotator cuff tendon heals by fibrovascular scar that is weaker than native tissue leading to repairs that are prone to failure. To investigate the utility of an amniotic-membrane-derived human allograft in improving tendon-bone healing and skeletal muscle architecture, a rotator cuff repair model in Sprague-Dawley rats was established, tendon biomechanical testing, single muscle fiber biomechanical testing, microcomputed tomography analysis, tendon and muscle histological analysis, and gene expression analysis were performed. Our findings demonstrated single muscle-fibers with larger cross-sectional area and greater maximum isometric and specific force in the augmented experimental repair (ER) group. Additionally, microcomputed tomography revealed a larger volume …

Coronary Revascularization Options For Females: A Meta-Analysis Of Randomized Controlled Trials, Tayyab Hussain Shah

Yale Medicine Thesis Digital Library

The totality of evidence for revascularization decisions between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for the treatment of multivessel coronary artery disease comes from predominantly male patients. Although societal guidelines do not provide sex specific recommendations, growing evidence suggests that revascularization outcomes may not be consistent between sexes. This study evaluates outcomes of CABG versus PCI in female patients with multivessel disease (MVD) and/or left main disease (LMD). We conducted a systematic search to identify randomized controlled trials (RCTs) comparing the long-term outcomes after PCI versus CABG in MVD and/or LMD. We extracted female specific data …

Defining Psychological Resilience And Determining Long-Term Mental And Physical Health Outcomes In Male And Female West Point Graduates, Melissa Thomas

Yale Medicine Thesis Digital Library

We examined what defines psychological resilience in graduates of the United States Military Academy at West Point, a special population that was selected and trained to adapt and excel in the face of risk factors that can adversely affect mental and physical health. We also assessed self-reported mental and physical health in this population and compared these data to other veteran and civilian populations to lay the groundwork for further investigations into the relationship of resilience to health outcomes. The aims of this study were to: 1) employ a novel approach to operationalizing psychological resilience, defined as adapting well and …