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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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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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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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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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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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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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Article ; Online: The impact of psoriasis on wellbeing and clinical outcomes in juvenile psoriatic arthritis.

Low, Jie Man / Hyrich, Kimme L / Ciurtin, Coziana / McErlane, Flora / Wedderburn, Lucy R

Rheumatology (Oxford, England)

2023

Abstract: Objectives: Juvenile psoriatic arthritis (JPsA) has varied clinical features that are distinctive to other juvenile idiopathic arthritis (JIA) categories. This study investigates whether such features impact patient-reported and clinical outcomes.: ... ...

Abstract	Objectives: Juvenile psoriatic arthritis (JPsA) has varied clinical features that are distinctive to other juvenile idiopathic arthritis (JIA) categories. This study investigates whether such features impact patient-reported and clinical outcomes. Methods: Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm VAS), functional ability (CHAQ), pain (10 cm VAS), health-related quality of life (CHQ psychosocial score), mood/depressive symptoms (MFQ) and parent psychosocial health (GHQ). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA, PaGA respectively). Patient-reported outcomes and outcome trajectories were compared in i) CYP with JPsA versus other JIA categories, ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. Results: There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8, 95% CI = 0.5-19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI 1.2, 4.6). Conclusion: CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes.
Language	English
Publishing date	2023-07-19
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/kead370
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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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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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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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