• Complex Transcriptional Regulation of the Fibroblast Growth Factor‐23 Gene by 1,25‐Dihydroxyvitamin D3: Evidence for Primary and Secondary Mechanisms

      Saini, Rimpi; The University of Arizona College of Medicine - Phoenix; Haussler, Mark R. (The University of Arizona., 2016-03-25)
      Fibroblast growth factor 23 (FGF23) is a circulating phosphaturic hormone synthesized in osteocytes and osteoblasts that corrects hyperphosphatemic states by inhibiting renal phosphate reabsorption via the fibroblast growth factor receptor‐1 and its klotho coreceptor. In a closed endocrine loop, 1,25‐dihydroxyvitamin D3 (1,25D) induces FGF23 expression in bone, with the phosphaturic peptide in turn acting at the kidney to feedback repress CYP27B1 to suppress production of 1,25D. FGF23‐null mice cannot correct the severe hyperphosphatemia and ectopic calcification that results from the 1,25D‐stimulated calcium and phosphate intestinal absorption and renal reabsorption. Furthermore, abnormal concentrations of FGF23 have been linked to several potentially fatal pathologies, including chronic kidney disease and cardiovascular events. FGF23 synthesis is induced by the 1,25D‐bound vitamin D receptor (VDR), resulting in FGF23‐signaled suppression of the phosphate transporters NaPi‐IIa and NaPi‐ IIc, decreasing renal phosphate reabsorption and resulting in urinary phosphate excretion. Previous reports document upregulation of FGF23 mRNA by 1,25D; however the exact molecular mechanism(s) for this phenomenon remain unknown. In preliminary research, we identified five functional vitamin D responsive elements (VDREs) in the human FGF23 gene region remote to the promoter that may directly control FGF23 gene transcription. However, these VDREs displayed only modest induction activity, implying that a secondary mechanism for transactivation by 1,25D must exist to explain the observed high magnitude induction of FGF23 mRNA and protein by vitamin D, in vivo, and in cultured osteoblasts. In the present study, we disprove our hypothesis that membrane and extracellular matrix proteins, namely klotho and/or osteopontin, induced by 1,25D‐liganded VDR, secondarily generate a signaling cascade to increase FGF23 production. Instead, by truncation and point mutagenesis, we characterized a novel cis‐regulatory module in the proximal promoter of mouse FGF23, located between ‐400 and ‐200 bp from the transcriptional start site. A ‐0.6 kb construct of the murine FGF23 promoter demonstrates a 4‐fold induction in response to 1,25D when transfected into human leukemia (K562) cells. Mutation of one of the ETS1 sites at ‐346 bp within this construct, or an adjacent VDRE/Nurr1 site, reduces the transcriptional response to 1,25D to that of a minimal ‐0.06 kb promoter construct. Thus, the composite ETS‐VDRE/Nurr1 cis‐element identified herein may function in 1,25D‐elicited induction of FGF23 in a primary mechanistic manner via a novel VDRE located at ‐334 bp in the murine FGF23 promoter, and/or in a secondary fashion through 1,25D‐primary transcriptional activation of ETS1 and Nurr1. Also, we demonstrate a significant 1.7‐ to 2.0‐fold increase in transcription of a ‐1.0 kb murine FGF23 promoter construct in response to high calcium exposure of MC3T3 mouse osteoblastic cells. Thus, the FGF23 proximal promoter harbors cis‐elements that drive responsiveness to 1,25D and calcium, agents that induce FGF23 to curtail the pathologic consequences of their excess. Our results contribute to the understanding of the complex transcriptional regulation of FGF23 by providing evidence for cis‐regulatory elements within the FGF23 proximal promoter that are responsive to primary and secondary actions of 1,25D and calcium. Such findings may influence future therapeutic modalities in the treatment of FGF23‐related pathologies.
    • Evaluation of Skin Cancer Screenings in Tucson, Arizona from 2006‐2013

      Romano, Gianna; The University of Arizona College of Medicine - Phoenix; Harris, Robin (The University of Arizona., 2016-03-25)
      Background: One out of every three cancer diagnoses is a skin cancer, and the incidence of both melanoma and non‐melanoma type skin cancers is increasing. Skin cancers, including melanoma, are typically treatable if detected early. However, there is insufficient evidence to support recommendations to establish population based skin cancer screening programs. The specific aims of this study are 1) to evaluate characteristics of participants who attend a community skin cancer screening event and who are referred for follow up due to suspicious lesions, 2) to determine the proportion of participants with suspicious lesions identified at a community skin cancer screening event who complied with a request to visit a dermatologist or primary care physician, and 3) to evaluate attitudes toward sun protection practices, and perceived risk of developing skin cancer among participants who attend a community skin cancer screening and have a suspicious skin lesion. Methods: The Skin Cancer Institute sponsored a series of community skin cancer screening events in Tucson, Arizona from 2006 to 2013. Participants completed an American Academy of Dermatology screening form prior to a skin examination by a dermatologist. Participants with suspicious lesions identified at the examination who agreed to be contacted again received questionnaires 4 months after the initial screening to assess compliance with follow‐up recommendations, and their sun protection practices and risk perceptions. Results: 1979 community members attended the skin cancer screenings. The majority of the participants were Caucasian, females, had blue eyes and brown hair, were college educated, had no prior personal or family history of skin cancer, had health insurance but did not have a regular dermatologist, reported that they had never been to a skin cancer screening before, and stated that without this screening that they would not have their skin examined. 748 (37.8%) of community members were referred and instructed to see a dermatologist for further evaluation of a skin lesion. Of the 441 participants with a suspicious lesion who consented to participate in the follow‐up study, 120 returned a questionnaire; 90 (75%) reported that they followed up with a dermatologist or physician, and 30 (25%) did not. Of the 90 participants who followed up, 53% received a skin biopsy. The self reported diagnoses from the biopsies of the suspicious skin lesions were the following: 1% atypical or dysplastic nevus, 21% actinic keratosis, 16% basal cell carcinoma, 8% squamous cell carcinoma, 2% melanoma, and 38% did not have skin cancer. Conclusions/Impact: This study demonstrated that 38% of community skin cancer screening participants were referred for follow up due to a suspicious skin lesion being identified during a skin cancer screening event. It also appeared that 75% of those who responded to the follow‐up questionnaire complied with the request within four months, although the response rate for the follow‐up questionnaire was low. Therefore, implementing a formal reminder system following the skin cancer screenings may increase the percentage of participants who follow up with a primary care physician or dermatologist after the screening for further evaluation of their suspicious skin lesion.
    • The Characteristics of Physicians Elected and Serving in State Legislatures and the United States Congress

      Petterson, Matthew; The University of Arizona College of Medicine - Phoenix; Derksen, Daniel (The University of Arizona., 2016-03-25)
      Physician participation in United States governance has a long and honorable history, dating to the nation’s inception. At a time of unprecedented change in health policy ‐ to control the growth of health care costs, to cover the uninsured through Affordable Care Act (ACA) provisions, to improve quality, to meet the demand for health services as the population grows and ages ‐ the need for physician leadership to guide policy interventions has never been greater. Yet physician‐legislator participation has declined. There is little data about physicians involved in shaping health policy in state or federal legislative branches. This study examines the characteristics of physician‐legislators at the federal and state levels, and compares them to U.S. physicians in general. Using rosters fixed on March 13, 2014, the study reviewed biographic and demographic information on physician‐legislators. The study’s four hypotheses were that physician‐legislators were more likely to be (1) men than women, (2) members of the Republican Party than the Democratic Party, (3) a non‐primary care physician than a primary care physician, and (4) elected in the states where they completed graduate medical education than where they attended college. Ninety‐five physician‐legislators were identified in 51 legislative bodies in 2014. Physician‐legislators were more likely to be male than female, to be Republican than Democrat, and to be practicing in a non‐primary care than in a primary care specialty. Physician‐legislators were less likely to be elected in the state where they completed graduate medical education training than where they attended college. No personal factor was identified that linked the majority of physician‐legislators to the state in which they were elected.
    • Comparison of Postoperative Respiratory Function in Neonates with Hypoplastic Left Heart Syndrome Following First Stage Palliation

      Pandurangi, Sindhu; The University of Arizona College of Medicine - Phoenix; Willis, Brigham (The University of Arizona., 2016-03-25)
      Purpose Available surgical procedures in the first stage of the palliation of hypoplastic left heart syndrome (HLHS) are currently the Norwood procedure with Blalock‐Taussing (BT) shunt, Norwood with a Sano shunt (5.0 mm right ventricular‐pulmonary artery conduit), or a hybrid procedure combining surgical pulmonary artery band placement and catheter‐based closure of the ductus arteriosus. Following any of the three procedures, it is necessary for patients to be mechanically ventilated for a period of time; however, little is known about the differences in pulmonary function and outcome among the three groups. Methods We conducted a retrospective chart review of 14 neonates who underwent stage 1 palliation for HLHS, by hybrid procedure or Norwood procedure with BT or Sano shunts, at Phoenix Children’s Hospital from September 2013‐December 2014. Demographic, hemodynamic, and outcome information was collected. Heart rate, respiratory rate, mean arterial pressure, end tidal carbon dioxide (ETCO2), cerebral and renal somatic oximetry, mean airway pressure, ratio of partial pressure of arterial oxygen to inspired oxygen (PaO2/FiO2), partial pressure of arterial carbon dioxide (PaCO2), dead space fraction (Vd/Vt), and dynamic compliance were measured preoperatively, postoperatively, and at multiple time points from 6 to 120 hours postoperatively. Respiratory data was collected using the NM3 monitor (Philips Respironics, Pittsburgh, PA). Outcome measures collected included maximum postoperative lactate, time to extubation, hospital length of stay, and mortality. Results Of the 14 patients, 7 received the Norwood with BT shunt, 5 received the Sano shunt, and 2 received the hybrid procedure. Through linear regression analysis of groups stratified by shunt size, we found that the Vd/Vt ratios of the Sano and 3.0 mm BT shunt groups were higher at earlier times points, but became indistinguishable by 48 hours postoperatively (p=0.02). Linear regression of the 3 surgical groups comparing Vd/Vt across all times points did not show any significant differences (p = 0.79). Linear regression of dynamic compliance among the three groups across all time points also was not significant (p = 0.72). No significant difference was observed in dynamic compliance across all time points when groups were stratified by shunt size (p = 0.33). Examining differences between BT and Sano groups at each time point from 0‐ 120 hours postoperatively using Mann Whitney U analysis did not reveal significance. Analysis of outcomes of length of mechanical ventilation (p=0.61), hospital length of stay (p =0.99), and mortality (p>0.99) also did not differ significantly among the 3 surgical groups. Conclusion Our study identified that the 3.0 mm BT and Sano shunt group had higher Vd/Vt ratios throughout the first 48 postoperative hours. No other differences were found in Vd/Vt or dynamic compliance when surgical groups or shunt sizes were compared. Despite the early differences noted, lack of differences in outcome measures suggests that these early differences have little influence on prognosis.
    • Racial/Ethnic Disparities in HIV Survival Among People Diagnosed with HIV in Arizona, 1998‐2012

      Mun, Elijah; The University of Arizona College of Medicine - Phoenix; Gonzalez, Jonathan (The University of Arizona., 2016-03-25)
      Objectives. We described the racial/ethnic disparities in survival among people diagnosed with HIV in Arizona from 1998 to 2012. We determined whether these disparities widened when adjusting for AIDS diagnosis, age at diagnosis, year of diagnosis, and gender. Methods. We compared survival from all causes between Whites and Blacks, Hispanics, Native Americans, Asians, and Multiple/Other races via Kaplan‐Meier survival curves and Cox proportional hazard models controlling for various clinical factors. Results. Multiple/Other races (1.85), Native Americans (1.28), and Blacks (1.19) have statistically significant higher hazard ratios in all‐cause mortality than Whites. When adjusting for AIDS diagnosis, these disparities widened and also showed Hispanics to have greater mortality [Multiple/Other races (2.53), Native Americans (1.44), Blacks (1.43), and Hispanics (1.22)]. Conclusions. Racial/ethnic minorities with HIV, specifically Black, Native Americans, and Multiple races, have significantly decreased overall survival. These disparities widen when considering the AIDS population. Further studies and resources could help identify the cause of these disparities and help generate a solution to diminish the survival gap.
    • Visual Findings in Neovascular Macular Degeneration Refractory to Bevacizumab after Intravitreal Aflibercept Therapy

      Moazez, Carmel; The University of Arizona College of Medicine - Phoenix; Reddy, Rahul (The University of Arizona., 2016-03-25)
      Neovascular (wet) age‐related macular degeneration (AMD) is associated with blindness in patient populations above 55 years of age, affecting approximately 2 million Americans. Intravitreal (IV) bevacizumab is widely employed in the treatment of wet AMD. Development of a novel pharmacologic intervention to match bevacizumab’s indications is possible with the advent of aflibercept. This study evaluated the optical coherence tomographic (OCT) findings and intraocular pressure after IV aflibercept therapy in patients with wet AMD refractory to IV bevacizumab therapy. This retrospective review of 29 patient records (30 eyes) demonstrated that 73% of patients did not show an increase in OCT. Furthermore, 83% of patients did not demonstrate an increase in intraocular pressure (IOP) and all patients had an IOP of 20 or less after three months of therapy. This study further explores the mean change per patient in retinal thickness via OCT as well as intraocular pressure. The results of this study demonstrate that aflibercept can improve visual findings in patients refractory to bevacizumab and therefore we recommend that patients be switched to it. Further, it is safe to use in patients with glaucoma as it will not increase the IOP.
    • Diagnosing Ventilator‐Associated Pneumonia in Burn Patients: Endotracheal Aspirates Versus Bronchoalveolar Lavage

      Lish, James; The University of Arizona College of Medicine - Phoenix; Foster, Kevin N. (The University of Arizona., 2016-03-25)
      Introduction: Ventilator‐associated pneumonia (VAP) is associated with increased mortality, ventilator days, intensive care unit days and length of stay, especially in the thermal burn patient. In addition to poorer patient outcomes it is estimated that VAP increases the cost of care, making the prevention of VAP a high priority within healthcare. While no “gold standard” diagnosis for VAP exists, criteria typically include clinical suspicion, radiography and microbiological testing. The purpose of this study was to correlate results of endotracheal tube swabs (ETT), endotracheal aspirates (TA) and broncheoalveolar lavage (BAL) in burn patients with suspected VAP. The goal of this study is to determine if TA sampling is a viable alternative to BAL in the diagnosis of VAP in burn patients. Methods: This was a non‐interventional prospective study of 42 adult burn patients with suspected VAP. Respiratory specimens via ETT, TA, and BAL were collected and cultured. Basic demographics, clinical signs and symptoms and culture results were collected and descriptive statistics were performed. Results: Concurrent cultures were performed on the 42 patients with suspected VAP. Correlations were done between TA, BAL and ETT. TA and BAL correlated 87% of the time while TA and ETT correlated 49% of the time. The correlation between ETT and BAL was 40%. Calculated sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) for TA and BAL were roughly equal, while the values for ETT were much lower. Conclusions: TA is nearly as reliable as BAL in identifying the causative organisms in VAP, and should be considered as an economical and easily obtained initial diagnostic test in burn patients suspected to have VAP.
    • Variability in the Interpretation of Elbow Fractures in Children

      Kraynov, Liliya; The University of Arizona College of Medicine - Phoenix; Zebulon, Timothy; Bulloch, Blake (The University of Arizona., 2016-03-25)
      Background and Significance The first physician to encounter a child with an elbow fracture is usually the emergency medicine (EM) physician. Many hospitals may not have access to immediate orthopedic consultation or “real-time” radiology reads, therefore, EM physicians have a great responsibility for an accurate diagnosis. Unfortunately, many EM physicians have little training in pediatric orthopedic injuries. The elbow's anatomy and radiographic features of the growing elbow increase the difficulty in determining an accurate diagnosis and proper treatment. Inaccurate interpretation of elbow fractures in children may lead to unnecessary or improper medical decisions. Accurate interpretation is especially important in rural settings where patients may need transportation to facilities with higher levels of care. Research Question This study aims to survey EM physicians and determine if certain elbow fractures are diagnosed inaccurately more frequently and if some physician characteristics share a relationship with the accuracy of diagnosis of pediatric fractures. The characteristics include area of specialization, annual ED volume, years of experience post residency training, and working in an academic versus non-academic department. Different types of fractures, including type 1 supracondylar, type 2 supracondylar, type 3 supracondylar, medial epicondyle, lateral epicondyle, and olecranon along with uninjured elbows were evaluated to determine if a particular type was misdiagnosed more frequently. Methods A 16-question multiple-choice paper survey was distributed to physicians working in academic and non-academic centers within adult or pediatric emergency departments. Questions included radiographs and asked the physician to determine which fracture existed, if any.Results Lateral epicondyle fractures were the most likely fractures to be misdiagnosed (22.12%), while type 3 supracondylar fractures were the most likely to be accurately diagnosed (95.5%). There was no significant difference in accuracy of diagnosis based on physicians working either in an academic department, non-academic department, or both. Those physicians who were board certified or board eligible in two or more specialties had a higher mean percent correct, as well as those who worked in pediatric emergency medicine. Conclusions While this study served to start clarifying the most frequently misdiagnosed pediatric fractures and whether physicians with particular characteristics were more likely to diagnose fractures accurately, further steady is necessary to draw a definitive conclusion. This study does shed light on which pediatric elbow fractures physicians misdiagnose more frequently. It is important for all emergency medicine physicians to keep in mind the types of fractures that are most commonly misdiagnosed as it can affect medical decision-making. This is an area where additional education about elbow fractures in the developing pediatric elbow may be needed.
    • Healthcare Worker Perceptions and Practices Regarding Influenza Vaccination

      Klassen, Aaron; The University of Arizona College of Medicine - Phoenix; Berisha, Vjollca (The University of Arizona., 2016-03-25)
      Background: Rates of influenza vaccination among healthcare workers (HCWs) are low despite the significant morbidity and mortality benefit to the HCWs, their patients and their families. Objective: To examine whether attitudes, perceptions and beliefs of HCWs about influenza and influenza vaccination affect their uptake of the seasonal influenza vaccine. Methods: Telephone interviews were conducted of HCWs during March 2011 to assess seasonal influenza vaccine uptake, attitudes regarding influenza vaccination, and perceptions of risk of influenza infection. Results: Telephone surveys were completed by 1,171 HCWs and of these 903 responded to all questions relevant to this analysis. Logistic regression models of rates for current, 2010-2011,i influenza vaccination season and preceding influenza vaccination seasons were performed. statistically significant (P<0.05) positive odds ratios for vaccination were found among providers, HCWs with more experience, those who favor mandatory workplace vaccination, believing that the vaccine protects family members, believing the average person is somewhat r very likely to be infected with influenza in a given year, not believing that the influenza vaccine will cause illness, and claiming a higher likelihood of vaccination if the vaccine were less costly or free. Of these, the strongest modifiable predictors of seasonal influenza vaccination uptake were a belief that the vaccine provides protection to the HCWs’ family members and a belief that the average person is somewhat or very likely to be infected with influenza in a given year. Conclusion Beliefs about influenza vaccination have significant effects on HCW seasonal influenza vaccine uptake. We recommend targeting these beliefs when designing educational programs for HCW regarding influenza vaccination. Conclusion: Beliefs about influenza vaccination have significant effects on HCW seasonal influenza vaccine uptake. We recommend targeting these beliefs when designing educational programs for HCW regarding influenza vaccination.
    • Management of Rhinosinusitis During Pregnancy: Systematic Review and Expert Panel Recommendations

      Jategaonkar, Ameya; The University of Arizona College of Medicine - Phoenix; Lal, Devyani (The University of Arizona., 2016-04)
      Background: Rhinosinusitis, both acute and chronic, represents a common disease. Approximately 29.6 million adults in the United States suffer from sinusitis with 11 million suffering from CRS1. The multicenter GA2LEN study showed that amongst lifetime nonsmokers, women were at a greater risk of being affected by chronic rhinosinusitis than men2. Various other rhinologic manifestations of pregnancy have also been described. Nevertheless, management of rhinosinusitis during pregnancy is poorly described in the literature. Objectives: 1. Conduct a systematic review of the literature for the management of acute and chronic rhinosinusitis (CRS) during pregnancy. 2. Make evidence based recommendations on the management of acute and chronic rhinosinusitis during pregnancy. Methods: A systematic review of the literature was conducted using MEDLINE and EMBASE databases. Search terms included “rhinitis” OR “sinusitis” OR “rhinosinusitis” AND “pregnant” OR “women” OR “gender”. Title, abstract, and full manuscript review was conducted. Full manuscripts including citations and references were reviewed if the abstract noted any gender specific outcomes. A multispecialty panel of experts in the fields of rhinology, allergyimmunology, and obstetrics‐gynecology was invited to review the systematic review. Recommendations were sought on the use of the following for the management of CRS during pregnancy: oral corticosteroids, antibiotics, leukotriene antagonists, topical corticosteroid sprays/irrigations/drops, aspirin desensitization, elective surgery for CRS, and vaginal birth vs. planned cesarean delivery for patients with history of skull base erosions or CSF rhinorrhea. Results: 3052 abstracts were screened, and 88 manuscripts were reviewed. No relevant level 1, 2 or 3 studies were found. Expert panel recommendations were synthesized. Conclusions: Several recommendations were made. These include continuing all modern topical corticosteroids for CRS maintenance, using pregnancy safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspiring therapy for desensitization in patients with aspirin exacerbated respiratory disease.
    • Outcomes for Epithelial Ovarian Cancers Diagnosed with Concomitant Venous Thromboembolism

      Hurtt, Callie; The University of Arizona College of Medicine - Phoenix; Bakkum‐Gamez, Jamie N. (The University of Arizona., 2016-03-25)
      Background and Significance Most large studies on venous thromboembolism (VTE) incidence in gynecologic cancer focus on prevention and management of postoperative VTE. Treatment for preexisting VTE at the time of diagnosis of epithelial ovarian cancer (EOC) includes careful risk assessments, weighing the benefits of debulking and risks of anticoagulation in the setting of a new VTE and new EOC diagnosis, respectively. We aimed to describe perioperative and cancer survival outcomes associated with concomitant diagnoses. Research Question To describe short‐term perioperative outcomes and overall survival (OS) among women who present with VTE at initial EOC diagnosis. Methods Women presenting with VTE within 30 days prior to EOC diagnosis between 1/2/2003 and 12/30/2011 who had primary debulking surgery (PDS) or chemotherapy (CT) alone were included. Descriptive statistics and the Kaplan‐Meier method were used to estimate OS from time of EOC diagnosis, with patient characteristics and process‐of‐care variables retrospectively abstracted. Results Of the 36 women with VTE within 30 days prior to EOC diagnosis, 28 (77.8%; mean age 64.2 years) underwent PDS and 8 (22.2%; mean age 61.4 years) received CT alone. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was ≤2 in 85.7% (n=24) of PDS patients compared to 62.5% (n=5) of CT patients. Advanced stage (III/IV) disease was diagnosed in 71.4% (n=20) of PDS group; all CT patients were advanced stage. Among those who underwent PDS, 26 (92.9%) had a preoperative IVC filter placed; 1 (12.5%) in the CT group received an IVC filter. Perioperative bleeding complications were 7.2% in the PDS group. Within the PDS group, median OS was 25.6 months while the CT group had median OS of 4.5 months.ConclusionsPreoperative VTE in EOC patients can be safely managed with low rates of bleeding complications. Poor OS in CT group may reflect worse overall health or more aggressive cancer. Median OS was notably shorter than previously published; IVC filter utilization on oncologicoutcomes in EOC warrants further investigation.
    • Evaluating CNS Lesions in HIV Patients: A Radiologic/Pathologic Review

      Hunter, Camille; The University of Arizona College of Medicine - Phoenix; Gridley, Daniel G.; Van Tassel, Dane; Fairbourn, Phil (The University of Arizona., 2016-03-25)
      Background and Significance. HIV/AIDS is a commonly encountered disease process in many cities and medical centers throughout the world. Approximately 35 million people live with HIV/AIDS worldwide, many of whom develop pathology of the central nervous system (CNS). Many HIV/AIDS patients undergo substantial morbidity and mortality with the development of CNS abnormalities including toxoplasmosis encephalitis (TE), progressive multifocal leukoencephalopathy (PML), primary central nervous system lymphoma (PCNSL), and other opportunistic infections. Especially in these immunocompromised patients, early accurate diagnosis can affect patient management, which is vital to patient survival. Research Question. We hypothesized that fellowship‐trained neuroradiologists are more accurate than general radiologists in the diagnosis of HIV related CNS lesions. Methods. Following institutional IRB approval, we retrospectively analyzed patients with known HIV infection who underwent radiologic imaging and subsequent biopsy of an identified neuropathologic lesion(s) at Maricopa Medical Center between January 2007 and January 2015. Diagnostic scan reports were analyzed to determine whether or not the correct diagnosis was provided in the impression, and rates of correct diagnosis were compared between fellowship trained neuroradiologists and a general radiologists. Results. Thirty‐three patients received neurologic imaging with MRI for a pathologically proven HIV/AIDS related illness with 78 total lesions identified. The correct diagnosis was mentioned in 79% (15/19) of cases read by a neuroradiologist, but only 43% (6/14) of cases read by a general radiologist. Overall, the correct diagnosis was mentioned in the initial impression in 21 of 33 (64%) cases. Chi‐squared analysis showed a statistically significant relationship in the number of mentioned correct diagnoses by neuroradiologists versus general radiologists (p=0.033). Conclusions. Our study suggests that the availability and utilization of specialty fellowship trained staff in radiology is an essential part of accurate early diagnosis. Taking an active role in the work up and diagnosis of specialized disease processes is essential for successful and comprehensive care, especially in our local community where HIV/AIDS support and treatment is on the cutting‐edge.
    • Effectiveness of Using Texture Analysis in Evaluating Heterogeneity in Breast Tumor and in Predicting Tumor Aggressiveness in Breast Cancer Patients

      Hopp, Alix; The University of Arizona College of Medicine - Phoenix; Korn, Ronald (The University of Arizona., 2016-03-25)
      Objective and Hypothesis We hypothesize that tumor heterogeneity or tissue complexity, as measured by quantitative texture analysis (QTA) on mammogram, is a marker of tumor aggressiveness in breast cancer patients. Methods Tumor heterogeneity was assessed using QTA on digital mammograms of 64 patients with invasive ductal carcinoma (IDC). QTA generates six different values – Mean, standard deviation (SD), mean positive pixel value (MPPV), entropy, kurtosis, and skewness. Tumor aggressiveness was assessed using patients’ Oncotype DX® Recurrence Score (RS), a proven genomic assay score that correlates with the rate of remote breast cancer recurrence. RS and hormonal receptor status ‐ estrogen receptor (ER) and progesterone receptor (PR) ‐ were collected from pathology reports. Data were analyzed using statistical tools including Spearman rank correlation, linear regression, and logistic regression. Results Linear regression analysis showed that QTA parameter, SD, was a good predictor of RS (F=6.89, p=0.0108, R2=0.0870) at SSF=0.4. When PR status was included as a predictor, PR status and QTA parameter Skewness‐Diff, achieved linear model of greater fit (F=15.302, p<0.0001, R2=0.2988) at SSF=1. Among PR+ patients, Skewness‐Diff was a good linear predictor of RS (F=9.36, p=0.0034, R2=0.1320) at SSF=0.8. Logistic regression analysis showed that QTA parameters were good predictors of high risk RS probability, using different cutoffs of 30 and 25 for high risk RS; these QTA parameters were Entropy‐Diff for RS>30 (chi2=10.98, p=0.0009, AUC=0.8424, SE=0.0717) and Mean‐Total for RS>25 (chi2=9.98, p=0.0016, AUC=0.7437, SE=0.0612). When PR status was included, logistic models of higher log‐likelihood chi2 were found with SD‐Diff for RS>30 (chi2=18.69, p=0.0001, AUC=0.9409, SE=0.0322), and with Mean‐Total for RS>25 (chi2=25.56, p<0.0001, AUC=0.8443, SE=0.0591). For PR+ patients, good predictors were SD‐Diff for RS>30 (chi2=6.87, p=0.0087, AUC=0.9212, SE=0.0515), and MPP‐Diff and Skewness‐Diff for RS>25 (chi2=16.17, p=0.0003, AUC=0.9103, SE=0.0482). Significance Quantitative measurement of breast cancer tumor heterogeneity using QTA on digital mammograms may be used as predictors of RS and can potentially allow a non‐invasive and cost‐effective way to quickly assess the likelihood of RS and high risk RS.
    • A Model for Improvement: Perinatal Depression Screening

      Hoidal, Kelsey; The University of Arizona College of Medicine - Phoenix; Brite, Kathleen (The University of Arizona., 2016-03-25)
      It is estimated that postpartum depression (PPD) occurs in 10‐20% of women, but fewer than half of cases are recognized.1 CDC survey data form 2004‐2008 utilizing the Pregnancy Risk Assessment Monitoring System (PRAMS) found that young mothers who identify with minority groups have the highest prevalence of PPD.3 Routine screening for PPD with a validated instrument, the Edinburgh Postnatal Depression Scale (EPDS), increased the rate of diagnosis of PPD nearly three times, according to one study.10 PPD screening can detect and mitigate depressive behavior and positively impact the lives of mothers and their children.7,8 In fact, the USPSTF recently published an evidence report which illustrated that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population, especially with additional treatment supports.11 It is a B recommendation to screen the general adult population, including pregnant and postpartum women, for depression. The Wesley Health Center, a busy, urban family medicine FQHC in downtown Phoenix, Arizona has a thorough prenatal care program that includes a postpartum visit. Numbers from 2011 indicate about 25% of the women who participated in the program returned to Wesley for their postpartum care. The postpartum visit includes a PPD screening using the EPDS, which is also well‐established for use prior to birth.10 It is hypothesized that increased patient education about PPD, increased vigilance about postpartum visit scheduling, and routine depression screening using the EPDS at 28 weeks gestational age and at the postpartum visit will improve PPD detection and treatment at Wesley. An intervention was performed in January 2013. It consisted of staff education about PPD and the EPDS, a new policy that all prenatal care patients receive the EPDS around 28 weeks gestation in addition to the postpartum visit, and an EMR checkbox indicating postpartum depression screening was performed and whether or not the patient is experiencing PPD. Screening rates between years were compared using chi‐squared testing. Patients were assigned to groups based on whether they received only prenatal care, only postpartum care, or both prenatal and postpartum care. Between the three data years, 2012 is the control year, 2013 is the year immediately after intervention, and 2014 is assessed for sustainability. There was a statistically significant difference in EPDS screening prior to birth in women who received both prenatal and postpartum care at WHC. For ante‐partum screening, 26.5 percent of women had the EPDS in 2012 versus 79.2 percent and 100 percent in 2013 and 2014, respectively. Postpartum screening was also found to be statistically significant between the years—26.5 percent, 66.7 percent, and 55.2 percent for 2012, 2013, and 2014, respectively. Although not statistically significant, there was a small increase in number of patients identified with depression in the group of women who received the EPDS prior to giving birth—an increase from 1 to 5 and 4 cases identified in 2012 versus 2013 and 2014, respectively. It was clear that increased staff education, a formalized screening system, and ante‐partum depression screening aid a busy, urban FQHC in addressing perinatal depression by identifying women at risk and offering treatment.
    • Analysis of the Proposed Implementation of a Public Health District in Maricopa County

      Hoffman, Laura; The University of Arizona College of Medicine - Phoenix; England, Bob; Barraza, Leila (The University of Arizona., 2016-03-25)
      Background: Since the number and variety of services that a public health department is able to provide is related to its financial resources, it is important that each department have secure funding. The Public Health District model, in which the public health department is mostly funded by a dedicated public tax, rather than as a dependent on the county’s overall budget, has been proposed as an option for the Maricopa County Department of Public Health (MCDPH). This model was implemented in neighboring Pinal County in 2007 and is funded by a 0.1% sales tax. Specific aims: Our study aims are: (1) analyze the current MCDPH funding structure in comparison to other similarly sized county-managed public health departments, as well as review the development and structure of the Pinal County Public Health Services District as a local reference; (2) project the likely financial effects of the implementation of a tax-based Public Health District in Maricopa County; and (3) assess the potential effects on MCDPH management and public health outcomes in Maricopa County. We hypothesize that the implementation of a Public Health District in Maricopa County will secure a source of stable and increased funding and allow for improved public health services. Methods: Specific Aim 1: Budget data for FY 2011-2012 was analyzed for revenue types and percent contribution for each county department in the comparison. Budget data for FY 2003- 2014 for Pinal and Maricopa counties was analyzed in a similar manner. Phone interview with Pinal County Director, Mr. Thomas Schryer, was completed regarding the development of the Public Health District model in Pinal County; Specific Aim 2: Revenue data from the Maricopa County Jail Excise Tax was reviewed and utilized as a proxy to estimate potential income generated by a 0.1% sales tax; Specific Aim 3: The 2012 Maricopa County Community Health Assessment was evaluated to identify areas of need. Results: Specific Aim 1: Funding structures varied greatly between county public health departments, though heavy reliance on government funds was a common theme. Pinal County demonstrated increased funding stability with an increase in overall revenue budget upon implementation of Public Health District model. Specific Aim 2: Estimated revenue from a 0.1% sales tax was calculated to be $70 million in FY 2014-2015, with potential average revenue of $92 million over the next ten years. Specific Aim 3: Top areas for health improvement in Maricopa County include obesity, diabetes, lung cancer, cardiovascular disease and access to care. Conclusion: The current funding structure of the MCDPH follows the trend of other similarly sized county-managed public health departments with a heavy reliance on government funds. The potential revenue generated from a 0.1% sales tax in Maricopa County would be sufficient to significantly decrease the department’s dependence on general county funds and government grants. The result is increased overall funding and financial stability, thus helping the department to better target area needs and improve public health outcomes.
    • Identifying an Oxygenation Index Threshold for Increased Mortality in Acute Respiratory Failure

      Hammond, Brandon; The University of Arizona College of Medicine - Phoenix; Dalton, Heidi; Willis, Brigham (The University of Arizona., 2016-03-25)
      Objectives: To examine current oxygenation index (OI) data and outcomes using EMR data to identify a specific OI values associated with outcome. Methods: Retrospective review of electronic medical record (EMR) data for patients age 1 month ‐ 20 years mechanically ventilated for >24 hours in the PICU. Serial, average and maximum OI values were calculated. Length of mechanical ventilation, hospital stay and outcome were assessed. Results: OI was calculated on 65 patients from EMR data, of which 6 died (9.2%). The median maximum OI was 10 for all patients, 17 for non‐survivors (NS), and 8 for survivors (S), (p=0.14 via Wilcoxon rank‐sum test). Odds ratios (OR) indicated 2.1 times increase odds of death (p=.08), 95% confidence interval (0.89–5.03) for each one‐percent increase in maximum OI. Average OI OR also revealed 2.1 times increase in odds of death (p=.14), 95% confidence interval (0.77–5.48). ROC analysis indicated a higher discriminate ability for max OI (AUC = 0.68) than average OI (AUC = .58). OI cut points for mortality were established. Mortality was unchanged until max OI >17, for which mortality nearly tripled at a value of 18% versus 6‐7% for range 0‐17. Conclusions: Serial assessment of OI values may allow creation of alert values for increased mortality risk and aid in development of clinical decision rules. Consideration for escalation of therapies for respiratory failure such as high frequency ventilation or ECMO at lower levels of OI than historically reported may be warranted. This study also helps to validate prior reports that OI is useful as a severity score for clinical research and outcome prediction.
    • BDNF Knockdown in the VTA Blocks Social Stress‐Induced Deficits in Social Behavior and Nucleus Accumbens ΔFosB Expression

      Hakes, Emelia; The University of Arizona College of Medicine - Phoenix; Hammer, Ron, Jr.; Nikulina, Ella (The University of Arizona., 2016-03-25)
      Social defeat stress, a salient stressor that translates readily from animal studies to humans, alters social approach behavior and induces brain‐derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA), as well as the stable transcription factor, ΔFosB, in the nucleus accumbens (NAc) of rats. However, it is unknown whether VTA BDNF is required for these effects of stress. Rats underwent stereotaxic surgery to receive bilateral intra‐VTA infusions of adeno‐associated virus inducing green fluorescent protein (AAV‐GFP) or GFP and short hairpin RNA directed against BDNF (shRNA‐BDNF). Following recovery, rats were subjected to control handling or social defeat stress, consisting of a brief confrontation between an aggressive resident and an experimental intruder rat every third day for 10 days. Social interaction was assessed in a social approach assay two weeks later. Following perfusion, brains were removed and processed for immunohistochemical analysis of ΔFosB expression. VTA BDNF knockdown attenuated the effect of social stress on weight gain, and increased social approach behavior, which is normally reduced by social stress. Furthermore, social stress increased NAc ΔFosB labeling in AAV‐GFP rats, but this effect was blocked by prior shRNA‐BDNF treatment. This study further implicates VTA BDNF signaling in the effects of stress on social behavior. VTA BDNF appears to be required for the long‐lasting effects of social stress on ΔFosB expression in the NAc. Thus, activation of BDNF signaling in mesolimbic circuits may underlie the persistent deficits of social behavior induced by stress exposure in some individuals.
    • Marijuana Use and the Risk of Depression: A Systematic Review and Meta‐Analysis

      Gentry, James; The University of Arizona College of Medicine - Phoenix; Campos-Outcalt, Douglas (The University of Arizona., 2016-03-25)
      Objective: To conduct a systematic review of the evidence pertinent to the relationship between marijuana use and depression and perform a meta‐analysis on the data in order to inform evidenced‐based practice. The question of interest is: Is marijuana use associated with increased risk of developing depression? Methods: The databases MEDLINE (PubMed), The Cochrane Library, CINAHL (EBSCO), psycINFO, and Google Scholar were searched for the topics of marijuana use and depression through October of 2013. Studies were included if they were systematic reviews, randomized controlled trials, prospective or retrospective cohort studies, or case‐control studies. No randomized controlled trials were discovered. Quality of cohort and case‐control studies was evaluated using the Newcastle‐Ottawa Quality Assessment Scale 1. Overall quality of evidence was determined using the GRADE methodology 2,3. The Bradford‐Hill criteria 4 were used to assess for causation. Studies were assessed by two reviewers. 173 articles were screened for eligibility. Of these fourteen articles were considered to fit the inclusion criteria. Nine homogeneous studies were included in the meta‐analysis. Results: The quality of the evidence reviewed is low to very low. It does not meet Bradford‐Hill criteria for causation. There is a slight positive correlation between marijuana use and onset of depression. However, those studies included in the meta‐analysis demonstrated a low overall pooled odds ratio (OR = 1.17; 95% CI = 1.06—1.29). Conclusion: The evidence suggests a slight positive correlation between marijuana use and depression but is not sufficient to draw a conclusion. This evidence is generally of very low quality. It does not demonstrate a dose response, and is without a significant magnitude of effect.
    • The Role of Injection Laryngoplasty (IL) in Treating Deep Interarytenoid Notch (DIN) Associated Dysphagia in Young Children

      Frantz, Garrett; The University of Arizona College of Medicine - Phoenix; Williams, Dana (The University of Arizona., 2016-04)
      BACKGROUND Deep Interarytenoid Notch (DIN) is the mildest form of laryngotracheoesophageal cleft defect and is frequently found in young children with dysphagia and aspiration. Treatment guidelines are not defined. Injection laryngoplasty (IL) is a surgical procedure injecting polymer gel into the issue around the defect. Our objective was to evaluate the efficacy of IL in pediatric populations with severe dysphagia and aspiration. METHODS We conducted a pilot retrospective chart review of DIN patients under 36 months who underwent IL at PCH. Severity of dysphagia before and after IL was measured using modified barium swallows (MBS) (scale 0‐10) and documented symptoms. Statistical analysis was done using paired two sample t‐test with a p value of 5 percent. RESULTS Patients with initial MBS above double honey (7) improved an average of 2.6 ±1.38 points while those with initial scores below 7 did not see a statistical change in MBS. At the end of the study period, the final MBS scores for both groups were statistically similar.CONCLUSIONS IL treatment for DIN associated dysphagia results in improvement of MBS scores and symptoms in toddlers with severe aspiration. Careful timing of IL impacts morbidity. Future prospective controlled studies are necessary to evaluate the role of IL and medical interventions in thickener wean and clinical improvement.
    • Implementation of a Pediatric Stroke Team: Outcomes and Resource Utilization

      Esque, Jacquelin; The University of Arizona College of Medicine - Phoenix; Buttram, Sandra (The University of Arizona., 2016-04)
      Background and Significance: Pediatric stroke is associated with significant morbidity and mortality. In an effort to improve diagnosis and patient management, we established a Pediatric Stroke Team (PST) available 24/7 in January 2012. Outcomes of patients before and after PST implementation are reported. Methods: Retrospective review of pediatric stroke patients (Jan 2009 ‐Dec 2012) at Phoenix Children’s Hospital in Phoenix, Arizona. Primary outcomes assessed were Glasgow Outcome Scale‐Extended Pediatric Revision (GOS‐E Peds) and discharge disposition. Hospital length of stay, time to neuroimaging, stroke therapies, and adherence to neuroprotective strategies (sodium, glucose, temperature) were also evaluated. Data were analyzed by Wilcoxon rank sum, Fisher’s exact, and chi‐square. Results: There were 64 patients pre‐PST and 30 post‐PST. Overall, GOS‐E Peds was improved post‐PST 2 [1, 3] vs. pre‐PST 3 [2, 6] (p = 0.004) with no change if deaths were excluded (post‐PST (2 [1, 2]) vs. pre‐PST (2 [1, 6]) (p = 0.030)). Discharge to home was more common in the post‐PST group (p = 0.018). Definitive neuroimaging tended to occur more quickly post‐PST 2h [1, 2.6] compared to pre‐PST 4.7h [1.3, 16.5] (p =0.16). Post‐PST patients appropriately received heparin (23%) more often than pre‐PST (6%) (p = 0.034) and had fewer episodes of hyperglycemia (3%) compared to pre‐PST (20%) (p = 0.033). There were no differences in episodes of fever, hyponatremia or hypoglycemia. Conclusions: Availability of a PST improved patient care and outcomes. Time to definitive neuroimaging was decreased, appropriate therapies were administered and adverse events (hyperglycemia) were decreased with PST management. We continue to strive for improved care of pediatric stroke patients.