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Statin Therapy For Elderly Patients Should Be Assessed For Each Individual, Raymond Gong 2016 Wayne State University School of Medicine

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


Osteopetrorickets Due To Snx10 Deficiency In Mice Results From Both Failed Osteoclast Activity And Loss Of Gastric Acid-Dependent Calcium Absorption, Liang Ye, Leslie R. Morse, Li Zhang, Hajime Sasaki, Jason C. Mills, Paul R. Odgren, Greg Sibbel, James R.L. Stanley, Gee Wong, Ariane Zamarioli, Ricardo A. Battaglino 2016 The Forsyth Institute

Osteopetrorickets Due To Snx10 Deficiency In Mice Results From Both Failed Osteoclast Activity And Loss Of Gastric Acid-Dependent Calcium Absorption, Liang Ye, Leslie R. Morse, Li Zhang, Hajime Sasaki, Jason C. Mills, Paul R. Odgren, Greg Sibbel, James R.L. Stanley, Gee Wong, Ariane Zamarioli, Ricardo A. Battaglino

Paul R. Odgren PhD

Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis ...


Efficacy And Safety Results From A Phase 3, Randomized, Placebo-Controlled Trial Of Subcutaneous Golimumab In Chinese Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy, Zhanguo Li, Fengchun Zhang, Jonathan Kay, Kaiyin Fei, Chenglong Han, Yanli Zhuang, Zhong Wu, Elizabeth C. Hsia 2016 Peking University

Efficacy And Safety Results From A Phase 3, Randomized, Placebo-Controlled Trial Of Subcutaneous Golimumab In Chinese Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy, Zhanguo Li, Fengchun Zhang, Jonathan Kay, Kaiyin Fei, Chenglong Han, Yanli Zhuang, Zhong Wu, Elizabeth C. Hsia

Jonathan Kay

AIM: The efficacy and safety of golimumab + methotrexate (MTX) were evaluated in Chinese patients with active rheumatoid arthritis (RA) despite MTX therapy. METHODS: Chinese patients (n = 264) were randomly assigned (1 : 1) to receive subcutaneous injections of placebo + MTX with crossover to golimumab 50 mg + MTX at week 24 (Group 1) or to golimumab 50 mg + MTX (Group 2) every 4 weeks. Group 1 patients with inadequate response entered blinded early escape to golimumab 50 mg + MTX at week 16. At least a 20% improvement in the American College of Rheumatology (ACR20) criteria at week 14 was the primary endpoint ...


Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis And Current Skin Involvement: A Phase Iii, Randomised, Controlled Trial (Palace 3), Christopher J. Edwards, Francisco J. Blanco, Jeffrey Crowley, Charles Birbara, Janusz Jaworski, Jacob Aelion, Randall M. Stevens, Adele Vessey, Xiaojiang Zhan, Paul Bird 2016 University Hospital Southampton

Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis And Current Skin Involvement: A Phase Iii, Randomised, Controlled Trial (Palace 3), Christopher J. Edwards, Francisco J. Blanco, Jeffrey Crowley, Charles Birbara, Janusz Jaworski, Jacob Aelion, Randall M. Stevens, Adele Vessey, Xiaojiang Zhan, Paul Bird

Open Access Articles

OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.

METHODS: Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed ...


Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu 2016 Chapman University

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 ...


Effective Pain Information Pre-Operatively Is Associated With Improved Functional Gain After Total Joint Replacement, Celeste A. Lemay, David Ayers, Patricia D. Franklin 2016 University of Massachusetts Medical School

Effective Pain Information Pre-Operatively Is Associated With Improved Functional Gain After Total Joint Replacement, Celeste A. Lemay, David Ayers, Patricia D. Franklin

UMass Center for Clinical and Translational Science Research Retreat

Objective: We evaluated receipt of pre-operative pain management education in a national prospective cohort on post-operative pain and function.

Methods: Preoperative, 2 week and 6 month postoperative data from a nationally representative cohort of 1404 primary unilateral TJR patients with a date of surgery between May 2011 and December 2014. Data included demographics, comorbid conditions, operative joint pain severity (HOOS/KOOS), musculoskeletal disease burden, physical function (SF36 PCS), and mental health (SF36 MCS). At 2 weeks post-op, patients were asked if they had received information prior to surgery about pain management options and if so, how helpful the information was ...


Correlates Of Hyaluronic Acid And Corticosteroid Injections Among Patients With Radiographically Confirmed Osteoarthritis, Shao-Hsien Liu, Catherine E. Dube, Jeffrey B. Driban, Timothy E. McAlindon, Charles Eaton, Kate L. Lapane 2016 University of Massachusettts Medical School

Correlates Of Hyaluronic Acid And Corticosteroid Injections Among Patients With Radiographically Confirmed Osteoarthritis, Shao-Hsien Liu, Catherine E. Dube, Jeffrey B. Driban, Timothy E. Mcalindon, Charles Eaton, Kate L. Lapane

UMass Center for Clinical and Translational Science Research Retreat

Objective: Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving them is scarce. We described use of injections among adults with radiographically confirmed knee OA and identified correlates of injection use.

Methods: We used publicly available data from Osteoarthritis Initiative and included participants with ≥ one radiographically confirmed knee OA (Kellgren-Lawrence grade (K-L) > 2) at baseline. We matched 415 participants reporting HA and/or CO during the 6 month before one of the first 7 annual follow-up assessments to 1,841 non-injection users ...


Using Interviews To Understand Patients’ Post-Operative Pain Management Educational Needs Before And After Elective Total Joint Replacement Surgery, Celeste A. Lemay, Patricia D. Franklin 2016 University of Massachusetts Medical School

Using Interviews To Understand Patients’ Post-Operative Pain Management Educational Needs Before And After Elective Total Joint Replacement Surgery, Celeste A. Lemay, Patricia D. Franklin

UMass Center for Clinical and Translational Science Research Retreat

Objective: To better understand the education needs of patients electing to have TJR in managing their pain in the post-operative period after discharge from the hospital.

Methods: An exploratory, descriptive, qualitative design. Convenience sample of people who reported that they had not received information about pain management prior to TJR surgery were recruited from 9 surgeon practices in 8 states to participate in telephone interviews, utilizing open-ended questions. Questions included: recollection of pre-op class attended and content; experiences with surgical pain after surgery and how it was managed; experiences with pain medicine; experience using non-medicine related pain reduction methods; suggestions ...


Patient Reported Outcomes In Arthritis, Tjr, And Physical Activity Research, Patricia D. Franklin 2016 University of Massachusetts Medical School

Patient Reported Outcomes In Arthritis, Tjr, And Physical Activity Research, Patricia D. Franklin

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "Biomechanical Gait Analysis for Improving Clinical Outcomes: Applications for Orthopedics, Geriatrics and Community Based Research," this presentation discusses the importance of patient reported outcomes (PRO) in clinical research and the PRO/physical activity translational research in osteoarthritis and and total joint replacement at UMass Medical School.


Examining Movement Function In Patients With Knee Osteoarthritis, Katherine A. Boyer 2016 University of Massachusetts Amherst

Examining Movement Function In Patients With Knee Osteoarthritis, Katherine A. Boyer

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "Biomechanical Gait Analysis for Improving Clinical Outcomes: Applications for Orthopedics, Geriatrics and Community Based Research," this presentation explores research on gait analysis and pain for patients with knee osteoarthritis.


Biosimilars In Rheumatology: What The Clinician Should Know, Gilberto Castaneda-Hernandez, Rodrigo Gonzalez-Ramirez, Jonathan Kay, Morton A. Scheinberg 2016 National Polytechnic Institute

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.


Examining Maternal Obesity Effects On Oogenesis, Follicular Development, And Embryonic Myogenesis, Chris Lindeman, Jennifer Wood 2016 University of Nebraska-Lincoln

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 ...


Huntington's Disease--A Review, Christen Dunn 2016 Liberty University

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 ...


Transgenic Drosophila For Investigating Dux4 And Frg1, Two Genes Associated With Facioscapulohumeral Muscular Dystrophy (Fshd), Takako I. Jones, Megan Parilla, Peter L. Jones 2016 University of Massachusetts Medical School

Transgenic Drosophila For Investigating Dux4 And Frg1, Two Genes Associated With Facioscapulohumeral Muscular Dystrophy (Fshd), Takako I. Jones, Megan Parilla, Peter L. Jones

Peter Jones Lab

Facioscapulohumeral muscular dystrophy (FSHD) is typically an adult onset dominant myopathy. Epigenetic changes in the chromosome 4q35 region linked to both forms of FSHD lead to a relaxation of repression and increased somatic expression of DUX4-fl (DUX4-full length), the pathogenic alternative splicing isoform of the DUX4 gene. DUX4-fl encodes a transcription factor expressed in healthy testis and pluripotent stem cells; however, in FSHD, increased levels of DUX4-fl in myogenic cells lead to aberrant regulation of target genes. DUX4-fl has proven difficult to study in vivo; thus, little is known about its normal and pathogenic roles. The endogenous expression of DUX4-fl ...


Promotion Of Inflammatory Arthritis By Interferon Regulatory Factor 5 In A Mouse Model, Pierre Duffau, Hanni Menn-Josephy, Carla Cuda, Salina Dominguez, Tamar Aprahamian, Amanda Watkins, Kei Yasuda, Paul Monach, Robert Lafyatis, Lisa Rice, G. Kenneth Haines, Ellen Gravallese, Rebecca Baum, Christophe Richez, Harris Perlman, Ramon Bonegio, Ian Rifkin 2016 Boston University School of Medicine

Promotion Of Inflammatory Arthritis By Interferon Regulatory Factor 5 In A Mouse Model, Pierre Duffau, Hanni Menn-Josephy, Carla Cuda, Salina Dominguez, Tamar Aprahamian, Amanda Watkins, Kei Yasuda, Paul Monach, Robert Lafyatis, Lisa Rice, G. Kenneth Haines, Ellen Gravallese, Rebecca Baum, Christophe Richez, Harris Perlman, Ramon Bonegio, Ian Rifkin

Ellen M. Gravallese

OBJECTIVE: Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development. METHODS: K/BxN serum-transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the ...


Skeletal Characterization Of Smurf2-Deficient Mice And In Vitro Analysis Of Smurf2-Deficient Chondrocytes, Henry Huang, Eric S. Veien, Hong Zhang, David C. Ayers, Jie Song 2016 University of Massachusetts Medical School

Skeletal Characterization Of Smurf2-Deficient Mice And In Vitro Analysis Of Smurf2-Deficient Chondrocytes, Henry Huang, Eric S. Veien, Hong Zhang, David C. Ayers, Jie Song

GSBS Student Publications

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene ...


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 Hsia, Benjamin Hsu, Michael Mack, Neil Goldstein, Jurgen Braun, Arthur Kavanaugh 2016 University of Massachusetts Medical School Worcester

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 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 ...


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 Smolen, Jonathan Kay, Mittie Doyle, Robert Landewe, Eric Matteson, Norman Gaylis, Jurgen Wollenhaupt, Frederick Murphy, Stephen Xu, Yiying Zhou, Elizabeth Hsia 2016 Medical University of Vienna

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 Smolen, Jonathan Kay, Mittie Doyle, Robert Landewe, Eric Matteson, Norman Gaylis, Jurgen Wollenhaupt, Frederick Murphy, Stephen Xu, Yiying Zhou, Elizabeth 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 ...


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 Radin, Lixia Jiao, Stefano Fiore, Tanya Momtahen, George Yancopoulos, Neil Stahl, Robert Inman 2016 Charité University Medicine Berlin

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 Radin, Lixia Jiao, Stefano Fiore, Tanya Momtahen, George Yancopoulos, Neil Stahl, Robert 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 ...


Factors Associated With Early Improvement In Low Back Pain After Total Hip Arthroplasty: A Multi-Center Prospective Cohort Analyses, Peter Chimenti, Christopher Drinkwater, Wenjun Li, Celeste Lemay, Patricia Franklin, Regis O'Keefe 2016 University of Rochester

Factors Associated With Early Improvement In Low Back Pain After Total Hip Arthroplasty: A Multi-Center Prospective Cohort Analyses, Peter Chimenti, Christopher Drinkwater, Wenjun Li, Celeste Lemay, Patricia Franklin, Regis O'Keefe

Wenjun Li

This study identified factors associated with an improvement in low back pain (LBP) at six-month follow-up after total hip arthroplasty (THA). Data from a national registry of 3054 patients were analyzed. Factors under analysis included demographics, comorbid conditions, operative and nonoperative joint pain severity, physical function, and mental health. Differences in these factors between patients with and without improvement in LBP were examined. Among patients reporting severe or moderate LBP preoperatively, 56% improved 6months after surgery. Patients without improvement were more likely to be on Medicare, have a high school education or less, have household income less than $45,000 ...


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