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  • 1
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    Online Resource
    Baseline characteristics of children with juvenile dermatomyositis enrolled in the first year of the new Childhood Arthritis and Rheumatology Research Alliance registry
    Springer Science and Business Media LLC ; 2022
    In:  Pediatric Rheumatology Vol. 20, No. 1 ( 2022-12)
    Details
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: To report baseline characteristics, patient reported outcomes and treatment of children with Juvenile Dermatomyositis (JDM) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods Children newly diagnosed with JDM were enrolled in the CARRA Registry from 41 pediatric rheumatology centers. Baseline patient demographics, disease characteristics, assessments, patient reported outcome and treatments were recorded. Results In the first year, 119 JDM participants were enrolled. Most were female (63.4%), and white (72.3%) with a median diagnosis age 8.0 years (IQR 4.0–11.5), and median age of disease onset 7.0 years (IQR 3.5–7.5). They had characteristic rashes (92.4%), elevated muscle enzymes (83.2%), physician global score 4.0 (IQR 2.5–5.0) and manual muscle testing score 63.5 (IQR 51.0–75.0). Calcinosis (3.4%) and interstitial lung disease ( 〈  1%) were uncommon. Myositis specific antibodies were measured and reported in nearly half of participants enrolled where anti-MJ followed by Anti-p155/140 were most common (11/49 and 7/53 respectively). Childhood Health Assessment Questionnaire (CHAQ) results showed mild-moderate disability (median 0.750, IQR 0.030–1.875), as did patient/parent global assessments of disease activity (median 3, patient IQR: 1.75–5.25; parent IQR: 1–7). Patient Reported Outcomes Measurement Information System (PROMIS®) Pediatric Global Health 7 scores, Pain Interference, Physical Function scores for Mobility, and Upper Extremity Function were commonly worse than 95% of the general pediatric population. Conclusions In its inaugural year, 119 JDM patients were successfully enrolled in participapte in the New CARRA Registy. This registry will provide the necessary foundation to advance clinical research to improve outcomes using traditional measures and patient reported outcomes. With the CARRA biorepository, this infrastructure will enable future translational research. Together, these efforts may aid in future clinical trials, including comparative effectiveness trials.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    URL: Article
    DOI: 10.1186/s12969-022-00709-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 2
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    Intraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry
    Springer Science and Business Media LLC ; 2022
    In:  Pediatric Rheumatology Vol. 20, No. 1 ( 2022-11-25)
    Details
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-11-25)
    Abstract: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. Methods We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. Results We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p   〈  0.01) and 12 months (81% vs 33%, p   〈  0.05). Conclusion While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    URL: Article
    DOI: 10.1186/s12969-022-00770-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 3
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    Patterns of etanercept use in juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry
    Springer Science and Business Media LLC ; 2021
    In:  Pediatric Rheumatology Vol. 19, No. 1 ( 2021-12)
    Details
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: We aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods The CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for whom the month and year of ETN initiation were available were included. Patterns of ETN and methotrexate (MTX) use were categorized as follows: combination therapy (ETN and MTX started concurrently), step-up therapy (MTX started first and ETN added later), switchers (MTX started and then stopped when or before ETN started), MTX add-on (ETN started first and MTX added later), and ETN only (no MTX use). Data were described using parametric and non-parametric statistics as appropriate. Results Two thousand thirty-two of the five thousand six hundred forty-one patients with JIA met inclusion criteria (74% female, median age at diagnosis 6.0 years [interquartile range 2.0, 11.0]. Most patients (66.9%) were treated with a non-biologic disease modifying anti-rheumatic drug (DMARD), primarily MTX, prior to ETN. There was significant variability in patterns of MTX use prior to starting ETN. Step-up therapy was the most common approach. Only 34.0% of persistent oligoarticular JIA patients continued treatment with a non-biologic DMARD 3 months or more after ETN initiation. ETN persistence overall was 66.3, 49.4, and 37.3% at 24, 36 and 48 months respectively. ETN persistence among spondyloarthritis patients (enthesitis related arthritis and psoriatic JIA) varied by MTX initiation pattern, with higher ETN persistence rates in those who initiated combination therapy (68.9%) and switchers/ETN only (73.3%) patients compared to step-up (65.4%) and MTX add-on (51.1%) therapy. Conclusion This study characterizes contemporary patterns of ETN use in the CARRA Registry. Treatment was largely in keeping with American College of Rheumatology guidelines.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    URL: Article
    DOI: 10.1186/s12969-021-00625-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
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    Community poverty level influences time to first pediatric rheumatology appointment in Polyarticular Juvenile Idiopathic Arthritis
    Springer Science and Business Media LLC ; 2021
    In:  Pediatric Rheumatology Vol. 19, No. 1 ( 2021-12)
    Details
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. Results A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level ( 〈  20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist ( p  = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p  = 0.038) to be seen by a rheumatologist compared to patients with 〈  20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ. Conclusion In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    URL: Article
    DOI: 10.1186/s12969-021-00610-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 5
    Online Resource
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    Social determinants of health influence disease activity and functional disability in Polyarticular Juvenile Idiopathic Arthritis
    Springer Science and Business Media LLC ; 2022
    In:  Pediatric Rheumatology Vol. 20, No. 1 ( 2022-12)
    Details
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: Social determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functional disability over the first year of treatment in pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Methods In this cohort study, unadjusted and adjusted generalized linear mixed effects models analyzed the effect of community poverty and other SDH on disease activity, using the clinical Juvenile Arthritis Disease Activity Score-10, and disability, using the Child Health Assessment Questionnaire, measured at baseline, 6, and 12 months. Results One thousand six hundred eighty-four patients were identified. High community poverty (≥20% living below the federal poverty level) was associated with increased odds of functional disability (OR 1.82, 95% CI 1.28-2.60) but was not statistically significant after adjustment (aOR 1.23, 95% CI 0.81-1.86) and was not associated with increased disease activity. Non-white race/ethnicity was associated with higher disease activity (aOR 2.48, 95% CI: 1.41-4.36). Lower self-reported household income was associated with higher disease activity and persistent functional disability. Public insurance (aOR 1.56, 95% CI 1.06-2.29) and low family education (aOR 1.89, 95% CI 1.14-3.12) was associated with persistent functional disability. Conclusion High community poverty level was associated with persistent functional disability in unadjusted analysis but not with persistent moderate to high disease activity. Race/ethnicity and other SDH were associated with persistent disease activity and functional disability.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    URL: Article
    DOI: 10.1186/s12969-022-00676-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 6
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    Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry
    Oxford University Press (OUP) ; 2023
    In:  Rheumatology Vol. 62, No. 2 ( 2023-02-01), p. 804-814
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 2 ( 2023-02-01), p. 804-814
    Abstract: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. Methods JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. Results Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. Conclusions Five trajectories of JIA disease activity, and associated baseline variables, were identified.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keac335
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 7
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    Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features
    Oxford University Press (OUP) ; 2023
    In:  Rheumatology Vol. 62, No. SI2 ( 2023-02-23), p. SI226-SI234
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. SI2 ( 2023-02-23), p. SI226-SI234
    Abstract: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keac428
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 8
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    Iron complexes of a tetraimidazole ligand as models for the lipoxygenase active site.
    Elsevier BV ; 1991
    In:  Journal of Inorganic Biochemistry Vol. 43, No. 2-3 ( 1991-8), p. 560-
    Details
    In: Journal of Inorganic Biochemistry, Elsevier BV, Vol. 43, No. 2-3 ( 1991-8), p. 560-
    Type of Medium: Online Resource
    ISSN: 0162-0134
    URL: Article
    DOI: 10.1016/0162-0134(91)84535-H
    RVK:
    VA 5310
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1991
    detail.hit.zdb_id: 1491314-8
    SSG: 12
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  • 9
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    Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy
    Wiley ; 2019
    In:  Arthritis & Rheumatology Vol. 71, No. 3 ( 2019-03), p. 451-459
    Details
    In: Arthritis & Rheumatology, Wiley, Vol. 71, No. 3 ( 2019-03), p. 451-459
    Abstract: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti–tumor necrosis factor (anti‐ TNF ) therapy and the occurrence of disease flare following withdrawal of anti‐ TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). Methods In this prospective, multicenter study, 137 patients with polyarticular‐course JIA whose disease was clinically inactive while receiving anti‐ TNF therapy were enrolled. Patients were observed for an initial 6‐month phase during which anti‐ TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti‐ TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti‐ TNF withdrawal. Spearman's rank correlation test, Mann‐Whitney U test, Kruskal‐Wallis test, receiver operating characteristic ( ROC ) curve, and Kaplan‐Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti‐ TNF withdrawal. Results Over the 6‐month initial phase with anti‐ TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular‐course JIA ; following anti‐ TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti‐ TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti‐ TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti‐ TNF withdrawal were inversely correlated with the time to disease flare (r = −0.36). Conclusion Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular‐course JIA , and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
    URL: Article
    DOI: 10.1002/art.2019.71.issue-3
    DOI: 10.1002/art.40727
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2754614-7
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  • 10
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    Functional characterization of variants of unknown significance (VUS) in patients and their responsiveness to targeted therapy drugs (TTD)
    Elsevier BV ; 2016
    In:  Annals of Oncology Vol. 27 ( 2016-10), p. vi403-
    Details
    In: Annals of Oncology, Elsevier BV, Vol. 27 ( 2016-10), p. vi403-
    Type of Medium: Online Resource
    ISSN: 0923-7534
    URL: Article
    DOI: 10.1093/annonc/mdw380.09
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2003498-2
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