Diseases Commons^™

Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals.

CASE PRESENTATION: In this study, a 4-year-old patient with a severe phenotype …

See, I’Ve Grown: A Service Delivery Model For Young Adults With Cleft/Lip Palate, Brenda Louw, Linda Vallino

ETSU Faculty Works

We compare the health needs between children and young adults with CL/P. Patient-reported experiences about the impact of a cleft are described. A service delivery model integrating quality of life into the ICF framework is presented. Lastly, transition of care for the young adult with CL/P is highlighted.

Nutrition Students’ Perception Of The Role Of The Slps In Treating People Living With Hiv/Aids, Stephanie Bare, Natalie Dubin, Haley Hawks, Kathleen Quinn, Brittany Ratliff, Brenda Louw

ETSU Faculty Works

This project explores nutrition students’ perceptions of SLPs' and Nutritionists’ role in healthcare needs of PLWHA through survey research. The results will describe participants’ perceptions of the SLPs' and Nutritionists’ roles in the healthcare needs of PLWHA. Recommendations are made regarding interprofessional training curricula for SLP and Nutrition students.

The Icf-Cy As Framework For International Collaboration To Improve Services For Children With Communication Disorders, Brenda Louw, Juan Bornman

ETSU Faculty Works

The purpose of this presentation is to describe the application of The International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) (WHO, 2007) as a framework for international collaboration with the aim of translating an outcomes measure and to field test the clinical applicability and cultural validity thereof.

When It Isn’T Always Lyme: Expanding The Differential Diagnosis For Acute-Onset Polyarthralgia In The West Virginia Eastern Panhandle, Natalie A. Moffett, Rosemarie Lorenzetti

Marshall Journal of Medicine

This case presentation discusses a 36 year-old female animal care worker presenting with an acute-onset polyarthropathy during the summer months in a Lyme endemic region. Though she appeared to be a good candidate for the diagnosis of Lyme borreliosis, her screening serology reported negative results and alternative diagnoses were considered. Her subsequent diagnosis with parvovirus B19 acts to remind the general practitioner to have confidence in the accuracy of a negative Lyme screen and, upon negative result, to expand the differential to include less common infections including parvovirus B19. It also highlights the need to remember parvovirus B19 in a …

The Changing Landscape Of Biosimilars In Rheumatology, Thomas Dorner, Vibeke Strand, Paul Cornes, Joao Goncalves, Laszlo Gulacsi, Jonathan Kay, Tore K. Kvien, Josef S. Smolen, Yoshiya Tanaka, Gerd R. Burmester

Jonathan Kay

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities …

Erythrocytes In Multiple Sclerosis – Forgotten Contributors To The Pathophysiology?, Kira Groen, Katherine A. Sanders, Rodney J. Scott, Lotti Tajouri, Jeannette Lechner-Scott

Lotti Tajouri

Multiple sclerosis (MS) is an autoimmune disease characterised by lymphocytic infiltration of the central nervous system and subsequent destruction of myelin and axons. On the background of a genetic predisposition to autoimmunity, environmental triggers are assumed to initiate the disease. The majority of MS research has focused on the pathological involvement of lymphocytes and other immune cells, yet a paucity of attention has been given to erythrocytes, which may play an important role in MS pathology. The following review briefly summarises how erythrocytes may contribute to MS pathology through impaired antioxidant capacity and altered haemorheological features. The effect of disease-modifying …

Disability And Return To Work Following Musculoskeletal Injury, Qiyun Shi

Electronic Thesis and Dissertation Repository

Musculoskeletal disorders (MSDs) are injuries, damage or disorders affecting the musculoskeletal system including muscles, ligaments, nerves, tendons, bones or cartilage etc. MSDs are highly prevalent and associated with sickness absence, reduced work efficiency, job changes and earlier retirement.. They also affect daily activity and social functioning. Although many MSDs are accompanied by minor symptoms and settled spontaneously, approximately 10% of the workforce with MSDs have difficulty resuming their original work or exit the workforce permanently. Return to work after MSDs is complex, and is influenced by many factors including physical, psychological, economic and social factors.

Although there are extensive studies …

A Comparison Of Cervical And Trunk Musculoskeletal Characteristics Between Female And Male Army Helicopter Pilots, Takashi Nagai, Karen A. Keenan, John P. Abt, Timothy C. Sell, Brian W. Smalley, Michael D. Wirt, Scott M. Lephart

International Journal of Aviation, Aeronautics, and Aerospace

Introduction: Neck pain (NP) and low back pain (LBP) are prevalent among military helicopter pilots. Although there have been few studies on sex differences in the NP/LBP prevalence in this population, females are shown to be at a greater risk of NP/LBP in civilian studies. This disparity may be due to musculoskeletal characteristics differences that predispose females for NP/LBP. The purpose of this study was to compare cervical and trunk musculoskeletal characteristics between male and female pilots. Methods: A total of 8 female pilots (Age: 27.6 ± 4.2yrs, HT: 166.1 ± 7.7cm, WT: 67.9 ± 10.6kg) were tested, and they …

Inpatient Versus Outpatient Total Hip Arthroplasty, Michael Pollock

Electronic Thesis and Dissertation Repository

We conducted a randomized controlled trial to evaluate patients undergoing a total hip arthroplasty (THA) who were discharged from the hospital either on the day of surgery (outpatient) or were admitted overnight following surgery (inpatient). Our primary outcome was the rate of serious adverse events during the first three months postoperatively. Secondary outcome measures included cost, patient satisfaction, functional outcomes, quality of life and pain. We found no statistically significant difference between the two groups in serious adverse events. We found that outpatient THA was less expensive from the perspectives of the hospital and ministry of health; but the difference …

Statin Therapy For Elderly Patients Should Be Assessed For Each Individual, Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623-30. doi:10.1016/S0140-6736(02)11600-X

Peroxisome Proliferator Activated Receptor Delta In Osteoarthritis, Anusha Ratneswaran

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) affects 1 in 10 Canadians and is a leading cause of mobility disability worldwide. This condition is characterized by cartilage degeneration, subchondral bone damage and inflammation of the synovium, resulting in pain and joint failure. No treatments exist to stop the progression of this disease, and its underlying molecular mechanisms remain largely unknown. We previously identified the peroxisome proliferator activated receptor (PPAR) nuclear receptor pathway as altered in OA cartilage. In-vitro studies identified PPARd as a promoter of catabolic activity in chondrocytes, providing the foundation for my overarching hypothesis that PPARd inhibition is protective in OA.

I commenced …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Health Care Transition Program For Adolescents With Spina Bifida, Teresa M. Scavone

Doctor of Nursing Practice Final Manuscripts

The purpose of this evidence-based project was to evaluate the feasibility of implementing an NP facilitated formal transition program for adolescents with Spina Bifida. There is an increased awareness of the need for health care transition for youth with special health care needs (YSHCN) due to the 2009-2010 Maternal Child Health Branch National Survey findings that only 40% of YSHCN receive adequate support for transition that meets the core outcome measures. Recent studies have investigated transition in youth with chronic disease specific conditions such as diabetes, cystic fibrosis, and congenital heart defects, and provide valuable insight into possible strategies for …

Biosimilars In Rheumatology: What The Clinician Should Know, Gilberto Castaneda-Hernandez, Rodrigo Gonzalez-Ramirez, Jonathan Kay, Morton A. Scheinberg

Jonathan Kay

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

Injury Risk Assessment Of The Femur In Children With Osteogenesis Imperfecta, Jessica Marie Fritz

Dissertations (1934 -)

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and decreased bone mass, which leads to high rates of bone fracture. OI has a prevalence of 1/5,000 to 1/10,000 in the United States. About 90% of persons with OI have a genetic mutation in the coding for collagen type I, which is the major protein of connective tissues, including bone. While its prevalence classifies it as a rare disease, it is the most common disorder of bone etiology. Until recently, little was known about the mechanics and materials of OI bone or their impact on fracture risk. …

Examining Maternal Obesity Effects On Oogenesis, Follicular Development, And Embryonic Myogenesis, Chris Lindeman, Jennifer Wood

UCARE Research Products

The CDC estimates that more than one-third of U.S. adults (approximately 78.6 million) are obese. Despite national efforts to combat this with diet and exercise, the number of obese adults and children continues to climb. It is critical to emphasize that obesity can lead to lifelong, chronic complications and health risks including hypertension, heart disease, and diabetes.

Diet and obesity also have important impacts on the reproductive health of female including the ability to become pregnant (fertility) and risk for complications during pregnancy. Furthermore, for women who do become pregnant, obesity can affect the development of the embryo and fetus, …

Global Engagement: Problem Solving And Information Exchange, Vinaya Manchaiah, Brenda Louw

ETSU Faculty Works

This interactive session provides opportunities (1) to share ideas for infusing global perspectives and goals into CAPCSD projects, conferences, and the work of committees and task forces; (2) to discuss ways to collaborate in an ongoing global engagement projects and help include content for 2017 conference; and (3) to create how-to guides for ethical and culturally attuned translational research, and clinical education, and service learning.

Huntington's Disease--A Review, Christen Dunn

The Kabod

Huntington’s disease is degenerative and effects both cognitive and motor functioning, beginning in the 20s and continuing a decline for about two decades until death. In this disease, the huntingtin gene on chromosome four codes for an abnormally elongated repeating CAG polypeptide sequence. This mutation causes an atrophy in the brain that translates into decreasing control of movements and other aspects of cognition. To date, there is no cure for Huntington’s disease, but there are treatments for many symptoms that accompany the disease. Even still, there are promising new methods that may be more beneficial to patients in the future.

Tocilizumab In Early Progressive Rheumatoid Arthritis: Function, A Randomised Controlled Trial, Gerd R. Burmester, William F. Rigby, Ronald F. Van Vollenhoven, Jonathan Kay, Andrea Rubbert-Roth, Ariella Kelman, Sophie Dimonaco, Nina Mitchell

Jonathan Kay

OBJECTIVES: The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). METHODS: In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28-erythrocyte sedimentation rate (ESR) < 2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week …

Golimumab In Patients With Active Rheumatoid Arthritis After Treatment With Tumor Necrosis Factor Inverted Question Mark Inhibitors: Findings With Up To Five Years Of Treatment In The Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Go-After Study, Josef S. Smolen, Jonathan Kay, Mittie Doyle, Robert Landewe, Eric L. Matteson, Norman Gaylis, Jurgen Wollenhaupt, Frederick T. Murphy, Stephen Xu, Yiying Zhou, Elizabeth C. Hsia

Jonathan Kay

Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor- inverted question mark (TNF)-inhibitor(s). Methods:Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA ( inverted question mark4 tender, inverted question mark4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group …

Golimumab 3-Year Safety Update: An Analysis Of Pooled Data From The Long-Term Extensions Of Randomised, Double-Blind, Placebo-Controlled Trials Conducted In Patients With Rheumatoid Arthritis, Psoriatic Arthritis Or Ankylosing Spondylitis, Jonathan Kay, Roy Fleischmann, Edward Keystone, Elizabeth C. Hsia, Benjamin Hsu, Michael Mack, Neil Goldstein, Jurgen Braun, Arthur Kavanaugh

Jonathan Kay

OBJECTIVE: To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials. METHODS: Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naive, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naive), with early escape at wk 16 (wk 28, methotrexate-naive); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety …

Sarilumab For The Treatment Of Ankylosing Spondylitis: Results Of A Phase Ii, Randomised, Double-Blind, Placebo-Controlled Study (Align), Joachim Sieper, Jurgen Braun, Jonathan Kay, Salvatore Badalamenti, Allen R. Radin, Lixia Jiao, Stefano Fiore, Tanya Momtahen, George D. Yancopoulos, Neil Stahl, Robert D. Inman

Jonathan Kay

OBJECTIVES: The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-alpha (IL-6Ralpha), in patients with ankylosing spondylitis (AS). METHODS: Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease …

An Ultrasonographic Analysis Of The Structures Of The Subacromial Space, As They Relate To The Postures Of Upper String Musicians, Elliot V. Smithson

Theses, Dissertations and Capstones

Background: The leading source of general population shoulder pain is subacromial impingement syndrome (SAIS) which can contribute to rotator cuff disease (RCD). 1 It has been reported that up to 12% of musicians end their musical career due to musculoskeletal injury.2 SAIS is a common source of shoulder pain in the bowing arm of upper string musicians.3 However, the mechanisms leading to shoulder pain in upper string musicians are not well known.

Purpose: The purpose of this study was to characterize aspects of the subacromial space anatomy while in standard playing positions of upper string musicians, specifically measurements …

Is Viscosupplementation Effective In Reducing Osteoarthritis Knee Pain?, Amalia Antonoplos

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not viscosupplementation is effective in reducing osteoarthritis knee pain

STUDY DESIGN: Review of three randomized, double blind, placebo control trials between 2009- 2010

DATA SOURCES: Three randomized, double blind, placebo control trials were found via PubMed and NCBI

OUTCOMES MEASURED: Each randomized control trial measured knee pain and/or patient satisfaction following their intervention (placebo or hyaluronic acid) in patients with knee osteoarthritis, which was measured via WOMAC pain scale and patient global assessment forms.

RESULTS: (P<0.05) for change in pain at 14-26 weeks after injection (NNT=6- 8 for Chevalier et al and 4 for Kul-Panza & Berker). Patient satisfaction was higher in the experimental groups as compared to the control with conclusions of NNT between 11 and 20 for Chevalier et al and Kul-Panza & Berker respectively. Chavelier et al found adverse events such as arthralgias and joint effusion in <10% of their study population (NNH=39). No dichotomous data was presented in Diacoglu et al; however an ANOVA was deemed statistically significant (p<0.01).

CONCLUSION: Review of these articles concludes that the use of hyaluronic …

Is Laser Therapy An Effective Alternative Treatment For Women With Fibromyalgia?, Michelle B. Astrove

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not, “Is the use of laser therapy an effective alternative treatment for women with fibromyalgia?”

STUDY DESIGN: Review of three English language primary studies, published between 2002 and 2013.

DATA SOURCES: Three randomized controlled trials (RCTs) were found using Cochrane Systematic Reviews. These studies analyzed the effectiveness of laser therapy in women with fibromyalgia.

OUTCOMES MEASURED: Main outcomes measured were improvement in pain, number of tender points, muscular spasm, skinfold tenderness, sleep disturbance, fatigue and morning stiffness measured by an ordinal likert scale, Pain and FM impact …

Is Acupuncture, Including Electroacupuncture, Effective In Treating Pain In Plantar Fasciitis?, Alicia Campiglia

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether the use of acupuncture, including electroacupuncture, is effective in treating pain in patients with plantar fasciitis.

STUDY DESIGN: Review of 3 RCTs published between 2011-current, all in the English language.

DATA SOURCES: Three RCTs analyzed the effectiveness of acupuncture therapy compared to a control group using alternate analgesic therapies. All studies were found using EBSCOhost and PubMed and were selected based on relevance to the proposed clinical question.

OUTCOMES MEASURED: Each of the 3 articles analyzed the effectiveness of treating pain with acupuncture treatment in patients diagnosed with …

Is Vitamin D Supplementation Effective At Reducing Idiopathic Musculoskeletal (Mss) Pain?, Darra O. Markland

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine “Is Vitamin D supplementation effective at reducing idiopathic musculoskeletal (MSS) pain?”

Study Design: Review of primary studies published between the years 2012-2014.

Data Sources: One double blind randomized controlled trial (RCT), one semi-crossover RCT, and one before and after observational study. These were found using Cochrane Review and PubMed databases.

Outcomes Measured: Clinical outcomes were measured in these studies utilizing the Visual Analogue Scale for Pain, the 5-point Likert Pain Scale, the Standard Nordic Questionnaires and numerical grading of pain level, and number of pain sites before and after …

Do Epidural Injections With Local Anesthetic With Steroids Have Superiority Over Injections With Local Anesthetic Alone When Treating Chronic Back Pain Due To An Intervertebral Disc Herniation In Men And Women Over 18 Years Old?, Julia S. Ross

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not, “Do epidural injections with local anesthetic with steroids have superiority over injections with local anesthetic alone when treating chronic back pain due to an intervertebral disc herniation in men and women over 18 years old?”

STUDY DESIGN: Review of three, double blind, randomized controlled trials (RCTs) published between 2011-2014, all in English language. The articles compared epidural injections containing local anesthetic with steroids to epidural injections containing local anesthetics alone.

DATA SOURCES: Three Randomized controlled trials found using PubMed. All articles were published in peer-reviewed journals …

Discovery Of Metabolic Biomarkers For Duchenne Muscular Dystrophy Within A Natural History Study., Simina M. Boca, Maki Nishida, Michael Harris, Shruti Rao, Amrita Cheema, Kirandeep Gill, Haeri Seol, Lauren P. Morgenroth, Erik Henricson, Craig M. Mcdonald, Jean K. Mah, Paula R. Clemens, Eric P. Hoffman, Yetrib Hathout, Subha Madhavan

Pediatrics Faculty Publications

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown …