Lengthening sleep reduces pain in childhood arthritis: a crossover randomised controlled trial.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study's aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen. METHODS: Patients with JIA (12-18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain. RESULTS: Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2-1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39-0.95). CONCLUSION: It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain. TRIAL REGISTRATION NUMBER: NCT04133662.

Choosing Wisely: The Canadian Rheumatology Association Pediatric Committee's List of Items Physicians and Patients Should Question.

OBJECTIVE: To develop a list of tests or treatments frequently used in pediatric rheumatology practice that may be unnecessary based on existing evidence. METHODS: A Choosing Wisely (CW) working group composed of 16 pediatric rheumatologists, 1 allied health professional, 1 parent, and 1 patient used the Delphi method to generate, rank, and refine a list of tests and treatments that may be unnecessary or harmful. The items with the highest content agreement and perceived impact were presented in a survey to all Canadian Rheumatology Association (CRA) physicians who practice pediatric rheumatology. Respondents were asked to rate their agreement and impact, and to rank the items. Five items with the highest composite scores and 2 additional items selected by the CW working group were put forward for literature review. RESULTS: The initial Delphi procedure generated 80 items. After 3 rounds, the list was narrowed to 13 items. The survey was completed by 41/81 (51%) CRA pediatric members across Canada. Respondent characteristics were similar to those of the CRA pediatric membership for self-reported gender, geographical location, and career stage. The highest composite score items were antinuclear antibody testing, drug toxicity monitoring, HLA-B27 testing, rheumatoid factor/anticyclic citrullinated peptide testing, and Lyme serology testing. Two additional items (numerous or repeated intraarticular corticosteroid injections, and autoinflammatory diseases genetic testing) were also selected. Literature review was performed for these 7 highest priority items. CONCLUSION: We have identified areas for quality improvement in the evaluation and treatment of rheumatic diseases in Canadian children.

Assessment of Orofacial Symptoms in Juvenile Idiopathic Arthritis: Validation of a Consensus-Based Short Patient Questionnaire.

OBJECTIVE: To develop, validate, and test the performance of patient-reported outcomes (PROs) in a short patient questionnaire (< 5 minutes in length) in order to assess the multidimensional aspects of orofacial symptoms related to juvenile idiopathic arthritis (JIA) among patients aged ≥ 10 years. METHODS: The study was conducted by an interdisciplinary task force from the Temporomandibular Joint Juvenile Arthritis Working Group. The project consisted of a multiphased approach including the following: (1) conceptual phase with online international survey of 167 healthcare workers, (2) item generation and drafting of preliminary questionnaire(s) (ie, face validity), (3) cognitive script interview and probing (ie, content validity; 16 patients with JIA), (4) assessment of construct validity (ie, convergence and divergence; 53 patients with JIA), (5) test of reliability, and (6) test of clinical performance and psychometric characteristics (95 patients with JIA). RESULTS: In total, 7 PROs were included in the final patient questionnaire: (1) pain frequency, (2) pain intensity, (3) pain location, (4) jaw function, (5) specific questions related to symptoms and dysfunction, (6) changes in face and jaw pain since last visit, and (7) changes in jaw function since last visit. In total, 80% of the patients were able to complete the questionnaire in less than 5 minutes. CONCLUSION: We have developed and validated a short patient questionnaire to assess the multidimensional aspects of JIA-related orofacial symptoms. The PROs included in our questionnaire show acceptable validity and reliability. The questionnaire is applicable to routine monitoring of subjects with JIA, as well as future research studies.

Management of Orofacial Manifestations of Juvenile Idiopathic Arthritis: Interdisciplinary Consensus-Based Recommendations.

Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA.

Discrete Choice Experiment on a Magnetic Resonance Imaging Scoring System for Temporomandibular Joints in Juvenile Idiopathic Arthritis.

OBJECTIVE: To determine the relative importance weights of items and grades of a newly developed additive outcome measure called the juvenile idiopathic arthritis (JIA) magnetic resonance imaging (MRI) scoring system for the temporomandibular joint (TMJ) (JAMRIS-TMJ). METHODS: An adaptive partial-profile, discrete choice experiment (DCE) survey using the 1000Minds platform was independently completed by members of an expert group consisting of radiologists and non-radiologist clinicians to determine the group-averaged relative weights for the JAMRIS-TMJ. Subsequently, an image-based vignette ranking exercise was done, during which experts individually rank ordered 14 patient vignettes for disease severity while blinded to the weights and unrestricted to JAMRIS-TMJ assessment criteria. Validity of the weighted JAMRIS-TMJ was tested by comparing the consensus-graded, DCE-weighted JAMRIS-TMJ score of the vignettes with their unrestricted image-based ranks provided by the experts. RESULTS: Nineteen experts completed the DCE survey, and 21 completed the vignette ranking exercise. Synovial thickening and joint enhancement showed higher weights per raw score compared to bone marrow items and effusion in the inflammatory domain, while erosions and condylar flattening showed nonlinear and higher weights compared to disk abnormalities in the damage domain. The weighted JAMRIS-TMJ score of the vignettes correlated highly with the ranks from the unrestricted comparison method, with median Spearman's ρ of 0.92 (interquartile range [IQR] 0.87-0.95) for the inflammation and 0.93 (IQR 0.90-0.94) for the damage domain. CONCLUSION: A DCE survey was used to quantify the importance weights of the items and grades of the JAMRIS-TMJ. The weighted score showed high convergent validity with an unrestricted, holistic vignette ranking method.

Clinical and psychosocial stress factors are associated with decline in physical activity over time in children with juvenile idiopathic arthritis.

BACKGROUND: Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). METHODS: In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. RESULTS: At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score - 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = - 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4-3.1) to 24 months (median and IQR: 2.1, 1.4-2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p <  0.001). CONCLUSION: Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.

Development and validation of the RACER (Readiness for Adult Care in Rheumatology) transition instrument in youth with juvenile idiopathic arthritis.

BACKGROUND: Current evidence suggests that many adolescents with juvenile idiopathic arthritis (JIA) do not successfully transfer to adult care, which can result in adverse health outcomes. Although a growing number of clinical programs have been designed to support healthcare transition, there is a lack of psychometrically sound instruments to evaluate their impact on development of transition-related knowledge and skills in youth with JIA. The purpose of this study was to develop and validate RACER (Readiness for Adult Care in Rheumatology), a self-administered instrument designed to measure stages of readiness for key transition-related skills in adolescents with JIA. METHODS: A phased approach was used to develop and evaluate the validity and reliability of RACER. Phase 1 A was a consensus conference with 19 key stakeholders to inform instrument domains and items. Phase 1B determined initial content validity using a sample of 30 adolescents with JIA and 15 clinical and research experts. Finally, Phase 2 was a prospective cohort study with repeated measures to evaluate the internal consistency, test-retest reliability, construct validity and responsiveness of the instrument within a sample of adolescents with JIA. RESULTS: In Phase 1 A, initial item generation yielded a total of 242 items across six domains from the consensus conference, which was subsequently reduced to a 32-item instrument. Phase 1B established the content validity of the instrument in adolescents with JIA. In the Phase 2 study, with a sample of 96 adolescents, the RACER instrument exhibited good internal consistency in five of its six subscales (Cronbach's α > 0.7), and strong test-retest reliability between the first two administrations (ICC = 0.83). It also showed robust convergent validity by highly correlating with measures of self-management (SMSAG, rho = 0.73) and transition (TRANSITION-Q, rho = 0.76). The RACER was not correlated with unrelated measures (discriminant validity; PedsQL, rho = 0.14). The RACER scores increased significantly over time as expected, supporting measure responsiveness. CONCLUSIONS: The RACER is a reliable and valid instrument which is sensitive to change for assessing transition readiness in adolescents with JIA.

Differences in Healthcare Transition Views, Practices, and Barriers Among North American Pediatric Rheumatology Clinicians From 2010 to 2018.

OBJECTIVE: Since 2010, the rheumatology community has developed guidelines and tools to improve healthcare transition. In this study, we aimed to compare current transition practices and beliefs among Childhood Arthritis and Rheumatology Research Alliance (CARRA) rheumatology providers with transition practices from a provider survey published in 2010. METHODS: In 2018, CARRA members completed a 25-item online survey about healthcare transition. Got Transition's Current Assessment of Health Care Transition Activities was used to measure clinical transition processes on a scale of 1 (basic) to 4 (comprehensive). Bivariate analyses were used to compare 2010 and 2018 survey findings. RESULTS: Over half of CARRA members completed the survey (202/396), including pediatric rheumatologists, adult- and pediatric-trained rheumatologists, pediatric rheumatology fellows, and advanced practice providers. The most common target age to begin transition planning was 15-17 years (49%). Most providers transferred patients prior to age 21 years (75%). Few providers used the American College of Rheumatology transition tools (31%) or have a dedicated transition clinic (23%). Only 17% had a transition policy in place, and 63% did not consistently address healthcare transition with patients. When compared to the 2010 survey, improvement was noted in 3 of 12 transition barriers: availability of adult primary care providers, availability of adult rheumatologists, and pediatric staff transition knowledge and skills (P < 0.001 for each). Nevertheless, the mean current assessment score was < 2 for each measurement. CONCLUSION: This study demonstrates improvement in certain transition barriers and practices since 2010, although implementation of structured transition processes remains inconsistent.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis.

OBJECTIVES: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity. METHODS: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits. RESULTS: At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = -0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor-negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later. CONCLUSION: Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

The iCanCope pain self-management application for adolescents with juvenile idiopathic arthritis: a pilot randomized controlled trial.

OBJECTIVES: To evaluate the feasibility and preliminary effectiveness of iCanCope with Pain (iCanCope), a smartphone-based pain self-management program, in adolescents with JIA. iCanCope featured symptom tracking, goal-setting, pain coping skills and social support. METHODS: A two-arm pilot randomized controlled trial was used to evaluate the iCanCope app compared with a version with symptom tracking only. Primary (feasibility) outcomes were: participant accrual/attrition rates, success of app deployment, acceptability and adherence. Secondary (preliminary effectiveness) outcomes were: pain intensity, pain-related activity limitations and health-related quality of life. Outcomes were assessed at baseline and 8 weeks. Adherence was defined as the proportion of completed symptom reports: 'low' (≤24%); 'low-moderate' (25-49%); 'high-moderate' (50-75%); or 'high' (76-100%). Linear mixed models were applied for preliminary effectiveness analyses as per intention-to-treat. RESULTS: Adolescents (N = 60) were recruited from three paediatric rheumatology centres. Rates of accrual and attrition were 82 and 13%, respectively. Both apps were deployed with high success (over 85%) and were rated as highly acceptable. Adherence was similar for both groups, with most participants demonstrating moderate-to-high adherence. Both groups exhibited a clinically meaningful reduction in pain intensity (≥1 point) that did not statistically differ between groups. There were no significant changes in activity limitations or health-related quality of life. CONCLUSION: The iCanCope pilot randomized controlled trial was feasible to implement in a paediatric rheumatology setting. Both apps were deployed successfully, with high acceptability, and were associated with moderate-to-high adherence. Preliminary reductions in pain intensity warrant a future trial to evaluate effectiveness of iCanCope in improving health outcomes in adolescents with JIA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02764346.

Comparing the Measurement Properties and Preferability of Patient-reported Outcome Measures in Pediatric Rheumatology: PROMIS vs CHAQ.

OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ), though widely used for assessments in pediatric rheumatology, has drawbacks, including low correlation to disease activity and ceiling effects. We sought to determine if any tools from the Patient Reported Outcomes Measurement Information System (PROMIS) improve on these shortcomings and/or are preferred by patients. METHODS: Patients 5-17 years of age with juvenile idiopathic arthritis (JIA) or juvenile dermatomyositis (JDM) were recruited from the rheumatology clinics at a Canadian children's hospital. Participants completed the CHAQ, 3 PROMIS measures (pain interference, mobility, and physical activity), and underwent a standard clinical assessment. RESULTS: Fifty-two patients participated, 25 with JIA and 27 with JDM. None of the PROMIS measures suffered from ceiling effects, whereas the CHAQ Disability Index (DI) and pain visual analog scales both did, with 50% and 20% of patients achieving the best possible scores, respectively. The PROMIS mobility was moderately correlated to the CHAQ-DI (rs -0.60, 95% CI -0.75 to -0.40), and the PROMIS pain interference was strongly correlated to the CHAQ pain score (rs 0.65, 95% CI 0.43-0.80). No measures correlated with disease activity. Patients preferred the PROMIS to the CHAQ. CONCLUSION: The PROMIS pain interference, mobility, and physical activity measures improve in some areas where the CHAQ is weak: they do not suffer from ceiling effects, and patients prefer the PROMIS tools. More work is needed to determine the correlation and responsiveness of the PROMIS tools to changes in disease activity over time before they should be widely adopted for clinical use.

Teens Taking Charge: A Randomized Controlled Trial of a Web-Based Self-Management Program With Telephone Support for Adolescents With Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a serious and potentially debilitating pediatric illness. Improved disease self-management may help to improve health outcomes. OBJECTIVE: This study aimed to evaluate the effectiveness of the Teens Taking Charge Web-based self-management intervention in reducing symptoms and improving health-related quality of life (HRQL) in adolescents with JIA compared with a Web-based education control condition. METHODS: Adolescents with JIA aged 12 to 18 years were recruited from 11 Canadian pediatric rheumatology centers. Caregivers were invited to participate along with their child. In addition to standard medical care, participants were randomized to receive either (1) the Teens Taking Charge self-management intervention or (2) a Web-based education control condition for a period of 12 weeks. Adolescents in the intervention group completed website modules addressing cognitive behavioral coping skills, stress management, and other self-management topics, while also receiving monthly telephone calls from a trained health coach. Adolescents in the education control group were instructed to view a series of preselected public JIA educational websites and received monthly calls from a coach who asked about their own best efforts at managing JIA. Caregivers in the intervention group completed website modules related to promoting independence and disease self-management in their child. Caregivers in the education control group were instructed to view a series of preselected public JIA educational websites. Outcome assessment occurred at baseline, 12 weeks (posttreatment), and at 6 and 12 months postrandomization. The primary outcomes were pain intensity, pain interference, and HRQL. Secondary outcomes were emotional symptoms, adherence, coping, knowledge, and self-efficacy. RESULTS: In total, 333 adolescents and 306 caregivers were enrolled. Significant overall reductions in pain intensity (P=.02) and pain interference (P=.007) were observed for intervention group participants compared with those in the education control group, after adjusting for baseline levels. There was a significant overall improvement in HRQL related to problems with pain (P=.02) and problems with daily activities (P=.01). There was also a significant difference in the intervention group over time (P=.008) for HRQL related to treatment problems, with the intervention group participants demonstrating improved HRQL by 12 months compared with education control group participants. Both groups showed nonsignificant improvements compared with baseline in other primary outcomes. There were no significant differences between the groups in any secondary outcomes or caregiver-reported outcomes. CONCLUSIONS: The results of this randomized trial suggest that the Teens Taking Charge Web-based intervention is effective at reducing both pain intensity and pain interference, as well as improving HRQL in adolescents with JIA, compared with education control. These effects are sustained for up to 12 months following program completion. The Teens Taking Charge program is now publicly available at no cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT01572896; https://clinicaltrials.gov/ct2/show/NCT01572896.

Associations of clinical and inflammatory biomarker clusters with juvenile idiopathic arthritis categories.

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.

A Canadian evaluation framework for quality improvement in childhood arthritis: key performance indicators of the process of care.

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.

Clinical and associated inflammatory biomarker features predictive of short-term outcomes in non-systemic juvenile idiopathic arthritis.

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.

Standardizing the Clinical Orofacial Examination in Juvenile Idiopathic Arthritis: An Interdisciplinary, Consensus-based, Short Screening Protocol.

OBJECTIVE: To develop a consensus-based, standardized, short (< 3 min) clinical examination protocol to assess the multidimensional, orofacial manifestations of juvenile idiopathic arthritis (JIA). METHODS: The study was conducted by a multidisciplinary task force from the Temporomandibular Joint Juvenile Arthritis Working Group (TMJaw). The study used an acknowledged sequential approach involving (1) a global multidisciplinary online questionnaire study, (2) a systematic literature review and consensus meetings to identify items for inclusion, (3) pilot testing of included items, (4) test of reliability in 22 subjects with JIA by 4 examiners, (5) test of construct validity in a case-control study involving 167 subjects, and (6) establishment of final recommendations. RESULTS: Six items were recommended for the final examination protocol: (1) clinician-assessed pain location, (2) temporomandibular (TMJ) joint pain on palpation (open and closed mouth), (3) mandibular deviation at maximal mouth opening (≥ 3 mm), (4) maximal unassisted mouth opening capacity, (5) frontal facial symmetry, and (6) facial profile. All recommended items showed acceptable reliability and construct validity. The average mean examination time was 2 min and 42 s (SD ± 38.5 s). CONCLUSION: A consensus-based, short clinical examination protocol was developed. The protocol takes less than 3 min to complete and provides information about orofacial symptoms, TMJ dysfunction, and dentofacial deformity. The standardized examination protocol is applicable to routine clinical care, as well as future research studies.

Standardizing Terminology and Assessment for Orofacial Conditions in Juvenile Idiopathic Arthritis: International, Multidisciplinary Consensus-based Recommendations.

OBJECTIVE: To propose multidisciplinary, consensus-based, standardization of operational terminology and method of assessment for temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA). METHODS: Using a sequential expert group-defined terminology and methods-of-assessment approach by (1) establishment of task force, (2) item generation, (3) working group consensus, (4) external expert content validity testing, and (5) multidisciplinary group of experts final Delphi survey consensus. RESULTS: Seven standardized operational terms were defined: TMJ arthritis, TMJ involvement, TMJ arthritis management, dentofacial deformity, TMJ deformity, TMJ symptoms, and TMJ dysfunction. CONCLUSION: Definition of 7 operational standardized terms provides an optimal platform for communication across healthcare providers involved in JIA-TMJ arthritis management.

Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome: differential diagnosis and review of the literature.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autosomal-dominant autoinflammatory disease of incomplete penetrance and variable expression. PAPA syndrome is the result of a mutation in the proline serine threonine phosphatase-interacting protein 1 (PSTPIP1/CD2BP1) gene located on chromosome 15, which results in an abnormal overproduction of the pro-inflammatory cytokine interleukin-1ß (IL-1). This syndrome clinically manifests as early onset of recurrent episodes of acute aseptic inflammation of the joints, generally occurring in the first two decades of life, followed by manifestation of characteristic skin lesions in the third decade, after an obvious decline in the joint symptoms. Although uncommon, the potential clinical implications of PAPA syndrome warrant an appropriate diagnosis in a timely fashion.

Prospective Determination of the Incidence and Risk Factors of New-Onset Uveitis in Juvenile Idiopathic Arthritis: The Research in Arthritis in Canadian Children Emphasizing Outcomes Cohort.

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 (<7 years) at JIA diagnosis (hazard ratio [HR] 8.29, P < 0.001), positive antinuclear antibody (ANA) test (HR 3.20, P < 0.001), oligoarthritis (HR 2.45, P = 0.002), polyarthritis rheumatoid factor negative (HR 1.65, P = 0.002), and female sex (HR 1.80, P = 0.02). In multivariable analysis, only young age at JIA diagnosis and ANA positivity were independent predictors of uveitis. CONCLUSION: Vigilant uveitis screening should continue for at least 5 years after JIA diagnosis, and priority for screening should be placed on young age (<7 years) at JIA diagnosis and a positive ANA test.

Orofacial symptoms and oral health-related quality of life in juvenile idiopathic arthritis: a two-year prospective observational study.

BACKGROUND: Little is known about the chronicity of orofacial symptoms and how this influences the oral health-related quality of life in juvenile idiopathic arthritis (JIA). Therefore, our objectives were to study the long-term changes in self-reported orofacial symptoms, and to define the impact of orofacial symptoms on oral health-related quality of life in JIA. METHODS: At baseline (T0), 157 consecutive JIA patients ≤20 years completed a patient pain questionnaire that incorporates domains related to the orofacial area. At the 2 year follow-up (T1), 113 patients completed the same questionnaire (response rate 72%) in addition to the Child Perception's Questionnaire; a validated 31-item questionnaire addressing oral health-related quality of life. RESULTS: At T0, 53% (60/113) of patients reported the presence of orofacial pain, and 36% (41/113) of patients reported compromised orofacial function. At T1, 77% (46/60) of patients with pain at T0 reported persistent pain, and 66% (27/41) of patients with functional disability at T0 reported persistent disability. Patients with orofacial symptoms reported a significantly greater prevalence of negative impact of orofacial conditions on general quality of life and within the domains of emotional and social well-being compared to asymptomatic patients. CONCLUSION: Self-reported orofacial pain and functional disability were common findings in a cohort of JIA patients followed over 2 years. These symptoms seem to persist over time in most patients, and have a significant negative impact on oral health-related quality of life.