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Objectives: To develop consensus-based recommendations for physician's global assessment of disease activity (PhGA) scoring and to standardise definitions of disease activity., Methods: An international task force of 34 members was assembled, and recommendations were developed in 3 phases: (1) 2 preliminary surveys of paediatric rheumatologists and a literature review; (2) 14 videoconference meetings, informed by multicriteria decision analysis and formal anonymous voting; and (3) a 2-day in-person consensus conference using structured nominal group technique discussions and formal voting. The threshold for achieving consensus was ≥78% of voting task force members. Agreement with the final statements was rated using a numerical rating scale from 0, strongly disagree, to 10, strongly agree., Results: Eighteen points to consider were agreed upon. All statements achieved consensus (≥78%), with a level of agreement ≥9.2. Points included the definition of disease activity in juvenile idiopathic arthritis (JIA), factors to assess in nonsystemic JIA and systemic JIA, consideration of available imaging and laboratory tests, the role of extra-articular manifestations, the evaluation of treatment, and the timing of PhGA scoring., Conclusions: The task force developed consensus-based recommendations when scoring the PhGA in nonsystemic and systemic JIA. These recommendations will lead to more reliable scoring of disease activity in patients with JIA., Competing Interests: Competing interests None of the authors received any support from commercial entities for the work reported in the current submitted manuscript. VR and AC reports that the project was supported by the 2022 Paediatric Rheumatology European Association (PReS)/Paediatric Rheumatology International Trials Organisation (PRINTO) grant, The Systemic JIA Foundation, the University Hospital of North Norway, the University of Tromsø, The Arctic University of Norway, and Grete Harbitz legacy against rheumatic diseases, Norway. All the authors of the paper attending the PhGA consensus conference in Tromsø, Norway, received reimbursement of travel expenses covered by the PRes/PRINTO grant, and the Systemic JIA Foundation. The accomodation in Tromsø and meeting facilities expenses were covered by funding from Grete Harbitz legacy, the University Hospital of North Norway and the University of Tromsø - The Arctic University of Norway. CB has received consulting fees from Swedish Orphan Biovitrum AB (SOBI) and Novartis. AC has an investigator initiated grant from Pfizer. AC has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer. BF has received grants from Canadian Institutes of Health Research (CIHR) and the institution. BF has received royalties or licenses from Hemophilia Joint Health Score (HJHS) and the institution. BF has received consulting fees from Pfizer, Cabaletta, and Data Safety and Monitoring Board (DSMB). BF reports participation on a data safety monitoring board or advisory board for Pfizer. JG reports that the project was funded by a competitive grant as stated in the manuscript. JG is the co-lead of the American College of Rheumatology Disease Criteria Subcommittee. DBH reports grant funding from Childhood Arthritis and Rheumatology Research Alliance-Arthritis Foundation and Danisco USA, Inc. DBH reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from American College of Rheumatology and honorarium for participating in JIA treatment guidelines. DBH reports support for attending meetings and/or travel from Childhood Arthritis and Rheumatology Research Alliance and American College of Rheumatology. DBH reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Childhood Arthritis and Rheumatology Research Alliance and membership of the steering committee. RML reports royalties and license from UpToDate and Elsevier. RML reports consulting fees from SOBI, Novartis, Sanofi, Akros Pharma, and Eli Lilly Canada. RML reports Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Eli Lilly, Sanofi, and Children's Hospital of Philadelphia. FM reports consulting fees from SOBI. FM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from SOBI and Novartis. FM reports support for attending meetings and/or travel from SOBI. FM reports participation on a data safety monitoring board or advisory board for SOBI. EMM reports grants or contracts from Pfizer and Agency for Healthcare Research and Quality. EMM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from American College of Rheumatology. EMM reports support for attending meetings and/or travel from American College of Rheumatology and Systemic JIA Foundation. EMM reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for the Pediatric Rheumatology Care and Outcomes Improvement Network. JM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events for Pfizer excite meeting Sept 2023 Melbourne speaker. CN reports PReS as support for the present manuscript. CN reports support for attending meetings and/or travel from PReS. AR reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Alexion, Novartis, Pfizer, SOBI, and Galapagos. AR is the President of the Pediatric Rheumatology European Society. JFS reports receiving a small Research grant from Pfizer. JFS reports Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer. MTw reports receiving travel support to attend the Consensus meeting. MTw is a committee chair of Childhood Arthritis and Rheumatology Research Alliance (CARRA) JIA. PV reports Support for attending meetings and/or travel from Pfizer, Novartis, and Orion. PV reports Participation on a Data Safety Monitoring Board or Advisory Board for Novartis. SJV reports grants from Dutch Arthritis Society Grant: InSyST (systemic JIA), Dutch Arthritis Society Grant: Longitudinal Research Support line 10 (LLP10), and PReS PRINTO Grant: Metaphor project, co-PI. SJV reports consulting fees from SOBI and Novartis. SJV reports Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from SOBI and Novartis. SJV reports Patents planned, issued or pending (PCT/EP2023/066764). SJV reports being Chair Kawasaki Disease Coronary Artery Aneurysm Prevention (KD CAAP) Trial Steering Committee, Co-principal investigator for Canada-Netherlands Personalized Medicine Network in Childhood Arthritis and Rheumatic Diseases (UCAN CAN-DU), and Chair Clinical Guideline Committee The European Reference Network-Rare Immunological Disorders (ERN-RITA). JV reports Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis and Eli Lily. JV reports Support for attending meetings and/or travel from Abbvie and Novartis. JV is a member of the PRES executive committee. PW reports grants from Patient-Centered Outcomes Research Institute, National Institutes of Health (NIH), National Institute of Arthritis and Muskuloskeletal and Skin Diseases (NIAMS) (1R01AR074098), and Spondylitis Association of America. PW reports Royalties or licenses from UpToDate. PW reports Consulting fees from Pfizer and Cerecor. PW is a Site investigator for Pfizer and Abbvie Clinical Trials. PW is an advisory board member of Lily, Biogen, and Novartis. PW reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Rheum Now Speaker (2022) and Spondyloarthritis Research and Treatment Network. The following authors have no conflicts of interest to disclose: AA, SA-H, MB, EB-D, MG, DJL, TL, SM-M, EN, NP, EP, CSM, RS, MTa., (Copyright © 2025 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

Objective: Health recommender systems (HRSs) are increasingly used to complement existing clinical decision-making processes, but their use for chronic diseases remains underexplored. Recognizing the importance of collaborative decision making (CDM) and patient engagement in chronic disease treatment, this review explored how HRSs support patients in managing their illness., Methods: A scoping review was conducted using the framework proposed by Arksey and O'Malley, advanced by Levac et al., in line with the PRISMA-ScR checklist. Quantitative (descriptive numerical summary) and qualitative (inductive content analysis) methods wered used to synthesize the data., Results: Forty-five articles were included in the final review, most commonly covering diabetes (9/45, 20%), mental health (9/45, 20.0%), and tobacco dependence (7/45, 15.6%). Behavior change theories (10/45, 22.2%) and authoritative sources (10/45, 22.2%) were the most commonly referenced sources for design and development work. From the thematic analysis, we conclude: (a) the main goal of HRSs is to induce behavior change, but limited research investigates their effectiveness in achieving this aim; (b) studies acknowledge that theories, models, frameworks, and/or guidelines help design HRSs to elicit specific behavior change, but they do not implement them; (c) connections between CDM and HRS purpose should be more explicit; and (d) HRSs can often offer other self-management services, such as progress tracking and chatbots., Conclusions: We recommend a greater emphasis on evaluation outcomes beyond algorithmic performance to determine HRS effectiveness and the creation of an evidence-driven, methodological approach to creating HRSs to optimize their use in enhancing patient care., Lay Summary: Our work aims to provide a summary of the current landscape of health recommender system (HRS) use for chronic disease management. HRSs are digital tools designed to help people manage their health by providing personalized recommendations based on their health history, behaviors, and preferences, enabling them to make more informed health decisions. Given the increased use of these tools for personalized care, and especially with advancements in generative artificial intelligence, understanding the current methods and evaluation processes used is integral to optimizing their effectiveness. Our findings show that HRSs are most used for diabetes, mental health, and tobacco dependence, but only a small percentage of publications directly reference and/or use relevant frameworks to help guide their design and evaluation processes. Furthermore, the goal for most of these HRSs is to induce behavior change, but there is limited research investigating how effective they are in accomplishing this. Given these findings, we recommend that evaluations shift their focus from algorithms to more holistic approaches and to be more intentional about the processes used when designing the tool to support an evidence-driven approach and ultimately create more effective and useful HRSs for chronic disease management., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Objective: To assess current treatment in macrophage activation syndrome (MAS) worldwide and to highlight any areas of major heterogeneity of practice., Methods: A systematic literature search was performed in both EMBASE and PubMed databases. Paper screening was done by two independent teams based on agreed criteria. Data extraction was standardized following the PICO framework. A panel of experts assessed paper validity, using the Joanna Briggs Institute appraisal tools and category of evidence (CoE) according to EULAR procedure., Results: Fifty-seven papers were finally included (80% retrospective case-series), describing 1148 patients with MAS: 889 systemic juvenile idiopathic arthritis (sJIA), 137 systemic lupus erythematosus (SLE), 69 Kawasaki disease (KD) and 53 other rheumatological conditions. Fourteen and 11 studies specified data on MAS associated to SLE and KD, respectively. All papers mentioned glucocorticoids (GCs), mostly methylprednisolone and prednisolone (90%); dexamethasone was used in 7% of patients. Ciclosporin was reported in a wide range of patients according to different cohorts. Anakinra was used in 179 MAS patients, with a favourable outcome in 83% of sJIA-MAS. Etoposide was described by 11 studies, mainly as part of HLH-94/04 protocol. Emapalumab was the only medication tested in a clinical trial in 14 sJIA-MAS, with 93% of MAS remission. Ruxolitinib was the most reported Janus kinase inhibitor in MAS., Conclusion: High-dose GCs together with IL-1 and IFNγ inhibitors have shown efficacy in MAS, especially in sJIA-associated MAS. However, the global level of evidence on MAS treatment, especially in other conditions, is still poor and requires standardized studies to be confirmed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: This study examined the comparability of venous and capillary blood samples with regard to routine chemistry analytes., Methods: Venous and capillary blood samples were collected from adult patients to assess comparability of alanine transaminase, albumin, alkaline phosphatase, apolipoprotein B, aspartate aminotransferase, total bilirubin, calcium, chloride, creatin kinase, creatinine, C-reactive protein, ferritin, folic acid, free T4, gamma glutamyltransferase, glucose, high density lipoprotein cholesterol, iron, lipase, lipoprotein a, magnesium, phosphate, postassium, prostate specific antigen, sodium, total cholesterol, total protein, transferrin, triglycerides, thyroid stimulating hormone, urate, urea, vitamin B12 and 25-hydroxyvitamin-D3. Furthermore, hemolysis-icterus-lipemia Index (HIL-Index) was measured for all samples. All measurements were performed using the Siemens Atellica ® CH or IH Analyzer. Deming regression analysis and mean relative differences between venous and capillary measurements of each analyte were contrasted with the desirable total allowable error (TEa) and Clinical Laboratory Improvement Amendments (CLIA) 2024 proposed acceptance limits for proficiency testing., Results: Deming regression and mean relative differences demonstrated excellent comparability between venous and capillary samples for most measured analytes., Conclusions: Capillary and venous samples showed comparable results for almost all studied chemistry analytes. Of the 33 studied analytes for which TEa criteria where available, 30 met TEa criteria. CLIA 2024 criteria where available for 29 of the studied analytes of which only glucose did not meet the criteria. In conclusion, capillary blood draw is a suitable alternative for venous blood sampling for measuring most of the investigated analytes. This benefits patients with fear of needles and might pave the way for remote self-sampling., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children. It can cause joint pain and permanent physical damage, which affects mobility and daily activities. The EQ-5D-Y-3L self-report version has been validated in JIA, but the validity of EQ-5D-Y-5L remains unknown. We examined the psychometric properties of the EQ-5D-Y-5L parent-proxy version among children with JIA., Methods: We used data from the Understanding Childhood Arthritis Network Canadian-Dutch collaboration study cohort, including patients with new-onset JIA, and those starting or stopping biologics. Clinical data and the parent-proxy version of the childhood health assessment questionnaire (CHAQ) and EQ-5D-Y-5L were collected. We evaluated the ceiling and floor effect; convergent and divergent validity using Spearman's rank correlation; known-group validity using one-way ANOVA (Analysis of Variance) and effect size; and informativity using Shannon's evenness index., Results: 467 patient visits representing 407 patients were analyzed. The EQ-5D-Y-5L had no ceiling/floor effect. The EQ-5D-Y-5L showed good convergent (e.g., EQ-5D-Y-5L pain/discomfort dimension vs. CHAQ pain index (Spearman's r = 0.74, 95% confidence interval (C.I.): 0.69-0.79)), divergent (e.g., EQ-5D-Y-5L pain/discomfort dimension vs. CHAQ eating dimension (Spearman's r = 0.19, 95% C.I.: 0.09-0.29)) and known-group validity (e.g., mean EQ-5D-Y-5L level summary score for patients with inactive versus active disease status, 6.34 vs. 10.52 (p < 0.001, effect size = 1.20 (95% C.I.: 0.95-1.45)). Shannon's evenness index ranged from 0.52 to 0.88, suggesting most dimensions had relatively even distributions., Conclusions: In this patient sample, EQ-5D-Y-5L parent-proxy version exhibited construct validity and informativity, suggesting the EQ-5D-Y-5L can be used to measure the quality of life of children with JIA., (© 2024. The Author(s).)

Background: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA)., Methods: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses., Results: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; β=-0.018, p=.035), except in the QFS group (β=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (M dif =.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658)., Conclusion: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients., Methods: This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal)., Results: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (-44.8%) and €6569/patient (-28.3%) in the first and second year post-withdrawal, respectively (P < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively., Conclusion: In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To evaluate the use of two self-management intervention strategies for persistent fatigue in adolescents and young adults with a fatigue syndrome or rheumatic condition., Design: A randomized crossover trial administering tailored lifestyle advice and generic dietary advice, each 12 weeks, with a four-week washout period between., Methods: Sixty participants (aged 12-29) were included. Tailoring was achieved through the PROfeel method. Dietary guidelines were conceptualized by the Netherlands Nutrition Centre. Questionnaires were used pre-post-interventions to measure primary outcome 'fatigue severity' (Checklist Individual Strength-8) and secondary outcomes 'self-efficacy' (Self-Efficacy Scale-28) and 'quality of life' (QoL) (Paediatric Quality of Life Inventory 4.0). Feasibility and adherence were self-rated on a scale of 1 to 10 (low to high). Linear mixed modelling was used to assess change over time, compare strategy effectiveness and study the impact of intervention order., Results: Fatigue severity, self-efficacy and QoL regarding 'physical' and 'emotional' functioning improved significantly over time (all p < .015). The average improvement of the two QoL subscales was clinically relevant, as was the fatigue improvement in 20 out of 46 participants who completed the trial and 5 dropouts. The interventions were equally effective, and intervention order did not impact the improvement level (p range  = .242-.984). The self-management strategies received similar feasibility (M = 6.45, SD = 1.91) and adherence (M = 7.67, SD = 1.67) ratings., Conclusions: As small to clinically relevant improvements were observed, self-management strategies might be particularly useful to bridge waiting time for guided treatments such as Cognitive Behavioural Therapy., (© 2023 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: To examine individual outcomes after tailored lifestyle (PROfeel) or generic dietary advice as self-management intervention for persistent fatigue in adolescents and young adults with a chronic condition, to compare participants who did and did not benefit and to explore changes to factors in the biopsychosocial model of fatigue after PROfeel., Method: A multiple single-case AB-phase design was embedded in a randomized crossover trial (N = 45). Intensive longitudinal data (ILD) on outcomes 'fatigue severity', 'self-efficacy' and 'quality of life' (QoL) were collected through weekly smartphone measurement for 20 weeks. ILD on biopsychosocial factors were collected through experience sampling methodology for 28 days pre-post first intervention. Baseline characteristics were compared with t-tests and chi-square tests. Permutation distancing tests were used to assess change over time in all ILD., Results: Regarding weekly measurements, nineteen participants (42.22%) showed small to large positive outcomes (d range  = .05 to 2.59), mostly after PROfeel. Eleven participants (24.44%) showed small to moderate negative outcomes (d range  = -.02 to -2.46), mostly after dietary advice. Fatigue severity improved most, followed by self-efficacy. Participants who benefitted showed higher QoL levels and lower fatigue and pain levels compared with others at baseline (all p < .02). When positive outcomes were observed after PROfeel, typically ≥1 biopsychosocial factor had been targeted successfully., Conclusion: Self-management advice has more potential when tailored to individual characteristics, including the biopsychosocial model of fatigue. PROfeel appears particularly useful as fatigue intervention for individuals with relatively less severe symptoms., (© 2024 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: To develop parent- and child-centered versions of the Juvenile Arthritis Disease Activity Score (JADAS) and to provide preliminary evidence of their validity., Methods: Validation analyses were conducted on two large multinational datasets of patients with juvenile idiopathic arthritis (JIA) and included assessment of construct validity, internal consistency and structure, discriminative validity, responsiveness to change, and predictive validity., Results: The parJADAS and patJADAS include four parent/patient-reported outcomes, each measured on a 0-10 scale: assessment of overall disease activity; rating of pain intensity; assessment of activity of joint disease; duration of morning stiffness. Both scores are calculated as the simple linear sum of the scores of their 4 components, which yields for both of them a global score of 0-40. The parJADAS and patJADAS demonstrated good construct validity, yielding high correlations with other JIA composite disease activity measures and moderate correlations with physician global rating and joint counts. Internal consistency was satisfactory, with Cronbach' s alpha > 0.80, and exploratory factor analysis showed that both indices are monodimensional. Both instruments discriminated well between different disease states, with discriminative ability being not affected by the presence of damage, proved able to predict important disease outcomes, and showed fair responsiveness to clinically important change, with standardized response mean of 0.71., Conclusion: Both parJADAS and patJADAS were found to possess good measurement properties and to serve as surrogate of physicians' evaluations. Regular home completion of the two instruments through digital technologies offers a suitable and pragmatic approach to deliver remote symptom monitoring and telehealth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined., Methods: This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy., Results: Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher's Exact)., Conclusions: Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy., (© 2024. The Author(s).)

Background: The recent Cardiovascular Disease in Adolescents with Chronic Disease (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left ventricular (LV) afterload and trigger a cascade of adverse arterioventricular interaction. Here, we investigate the relation between aortic changes and LV function in the CDACD study participants., Methods: This cross-sectional study included 114 adolescents 12-18 years old with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (n = 20), and healthy controls (n = 25). Aortic pulse wave velocity (PWV), which reflects aortic stiffness, and aortic wall thickness (AWT) were assessed with cardiovascular magnetic resonance imaging (CMR). Echocardiography was employed to study conventional markers of LV function, as well as LV global longitudinal strain (LVGLS), which is an established (pre)clinical marker of LV dysfunction., Results: First, aortic PWV and AWT were increased in all chronic disease groups, compared to controls. Second, in adolescents with CoA, JIA, and obesity, echocardiography showed a decreased LVGLS, while LV dimensions and conventional LV function markers were similar to controls. Third, multivariable linear regression identified aortic PWV as the most important determinant of their decreased LVGLS (standardized β -0.522, p < 0.001)., Conclusions: The decreased LVGLS in several adolescent chronic disease groups was associated with enhanced aortic PWV, which might reflect adverse arterioventricular interaction. Whether the decreased LVGLS in the chronic disease groups could negatively impact their long-term cardiovascular outcomes requires further study., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No author had any financial interest in the subject matter discussed in the submitted manuscript. No conflict of interest needs to be disclosed. All authors state that this study complies with the Declaration of Helsinki., (© 2024 Published by Elsevier B.V.)

Objectives: To evaluate immunogenicity, effectiveness and safety of COVID-19 vaccination in patients with pediatric autoimmune inflammatory rheumatic disease (pedAIIRD)., Methods: A prospective cohort study was performed at the pediatric rheumatology department of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Vaccination dates, COVID-19 cases and vaccine-related adverse events (AEs) were registered for all pedAIIRD patients during regular clinic visits from March 2021 - August 2022. SARS-CoV-2 IgG antibody levels and T-cell responses were measured from serum samples after vaccination, and clinical and drug therapy data were collected from electronic medical records. Rate of COVID-19 disease was compared between vaccinated and unvaccinated patients in a time-varying Cox regression analysis., Results: A total of 157 patients were included in this study and 88 % had juvenile idiopathic arthritis (JIA). One hundred thirty-seven patients were fully vaccinated, of which 47 % used biological agents at the time of vaccination, and 20 patients were unvaccinated. Geometric mean concentrations (GMCs) of post-vaccine antibody levels against SARS-CoV-2 were above the threshold for positivity in patients who did and did not use biological agents at the time of vaccination, although biological users demonstrated significantly lower antibody levels (adjusted GMC ratio: 0.38, 95 % CI: 0.21 - 0.70). T-cell responses were adequate in all but two patients (9 %). The adjusted rate of reported COVID-19 was significantly lower for fully vaccinated patients compared to non-vaccinated patients (HR: 0.53, 95 % CI: 0.29 - 0.97). JIA disease activity scores were not significantly different after vaccination, and no serious AEs were reported., Conclusions: COVID-19 mRNA vaccines were immunogenic (both cellular and humoral), effective and safe in a large cohort of pedAIIRD patients despite their use of immunosuppressive medication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity., Methods: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement., Results: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity., Conclusion: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erin Balay-Dustrude reports travel was provided by Omeract - Outcome Measures in Rheumatology. Ben Horgan reports travel was provided by Omeract - Outcome Measures in Rheumatology. Grayson Shultz reports travel was provided by Omeract - Outcome Measures in Rheumatology. Alessandro Consolaro reports a relationship with Pfizer that includes: funding grants and speaking and lecture fees. Joost F. Swart reports a relationship with Amgen Inc that includes: consulting or advisory. Esi M Morgan reports a relationship with Pfizer that includes: funding grants. Esi M Morgan reports a relationship with Agency for Healthcare Research and Quality that includes: funding grants. Esi M Morgan reports a relationship with American College of Rheumatology that includes: speaking and lecture fees and travel reimbursement. Esi M Morgan reports a relationship with Pediatric Rheumatology Care and Outcomes Improvement Network that includes: board membership., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Human leukocyte antigen (HLA)-DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of patients with new-onset sJIA treated with anakinra as first-line therapy., Methods: HLA and IL1RN risk alleles were identified via whole-genome sequencing. Treatment responses and complications were compared between carriers versus noncarriers., Results: Seventeen of 65 patients (26%) carried HLA-DRB1*15:01, comparable with the general population, and there was enrichment for HLA-DRB1*11:01, a known risk locus for sJIA. The rates of clinical inactive disease (CID) at 6 months, 1 year, and 2 years were generally high, irrespective of HLA-DRB1 or IL1RN variants, but significantly lower in carriers of an HLA-DRB1*11:01 allele. One patient, an HLA-DRB1*15:01 carrier, developed sJIA-LD. Of the three patients with severe drug reactions to biologics, one carried HLA-DRB1*15:01. The prevalence of eosinophilia did not significantly differ between HLA-DRB1*15:01 carriers and noncarriers at disease onset (6.2% vs 14.9%, P = 0.67) nor after the start of anakinra (35.3% vs 37.5% in the first 2 years of disease)., Conclusion: We observed high rates of CID using anakinra as first-line treatment irrespective of HLA-DRB1 or IL1RN variants. Only one of the 17 HLA-DRB1*15:01 carriers developed sJIA-LD, and of the three patients with drug reactions to biologics, only one carried HLA-DRB1*15:01. Although thorough monitoring for the development of drug hypersensitivity and refractory disease courses in sJIA, including sJIA-LD, remains important, our data support the early start of biologic therapy in patients with new-onset sJIA irrespective of HLA-DRB1 background or IL1RN variants., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The COVID-19 pandemic has affected patient care in general. We aimed to analyze the impact of the pandemic on pediatric rheumatology practice., Methods: An online survey including 22 questions was created by the representatives of the Emerging RheumatoloGists and rEsearchers (EMERGE) group of the Pediatric Rheumatology European Society (PReS) on SurveyMonkey. The descriptive analysis of the responses was performed on SurveyMonkey., Results: Overall, 469 pediatric rheumatologists (F/M: 2.9) from 70 countries completed the survey. The practice of drug prescription is not affected by the pandemic, according to 65.3 % of the respondents, while 24.3 % and 16.5 % are prescribing biologic drugs and corticosteroids less often, respectively. Over 40 % of the respondents have seen an increased number of patients with vasculitis or chilblains during the pandemic. One-third of the respondents stated no adjustments in their clinical practice after 2.5 years of COVID-19 pandemic. The rest indicated implementing various changes, with an emphasis on incorporating telemedicine. Telemedicine constitutes ≥10 % of the clinical practice for one-third of the participants. Nonetheless, 35.5 % agree that there are still delays in patient care due to the pandemic. However, most (∼90 %) think our practice is returning to the pre-pandemic routine., Conclusion: The findings of our study indicate a significant alteration in pediatric rheumatology practice due to the pandemic. This includes increased caution when prescribing anti-rheumatic drugs, a transition towards telemedicine utilization, delays in routine care, and a rise in COVID-19-related inflammatory conditions. It is imperative to address these aspects in order to improve patient care in pediatric rheumatology., Competing Interests: Declaration of Competing Interest Gmuca S is supported by NIAMS of the National Institutes of Health under award number K23AR081409 (Gmuca). The content of the manuscript is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. Other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and comprises of multiple subtypes. The most relevant disease subtypes, grouped upon current insight in disease mechanisms, are nonsystemic (oligo- and polyarticular) JIA and systemic JIA (sJIA). In this review, we summarize some of the main proposed mechanisms of disease in both nonsystemic and sJIA and discuss how current therapeutic modalities target some of the pathogenic immune pathways. Chronic inflammation in nonsystemic JIA is the result of a complex interplay between effector and regulatory immune cell subsets, with adaptive immune cells, specifically T-cell subsets and antigen-presenting cells, in a central role. There is, however, also innate immune cell contribution. SJIA is nowadays recognized as an acquired chronic inflammatory disorder with striking autoinflammatory features in the first phase of the disease. Some sJIA patients develop a refractory disease course, with indications for involvement of adaptive immune pathways as well. Currently, therapeutic strategies are directed at suppressing effector mechanisms in both non-systemic and sJIA. These strategies are often not yet optimally tuned nor timed to the known active mechanisms of disease in individual patients in both non-systemic and sJIA. We discuss current treatment strategies in JIA, specifically the 'Step-up' and 'Treat to Target approach' and explore how increased insight into the biology of disease may translate into future more targeted strategies for this chronic inflammatory disease at relevant time points: preclinical disease, active disease, and clinically inactive disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)