• Assessment of the Analgesic Efficacy of Intravenous Ibuprofen in Biliary Colic

      Zurcher, Kenneth; The University of Arizona College of Medicine - Phoenix; Quan, Dan (The University of Arizona., 2017-05-22)
      It is estimated over 20 million people aged 20‐74 have gallbladder disease, with biliary colic being a common and painful symptom in these patients. Likely due to the relatively recent approval of intravenous ibuprofen use for fever and pain in adults, no assessment of its analgesic efficacy for biliary colic currently exists in the literature. In this double‐blind, randomized, controlled trial we aim to assess the analgesic efficacy of intravenous (IV) ibuprofen given in the emergency department (ED) for the treatment of biliary colic. Analgesic efficacy was evaluated using a visual analog scale (VAS) to assess for a decrease in pain scores. A VAS score decrease of 33% in relation to the VAS taken at the time of therapy drug administration was considered a minimum clinically important difference (MCID) in patient‐perceived pain. A VAS was administered in triage upon enrollment, at the time of therapy administration, at 15‐minute intervals during the first hour post‐administration, and 30‐minute intervals in the second hour. As the standard of care for suspected biliary colic at the study institution is administration of a one‐time dose of IV morphine, patients were not denied initial morphine analgesia and were permitted to receive “rescue” morphine analgesia at any point during their ED course. A total of 22 patients completed the study. 9 were randomized to the IV ibuprofen arm, 9 to placebo, and 4 were excluded for a diagnosis other than biliary colic. Mean VAS values at time 0 to time 120 decreased from 5.78 to 2.31 in the ibuprofen group, and from 5.89 to 2.67 in the control group. There was no statistically significant difference in treatment status of ibuprofen vs. placebo (p‐value (p.) 0.93), though there was a significant decrease in the measured VAS scores over time (0 minutes to 120 minutes, p.0.031) in both ibuprofen and placebo groups. A statistically significant and clinically important decrease in average VAS scores were seen in both placebo and ibuprofen groups (55% and 60%, respectively). There was no difference in time needed to achieve a clinically significant reduction in pain between groups. The sample size of this study may be inadequate to fully assess the analgesic efficacy of IV ibuprofen for biliary colic. In the analysis group (n=18) no significant difference in treatment status of ibuprofen vs. placebo was seen, however there was a statistically and clinically significant decrease in pain in both groups. Two potential confounding factors may have affected the trial’s results: administration of standard‐of‐care IV morphine following initial triage assessment, and the inherent episodic and self‐limited nature of biliary colic.
    • Does Adjunctive Pain Control with Dexmedetomidine Improve Outcomes in Patients with Adolescent Idiopathic Scoliosis?

      Spaulding, Kole; The University of Arizona College of Medicine - Phoenix; Shrader, M. Wade (The University of Arizona., 2017-05-19)
      Adolescent Idiopathic Scoliosis (AIS) is typically treated surgically by Posterior Spinal Fusion (PSF) surgery. Intravenous analgesics and oral opioids are commonly used for pain management. Several adjunct therapies are used in addition to the standard treatments. One of these therapies is the use of dexmedetomidine (dex). Though dex has been found to be an effective sedative for post‐operative patients, there are also several adverse effects that are associated with its use. The purpose of this study was to investigate the effectiveness and overall benefit of using dex for pain control for patients undergoing PSF for AIS. IRB approval was obtained. A group of 43 patients with AIS undergoing PSF and using Dex for adjunctive pain control were matched with 43 patients who did not use Dex. The groups were matched based on gender, age, height, weight, and level of spinal fusion. During the patients’ post‐operative hospital stay, the total opioid use and clinical pain scores were compared between the two groups using t‐tests, with significance set at p<0.05. Total opiate use was 239.6 morphine equivalent doses in the non‐Dex (control) group and 246.2 in the group that received Dex (p=0.72). The average pain score in the control group was 2.3, and the group that received Dex was 2.6 (p =0.43). There were no differences in the complication rate between the two groups, specifically the oversedation rates and pulmonary complications. Lastly, the average length of stay for the control group was 4.8 days compared to the dex group, which was 5.0 days (p=0.35). Although adjunctive pain modalities may be very useful in the treatment of postoperative pain after PSF in patients with AIS, the use of Dex in this cohort did not improve pain scores, lower opioid use, or lower the LOS. Based on these results, we do not recommend the routine use of dexmedetomidine as an adjunctive pain control modality. Adjunctive modalities are important in pain control in patients with AIS undergoing PSF, but the use of dexmedotomidine was not effective in improving pain control.
    • 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.
    • Triage of Trauma Patients Injured By Large Animals: Do Urban Doctors Undertriage?

      Stevenson, Justin; The University of Arizona College of Medicine - Phoenix; Katz, Eric (The University of Arizona., 2017-05-19)
      In the United States the responsibility to develop criteria for trauma patient’s triage status rests upon individual hospitals rather than the American College of Surgeons. Traumatic injuries from large animals represent a potential need for expanded hospital resources. Urban emergency departments are less likely to regularly see patients with large‐animal related injuries and might be expected to underestimate the predicted injuries. There is scarce research on the topic of initial triage designation for large‐animal related injuries. The aim of this study is to investigate the adequacy of the initial triage designation given to patients presenting with injuries from animals larger than themselves at an urban, safety net, academic Emergency Department and Trauma Center (ACS Level 1 Adult, Level 2 Pediatric). A retrospective chart review was performed on patients presenting to the emergency department (ED) from Jan 2006 until September 2015 with injuries resulting from animals larger than the patient. A total of 213 patients met the inclusion criteria. Our study found that trauma patients injured by large animals who are triaged as low priority have dispositions that are not statistically different from those with higher initial prioritization.
    • 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.
    • Systematic Review and Meta‐Analysis of Clinical Outcomes of Fractures Fixed with the Surgical Implant Generation Network (SIGN) Intramedullary Nail

      Sonenthal, Nechama; The University of Arizona College of Medicine - Phoenix; McLaren, Alex (The University of Arizona., 2017-05-18)
      The (Surgical Implant Generation Network) SIGN Intramedullary (IM) nail is designed to fix long bone fractures without using a costly C‐arm imaging device. It is distributed for free to countries in need, allowing for elevation of care from the standard, lengthy traction treatment in those countries to clinically superior IM nailing. This paper compares the clinical outcomes of the SIGN IM nail to those of the IM nails used in developed countries with use of a C‐arm. The terms “Surgical Implant Generation Network” and “union” were searched in four databases. Primary studies of SIGN IM nails were included and their outcomes, including union rate, time to union, and complications, were recorded and compared to historical data of IM nails used in developed countries. Overall, there is a similar union rate in bones fixed with SIGN IM nails (94.6%) versus bones fixed with IM nails in developed countries (92.3%) (p = 0.009, OR = 1.67), while some bone types (tibia and femur) demonstrated a lower union rate when individually stratified (p = 0.008, OR = 0.26 and p = 0.002 and OR = 0.15, respectively). Mean time to union for all bone types combined showed no significant difference between SIGN IM nails and IM nails used in developed countries (p = 0.26). Complications rates were similar between SIGN IM nails and IM nails used in developed countries. It is possible for the SIGN IM nail to be used to fix long bone fractures in developing countries with outcomes comparable to the IM nail used in developed countries.
    • The Use of Pulmonary Dead Space Fraction to Identify Risk of Prolonged Mechanical Ventilation in Children after Cardiac Surgery

      Siddiqui, Muniza; The University of Arizona College of Medicine - Phoenix; Willis, Brigham (The University of Arizona., 2017-05-18)
      Children with prolonged mechanical ventilation after cardiac surgery have a higher risk for poor outcome due to a variety of ventilator‐associated morbidities. It therefore becomes essential to identify these children at higher risk of prolonged mechanical ventilation as well as find methods to identify children ready to be extubated as early as possible to avoid these complications. One physiological variable, the pulmonary dead space fraction (VD/VT), has been suggested as a possible indicator of prolonged mechanical ventilation. VD/VT essentially measures the amount of ventilated air that is unable to participate in gas exchange. Can VD/VT be used successfully in children undergoing cardiac surgery to identify those at risk for prolonged mechanical ventilation and identify those ready for extubation? Retrospective chart review of 461 patients at Phoenix Children’s Hospital in the Pediatric Cardiac Intensive Care Unit since the initiation of standard application of the Philips NM3 monitors in October 2013 through December 2014. From the 461 patients screened, only 99 patients met all the inclusion criteria. These 99 patients consisted of 29 patients with balanced single ventricle physiology and 61 patients with two ventricle physiology. Initial postoperative and pre‐extubation VD/VT values correlated with length of mechanical ventilation for patients with two ventricle physiology but not for patients with single ventricle physiology. Additionally, pre‐extubation VD/VT values of greater than 0.5 indicated higher rates of extubation failure in two ventricle patients. Conclusion: For children with two ventricle physiology undergoing cardiac surgery, VD/VT should be used clinically to estimate the length of mechanical ventilation for these children. VD/VT should also be checked in these patients before attempting to extubate. If VD/VT is found to be higher than 0.5, extubation should not be attempted since the patient is at a much higher risk for extubation failure.
    • Follow-Up Instrument Development and Results from a Trial Cohort for Graduates of the Integrative Medicine in Residency Certificate Program

      Perkins, Jaime; The University of Arizona College of Medicine - Phoenix; McClafferty, Hilary; Brooks, Audrey (The University of Arizona., 2017-05-18)
      Integrative medicine (IM) is a unique clinical paradigm that may be applied across numerous healthcare professions and diverse settings. With its focus on whole person health and lifestyle medicine, it advocates utilizing complementary and alternative medicine in addition to traditional treatments in order to achieve an individual’s optimal wellness. Literature supports how significantly this distinctive, promising field of practice can help reduce overall healthcare costs, alleviate the heavy burden of chronic disease, bolster efforts focused on preventive measures, and improve both patient outcomes along with practitioner wellbeing. In order to meet a growing demand for easily accessible, ongoing professional education in IM, the Arizona Center for Integrative Medicine launched an innovative curriculum called the Integrative Medicine in Residency (IMR). This online, two hundred hour, integrative course premiered with eight Family Medicine Residencies across the United States. The purpose behind this study was to aid in developing an appropriate compilation of instruments for a long-term follow‐up questionnaire for IMR graduates, distribute the survey to a trial cohort, and present a summary of the pilot survey results. The instrument was developed in order to: provide feedback on the course, aid in future program modification, determine how graduates implement what they learned through IMR, identify barriers to care, and help distinguish areas where physicians may need additional support to better incorporate IM into practice. The final forty‐four‐question survey, with quantitative and qualitative measures, was distributed in 2015 over three months to residents that graduated between 2011‐2014 via their program directors. All candidates were sent an email with an embedded link to Survey Monkey. Through this series of online, self‐reported responses, the questionnaire was filled out in real time and results were auto‐populated into a secure excel file for further statistical analysis. Our trial cohort attained valuable responses from thirty‐one graduates. Results demonstrated that students were largely satisfied with their education and pleased with the personal and professional impacts following their IMR training; however, barriers to care most notably reported were time, cost, and patient receptivity. This study emphasizes the importance of providing easy access to ongoing IM education for physicians, while also highlighting the equal importance of future research into how to better support healthcare providers seeking to provide the comprehensive IM therapy all patients deserve.
    • Evaluation of an Opt-Out HIV Screening Program in the Maricopa County Jails

      Nelson, Erin Da‐Hye; The University of Arizona College of Medicine - Phoenix; Taylor, Melanie; Mullany, Charles (The University of Arizona., 2017-05-12)
      Since inmates are a population disproportionately affected by HIV, correctional settings are important sites for delivering HIV services. The Maricopa county (Phoenix Area) jail system is the 4th largest in the nation. In 2011, the Maricopa County Correctional Health Service implemented an opt‐out HIV screening program for individuals booked into the Maricopa County Jails (MCJ). The aims of this study were to determine for the years 2012‐2014: • The number of inmates screened for HIV • The HIV positivity rate • The number of newly diagnosed patients • The clinical characteristics of the newly diagnosed HIV positive patients Five to seven days after booking, inmates are offered HIV screening. These laboratory records were used to determine the number of inmates tested and positivity. Prior history of previous HIV diagnosis was obtained from Maricopa public health records. Retrospective chart review of the MCJ health and case management records, including Ryan White forms, was performed to gather gender, age, race/ethnicity, sexual orientation, drug use, homelessness and co‐morbidities of newly HIV‐infected persons, such as Hepatitis C and prior STDs. Categorical factors were compared between groups with the Chi‐square test. Means were compared using a standard t test. P values ≤0.05 were considered significant. A total of 319,575 persons were booked and 46,346 were screened (14.5%) for HIV during the study period. The majority of booked inmates were male (76.9%) and Caucasian (50.8%). The mean age of inmates was 36 years. There were 70 newly HIV‐diagnosed patients. Chi squared and t tests comparing newly diagnosed individuals to the general jail population revealed statistical significance for male gender (p=0.02), African American race (p=0.04), and age (p=0.003). Undiagnosed HIV, including AIDS (CD4 counts <200), is an important issue among individuals booked into the MCJ. Compared to the general jail population, HIV is more likely to be diagnosed in males rather than females, younger patients, and African‐American patients. Additionally, IV drug use, polysubstance abuse, other STDs (particularly syphilis), high risk sexual activity, Hepatitis C and homelessness were common among HIV positive patients. Surveillance should be continued and include more patient education on the importance of screening. Furthermore, targeting high‐risk populations may result in even greater numbers of individuals being diagnosed and treated. Within the next year, all patients at the MCJ will also be offered screening for Hepatitis C, chlamydia, gonorrhea and syphilis. This may also result in more patients agreeing to be screened, and subsequently diagnosed with HIV.
    • Effects of High Vs. Reduced‐Dose Melphalan For Autologous Bone Marrow Transplantation in Multiple Myeloma On Pulmonary Function: A Longitudinal Study

      Nikolich‐Zugich, Tijana; The University of Arizona College of Medicine - Phoenix; Knox, Kenneth (The University of Arizona., 2017-05-12)
      Bone marrow transplants (BMT, also hematopoietic stem cell transplants or HSCT/SCT) are one of the greatest medical achievements of the 20th century. They offer a treatment for a host of malignant and nonmalignant hematopoietic disorders, genetic diseases and solid tumors that could otherwise be fatal. Studies have found that 60% of patients undergoing BMT develop pulmonary complications (PC), and 1/3 of those require intensive care after transplantation. Despite the potential pneumotoxicity of induction agents, to date there have been no longitudinal studies following pulmonary function in this high‐risk patient population. This study reviewed patient who underwent autogeneic bone marrow transplant for multiple myeloma at Banner University Medical Center – Tucson (formerly University of Arizona Health Network) from January 1, 2003 through December 31, 2013. Pretransplant evaluatin and pulmonary function testing data were obtained and stratified between high dose (standard) Melphalan (200 mg/ms2) and reduced dose (140 mg/ms2). Statistically significant differences were present between the 2 groups at baseline for DLCO but disappeared at 6 and 12‐month followup, while a statistically significant difference for FEV1/FVC ratio was seen at baseline and 6 months but disappeared at 12‐month follow‐up. There were no statistically significant differences seen with FEV1 between the two groups. Given there is no difference in mortality and relapse outcomes between the groups, the standard of care dosing for Melphalan is not associated with an increase in pulmonary morbidity.
    • Histologic Comparison of Pressure and Autoimmune Wounds

      Nanda, Alisha; The University of Arizona College of Medicine - Phoenix; Gottlieb, Marc (The University of Arizona., 2017-05-12)
      The cell make‐up and architecture of a wound is generally not explored before treatment is started. This pilot study will potentially be able to differentiate the histologic makeup of different wound etiologies and therefore start to elucidate a more targeted therapy to treat a wound with the hypothesis that etiology of wound is associated with a set of histologic characteristics. 12 samples of pressure wounds and 13 samples of autoimmune connective tissue wounds were examined and characterized under microscopy. Types of cells, necrosis, granulation, and inflammation, among other characteristics were studied. The autoimmune wounds displayed a statistically significant increase in lymphocytes, chronic inflammation, and fibrosis than in the pressure wounds. There are apparent differences in histology and morphology of wounds of different etiologies, as hypothesized. This suggests the possibility of requiring specific treatments for the varying wound types.
    • Clinical Symptoms and Modified Barium Swallow (MBS) Score in Evaluation of Pediatric Patients with Dysphagia and Aspiration

      Monks, Sarah; The University of Arizona College of Medicine - Phoenix; Williams, Dana (The University of Arizona., 2017-05-12)
      Dysphagia with aspiration (DA) is the most common presenting symptom of patients at Phoenix Children’s Hospital’s Aerodigestive Clinic (ADC). Dysphagia with aspiration is associated with respiratory and gastrointestinal symptoms, chronic oral thickener use to prevent aspiration, secondary constipation, and occasionally, enteral tube dependency. MBS is considered the gold standard in instrumental assessment of dysphagia; it is used to evaluate severity and guide thickener treatment of DA patients, monitor progress with serial studies, and for re‐evaluation after intervention when appropriate. Previous evaluation of patients with deep interarytenoid notch given laryngoplasty injection included patients with improvement in symptoms despite post‐intervention MBS scores worsening, and vice versa, challenging the use of MBS as a longitudinal tool in clinical evaluation of patients with dysphagia and aspiration. Is MBS severity score reflective of clinical symptoms in pediatric patients with dysphagia and aspiration? A clinical questionnaire of DA symptoms was developed with input from the ADC physicians. The questionnaire was administered over 3 months to patients aged 1‐3 years who had an MBS evaluation within 6 months of their initial ADC visit, standard of care for patients with DA. 17 symptoms (12 GI and 5 pulmonary) were given a numerical score 0‐4 based on parent recall of frequency. MBS was scored 1‐10 on the thickness of liquid recommended for aspiration prevention. Individual symptoms and symptom sets (total questionnaire score, GI score, pulmonary score) were compared to MBS score using linear regression model. 30 patients were surveyed with median MBS score of 6 and range from 0 to 8. 18 patients had an MBS score above 6. Median questionnaire score was 18, with a range from 4 to 53. All analysis showed no significant correlation between individual symptoms or symptom sets and MBS score; the highest R2 value for any individual symptoms was 0.05. Among ADC patients with DA, MBS severity score did not correlate with severity or specificity of symptoms, questioning the use of MBS as a tool for diagnosing severity of persistent DA or as a repetitive tool in assessing response to laryngeal cleft surgical interventions and thickener wean therapy. These findings challenge the use of repetitive MBS in the ADC patient population. Our ultimate goal is to develop a combined clinical and radiologic tool that would minimize radiation exposure and unnecessary thickener treatment while promoting best clinical outcomes.
    • The Seasonality of Eosinophilic Esophagitis Flares in Children and Adolescents in Arizona

      Manley, Kelsi; The University of Arizona College of Medicine - Phoenix; Williams, Dana (The University of Arizona., 2017-05-11)
      Aeroallergens are implicated in the pathogenesis of eosinophilic esophagitis, which has a recurrent or relapsing nature. We aim to determine the incidence of seasonal disease recurrence, referred to as flares, of eosinophilic esophagitis in patients in Arizona with eosinophilic esophagitis in remission, and to characterize the presence of allergy and other disease co‐morbidities in patients that experience disease flare. A retrospective study was performed by analyzing data from visits of patients aged 5 to 18 years coded for eosinophilic esophagitis in remission seen by the Phoenix Children’s Hospital Pediatric Gastroenterology Department between June 2010 and June 2011. The data included 148 patients and 326 clinical visits. Data identified demographic information, allergy, and other disease co‐morbidities. Arizona seasons were defined as: spring from February 15 to June 15, and fall from September 1 to November 30, according to the typical pattern of allergen pollination. To analyze incidence and season of flares, statistical methods used included the Chi‐square tests and logistic regressions. Ninety‐four of 148 patients (63.5%) flared during the study period. An increased incidence of flares in the fall compared with other seasons was statistically significant (p = 0.041). Flares in the spring also had an increased incidence. Of the 94 patients that flared, 70 patients (74.5%) had environmental allergy, 83 (88.3%) had food allergy, and 66 (70.2%) had both environmental and food allergy. Our findings suggest a role for seasonal environmental allergens in the pathogenesis of eosinophilic esophagitis and disease flares in children in Arizona, particularly those with food allergy, environmental allergy, or both.
    • Tumor Associated Antigens Harbor Readily Defined and Universally Immunogenic Regions Relevant For Cancer Immunotherapy

      McCurry, Dustin; The University of Arizona College of Medicine - Phoenix; Cohen, Peter; Gendler, Sandra (The University of Arizona., 2017-05-11)
      Recent advances in cancer immunology, highlighted by immune checkpoint inhibitors, have demonstrated that immunotherapy is a viable option in the oncologist’s armamentarium. Despite these advances, many patients are nonresponders. Preliminary studies have suggested that non-responders lack a de-novo anti-tumor antigen immune response that can be unmasked by checkpoint blockade; thus, strategies to induce anti-tumor immune responses are needed. We hypothesized that many tumor associated antigens (Ag) are readily susceptible to immune attack, but only in the context of identifying the tumor antigen epitopes that can reliably initiate an immune response, regardless of individual patient human leukocyte antigen (HLA) haplotype restrictions. We further hypothesized that epitope prediction strategies which seek to identify pan- or highly promiscuous-HLA binding epitopes would reduce the number of potential candidates and be more likely to accurately identify high-priority tumor Ag epitopes. Utilizing known HLA-serotype frequencies and setting a threshold of ninety percent of population coverage, regardless of race or ethnicity, twenty-nine different HLA-DRB1 haplotypes were chosen for antigen prediction utilizing the open source epitope prediction algorithm netMHCIIpan. Predictions were also performed for HLA-A serotypes utilizing the open source algorithm netMHCpan. Predicted epitopes were synthesized in the form of synthetic long peptides and tested in immune system sensitization assays involving unfractionated peripheral blood mononuclear cells (PBMC). Briefly, PBMC were subjected to a two-step culture, first synchronizing their exposure to the long peptides with aggressive surrogate activation of innate immunity, followed by IL-7-modulated T-cell hyperexpansion. Predictions resulted in identification of highly promiscuous-HLA binding epitopes. Unexpectedly, these epitopes clustered together forming high priority regions: unique “hot spots” with high densities of promiscuous HLA-binding epitopes from the widely expressed oncoproteins MUC1, HER2/neu and CMV-pp65 (p<0.0001, for predicted HLA-DRB1 binding affinities, compared to non-hot spot regions). Added synthetic long peptides (>20aa) derived from “hot spot” regions of MUC1, HER2/neu, and CMVpp65 reliably produced selective and sustained expansion of both CD4+ and CD8+ peptide-specific, interferon-γ (IFNγ)-producing Tcells when synchronized with step 2 exposure to exogenous IL-7 (p<0.0001 and p=0.0048, for CD4+ and CD8+ Ag-specific T-cells, respectively, compared to T-cells directed against peptides from non-hot spot regions). “Hot spot” peptide Ag-specific T-cells preferentially recognized endogenous tumor derived MUC1, either in MUC1 expressing tumor cell killing assays (p=0.038, compared to non-peptide Ag-specific T-cells) or as MUC1 tumor lysate when pulsed onto restimulatory PBMC (p=0.022 and 0.025, for CD4+ and CD8+ T-cells, respectively, compared to T-cells directed against peptides from non-hot spot regions). This mechanistically rational antigen selection sequence, effective even for unvaccinated donors, regardless of HLA-haplotype, enables rapid identification of tumor protein regions relevant for cancer immunology, including adoptive immunotherapy, vaccines, and even identification of tumor neo-antigens unique to each patient.
    • Training of Community Health Workers: Recognition of Maternal, Neonatal and Pediatric Illness

      McCabe, Chris; The University of Arizona College of Medicine - Phoenix; Yoblonski, Lara (The University of Arizona, 2017-05-11)
      This systematic review focuses on improving recognition and treatment of acute medical conditions in pregnant women, infants and children in low and middle income countries by Community Health Workers (CHWs). By examining critically selected articles from different electronic databases, this review seeks to organize and present the important characteristics of a training program aimed at reducing maternal, neonatal and childhood mortality. Data in the form of peer‐reviewed and published articles were collected using three public databases – PubMed, Ovid and EMBASE – using specific search terms. Greater than 300 articles where found using the specific search terms. Those articles were then processed through a series of inclusion and exclusion criteria resulting in a cohort of papers which were then individually analyzed for content. After critical analysis of all 15 publications included in the study, it becomes clear that training programs are incredibly diverse. These four aspects of training programs appear to be the most variable between the studies: size of the training program, length of the training program, training assessment and follow‐up refresher courses. Training programs that are shorter in duration or greater in class number do not seem to be any less effective than longer programs with fewer participants. Future studies should be performed in which one training program with identical training techniques, lengths, and focuses is taught in different regions. The impact that this study has on the literature is as follows: Training programs of shorter duration seem to be as effective as their longer counterparts. Finally, there is a clear need for more robust, standardized and geographically and culturally diverse training programs to more effectively study training methods.
    • The Role of Gilt in the Cross Presentation of the Melanoma Antigen gp100

      Johnson, Kenneth; The University of Arizona College of Medicine - Phoenix; Hastings, Karen Taraszka (The University of Arizona., 2017-05-10)
      In this study we examine the utility of using CD8+ T cell hybridomas to measure the ability of bone marrow dendritic cells (BMDCs) to internalize cancer proteins and display them to cytotoxic T cells, a process termed cross‐presentation. We test the ability of a newly generated T cell hybridoma called BUSA14 to detect cross‐presentation of the melanoma antigen gp100. BUSA14 produces a dose‐dependent response to human and mouse gp100 peptides. However, cross‐presentation of gp100 by BMDCs using SK‐MEL‐28 human melanoma cell lysates or direct MHC class I‐restricted presentation by B16 murine melanoma cells was not detected. Both SKMEL‐28 and B16 cells express gp100 protein by immunoblot, and gp100 as a membrane bound protein may be concentrated by cell fractionation techniques. We validated our crosspresentation assay with another T cell hybridoma B3Z to detect cross‐presentation of the model antigen ovalbumin. Lastly, we determined that although BUSA14 expresses the coreceptor CD8, BUSA14 lacks CD3 expression, which likely impairs the ability of this hybridoma to respond to engagement of the T cell receptor and contributes to the inability to detect presentation of native gp100 protein. To resolve these issues, we plan to use primary gp100‐specific T cells from pmel mice expressing the same T cell receptor as the BUSA14 hybridoma to detect presentation of gp100 protein. Ultimately, we plan to evaluate the requirements for cross‐presentation of gp100, including a role for gamma‐interferon‐inducible lysosomal thiol reductase (GILT), a disulfide bond reducing enzyme.
    • The Effectiveness of Military Medicine in Counterinsurgency Campaigns

      Ly, Jane; The University of Arizona College of Medicine - Phoenix; Beyda, David (The University of Arizona., 2017-05-10)
      While medical diplomacy has played a large role in US counterinsurgency (COIN) campaigns, few studies have been done to show their effectiveness. This study is a systematic review based on literature published by July 2014, looking at military medicine’s role in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Both scientific and military databases were searched and yielded an initial 1,204 papers; however, these were later narrowed down to four articles, mostly restricted by the requirement of structured, scientific methods. These four studies were not well‐powered and focused on such different topics that no real conclusion could be drawn on the topic. In the end, the real value of the study was to show that despite the significant amount of resources poured into these COIN medical operations, very little study has been done to see if they have any effect.
    • 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.
    • 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.
    • Comparing Transcutaneous to Serum Bilirubin after Phototherapy in the Outpatient Setting

      Makarova, Natasha; The University of Arizona College of Medicine - Phoenix; McMahon, Shawn (The University of Arizona., 2017-05-10)
      Currently few studies have investigated the accuracy of using transcutaneous bilirubinometry after phototherapy especially in the outpatient setting. The purpose of this study was to evaluate the accuracy of transcutaneous bilirubin measurements (TCB) after phototherapy for neonates with jaundice. At the Maricopa Integrated Health System, neonates who undergo phototherapy for hyperbilirubinemia come in for outpatient follow‐up at the Comprehensive Health Center following their discharge. For those neonates, current protocol calls for serum bilirubin (TSB) to be measured to properly monitor bilirubin levels, however transcutaneous measurements were made and recorded as well. In this study, we compared the values of total serum bilirubin and transcutaneous bilirubin in jaundiced neonates who underwent phototherapy. From October 2013‐April 2015, a total 67 healthy infants were seen in the Pediatric Clinic who had received phototherapy in our hospital, only 36 (54%) of those met minimum data criteria to be included in the study. The absolute difference between mean serum bilirubin and transcutaneous bilirubinometry in healthy outpatient newborns who received inpatient phototherapy was 0.4 and is clinically insignificant. The average time from hospital discharge to return to clinic was 47 hours. We conclude that for the outpatient physician, transcutaneous bilirubinometry can be used following phototherapy, which facilitates faster, more convenient, and painless follow‐up visits.