145 results on '"Rose CD"'
Search Results
2. Long-term outcomes of pediatric infections: from traditional infectious diseases to long Covid
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Buonsenso, D, Gennaro, LD, Rose, CD, Morello, R, D'Ilario, F, Zampino, G, Piazza, M, Boner, AL, Iraci, C, O'Connell, S, Cohen, VB, Esposito, S, Munblit, D, Reena, J, Sigfrid, L, and Valentini, P
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Microbiology (medical) ,Post-Acute COVID-19 Syndrome ,Italy ,SARS-CoV-2 ,COVID-19 ,Humans ,Child ,Communicable Diseases ,Microbiology - Abstract
There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long Covid and lessons learnt from a pediatric post-Covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.The authors analyze the recent evidence on pediatric long Covid and lessons learnt from a pediatric post-Covid unit in Rome, Italy. Also, we analyze the long-term effects of other infectious diseases.
- Published
- 2022
3. The Overdiagnosis of Lyme Disease in Children Residing in an Endemic Area
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Fawcett Pt, Rose Cd, Robert A. Doughty, and Gibney Km
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medicine.medical_specialty ,Pediatrics ,Adolescent ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Lyme disease ,Borrelia burgdorferi Group ,030225 pediatrics ,Humans ,Medicine ,Serologic Tests ,Family history ,Overdiagnosis ,Child ,Retrospective Studies ,Lyme Disease ,New Jersey ,business.industry ,Medical record ,Infant ,Retrospective cohort study ,Pennsylvania ,Delaware ,medicine.disease ,Antibodies, Bacterial ,Surgery ,El Niño ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Population study ,Morbidity ,business - Abstract
The medical records of 227 children ages 1 to 19 years referred to the Lyme disease pediatric clinic over a 32-month period since May 1990 were reviewed. Clinico-serologic criteria for a positive diagnosis were applied. One hundred thirty-eight of 227 referred children did not fulfill those criteria and became the study population. Four subsets of patients emerged: (1) 54 patients with predominantly subjective symptoms; (2) 52 patients with objective evidence for an alternative diagnosis; (3) eight patients who had documented infection in the past and continued with symptoms after antibiotic treatment; and (4) 24 patients with a history of tick attachment or prenatal/family history of Lyme disease. Serologic testing data from commercial laboratories were available for the 54 children from the "predominantly subjective" group; 50% were negative, and 50% were borderline or positive. Ninety-two percent of these patients were negative at retesting by our enzyme-linked immunosorbent assay (ELISA) and 100% were negative by Western blot. Fifty-seven percent of these patients had received treatment prior to our evaluation. Children residing in an endemic area who present with vague symptoms are being diagnosed with and treated for Lyme disease without clinical or serologic documentation. In addition, fear in the lay community may be inducing doctors to diagnose Lyme disease in patients with symptoms that may be suggestive of an alternative diagnosis.
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- 1994
4. Physician Beliefs, Attitudes, and Approaches Toward Lyme Disease in an Endemic Area
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Gregory M. Caputo, Stephen C. Eppes, Joel D. Klein, and Rose Cd
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Adult ,Health Knowledge, Attitudes, Practice ,Pediatrics ,medicine.medical_specialty ,Enzyme-Linked Immunosorbent Assay ,Lyme Arthritis ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Lyme disease ,030225 pediatrics ,medicine ,Humans ,Practice Patterns, Physicians' ,Doxycycline ,Lyme Disease ,business.industry ,Ceftriaxone ,Amoxicillin ,medicine.disease ,LYME ,Surgery ,Clinical trial ,Pediatrics, Perinatology and Child Health ,business ,Meningitis ,medicine.drug - Abstract
To assess the beliefs and practice habits regarding Lyme disease among practitioners, questionnaires were sent to physicians in a seven-county Lyme-endemic region. One hundred twenty-four evaluable responses were returned from 53 family physicians, 39 pediatricians, 27 internists, and five subspecialists who diagnosed three to four cases of Lyme disease per year, on average. The majority presented with erythema migrans (EM) or other early symptoms, although arthritis was the presenting sign in 16%. The enzyme-linked immunosorbent assay (ELISA) was the most frequently ordered diagnostic test, but 45% of respondents did not specify which test when ordering Lyme serology. The majority would use amoxicillin or doxycycline to treat EM in children or adults, respectively. Nearly all would use ceftriaxone for meningitis, and half would use it to treat Lyme arthritis or Bell's palsy. Physicians differed markedly in the duration of therapy they would prescribe. Eighty-three percent would treat a patient for possible Lyme disease with antibiotics (many intravenously), even in the absence of EM or positive serology. Thirty-five percent of practitioners prescribed antibiotics for deer-tick bites. Our survey documents significant variation in approaches to Lyme disease among primary-care physicians and suggests the need for well-designed clinical trials, continuing basic research, and physician education.
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- 1994
5. Pediatric Lyme Arthritis: Clinical Spectrum and Outcome
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Rose Cd, Gibney Km, Stephen C. Eppes, Paul T. Fawcett, Joel D. Klein, and R A Doughty
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Male ,medicine.medical_specialty ,Adolescent ,Anti-nuclear antibody ,Spondyloarthropathy ,Arthritis ,Lyme Arthritis ,Serology ,Lyme disease ,Internal medicine ,medicine ,Humans ,Serologic Tests ,Orthopedics and Sports Medicine ,Longitudinal Studies ,Child ,Doxycycline ,Arthritis, Infectious ,Lyme Disease ,business.industry ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,Surgery ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,Juvenile rheumatoid arthritis ,medicine.drug - Abstract
A cohort of children with Lyme arthritis was used to evaluate the clinical and serologic profile of the disease. During a 42-month period (June 1989 to December 1991), 44 patients (13 girls and 31 boys, ages 4-18 years) were included and followed for 6-36 months. Inclusion required the presence of arthritis, as well as positive serology. Thirty-four children with juvenile rheumatoid arthritis or spondyloarthropathy were used as a serologic comparison group. Five different patterns of arthritis were found. Preceding erythema migrans was seen in seven children. Antinuclear antibodies were positive in 30% of the patients. Three treatments were used and selected according to physician preference, patient age, and presence of extraarticular disease: amoxicillin, doxycycline, and ceftriaxone. Articular disease reached complete resolution in all patients within 2-12 weeks. Lyme arthritis in children may mimic other pediatric arthritides. Prognosis for children with clearly defined Lyme arthritis was excellent.
- Published
- 1994
6. Principles of Aquatic Hazard Evaluation as Applied to Ocean-Disposed Wastes
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Rose, CD, primary and Ward, TJ, additional
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7. PW03-016 – Blau prospective cohort study: articular outcomes
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Rose, CD, primary, Cimaz, R, additional, Thomee, C, additional, Khubchandani, R, additional, Espada, G, additional, Russo, R, additional, Harjacek, M, additional, Bader-Meunier, B, additional, Brissaud, P, additional, Wulffraat, N, additional, Vastert, S, additional, Merino, R, additional, Naranjo-Hernandez, A, additional, Oliveira-Knupp, S, additional, Mackensen, F, additional, Arostegui, J, additional, Anton, J, additional, Fernandez-Martin, J, additional, and Wouters, C, additional
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- 2013
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8. OR3-002 – Blau Syndrome cohort study: ocular outcome
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Rose, CD, primary, Cimaz, R, additional, Thomee, C, additional, Khubchandani, R, additional, Espada, G, additional, Russo, R, additional, Harjacek, M, additional, Bader-Meunier, B, additional, Brissaud, P, additional, Wulffraat, N, additional, Vastert, S, additional, Merino, R, additional, Naranjo-Hernandez, A, additional, Knupp, S Oliveira, additional, Mackenson, F, additional, Arostegui, J, additional, Lopez, J Anton, additional, Fernandez-Martin, J, additional, and Wouters, C, additional
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- 2013
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9. Correlation of seroreactivity with response to antibiotics in pediatric Lyme borreliosis
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Rose Cd, Robert A. Doughty, Fawcett Pt, and Gibney Km
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Microbiology (medical) ,myalgia ,medicine.medical_specialty ,medicine.drug_class ,Clinical Biochemistry ,Immunology ,Antibiotics ,Population ,Immunoblotting ,Enzyme-Linked Immunosorbent Assay ,Serology ,Lyme disease ,Borrelia burgdorferi Group ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,Borrelia burgdorferi ,education ,Child ,education.field_of_study ,Lyme Disease ,biology ,business.industry ,Drug Resistance, Microbial ,biology.organism_classification ,medicine.disease ,bacterial infections and mycoses ,LYME ,Anti-Bacterial Agents ,Ixodes scapularis ,medicine.symptom ,business ,Biomarkers ,Research Article - Abstract
Response to treatment with antibiotics was compared with serologic reactivity and clinical symptoms in a pediatric population with presumptive diagnoses of Lyme borreliosis. The population analyzed for this study consisted of a subset of a larger Lyme clinic population being monitored as part of a prospective study on pediatric Lyme borreliosis. All patients resided in an area in which Ixodes scapularis and Borrelia burgdorferi are considered endemic. Serum from patients was tested by enzyme-linked immunosorbent assay and Western blotting. Response to antibiotics was evaluated by members of a pediatric Lyme clinic. Results showed that positive serologic test results correlate with a favorable response to antibiotics, as does the presence of erythema migrans (EM), regardless of serologic status. Seronegative patients without EM had chronic fatigue and arthralgia and/or myalgia as primary symptoms and did not respond to antibiotics, even when multiple courses of treatment were given. These results indicate that serologic tests designed to have high specificity can reliably rule out Lyme borreliosis in patients with chronic symptoms, thus preventing unnecessary treatment with antibiotics.
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- 1997
10. Calibration and Testing of On-Line Coal Analyzers
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Dean, SW, primary and Rose, CD, additional
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- 2004
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11. Overgrazing of a large seagrass bed by the sea urchin Lytechinus variegatus in Outer Florida Bay
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Rose, CD, primary, Sharp, WC, additional, Kenworthy, WJ, additional, Hunt, JH, additional, Lyons, WG, additional, Prager, EJ, additional, Valentine, JF, additional, Hall, MO, additional, Whitfield, PE, additional, and Fourqurean, JW, additional
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- 1999
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12. Effects of community structure on the seagrass Thalassia testudinum
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Rose, CD, primary and Dawes, CJ, additional
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- 1999
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13. IDENTIFYING AND MANAGING LYME DISEASE IN CHILDREN
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Rose Cd, Paul T. Fawcett, and Gibney Km
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medicine.medical_specialty ,Lyme disease ,business.industry ,Pediatrics, Perinatology and Child Health ,Medicine ,Orthopedics and Sports Medicine ,General Medicine ,business ,Intensive care medicine ,medicine.disease - Published
- 1997
14. Interventions delivered in clinical settings are effective in reducing risk of HIV transmission among people living with HIV: results from the Health Resources and Services Administration (HRSA)'s Special Projects of National Significance initiative.
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Myers JJ, Shade SB, Rose CD, Koester K, Maiorana A, Malitz FE, Bie J, Kang-Dufour M, and Martin SF
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- 2010
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15. Parenteral methotrexate: effective shelf-life following initial puncture of preservative-protected vial
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Smith Christopher, Rose Cd, and Patricia G. Hunt
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medicine.medical_specialty ,Preservative ,business.industry ,Immunology ,Shelf life ,Vial ,Surgery ,Rheumatology ,Anesthesia ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,Methotrexate ,business ,medicine.drug - Published
- 1995
16. Peer cluster theory and adolescent alcohol use: an explanation of alcohol use and a comparative analysis between two causal models.
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Rose CD
- Abstract
This study tests the premise of peer cluster theory as it applies to individual alcohol use, and makes a comparative analysis between its ability to explain alcohol use and marijuana use. Using the results of a 1996 drug and alcohol survey of 1312 Western Kentucky University students, path analysis was used to measure the influence of six of peer cluster theory's psychosocial characteristics on the percentage of the respondent's college friends who use alcohol. All of these variables were then regressed on the respondent's alcohol use. The results of the causal models did show some support for peer cluster theory. The direct effect of the student's association with alcohol-using peers on individual alcohol use was shown to have the strongest direct influence on this outcome variable. However, a few limitations of this theoretical perspective were identified. The causal model for alcohol use showed that the indirect influence of two of these psychosocial characteristics (parental attitudes on alcohol use and success in school) was weaker than their direct influence on individual alcohol use. And, the comparative analysis showed that peer cluster theory is better suited to explain the use of marijuana than the use of alcohol. [ABSTRACT FROM AUTHOR]
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- 1999
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17. Granulomatous nephritis associated with R334Q mutation in NOD2.
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Meiorin SM, Espada G, Costa CE, Tartara A, De Matteo E, Wouters C, Martin TM, and Rose CD
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- 2007
18. Variances in Sampling Streams of Coal
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Rose, CD
- Abstract
Beginning with the postulate that the serial correlation in an infinite population is invariant with respect to segment mass, expressions are developed for variance as a function of mass and expected variance of the mean using random, stratified random, or systematic sampling of a linear population. The expression for variance as a function of mass is shown to agree well with data from one coal experiment and to be the same as an empirical formula developed from agricultural experiments.
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- 1983
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19. Variances in Sampling Streams of Coal
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Horstman, R, primary, Peters, KA, additional, Meltzer, RL, additional, Vieth, MB, additional, and Rose, CD, additional
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- 1983
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20. Identification of Blau Syndrome disease signatures
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Valencia X, Gough P, Votta B, Miller M, Connor J, Lipshutz D, Magid-Slav M, Cooper D, Wang L, Foley KP, Wouters CH, Rosé CD, and Bertin J
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Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Published
- 2011
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21. Atypical onset as predictor of poor outcome in Pediatric Systemic Lupus Erythematosus (pSLE)
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Taddio A, Rossetto E, Lepore L, Brescia AC, Bracaglia C, Caminiti S, Cortis E, Rigante D, Stabile A, Montico M, Ronfani L, and Rosé CD
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Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Published
- 2008
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22. Local vs central institutional review boards for multicenter studies.
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Rose CD, McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting GR, and Rosé, Carlos D
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- 2003
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23. Treatment of Kawasaki disease.
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Inoue Y, Kobayashi T, Morikawa A, Taddio A, Rose CD, Greil GF, Manning WJ, Newburger JW, Sleeper LA, and Burns JC
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- 2007
24. Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.
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Saito K, Gabbeta A, Mulvihill E, Al-Jaberi L, Beukelman T, Lewis JD, Rose CD, Strom BL, and Horton DB
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- Humans, Child, Female, Male, Adolescent, Child, Preschool, Disease Progression, Predictive Value of Tests, Arthritis, Juvenile drug therapy, Algorithms, Antirheumatic Agents therapeutic use, Electronic Health Records statistics & numerical data, Glucocorticoids therapeutic use, Glucocorticoids administration & dosage, Glucocorticoids adverse effects
- Abstract
Purpose: To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity., Methods: Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics., Results: Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%)., Conclusion: An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)
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- 2024
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25. Impact of the COVID-19 Pandemic on the Management of Juvenile Idiopathic Arthritis: Analysis of United States Commercial Insurance Data.
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Horton DB, Yang Y, Neikirk A, Huang C, Crystal S, Davidow A, Haynes K, Gerhard T, Rose CD, Strom BL, and Parlett L
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- Child, Humans, Pandemics, Quality of Life, Retrospective Studies, Glucocorticoids therapeutic use, COVID-19 epidemiology, Arthritis, Juvenile drug therapy, Arthritis, Juvenile epidemiology, Antirheumatic Agents therapeutic use, Insurance
- Abstract
Background/objective: Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort., Methods: We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago)., Results: Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic., Conclusions: In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life., Competing Interests: Disclosures: D.B.H. has received salary support and grant funding related to JIA from the Childhood Arthritis and Rheumatology Research Alliance, and honorarium related to JIA from the American College of Rheumatology, and unrelated grant funding from Danisco USA, Inc. Y.Y., A.L.N., and L.E.P. are employees of Carelon Research, Inc. Kevin Haynes is an employee of Janssen Research & Development. C.D.R. provides consultation to AbbVie and Novartis about therapies for JIA and advises the Department of Health and Human Services on autoimmune vaccine injuries. B.L.S. has received consulting fees from AbbVie and the Consumer Healthcare Products Association. L.E.P. has received research support from Sanofi unrelated to this work. C.H., S.C., A.D., and T.G. report no potential conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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26. Multinucleation resets human macrophages for specialized functions at the expense of their identity.
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Ahmadzadeh K, Pereira M, Vanoppen M, Bernaerts E, Ko JH, Mitera T, Maksoudian C, Manshian BB, Soenen S, Rose CD, Matthys P, Wouters C, and Behmoaras J
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- 2023
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27. Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.
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Ahmadzadeh K, Vanoppen M, Rose CD, Matthys P, and Wouters CH
- Abstract
Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to form multinucleated giant cells. Based on their morphology and functional characteristics, there are in general three types of multinucleated giant cells including osteoclasts, foreign body giant cells and Langhans giant cells. Osteoclasts are bone resorbing cells and under physiological conditions they participate in bone remodeling. However, under pathological conditions such as rheumatoid arthritis and osteoporosis, osteoclasts are responsible for bone destruction and bone loss. Foreign body giant cells and Langhans giant cells appear only under pathological conditions. While foreign body giant cells are found in immune reactions against foreign material, including implants, Langhans giant cells are associated with granulomas in infectious and non-infectious diseases. The functionality and fusion mechanism of osteoclasts are being elucidated, however, our knowledge on the functions of foreign body giant cells and Langhans giant cells is limited. In this review, we describe and compare the phenotypic aspects, biological and functional activities of the three types of multinucleated giant cells. Furthermore, we provide an overview of the multinucleation process and highlight key molecules in the different phases of macrophage fusion., Competing Interests: CW obtained unrestricted grants to KU Leuven from Novartis, Roche, GSK immuno-inflammation and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahmadzadeh, Vanoppen, Rose, Matthys and Wouters.)
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- 2022
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28. The culture microenvironment of juvenile idiopathic arthritis synovial fibroblasts is favorable for endochondral bone formation through BMP4 and repressed by chondrocytes.
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Simonds MM, Schlefman AR, McCahan SM, Sullivan KE, Rose CD, and Brescia AMC
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- Arthritis, Juvenile complications, Arthritis, Juvenile metabolism, Cells, Cultured, Cellular Microenvironment drug effects, Cellular Microenvironment physiology, Chondrocytes physiology, Culture Media, Conditioned pharmacology, Gene Expression Regulation, Humans, Signal Transduction drug effects, Bone Morphogenetic Protein 4 antagonists & inhibitors, Bone Morphogenetic Protein 4 metabolism, Growth Disorders etiology, Growth Disorders metabolism, Osteogenesis drug effects, Osteogenesis physiology, Receptor, Transforming Growth Factor-beta Type I antagonists & inhibitors, Receptor, Transforming Growth Factor-beta Type I metabolism, Synoviocytes metabolism, TGF-beta Superfamily Proteins metabolism
- Abstract
Background: We examined influences of conditioned media from chondrocytes (Ch) on juvenile idiopathic arthritis synovial fibroblasts (JFLS) and potential for JFLS to undergo endochondral bone formation (EBF)., Methods: Primary cells from three control fibroblast-like synoviocytes (CFLS) and three JFLS were cultured in Ch-conditioned media and compared with untreated fibroblast-like synoviocytes (FLS). RNA was analyzed by ClariomS microarray. FLS cells cultured in conditioned media were exposed to either TGFBR1 inhibitor LY3200882 or exogenous BMP4 and compared with FLS cultured in conditioned media from Ch (JFLS-Ch). Media supernatants were analyzed by ELISA., Results: In culture, JFLS downregulate BMP2 and its receptor BMPR1a while upregulating BMP antagonists (NOG and CHRD) and express genes (MMP9, PCNA, MMP12) and proteins (COL2, COLX, COMP) associated with chondrocytes. Important TGFβ superfamily member gene expression (TGFBI, MMP9, COL1A1, SOX6, and MMP2) is downregulated when JFLS are cultured in Ch-conditioned media. COL2, COLX and COMP protein expression decreases in JFLS-Ch. BMP antagonist protein (NOG, CHRD, GREM, and FST) secretion is significantly increased in JFLS-Ch. Protein phosphorylation increases in JFLS-Ch exposed to exogenous BMP4, and chondrocyte-like phenotype is restored in BMP4 presence, evidenced by increased secretion of COL2 and COLX. Inhibition of TGFBR1 in JFLS-Ch results in overexpression of COL2., Conclusions: JFLS are chondrocyte-like, and Ch-conditioned media can abrogate this phenotype. The addition of exogenous BMP4 causes JFLS-Ch to restore this chondrocyte-like phenotype, suggesting that JFLS create a microenvironment favorable for endochondral bone formation, thereby contributing to joint growth disturbances in juvenile idiopathic arthritis.
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- 2021
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29. Juvenile idiopathic arthritis fibroblast-like synoviocytes influence chondrocytes to alter BMP antagonist expression demonstrating an interaction between the two prominent cell types involved in endochondral bone formation.
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Simonds MM, Schlefman AR, McCahan SM, Sullivan KE, Rose CD, and Brescia AC
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- Cell Communication, Cell Differentiation genetics, Cells, Cultured, Collagen metabolism, Gene Expression Regulation, Humans, Arthritis, Juvenile metabolism, Arthritis, Juvenile pathology, Bone Morphogenetic Protein 4 genetics, Bone Morphogenetic Protein 4 metabolism, Carrier Proteins genetics, Carrier Proteins metabolism, Chondrocytes metabolism, Chondrocytes pathology, Hyperostosis metabolism, Synoviocytes metabolism, Synoviocytes pathology
- Abstract
Background: To examine critical interactions between juvenile idiopathic arthritis synovial fibroblasts (JFLS) and chondrocytes (Ch), and their role in bony overgrowth seen in patients with juvenile idiopathic arthritis (JIA)., Methods: Control (CFLS) and JFLS were cultured in synoviocyte media containing recombinant BMP4. Ch were cultured in either CFLS or JFLS conditioned-media without stimulation. Media supernatants were analyzed by ELISA. RNA from conditioned media experiment was analyzed by ClariomS microarray., Results: As expected, genes expressed in untreated JFLS and CFLS cultured in synoviocyte media were similar to each other and this expression differed from untreated Ch cultured in chondrocyte media. JFLS favor BMP ligand gene expression while downregulating TGFβ receptors' expression. Noggin and chordin, antagonists with high affinity for BMP4, are JFLS- but not Ch-preferred regulators of BMP signaling. Compared to Ch, JFLS overexpress collagen X (COLX), a marker of chondrocyte hypertrophy. Exogenous BMP4 causes JFLS to significantly decrease expression of noggin and collagen II (COL2), a marker of chondrocyte proliferation, and causes overexpression of COLX and alkaline-phosphatase (ALP). Chondrocytes cultured in JFLS-conditioned media (Ch-JFLS) express BMP genes and favor chordin protein expression over other antagonists. Ch-JFLS have significantly increased expression of COL2 and significantly decreased expression of COLX., Conclusions: These data suggest JFLS, in the presence of BMP4, undergo hypertrophy and that JFLS-conditioned media influence chondrocytes to become highly proliferative. To the authors' knowledge, no prior study has shown that JFLS and chondrocytes play a direct role in the bony overgrowth in joints of patients with JIA and that BMPs or regulation of these growth factors influence the interaction between two prominent synovial cell types.
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- 2020
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30. SCO-Spondin Defects and Neuroinflammation Are Conserved Mechanisms Driving Spinal Deformity across Genetic Models of Idiopathic Scoliosis.
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Rose CD, Pompili D, Henke K, Van Gennip JLM, Meyer-Miner A, Rana R, Gobron S, Harris MP, Nitz M, and Ciruna B
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- Animals, Cell Adhesion Molecules, Neuronal metabolism, Disease Models, Animal, Humans, Spinal Cord abnormalities, Spinal Cord growth & development, Spine abnormalities, Zebrafish growth & development, Cell Adhesion Molecules, Neuronal genetics, Cerebral Ventricles metabolism, Inflammation physiopathology, Morphogenesis, Spinal Cord immunology, Spine growth & development, Zebrafish abnormalities
- Abstract
Adolescent idiopathic scoliosis (AIS) affects 3% to 4% of children between the ages of 11 and 18 [1, 2]. This disorder, characterized by abnormal three-dimensional spinal curvatures that typically develop during periods of rapid growth, occurs in the absence of congenital vertebral malformations or neuromuscular defects [1]. Genetic heterogeneity [3] and a historical lack of appropriate animal models [4] have confounded basic understanding of AIS biology; thus, treatment options remain limited [5, 6]. Recently, genetic studies using zebrafish have linked idiopathic-like scoliosis to irregularities in motile cilia-mediated cerebrospinal fluid flow [7-9]. However, because loss of cilia motility in human primary ciliary dyskinesia patients is not fully associated with scoliosis [10, 11], other pathogenic mechanisms remain to be determined. Here, we demonstrate that zebrafish scospondin (sspo) mutants develop late-onset idiopathic-like spinal curvatures in the absence of obvious cilia motility defects. Sspo is a large secreted glycoprotein functionally associated with the subcommissural organ and Reissner's fiber [12]-ancient and enigmatic organs of the brain ventricular system reported to govern cerebrospinal fluid homeostasis [13, 14], neurogenesis [12, 15-18], and embryonic morphogenesis [19]. We demonstrate that irregular deposition of Sspo within brain ventricles is associated with idiopathic-like scoliosis across diverse genetic models. Furthermore, Sspo defects are sufficient to induce oxidative stress and neuroinflammatory responses implicated in AIS pathogenesis [9]. Through screening for chemical suppressors of sspo mutant phenotypes, we also identify potent agents capable of blocking severe juvenile spine deformity. Our work thus defines a new preclinical model of AIS and provides tools to realize novel therapeutic strategies., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2020
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31. Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension.
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Spyropoulos F, Vitali SH, Touma M, Rose CD, Petty CR, Levy P, Kourembanas S, and Christou H
- Abstract
Echocardiography is the gold standard non-invasive technique to diagnose pulmonary hypertension. It is also an important modality used to monitor disease progression and response to treatment in patients with pulmonary hypertension. Surprisingly, only few studies have been conducted to validate and standardize echocardiographic parameters in experimental animal models of pulmonary hypertension. We sought to define cut-off values for both invasive and non-invasive measures of pulmonary hemodynamics and right ventricular hypertrophy that would reliably diagnose pulmonary hypertension in three different rat models. The study was designed in two phases: (1) a derivation phase to establish the cut-off values for invasive measures of right ventricular systolic pressure, Fulton's index (right ventricular weight/left ventricle + septum weight), right ventricular to body weight ratio, and non-invasive echocardiographic measures of pulmonary arterial acceleration time, pulmonary arterial acceleration time to ejection time ratio and right ventricular wall thickness in diastole in the hypoxic and monocrotaline rat models of pulmonary hypertension and (2) a validation phase to test the performance of the cut-off values in predicting pulmonary hypertension in an independent cohort of rats with Sugen/hypoxia-induced pulmonary hypertension. Our study demonstrates that right ventricular systolic pressure ≥35.5 mmHg and Fulton's Index ≥0.34 are highly sensitive (>94%) and specific (>91%) cut-offs to distinguish animals with pulmonary hypertension from controls. When pulmonary arterial acceleration time/ejection time and right ventricular wall thickness in diastole were both measured, a result of either pulmonary arterial acceleration time/ejection time ≤0.25 or right ventricular wall thickness in diastole ≥1.03 mm detected right ventricular systolic pressure ≥35.5 mmHg or Fulton's Index ≥0.34 with a sensitivity of 88% and specificity of 100%. With properly validated non-invasive echocardiography measures of right ventricular performance in rats that accurately predict invasive measures of pulmonary hemodynamics, future studies can now utilize these markers to test the efficacy of different treatments with preclinical therapeutic modeling., (© The Author(s) 2020.)
- Published
- 2020
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32. The Relationship Between Physical Activity and Cardiorespiratory Fitness Among People Living With Human Immunodeficiency Virus Throughout the Life Span.
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Webel AR, Perazzo J, Phillips JC, Nokes KM, Rentrope C, Schnall R, Musanti R, Adams Tufts K, Sefcik E, Hamilton MJ, Portillo C, Chaiphibalsarisdi P, Orton P, Davis L, and Rose CD
- Subjects
- Age Factors, Cardiovascular Diseases prevention & control, Cross-Sectional Studies, Female, Health Behavior, Humans, Male, Middle Aged, Self Report, Sex Factors, Thailand epidemiology, United States epidemiology, Walk Test, Cardiorespiratory Fitness, Exercise, HIV Infections epidemiology
- Abstract
Background: People living with human immunodeficiency virus (PLHIV) are at an increased risk for developing cardiovascular disease (CVD). Physical activity and cardiorespiratory fitness in PLHIV are poorly understood., Objective: The aims of this study were to describe physical activity and cardiorespiratory fitness by sex and age and to examine the association between physical activity and cardiorespiratory fitness in PLHIV, controlling for covariates., Methods: Seven hundred two PLHIV participated in a cross-sectional study and completed validated measures of self-reported physical activity (7-day Physical Activity Recall) and cardiorespiratory fitness (6-minute walk test). Participants were recruited from 7 diverse sites in the United States and Thailand, and data were analyzed using descriptive statistics and multiple regression to examine the relationship between physical activity and cardiorespiratory fitness., Results: On average, participants self-reported engaging in 115 minutes of, mostly light (75%), physical activity. Men reported twice the amount of physical activity as women (155 vs 73 minutes, P = .01). Participants' ability to achieve their predicted 6-minute walk test distances was similar between men (68%) and women (69%) (P > .01). For women, vigorous physical activity was associated with a 6.6% increase in cardiorespiratory fitness and being temporarily unemployed was associated with an 18% decline in cardiorespiratory fitness. Cardiorespiratory fitness increased with age (P < .01)., Conclusions: Weekly physical activity of people living with human immunodeficiency virus averaged 85 minutes of mostly light activity, well below the recommended 150 minutes of moderate activity. Vigorous physical activity was associated with improved cardiorespiratory fitness in women, but not men. Although PLHIV would benefit from interventions to increase physical activity, our data suggest a need to develop sex-specific physical activity strategies.
- Published
- 2019
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33. Intraarticular Glucocorticoid Injection as Second-line Treatment for Lyme Arthritis in Children.
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Horton DB, Taxter AJ, Davidow AL, Groh BP, Sherry DD, and Rose CD
- Subjects
- Adolescent, Anti-Bacterial Agents therapeutic use, Child, Child, Preschool, Female, Glucocorticoids administration & dosage, Humans, Injections, Intra-Articular, Male, Retreatment, Treatment Outcome, Glucocorticoids therapeutic use, Lyme Disease drug therapy
- Abstract
Objective: To determine whether second-line intraarticular glucocorticoid (IAGC) injection improves outcomes in children with persistently active Lyme arthritis after initial antibiotics., Methods: We conducted an observational comparative effectiveness study through chart review within 3 pediatric rheumatology centers with distinct clinical approaches to second-line treatment of Lyme arthritis. We primarily compared children receiving second-line IAGC to children receiving a second course of antibiotics alone. We evaluated the risk of developing antibiotic-refractory Lyme arthritis (ARLA) using logistic regression and the time to clinical resolution of Lyme arthritis using Cox regression., Results: Of 112 children with persistently active Lyme arthritis after first-line antibiotics, 18 children received second-line IAGC (13 with concomitant oral antibiotics). Compared to children receiving second-line oral antibiotics alone, children treated with IAGC had similar baseline characteristics but lower rates of ARLA (17% vs 44%; OR 0.3, 95% CI 0.1-0.95; p = 0.04) and faster rates of clinical resolution (HR 2.2, 95% CI 1.2-3.9; p = 0.01). Children in IAGC and oral antibiotic cohorts did not differ in treatment-associated adverse events. Among children receiving second-line IAGC, outcomes appeared similar irrespective of use of concomitant antibiotics. Outcomes were also similar between intravenous (IV) and oral antibiotic-treated cohorts, but older children seemed to respond more favorably to IV therapy. IV antibiotics were also associated with higher rates of toxicity., Conclusion: IAGC injection appears to be an effective and safe second-line strategy for persistent Lyme arthritis in children, associated with rapid clinical resolution and reduced need for additional treatment.
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- 2019
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34. Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study.
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Horton DB, Taxter AJ, Davidow AL, Groh B, Sherry DD, and Rose CD
- Subjects
- Adolescent, Case-Control Studies, Child, Female, Humans, Lyme Disease diagnosis, Male, Severity of Illness Index, Treatment Failure, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Lyme Disease drug therapy
- Abstract
Objective: Few factors have consistently been linked to antibiotic-refractory Lyme arthritis (ARLA). We sought to identify clinical and treatment factors associated with pediatric ARLA., Methods: We performed a case-control study in 3 pediatric rheumatology clinics in a Lyme-endemic region (2000-2013). Eligible children were aged ≤ 18 years with arthritis and had positive testing for Lyme disease by Western blot. Cases were 49 children with persistently active arthritis despite ≥ 8 weeks of oral antibiotics or ≥ 2 weeks of parenteral antibiotics; controls were 188 children whose arthritis resolved within 3 months of starting antibiotics. We compared preselected demographic, clinical, and treatment factors between groups using logistic regression., Results: Characteristics positively associated with ARLA were age ≥ 10 years, prolonged arthritis at diagnosis, knee-only arthritis, and worsening after starting antibiotics. In contrast, children with fever, severe pain, or other signs of systemic inflammation were more likely to respond quickly to treatment. Secondarily, low-dose amoxicillin and treatment nonadherence were also linked to higher risk of ARLA. Greater antibiotic use for children with ARLA was accompanied by higher rates of treatment-associated adverse events (37% vs 15%) and resultant hospitalization (6% vs 1%)., Conclusion: Older children and those with prolonged arthritis, arthritis limited to the knees, or poor initial response to antibiotics are more likely to have antibiotic-refractory disease and treatment-associated toxicity. Children with severe symptoms of systemic inflammation have more favorable outcomes. For children with persistently active Lyme arthritis after 2 antibiotic courses, pediatricians should consider starting antiinflammatory treatment and referring to a pediatric rheumatologist.
- Published
- 2019
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35. Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis.
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Hinks A, Marion MC, Cobb J, Comeau ME, Sudman M, Ainsworth HC, Bowes J, Becker ML, Bohnsack JF, Haas JP, Lovell DJ, Mellins ED, Nelson JL, Nordal E, Punaro M, Reed AM, Rose CD, Rosenberg AM, Rygg M, Smith SL, Stevens AM, Videm V, Wallace CA, Wedderburn LR, Yarwood A, Yeung RSM, Langefeld CD, Thompson SD, Thomson W, and Prahalad S
- Subjects
- Adolescent, Adult, Arthritis, Juvenile immunology, Arthritis, Rheumatoid immunology, Child, Female, Genotype, Humans, Logistic Models, Male, Phenotype, Polymorphism, Single Nucleotide, Rheumatoid Factor immunology, Arthritis, Juvenile genetics, Arthritis, Rheumatoid genetics, Autoantibodies genetics, Genetic Profile, Rheumatoid Factor genetics
- Abstract
Objective: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies., Methods: Patients with RF-positive polyarticular JIA (n = 340) and controls (n = 14,412) were genotyped using the Immunochip array. Single-nucleotide polymorphisms were tested for association using a logistic regression model adjusting for admixture proportions. We calculated weighted genetic risk scores (wGRS) of reported RA and JIA risk loci, and we compared the ability of these wGRS to predict RF-positive polyarticular JIA., Results: As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (P = 5.51 × 10
-31 ). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated with RF-positive polyarticular JIA (P < 0.05). The RA wGRS predicted RF-positive polyarticular JIA (area under the curve [AUC] 0.71) better than did the oligoarticular/RF-negative polyarticular JIA wGRS (AUC 0.59). The genetic profile of patients with RF-positive polyarticular JIA was more similar to that of RA patients with age at onset 16-29 years than to that of RA patients with age at onset ≥70 years., Conclusion: RF-positive polyarticular JIA is genetically more similar to adult RA than to the most common JIA categories and thus appears to be a childhood-onset presentation of autoantibody-positive RA. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies., (© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)- Published
- 2018
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36. Blau Syndrome-Associated Uveitis: Preliminary Results From an International Prospective Interventional Case Series.
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Sarens IL, Casteels I, Anton J, Bader-Meunier B, Brissaud P, Chédeville G, Cimaz R, Dick AD, Espada G, Fernandez-Martin J, Guly CM, Hachulla E, Harjacek M, Khubchandani R, Mackensen F, Merino R, Modesto C, Naranjo A, Oliveira-Knupp S, Özen S, Pajot C, Ramanan AV, Russo R, Susic G, Thatayatikom A, Thomée C, Vastert S, Bertin J, Arostegui JI, Rose CD, and Wouters CH
- Subjects
- Adolescent, Adult, Antihypertensive Agents therapeutic use, Arthritis drug therapy, Arthritis physiopathology, Child, Child, Preschool, Choroiditis diagnosis, Choroiditis drug therapy, Choroiditis physiopathology, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Global Health, Glucocorticoids therapeutic use, Humans, Immunosuppressive Agents therapeutic use, Infant, Male, Middle Aged, Multifocal Choroiditis, Prospective Studies, Sarcoidosis, Synovitis drug therapy, Synovitis physiopathology, Uveitis drug therapy, Uveitis physiopathology, Visual Acuity physiology, Arthritis diagnosis, Synovitis diagnosis, Uveitis diagnosis
- Abstract
Purpose: Provide baseline and preliminary follow-up results in a 5-year longitudinal study of Blau syndrome., Design: Multicenter, prospective interventional case series., Methods: Baseline data from 50 patients from 25 centers worldwide, and follow-up data for patients followed 1, 2, or 3 years at the end of study enrollment. Ophthalmic data were collected at baseline and yearly visits by means of a standardized collection form., Results: Median age at onset of eye disease was 60 months and duration of eye disease at baseline 145 months. At baseline 38 patients (78%) had uveitis, which was bilateral in 37 (97%). Eight patients (21%) had moderate to severe visual impairment. Panuveitis was found in 38 eyes (51%), with characteristic multifocal choroidal infiltrates in 29 eyes (39%). Optic disc pallor in 9 eyes (12%) and peripapillary nodules in 9 eyes (12%) were the commonest signs of optic nerve involvement. Active anterior chamber inflammation was noted in 30 eyes (40%) at baseline and in 16 (34%), 17 (57%), and 11 (61%) eyes at 1, 2, and 3 years, respectively. Panuveitis was associated with longer disease duration. At baseline, 56 eyes (75%) were on topical corticosteroids. Twenty-six patients (68%) received a combination of systemic corticosteroids and immunomodulatory therapy., Conclusions: Blau uveitis is characterized by progressive panuveitis with multifocal choroiditis, resulting in severe ocular morbidity despite continuous systemic and local immunomodulatory therapy. The frequency and severity of Blau uveitis highlight the need for close ophthalmologic surveillance as well as a search for more effective therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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37. Understanding Health Literacy for People Living With HIV: Locations of Learning.
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Lindgren TG, Reyes D, Eller L, Wantland D, Portillo C, Holzemer WL, Matshediso E, Corless I, Kemppainen J, Mogobe KD, Webel A, Nokes K, Nicholas P, Rivero Mendez M, Reid P, Baez SS, Johnson MO, Cuca Y, and Rose CD
- Subjects
- Adult, Botswana, Delivery of Health Care, Female, Focus Groups, Humans, Male, Middle Aged, Puerto Rico, Qualitative Research, United States, Confidentiality, HIV Infections psychology, Health Knowledge, Attitudes, Practice, Health Literacy methods, Patient Education as Topic methods, Trust
- Abstract
Health literacy, including people's abilities to access, process, and comprehend health-related information, has become an important component in the management of complex and chronic diseases such as HIV infection. Clinical measures of health literacy that focus on patients' abilities to follow plans of care ignore the multidimensionality of health literacy. Our thematic analysis of 28 focus groups from a qualitative, multisite, multinational study exploring information practices of people living with HIV (PLWH) demonstrated the importance of location as a dimension of health literacy. Clinical care and conceptual/virtual locations (media/Internet and research studies) were used by PLWH to learn about HIV and how to live successfully with HIV. Nonclinical spaces where PLWH could safely discuss issues such as disclosure and life problems were noted. Expanding clinical perspectives of health literacy to include location, assessing the what and where of learning, and trusted purveyors of knowledge could help providers improve patient engagement in care., (Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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38. Prior to extension, Transcriptomes of fibroblast-like Synoviocytes from extended and Polyarticular juvenile idiopathic arthritis are indistinguishable.
- Author
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Brescia AC, Simonds MM, McCahan SM, Sullivan KE, and Rose CD
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- Adolescent, Arthritis, Juvenile diagnosis, Arthritis, Juvenile genetics, Cell Culture Techniques, Child, Child, Preschool, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Microarray Analysis, Real-Time Polymerase Chain Reaction, Synovial Fluid cytology, Transcriptome genetics, Arthritis, Juvenile metabolism, Biomarkers metabolism, Synoviocytes metabolism
- Abstract
Background: Our intent was to identify differences between the transcriptome of fibroblast-like synoviocytes (FLS) in oligoarticular juvenile idiopathic arthritis (JIA) before extension when compared to persistent subtype of JIA, when the two are clinically indistinguishable. Additionally, we sought to determine if differences between the transcriptomes of FLS from extended-to-be and polyarticular course JIA could be detected. Our hypothesis was that intrinsic differences in the transcriptome of the FLS from extended-to-be JIA would distinguish them from persistent oligoarticular JIA, before the course is clinically apparent., Methods: Global gene expression was defined in cultured FLS from 6 controls, 12 JIA with persistent course, 7 JIA prior to extension (extended-to-be), 4 JIA with extended course and 6 polyarticular onset, using Affymetrix Human GeneChips 133plus2.0., Results: Bioconductor Linear Models for Microarray Analysis revealed 22 probesets with differential expression between persistent and extended-to-be FLS at 15% FDR, however only 2 probesets distinguished extended-to-be from extended and none distinguished extended-to-be and polyarticular at 15% FDR. Differences in extended and polyarticular gene expression profiles were not detected. Confirmation of select genes was done on the RNA level by RT-qPCR and on the protein level in synovial fluid by ELISA., Conclusions: The transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. Additionally, the transcriptome of extended-to-be and polyarticular course, including those who have already extended, are indistinguishable. These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be "latent polyarticular" at onset. These differences can be used to develop early biomarkers of disease course, allowing for better-informed treatment decisions.
- Published
- 2018
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39. The Relationship of Repeated Technical Assistance Support Visits to the Delivery of Positive Health, Dignity, and Prevention (PHDP) Messages by Healthcare Providers in Mozambique: A Longitudinal Multilevel Analysis.
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Gutin SA, Amico KR, Hunguana E, Munguambe AO, and Rose CD
- Subjects
- Adult, Evidence-Based Medicine, Female, HIV Infections epidemiology, Humans, Longitudinal Studies, Male, Mozambique epidemiology, Multilevel Analysis, Personhood, Young Adult, HIV Infections prevention & control, HIV Infections psychology, Health Personnel psychology
- Abstract
Background: Positive health, dignity, and prevention (PHDP) is Mozambique's strategy to engage clinicians in the delivery of prevention messages to their HIV-positive clients. This national implementation strategy uses provider trainings on offering key messages and focuses on intervening on 9 evidence-based risk reduction areas. We investigated the impact of longitudinal technical assistance (TA) as an addition to this basic training., Methods: We followed 153 healthcare providers in 5 Mozambican provinces over 6 months to evaluate the impact of on-site, observation-based TA on PHDP implementation. Longitudinal multilevel models were estimated to model change in PHDP message delivery over time among individual providers., Results: With each additional TA visit, providers delivered about 1 additional PHDP message ( P < .001); clinicians and nonclinicians started at about the same baseline level, but clinicians improved more quickly ( P = .004). Message delivery varied by practice sector; maternal and child health sectors outperformed other sectors., Conclusion: Longitudinal TA helped reach the programmatic goals of the PHDP program in Mozambique.
- Published
- 2017
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40. Oral glucocorticoid use and osteonecrosis in children and adults with chronic inflammatory diseases: a population-based cohort study.
- Author
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Horton DB, Haynes K, Denburg MR, Thacker MM, Rose CD, Putt ME, Leonard MB, and Strom BL
- Subjects
- Administration, Oral, Adolescent, Adult, Arthritis, Rheumatoid drug therapy, Asthma drug therapy, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Glucocorticoids therapeutic use, Humans, Inflammatory Bowel Diseases drug therapy, Lupus Erythematosus, Systemic drug therapy, Male, Middle Aged, Proportional Hazards Models, Psoriasis drug therapy, Retrospective Studies, Young Adult, Chronic Disease drug therapy, Glucocorticoids adverse effects, Inflammation drug therapy, Osteonecrosis chemically induced
- Abstract
Objectives: We studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases., Design: Retrospective cohort study., Setting: Population-representative data (1994-2013) from general practices in the UK., Participants: Children and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus., Exposures: Oral glucocorticoid patterns., Primary and Secondary Outcome Measures: Diagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective., Results: After adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18-49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2-9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10-17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases., Conclusions: Glucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small., Competing Interests: Competing interests: KH is an employee of HealthCore, a wholly owned research subsidiary of Anthem; MRD has received grant funding from Genentech and Mallinckrodt Pharmaceuticals and has consulted for Infiniti Medical, outside the submitted work; CDR has received grant funding from GSK, outside the submitted work; MBL has consulted for Amgen and Novartis, outside the submitted work; BLS has received grant funding from AstraZeneca and Takeda and has consulted for Abbott, AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Endo Laboratories, GSK, Ikenna Ogbaa/Lexicon Pharmaceutical, LASER Europe Limited, Lilly, Lundbeck, Novartis, Novo Nordisk Pharmaceuticals, Otsuka, Pfizer, Pierre Fabre Dermatologie, Roche, Sanofi, Takeda, Teva, UCB and ViiV Healthcare, outside the submitted work. The remaining authors (DBH, MMT, MEP) have declared that no competing interests exist., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2017
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41. Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 2 of 2).
- Author
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Rose CD
- Subjects
- Child, Humans, Pediatricians, Biomedical Research ethics, Ethics Committees, Research ethics, Ethics, Research, Informed Consent legislation & jurisprudence
- Abstract
In part 1 of this series, we discussed the historical, ethical, and legal background that provides justification for the current system of protection of subjects of human experimentation. We also discussed briefly the implementation of those principles in institutional review board (IRB) operations. In part 2, we focus on legislation dealing with pediatric research, the rules and ethics of assent, and then turn our attention to minimal-risk studies. To that end, we discuss the minimal-risk threshold and the process of balancing benefit and risk in IRB decisions for pediatric studies. We define the notion of consent waiver as well as the procedures for expedited review, management of adverse events, and amendments to approved protocol. Finally, we mention some miscellaneous issues, including central and commercial IRB, reliance agreements, biobanks, and sample shipping regulations., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)
- Published
- 2017
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42. Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.
- Author
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Brescia AC, Simonds MM, Sullivan KE, and Rose CD
- Subjects
- Adolescent, Chemokines biosynthesis, Child, Child, Preschool, Female, Humans, Inflammation metabolism, Male, NF-kappa B metabolism, Synovial Fluid metabolism, Arthritis, Juvenile metabolism, Arthritis, Juvenile pathology, Chemokines metabolism, Fibroblasts pathology, Signal Transduction, Synoviocytes metabolism, Synoviocytes pathology
- Abstract
Purpose: The goal is to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins., Experimental Design: Expression of 89 cytokines and chemokines is determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls are also examined for protein expression. Ingenuity Pathway Analysis (IPA) is revealed top pathways and upstream regulators of significant proteins., Results: Protein studies is revealed that JIA FLS release pro-inflammatory cytokines and chemokines, including IL-4, IL-6, IL-17, CXCL1, and CXCL6, and lose expression of important regulator signals, such as IL-10 and TIMP2. Of the 84 proteins differentially expressed between controls and JIA in the synovial fluid, 1/3 (29 proteins) are differentially expressed in the cell culture supernatants of JIA and control FLS. ELISA of cell culture supernatants and synovial fluid confirmed seven key proteins., Conclusion and Clinical Relevance: JIA FLS are central to perpetuation of inflammation in JIA, including trafficking of inflammatory cells and effects on the extracellular matrix. These cells express key disease-specific chemokines that, with further refinement, may allow us to tailor therapy appropriately., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
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43. Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 1 of 2).
- Author
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Rose CD
- Subjects
- Biomedical Research history, Biomedical Research legislation & jurisprudence, Child, Clinical Trials as Topic ethics, Drug Discovery ethics, History, 20th Century, Human Experimentation ethics, Human Experimentation history, Human Experimentation legislation & jurisprudence, Humans, Informed Consent By Minors ethics, Multicenter Studies as Topic ethics, United States, Biomedical Research ethics, Ethics Committees, Research, Pediatricians ethics
- Abstract
As human experimentation continues to grow into an ever more complex and sophisticated endeavor, the relevant ethical and regulatory structures become more intricate. When pediatricians and general practitioners are invited by pharmaceutical companies to enroll their offices in a clinical trial or a multicenter observational study or when they develop their own research questions, they frequently find themselves at a loss in the human research environment. The legal and regulatory complexity may have an unintended deterring effect at a time when office-based high quality pediatric research is urgently needed to support evidence-based medicine. Unfortunately, in many instances, unaware practitioners become involved in low-risk research activities without knowing it and become entangled in legal, auditing, and compliance procedures. This paper, written in 2 parts, aims at providing a general guidance on the principles that regulate human research with a focus on pediatrics. Part 1 discusses the history, the legal framework, and the consent process and highlights some practical aspects of initial protocol submission, continued review, and institutional review board determinations with the main focus on multicenter clinical trials (industry-sponsored research). Part 2 focuses on pediatric research regulation, also known as subpart-D, and minimal risk research, which encompasses many research activities aimed at addressing questions that may emerge in pediatricians' practices (investigator-initiated research)., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)
- Published
- 2017
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44. Blau Syndrome: A Systemic Granulomatous Disease of Cutaneous Onset and Phenotypic Complexity.
- Author
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Rose CD
- Subjects
- Arthritis diagnosis, Humans, Mutation, Phenotype, Sarcoidosis, Synovitis diagnosis, Uveitis diagnosis, Arthritis genetics, Nod2 Signaling Adaptor Protein genetics, Synovitis genetics, Uveitis genetics
- Published
- 2017
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45. Social Stigma and Childbearing for Women Living With HIV/AIDS.
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Cuca YP and Rose CD
- Subjects
- Acquired Immunodeficiency Syndrome, Adult, Decision Making, Female, Health Personnel, Humans, HIV Infections psychology, Pregnancy psychology, Social Stigma
- Abstract
As more women become infected with HIV, the issue of childbearing becomes increasingly salient. A more nuanced understanding of women's situations is needed to provide high-quality and relevant services and support. We examined reproductive decision making among 20 women living with HIV through in-depth interviews. These women made decisions within situations of chaos, instability, and trauma, which often limited their ability to make truly informed choices about their lives and childbearing. Despite their HIV, many of the women wanted children, but experienced stigmatization related both to their HIV and to their decisions to have children. This stigmatization came from multiple sources, including health care providers, some of whom encouraged their patients to abort pregnancies because of their HIV. Participants, however, demonstrated resistance to stigmatization, through building supportive communities and developing trusting relationships with HIV providers. These results support the need for specialized HIV care for women of childbearing age., (© The Author(s) 2015.)
- Published
- 2016
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46. Epidemiology of Clostridium difficile Infection-Associated Reactive Arthritis in Children: An Underdiagnosed, Potentially Morbid Condition.
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Horton DB, Strom BL, Putt ME, Rose CD, Sherry DD, and Sammons JS
- Subjects
- Adolescent, Arthritis, Reactive diagnosis, Case-Control Studies, Child, Child, Preschool, Clostridium Infections diagnosis, Delaware epidemiology, Diagnosis, Differential, Diagnostic Errors statistics & numerical data, Female, Florida epidemiology, Follow-Up Studies, Humans, Incidence, Logistic Models, Male, Philadelphia epidemiology, Retrospective Studies, Young Adult, Arthritis, Reactive epidemiology, Clostridium Infections epidemiology
- Abstract
Importance: The incidence of Clostridium difficile infection has increased among children. The epidemiology of pediatric C difficile infection-associated reactive arthritis is poorly understood., Objective: To characterize the incidence, recognition, and distinguishing clinical features of pediatric C difficile infection-associated reactive arthritis among children with C difficile infection., Design, Setting, and Participants: In this cohort and nested case-control study using electronic health records from January 1, 2004, to December 31, 2013, across 3 geographically diverse pediatric health care networks, we screened for reactive arthritis among 148 children between ages 2 and 21 years with diagnostic or procedural codes suggesting musculoskeletal disease associated with C difficile diagnosis or positive testing. We identified 26 cases with acute arthritis or tenosynovitis within 4 weeks before to 12 weeks after confirmed C difficile infection with (1) no alternative explanation for arthritis and (2) negative synovial cultures (if obtained). Network-matched C difficile-infected controls without arthritis were randomly selected at the time of cohort member C difficile infections., Main Outcomes and Measures: Incidence of C difficile infection-associated reactive arthritis was calculated based on (1) pediatric source population and (2) children with C difficile infection. Characteristics of cases and controls were compared using conditional logistic regression., Results: Based on the cases identified within the source population of the 3 hospital networks, we estimated that C difficile infection-associated reactive arthritis incidence was 5.0 cases per million person-years (95% CI, 3.0-7.8). Reactive arthritis affected 1.4% of children with C difficile infection yearly (95% CI 0.8%-2.3%). Joint symptoms began a median of 10.5 days after initial gastrointestinal symptoms, often accompanied by fever (n = 15 [58%]) or rash (n = 14 [54%]). Only 35% of cases of C difficile infection-associated reactive arthritis were correctly diagnosed by treating health care professionals (range across centers, 0%-64%). Five affected children (19%) were treated for presumed culture-negative septic hip arthritis despite having prior postantibiotic diarrhea and/or other involved joints. Compared with controls, cases of C difficile infection-associated reactive arthritis were less likely to have underlying chronic conditions (odds ratio [OR], 0.3; 95% CI, 0.1-0.8). Although all cases had community-onset C difficile infection and fewer comorbidities, they were more likely to be treated in emergency departments and/or hospitalized (OR, 7.1; 95% CI, 1.6-31.7)., Conclusions and Relevance: C difficile infection-associated reactive arthritis is an underdiagnosed, potentially morbid reactive arthritis associated with C difficile infection occasionally misdiagnosed as septic arthritis. Given the rising incidence of pediatric C difficile infections, better recognition of its associated reactive arthritis is needed.
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- 2016
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47. Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension.
- Author
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Liu F, Haeger CM, Dieffenbach PB, Sicard D, Chrobak I, Coronata AM, Suárez Velandia MM, Vitali S, Colas RA, Norris PC, Marinković A, Liu X, Ma J, Rose CD, Lee SJ, Comhair SA, Erzurum SC, McDonald JD, Serhan CN, Walsh SR, Tschumperlin DJ, and Fredenburgh LE
- Abstract
Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2-derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I
2 analog abrogated monocrotaline-induced PA stiffening and attenuated stiffness-dependent increases in proliferation, matrix deposition, and contraction in PASMC. Our results suggest a pivotal role for early PA stiffening in PH and demonstrate the therapeutic potential of interrupting mechanobiological feedback amplification of vascular remodeling in experimental PH.- Published
- 2016
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48. The HIV Primary Care Workforce of Tomorrow: The UCSF Integrated HIV/AIDS Primary Care Capacity Nurse Practitioner Program.
- Author
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Portillo CJ, Stringari-Murray S, Fox CB, Monasterio E, and Rose CD
- Subjects
- California, Curriculum, Educational Measurement, Humans, Program Evaluation, Specialties, Nursing education, Workforce, Delivery of Health Care organization & administration, Education, Nursing, Graduate, HIV Infections nursing, Nurse Practitioners education, Primary Health Care, Program Development
- Abstract
The increasing demand for primary care services and the current health care workforce shortage is predicted to cause drastic reductions in the number of clinicians who are competent to provide HIV care. For the past decade, the University of California, San Francisco (UCSF) School of Nursing has provided HIV specialty education for Advanced Practice Nursing students in the Master's curriculum. In 2013, UCSF was funded by the Health Resources Services Administration to establish a nurse practitioner (NP) HIV primary care education program to expand the number of NPs prepared to provide culturally appropriate comprehensive HIV primary care. To this end, UCSF faculty have developed and validated a set of HIV Primary Care entry-level NP competencies, integrated general HIV knowledge into the NP curriculum, and enhanced our current HIV Specialty curriculum and clinical training. Described herein is UCSF's Integrated HIV/AIDS Primary Care Capacity Nurse Practitioner Program., (Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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49. Antibiotic Exposure, Infection, and the Development of Pediatric Psoriasis: A Nested Case-Control Study.
- Author
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Horton DB, Scott FI, Haynes K, Putt ME, Rose CD, Lewis JD, and Strom BL
- Subjects
- Adolescent, Anti-Bacterial Agents adverse effects, Case-Control Studies, Child, Child, Preschool, Databases, Factual, Female, Humans, Infant, Logistic Models, Male, Psoriasis etiology, Streptococcal Infections complications, Streptococcus pyogenes isolation & purification, United Kingdom, Virus Diseases complications, Anti-Bacterial Agents administration & dosage, Psoriasis epidemiology, Streptococcal Infections epidemiology, Virus Diseases epidemiology
- Abstract
Importance: Antibiotics disrupt human microbiota and have been associated with several pediatric autoimmune diseases. Psoriasis activity has been linked to group A streptococcal and viral infections., Objective: To determine whether antibiotic exposure and infections are independently associated with incident psoriasis in children., Design, Setting, and Participants: This nested case-control study used data from the Health Improvement Network database, a population-representative electronic health records database from the United Kingdom, from June 27, 1994, through January 15, 2013. Data were analyzed from September 17, 2014, through August 12, 2015. Children aged 1 to 15 years with newly diagnosed psoriasis (n = 845) were compared with age- and sex-matched controls (n = 8450) randomly chosen at the time of psoriasis diagnosis from general practices with at least one case, excluding children with immunodeficiency, inflammatory bowel disease, and juvenile arthritis., Exposures: Systemic antibacterial prescriptions and infections of the skin and other sites within 2 years before psoriasis diagnosis., Main Outcomes and Measures: Incident psoriasis as determined by validated diagnostic codes. The association of antibiotic exposure and infections with incident psoriasis was determined by conditional logistic regression, adjusting for confounders., Results: After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2-1.7) and other sites (aOR, 1.3; 95% CI, 1.1-1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3-1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9-1.4) were associated with psoriasis. Results were similar when using a lifetime exposure window. Different classes of antibiotics and age of first antibiotic exposure were also not associated with psoriasis. The findings did not substantively change when excluding periods of varying length before diagnosis., Conclusions and Relevance: Infections are associated with the development of pediatric psoriasis, but antibiotics do not appear to contribute substantially to that risk.
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- 2016
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50. Language and Culture in Health Literacy for People Living with HIV: Perspectives of Health Care Providers and Professional Care Team Members.
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Mogobe KD, Shaibu S, Matshediso E, Sabone M, Ntsayagae E, Nicholas PK, Portillo CJ, Corless IB, Rose CD, Johnson MO, Webel A, Cuca Y, Rivero-Méndez M, Solís Báez SS, Nokes K, Reyes D, Kemppainen J, Reid P, Sanzero Eller L, Lindgren T, Holzemer WL, and Wantland D
- Abstract
Low health literacy has been linked to inadequate engagement in care and may serve as a contributor to poor health outcomes among people living with HIV and AIDS. The purpose of this paper was to examine the perspectives of health care providers and professional care team members regarding health literacy in HIV disease. A secondary data analysis was conducted from a qualitative study aimed at understanding factors that help an HIV positive person to manage their HIV disease. Data were collected from sites in Botswana, the US, and Puerto Rico. In the parent study, data were collected through focus group discussions with 135 people living with HIV, 32 HIV health care providers (HCPs), and 39 HIV professional care team members (PCTMs). SPSS was used to analyze quantitative data while ATLAS.ti was used to analyze qualitative data. The findings from analyses of the perspectives of HCPs/PCTMs suggested that linguistic and cultural factors were important themes in the exchange of HIV information between health care providers and PLHIV. These themes included ineffective communication, health seeking behavior, cultural facilitators, and complementary and alternative/traditional healing methods. Thus, this study suggests that language and culture have a major role in health literacy for PLHIV.
- Published
- 2016
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