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  1. Book ; Online ; E-Book: Textbook of pediatric rheumatology

    Petty, Ross E. / Laxer, Ronald M. / Lindsley, Carol B. / Wedderburn, Lucy R. / Mellins, Elizabeth D. / Fuhlbrigge, Robert C.

    (Expert consult)

    2022  

    Title variant Pediatric rheumatology
    Author's details Ross E. Petty, Ronald M. Laxer, Carol B. Lindsley, Lucy R. Wedderburn, Elizabeth D. Mellins, Robert C. Fuhlbrigge
    Series title Expert consult
    Keywords Electronic books
    Language English
    Size 1 Online-Ressource (748 Seiten), Illustrationen, Diagramme
    Edition Eight edition
    Publisher Elsevier
    Publishing place Philadelphia, PA
    Publishing country United States
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT020937720
    ISBN 978-0-323-63653-7 ; 9780323636520 ; 0-323-63653-5 ; 0323636527
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts.

    Shoop-Worrall, Stephanie J W / Lawson-Tovey, Saskia / Wedderburn, Lucy R / Hyrich, Kimme L / Geifman, Nophar

    EBioMedicine

    2024  Volume 100, Page(s) 104946

    Abstract: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate ... ...

    Abstract Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures.
    Methods: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment.
    Findings: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns.
    Interpretation: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA.
    Funding: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.
    MeSH term(s) Child ; Humans ; Adolescent ; Methotrexate/adverse effects ; Arthritis, Juvenile/drug therapy ; Prospective Studies ; Artificial Intelligence ; Antirheumatic Agents/adverse effects ; Machine Learning ; United Kingdom ; Treatment Outcome
    Chemical Substances Methotrexate (YL5FZ2Y5U1) ; Antirheumatic Agents
    Language English
    Publishing date 2024-01-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2023.104946
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  3. Article ; Online: Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care.

    Papadopoulou, Charalampia / Chew, Christine / Wilkinson, Meredyth G Ll / McCann, Liza / Wedderburn, Lucy R

    Nature reviews. Rheumatology

    2023  Volume 19, Issue 6, Page(s) 343–362

    Abstract: The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, ... ...

    Abstract The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.
    MeSH term(s) Humans ; Myositis/diagnosis ; Myositis/therapy ; Autoantibodies ; Autoimmune Diseases ; Phenotype ; Prognosis
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2023-05-15
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-023-00967-9
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  4. Article: Designing, Developing, and Testing a Chatbot for Parents and Caregivers of Children and Young People With Rheumatological Conditions (the IMPACT Study): Protocol for a Co-Designed Proof-of-Concept Study.

    Livermore, Polly / Kupiec, Klaudia / Wedderburn, Lucy R / Knight, Andrea / Solebo, Ameenat L / Shafran, Roz / Robert, Glenn / Sebire, N J / Gibson, Faith

    JMIR research protocols

    2024  Volume 13, Page(s) e57238

    Abstract: Background: Pediatric rheumatology is a term that encompasses over 80 conditions affecting different organs and systems. Children and young people with rheumatological chronic conditions are known to have high levels of mental health problems and ... ...

    Abstract Background: Pediatric rheumatology is a term that encompasses over 80 conditions affecting different organs and systems. Children and young people with rheumatological chronic conditions are known to have high levels of mental health problems and therefore are at risk of poor health outcomes. Clinical psychologists can help children and young people manage the daily difficulties of living with one of these conditions; however, there are insufficient pediatric psychologists in the United Kingdom. We urgently need to consider other ways of providing early, essential support to improve their current well-being. One way of doing this is to empower parents and caregivers to have more of the answers that their children and young people need to support them further between their hospital appointments.
    Objective: The objective of this co-designed proof-of-concept study is to design, develop, and test a chatbot intervention to support parents and caregivers of children and young people with rheumatological conditions.
    Methods: This study will explore the needs and views of children and young people with rheumatological conditions, their siblings, parents, and caregivers, as well as health care professionals working in pediatric rheumatology. We will ask approximately 100 participants in focus groups where they think the gaps are in current clinical care and what ideas they have for improving upon them. Creative experience-based co-design workshops will then decide upon top priorities to develop further while informing the appearance, functionality, and practical delivery of a chatbot intervention. Upon completion of a minimum viable product, approximately 100 parents and caregivers will user-test the chatbot intervention in an iterative sprint methodology to determine its worth as a mechanism for support for parents.
    Results: A total of 73 children, young people, parents, caregivers, and health care professionals have so far been enrolled in the study, which began in November 2023. The anticipated completion date of the study is April 2026. The data analysis is expected to be completed in January 2026, with the results being published in April 2026.
    Conclusions: This study will provide evidence on the accessibility, acceptability, and usability of a chatbot intervention for parents and caregivers of children and young people with rheumatological conditions. If proven useful, it could lead to a future efficacy trial of one of the first chatbot interventions to provide targeted and user-suggested support for parents and caregivers of children with chronic health conditions in health care services. This study is unique in that it will detail the needs and wants of children, young people, siblings, parents, and caregivers to improve the current support given to families living with pediatric rheumatological conditions. It will be conducted across the whole of the United Kingdom for all pediatric rheumatological conditions at all stages of the disease trajectory.
    International registered report identifier (irrid): DERR1-10.2196/57238.
    Language English
    Publishing date 2024-04-03
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 2719222-2
    ISSN 1929-0748
    ISSN 1929-0748
    DOI 10.2196/57238
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  5. Article ; Online: Overlap of International League of Associations for Rheumatology and Preliminary Pediatric Rheumatology International Trials Organization Classification Criteria for Nonsystemic Juvenile Idiopathic Arthritis in an Established UK Multicentre Inception Cohort.

    Shoop-Worrall, Stephanie J W / Macintyre, Vanessa G / Ciurtin, Coziana / Cleary, Gavin / McErlane, Flora / Wedderburn, Lucy R / Hyrich, Kimme L

    Arthritis care & research

    2024  

    Abstract: Objective: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile ...

    Abstract Objective: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA).
    Methods: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described.
    Results: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis- and ILAR enthesitis-related JIA categories. The PRINTO rheumatoid factor (RF)-positive category was composed of 48% ILAR RF-positive polyarthritis and 52% undifferentiated JIA. The early-onset antinuclear antibodies-positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF-negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis-related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR.
    Conclusion: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified.
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645059-3
    ISSN 2151-4658 ; 0893-7524 ; 2151-464X
    ISSN (online) 2151-4658
    ISSN 0893-7524 ; 2151-464X
    DOI 10.1002/acr.25296
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  6. Article ; Online: Economic evaluation of a trial exploring the effects of a web-based support tool for parents of children with juvenile idiopathic arthritis.

    Flood, Chris / Hirani, Shashivadan P / Mulligan, Kathleen / Taylor, Jo / Harris, Sally / Wedderburn, Lucy R / Newman, Stanton P

    Rheumatology (Oxford, England)

    2024  

    Abstract: Objective: To explore the cost-effectiveness of a web-based support tool for parents of children with Juvenile Idiopathic Arthritis.: Methods: A multi-centred randomised controlled trial was conducted in paediatric rheumatology centres in England. ... ...

    Abstract Objective: To explore the cost-effectiveness of a web-based support tool for parents of children with Juvenile Idiopathic Arthritis.
    Methods: A multi-centred randomised controlled trial was conducted in paediatric rheumatology centres in England. The WebParC intervention consisted of online information about JIA and its treatment and a toolkit using cognitive-behavioural therapy principles to support parents manage their child's JIA. An economic evaluation was performed alongside the trial involving 220 parents. The primary outcome was the self-report Pediatric Inventory for Parents measure of illness-related parenting stress, with two dimensions; difficulty and frequency. These measures along with costs were assessed post intervention at 4 months and 12 months. Costs were calculated for healthcare usage using a UK NHS economic perspective. Data was collected and analysed on the impact of caring costs on families. Uncertainty around cost effectiveness was explored using bootstrapping and cost-effectiveness acceptability curves.
    Results: The intervention arm showed improved average Pediatric Inventory for Parents scores for the dimensions of frequency and difficulty, of 1.5 and 3.6 respectively at 4 months and. 0.35 and 0.39 at 12 months, representing improved PIP scores for the intervention arm. At both 4 and 12 month follow up the average total cost per case was higher in the control group when compared with the intervention arm with mean differences of £360 (95% CI £29.6 to £691) at 4 months and £203 (95% CI £16 to £390) at 12 months. The probability of the intervention being cost effective ranged between 49% and 54%.
    Conclusion: The WebParC intervention led to reductions in primary and secondary healthcare resource use and costs at 4 and 12 months. The intervention demonstrated particular savings for rheumatology services at both follow ups. Future economies of scale could be realised by health providers with increased opportunities for cost effectiveness over time.
    Trial registration: ISRCTN, ISRCTN13159730.
    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae188
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  7. Article: Juvenile dermatomyositis. Where are we now?

    McCann, Liza J / Livermore, Polly / Wilkinson, Meredyth G Ll / Wedderburn, Lucy R

    Clinical and experimental rheumatology

    2022  Volume 40, Issue 2, Page(s) 394–403

    Abstract: Juvenile onset idiopathic inflammatory myopathy (IIM) has many similarities and distinct differences from adult-onset disease. This review will focus on recent developments in understanding and treatment of juvenile dermatomyositis (JDM), the most common ...

    Abstract Juvenile onset idiopathic inflammatory myopathy (IIM) has many similarities and distinct differences from adult-onset disease. This review will focus on recent developments in understanding and treatment of juvenile dermatomyositis (JDM), the most common disease sub-type of IIM in childhood. JDM is a systemic immune mediated vasculopathy, increasingly recognised as a group of distinct phenotypes with variable presentation and outlook. This overview will describe long-term outlook and disease course including health-related quality of life and emerging treatments.
    MeSH term(s) Dermatomyositis/diagnosis ; Dermatomyositis/therapy ; Disease Progression ; Humans ; Myositis/therapy ; Quality of Life ; Vascular Diseases
    Language English
    Publishing date 2022-02-07
    Publishing country Italy
    Document type Journal Article ; Review
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    DOI 10.55563/clinexprheumatol/56ilob
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  8. Article ; Online: The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource.

    Lawson-Tovey, Saskia / Smith, Samantha Louise / Geifman, Nophar / Shoop-Worrall, Stephanie / Ng, Sandra / Barnes, Michael R / Wedderburn, Lucy R / Hyrich, Kimme L

    Pediatric rheumatology online journal

    2023  Volume 21, Issue 1, Page(s) 70

    Abstract: Background: CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges ... ...

    Abstract Background: CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset.
    Methods: Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies.
    Results: Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation.
    Conclusions: Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration.
    MeSH term(s) Child ; Humans ; Arthritis, Juvenile/drug therapy ; Methotrexate/therapeutic use ; Precision Medicine ; Tumor Necrosis Factor Inhibitors
    Chemical Substances Methotrexate (YL5FZ2Y5U1) ; Tumor Necrosis Factor Inhibitors
    Language English
    Publishing date 2023-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2279468-2
    ISSN 1546-0096 ; 1546-0096
    ISSN (online) 1546-0096
    ISSN 1546-0096
    DOI 10.1186/s12969-023-00839-2
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  9. Article ; Online: Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis.

    Wedderburn, Lucy R / Ramanan, Athimalaipet V / Croft, Adam P / Hyrich, Kimme L / Dick, Andrew D

    Annals of the rheumatic diseases

    2022  Volume 82, Issue 4, Page(s) 449–456

    Abstract: In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple ...

    Abstract In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.
    MeSH term(s) Child ; Adult ; Humans ; Adolescent ; Arthritis, Juvenile/drug therapy ; Precision Medicine ; Registries
    Language English
    Publishing date 2022-12-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard-2022-222553
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  10. Article ; Online: The Effects of a Web-Based Tool for Parents of Children With Juvenile Idiopathic Arthritis: Randomized Controlled Trial.

    Mulligan, Kathleen / Hirani, Shashivadan P / Harris, Sally / Taylor, Jo / Wedderburn, Lucy R / Newman, Stanton

    Journal of medical Internet research

    2022  Volume 24, Issue 5, Page(s) e29787

    Abstract: Background: Juvenile idiopathic arthritis (JIA) is a group of autoinflammatory diseases that cause pain and disability if not controlled by treatment. Parenting a child with JIA is stressful for parents, who express concerns about their child's ... ...

    Abstract Background: Juvenile idiopathic arthritis (JIA) is a group of autoinflammatory diseases that cause pain and disability if not controlled by treatment. Parenting a child with JIA is stressful for parents, who express concerns about their child's treatment and may experience anxiety and powerlessness concerning their child's illness. Parenting stress is greater in parents of children with chronic illness than in those with healthy children and is related to poorer psychological adjustment in both parents and children. It is therefore important to develop interventions to support parents. This paper reports the evaluation of a web-based tool that provides information and practical skills to help increase parents' confidence in managing their child's illness and reduce parenting stress.
    Objective: The aim of this study is to evaluate the benefits of a web-based tool (WebParC) for parents of children with recently diagnosed JIA.
    Methods: A multicentered randomized controlled trial was conducted at pediatric rheumatology centers in England. We recruited parents of children aged ≤12 years who had been diagnosed with JIA within the previous 6 months. They were randomized to the intervention (WebParC access plus standard care) or the control (standard care alone) and followed up 4 months and 12 months after randomization. Where both parents participated, they were randomized by household to the same trial arm. The WebParC intervention consists of information about JIA and its treatment plus a toolkit, based on cognitive behavioral therapy, to help parents develop skills to manage JIA-related issues. The primary outcome was the self-report Pediatric Inventory for Parents measure of illness-related parenting stress. The secondary outcomes were parental mood, self-efficacy, coping, effectiveness of participation in their child's health care, satisfaction with health care, and child's health-related quality of life.
    Results: A total of 203 households comprising 220 parents were randomized to the intervention (100/203, 49.3%) or control (103/203, 50.7%) arm. Follow-up assessments were completed by 65.5% (133/203) of the households at 4 months (intervention 60/100, 60%, and control 73/103, 70.9%) and 61.1% (124/203) of the households at 12 months (intervention 58/100, 58%, and control 66/103, 64.1%). A main effect of the trial arm was found on the Pediatric Inventory for Parents: the intervention participants reported less frequency (subscales communication F
    Conclusions: The WebParC website for parents of children with JIA reduced illness-related parenting stress. This web-based intervention offers a feasible preventive approach for parents of children with JIA and potentially could be adapted and evaluated for parents of children with other chronic illnesses.
    Trial registration: International Standard Randomized Controlled Trial Number (ISRCTN) 13159730; http://www.isrctn.com/ISRCTN13159730.
    MeSH term(s) Arthritis, Juvenile/psychology ; Arthritis, Juvenile/therapy ; Child ; Humans ; Internet ; Parenting/psychology ; Parents/psychology ; Quality of Life/psychology
    Language English
    Publishing date 2022-05-12
    Publishing country Canada
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028830-X
    ISSN 1438-8871 ; 1438-8871
    ISSN (online) 1438-8871
    ISSN 1438-8871
    DOI 10.2196/29787
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