Publications by authors named "Shirley Tse"

61 Publications

Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: Results from the ReACCh-Out cohort.

Rheumatology (Oxford) 2021 Jan 28. Epub 2021 Jan 28.

Division of Pediatric Rheumatology, British Columbia Children's Hospital, and Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Structural equation modelling (SEM) 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 juvenile idiopathic arthritis (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: 1) diagnosis, 2) 3-9 months after diagnosis, 3) flare, 4) remission on medications, 5) remission off medications. Following SEM, 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 root causes of decreased HRQoL in children with JIA, with pain, functional impairments and participation restrictions as mediators for disease activity; and psychosocial effects and side effects as mediators for treatment intensity.
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http://dx.doi.org/10.1093/rheumatology/keab079DOI Listing
January 2021

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

J Rheumatol 2020 Oct 15. Epub 2020 Oct 15.

The BBOP Study was supported by The Canadian Institutes of Health Research (FRN #82517); The Arthritis Society (Canada), Canadian Arthritis Network (SRI-IJD-01); University of Saskatchewan; The Clinical Research Centre of the Centre Hospitalier Universitaire de Sherbrooke; University of British Columbia; McGill University; Memorial University; Manitoba Institute of Child Health; Children's Health Research Trust Fund; Jim Pattison Children's Hospital Foundation of Saskatchewan; The Pediatric Rheumatic Disease Research and Innovation Laboratory, University of Saskatchewan; The Haslam Research Fund, University of Saskatchewan; and The Kleiman Fund, University of Saskatchewan. E. Rezaei, MD, PhD, A.M. Rosenberg, MD, Departments of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan; M.M. Newkirk, PhD, Department of Medicine, McGill University Health Center, Montreal, Quebec; Z. Li, MSc, RC-CHUM, University of Montreal, Montreal, Quebec; J.R. Gordon, PhD, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan; K.G. Oen, MD, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba; S.M. Benseler, MD, PhD, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta; G. Boire, MD, Département de Médecine, Université de Sherbrooke, Sherbrooke, Quebec; D.A. Cabral, MD, K. Houghton, MD, K.A. Morishita, MD, R.E. Petty, MD, PhD, L.B. Tucker, MD, S.E. Turvey, MD, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia; S. Campillo, MD, G. Chédeville, MD, R. Scuccimarri, MD, Department of Pediatrics, McGill University Health Center, Montreal, Quebec; A.L. Chetaille, MD, Département de Médecine le Centre Hospitalier Universitaire de Quebec, Quebec City, Quebec; P. Dancey, MD, Department of Pediatrics, Janeway Children's Health and Rehabilitation Centre, St. John's, Newfoundland; C. Duffy, MD, R. Jurencak, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario; K. Watanabe Duffy, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario; A.M. Huber, MD, B. Lang, MD, S.E. Ramsey, MD, E. Stringer, MD, Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia; J. Roth, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario; R. Schneider, MD, L. Spiegel, MD, S.M. Tse, MD, R.S. Yeung, MD, PhD, Department of Paediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario, Canada. The authors declare no conflict of interest. Address correspondence to Dr. A.M. Rosenberg, Department of Pediatrics, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK S7N 0W8, Canada. Email: Accepted for publication October 2, 2020.

Objective: 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; = 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; = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = -0.235, = 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.
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http://dx.doi.org/10.3899/jrheum.200391DOI Listing
October 2020

Whole-Body MRI Quantification for Assessment of Bone Lesions in Chronic Nonbacterial Osteomyelitis Patients Treated With Pamidronate: A Prevalence, Reproducibility, and Responsiveness Study.

J Rheumatol 2020 Sep 15. Epub 2020 Sep 15.

J. Panwar, MD, FRCR, Department of Radiodiagnosis, Christian Medical College and Hospital, Vellore, India and Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, Ontario; M. Tolend, BSc, A.S. Doria, MD, PhD, MSc, MBA, J. Stimec, MD, FRCPC, Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, Ontario; L. Lim, MD, FRCPC, Division of Pediatric Rheumatology, Department of Pediatrics, University of Alberta, Edmonton, Alberta; S.M. Tse, MD, FRCPC, R.M. Laxer, MDCM, FRCPC, Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. The authors declare no conflicts of interest. Address correspondence to Dr. J. Panwar, Department of Radiodiagnosis, Christian Medical College and Hospital, Vellore 632004, India, and Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON M5G 1X8, Canada. Email: Accepted for publication September 5, 2020.

Objective: The purpose of this study was (1) to assess the interreader reliability in detecting and scoring the inflammatory bone lesions in pediatric patients with chronic nonbacterial osteomyelitis (CNO) by using whole-body magnetic resonance imaging (WB-MRI), and (2) to evaluate the responsiveness of the MRI-detected CNO lesions to pamidronate therapy.

Methods: Eighty-eight WB-MRI examinations were independently reviewed and scored by 2 radiologists blinded to clinical details in 32 retrospectively enrolled pediatric patients with CNO. Inflammatory bone lesions, soft tissue abnormality, and bony structural changes were scored before and after pamidronate therapy. Lesion responsiveness was calculated by using standardized response mean and interreader reliability was assessed by k statistics.

Results: There was good to excellent interreader agreement for the detection and quantification of bone lesions. After the first cycle of pamidronate in all 32 patients, 96 of the 279 lesions (34%; after excluding 108 lesions of hand and feet) resolved, whereas in a subset of 11 patients with 2 or more cycles, 76% of lesions resolved after the second cycle. Twenty-one (7.5%) lesions worsened and 46 (16.4%) new lesions developed after 1 cycle in all 32 patients. In these 11 patients, the number of worsened lesions reduced to 2 (2%) and new lesions to 14 (14.9%) after the second cycle as detected on MRI. Vertebral lesions had the highest response to treatment.

Conclusion: WB-MRI is a reliable tool for objective quantification and assessment of response to treatment of pediatric CNO bone lesions and could be used to monitor disease activity for clinical and research purposes.
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http://dx.doi.org/10.3899/jrheum.200329DOI Listing
September 2020

"It's Not Just About Getting Along": Exploring Learning Through the Discourse and Practice of Interprofessional Collaboration.

Acad Med 2020 11;95(11S Association of American Medical Colleges Learn Serve Lead: Proceedings of the 59th Annual Research in Medical Education Presentations):S73-S80

M.A. Martimianakis is associate professor, scientist, and associate director, collaboration and partnerships, Department of Paediatrics and The Wilson Centre, University of Toronto, Toronto, Ontario, Canada; ORCID: http://orcid.org/0000-0002-2531-3156. O. Fernando is research associate, Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; ORCID: http://orcid.org/0000-0002-4600-9399. R. Schneider is professor, Division of Rheumatology, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. S. Tse is associate professor, Division of Rheumatology, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada. M. Mylopoulos is associate professor, scientist, and associate director of training programs, Department of Pediatrics and The Wilson Centre, University of Toronto, Toronto, Ontario, Canada; ORCID: http://orcid.org/0000-0003-0012-5375.

Purpose: Interprofessional collaboration (IPC) is a necessary competency for all professionals. However, IPC can be fraught with politics leading to variable uptake and execution. The authors set out to understand how trainees come to appreciate the value of the "team" in their learning and to describe the type of learning related to IPC afforded to trainees in a highly collaborative complex care context.

Method: The authors conducted 72 hours of observations of pediatric rheumatology settings at a large pediatric hospital across 18 months. They interviewed 10 health professionals and analyzed an archive of texts to ascertain how the field of pediatric rheumatology conceptualizes the role of IPC. They used the concept of governmentality and critical discourse analysis to describe how values of collaboration enabled learning and theories of expertise to understand how learning was enacted and perceived.

Results: Collaboration was perceived to be a product of providing good rheumatological care, which in this case, aligned well with hospital model of IPC. This alignment afforded trainees learning opportunities beyond preparing them to get along with other health professionals. IPC, when role modeled during problem solving, created the conditions for learning "why" collaboration is important for clinical expertise.

Conclusions: By critically examining the relationship between discourse, practice, and learning, the authors have described how practices that underpin collaboration as a clinical competency are distinct from collaboration as cultural work contributing to civility within teams and across the organization.
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http://dx.doi.org/10.1097/ACM.0000000000003637DOI Listing
November 2020

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

J Med Internet Res 2020 07 29;22(7):e16234. Epub 2020 Jul 29.

Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.2196/16234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424488PMC
July 2020

Image guided sacroiliac joint corticosteroid injections in children: an 18-year single-center retrospective study.

Pediatr Rheumatol Online J 2020 Jun 17;18(1):52. Epub 2020 Jun 17.

Division of Image Guided Therapy, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Background: Sacroiliitis is commonly seen in enthesitis-related arthritis (ERA), a subtype of juvenile idiopathic arthritis (JIA). Sacroiliitis is characterized by the inflammation of the sacroiliac (SI) joints (+/- adjacent tissues). The treatment options include systemic therapy with or without corticosteroid SI joint injections. Image guided SI joint injections are frequently requested in pediatric patients with sacroiliitis. The purpose of this study was to evaluate the feasibility and efficacy of SI joint injections in children with sacroiliitis.

Methods: A retrospective study of patients referred to Interventional Radiology (IR) for SI joint corticosteroid injections (2000-2018). Clinical information was collected from Electronic Patient Charts and procedural details from PACS. Efficacy was determined clinically, by MRI, or both when available.

Results: 50 patients (13.8 years; M:F = 35:15) underwent image-guided SI joint corticosteroid injections. Most common indications were JIA (84%) and inflammatory bowel disease (14%). 80% had bilateral injections. 80% were performed under general anesthesia and 20% under sedation. The corticosteroid of choice was triamcinolone hexacetonide in 98% of patients. Needle guidance and confirmation was performed using CT and fluoroscopy (54%), Cone Beam CT (CBCT, 46%), with initial ultrasound assistance in 34%. All procedures were technically successful without any complications. 32/50 patients had long-term follow-up (2 years); 21/32 (66%) had clinical improvement within 3-months. Of 15 patients who had both pre- and post-procedure MRIs, 93% showed short-term improvement. At 2 years, 6% of patients were in remission, 44% continued the same treatment and 47% escalated treatment.

Conclusion: Image-guided SI joint injections are safe and technically feasible in children. Imaging modalities for guidance have evolved, with CBCT being the current first choice. Most patients showed short-term clinical and imaging improvement, requiring long-term maintenance or escalation of medical treatment.
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http://dx.doi.org/10.1186/s12969-020-00435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301971PMC
June 2020

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

Rheumatology (Oxford) 2020 05;59(5):1066-1075

Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada.

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.
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http://dx.doi.org/10.1093/rheumatology/kez382DOI Listing
May 2020

Toward Developing a Semiquantitative Whole Body-MRI Scoring for Juvenile Idiopathic Arthritis: Critical Appraisal of the State of the Art, Challenges, and Opportunities.

Acad Radiol 2021 02 3;28(2):271-286. Epub 2020 Mar 3.

Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada. Electronic address:

With powerful new therapies available for management of juvenile idiopathic arthritis (JIA), early diagnosis leading to appropriate treatment may prevent long-term structural joint damage. Although magnetic resonance imaging (MRI) is typically used to assess individual body parts, indications for whole body (WB) MRI are increasing. Its utility as a diagnostic and monitoring tool has already been widely investigated in adult rheumatology patients, but less so in pediatric rheumatologic patients. This paper is a comprehensive review of scoring systems and a proposal for the conceptual development of a WB-MRI scoring system for the evaluation of JIA. In this review we identify, summarize, and critically appraise the available literature on the use of WB-MRI in inflammatory arthritis, addressing relevant considerations on components of a classification system that can lead to the development of a future pediatric WB-MRI scoring system for use in children with JIA. We also discuss advantages and challenges of developing such a WB-MRI scoring system for assessment of JIA and outline next steps toward the conceptual development of this scoring system.
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http://dx.doi.org/10.1016/j.acra.2020.01.022DOI Listing
February 2021

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

Rheumatology (Oxford) 2020 09;59(9):2402-2411

Department of PediatricsUniversity of Saskatchewan, Saskatoon, SK, Canada.

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.
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http://dx.doi.org/10.1093/rheumatology/kez615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449798PMC
September 2020

Gain-of-function mutations in a member of the Src family kinases cause autoinflammatory bone disease in mice and humans.

Proc Natl Acad Sci U S A 2019 06 28;116(24):11872-11877. Epub 2019 May 28.

Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Autoinflammatory syndromes are characterized by dysregulation of the innate immune response with subsequent episodes of acute spontaneous inflammation. Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that presents with bone pain and localized swelling. mice, isolated from a mutagenesis screen, exhibit a spontaneous inflammatory paw phenotype that includes sterile osteomyelitis and systemic reduced bone mineral density. To elucidate the molecular basis of the disease, positional cloning of the causative gene for was attempted. Using a candidate gene approach, a missense mutation in the C-terminal region of , a member of Src family tyrosine kinases (SFKs), was identified. For functional confirmation, additional mutations at the N terminus of were introduced in mice by CRISPR/Cas9-mediated genome editing. N-terminal deleterious mutations of abolished the inflammatory phenotype in mice, but in-frame and missense mutations in the same region continue to exhibit the phenotype. The fact that null mutant mice are morphologically normal suggests that the inflammation in this model depends on Fgr products. Furthermore, the levels of C-terminal negative regulatory phosphorylation of Fgr are distinctly reduced compared with that of wild-type Fgr. In addition, whole-exome sequencing of 99 CRMO patients including 88 trios (proband and parents) identified 13 patients with heterozygous coding sequence variants in , including two missense mutant proteins that affect kinase activity. Our results strongly indicate that gain-of-function mutations in are involved in sterile osteomyelitis, and thus targeting SFKs using specific inhibitors may allow for efficient treatment of the disease.
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http://dx.doi.org/10.1073/pnas.1819825116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6575637PMC
June 2019

Real-World Effectiveness of Common Treatment Strategies for Juvenile Idiopathic Arthritis: Results From a Canadian Cohort.

Arthritis Care Res (Hoboken) 2020 07 5;72(7):897-906. Epub 2020 Jun 5.

British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

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 <5 joints were involved, with a 54.4% success rate (95% confidence interval [95% CI] 50.3-58.6). NSAIDs plus joint injections had a 64.7% success rate (95% CI 59.8-69.7). Adding methotrexate to NSAIDs and/or joint injections (attempted 566 times) had a 60.5% success rate (95% CI 55.7-65.3). In adjusted analyses, each additional active joint reduced chances of success for treatment with NSAIDs (odds ratio [OR] 0.90 [95% CI 0.85-0.94]) and for methotrexate combinations (OR 0.96 [95% CI 0.94-0.99]). Each additional year after disease onset reduced chances of success for treatment with methotrexate combinations (OR 0.83 [95% CI 0.72-0.95]).

Conclusion: These real-world effectiveness estimates show that conventional nonbiologic treatment strategies that are recommended in current guidelines are effective in achieving treatment targets in many children with JIA.
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http://dx.doi.org/10.1002/acr.23922DOI Listing
July 2020

Imaging findings of mixed connective tissue disease in children and adolescents: a case series.

Jpn J Radiol 2019 May 14;37(5):371-379. Epub 2019 Mar 14.

Department of Rheumatology, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Mixed connective tissue disease (MCTD) is a rare disease in children and adolescents which overlaps features of juvenile idiopathic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. We have provided an image-based approach for evaluation of MCTD in children and adolescents, outlying the most frequent imaging findings. This approach would aid imagers and clinicians to consider the diagnosis of this rare entity and be able to make an accurate list of differential diagnosis for complex rheumatologic diseases such as MCTD, thus facilitating the ultimate goal of early diagnosis and optimal management of affected children.
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http://dx.doi.org/10.1007/s11604-019-00824-4DOI Listing
May 2019

Diagnostic Accuracy of MRI-Based Sacroiliitis Scoring Systems: A Systematic Review.

AJR Am J Roentgenol 2019 Mar 12:1-14. Epub 2019 Mar 12.

1 Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Objective: Accurate and reproducible MRI assessment of the sacroiliac joint (SIJ) is challenging. Numerous scoring systems have been proposed to facilitate consistent SIJ assessment. The purpose of this article is to evaluate the diagnostic accuracy and reliability of existing MRI-based SIJ scoring systems for the evaluation of spondyloarthropathy.

Conclusion: Among existing methods, there is fair (grade B) evidence to recommend the Spondyloarthropathy Research Consortium of Canada scoring systems as tools for MRI evaluation of the SIJ. However, limited data on criterion validity limit assessment of scoring system accuracy.
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http://dx.doi.org/10.2214/AJR.17.19429DOI Listing
March 2019

Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging Score (OMERACT JAMRIS-SIJ).

J Rheumatol 2019 09 15;46(9):1192-1197. Epub 2019 Feb 15.

From the Institute of Medical Sciences, Faculty of Medicine, University of Toronto; Department of Diagnostic Imaging, The Hospital for Sick Children; Department of Translational Medicine, SickKids Research Institute, Peter Gilgan Center for Research and Learning; Dalla Lana School of Public Health, University of Toronto; Division of Rheumatology, The Hospital for Sick Children, University of Toronto; Department of Medical Imaging, University of Toronto; Department of Rheumatology, Center for Prognosis Studies in Rheumatologic Diseases, Toronto Western Hospital, Toronto, Ontario; Department of Rheumatology, University of Alberta; Department of Radiology and Diagnostic Imaging, University of Alberta; Division of Pediatric Rheumatology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds, UK; Department of Rheumatology, Leiden University Medical Center, Leiden; Reade | Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands; University of Pennsylvania Perelman School of Medicine, Division of Rheumatology, Children's Hospital of Philadelphia and Departments of Pediatric and Epidemiology, Philadelphia, Pennsylvania; Department of Radiology, Nemours Children's Hospital and Health System, Orlando, Florida, USA; Department of Radiology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland; Department of Radiology and Medical Imaging, Ghent University Hospital, Ghent, Belgium; Department of Radiology, Hospital Sant Joan de Deu, Barcelona, Spain; Department of Radiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany; Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India; State University of Campina-UNICAMP, Department of Internal Medicine, Cidade Universitaria, Sao Paulo, Brazil.

Objective: To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis.

Methods: An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists.

Results: Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis, and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion, and ankylosis were defined for assessing structural joint changes.

Conclusion: Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the OMERACT Juvenile Arthritis MRI SIJ scoring system (OMERACT JAMRIS-SIJ).
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http://dx.doi.org/10.3899/jrheum.181115DOI Listing
September 2019

Spondyloarthritis Research Consortium of Canada Scoring System for Sacroiliitis in Juvenile Spondyloarthritis/Enthesitis-related Arthritis: A Reliability, Validity, and Responsiveness Study.

J Rheumatol 2019 06 1;46(6):636-644. Epub 2019 Feb 1.

From the Joint Department of Medical Imaging, University Health Network, University of Toronto; Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto; Division of Pediatric Rheumatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario; Division of Pediatric Rheumatology, Department of Pediatrics, The University of Alberta, Edmonton, Alberta; Kanchi Kamakoti CHILDS Trust Hospital, Chennai; Department of Radiology, Christian Medical College, Vellore, India; Makassed Hospital, Jerusalem, Israel; Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.

Objective: Intra- and interreader reliability, construct validity, and responsiveness of the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) scoring system were investigated for scoring sacroiliitis in patients with juvenile spondyloarthritis (JSpA)/enthesitis-related arthritis (ERA) who have received biologic and/or nonbiologic treatment.

Methods: Ninety whole-body MRI examinations with dedicated oblique coronal planes of the sacroiliac joints in 46 patients were independently reviewed and scored by 2 pediatric musculoskeletal radiologists, blinded to clinical details, using the SPARCC system. Intra- and interreader reliability was assessed by intraclass correlation coefficients (ICC). Construct validity testing was done by (1) correlating the SPARCC MRI scores of sacroiliitis with clinical disease activity indicators (cross-sectional validity), and (2) correlating the change in the MRI score with the change in clinical indicators before and after treatment (longitudinal validity). Responsiveness of the MRI and clinical indicators was also evaluated, grouped by biologic and nonbiologic treatment.

Results: When applied in children with JSpA/ERA, the SPARCC showed almost perfect intra- and interreader reliability (ICC 0.79-1.00). There was poor cross-sectional and longitudinal correlation between clinical assessment indicators and MRI scoring. SPARCC scores showed higher responsiveness to treatment-related change than most clinical outcome measures. Three clinical outcome measures correlated longitudinally with SPARCC score in nonbiologic treatment: active joint count (r = 0.72, p < 0.001), FABER (Flexion, Abduction, External Rotation) test (r = 0.58, p = 0.012), and physician's global assessment (r = 0.61, p = 0.034).

Conclusion: The SPARCC MRI scoring system is a reliable tool with relatively higher responsiveness than clinical indicators and is suitable for objective quantification of sacroiliitis when applied to pediatric patients with JSpA/ERA.
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http://dx.doi.org/10.3899/jrheum.180222DOI Listing
June 2019

Recurrent oral ulcerations following heart transplant in a pediatric patient: A diagnostic dilemma.

Pediatr Transplant 2018 11 12;22(7):e13264. Epub 2018 Jul 12.

Division of Hematology and Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Oral ulceration is a non-specific clinical finding with many potential causes. The persistence of oral ulcers in the context of a patient post-SOT is concerning for PTLD. There is growing evidence that SOT recipients may also be at higher risk of autoimmune diseases. This case report describes a pediatric patient with persistent oral ulcers after heart transplant, who underwent an extensive workup for PTLD, including repeat investigations, with a subsequent diagnosis of Behçet's disease.
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http://dx.doi.org/10.1111/petr.13264DOI Listing
November 2018

Development of neoplasms in pediatric patients with rheumatic disease exposed to anti-tumor necrosis factor therapies: a single Centre retrospective study.

Pediatr Rheumatol Online J 2018 Mar 14;16(1):17. Epub 2018 Mar 14.

Division of Rheumatology, SickKids, University of Toronto, 555 University Ave, Room 8253 Burton Wing, Toronto, ON, M5G 1X8, Canada.

Background: Anti-TNF (Tumor necrosis factor) therapy is effective in treating pediatric patients with refractory rheumatic disease. There is however a concern that anti-TNF usage may increase the risk of malignancy. Reports on specific types of malignancy in this patient population have been emerging over the past decade, but there is a need for additional malignancy reports, as these events are rare. Therefore, a retrospective chart review was performed on the biologic database of pediatric rheumatology patients at The Hospital for Sick Children (SickKids) from 1997 to 2013 for neoplasms, patient demographic information and rheumatologic treatment course.

Findings: 6/357 (1.68%) rheumatology patients treated with anti-TNF therapy between 1997 and 2013 developed neoplasms. One patient had two malignancies. One patient had a benign neoplasm. Cases were exposed to etanercept, infliximab or both. Neoplasms developed late after anti-TNF exposure (median 5.0 years) and infliximab treatment was associated with a shorter time to malignancy. The neoplasms identified were as follows: 2 renal clear cell carcinoma, 1 pilomatricoma, 1 nasopharyngeal carcinoma, 1 Ewing's sarcoma, 1 hepatic T-cell lymphoma, 1 lymphoproliferative disease.

Conclusions: The malignancy rate at our centre is low, however more than half of the neoplasms identified were rare and unusual in the pediatric population. The 5-year malignancy-free probability for patients with juvenile idiopathic arthritis (JIA) treated with biologic therapy was 97% from our database. Long-term screening for rare neoplasms is important as part of the safety monitoring for any pediatric rheumatology patient receiving anti-TNF therapy.
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http://dx.doi.org/10.1186/s12969-018-0233-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853069PMC
March 2018

Trajectories of pain severity in juvenile idiopathic arthritis: results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.

Pain 2018 01;159(1):57-66

Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

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.
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http://dx.doi.org/10.1097/j.pain.0000000000001064DOI Listing
January 2018

Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

Pediatr Rheumatol Online J 2017 Aug 22;15(1):68. Epub 2017 Aug 22.

From British Columbia Children's Hospital and University of British Columbia, Vancouver, Canada.

Background: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

Methods: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.

Results: One thousand one hundred forty seven children were followed for median 35.5 months. Mean Z-scores, and the point prevalence of short stature (height < 2.5th percentile, 2.5% to 3.4%) and obesity (BMI > 95th percentile, 15.8% to 16.4%) remained unchanged in the whole cohort. Thirty-three children (2.9%) developed new-onset short stature, while 27 (2.4%) developed tall stature (>97.5th percentile). Children with systemic arthritis (n = 77) had an estimated 3-year cumulative incidence of 9.3% (95%CI: 4.3-19.7) for new-onset short stature and 34.4% (23-49.4) for obesity. Most children (81.7%) received no systemic corticosteroids, but 1 mg/Kg/day prednisone-equivalent maintained for 6 months corresponded to a drop of 0.64 height Z-scores (0.56-0.82) and an increase of 0.74 BMI Z-scores (0.56-0.92). An increase of 1 in the 10-cm physician global assessment of disease activity maintained for 6 months corresponded to a drop of 0.01 height Z-scores (0-0.02).

Conclusions: Most children in this modern JIA cohort grew and gained weight as children in the general population. About 1 in 10 children who had systemic arthritis, uncontrolled disease and/or prolonged corticosteroid use, had increased risk of growth impairment.
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http://dx.doi.org/10.1186/s12969-017-0196-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567720PMC
August 2017

Malignancy incidence in 5294 patients with juvenile arthritis.

RMD Open 2016 2;2(1):e000212. Epub 2016 May 2.

Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.

Objective: To determine cancer incidence in a large clinical juvenile-onset arthritis population.

Methods: We combined data from 6 existing North American juvenile-onset arthritis cohorts. Patients with juvenile-onset arthritis were linked to regional cancer registries to detect incident cancers after cohort entry, defined as first date seen in the paediatric rheumatology clinic. The expected number of malignancies was obtained by multiplying the person-years observed (defined from cohort entry to end of follow-up) by the geographically matched age, sex and calendar year-specific cancer rates. The standardised incidence ratios (SIR; ratio of cancers observed to expected) were generated, with 95% CIs.

Results: The 6 juvenile arthritis registries provided a total of 5294 patients. The mean age at cohort entry was 8.9 (SD 5.0) years and 68% of participants were female. The mean duration of follow-up was 6.8 years with a total of 36 063 person-years spanning 1978-2012. During follow-up, 9 invasive cancers occurred, compared with 10.9 expected (SIR 0.82, 95% CI 0.38 to 1.5). 3 of these were haematological (Hodgkin's, non-Hodgkin's lymphoma and leukaemia). 6 of the patients with cancer were exposed to disease-modifying drugs; 5 of these had also been exposed to biological agents.

Conclusions: We did not clearly demonstrate an increase in overall malignancy risk in patients with juvenile-onset arthritis followed for an average of almost 7 years. 3 of the 9 observed cancers were haematological. 5 of the cancers arose in children exposed to biological agents. Longer follow-up of this population is warranted, with further study of drug effects.
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http://dx.doi.org/10.1136/rmdopen-2015-000212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860862PMC
May 2016

'It might hurt, but you have to push through the pain': Perspectives on physical activity from children with juvenile idiopathic arthritis and their parents.

J Child Health Care 2016 Dec 25;20(4):428-436. Epub 2016 Jul 25.

1 University of British Columbia, Vancouver, Canada.

Our primary objective was to gather perspectives of children diagnosed with juvenile idiopathic arthritis (JIA) and their parents as they relate to physical activity (PA) participation. To do so, we conducted a study on 23 children diagnosed with JIA and their parents ( N = 29). We used convenience sampling to recruit participants and qualitative method- logies (one-on-one semi-structured interviews). We adopted a five-step framework analysis to categorize data into themes. Children and their parents described factors that act to facilitate or hinder PA participation. Pain was the most commonly highlighted PA barrier described by children and their parents. However, children who were newly diagnosed with JIA and their parents were more likely to highlight pain as a barrier than were child/parent dyads where children had been previously diagnosed.
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http://dx.doi.org/10.1177/1367493516632616DOI Listing
December 2016

A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis-Related Arthritis.

Arthritis Care Res (Hoboken) 2015 Nov;67(11):1503-12

AbbVie, North Chicago, Illinois.

Objective: Enthesitis-related arthritis (ERA) is a juvenile idiopathic arthritis (JIA) category, primarily affecting entheses and peripheral joints. This study evaluated efficacy, safety, and pharmacokinetics of adalimumab versus placebo in patients with ERA.

Methods: This is a phase III, multicenter, randomized double-blind study in patients ages ≥6 to <18 years with ERA treated with adalimumab (24 mg/m(2) , maximum dose 40 mg every other week) or placebo for 12 weeks, followed by up to 192 weeks of open-label adalimumab. The primary end point was percent change from baseline in number of active joints with arthritis (AJC) at week 12. Samples were collected to determine adalimumab serum concentrations. Adverse events (AEs) were assessed throughout the study.

Results: Forty-six patients were randomized (31 adalimumab/15 placebo). At baseline, mean age was 12.9 years, mean duration of ERA symptoms was 2.6 years, mean AJC was 7.8, and mean enthesitis count was 8.1. Mean percent change from baseline in AJC at week 12 was greater in the adalimumab group versus placebo (-62.6% versus -11.6%; P = 0.039). Most secondary variables favored adalimumab versus placebo at week 12. Treatment response further increased with continued adalimumab therapy through week 52. Mean steady-state adalimumab serum concentrations were 7.5-11.8 μg/ml, similar to patients age ≥2 years with polyarticular JIA. AE rates were similar between placebo and adalimumab: any AE (53.3% versus 67.7%), serious AEs (0% versus 3.2%), and infectious AEs (20.0% versus 29.0%).

Conclusion: Adalimumab reduced signs and symptoms of ERA at week 12, with improvement sustained through week 52. The safety profile was consistent with previous adalimumab studies.
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http://dx.doi.org/10.1002/acr.22657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057351PMC
November 2015

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

Ann Rheum Dis 2016 06 18;75(6):1092-8. Epub 2015 May 18.

British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare.

Methods: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression.

Results: 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare.

Conclusions: In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.
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http://dx.doi.org/10.1136/annrheumdis-2014-207164DOI Listing
June 2016

Whole-body MRI of juvenile spondyloarthritis: protocols and pictorial review of characteristic patterns.

Pediatr Radiol 2015 Apr 21;45(5):754-62. Epub 2015 Apr 21.

Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA,

Spondyloarthritides are a group of inflammatory rheumatological diseases that cause arthritis with a predilection for spinal or sacroiliac involvement in addition to a high association with HLA-B27. Juvenile spondyloarthritis is distinct from adult spondyloarthritis and manifests more frequently as peripheral arthritis and enthesitis. Consequently juvenile spondyloarthritis is often referred to as enthesitis-related arthritis (ERA) subtype under the juvenile idiopathic arthritis (JIA) classification criteria. The American College of Rheumatology Treatment Recommendations for JIA, including ERA, are based on the following clinical parameters: current treatment, disease activity and the presence of poor prognostic features. The MRI features of juvenile spondyloarthritis include marrow edema, peri-enthesal soft-tissue swelling and edema, synovitis and joint or bursal fluid. Marrow edema is nonspecific and can be seen with other pathologies as well as in healthy subjects, and this is an important pitfall to consider. With further longitudinal study and validation, however, whole-body MRI with dedicated images of the more commonly affected areas such as the spine, sacroiliac joints, hips, knees, ankles and feet can serve as a more objective tool compared to clinical exam for early detection and monitoring of disease activity and ultimately direct therapeutic management.
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http://dx.doi.org/10.1007/s00247-015-3319-7DOI Listing
April 2015

Radiographic manifestations in Pfeiffer syndrome.

Arthritis Rheumatol 2015 May;67(8):2282

The Hospital for Sick Children, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1002/art.39156DOI Listing
May 2015

2014 Update of the Canadian Rheumatology Association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part I: principles of the management of spondyloarthritis in Canada.

J Rheumatol 2015 Apr 15;42(4):654-64. Epub 2015 Feb 15.

From the University of Western Ontario, London; University of Toronto; The Hospital for Sick Children; Toronto Western Research Institute University Health Network; Division of Rheumatology, Department of Medicine, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; Canadian Spondylitis Association, Toronto; Southlake Regional Health Centre, Newmarket, Ontario; University of British Columbia, Vancouver; University of North British Columbia, Prince George, British Columbia; Laval University, Quebec City, Quebec; Department of Medicine, University of Calgary, Calgary, Alberta; Memorial University, St. John's, Newfoundland, Canada.S. Rohekar, BSc, MD, FRCPC, MSc (Clin. Epi.), Associate Professor of Medicine, University of Western Ontario; J. Chan, BSc, MD, FRCPC; C. Flanagan, MDCM, Clinical Assistant Professor of Medicine, University of British Columbia; S.M. Tse, MD, FRCPC, Associate Professor of Medicine, University of Toronto, The Hospital for Sick Children; N. Haroon, MD, PhD, DM, Assistant Professor of Medicine, University of Toronto, Toronto Western Research Institute University Health Network; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor of Medicine, University of Toronto, and Division of Rheumatology, Department of Medicine, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; L. Bessette, MD, MSc, FRCPC, Assistant Professor of Medicine; K. Adams, BSc, MD, FRCPC, Associate Professor of Medicine, Laval University; D. Mosher, MD, FRCPC, Professor of Medicine, Department of Medicine, University of Calgary; K.J. Keen, PhD, PStat, PStat(ASA), Associate Professor of Mathematics and Statistics, University of North British Columbia; M. Mallinson, BA, MA, President, Canadian Spondylitis Association; C. Thorne, MD, FRCPC, Assistant Professor of Medicine, University of Toronto, Southlake Regional Health Centre; P. Rahman, MD, FRCPC, Associate Dean, Clinical Research and Professor of Medicine, Memorial Unive

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA).

Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference. A survey was sent to the membership of the CRA to obtain an extended review that was used to finalize the recommendations.

Results: Guidelines for the management of SpA were created. Part I focuses on the principles of management of SpA in Canada and includes 6 general management principles, 5 ethical considerations, target groups for treatment recommendations, 2 wait time recommendations, and recommendations for disease monitoring. Also included are 6 modifications for application to juvenile SpA.

Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that the implementation of these recommendations will promote best practices in the treatment of SpA.
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http://dx.doi.org/10.3899/jrheum.141000DOI Listing
April 2015

2014 Update of the Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Treatment Recommendations for the Management of Spondyloarthritis. Part II: Specific Management Recommendations.

J Rheumatol 2015 Apr 15;42(4):665-81. Epub 2015 Feb 15.

From the University of Western Ontario, London; University of Toronto; The Hospital for Sick Children; Toronto Western Research Institute University Health Network; Division of Rheumatology, Department of Medicine, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; Canadian Spondylitis Association, Toronto; University of Toronto, Southlake Regional Health Centre, Newmarket, Ontario, Canada; University of British Columbia, Vancouver; University of North British Columbia, Prince George, British Columbia; Laval University, Quebec City, Quebec; Department of Medicine, University of Calgary, Calgary, Alberta; Memorial University, St. John's, Newfoundland, Canada.S. Rohekar, BSc, MD, FRCPC, MSc (Clin. Epi.), Associate Professor of Medicine, University of Western Ontario; J. Chan, BSc, MD, FRCPC; C. Flanagan, MDCM, Clinical Assistant Professor of Medicine, University of British Columbia; S.M. Tse, MD, FRCPC, Associate Professor of Medicine, University of Toronto, The Hospital for Sick Children; N. Haroon, MD, PhD, DM, Assistant Professor of Medicine, University of Toronto, Toronto Western Research Institute University Health Network; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor of Medicine, University of Toronto, and Division of Rheumatology, Department of Medicine, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; L. Bessette, MD, MSc, FRCPC, Assistant Professor of Medicine; K. Adams, BSc, MD, FRCPC, Associate Professor of Medicine, Laval University; D. Mosher, MD, FRCPC, Professor of Medicine, Department of Medicine, University of Calgary; K.J. Keen, PhD, PStat, PStat(ASA), Associate Professor of Mathematics and Statistics, University of North British Columbia; M. Mallinson, BA, MA, President, Canadian Spondylitis Association; C. Thorne, MD, FRCPC Assistant Professor of Medicine, University of Toronto, Southlake Regional Health Centre; P. Rahman, MD, FRCPC, Associate Dean, Clinical Research and Profess

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA).

Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference.

Results: Recommendations for the management of SpA were created. Part II: Specific Management Recommendations addresses management with nonpharmacologic methods, nonsteroidal anti-inflammatories and analgesics, disease-modifying antirheumatic drugs, antibiotics, tumor necrosis factor inhibitors, other biologic agents, and surgery. Also included are 10 modifications for application to juvenile SpA.

Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that implementation of these recommendations will promote best practices in the treatment of SpA.
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http://dx.doi.org/10.3899/jrheum.141001DOI Listing
April 2015

Trying to improve care: the Morbidity and Mortality Conference in a division of rheumatology.

J Rheumatol 2014 Dec 1;41(12):2452-8. Epub 2014 Nov 1.

From the Division of Rheumatology, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton; Division of Rheumatology, Department of Pediatrics, Department of Medicine, The Hospital for Sick Children; Dalla Lana School of Public Health; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.M. Batthish, MD, Division of Rheumatology, Department of Pediatrics, McMaster Children's Hospital, McMaster University; S.M.L. Tse, MD, Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto; B.M. Feldman, MD, Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, Dalla Lana School of Public Health, University of Toronto; G.R. Baker, PhD, Institute of Health Policy, Management and Evaluation, University of Toronto; R.M. Laxer, MD, Division of Rheumatology, Departments of Pediatrics and Medicine, The Hospital for Sick Children, University of Toronto.

Objective: To describe the frequency and types of reported adverse events and system improvement recommendations in the Morbidity and Mortality Conference (M&MC) within the Division of Rheumatology at The Hospital for Sick Children, Toronto, Ontario, Canada (SickKids).

Methods: A 5-year retrospective review of the M&MC within the Division of Rheumatology at SickKids was completed. Descriptive data including the number and types of events reported were collected. Events were categorized using an adaptation of the National Coordinating Council for Medication Error Reporting and Prevention Index. Recommendations were classified according to the Institute for Safe Medication Practices Canada.

Results: Between January 2007 and December 2011, 30 regularly scheduled M&MC were held. Eighty-three cases were reviewed. The most common types of reported events were related to "miscommunication" (34.9%), "treatment/test/procedure" (22.9%), "adverse drug reactions" (12.0%), and "medication errors" (8.4%). Category A events ("an event that has the capacity to cause error") were the most common with 39.8% of the cases, followed by Category C events ("an event occurred that reached the patient, but did not cause harm") with 28.9%. Eighty-nine recommendations were made. Over half of these were classified as "information" (58.4%), followed by 11 "rules and policies" recommendations (12.4%). Of the 36 action items generated from these recommendations, most are either complete or ongoing.

Conclusion: The M&MC within the Division of Rheumatology reviews a variety of events. Increased reporting of adverse events can lead to system improvements, and has the potential to improve and promote safer healthcare.
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http://dx.doi.org/10.3899/jrheum.140203DOI Listing
December 2014

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort.

Ann Rheum Dis 2015 Oct 19;74(10):1854-60. Epub 2014 May 19.

Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Canada.

Objective: To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments.

Methods: Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan-Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments.

Results: In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46-57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA.

Conclusions: Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.
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http://dx.doi.org/10.1136/annrheumdis-2014-205372DOI Listing
October 2015