• Identification of Apnea Events Using a Chest‐Worn Physical Activity Monitor

      Salazar, Eduardo; The University of Arizona College of Medicine - Phoenix; Buman, Matthew (The University of Arizona., 2017-05-25)
      Obstructive sleep apnea (OSA) is a condition characterized by upper airway obstruction during sleep causing intermittent hypoxia and nighttime awakening. It is a common condition in the United States that is often undiagnosed. It is a significant risk factor for decreased daytime productivity, quality of life, cardiovascular disease, and death. The current gold standard for diagnosis of OSA is laboratory‐based polysomnography (PSG). While PSG is necessary for the diagnosis and monitoring of OSA, many patients have limited access to PSG due to wait times at PSG laboratories or economic or geographic limitations. Portable sleep monitoring has been studied as a possible solution for patients who do not have access to timely PSG. This study aimed to use the Zephyr BioHarness 3, a chest‐worn physical activity monitor that records movement and physiologic data in real‐time, to detect apnea events in patients with suspected OSA undergoing single‐night laboratory PSG. Twenty patients underwent single‐night laboratory‐based PSG while simultaneously wearing the Zephyr BioHarness 3. The Zephyr BioHarness 3 data was analyzed using three methods. First, apnea events were identified in 10‐second windows of Zephyr data via support vector machine, logistic regression, and neural network (sensitivity = 76.0 ± 0.3%, specificity = 62.7 ± 0.2%, accuracy = 63.7 ± 0.1%). Second, apnea events were identified using the mean, median, and variance of the 10‐second windows (sensitivity = 72.3 ± 0.3%, specificity = 69.4 ± 0.1%), accuracy 69.6 ± 0.1%). Third, apnea events were identified using phase‐space transformation of the Zephyr BioHarness 3 data (sensitivity = 76.9 ± 0.3%, specificity = 77.9 ± 0.1 %, accuracy = 77.9 ± 0.1%). The Zephyr BioHarness shows initial promise as a possible OSA screening tool for patients suspected of OSA but who lack access to timely laboratory‐based PSG.
    • Identifying Barriers to Enrollment of Diverse Populations in Arizona Following the Initial Open Enrollment Period of the Affordable Care Act

      Moseley, Joseph; The University of Arizona College of Medicine - Phoenix; VanPelt, Kim (The University of Arizona., 2017-06-06)
      While it is known that over 266,000 Arizonans enrolled in health coverage through the federal Marketplace and Medicaid from October 2013 through May 2014, little analysis has been performed to examine whether enrollment by diverse racial and ethnic groups sufficiently reduced disparities in coverage. We obtained publicly available data from the Census Bureau comparing rates of uninsured by race/ethnicity from 2013 to 2014 in Arizona from the American Community Survey. The uninsured rate in Arizona for the total civilian no institutionalized population dropped from 17% in 2013 to 13.6% in 2014. The uninsured rate in Arizona for whites declined from 15.7% to 12.2%, for African Americans declined from 17.4% to 11.1%, for American Indian/Alaskan Natives declined from 26.9% to 24.1%, for Asian Americans declined from 15.1% to 11.0% and for Hispanic/Latino declined from 27.5% to 22.2%. We conducted interviews with nine community organizations in order to identify barriers that must be addressed moving forward to lessen insurance coverage disparities among various minority groups. Technological literacy and functionality, lack of funding, lack of personnel, physical vastness of many populations, language, and cultural differences were commonly identified as barriers to enrollment. Mistrust of government and confusion regarding the specific provisions within the ACA pertaining to Native individuals were also cited.
    • Identifying Genetic Pleiotropy through a Literature-wide Association Study (LitWAS) and a Phenotype Association Study (PheWAS) in the Age-related Eye Disease Study 2 (AREDS2)

      Simmons, Michael; The University of Arizona College of Medicine - Phoenix; Lu, Zhiyong (The University of Arizona., 2017-05-26)
      Genetic association studies simplify genotype‐phenotype relationship investigation by considering only the presence of a given polymorphism and the presence or absence of a given downstream phenotype. Although such associations do not indicate causation, collections of phenotypes sharing association with a single genetic polymorphism may provide valuable mechanistic insights. In this thesis we explore such genetic pleiotropy with Deep Phenotype Association Studies (DeePAS) using data from the Age‐Related Eye Study 2 (AREDS2). We also employ a novel text mining approach to extract pleiotropic associations from the published literature as a hypothesis generation mechanism. Is it possible to identify pleiotropic genetic associations across multiple published abstracts and validate these in data from AREDS2? Data from the AREDS2 trial includes 123 phenotypes including AMD features, other ocular conditions, cognitive function and cardiovascular, neurological, gastrointestinal and endocrine disease. A previously validated relationship extraction algorithm was used to isolate descriptions of genetic associations with these phenotypes in MEDLINE abstracts. Results were filtered to exclude negated findings and normalize variant mentions. Genotype data was available for 1826 AREDS2 participants. A DeePAS was performed by evaluating the association between selected SNPs and all available phenotypes. Associations that remained significant after Bonferroni‐correction were replicated in AREDS. LitWAS analysis identified 9372 SNPs with literature support for at least two distinct phenotypes, with an average of 3.1 phenotypes/SNP. PheWAS analyses revealed that two variants of the ARMS2‐HTRA1 locus at 10q26, rs10490924 and rs3750846, were significantly associated with sub‐retinal hemorrhage in AMD (rs3750846 OR 1.79 (1.41‐2.27), p=1.17*10‐7). This associated remained significant even in populations of participants with neovascular AMD. Furthermore, odds ratios for the development of sub‐retinal hemorrhage in the presence of the rs3750846 SNP were similar between incident and prevalent AREDS2 sub‐populations (OR: 1.94 vs 1.75). This association was also replicated in data from the AREDS trial. No literature‐defined pleiotropic associations tested remained significant after multiple‐testing correction. The rs3750846 variant of the ARMS2‐HTRA1 locus is associated with sub‐retinal hemorrhage. Automatic literature mining, when paired with clinical data, is a promising method for exploring genotype‐phenotype relationships.
    • Imaging for Chest Pain Assessment: An Algorithmic Approach Using Noninvasive Modalities to Define Medical vs. Interventional Treatment

      Graber, Taylor; The University of Arizona College of Medicine - Phoenix; Hamburg, Robert (The University of Arizona., 2017-05-09)
      To analyze the roles of CCTA, MPI, and CC to formulate a sequential clinical algorithm to use in patients with chest pain, risk factors for CAD, and an abnormal EKG. The goals of the study are to streamline and refine workup, to decrease radiation exposure to patients, and to contain costs. 39 patients underwent CCTA, MPI, and CC within 30 months of each other. CCTA was used to categorize mild, moderate, or severe CAD. MPI used SSS, SDS, TID, and formal reading to define mild, moderate, or severe physiologic ischemia. CC and coronary intervention cine films were analyzed to define and treat anatomical CAD medically or by intervention. Results: There was strong correlation between CCTA, CC, and treatment type (p<0.0001). CCTA was able to stratify all patients with mild or severe ischemia to appropriate treatment groups, and to reduce the need for MPI. With moderate ischemia from CCTA, the additional use of MPI could have reduced the need for 16/18 (89%) patients who underwent CC to undergo further testing. No patients with mild or moderate CAD by CCTA, followed by mild to moderate physiologic ischemia by MPI, needed CC or intervention. 37/39 patients (95%) could have avoided one or more tests using our algorithm. CCTA followed by MPI may be used in symptomatic patients with risk factors for CAD and an abnormal EKG to stratify mild and moderate CAD, and to thereby avoid cardiac catheterization. Our algorithm could lead to savings in healthcare expenditures, save patients from unnecessary invasive procedures, decrease radiation exposure, and total cost.
    • The Impact of Short-Term Medical Missions on Health Care Sustainability in Low-Income and Developing Communities: A Systematic Review

      Lansky, Charlotte; The University of Arizona College of Medicine - Phoenix; Conklin‐Aguilera, Cody (The University of Arizona., 2017-05-10)
      Short‐term surgical missions (STSMs) provide an opportunity for the global health care community to address the surgical needs of developing communities worldwide. Conditions that require a one‐time intervention, such as cleft lip and palate, clearly demonstrate the positive impact these short‐term missions can have on the individual patient. However, the long‐term impact on the local health care system, economy, and community is less clear. Many in the global health care community believe that STSMs should seek to have a long‐term impact by establishing sustainable health care programs. Information regarding the impact of STSMs is scarce, however, due to limited regulation, research, and data from short‐term missions. This study investigates how short‐term international missions impact health care sustainability in low‐income and developing communities. This study uses a systematic review to investigate the impact of STSMs on health care sustainability. Additional outcomes included education and skills‐transfer, cost‐effectiveness, and cultural awareness. 15 articles were included in the study. The following outcomes were found: sustainability in 9 studies, education and skills‐transfer in 5, cost‐effectiveness in 4, and cultural awareness in 3. STSMs can successfully establish sustainable programs abroad. Factors that contribute to this success include education and training of host providers, cost‐effective services, and cultural awareness. Understanding the complex dynamic between STSMs and developing communities is key to developing effective and sustainable programs that offer long‐term benefits to those communities.
    • Influence of Age on the Rate of Estimated Retinal Ganglion Cell Counts in Healthy Eyes

      Liao, Joseph; The University of Arizona College of Medicine - Phoenix; Medeiros, Felipe; Gracitelli, Carolina (The University of Arizona., 2017-05-10)
      To evaluate aging effects on estimated retinal ganglion cell (RGC) counts in healthy eyes. This was a longitudinal observational cohort study involving 100 eyes of 50 healthy patients recruited from Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). Subjects were followed for an average of 4.9 ± 2.6 years. All patients underwent standard automated perimetry (SAP) visual field testing and optical coherence tomography (OCT) on follow‐up visits. Estimated RGC counts were obtained by a previously described method using SAP sensitivity thresholds and OCT retinal nerve fiber layer measurements. Linear mixed effects models were used to investigate the relationship between age and rates of change in estimated RGC counts over time. The mean age at baseline was 49.4 ± 16.2 years, ranging from 22.9 to 90.0 years. At baseline, average estimated RGC count was 1,144,010 ± 222,084 cells. In univariable model, the rate of change in estimated RGC count was ‐6,880 ± 2,398 cells/year (P = 0.004). Analyses were also performed adjusting for baseline age, gender, race, OCT signal strength and axial length. After adjusting for confounding factors, the rate of estimated RGC loss was ‐6,276 ± 2,441 cells/year (P = 0.010) in healthy eyes. There was a significant age‐related decline in estimated RGC counts obtained from combining information from structural and functional tests. After accounting for confounding factors, the age‐related decline found was similar to those obtained in previous histologic studies reported on the literature.
    • Is HPV a Culprit For Breast Carcinoma? A Retrospective Study

      Starobinska, Ella; The University of Arizona College of Medicine - Phoenix; Mehta, Divyesh (The University of Arizona., 2017-05-19)
      The role of viruses in most common cancers is undoubtedly important, yet highly underestimated. Human Papilloma Virus (HPV) has been implicated with 99.7% of cervical cancers and its oncogenic mechanism has been clearly identified. The association of cervical cancer with 90% of triple negative breast cancer (TNBC) cases in African countries creates an intriguing possibility of HPV being a candidate oncovirus for breast cancer. In fact, numerous recent tissue studies conducted throughout the world detected HPV DNA in breast cancer tissues of patients with cervical cancer, while high‐risk HPV types (16, 18, 33) were present in invasive ductal carcinomas. 5,6 Prevalence of HPV varied from 4% in Mexican to 86% in American women. The virus was noted to be present in tumor tissue only, with the exception of one study, which identified lower concentration of HPV in normal tissue. 7 Although substantial evidence exists supporting involvement of HPV in breast cancer, no clinical studies have been conducted to elucidate this relationship. The goal of our retrospective chart review was to examine the association of breast cancer and HPV‐related cervical dysplasia in a cohort of women in urban setting. 15% (39/260) had abnormal Pap‐smear, while 8% (16/198) were HPVpositive. No statistically significant difference of Pap‐smear abnormality or of HPV positivity were detected among the groups in all categories. However, we noticed that non‐luminal breast cancers, double negative and triple negative (DN and TN), have higher rate of HPV positivity: 13.3% non‐luminal vs. 6.3% of luminal breast cancers, 12.5% DN breast cancers and 11.5% of TN vs. 6.4% of luminal A and 6.3% of luminal B. This creates an intriguing possibility that HPV might be associated with more than 50% increase of incidence rates of non‐luminal breast cancers, suggesting a need for larger scale studies to confirm this association.
    • Is Prehospital Emergency Telemedicine Implementation Feasible In Non‐Traditional EMS Settings: A Systematic Literature Review

      Guevorkian, Mark; The University of Arizona College of Medicine - Phoenix; Manriquez, Maria; Stapczynski, Steve (The University of Arizona., 2017-05-25)
      The rate of technology expansion is rapidly covering even the most remote parts of the globe and in the lowest resource settings. With globalization however, low and middle income areas are facing emerging health issues such as injuries and chronic medical conditions. With these illnesses, there are inevitable demands on emergency services. It has been thought that technology be utilized to augment emergency medical care in such settings where formal Emergency Medical Services. To aggregate and analyze the existing literature on the topic a systematic literature review was conducted. This study analyzed the existing literature on prehospital emergency care in settings in which no formal EMS services were utilized. Four databases were searched with inclusion and exclusion criteria, yielding 1782 results. The initial screening excluded all but 21 articles. Of the 21 articles in full review, 15 were included in the final review. Studies included in the final review were grouped into those reporting outcomes from five categories: Feasibility, Quality of Care, Response Time, Patient Outcomes, and Cost Effectiveness. Only one study was identified to be of high quality. There was a lack of studies with adequate statistical analysis to conduct statistical aggregation. Most studies however reported prehospital telemedicine in settings without EMS to be feasible, provide quality care, are be cost effective. However, the lack of statistical analysis makes it difficult to make conclusions. Also, several studies did show response time of a trained basic life support volunteer to be faster than EMS in many of the settings. But no positive health outcomes were observed in patients treated with projects utilizing technology in the prehospital setting. The prehospital emergency medicine setting is a young field of study that may have significant hurdles in application. The studies conducted have shown promise in the use of technology in prehospital settings without formal EMS services, but are not robust enough to make strong conclusions or recommendations that could be put into practice. Thus, more robust, statistically oriented research is imperative in the field so that we can fully explore the potential of technology in the prehospital setting, especially in low resource and rural settings without formal EMS services. With more robust studies, we can hope to integrate new technologies into practice and better serve the populations without adequate EMS coverage to provide more timely emergency care.
    • Knowledge Retention of the Rural Trauma Team Development Course

      Bennett, Brock; The University of Arizona College of Medicine - Phoenix; Detlefs, Corey (The University of Arizona., 2017-04-24)
      The Rural Trauma Team Development Course (RTTDC) is a one day course given to trauma personnel at various rural medical centers across the United States with the goal of improving care to injured patients in such areas. The purpose of this study is to determine the retention of RTTDC knowledge by those trained, as well as the migration rates of trainees out of these sites. The teaching of the RTTDC includes both pre‐test and post‐test assessments to ensure proper skills were learned. There was a statistically significant increase in score from the average course pre‐test score of 76.9% to the average course post‐test score of 92.1%. At this interim analysis, plotting the study post‐test scores over time since the course was given does reveal a pattern of decreased scores over time. The average study post‐test score of 88.8% is only slightly below the average initial post‐test score of 92.1%, though this was not significant. When assessed by individual questions, the participants scored significantly worse with questions addressing initial approach to the trauma patient and management of burn patients. There was no significant difference in scores between trauma team role. In this data set, the percentage of trainees remaining at course sites was 100%, though this was not expected based on previous studies. Our goal of 200 participants to achieve power has not been met at this time, but this could be established if more sites become involved, thus providing significant feedback for possible course revision.
    • Novel Patient‐Centered Diabetes Education Program: A Study to Assess The Feasibility, Design, Implementation, and Impact On Patients

      Davis, Amy; The University of Arizona College of Medicine - Phoenix; Rehman, Shakaib (The University of Arizona., 2017-05-08)
      Type 2 diabetes (T2D) continues to be a growing public health concern and will be the seventh leading cause of death by 2030.  Education programs have shown to be moderately effective in disease management, but there are little known about interactive patient‐centered diabetes programs.  This study implemented a single‐group pretest‐posttest quasi‐experimental design including a three‐session novel patient‐centered diabetes education program at the Phoenix Veterans Affairs Medical Center using the model originally developed by Esden and Nichols.  Measurements were obtained using validated and reliable instruments from Michigan Diabetes Research Training Center (MDRTC), which included the Brief Diabetes Knowledge Test (BDKT) and Diabetes Empowerment Scale (DES), and a participant satisfaction survey.  Results showed participants’ knowledge of diabetes was higher at three months follow up (M = 17; SD = 4.64) than at baseline/pretest (M = 13.8; SD = 2.95) with a 23 percent change in knowledge scores from baseline 95% CI [0.24,6.16], with corrected Cohen’s dunbiased = 0.66 (i.e., medium effect).  There was very good pre‐test reliability for the DES subscales: “managing the psychosocial aspects of diabetes” (0.93), “assessing dissatisfaction and readiness to change (0.83), “setting and achieving goals” (0.88).  Despite moderate effects in these 3 subscales, there were no statistically significant differences in posttest scores.  In conclusion, Esden and Nichol’s model was successfully replicated in the VA Heath Care setting, and future work with a larger sample size and matched control is needed to further validate the results found in this study. 
    • Predicting Patient Response to Cancer Immunotherapy Using Quantitative Computed Tomography Based Texture Analysis

      Gordon, Joshua; The University of Arizona College of Medicine - Phoenix; Korn, Ronald (The University of Arizona., 2017-05-08)
      Cancer therapies have evolved continuously, with the newest class being immunotherapies targeting the PD‐L1/PD‐1 pathway. This pathway is often overexpressed in malignancies, which allow the aberrant cells to evade the body’s natural immune response that would normally eliminate them. The novel therapies currently being investigated are monoclonal antibodies that target either the PD‐L1 on the tumor cell or the PD‐1 on the lymphocyte. Considering there are significant toxicities with these therapies, namely gastrointestinal and endocrine adverse effects, a predictive tool that could allow physicians which patients are likely to respond to these immunotherapies could spare patients unnecessary therapy and potential economic harm. Since repetitive imaging of patients with cancer is necessary to monitor treatment response, advanced imaging analysis techniques on standard of care images, such as CT scans may provide insights into tumor patterns that could help to predict treatment response. Quantitative texture analysis (QTA) of computed tomography scans has been used in various settings to examine tissue heterogeneity as a predictive biomarker of response; we hypothesized that QTA may have potential value in predicting tumor response to immunotherapy. We performed a QTA on standard of care CT scans from patients to determine if a unique textural imaging signature could be identified that would serve as a predictive biomarker for response to PD‐L1/PD‐1 therapies in subjects with solid tumor malignancies in the lungs, liver, and lymph nodes. This study examined the diagnostic standard of care CT scans of the chest, abdomen, and pelvis (CT CAP) at baseline and follow‐up, which were acquired as part of routine clinical care for tumor staging and treatment response in 20 subjects whose personal health care information was removed prior to analysis. Regions of interest (ROI) were drawn around all identifiable tumor lesions on baseline CT scans provided that tumors were of reasonable size (>10 mm in diameter) and conspicuity. CT texture analysis was performed on these lesions to obtain a histogram readout of tumor texture based upon tissue densities on a per pixel bases. The output values from the QTA platform provided an estimate of tumor signal properties as expressed as the mean pixel density, standard deviation, entropy, kurtosis, skewness, and mean positive pixel values. Each subject was designated as achieving either a RECIST based treatment response or not. Statistical modeling was then conducted using regression techniques. There was no identifiable signature when examining all of the lesions together, but there were statistically significant correlations noted between QTA and RECIST responses for lung‐based lesions. The QTA derived mean pixel density parameter was a major component of separating out responders from non‐response. Of the 14 lung lesions (8 responder vs. 6 nonresponder) there was a significant difference in the mean density with a threshold cutoff of 11.91 (p < 0.0001). A Mann‐Whitney U‐test was performed on the total data set yielding a Z statistic of 2.6 (p=0.0092). Despite the relatively small number of patients in this initial study, there were promising findings regarding the mean density of lesions, suggesting that texture analysis can be used to predict if patients respond to PD‐L1/PD‐1 inhibitors. Further investigation is warranted in a larger population that can be differentiated by tumor type to validate these results.
    • Predictors of Primary Care Career Choice: A Review of AMCAS Applications of Four Graduating Classes at a New Medical School

      Korenstein, Alyssa; The University of Arizona College of Medicine - Phoenix; Cunningham, Tara K. (The University of Arizona., 2017-05-10)
      The United States (U.S.) is currently facing a shortage of primary care physicians, an issue particularly salient in Arizona. The purpose of this project is to investigate predictors of students entering primary care specialties that may be apparent from their American Medical College Application Service (AMCAS) applications, in order to best serve the needs of the physician workforce. We hypothesized that factors such as female gender, older age at application (“non‐traditional” students), and being raised in a rural/underserved community background may be predictors of students who choose primary care fields. AMCAS applications are completed by aspiring medical students and contain demographic information including gender, age, race, languages spoken, and family/community characteristics. Data provided also include academic factors such as college major, grade point average (GPA), and Medical College Admissions Test (MCAT) scores. Other subjective data reported by applicants include descriptions of extracurricular activities and a personal statement. The National Resident Matching Program (NRMP) is the system used by graduating students during the last semester of medical school to match students with their choice of specialty and the residency program wherein they will spend an additional three years, minimum, in training. Based on the Association of American Medical Colleges (AAMC) designations, we are considering primary care to be Family Medicine, Pediatrics, Internal Medicine, and Medicine‐Pediatrics. We examined data from AMCAS applications of all 149 students who graduated from the University of Arizona College of Medicine‐Phoenix between 2011‐2014, and compared to their NRMP match outcomes. Comparisons were made between non‐primary care versus primary care‐overall, as well as Family Medicine alone versus all other matches given the increasing rate of specialization within Internal Medicine and Pediatrics. Multiple logistic regression revealed two predictors of primary care career choice compared to non‐primary care: having more siblings (P=.003) and non‐physician parents (P=.017). Specific to Family Medicine, several predictors were identified compared to the non‐Family Medicine cohort: a slightly greater percentage of earned community college credits (P=.03), lower MCAT physical science (P=.009), higher MCAT verbal scores (P=.02), and lower paternal education (P=.003). Our analyses suggest having a greater number of siblings and non‐physician parents may predict primary care career choice. Specific to Family Medicine, academic factors including community college enrollment and MCAT scores may be of predictive value. Though the exact implications behind these findings are unclear, it is important to continually examine such data as medical schools can shape admissions selection criteria targeted at increasing the number of graduates seeking careers in primary care.
    • Primary Melanoma tumor immune contexture analysis: T regulatory cell to T effector cell ratio as related to MHC class II and GILT expression

      Cole, Lauren; The University of Arizona College of Medicine - Phoenix; Hastings, Karen (The University of Arizona., 2017-04-28)
      Histopathologic examination of the tumor microenvironment demonstrates the presence of a vast repertoire of infiltrating lymphocytes and antigen presenting cells (APC’s). Recent studies establish a strong correlation between the tumor microenvironment cell composition and prognostic value in terms of cell type, location and ratio, referred to as a tumor’s immunoscore. More specifically, the relationship between T regulatory (Treg) cell to T effector (Teff) cell percentage predominates as a mechanism of tumor immune evasion. Further investigation of the factors influencing the development of Treg and Teff cells is therefore warranted. Gammainterferon‐inducible lysosomal thiol reductase (GILT) acts to influence antigenic processing and presentation by MHC class II cells, ultimately impacting lymphocyte development. Evaluation of the role of GILT expression in MHC class II+ APC’s with respect to Treg and Teff cell development in primary melanoma lesions, to our knowledge, has not been reported. Therefore our investigation focuses on elucidating a plausible relationship between GILT presence and Treg to Teff cell ratio. The aim of our study is to examine a possible association between GILT expression in APC’s and Treg:Teff cell ratio. We hypothesized GILT expression in melanoma cells would result in a decreased Treg to Teff ratio or an enhanced T cell‐mediated response. Our study included 17 de‐identified primary melanoma specimens previously stained and scored for Treg, Teff, CD8, MHC class II and GILT. Scoring was performed through identification of four areas per specimen with highest Treg and Teff cell density. These four areas were then averaged with ± standard deviation (SD). With use of landmark association, these four areas were identified and scored for MHC class II and GILT in APC’s and tumor cells with consideration to presence/absence, intensity and frequency of staining. Statistical significance was not reached relative to our hypothesized relationship of a decreased Treg to Teff cell ratio in the presence of GILT+ MHC class II. Similarly, we did not reach statistical significance when comparing individual cell types to GILT, MHC class II and GILT + MHC class. In our study, we were unable reach statistical significance relative to our proposed correlation between MHC class II and GILT presence leading to a decreased Treg to Teff cell ratio or enhanced T‐cell mediated immune response. A major limitation of our study included the small sample size leading to a probable type II error, prompting the need for further investigation of the factors influencing the Treg to Teff cell ratio within the melanoma tumor microenvironment on a larger scale.
    • Prophylactic Anticholinergic Medications to Prevent Drug-Induced Extrapyramidal Symptoms: A Systematic Review

      Dare, Reese; The University of Arizona College of Medicine - Phoenix; Stapczynski, J. Stephan (The University of Arizona, 2017-04-28)
      Neuroleptic medications are commonly administered in the emergency department but are known to induce extrapyramidal symptoms (EPS) in some patients; typically dystonia and akathisia. This systematic review will examine if adjunctive medications are efficacious when given in conjunction with neuroleptic medications to prevent these extrapyramidal symptoms. The Central, DARE, LILACS, PubMed, CINAHL, and OVID databases were searched for relevant articles between January 2014 and February 2016. Inclusion criteria required the article to be a randomized controlled trial; administer an anticholinergic medication given concurrently or just prior to treatment with medications with known extrapyramidal side effects; and be published in English. The initial search strategy yielded 1222 prospective articles of which 1208 were excluded by title and/or abstract. Fourteen articles were retrieved in full text and independently reviewed by each author. Seven 7 RCTs representing 645 patients were determined to be appropriate for analysis. Meta‐analysis of 5 studies found a significant effect (OR 0.4 with 95% CI 0.23‐0.71) for utilizing anticholinergic adjunct medications in the prevention of EPS for 60 minutes after administration. No reduction was found (OR 1.14 with 95% CI 0.01‐164) in EPS after 60 minutes in meta‐analysis of 2 studies with opposing results. Adjunctive anticholinergic medication was effective in reducing symptoms of dystonia (OR 0.13 with 95% CI 0.04‐0.43) but not in reducing symptoms of akathisia (OR 0.74 with 95% CI 0.27‐1.98). This systematic review found that anticholinergic adjuvant anticholinergic treatment reduced EPS induced by antipsychotic medications during 60 minutes after administration, with the greatest reduction in dystonic symptoms.
    • Prospective Detection of Chemoradiation Resistance in Patients with Locally Advanced Esophageal Adenocarcinoma

      Veaco, Jennifer Mitchell; The University of Arizona College of Medicine - Phoenix; Stone, John F. (The University of Arizona., 2017)
      Approximately 25% of patients with locoregional esophageal adenocarcinoma (EC) are resistant (marked by minimal tumor regression; TRG 3) to preoperative chemoradiation, including 5FU‐based and CROSS regimens. Previously, an immunohistochemistry (IHC) test that accurately identifies patients as responders (TRG 0‐2) or non‐responders (TRG 3) to neoadjuvant CTRT was developed and validated. The current study was designed to identify gene expression profile (GEP) signatures able to predict response to preoperative treatment. Methods: Formalin‐fixed, paraffin‐embedded (FFPE) tumor tissue from 24 diagnostic biopsies (14 responders, 10 non‐responders) was collected. RNA was isolated, and RT‐PCR performed to assess the expression of 96 candidate genes chosen from in silicoanalysis. Genetic signatures incorporating genes with significant expression differences in pathologically determined responders versus non‐responders were identified, and linear and non‐linear predictive modeling methods were used to assess the accuracy of the signatures for predicting treatment response. Cross validation was performed to attain corrected accuracy values. Ten‐, 18‐, and 24‐gene signatures were identified with significantly different gene expression levels in responders compared to non‐responders (p < 0.05). Functional groups represented by the signatures included DNA damage repair, extracellular matrix remodeling, and 5FU metabolism. Partial Least Squares (PLS) prediction of treatment response was compared to pathologic TRG determined by blinded pathologic reading, and resulted in an area under the curve (AUC) of 0.99 and overall accuracy of 100% for the 24‐gene signature. Corrected AUC of 0.99 and accuracy of 95% resulted from five‐fold cross validation with 20 iterations. Heatmap analysis of the 24‐gene signature separated the EC cases into two distinct clusters, the first with 93% responders and the second with 90% non‐responders. The current study identifies novel gene signatures able to accurately predict EC patient response to preoperative treatment. The GEP may allow non‐responders to avoid unnecessary toxicities associated with chemoradiation therapy.
    • Qualitative Assessment of Activated Microglia and Astrocytes in Focal Cortical Dysplasia: Case Series of Pediatric Patients

      Yee, Nicole; The University of Arizona College of Medicine - Phoenix; Lifshitz, Jonathan; Adelson, P. David (The University of Arizona., 2017-05-22)
      Epilepsy is the most common neurologic condition seen in children. Focal cortical dysplasia (FCD), a seizure disorder characterized by abnormal cortical laminar development, comprises approximately 75% of medically intractable epilepsies in the pediatric population. A greater appreciation of the pathology and intrinsic properties of the epileptogenic zone may help in understanding why FCD lesions are drug‐resistant, and could potentially lead to more effective treatments in the pediatric population. Neuronal support cells such as microglia and astrocytes have shown to have a role in FCD pathology. These cells are also activated during aging and traumatic brain injury as evidence by morphological change. This study aims to characterize the spatial distribution of microglia and astrocytes using immunohistochemistry in dysplastic tissue of eight male pediatric patients diagnosed with FCD. Cortical specimens from patients who underwent surgical resection of focally dysplastic cortex at Phoenix Children’s Hospital between 2008 and 2014 were examined using immunohistochemistry. Primary antibodies against GFAP and Iba1, as well as structural staining using hematoxylin and eosin (H&E), were incubated on sections and further analyzed using bright‐field microscopy. A pattern of perivascular activated microglia was observed in five patients around at least one blood vessel, while a pattern of non‐localized ramified microglia was observed in the other three patients. No identifiable pattern of astrocytic distribution was found. Thus, distinct patterns of microglia, rather than astrocytes, suggest dual underlying mechanisms of epileptogenesis.
    • Quality of Life and Pain After Transobturator Mesh Placement

      Coyne, Catherine A.; The University of Arizona College of Medicine - Phoenix; Hibner, Michael (The University of Arizona, 2017-04-28)
      Extreme controversy surrounds the uncertainty of pelvic mesh and sling devices to essentially cure patients of stress urinary incontinence (SUI). A relatively new product that has taken the market by storm is the tension free Vaginal Tape‐ Obturator (TVT‐O) mesh by Ethicon, Gynecare. It has obtained Center for Disease Control approval and labeled a “clinically proven, safe product with a 90% cure rate for urinary incontinence,” according to the manufactures website (Ethicon, Gynecare)4, 8. One side effect that is known about this particular device is its ability to leave patients post surgery with unbearable, chronic pelvic pain2. Although the mesh is needed to prevent urinary incontinence, it is pivotal that the quality of life of our patients does not suffer appreciably with elective, non‐life threatening procedures. Another common mesh product is the pelvic sling by Monarc. One‐study reports more than 95 percent of patients who underwent elective surgery with the insertion of Monarc sling achieved complete dryness and did not require the use of pads following the procedure22. These are successful outcomes, but what occurs with the minority of patients that have unfavorable outcomes such as chronic pain12, 15, 16? A retrospective study was completed to deduce the onset of pain and severity of pain caused by the TVT‐O mesh and Monarc mesh‐utilizing data from Dr. Hibner’s patients. There were 19 chronic pelvic pain patients with an average age of 50, standard deviation of 11 years, seen by Dr. Hibner and his colleagues. These patients completed the International Pelvic Pain assessment form upon their first visit to the office and SF‐36 scores of physical and mental scores were obtained. Results found physical scores of 29.5 and mental scores of 36 in pelvic pain patients, which were higher than certain other chronic, medical diseases1. We were able to conclude that patients with pelvic pain from mesh have lower physical and mental SF‐36 scores than patients with other chronic diseases representing a decreased quality of life overall.
    • Quantitative Factors Correlated with Increased Length of Stay for Adult Patients Presenting to the Emergency Department with Abdominal and Pelvic Pain

      Spiro, Joshua; The University of Arizona College of Medicine - Phoenix; Yarmush, Joel (The University of Arizona., 2017-05-19)
      Abdominal/pelvic pain is one of the most common reasons that patients present to hospital emergency departments (ED). With 129.8 million emergency department visits per year nationally, efficient triage and admission of these patients from the ED is essential. At the New York Methodist Hospital (NYMH) ED, patients presenting with abdominal/pelvic pain are evaluated based on a series of factors such as pain scores, past medical history, physical exam, and laboratory tests. Depending on these factors, clinicians observe, evaluate, and treat their patients requiring varying lengths of stay in the emergency department before either being discharged or admitted to the hospital. Physicians must weigh the benefits and risks of each evaluation they perform knowing that their resources may be needed more urgently by other patients. Determine the quantitative factors correlated with an increased length of stay for adults presenting to the emergency department with abdominal or pelvic pain. Increases in factors such as age, pain, BMI, and vital signs will correlate with an increased length of stay in the emergency department as well as an increased rate of admission to the hospital. Data regarding the above factors were abstracted from a sample of adult patients (n=347) presenting to the New York Methodist hospital emergency department from June 1st, 2013 to May 31st, 2014. The review of patients presenting to the emergency department with abdominal/pelvic pain demonstrated that patients with lengths of stay greater than four hours had a significantly higher value for age, weight, BMI, and blood pressure compared to those with lengths of stay less than four hours. Additionally, patients that were admitted to the hospital had a statistically significantly higher value for age, pain scores, systolic blood pressure, and heart rate. The identification of factors associated with longer lengths of stay provides the first step in identifying how to improve patients’ access to care in a more time efficient manner. Understanding what factors account for delays in care and discharge will allow for more efficient allocation of time and resources to the patients that need it most.
    • Radiology Reporting Preferences of Non‐Radiologist Ordering Clinicians: Prose? Do you even list?

      Al‐Abbadi, Tabarik; The University of Arizona College of Medicine - Phoenix; Gridley, Daniel (The University of Arizona., 2017-04-20)
      The purpose of this survey was to expand the limited knowledge regarding non-radiologist physician preferences in radiology report styles and content.
    • Reproductive Life Planning in the Refugee Community: Focus on the Role of Men and Religion

      Hussain, Jawad; The University of Arizona College of Medicine - Phoenix; Johnson‐Agbakwu, Crista (The University of Arizona., 2017-05-09)
      Health literacy is the degree to which individuals have the capacity to understand basic health information and services needed to make appropriate health decisions. Women seen at Maricopa Integrated Health System (MIHS) Refugee Women’s Health Clinic (RWHC) are routinely offered education on developing a Reproductive Life Plan (RLP). In order to influence women’s reproductive health and medical decision‐making, there is a need to tailor RLP counseling to engage their male partners in the refugee community. We aimed to assess increased knowledge on preconception care related to the importance of developing a RLP, perspectives on birth spacing, and the influence of men as well as religion in medical decision‐making. We aimed to identify the refugee community’s receptivity to culturally and linguistically appropriate audiovisual modalities. Study participants comprised 120 refugees (39 men and 81 women) including couples, across the respective target languages with pre‐ and post‐Likert scale surveys assessing perspectives on RLP, birth spacing, the role of religion, and readiness for behavior change. Summary statistics examined changes in pre‐ and post‐Likert scale survey responses with responses dichotomized as Strongly agree/Agree compared against all other responses. A higher frequency of male respondents agreed about knowing what RLP means in the posttest relative to pretest (71.8% to 89.7%, P = 0.016) as well as 'Not having children…' (41% to 64.1%, P=0.035). Female respondents were more likely to agree to 'Know what RLP means' (76.5% to 86.4%, P =0.039) and 'Having a baby soon after…' (65.4% to 76.5%, P =0.035) after the training. They also were less likely to agree that 'RLP is about birth control' (71.6% to 59.3%, P =0.021). Amongst Muslim participants, we found improvement in knowing what RLP means (65.5% to 87.9%) and that it is important for men to have a RLP (67.2% to 84.5%). Cronbach’s alpha was used to measure internal inconsistency, with most values less than 0.5 and deemed unacceptable. Only one value, birth spacing, was > 0.6 and deemed questionable. There was the same degree of concordance, yet there also was discordance in the direction of opinions between women and men pre vs post‐test answers. When comparing couples pre and posttest, there was no significant differences observed across genders. This is the first reported U.S. initiative to provide a culturally and linguistically appropriate preconception health education. Project had demonstrated ability to mobilize several ethnic communities around the RLP. Respondents among both genders were more likely to agree about knowing what RLP means. The most challenging aspect of our community mobilization efforts was recruiting a larger sample size. Another limitation was the use of the Likert scale in a population with low literacy as there were some discrepancies in responses to negatively‐worded questions. Future studies could use a visual analog scale of smiley faces to assist those with limited literacy and incorporate a more global feel.