• Marijuana Smoking and the Risk of Developing COPD, Lung Cancer, And/or Chronic Respiratory Symptoms: A Systematic Review

      Byers, Chris; The University of Arizona College of Medicine - Phoenix; Campos-Outcalt, Douglas (The University of Arizona., 2017-06-01)
      The aim of this study is to conduct a systematic review of the existing evidence on marijuana use and its association, or the absence of an association, with an increased risk of developing chronic obstructive pulmonary disease (COPD), lung cancer, and/or chronic respiratory symptoms. We hypothesize that a systematic review will not demonstrate sufficient evidence to determine that marijuana use increases the risk of developing COPD, lung cancer, and/or chronic respiratory symptoms. The term “chronic respiratory symptoms” encompasses the following: cough, sputum production, wheeze, shortness of breath, acute bronchitis, and chest tightness. The following databases were searched for the topics of marijuana smoking, COPD, lung cancer, and chronic respiratory symptoms: MEDLINE (PubMed/OvidSP), the Cochrane Controlled Trials Register, the Cochrane Database of Systematic Reviews, PsycINFO, the Database of Abstracts of Reviews of Effects, and Google Scholar. The search ended September 7th, 2016. Studies were initially limited only by the requirement that they were based upon human research and published in English. Studies were included if they were systematic reviews, randomized controlled trials (RCTs), prospective or retrospective cohort studies, case control studies, or cross‐sectional studies. A total of 739 articles were screened for eligibility, 17 unique studies met the inclusion criteria and underwent qualitative analysis1‐17. The quality of systematic reviews was evaluated using the AMSTAR criteria18; cohort, case‐control, and cross sectional studies were evaluated based upon the Newcastle‐Ottawa Quality Assessment Scale (NOS) 19. No RCTs were identified. The overall quality of the evidence for each outcome was determined by utilizing the GRADE methodology20‐21. Studies were primarily assessed by a single reviewer, with random validation of assessments on a limited number of studies by a second reviewer. Overall, there is very low quality evidence that assesses for an association between marijuana smoking and an increased risk of developing lung cancer, COPD, and/or chronic respiratory symptoms. There was no conclusive finding for lung cancer and COPD. However, seven of eight studies concluded that there was an association between marijuana use and chronic respiratory symptoms. The totality of evidence describing any associations between marijuana smoking and the risk of developing lung cancer, COPD, and/or chronic respiratory symptoms is not strong enough to confidently state that marijuana use is associated with any of these chronic pulmonary conditions. Of all the evidence examined in this systematic review, the most convincing appears to be that relating to a potential positive association between marijuana smoking and the risk of developing chronic respiratory symptoms. Unfortunately, the overall quality of evidence was very low due to significant methodological weaknesses within the studies. Thus, there is insufficient evidence in the current literature to make a definitive statement regarding this possible association.
    • Healthcare Access among Adults with Frequent Mental Distress

      Khan, Khalid Salim; The University of Arizona College of Medicine - Phoenix; Hussaini, Khaleel; Rahman, Shakaib; Shennib, Hani (The University of Arizona., 2016-05-04)
      Objective: Mental health plays a central role in the well‐being of individuals. Understanding the factors that influence mental wellness is critical in order to develop effective policy that addresses the burden of mental illness in society. The objective of this study is to identify a possible relationship between healthcare access and the presence of mental distress in individuals. Methods: Logistic regression was performed using cross sectional data from a CDC developed nationwide behavioral health surveillance program (BRFSS, 2013‐4). Odds ratios were estimated using frequent mental distress as the outcome of interest while adjusting for confounding variables such as smoking, binge drinking, obesity, etc. Six models were estimated utilizing our hypothesized variables of interest. Results: The calculated adjusted odds ratios (AOR) and confidence intervals (CI) demonstrated a positive correlation between certain variables measuring access to healthcare and the reporting of frequent mental distress, agreeing with the hypothesis. Those variables were financial cost preventing access to medical care (AOR [2], CI [1.9‐2.1]) as well as a span of more than 2 years having elapsed since a routine medical checkup by a healthcare provider (AOR [1.1], CI [1.1‐ 1.2]). The opposite effect was demonstrated in individuals who had no insurance coverage (AOR [.8], CI [.7‐.9]), which was contrary to the hypothesis. Conclusion: After adjusting for confounding variables, a strong relationship exists between individuals who are not able to see a physician due to cost, and the presence of frequent mental distress. Frequent mental distress is also increased in individuals who have not had a routine medical checkup with a physician in the last 2 years.
    • The Use of Clinical Decision Rules to Reduce Unnecessary Head Ct Scans in Pediatric Populations

      Barrett, Jeffrey; The University of Arizona College of Medicine - Phoenix; Panchanathan, Sarada (The University of Arizona., 2016-04-20)
      Background: Head computed tomography (CT) imaging is the gold standard study for rapidly identifying emergent traumatic brain injuries (TBIs). Exposure to the ionizing radiation utilized in CT increases lifetime risk for developing neoplasms. Currently there is little consensus on appropriate use of CT imaging for children with mild head injury. Clinical decision rules (CDRs) have been developed to identify children at very low risk of clinically significant brain injury. While these CDRs have been validated, their implementation has not been as well studied. Objective: To evaluate the efficacy of two CDRs in decreasing CT scan rate without missing clinically significant brain injuries. The two CDRs used in this study were the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) and the Pediatric Emergency Care Applied Research Network (PECARN) algorithm. Both variations of the PECARN criteria for age 2 years and older and age <2 years were studied. Design/Methods: The medical records for patients with the diagnosis of head injury evaluated at the Maricopa Medical Center Pediatric Emergency Department for all of 2011 and 2012 were reviewed. A total of 331 charts were identified. The PECARN and CHALICE inclusion criteria and algorithms were applied to these charts to determine if the patients met criteria for CT scan. Patients with suspected non‐accidental injuries were excluded. Results: Of 331 patients, 238 met the inclusion criteria for CHALICE. 96 (40.3%) had CT scans performed. According to the algorithm, only 52 (21.8%) met criteria, which is an absolute rate reduction of 18.5%. One TBI was missed. 129 patients met the inclusion criteria for PECARN age 2 years and older. 73 (56.6%) had CT scans performed. 61 (47.2%) met criteria resulting in an absolute rate reduction of 9.4%. No TBIs were missed. 74 patients met inclusion criteria for PECARN age <2 years. Of these, 25 (33.7%) had CT scans performed and the same number met criteria resulting in no change in number of scans. One TBI was missed. Conclusions: Both the CHALICE and PECARN CDRs have the potential to reduce scan rates in our home institution. The CHALICE CDR would have resulted in a greater reduction in CT scans. PECARN also would have reduced the number of scans in children 2 years and older, but not in children <2 years old. The TBI that did not meet CDR criteria was also missed by clinical suspicion and a CT scan done on a later encounter was suspicious for a non‐accidental injury.
    • Injections of Bone Marrow Aspirate Concentrate as Treatment for Discogenic Pain

      Shillington, Jon Mark; The University of Arizona College of Medicine - Phoenix; Wolff, Michael (The University of Arizona., 2016-04-20)
      Low back pain (LBP) is one of the most common musculoskeletal pain complaints, affecting up to 84% of the U.S. adult population. In the United States, the highest rate of incidence is between the ages of 45 and 64 years. The causes for LBP are complex and of multiple origins, but one of the primary causes is mechanical low back pain that is discogenic in etiology. This can be secondary to either internal disc disruption (IDD) and/or degeneration of the intervertebral disc (IVD), also known as degenerative disc disease (DDD) [10,11]. Combined physical and medical therapies are successful in relieving pain in approximately 90% of cases of low back pain. However, the remaining 10% become chronic and generate a serious public health problem, known as chronic low--‐back pain (CLBP). CLBP decreases both the quality of life and the labor capacity of the patient. As specific diagnostic procedures for LBP have improved, discogenic pain has been identified as the primary cause of CLBP amongst adults. Within the classification of discogenic pain, the most common specific cause of pain – up to 42% of LBP complaints – is internal disc disruption (IDD), with other distinguishable causes including disc herniation, degenerative disc disease (DDD), and instability of the lumbar segment [10]. Effective treatment for discogenic LBP – and therefore for CLBP – would provide significant relief for individuals as well as for the overall health care system and the employers affected by the patients’ condition. One promising treatment option involves the use of Mesenchymal Stem Cells (MSC), which may allow for regeneration of the disc itself. Treatment with MSCs via injections derived from autologous concentrated Bone Marrow Aspirate (cBMA) would capitalize on the regenerative potential of MSCs while reducing the risk of infection or rejection, both significant risks of treatment from a heterologous source. This project analyzed data collected from 33 patients with confirmed discogenic LBP, who were treated with intradiscal injections of autologous concentrated Bone Marrow Aspirate. After initial treatment, patients were monitored through follow up visits and questionnaires (VAS, Oswestry, SF--‐36) to determine the efficacy of treatment. The areas of interest for this study were intentionally narrow. This study sought to identify specifically the patients’ self--‐reported pain and functioning levels from 2 weeks post--‐treatment to 12 months post--‐treatment. Those reports were gathered using the aforementioned instruments and synthesized to show overall trends and statistically significant changes in the patients’ self--‐ assessment. The patients were also asked to give an overall impression of whether or not their back pain had improved post treatment. While admittedly limited in authority compared to a double--‐blind, randomized, controlled trial, the information was gathered from the patients with the hopes of augmenting ongoing research related to innovative treatments for discogenic LBP and of identifying new areas for further, future research.
    • The Interaction of β-catenin, Vitamin D, Resveratrol, and Two Common VDR Polymorphic Variants in Colorectal Carcinogenesis

      Van Pelt, Chad; The University of Arizona College of Medicine - Phoenix; Jurutka, Peter (The University of Arizona., 2016-04-20)
      Vitamin D and resveratrol have been widely researched in recent years, especially their apparent abilities to impact a host of physiological processes. Resveratrol, a phytoalexin found in various berries, peanuts, and other vegetables, is purported to possess anti-aging, anti-inflammatory, antioxidant, anticancer, neuroprotective, and antiarthritic properties, while the classical endocrine functions of vitamin D are the control of calcium and phosphate homeostasis. The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is typically synthesized in the kidney, bound to vitamin D binding protein, and shuttled to cellular target sites. Mounting data on the effect of locally synthesized 1,25D in immune, epithelial, neural, and other tissues have led to an increased awareness of the myriad functions of vitamin D, including detoxification, cellular aging and its modulation, immune regulation, neurotransmitter activity, and metabolic control. Both endocrine and intracrine actions of vitamin D are mediated by the vitamin D receptor (VDR), a nuclear receptor that controls vitamin D-directed transcription of target genes. Importantly, the VDR has numerous polymorphisms, one of which results in two phenotypically distinct isoforms, designated M1 and M4. VDR M4 is postulated to be more active than M1 in vitamin D-dependent transactivation. Variable binding affinities between the two isoforms and VDR interacting proteins such as TFIIB and RXR have also been observed. Another protein known to interact with VDR is β-catenin, the mediator of the Wnt/β-catenin signaling pathway that can drive colorectal carcinogenesis. The goal of this study was to investigate the ability of vitamin D and resveratrol to regulate the Wnt/β-catenin system via stimulation of β-catenin-VDR (both M1 and M4) interaction and subsequent inhibition of β-catenin-mediated transcription. The current data reported herein support and extend previous work by demonstrating that VDR binds directly to β-catenin and that both vitamin D and resveratrol appear to enhance this interaction. We also present data that 1,25D-stimulated VDR is capable of inhibiting β-catenin transcriptional activity. Significantly, we have shown that the two common VDR polymorphisms M1 and M4, are functionally variable, both in their induction of vitamin D-dependent genes and in their inhibition of β-catenin-mediated transcription. VDR M4 exhibits both elevated transactivation and amplified capacity for β-catenin suppression compared to M1, and studies employing site-directed mutagenesis of VDR implicate the glutamic acid at position 2 as being responsible for the reduced activity of the M1 variant. Both polymorphic VDR variants display 1,25D-mediated enhancement of -catenin association, with the M1 SNP possessing a lower basal (-1,25D) binding to this protein partner but a higher fold stimulation in -catenin interaction in the presence of 1,25D. Taken together, these data support the notions that VDR influences pathways important for colorectal carcinoma (CRC) development, and that supplementation with vitamin D and resveratrol may reduce colon cancer risk in the general population, especially in individuals with the less active M1 VDR polymorphism. A comprehensive understanding of 1,25D and resveratrol action in VDR signaling may allow for a more personalized approach toward treating vitamin D–related disorders and evaluating risk for carcinogenesis.
    • Safety and Visual Outcomes of Novel Abexterno Akreos® Single Pass Method of Transscleral Sutured Posterior Chamber IOL Implantation for Scleral Fixation of IOL

      Wallman, Andrew; The University of Arizona College of Medicine - Phoenix; Monson, Bryan (The University of Arizona., 2016-04-20)
      We present the safety and efficacy of a novel transscleral sutured posterior chamber intraocular lens (TSSPCIOL) implantation approach utilizing 25 gauge vitrectomy and a foldable posterior chamber intraocular lens implant (AKREOS AO60, Bausch & Lomb). 80 consecutive eyes that underwent single surgeon TSSPCIOL implantation between October 2008 and July 2012 at a referral‐based retina institution were analyzed for best spectacle‐corrected visual acuity (BCVA) and safety indicators. Postoperative complications included retinal detachment in 2 eyes (2.5%), Irvine‐Gass cystoid macular edema in 3 eyes (3.75%), with 2 of those cases occurring late, persistent postoperative corneal edema in 1 eye (1.25%), hyphema in 2 eyes (2.5%) and 1 case of postoperative vitreous hemorrhage with spontaneous clearing. The modified external approach with AKREOS® TSSPCIOL placement with 25 gauge vitrectomy has relatively few complications, improves visual acuity in patients requiring TSSPCIOL, and offers several advantages over traditional anterior chamber or conventional scleral sutured techniques.
    • The Proportion of Adolescents Complaining of Anterior Knee Pain with Osteochondritis Dissecans and the Utility of Screening Radiographs in its Diagnosis.

      MacKenzie, James; The University of Arizona College of Medicine - Phoenix; Vaughn, Jeffrey M.; Shrader, M. Wade (The University of Arizona., 2016-04-01)
      Osteochondritis dissecans is a rare condition which can cause disabling knee pain in adolescents. Treatment and prognosis hinges upon the stage of the lesion and early detection is paramount 1‐3. Until recently, epidemiologic information regarding OCD in adolescents was unavailable. However in 2013 Kessler et al. demonstrated an incidence of 9.5/100,000 in the general adolescent population 4. Chief complains from patients with OCD usually localize pain to the knee joint line, but less commonly, patients may complain of anterior knee pain. This retrospective chart review looked at the amount of OCD diagnoses in adolescents specifically complaining of anterior knee pain without causative trauma in the years 2009 and 2010 at a major children’s hospital. It was noted that 7.5% of children with this presentation had a diagnosis of OCD. This number was over three orders of magnitude higher than the incidence seen in the general adolescent population as established by Kessler and may support the use of screening radiographs in this subset of patients to detect OCD in its early stages.
    • Inferior Vena Cava Filter Fracture and Migration to the Heart: A Review of the Literature and Case Report

      Bowles, Brad; The University of Arizona College of Medicine - Phoenix; Shennib, Hani (The University of Arizona., 2016-04-01)
      Background and Significance: The utilization of IVC filters for pulmonary embolism prevention has increased significantly over the past decade as the indications continue to expand. Although the risks associated with IVC filters are small, a well‐known complication is filter fracture and subsequent embolization of the fragment. Case reports have been published on the devastating effects of fragment migration to the heart, causing intense chest pain, pericardial effusion, cardiac tamponade and death. Research Question: There is a paucity of experience and guidelines for treating patients with a metallic foreign object lodged within the heart. Is there a consensus on the proper management of these cases? How do these patients present and what are the outcomes of treatment? Some clinicians have chosen to observe and monitor, while others have gone to the operating room for open‐heart surgery and retrieval of the fragment. Methods: In an attempt to answer these questions, a systematic review of the published literature was conducted between 1985 and 2015. Only articles related to IVC filter fracture and subsequent fragment migration to the heart were included. The clinical presentation, workup, management, treatment and outcomes were collected as available. Results: A total of 23 articles were published consisting of a prospective study, retrospective series and case reports. There were 37 migrated fragment to the heart reported in 29 patients. The most common clinical presentations were chest pain (69.0%) and no symptoms (27.6%). Regarding treatment, ten patients underwent observation, three had successful endovascular retrieval, 12 went to the operating room for open‐heart surgery and four cases were unreported. Of the 12 patients with reported pericardial effusion, 11 (91.7%) underwent open surgical repair. Of the eight asymptomatic patients, seven (87.5%) were ultimately in observation and the management of the other was unreported. Conclusions: There appears to be a consensus in the literature that observation and close follow up are appropriate options for asymptomatic patients. Symptomatic patients with pericardial effusion may benefit from open‐heart surgery. Cardiovascular compromise such as cardiac tamponade should be managed with open surgery. Based upon these findings and other details in the cases, we have proposed a management algorithm.
    • “It’s About Heart”: A Qualitative Study of Rural Family Physician Training Needs.

      Varner, Samantha; The University of Arizona College of Medicine - Phoenix; Brown, Steven (The University of Arizona., 2016-04)
      Efforts to reduce a chronic physician shortage and meet the needs of rural communities face long standing challenges such as physician recruitment and retention. While these topics have been researched at length, issues surrounding the contribution of training specifically geared toward the needs of the Southwest’s rural communities are not well understood. The goal of this investigation is to discuss with rural family physicians the realities of rural practice and to determine what, if any, skills and competencies are specific to rural family practice and that, if addressed in training, would increase the number of students and residents pursuing rural family medicine and increase the number of physicians in rural areas. Methods: Physicians throughout rural areas in the Southwest meeting the role of thought leader were interviewed. Chain sampling was used to generate diversity of ideas. Interviews were conducted in person or by phone using a semi‐structured format and a topic guide. Participants were asked to discuss what skills they feel are important to a successful practice in a rural community, the degree to which the competencies were covered in their residency training, and how having or not having these skills might affect job satisfaction and retention. Interviews were recorded and transcribed. Transcripts were analyzed by a two person committee for repeating themes. Results: Seven major repeating themes were evident in the data. Of these residency training type, individual resilience, comfort with lack of resources, community were some of the most common and important to participants. Conclusion: This study has shown that the challenges to recruitment and retention of family physicians in rural areas are many and complex. These results combined with the extensive literature studying successful recruitment and retention programs demonstrates the enormous potential that exists in a multifactorial approach to rural recruitment and retention to meet the tremendous need for more family physicians in rural areas.
    • 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.
    • Label‐free Microscopic Assessment of Glioblastoma Biopsy Specimens Prior to Biobanking

      Zehri, Aqib; The University of Arizona College of Medicine - Phoenix; Preul, Mark (The University of Arizona., 2016-04)
      Introduction: Glioblastoma is the most common primary brain tumor with a median 12‐ to 15‐ month patient survival. Improving patient survival involves better understanding the biological mechanisms of glioblastoma tumorigenesis and seeking targeted molecular therapies. Central to furthering these advances is the collection and storage of surgical biopsies (biobanking) for research. We addressed an imaging modality, confocal reflectance microscopy (CRM), for safely screening glioblastoma biopsy samples prior to biobanking to increase the quality of tissue provided for research and clinical trials. We hypothesize that CRM is a safe and effective method for screening specimens prior to biobanking. Methods: Intracranial implantation of human glioma cells was performed to create glioblastoma xenografts. Rodents xenografts were anesthetized to collect whole brain specimens, which were sectioned into tumor containing slices. One set of slices were incubated with DAPI and imaged. A coefficient of determination analysis was then used to compare cells identified with CRM to cells labeled with DAPI. The other set of slices were imaged using CRM at various time points and subsequently frozen for later analysis of DNA, RNA, and protein integrity. We subsequently imaged human glioma biopsies with CRM to determine cellularity and necrosis. Results: CRM provides definitive contrast between cell nuclei, cytoplasm, and extracellular tissue to help identify tumor regions, margins, and acellular regions of animal glioblastoma specimens without altering DNA, RNA, or protein expression of imaged tissue. When imaging fresh human biopsy samples, CRM can differentiate a cellular glioblastoma biopsy from a necrotic biopsy. Conclusion: These data illustrate CRM’s potential for rapidly and safely screening clinical biopsy samples prior to biobanking, which demonstrates its potential as an effective screening technique that can improve the quality of tissue biobanked for patients with glioblastoma.
    • 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.
    • Acute Exercise Alters Promoter Methylation in Human Skeletal Muscle

      DeMenna, Jacob; The University of Arizona College of Medicine - Phoenix; Coletta, Dawn (The University of Arizona., 2016-04)
      Background And Significance: Insulin resistance is an underlying disease of obesity and type 2 diabetes, which is a metabolic health crisis in the United States. Insulin resistance is caused by a combination of environmental and genetic factors. Understanding the epigenetic factors, specifically DNA methylation and how it influences the expression of genes linked to insulin resistance is of critical importance. Research Question: In this project, we set out to identify patterns of changes in DNA methylation in response to an acute exercise in healthy control subjects. Methods: Five lean (BMI = 23.6 ± 3.3 kg/m2) volunteers underwent a euglycemic hyperinsulinemic clamp with a baseline muscle biopsy and a single bout of aerobic exercise on a stationary bicycle for 48 minutes, rotating between 70 and 90% of VO2max, with a muscle biopsy taken 24 hours after completing the exercise. DNA was isolated from the baseline and 24 hours muscle biopsy, and next‐generation reduced representation bisulfite sequencing (RRBS) was performed, with analysis of the data using methylSig, and KEGG pathway analysis. Results: RRBS analysis captured 676,937 methylation sites, and of these 47,459 were differently methylated following acute exercise (P<0.05) with 4,574 sites occurring in promoter and untranslated (5’ and 3’) regions. The site with the greatest increase in methylation was within the gene NADP(+) ‐dependent malic enzyme cytosolic form (ME1) that demonstrated a significant methylation difference of +63.3%. A site in the gene for adenomatosis polyposis coli down‐regulated 1‐like (APCDD1L) was observed to have the most significant decrease in methylation by ‐65.3%. The gene with the highest incidence of differentially methylated sites was the gene for cardiomyopathy associated 5 (CMYA5) with 11 sites demonstrating a mean increase in methylation of 30.47%. The gene family with sequence similarity 176, member B protein (FAM176B) had the highest frequency of methylated sites (n=7) that were decreased in methylation with a mean decrease of ‐24.28%. KEGG pathway analysis was performed, which revealed significant (P<0.05) increases in methylation in the pathways of Wnt signaling, Heterotrimeric G‐protein signaling ‐Gi alpha and Gs alpha mediated, Cadherin signaling, Melanogenesis, Axon Guidance, and Neuroactive ligand‐receptor interaction. Significantly 4 enriched pathways with decreased methylation post exercise demonstrated one pathway, the Calcium signaling pathway. Conclusion: Our data demonstrates that a single bout of exercise can alter the DNA methylation pattern in skeletal muscle. Changes were observed in genes related to metabolic pathways, supporting previously published findings of changes in mRNA and proteins involved in metabolism following exercise. Future work is warranted with obese and type 2 diabetic participants to explore the differences in response to exercise between these groups.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.