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The aim of the Paediatric Rheumatology International Trials Organisation (PRINTO) juvenile idiopathic arthritis (JIA) classification criteria, which is still in development, is to identify homogeneous groups of JIA patients. This study was undertaken to compare International League of Associations for Rheumatology (ILAR) JIA classification criteria and PRINTO JIA classification criteria using data from the ReACCh-Out (Research in Arthritis in Canadian Children, Emphasizing Outcomes) cohort.We used clinicobiologic data recorded within 7 months of diagnosis to assign a diagnosis of JIA and identify subcategories of JIA among 1,228 patients according to the 2 JIA classification systems. We compared the proportions of patients classified and the alignment of classification categories with clinicobiologic subtypes and adult arthritis types.The PRINTO criteria classified 244 patients (19.9%) as having early-onset antinuclear antibody-positive JIA, 157 (12.8%) as having enthesitis/spondylitis-related JIA, 38 (3.1%) as having systemic JIA, and 10 (0.8%) as having rheumatoid factor-positive JIA. A total of 12% of patients were unclassifiable using the ILAR criteria, while 63.3% were unclassifiable using the PRINTO criteria (777 with other JIA and 2 with unclassified JIA). In sensitivity analyses,50% of patients remained unclassifiable using the PRINTO criteria. Compared to the PRINTO criteria, ILAR JIA categories aligned better with clinicobiologic subtypes in 131 patients (χCurrently identified PRINTO disorders can only be used to classify a minority of JIA patients, leaving a large proportion of JIA patients with other disorders requiring further characterization. Current PRINTO JIA classification criteria do not align better with clinicobiologic subtypes or adult forms of arthritis compared with the older ILAR classification system.

Objective The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS). Methods A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017–2018 formed a development cohort, and 220 children enrolled in 2019–2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): ‘Is it hard for your child to run and play BECAUSE OF ARTHRITIS?’ (‘Hard’ 0–10), and ‘Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?’ (‘Help’, 0–10). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort. Results Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0. Conclusion This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment.

OBJECTIVE. To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS. We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS. Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION. This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

OBJECTIVE. To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS. We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS. Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION. This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

Objective The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada. Methods Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively. Results The median time from symptom onset to first assessment was 138 (IQR 64–365) days pre-pandemic vs 146 (IQR 83–359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020. Conclusions We did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved.

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA). The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P.05). The prevalence of 25(OH)D deficiency (30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation.

Leukoplakia is one of the most frequently found lesions in the oral cavity, with a probability of 17 to 24% of becoming malignant cells in a period of 30 years.To identify differentially expressed gene profiles of leukoplakia and its progression to oral squamous cell carcinoma, essential for the discovery of new biomarkers to predict and prevent the presence of diseases in the oral cavity.Initially, gene profiles of GSE85514 and GSE160042 from the Gene Expression Omnibus database were used. Differentially expressed genes were identified using GEO2R. The CLUEGO plugin in Cytoscape was used for DEG functionality and enrichment analysis. Finally, a protein-protein interaction (PPI) network was constructed using Cytoscape from data collected online from the STRING server.According to the MCC algorithm, the 10 most found gene sequences were HNRNPU, SMC1A, PAFAH1B1, EHMT1, SPTBN4, OLFM1, NCAM1, SF3B3, FGF2, and UBE2I; with HNRNPU, SMC1A, and PAFAH1B1 being the most representative of the modules.We were able to describe the gene sequences that promote the progression from leukoplakia to oral squamous cell carcinoma. Within these genes, the HNRNPU, SMC1A, and PAFAH1B1 constitute the main promising therapeutic targets to counteract the progression of oral cancer, they could also be important biomarkers for the diagnosis and classification of the disease.

Objective Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. Methods Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3–9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. Results We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. Conclusion Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.

Objective To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA. Methods Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan–Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups. Results A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs. Conclusion Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis.

OBJECTIVE Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real-world effectiveness of simple JIA treatment strategies recommended in current guidelines. METHODS Children with JIA who were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. RESULTS A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when

Objective To assess long-term outcomes of children with JIA diagnosed in the biologic era. Methods Chart review of patients prospectively enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort at two Canadian centres. Inactive disease and remission were defined according to Wallace criteria. Results We included 247 of 254 (97%) eligible patients diagnosed 2005–10. At the last follow-up visit at a median age of 16.9 years, 47% were in remission off medications, 25% in remission on medications and 27% had active disease; 51% were on at least one anti-rheumatic medication (22% on biologics). Patients with systemic JIA had the highest frequency of remission off medications (70%) and patients with RF-positive polyarthritis had the lowest (18%) (P Conclusion Relative to historical cohorts, this study suggests a reduction in JIA permanent damage, a more favourable prognosis for systemic JIA and a lower progression to oligoarthritis extended category. However, in an era of biologic therapy, one in four patients with JIA still enter adulthood with active disease and one in two still on treatment.

OBJECTIVE Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors. METHODS Data were reported every 6 months for 2 years, then yearly to 5 years. Incidence was determined by Kaplan-Meier estimators with time of JIA diagnosis as the reference point. Univariate log-rank analysis identified risk factors and Cox regression determined independent predictors. RESULTS In total, 1,183 patients who enrolled within 6 months of JIA diagnosis met inclusion criteria, median age at diagnosis of 9.0 years (interquartile range [IQR] 3.8-12.9), median follow-up of 35.2 months (IQR 22.7-48.3). Of these patients, 87 developed uveitis after enrollment. The incidence of new-onset uveitis was 2.8% per year (95% confidence interval [95% CI] 2.0-3.5) in the first 5 years. The annual incidence decreased during follow-up but remained at 2.1% (95% CI 0-4.5) in the fifth year, although confidence intervals overlapped. Uveitis was associated with young age (

Objective To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories. Methods A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers. Probabilistic principal component analysis identified sets of composite variables, or principal components, from 191 original variables. To discern new clinical-biomarker clusters (clusters), Gaussian mixture models were fit to the data. Newly-defined clusters and JIA categories were compared. Agreement between the two was assessed using Kruskal–Wallis analyses and contingency plots. Results Three principal components recovered 35% (three clusters) and 40% (five clusters) of the variance in patient profiles in visits 1 and 2, respectively. None of the clusters aligned precisely with any of the seven JIA categories but rather spanned multiple categories. Results demonstrated that the newly defined clinical-biomarker lustres are more homogeneous than JIA categories. Conclusion Applying unsupervised data mining to clinical and inflammatory biomarker data discerns discrete clusters that intersect multiple JIA categories. Results suggest that certain groups of patients within different JIA categories are more aligned pathobiologically than their separate clinical categorizations suggest. Applying data mining analyses to complex datasets can generate insights into JIA pathogenesis and could contribute to biologically based refinements in JIA classification.

OBJECTIVE: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). METHODS: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. RESULTS: Due to limitations of the literature with very low quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmology screening of children with JIA is recommended because of the risk of uveitis and frequency of screening should be based on individual risk factors. Regular ophthalmology monitoring of children with uveitis is recommended and intervals should be based on ocular examination findings and treatment regimen. Ophthalmology monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors, adalimumab and infliximab, are recommended when systemic treatment is needed for the management of uveitis. Timely addition of non-biologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. CONCLUSION: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes.Youth18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (1.5mg/kg/day) starting doses of oral glucocorticoids.Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes.Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.

To describe the frequency and severity of parent-reported medication side effects (SEs) in children with juvenile idiopathic arthritis (JIA) relative to physician-reported actionable adverse events (AEs), and to assess their impact on health-related quality of life (HRQoL).Newly diagnosed JIA patients recruited between 2017 and 2019 to the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry were included. Parents reported presence and severity (0 = no problem, 10 = very severe) of medication SEs at every clinic visit. Physicians were asked to report any actionable AE. HRQoL was assessed using the Quality of My Life (QoML) questionnaire (0 = the worst, 10 = the best) and parent's global assessment (0 = very well, 10 = very poor). Analyses included proportion of visits with SEs or actionable AEs, cumulative incidence by Kaplan-Meier methods, and HRQoL impact measured with longitudinal mixed-effects models.SEs were reported at 371 of 884 (42%) visits (95% confidence interval [95% CI] 39, 45%) in 249 patients, with a median of 2 SEs per visit (interquartile range [IQR] 1-3), and median severity of 3 (IQR 1.5-5). Most SEs were gastrointestinal (32.5% of visits) or behavioral/psychiatric (22.4%). SE frequency was lowest with nonsteroidal antiinflammatory drugs alone (34.7%) and highest with prednisone and methotrexate combinations (66%). SE cumulative incidence was 67% (95% CI 59, 75) within 1 year of diagnosis, and 36% (95% CI 28, 44) for actionable AEs. Parent global and QoML scores were worse with SEs present; the impact persisted after adjusting for pain and number of active joints.Parents report that two-thirds of children with JIA experience SEs impacting their HRQoL within 1 year of diagnosis. SE mitigation strategies are needed in managing JIA.

Objective To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling. Methods Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes. Results From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively. Conclusion A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA.

Background Validated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canadian patients with JIA. Methods We used data from 513 subjects at the 3-year follow-up from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcomes were non-achievement of remission, severe disease course, and functional disability. The Nordic models were evaluated exactly as published and after fine-tuning the logistic regression coefficients using multiple data splits of the Canadian cohort. Missing data was handled with multiple imputation, and prediction ability was assessed with C-indices. C-index values > 0.7 were deemed to reflect helpful prediction. Results Overall, 81% of evaluable patients did not achieve remission off medications, 15% experienced a severe disease course, and 38% reported disability (CHAQ score > 0). The Nordic model for predicting non-achievement of remission had a C-index of 0.68 (95% CI 0.62–0.74), and 0.74 (0.67–0.80) after fine-tuning. For prediction of severe disease course, it had a C-index of 0.69 (0.61–0.78), and 0.79 (0.68–0.91) after fine-tuning. The fine-tuned Nordic model identified 85% of the cohort as low risk for a severe disease course ( 60% chance). The Nordic model to predict functional disability had a C-index of 0.57 (0.50–0.63), and 0.51 (0.39–0.63) after fine-tuning. Conclusions Fine-tuned Nordic models, combining active joint count, physician global assessment of disease activity, morning stiffness, and ankle involvement, predicted well non-achievement of remission and severe disease course in Canadian patients with JIA. The Nordic model for predicting disability could not predict functional disability in Canadian patients.

Objective Kawasaki disease (KD) is an acute childhood vasculitis that may result in coronary aneurysms. Treatment of KD with a single infusion of 2 gm/kg intravenous immunoglobulin (IVIG) is well established, but acetylsalicylic acid (ASA) dose remains controversial. Our primary objective was to determine the difference in the incidence of IVIG resistance between 2 ASA doses. Our secondary objective was to compare the duration of hospital stay and the incidence of coronary artery aneurysm. Methods We reviewed charts of patients with KD from 2 Canadian centers to assess the impact of ASA dose on IVIG resistance (operationally defined as administration of a second dose of IVIG). Both centers used standard IVIG dosing, but center 1 used low-dose ASA from diagnosis (3-5 mg/kg/day) while center 2 used initial high-dose ASA (80-100 mg/kg/day). Results There were no significant differences in baseline characteristics between the 2 centers. Retreatment with a second dose of IVIG was required in 28 of 122 patients (23%) treated with low-dose ASA, and in 11 of 127 patients (8.7%) treated with high-dose ASA in center 1 and center 2, respectively (P = 0.003). After adjusting for confounders, low-dose ASA was associated with higher odds of IVIG resistance (OR 3.2 [95% confidence interval 1.1, 9.1]). The mean duration of hospital stay was 4.1 and 4.7 days, respectively (P = 0.37). Coronary artery aneurysms were seen in 2 of 117 and 6 of 125 patients from centers 1 and 2, respectively (P = 0.28). Conclusion Low-dose ASA was associated with 3-times higher odds of IVIG retreatment compared to high-dose ASA, with no significant difference in duration of hospital stay or incidence of coronary artery aneurysms.

Background The evaluation of quality of care in juvenile idiopathic arthritis (JIA) is critical for advancing patient outcomes but is not currently part of routine care across all centers in Canada. The study objective is to review the current landscape of JIA quality measures and use expert panel consensus to define key performance indicators (KPIs) that are important and feasible to collect for routine monitoring in JIA care in Canada. Methods Thirty-seven candidate KPIs identified from a systematic review were reviewed for inclusion by a working group including 3 pediatric rheumatologists. A shortlist of 14 KPIs was then assessed using a 3-round modified Delphi panel based on the RAND/UCLA Appropriateness Method. Ten panelists across Canada participated based on their expertise in JIA, quality measurement, or lived experience as a parent of a child with JIA. During rounds 1 and 3, panelists rated each KPI on a 1–9 Likert scale on themes of importance, feasibility, and priority. In round 2, panelists participated in a moderated in-person discussion that resulted in minor modifications to some KPIs. KPIs with median scores of ≥ 7 on all 3 questions without disagreement were included in the framework. Results Ten KPIs met the criteria for inclusion after round 3. Five KPIs addressed patient assessments: pain, joint count, functional status, global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score (cJADAS). Three KPIs examined access to care: wait times for consultation, access to pediatric rheumatologists within 1 year of diagnosis, and frequency of clinical follow-up. Safety was addressed through KPIs on tuberculous screening and laboratory monitoring. KPIs examining functional status using the Childhood Health Assessment Questionnaire (CHAQ), quality of life, uveitis, and patient satisfaction were excluded due to concerns about feasibility of measurement. Conclusions The proposed KPIs build upon existing KPIs and address important processes of care that should be measured to improve the quality of JIA care. The feasibility of capturing these measures will be tested in various data sources including the Understanding Childhood Arthritis Network (UCAN) studies. Subsequent work should focus on development of meaningful outcome KPIs to drive JIA quality improvement in Canada and beyond.

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.

Objectives: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life. Methods and results: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain -of function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE). Conclusions: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course. Crown Copyright (C) 2016 Published by Elsevier Inc All rights reserved

Objective.We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.Methods.Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development.Results.Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile.Conclusion.Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

Background Validation of clinical prediction tools for juvenile idiopathic arthritis (JIA) in populations different than those in which they were first developed is essential to understand their applicability across healthcare settings. Objectives To determine if clinical prediction tools to predict 1) non-achievement of remission off medication and 2) functional disability, developed in the Nordic cohort1 can be directly applied to JIA patients in the Canadian Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort; and to assess performance of the prediction tools if model parameters are fine-tuned to the Canadian cohort. Methods Since the Nordic models were developed to predict outcomes 8 years after disease onset but the follow-up of the ReACCh-Out cohort was shorter, we chose to cross-validate the tools in a subpopulation of 513 subjects at the 3 years follow-up (3.75 years after onset). Attainment of remission off medications was determined by a panel of 3 pediatric rheumatologists as previously described2 and functional disability was defined as a Childhood Health Assessment Questionnaire Disability Index (CHAQ)>0. Missing data was handled with multiple imputation by chained equations and prediction ability was assessed with c-index and Receiver Operator Characteristic (ROC) curves. The Nordic models were first evaluated exactly as published on the entire Canadian cohort. Then we fine-tuned the model coefficients using repeated runs of cross-validation in the Canadian cohort. This way, fine-tuned models were tested in patients not included in the fine-tuning process while also minimizing the standard error of prediction. Results In total, 408 of 506 evaluable patients (81%) were not on remission and 137 of 361 evaluable patients (38%) had functional disability at the 3-year visit. The Nordic model for predicting non-achievement of remission had a c-index of 0.68 (95%CI 0.62-0.74) when directly applied, and a c-index of 0.74 (0.70-0.78) when it was fine-tuned for the Canadian population. The latter values are comparable to those reported in the Nordic cohort (median AUC 0.78, IQR 0.72-0.82). Table 1 shows fine-tuned coefficient values along-side the original values. The Nordic model for predicting functional disability had a c-index of 0.57 (0.50-0.63) when directly applied, and fine-tuning failed to improve its performance, a c-index of 0.53 (0.43-0.63). Figure 1 shows ROC curves for fine-tuned models in the multiple splits. Conclusion After fine-tuning of coefficients, the Nordic model for prediction of non-achievement of remission had similar prediction ability in Canadian patients with JIA. We could not confirm the validity of the Nordic model for prediction of functional disability in Canadian patients. References [1] Rypdal V, Arnstad ED, Aalto K, et al. Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the Nordic cohort study. Arthritis Research & Therapy2018;20:91 [2] Guzman J, Oen K, Tucker LB, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis.2015;74:1854-60 Disclosure of Interests None declared

Background Models predicting outcome in juvenile idiopathic arthritis (JIA) have recently been proposed by Guzman et al.1 and Rypdal et al.2 Guzman et al. constructed a model for predicting severe disease course derived from the ReACCh-Out study, and Rypdal et al. constructed models for prediction of non-remission, functional disability and joint damage. Objectives To validate methods for prediction of long-term outcome in JIA by testing the ability of Guzman’s model and Rypdal’s model to predict severe disease course (the ReACCh-Out outcome) in the Nordic cohort. Methods The Nordic cohort is a prospective longitudinal multicenter cohort from defined geographical areas of 4 Nordic countries. Children with a baseline and an 8-year study visit were included. Missing data were imputed using low rank matrix factorization3, and a K-medoids algorithm4 was used to identify clusters corresponding to severe disease course in the ReACCh-Out study. With this outcome, the prediction model of Guzman et al. was tested with no re-estimation of parameters. A Receiver operating characteristic (ROC) curve and the corresponding area under the curve (AUC) were computed. For the same outcome, prediction models were built using the method of Rypdal et al. on randomly sampled training sets, and tested on disjoint validation sets. Results In the Nordic cohort 98/440 (22%) patients were identified with a severe disease course. This ratio is similar to the 125/610 (20%) found in the ReACCh-Out study. Characteristics of groups of patients with severe and non-severe disease course are similar in the two cohorts. The model of Guzman et al. had an AUC of 0.85 for prediction of severe disease course and an AUC of 0.66 for predicting remission off medication. In repeated cross-validations, the model of Rypdal et al. had a median AUC of 0.90 (IQR 0.86-0.92) for prediction of severe disease course, and a median AUC of 0.78 (IQR 0.72–0.82) for remission off medication. Conclusion Tests in the Nordic cohort validate the ability of the model of Guzman et al. to predict severe disease course. Repeated cross-validations of the model of Rypdal et al. indicate that validation results are highly dependent of the chosen outcome, and that prediction of long-term remission status is more challenging than prediction of a severe disease course. References [1] Guzman, J. et al., Predicting Which Children with Juvenile Idiopathic Arthritis Will Have a Severe Disease Course: Results from the ReACCh-Out Cohort, J Rheumatol, 44, 230-240, 2017. [2] Rypdal, V. et al., Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the Nordic cohort study, Arthritis Res Ther, 20, 91, 2018. [3] Liu, G. et al., Robust subspace segmentation by low-rank representation, Proceedings of the 27th International Conference on International Conference on Machine Learning, 663-670, 2010. [4] Park, H.-S. et al., A simple and fast algorithm for K-medoids clustering, Expert Systems with Applications, 36, 3336-3341, 2009. Disclosure of Interests Veronika Rypdal: None declared, Jaime Guzman: None declared, Andrew Henrey: None declared, Thomas Loughin: None declared, Mia Glerup: None declared, Anders Fasth: None declared, Ellen Dalen Arnstad: None declared, Lillemor Berntson Consultant for: AbbVie, Speakers bureau: AbbVie, Susan Nielsen: None declared, Marek Zak: None declared, Marite Rygg: None declared, Kristiina Aalto: None declared, Troels Herlin: None declared, Martin Rypdal: None declared, Ellen Nordal: None declared

Background Treatments for juvenile idiopathic arthritis (JIA) are changing rapidly. Healthcare providers and families require up-to-date knowledge of current treatment practices and expected outcomes to inform their decisions. Objectives To assess changes in treatment practices and outcomes for children in a new Canadian inception cohort diagnosed with JIA in 2017-2018, compared to children in the Research in Arthritis in Canadian Children emphasizing Outcomes cohort (ReACCh-Out) diagnosed in 2005-2010 1. Methods A new investigator-driven Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry was started in February 2017 to prospectively collect information on children enrolled within 3 months of JIA diagnosis. Information about disease activity, treatments, outcomes and adverse events is collected at all clinic visits. Registry data were extracted in October 2018 and clinical characteristics at presentation, use of anti-rheumatic medications, attainment of inactive disease, cJADAS10 scores and adverse events were described. Selected findings were compared to those observed in the ReACCh-Out cohort. The proportion of patients (cumulative incidence) receiving various treatments and their outcomes were estimated with Kaplan Meier survival methods. Results A total of 166 patients enrolled a median of 6 weeks after diagnosis at 10 centres were included. Median age at diagnosis was 9 years (IQR 3, 13), 61% were female and 51% had oligoarthritis. At enrolment, subjects had a median of 2 active joints (IQR 1, 3), a Physician Global Assessment of 3 (1.5, 4) and a Parent Global Assessment of 1 (0, 3). The median cJADAS10 score was 6.5 (4, 10). Table 1 compares baseline characteristics and the cumulative incidence of medication use and inactive disease at one year after diagnosis with those observed in the ReACCh-Out cohort, diagnosed on average 10 years earlier. Figure 1 shows the Kaplan Meier curves for attainment of inactive disease. Conclusion In Canada, treatments for newly diagnosed patients with JIA have intensified in the last 10 years, and 35% will now start their first biologic within 1 year of diagnosis. Short-term outcomes have improved, 81% of current patients now attaining inactive disease within one year of diagnosis. Funding: The Arthritis Society, Canada. References [1] Guzman J, Oen K, Tucker LB, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis.2015;74:1854-60 Acknowledgement Funding: The Arthritis Society, Canada. Disclosure of Interests Jaime Guzman: None declared, Michelle Batthish Speakers bureau: Novartis, Abbvie, Roberta Berard: None declared, Roxana Bolaria: None declared, David Cabral: None declared, Gaelle Chedeville: None declared, Ciaran Duffy: None declared, Kerstin Gerhold: None declared, Tommy Gerschman: None declared, Adam Huber: None declared, Jean-Philippe Proulx-Gauthier: None declared, Alan Rosenberg: None declared, Dax Rumsey: None declared, Heinrike Schmeling Grant/research support from: F. Hoffmann-La Roche Ltd, Natalie Shiff: None declared, Gordon Soon: None declared, Lori Tucker: None declared

To summarize current research on the prediction of severe disease or remission in children with juvenile arthritis, and define further steps needed towards developing prediction tools with sufficient accuracy for clinical use.High disease activity, poor patient-reported outcomes, ankle or wrist involvement, and a longer time from onset to the start of treatment herald a severe disease course and a low chance of remission. Other studies confirmed that age less than 7 years and positive ANA are the strongest predictors of uveitis development. Preliminary evidence suggests ultrasound findings may predict flare in patients with clinically inactive disease, and several new biomarkers show promise. A few prediction tools that combine predictors to estimate the chance of remission or a severe disease course in the medium-term to long-term have shown good accuracy when internally validated in the population in which they were developed.Promising candidate tools for predicting disease severity and long-term remission in juvenile arthritis are now available. These tools need external validation in other populations, and ideally formal trials to assess whether their use in practice improves patient outcomes. We are definitively getting closer, but we are not there yet.

OBJECTIVE: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting with non-systemic polyarthritis, sacroiliitis, or enthesitis. METHODS: PICO (population/intervention/comparator/outcome) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. RESULTS: 39 recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was “very low” or “low” for 90% of recommendations. Recommendations are provided for the use of nonsteroidal anti-inflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. CONCLUSION: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Objective: To evaluate the usefulness of the serum concentration of nine matrix metalloproteinases (MMPs) as biomarkers of spontaneous abortion.Methods: A retrospective nested cohort case–control s...

Renewable energy systems have been used in many areas. However, little attention has been paid to investigating off-grid renewable systems for farming. In this project, wind power and energy storage are used to design a realistic renewable energy system to supply power to an average California farm. The system provides clean wind energy for typical household appliances and farming purposes such as irrigation. A scaled-down prototype of the system is implemented for validation of the theoretical design. The design calculation and validation results show that the renewable energy system is capable to supply sufficient power to the farm, independently from utility power grid. Some valuable experiences are obtained regarding selection and operation of the prototype components.

BackgroundModels to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA.MethodsThe Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction.ResultsThe Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83–0.87) for prediction of severe disease course and a C-index of 0.66 (0.63–0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80–0.89) and 0.69 (0.65–0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86–0.92).ConclusionsExternal validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.

The medical management of juvenile idiopathic arthritis (JIA) and its complications has undergone significant changes in the last decade, a result largely of the introduction of biologics and increased availability of expertise in the diagnosis and management of rheumatic diseases in children and adolescents. The result is that clinical outcome has improved and complete disease control can often be achieved1. In 2010, the British Society for Paediatric and Adolescent Rheumatology (BSPAR) proposed guidelines for the optimal management of children and adolescents with JIA2. This advocacy statement emphasizes the importance of empowering children and their caregivers, facilitating early detection of JIA, prompt referral to a team of health professionals who are expert in the diagnosis and management of childhood rheumatic diseases, prompt access to all appropriate pharmacologic and biologic therapies, and regular followup and monitoring. The Canadian Wait Time Alliance sets acceptable wait times as 4 weeks in children with JIA, other than systemic onset JIA, and within 7 days of disease onset for children with systemic onset JIA. Screening for asymptomatic uveitis should take place within 4 weeks of the diagnosis of JIA3. Ideally, children and adolescents with JIA should be managed by a team of health professionals with training and experience in pediatric rheumatology given … Address correspondence to Dr. R.E. Petty, Division of Rheumatology, Department of Pediatrics, University of British Columbia, British Columbia’s Children’s Hospital, 4480 Oak St., Room K4-114, Vancouver, British Columbia V6H 3V4, Canada; E-mail: rpetty{at}cw.bc.ca

Background:The introduction of biologics has transformed care for children with systemic juvenile idiopathic arthritis (SJIA). Differences in treatment approaches between countries and how they have changed over time are not well studied.Objectives:We contrast the initial features, treatment and 12-month outcome in SJIA across 10 JIA registers in Europe and North America.Methods:Data were extracted locally from 10 Registers including manifestations at diagnosis, medication use over first year and outcomes (Physician Global Assessment (PGA), active joint count (AJC)) at 12 months. Data was compared before/after 2012 to assess change over time. Weighted (w) means were used to adjust for varying number of patients/Register.Results:1,149 patients; 553 had medication data for 2012-2018; primarily female and Caucasian; median age at diagnosis 5.3-8 years. Median duration of symptoms prior to first visit varied (0-3.3 months). Glucocorticoid (GC) use was common in the first year (w_average 72% (range 33-96%)). Biologic use included IL-1, IL-6 and TNF inhibitors. The proportion of patients treated with biologics, primarily anakinra, increased after 2012 (Table 1). W_mean PGA and AJC at the 12±3 month visit were 1.55 and 1.57, respectively (Table 2). At one year, the proportion of patients prescribed GC varied (w_mean 40%, range 26-60%).Conclusion:Analysis of SJIA patients across 10 countries show that time to first rheumatology visit was highly variable. Although local factors influence treatment decisions, biologic use increased after 2011; anakinra most common. Nearly 75% of patients were prescribed steroids within the first year but seemed to decrease after 1 year. More study is needed on long-term outcomes in SJIA patients within this modern era.1: Medication Usage within First Year (pre/post 2012 where available)Glucocorticoids (IV+PO)%Methotrexate%Biologic%Anti-IL-1%Anakinra%Tocilizumab%USA2010-2011n=922563333330USA2012-2018n=91501771705717Canada2005-2010n=8876601710100UK2001-2011n=69787110330UK2012-2018n=31485829191919Portugal2008-2011n=7342364330Portugal2012-2018n=19744732161621Sweden2009-2015n=50964662302830Denmark1997-2011n=83864013662Denmark2012-2018n=325012.575636319Turkey2000-2011n=71937758423720Turkey2012-2018n=11498524032289Germany2000-2011n=27173621376Germany2012-2018n=249574727191020Norway1997-2011n=26816212448Norway2012-2018n=510060100202080Finland2006-2011n=12424217008Finland2012-2018n=1225880082: Clinical Outcomes at 12 Months -all yearsAJCMedian [IQR]PGAMedian [IQR]GC Use, %USA0 [0, 0]0 [0,0]47Canada0 [0, 2]0.1 [0, 2.7]41UK0 [0, 0]0.5 [0, 1.7]53Portugal0 [0, 0]0.3 [0, 1]53Sweden0 [0, 0.5]0 [0, 0.5]31Denmark0 [0, 0]-26Turkey4 [2, 7]4 [3, 7]60Germany0 [0, 1]0 [0,2]36Norway0 [0, 0]0.5 [0, 2]45Finland0 [0, 0]0 [0, 0]33Disclosure of Interests:Mary Beth Son: None declared, Yukiko Kimura Consultant of: Genetech, Kristiina Aalto: None declared, Lillemor Berntson: None declared, Johnathan Dallas: None declared, Ciaran Duffy: None declared, Mia Glerup: None declared, Jaime Guzman: None declared, Troels Herlin: None declared, Petteri Hovi: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Jens Klotsche: None declared, Bo Magnusson: None declared, Vanessa McItyre: None declared, Ellen Nordal: None declared, Seza Özen: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Betül Sözeri: None declared, Timothy Beukelman Consultant of: UCB, Novartis

Objective To estimate the impact of enthesitis on patient-reported outcomes in children with juvenile idiopathic arthritis (JIA), irrespective of JIA category. Methods Children enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort were studied. Entheseal tenderness by physician examination in 33 defined locations, Juvenile Arthritis Quality of Life Questionnaire (JAQQ), Quality of My Life (QoML) Questionnaire, Childhood Health Assessment Questionnaire (C-HAQ), and a pain visual analog scale were completed at enrollment, every 6 months for 2 years, and then yearly up to 5 years. Analyses consisted of descriptive statistics, linear mixed models for longitudinal data, and analysis of covariance. Results Among 1,371 patients followed for a median of 35.3 months (interquartile range 22.1, 49.2), 214 (16%) had enthesitis, of whom 137 (64%) were classified as having enthesitis-related arthritis. After adjusting for JIA category and covariates, children with enthesitis reported higher JAQQ (mean raw score 2.71 versus 2.16, adjusted difference 0.41 points; 95% confidence interval [95% CI] 0.22, 0.59), higher C-HAQ (0.47 versus 0.31, adjusted difference 0.14 points; 95% CI 0.07, 0.22), higher pain (3.01 versus 1.68, adjusted difference 0.94 points; 95% CI 0.64, 1.25), and lower QoML (7.02 versus 8.23, adjusted difference -0.80 points; 95% CI -1.09, -0.51) scores than children without enthesitis. These differences persisted up to 5 years. Conclusion Children with enthesitis, regardless of JIA category, report worse patient-reported outcomes than those without enthesitis. Thus, enthesitis should be assessed in all children with JIA.

BACKGROUND: Evidence-based resource allocation in the public health care sector requires reliable economic evaluations that are different from those needed in the commercial sector. AIMS: To describe a framework for conducting economic evaluations of occupational health and safety (OHS) programmes in health care developed with sector stakeholders. To define key resources and outcomes to be considered in economic evaluations of OHS programmes and to integrate these into a comprehensive framework. METHODS: Participatory action research supported by mixed qualitative and quantitative methods, including a multi-stakeholder working group, 25 key informant interviews, a 41-member Delphi panel and structured nominal group discussions. RESULTS: We found three resources had top priority: OHS staff time, training the workers and programme planning, promotion and evaluation. Similarly, five outcomes had top priority: number of injuries, safety climate, job satisfaction, quality of care and work days lost. The resulting framework was built around seven principles of good practice that stakeholders can use to assist them in conducting economic evaluations of OHS programmes. CONCLUSIONS: Use of a framework resulting from this participatory action research approach may increase the quality of economic evaluations of OHS programmes and facilitate programme comparisons for evidence-based resource allocation decisions. The principles may be applicable to other service sectors funded from general taxes and more broadly to economic evaluations of OHS programmes in general. Language: en