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Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge 2017 George Washington University

Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge

Pediatrics Faculty Publications

Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention ...


Age-Dependent Changes In The Articular Cartilage And Subchondral Bone Of C57bl/6 Mice After Surgical Destabilization Of Medial Meniscus, Henry Huang, Jordan D. Skelly, David C. Ayers, Jie Song 2017 University of Massachusetts Medical School

Age-Dependent Changes In The Articular Cartilage And Subchondral Bone Of C57bl/6 Mice After Surgical Destabilization Of Medial Meniscus, Henry Huang, Jordan D. Skelly, David C. Ayers, Jie Song

Jie Song

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores ...


Using Mhealth App To Support Treatment Decision-Making For Knee Arthritis: Patient Perspective, Hua Zheng, Bengisu Tulu, Wonchan Choi, Patricia Franklin 2017 University of Massachusetts Medical School

Using Mhealth App To Support Treatment Decision-Making For Knee Arthritis: Patient Perspective, Hua Zheng, Bengisu Tulu, Wonchan Choi, Patricia Franklin

Patricia D. Franklin

Introduction: Mobile health (mHealth) technology can be used to integrate into medical decision-making for patients with advanced knee arthritis. We explored patient preferences on content and design of a mobile health app to facilitate daily symptom capture and summary feedback reporting, in order to inform treatment decisions, including use of total knee replacement surgery (TKR).

Methods: Patient focus groups were conducted to gather requirements for mHealth app development and to refine the design and content of the app. Clinician (physical therapist, surgeon) interviews were conducted to understand clinician expectations from the summary trend report generated by the app.

Results: Sixteen ...


Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer 2017 DePaul University

Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer

DePaul Discoveries

Reduction of stressors and anxiety levels in adolescents with chronic illnesses is a critical concept in pediatric health care in America today. The many stressors associated with chronic illness include displaying physical and mental differences, social stigma, financial difficulty, and family stress. These stressors may affect the adolescent’s ability to learn and cope in everyday life. The current research was a critical review of the literature examining studies done with adolescents coping with chronic diseases and illnesses. The aim was to analyze the most efficacious non-pharmacological methods for reducing stressors in adolescents with chronic illness. A critical review of ...


Tocilizumab Combination Therapy Or Monotherapy Or Methotrexate Monotherapy In Methotrexate-Naive Patients With Early Rheumatoid Arthritis: 2-Year Clinical And Radiographic Results From The Randomised, Placebo-Controlled Function Trial, Gerd R. Burmester, William F. Rigby, Ronald F. van Vollenhoven, Jonathan Kay, Andrea Rubbert-Roth, Ricardo Blanco, Alysha Kadva, Sophie Dimonaco 2017 Charite-Universitatsmedizin Berlin

Tocilizumab Combination Therapy Or Monotherapy Or Methotrexate Monotherapy In Methotrexate-Naive Patients With Early Rheumatoid Arthritis: 2-Year Clinical And Radiographic Results From The Randomised, Placebo-Controlled Function Trial, Gerd R. Burmester, William F. Rigby, Ronald F. Van Vollenhoven, Jonathan Kay, Andrea Rubbert-Roth, Ricardo Blanco, Alysha Kadva, Sophie Dimonaco

Open Access Articles

OBJECTIVE: Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.

METHODS: Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) < /=3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory.

RESULTS: Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission ( < 2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports.

CONCLUSIONS: Patients with early RA treated with ...


Fatigue In Children And Adolescents With Duchenne Muscular Dystrophy, Basmah El-Aloul 2017 The University of Western Ontario

Fatigue In Children And Adolescents With Duchenne Muscular Dystrophy, Basmah El-Aloul

Electronic Thesis and Dissertation Repository

Fatigue was recently reported to be the largest predictor of poor health-related quality of life (HRQOL) in children and adolescents with Duchenne muscular dystrophy (DMD). The objectives of this thesis were to describe fatigue from patients’ and parents’ perspectives and to explore associations of patient characteristics with fatigue in children and adolescents with DMD using a multicentre cross-sectional study design. Eligible patients and their parents were identified via the Canadian Neuromuscular Disease Registry and received mailed paper questionnaires. Children and adolescents with DMD experienced greater fatigue compared to healthy controls from published data. Fatigue was a significant issue in children ...


Infusion-Related Reactions With Pegloticase, A Recombinant Uricase For The Treatment Of Chronic Gout Refractory To Conventional Therapy, Herbert S. B. Baraf, Robert A. Yood, Faith D. Ottery, John S. Sundy, Michael A. Becker 2017 Center for Rheumatology & Bone Research

Infusion-Related Reactions With Pegloticase, A Recombinant Uricase For The Treatment Of Chronic Gout Refractory To Conventional Therapy, Herbert S. B. Baraf, Robert A. Yood, Faith D. Ottery, John S. Sundy, Michael A. Becker

Robert A. Yood

BACKGROUND: In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported.

OBJECTIVE: The objective of this study was to provide a detailed account of IRs with pegloticase therapy.

METHODS: Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse ...


Validity Of The Nurses' Health Study Physical Activity Questionnaire In Estimating Physical Activity In Adults With Rheumatoid Arthritis, Thomas Quinn, Michelle Frits, Johan von Heideken, Christine Iannaccone, Nancy A. Shadick, Michael Weinblatt, Maura D. Iversen 2017 University of Massachusetts Medical School

Validity Of The Nurses' Health Study Physical Activity Questionnaire In Estimating Physical Activity In Adults With Rheumatoid Arthritis, Thomas Quinn, Michelle Frits, Johan Von Heideken, Christine Iannaccone, Nancy A. Shadick, Michael Weinblatt, Maura D. Iversen

Open Access Articles

BACKGROUND: Patients with rheumatoid arthritis (RA) demonstrate reduced aerobic capacity, excess cardiovascular risk, mobility limitations and are less physically active than their healthy peers. Physical activity may decrease RA disease activity through its anti-inflammatory effects and psychological and health benefits. To successfully manage RA symptoms and reduce cardiovascular risks associated with RA through increased physical activity (PA), accurate physical activity assessments are critical. Accelerometry is an objective physical activity measure, but not widely used. Validity of the Nurses' Health Study physical activity questionnaire II (NHSPAQ) has not been determined for estimation of physical activity in RA. This study examined NHSPAQ ...


Comparative Effectiveness Of Abatacept Versus Tocilizumab In Rheumatoid Arthritis Patients With Prior Tnfi Exposure In The Us Corrona Registry, Leslie R. Harrold, George W. Reed, Daniel H. Solomon, Jeffrey R. Curtis, Mei Liu, Jeffrey D. Greenberg, Joel M. Kremer 2017 University of Massachusetts Medical School

Comparative Effectiveness Of Abatacept Versus Tocilizumab In Rheumatoid Arthritis Patients With Prior Tnfi Exposure In The Us Corrona Registry, Leslie R. Harrold, George W. Reed, Daniel H. Solomon, Jeffrey R. Curtis, Mei Liu, Jeffrey D. Greenberg, Joel M. Kremer

Leslie R. Harrold

BACKGROUND: We compared the effectiveness of abatacept (ABA) vs tocilizumab (TCA) in tumor necrosis factor inhibitor (TNFi) experienced patients. METHODS: We identified rheumatoid arthritis (RA) patients from a large observational US cohort (1 January 2010-31 May 2014) who had discontinued at least one TNFi and initiated ABA or TCZ in moderate or high disease activity based on the Clinical Disease Activity Index (CDAI) and had no prior exposure to the comparator drug. Using propensity score matching (1:1) stratified by prior TNF use (1 TNFi vs ≥2 TNFis), effectiveness at 6 months after initiation was evaluated. Mean change in CDAI ...


Using Mhealth App To Support Tkr Decision Making For Knee Arthritis Patients, Hua Zheng, Bengisu Tulu, Wonchan Choi, Patricia D. Franklin 2017 University of Massachusetts Medical School

Using Mhealth App To Support Tkr Decision Making For Knee Arthritis Patients, Hua Zheng, Bengisu Tulu, Wonchan Choi, Patricia D. Franklin

UMass Center for Clinical and Translational Science Research Retreat

Introduction: Mobile health (mHealth) technology can be used to integrate into medical decision making for patients with advanced knee arthritis. We explored patient preferences on content and design of a mobile health app to facilitate daily symptom capture and summary feedback reporting, in order to inform treatment decisions, including use of total knee replacement surgery (TKR).

Methods: We developed an Android-based smart phone app for knee arthritis patients to assess arthritis symptoms and individual readiness for TKR surgery. Patient focus groups were conducted to gather requirements for mHealth app development and to refine the design and content of the app ...


C1qbp Inhibits Dux4-Dependent Gene Activation And Can Be Targeted With 4mu, Alec M. DeSimone, Genila Bibat, Kathryn Wagner, Guido Stadler, Woodring E. Wright, John D. Leszyk, Charles P. Emerson Jr. 2017 University of Massachusetts Medical School

C1qbp Inhibits Dux4-Dependent Gene Activation And Can Be Targeted With 4mu, Alec M. Desimone, Genila Bibat, Kathryn Wagner, Guido Stadler, Woodring E. Wright, John D. Leszyk, Charles P. Emerson Jr.

UMass Center for Clinical and Translational Science Research Retreat

FSHD is linked to the misexpression of the DUX4 gene contained within the D4Z4 repeat array on chromosome 4. The gene encodes the DUX4 protein, a cytotoxic transcription factor that presumably causes the symptoms of the disease. However, individuals have been identified who express DUX4 in their muscle biopsies, but who remain asymptomatic, suggesting that there are other factors that modify FSHD penetrance or severity. We hypothesized that an FSHD-modifying factor would physically interact with DUX4, and we took a proteomic approach to identify DUX4-interacting proteins. We identified the multifunctional C1QBP protein as one such factor. C1QBP is known to ...


The Smoking Paradox In The Development Of Psoriatic Arthritis Among Psoriasis Patients – A Population-Based Study, Uyen-Sa D. T. Nguyen, Yuqing Zhang, Na Lu, Qiong Louie-Gao, Jingbo Niu, Thorvador J. Love, Alexis Ogdie, Joel M. Gelfand, Michael P. LaValley, Maureen Dubreuil, Jeffrey A. Sparks, Elizabeth W. Karlson, Hyon K. Choi 2017 University of Massachusetts Medical School

The Smoking Paradox In The Development Of Psoriatic Arthritis Among Psoriasis Patients – A Population-Based Study, Uyen-Sa D. T. Nguyen, Yuqing Zhang, Na Lu, Qiong Louie-Gao, Jingbo Niu, Thorvador J. Love, Alexis Ogdie, Joel M. Gelfand, Michael P. Lavalley, Maureen Dubreuil, Jeffrey A. Sparks, Elizabeth W. Karlson, Hyon K. Choi

UMass Center for Clinical and Translational Science Research Retreat

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic mechanisms behind this paradox.

Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among psoriasis patients. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders.

Results: Of 6.65 million subjects without PsA ...


Macroglossia In Inclusion Body Myositis, Jatinder S. Patti, Kate Daniello, Lan Qin 2017 University of Massachusetts Medical School

Macroglossia In Inclusion Body Myositis, Jatinder S. Patti, Kate Daniello, Lan Qin

UMass Center for Clinical and Translational Science Research Retreat

OBJECTIVE: Discussion of a case of Inclusion body myositis (IBM) associated with macroglossia.

INTRODUCTION: IBM is one of the idiopathic inflammatory myopathies. Exact pathogenesis is unclear but there is an evidence of dysregulation of antigen driven immune response involving T cells. Typical onset is slowly progressive impacting quadriceps often more than hip flexors, ankle dorsiflexors and distal forearm flexor muscles. Swallowing difficulties often are present and mild facial weakness can be seen. Macroglossia has never been reported in association with IBM. In fact inflammatory myopathies of tongue are a rarity.

DESIGN: A case report of a 68 year old woman ...


Dermatomyositis As Paraneoplastic Manifestation Of Tonsillar Squamous Cell Carcinoma, Jatinder S. Patti, Kate Daniello, Lan Qin 2017 University of Massachusetts Medical School

Dermatomyositis As Paraneoplastic Manifestation Of Tonsillar Squamous Cell Carcinoma, Jatinder S. Patti, Kate Daniello, Lan Qin

UMass Center for Clinical and Translational Science Research Retreat

OBJECTIVE: Discussion of a rare case of dermatomyositis associated with tonsillar neoplasm in an African American woman.

BACKGROUND: Dermatomyositis is a syndrome of inflamatory myopathy with multiorgan manifestations which has been linked to immune dysregulation and neoplasia.

INTRODUCTION: Many studies have shown five to seven fold increased risk of developing malignancy with dermatomyositis within two years of presentation. Most common cancers reported are adenocarcinomas of lung, breast, ovaries, stomach, pancreas and bladder. Dermatomyositis as a paraneoplastic manifestation of tonsillar squamous cell carcinoma has not previously been described.

DESIGN: This is a case report of a 52 year old woman who ...


Effects Of Glucosamine Versus Chondroitin Sulfate In Reducing Joint Space Narrowing In Knee Osteoarthritis, Caroline Horton, Ashani Andrews 2017 James Madison University

Effects Of Glucosamine Versus Chondroitin Sulfate In Reducing Joint Space Narrowing In Knee Osteoarthritis, Caroline Horton, Ashani Andrews

Physician Assistant Capstones

Objective: To determine if over the counter supplements, chondroitin sulfate and glucosamine, in combination or alone, are effective in the treatment of joint space narrowing (JSN) in knee osteoarthritis.

Design: Systematic Literature Review

Methods: Database search of PubMed and MEDLINE using the search terms “glucosamine”, “chondroitin sulfate”, “osteoarthritis”, and joint space narrowing. Filters were implemented to include articles that only dealt with human subjects, that were published in 2000 or later, and were full-text. Articles were excluded if they were cohort studies, reviews, non-English papers, or had pain as the only outcome.

Results: Sawitzke et al.primary outcomes revealed no ...


Clinical And Demographic Factors Associated With Change And Maintenance Of Disease Severity In A Large Registry Of Patients With Rheumatoid Arthritis, George W. Reed, David H. Collier, Andrew S. Koenig, Katherine C. Saunders, Dimitrios A. Pappas, Heather J. Litman, Joel M. Kremer, Sameer Kotak 2017 University of Massachusetts Medical School

Clinical And Demographic Factors Associated With Change And Maintenance Of Disease Severity In A Large Registry Of Patients With Rheumatoid Arthritis, George W. Reed, David H. Collier, Andrew S. Koenig, Katherine C. Saunders, Dimitrios A. Pappas, Heather J. Litman, Joel M. Kremer, Sameer Kotak

Open Access Articles

BACKGROUND: We examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA).

METHODS: Data from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low ( < /=10), moderate ( > 10 and < /=22), and severe ( > 22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were ...


Factors In Patient Responsiveness To Directional Preference-Matched Treatment Of Neck Pain With Or Without Upper Extremity Radiation, Benjamin Holmes, Ruta Brazauskas, Laura D. Cassidy, Rachel A. Wiegand 2017 Aurora Sheboygan Clinic Spine Institute; Medical College of Wisconsin

Factors In Patient Responsiveness To Directional Preference-Matched Treatment Of Neck Pain With Or Without Upper Extremity Radiation, Benjamin Holmes, Ruta Brazauskas, Laura D. Cassidy, Rachel A. Wiegand

Journal of Patient-Centered Research and Reviews

Purpose

Patient-related predictive factors in responsiveness to directional preference therapy for neck pain with or without upper extremity radiation (NP/R) have not been reported. A directional preference is any neck movement that, when performed repeatedly to end range, results in centralization and/or alleviation of NP/R. It was hypothesized that patient compliance with a prescribed, directional preference-matched home exercise program would improve positive responsiveness to NP/R treatment.

Methods

Patient-related factors thought to affect responsiveness to care were collected retrospectively from charts and de-identified for patients with NP/R who underwent chiropractic treatment at a multispecialty spine clinic ...


Impact Of Prior Biologic Use On Persistence Of Treatment In Patients With Psoriatic Arthritis Enrolled In The Us Corrona Registry, Leslie R. Harrold, Bradley S. Stolshek, Sabrina Rebello, David H. Collier, Alex Mutebi, Sally W. Wade, Wendi Malley, Jeffrey D. Greenberg, Carol J. Etzel 2017 University of Massachusetts Medical School

Impact Of Prior Biologic Use On Persistence Of Treatment In Patients With Psoriatic Arthritis Enrolled In The Us Corrona Registry, Leslie R. Harrold, Bradley S. Stolshek, Sabrina Rebello, David H. Collier, Alex Mutebi, Sally W. Wade, Wendi Malley, Jeffrey D. Greenberg, Carol J. Etzel

University of Massachusetts Medical School Faculty Publications

Psoriatic arthritis (PsA) is a chronic condition characterized by a diverse set of symptoms, from swollen joints to nail disease to skin disease. A variety of treatment options are available, including tumor necrosis factor inhibitors (TNFis). Little is known about treatment persistence in patients with PsA who initiate TNFi therapy, with and without prior biologic use. This study assessed persistence in these subgroups of patients with PsA and identified factors associated with persistence. This retrospective study utilized data from the Corrona registry of patients with PsA-with or without prior biologic experience-who initiated TNFi therapy between October 1, 2002, and March ...


Differential Burden Of Musculoskeletal Pain In African Americans And Whites Patients At The Time Of Total Joint Replacement Surgery, Leslie R. Harrold, Anthony Porter, Philip C. Noble, David C. Ayers, Jeroan J. Allison, Patricia D. Franklin 2017 University of Massachusetts Medical School

Differential Burden Of Musculoskeletal Pain In African Americans And Whites Patients At The Time Of Total Joint Replacement Surgery, Leslie R. Harrold, Anthony Porter, Philip C. Noble, David C. Ayers, Jeroan J. Allison, Patricia D. Franklin

Orthopedics and Physical Rehabilitation Publications and Presentations

Objective: African Americans patients have greater operative joint pain and functional limitation at the time of total joint replacement (TJR) compared to white patients. We examined the factors associated with this apparent disparity.

Methods: A consecutive sample of 5745 patients with advanced knee and hip osteoarthritis [who elected to undergo TJR in 2011-201] reported, preoperatively, medical comorbidities, operative and non-operative hip/ knee pain using Hip and Knee Disability and Osteoarthritis Outcome Scores (HOOS/KOOS), function using Short Form 36 Physical Component Score (PCS). Total burden of musculoskeletal pain was quantified as moderate/severe pain in non-operative hip and knee joints ...


Varying The Item Format Improved The Range Of Measurement In Patient-Reported Outcome Measures Assessing Physical Function, Gregor Liegl, Barbara L. Gandek, H. Felix Fischer, Jakob B. Bjorner, John E. Ware Jr., Matthias S. F. Rose, James F. Fries, Sandra Nolte 2017 Charité - Universitätsmedizin Berlin

Varying The Item Format Improved The Range Of Measurement In Patient-Reported Outcome Measures Assessing Physical Function, Gregor Liegl, Barbara L. Gandek, H. Felix Fischer, Jakob B. Bjorner, John E. Ware Jr., Matthias S. F. Rose, James F. Fries, Sandra Nolte

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement ...


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