Medicine and Health Sciences Commons^™

Simulations For Designing And Interpreting Intervention Trials In Infectious Diseases., M Elizabeth Halloran, Kari Auranen, Sarah Baird, Nicole E Basta, Steven E Bellan, +Several Additional Authors

Global Health Faculty Publications

BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods.

DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, …

Safety And Efficacy Of Apremilast Through 104 Weeks In Patients With Moderate To Severe Psoriasis Who Continued On Apremilast Or Switched From Etanercept Treatment: Findings From The Liberate Study., K Reich, M Gooderham, A Bewley, L Green, J Soung, R Petric, J Marcsisin, J Cirulli, R Chen, V Piguet

Dermatology Faculty Publications

Background

Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis.

Objective

To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.

Methods

Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and …

Knowledge Retention Across Curricular Models: An International Collaboration, Rosalyn Jurjus, Abdo Jurjus, Gisela Butera

Anatomy and Regenerative Biology Faculty Posters and Presentations

Program symposium.

Prevalence Of Chronic Obstructive Pulmonary Disease (Copd) In China In 1990 And 2010., Kit Yee Chan, Xue Li, Wanjing Chen, Peige Song, Nuen Wing Katy Wong, Adrienne N Poon, Weiyan Jian, Ireneous N Soyiri, Simon Cousens, Davies Adeloye, Aziz Sheikh, Harry Campbell, Igor Rudan, Global Health Epidemiology Research Group (Gherg).

Medicine Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020. In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden. An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.

Methods: We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of …

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors

Neurology Faculty Publications

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, …

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 …

Clinical And Serological Features Of Systemic Sclerosis In A Multicenter African American Cohort: Analysis Of The Genome Research In African American Scleroderma Patients Clinical Database, Nadia Morgan, Ami Shah, Maureen Mayes, Robyn Domsic, Thomas Medsger, Victoria K. Shanmugam, +Several Additional Authors

Medicine Faculty Publications

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).

African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.

The study population included …

Confirmation That Mat1a P.Ala259val Mutation Causes Autosomal Dominant Hypermethioninemia, M J. Muriello, S Viall, T Bottiglieri, K Cusmano-Ozog, C R. Ferreira

Pediatrics Faculty Publications

Methionine adenosyltransferase (MAT) I/III deficiency is an inborn error of metabolism caused by mutations in MAT1A, encoding the catalytic subunit of MAT responsible for the synthesis of S-adenosylmethionine, and is characterized by persistent hypermethioninemia. While historically considered a recessive disorder, a milder autosomal dominant form of MAT I/III deficiency occurs, though only the most common mutation p.Arg264His has ample evidence to prove dominant inheritance. We report a case of hypermethioninemia caused by the p.Ala259Val substitution and provide evidence of autosomal dominant inheritance by showing both maternal inheritance of the mutation and concomitant hypermethioninemia. The p.Ala259Val mutation falls in the …

Plasma Fibroblast Growth Factor-21 Levels In Patients With Inborn Errors Of Metabolism, Brian Kirmse, Juan Cabrera-Luque, Omar Ayyub, Kristina Cusmano-Ozog, Kimberly A. Chapman, Marshall L. Summar

Pediatrics Faculty Publications

Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction. We measured plasma FGF21 by ELISA in patients with and without IEM. FGF21 levels were higher in patients with IEM compared to without IEM (370 pg/dL vs. 0–65 pg/dL). Further study of FGF21 as a biomarker in IEM is warranted.

Significant Correlation Between Regional Tissue Oxygen Saturation And Vital Signs Of Critically Ill Infants, Beri Massa-Buck, Virginia Amendola, Reagan Mccloskey, Khodayar Rais-Bahrami

Pediatrics Faculty Publications

Background: Near-infrared spectroscopy (NIRS) has been used to noninvasively measure specific tissue oxygen saturation (StO2) continuously. Cerebral autoregulation status can be derived from NIRS and arterial blood pressure. The relationship of both cerebral and somatic StO2, fractional tissue oxygen extraction (FTOE), and cerebro-splanchnic oxygenation ratio (CSOR) to measured vital signs parameters for NICU patients has not been well studied.

Objective: Determine if significant relationships between brain and somatic StO2, brain and somatic FTOE, and CSOR parameters to vital signs for neonates exist. Assess relationship between pressure passivity index, cerebral autoregulation and mean blood pressure (MBP).

Design/Methods: Neonates weighing <5 >kg, preferentially …

Effect Of Src Kinase Inhibition On Cytochrome C, Smac/Diablo And Apoptosis Inducing Factor (Aif) Following Cerebral Hypoxia-Ischemia In Newborn Piglets., Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis, Maria Delivoria-Papadopoulos

Pediatrics Faculty Publications

We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E and biochemical enzyme assays to determine the role of Src kinase on …

A Case Report Of Successful Management Of Clostridium Difficile Colitis With Antegrade Fidaxomicin Through A Mucous Fistula Obviating The Need For Subtotal Colectomy., Suzanne Arnott, Matthew Skancke, Sheena Chen, Bruce Abell

Surgery Faculty Publications

Introduction

Clostridium difficile is the most common cause of healthcare-associated infections and can have devastating morbidity and mortality. Traditional treatment algorithms involve intravenous metronidazole and enteric metronidazole or vancomycin. Fidaxomicin (DificidR) targets “switch regions” within RNA polymerases and effectively kills clostridium difficile bacteria and is typically administered orally primarily or through a naso/oro-gastric conduit.

Presentation of case

55-year-old with a recent elective surgical procedure was hospitalized with multifocal pneumonia and subsequently developed clostridium difficile colitis. This patient failed the standard medical therapy for clostridium difficile colitis, decompensated and required surgical exploration, partial colectomy and mucous fistula creation. Following her surgery, …

Non-Invasive Placental Perfusion Imaging In Pregnancies Complicated By Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled Mri., Zungho Zun, Greg Zaharchuk, Nickie N Andescavage, Mary T Donofrio, Catherine Limperopoulos

Pediatrics Faculty Publications

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental …

Weight Management And Physical Activity Throughout The Cancer Care Continuum., Wendy Demark-Wahnefried, Kathryn H Schmitz, Catherine M Alfano, Jennifer R Bail, Pamela J Goodwin, Cynthia A Thomson, Don W Bradley, Kerry S Courneya, Christie A Befort, Crystal S Denlinger, Jennifer A Ligibel, William H Dietz, Melinda R Stolley, Melinda L Irwin, Marcas M Bamman, Caroline M Apovian, Bernardine M Pinto, Kathleen Y Wolin, Rachel M Ballard, Andrew J Dannenberg, Elizabeth G Eakin, Matt M Longjohn, Susan D Raffa, Lucile L Adams-Campbell, Joanne S Buzaglo, Sharyl J Nass, Greta M Massetti, Erin P Balogh, Elizabeth S Kraft, Anand K Parekh, Darshak M Sanghavi, G Stephen Morris, Karen Basen-Engquist

Global Health Faculty Publications

Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, "Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum." Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the …

Clinical Evaluation Of The Cepheid Xpert® Tv Assay For Detection Of Trichomonas Vaginalis With Prospectively Collected Female And Male Specimens., Jane R Schwebke, C A Gaydos, T Davis, J Marrazzo, D Furgerson, S N Taylor, B Smith, L H Bachmann, R Ackerman, T Spurrell, D Ferris, C A Burnham, H Reno, J Lebed, D Eisenberg, P Kerndt, S Philip, J Jordan, N Quigley

Epidemiology Faculty Publications

Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and acquisition/transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA-cleared in the United States for detection of Trichomonas vaginalis (TV) in specimens from both women and men. This current study reports the results of a multicenter study recently conducted using the Xpert TV Assay to test specimens from both men and women. On-demand results were available in as little as 40 minutes for positive specimens. A total of 1867 women and 4791 men were eligible for inclusion in the analysis. …

Transcriptional Alterations In Hereditary And Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors According To Genotype., Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew

Surgery Faculty Publications

BACKGROUND

Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.

METHODS

Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed …

Association Of Teen Mothers' And Grandmothers' Parenting Capacities With Child Development: A Study Protocol., Damali Wilson, Deborah Gross, Stacy Hodgkinson, Kirby Deater-Deckard

Pediatrics Faculty Publications

Children born to teen mothers may experience less responsive and supportive parenting and are at heightened risk for a range of social, developmental, and health issues. There is literature to support the positive impact of grandmothers on teen parents and their children. However, what if the teen's mother is also limited in her parenting capacities? How do parenting capacities across these two generations of mothers affect the developing child? In this ongoing study we are examining two important aspects of parenting capacities, attachment quality and executive functioning, in teen mothers (TM) and their biological, co- residing mothers or grandmothers (GM …

Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar

Exercise and Nutrition Sciences Faculty Publications

Background

Age related decline in physical function is a significant concern affecting the quality of life of older individuals.

Methods

We examined the associations between baseline overall cardiovascular health (CVH), its components, and physical function in 906 men and women from the InCHIANTI cohort. Physical function was assessed using the Short Performance Physical Battery and poor physical function was defined as an Short Performance Physical Battery score less than 10. Overall CVH score, ranging from 0 to 12 in the cohort, was operationalized using adherence to ideal levels for health behaviors including smoking status, physical activity, body mass index, and …

Decentralised Training For Medical Students: A Scoping Review., Marietjie De Villiers, Susan Van Schalkwyk, Julia Blitz, Ian Couper, Kalavani Moodley, Zohray Talib, Taryn Young

Medicine Faculty Publications

BACKGROUND: Increasingly, medical students are trained at sites away from the tertiary academic health centre. A growing body of literature identifies the benefits of decentralised clinical training for students, the health services and the community. A scoping review was done to identify approaches to decentralised training, how these have been implemented and what the outcomes of these approaches have been in an effort to provide a knowledge base towards developing a model for decentralised training for undergraduate medical students in lower and middle-income countries (LMICs).

METHODS: Using a comprehensive search strategy, the following databases were searched, namely EBSCO Host, ERIC, …

Effect Of Intranasally Delivered Rh-Vegf165 On Angiogenesis Following Cerebral Hypoxia-Ischemia In The Cerebral Cortex Of Newborn Piglets., Amit Jain, Panagiotis Kratimenos, Ioannis Koutroulis, Amishi Jain, Amulya Buddhavarapu, Jahan Ara

Pediatrics Faculty Publications

Background: Vascular endothelial growth factor (VEGF) stimulates vascular genesis and angiogenesis. Cerebral Hypoxia-Ischemia (HI) leads to the reduction of vasculature in the cerebral cortex of newborn piglets.

Objective: The present study tests the hypothesis that post-hypoxia intranasal administration of recombinant human VEGF₁₆₅ (rh-VEGF165) for 3 days increases the vascular density in the cerebral cortex of newborn piglets without promoting neovascularization.

Design/Methods: Ventilated newborn piglets were divided into three groups (n = 5/group): normoxic (Nx), hypoxic-ischemic (HI), and HI treated with intranasal rh-VEGF165rh-VEGF165 (HI-VEGF). HI piglets were exposed to HI (0.05 FiO2) for 30 min. Recombinant h-VEGF165 (100 ng/kg) …

Time In Therapeutic Range, As A Determinant Of All-Cause Mortality In Patients With Hypertension., Michael Doumas, Costas Tsioufis, Ross Fletcher, Richard Amdur, Charles Faselis, Vasilios Papademetriou

Medicine Faculty Publications

BACKGROUND: Accumulating evidence indicates that reducing systolic blood pressure (BP) tooutcomes; however, an optimal level has not yet been determined. Many population studies or post hoc analyses suggest a target systolic BP between 120 and 140 mm Hg with increased risk above and below that range. We tested the hypothesis that consistent control of systolic BP between 120 and 140 mm Hg-time in therapeutic range-is a strong determinant of all-cause mortality among US veterans.

METHODS AND RESULTS: A total of 689 051 individuals from 15 Veterans Administration Medical Centers were followed over a 10-year period. Participants were classified as hypertensive, …

Introducing Trainees To Academic Medicine Career Roles And Responsibilities, Cristina Fernandez, Raymond Lucas, Maria Soto-Greene, John Sanchez

E-Learning Modules

Reproduced with permission of the American Association of Medical Colleges. Link to original publication

Thyroid Cancer: Is It All In The Genes?, Electron Kebebew

Surgery Faculty Publications

No abstract provided.

Himmelfarb Library Liaison Letter - November 2017, George Washington University, Himmelfarb Health Sciences Library

Himmelfarb Library Liaison Letters

No abstract provided.

Improving Detection Of Mental Health Problems In Community Settings In Nepal: Development And Pilot Testing Of The Community Informant Detection Tool, Prasansa Subba, Nagendra P. Luitel, Brandon A. Kohrt, Mark Jordans

Psychiatry and Behavioral Sciences Faculty Publications

Background

Despite increasing efforts to expand availability of mental health services throughout the world, there continues to be limited utilization of these services by persons with mental illness and their families. Community-based detection that facilitates identification and referral of people with mental health problems has been advocated as an effective strategy to increase help-seeking and service utilization. The Community Informant Detection Tool (CIDT) was developed for the community informants to identify people with depression, psychosis, alcohol use problems, epilepsy, and child behavioral problems in community settings. The CIDT has been validated in Nepal and found to be effective in promoting …

Clinical Risks And Healthcare Utilization Of Hematopoietic Cell Transplantation For Sickle Cell Disease In The Usa Using Merged Databases., Staci D Arnold, Ruta Brazauskas, Naya He, Yimei Li, Richard Aplenc, Zhezhen Jin, Allistair Abraham, +Several Additional Authors

Pediatrics Faculty Publications

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 >years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of …

Cost-Effectiveness Analysis Of Neonatal Screening Of Critical Congenital Heart Defects In China., Ruoyan Gai Tobe, Gerard R Martin, Fuhai Li, Akinori Moriichi, Bin Wu, Rintaro Mori

Pediatrics Faculty Publications

Background: Pulse oximetry screening is a highly accurate tool for the early detection of critical congenital heart disease (CCHD) in newborn infants. As the technique is simple, noninvasive, and inexpensive, it has potentially significant benefits for developing countries. The aim of this study is to provide information for future clinical and health policy decisions by assessing the costeffectiveness of CCHD screening in China.

Methods and Findings: We developed a cohort model to evaluate the cost-effectiveness of screening all Chinese newborns annually using 3 possible screening options compared to no intervention: pulse oximetry alone, clinical assessment alone, and pulse oximetry as …

Evolution Of Knowledge, Awareness, And Practices Regarding Zika Virus From 2016 To 2017, Quinton Katler, Prachi Godiwala, Charles J. Macri, Beth Pineles, Gary Simon, Aileen Chang, Homa Ahmadzia

Obstetrics and Gynecology Faculty Publications

Objective. Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns.

Study Design. The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4.

Results. Significant …

Geographic Disparities In The Distribution Of The U.S. Gynecologic Oncology Workforce: A Society Of Gynecologic Oncology Study, Stephanie Ricci, Ana Tergas, Kara Roche, Melissa Fairbairn, Kimberly Levinson, Micael Lopez-Acevedo, +Several Additional Authors

Obstetrics and Gynecology Faculty Publications

A recent ASCO workforce study projects a significant shortage of oncologists in the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study aim was to determine the patterns of distribution of U.S. gynecologic oncologists (GO) and to identify provider-based attitudes and barriers that may prevent GOs from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited to participate in an on-line survey regarding geographic distribution and participation in outreach care. A total of 320 GOs (43%) responded; median age range was 35–45 years and 57% were male. Most practiced in an urban setting (72%) at …