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  • 1
    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
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 2
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 3
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 4
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2279468-2
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  • 5
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2279468-2
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  • 6
    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
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2279468-2
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  • 7
    In: Lupus, SAGE Publications, Vol. 26, No. 9 ( 2017-08), p. 927-936
    Abstract: The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score 〉 10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2008035-9
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  • 8
    In: Lupus, SAGE Publications, Vol. 25, No. 9 ( 2016-08), p. 1012-1018
    Abstract: To evaluate candidate biomarkers to predict future renal function decline (RFD) in children and adults with lupus nephritis (LN). Methods At the time of enrollment into prospective observational LN cohort studies liver-type fatty acid binding protein (LFABP), albumin, monocyte chemoattractant protein-1 (MCP-1), uromodulin, transferrin, and hepcidin were measured in urine samples of two cohorts of patients with LN, one followed at a pediatric (cohort-1; n = 28) and one at an adult institution (cohort-2; n = 69). The primary outcome was RFD, defined in cohort-1 as a decrease in estimated glomerular filtration rate (eGFR) of ≥20% and in cohort-2 as a sustained increase of ≥25% in serum creatinine concentration (SCr), both from baseline. Results All patients ( n = 97) had normal eGFR or SCr at the time of urine collection at baseline. RFD occurred in 29% (8/28) of patients in cohort-1 during a mean follow-up of 6.1 months, and in 30% (21/69) of those in cohort-2 during a mean follow-up of 60 months. Individually, in cohort-1, levels of MCP-1, transferrin, LFABP, and albumin were higher in the RFD group than those who maintained renal function, with statistical significance for LFABP and albumin. In cohort-2 the RFD group also had higher levels of urine MCP-1 and albumin than others. The combination of LFABP, MCP-1, albumin, and transferrin had good predictive accuracy for RFD in both cohorts (area under the ROC curve = 0.77–0.82). Conclusion The combinatorial urine biomarker LFABP, MCP-1, albumin, and transferrin shows promise as a predictor of renal functional decline in LN, and warrants further investigation.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2008035-9
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  • 9
    In: Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 5, No. 51 ( 2020-09-18)
    Abstract: T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.
    Type of Medium: Online Resource
    ISSN: 2470-9468
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
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  • 10
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 16 ( 2022-08-22), p. 4926-
    Abstract: Background: The arterial blood gas (ABG) parameters of patients admitted to intensive care units (ICUs) with acute neuromuscular respiratory failure (NMRF) and non-NMRF have not been defined or compared in the literature. Methods: We retrospectively collected the initial ABG parameters (pH, PaCO2, PaO2, and HCO3) of patients admitted to ICUs with acute respiratory failure. We compared ABG parameter ranges and the prevalence of abnormalities in NMRF versus non-NMRF and its categories, including primary pulmonary disease (PPD) (chronic obstructive pulmonary disease, asthma, and bronchiectasis), pneumonia, and pulmonary edema. Results: We included 287 patients (NMRF, n = 69; non-NMRF, n = 218). The difference between NMRF and non-NMRF included the median (interquartile range (IQR)) of pH (7.39 (7.32–7.43), 7.33 (7.22–7.39), p 〈 0.001), PaO2 (86.9 (71.4–123), 79.6 (64.6–99.1) mmHg, p = 0.02), and HCO3 (24.85 (22.9–27.8), 23.4 (19.4–26.8) mmol/L, p = 0.006). We found differences in the median of PaCO2 in NMRF (41.5 mmHg) versus PPD (63.3 mmHg), PaO2 in NMRF (86.9 mmHg) versus pneumonia (74.3 mmHg), and HCO3 in NMRF (24.8 mmol/L) versus pulmonary edema (20.9 mmol/L) (all p 〈 0.01). NMRF compared to non-NMRF patients had a lower frequency of hypercarbia (24.6% versus 39.9%) and hypoxia (33.8% versus 50.5%) (all p 〈 0.05). NMRF compared to PPD patients had lower frequency of combined hypoxia and hypercarbia (13.2% versus 37.8%) but more frequently isolated high bicarbonate (33.8% versus 8.9%) (all p 〈 0.001). Conclusions: The ranges of ABG changes in NMRF patients differed from those of non-NMRF patients, with a greater reduction in PaO2 in non-NMRF than in NMRF patients. Combined hypoxemia and hypercarbia were most frequent in PPD patients, whereas isolated high bicarbonate was most frequent in NMRF patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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