Shirley M. L. Tse

An Internet-based Self-management Program with Telephone Support for Adolescents with Arthritis: A Pilot Randomized Controlled Trial

Objective. To determine the feasibility of a 12-week Internet-based self-management program of disease-specific information, self-management strategies, and social support with telephone support for youth with juvenile idiopathic arthritis (JIA) and their parents, aimed at reducing physical and emotional symptoms and improving health-related quality of life (HRQOL). Methods. A nonblind pilot randomized controlled trial (NCT01011179) was conducted to test the feasibility of the “Teens Taking Charge: Managing Arthritis Online” Internet intervention across 4 tertiary-level centers in Canada. Participants were 46 adolescents with JIA, ages 12 to 18 years, and 1 parent for each participant, who were randomized to the control arm (n = 24) or the Internet intervention (n = 22). Results. The 2 groups were comparable on demographic and disease-related variables and treatment expectation at baseline. Attrition rates were 18.1% and 20.8%, respectively, from experimental and control groups. Ninety-one percent of participants randomized to the experimental group completed all 12 online modules and weekly phone calls with a coach in an average of 14.7 weeks (SD 2.1). The control group completed 90% of weekly attention-control phone calls. The Internet treatment was rated as acceptable by all youth and their parents. In posttreatment the experimental group had significantly higher knowledge (p < 0.001, effect size 1.32) and lower average weekly pain intensity (p = 0.03, effect size 0.78). There were no significant group differences in HRQOL, self-efficacy, adherence, and stress posttreatment. Conclusion. Findings support the feasibility (acceptability, compliance, and user satisfaction) and initial efficacy of Internet delivery of a self-management program for improving disease-specific knowledge and reducing pain in youth with JIA.

Differential Role of Actin, Clathrin, and Dynamin in Fcγ Receptor-mediated Endocytosis and Phagocytosis

Clustering of macrophage Fcγ receptors by multimeric immunoglobulin complexes leads to their internalization. Formation of small aggregates leads to endocytosis, whereas large particulate complexes induce phagocytosis. In RAW-264.7 macrophages, Fcγ receptor endocytosis was found to be dependent on clathrin and dynamin and insensitive to cytochalasin. Clathrin also associates with nascent phagosomes, and earlier observations suggested that it plays an essential role in phagosome formation. However, we find that phagocytosis of IgG-coated large (≥3 μm) particles was unaffected by inhibition of dynamin or by reducing the expression of clathrin using antisense mRNA but was eliminated by cytochalasin, implying a distinct mechanism dependent on actin assembly. The uptake of smaller particles (≤1 μm) was only partially blocked by cytochalasin. Remarkably, the cytochalasin-resistant component was also insensitive to dominant-negative dynamin I and to clathrin antisense mRNA, implying the existence of a third internalization mechanism, independent of actin, dynamin, and clathrin. The uptake of small particles occurred by a process distinct from fluid phase pinocytosis, because it was not inhibited by dominant-negative Rab5. The insensitivity of phagocytosis to dominant-negative dynamin I enabled us to test the role of dynamin in phagosomal maturation. Although internalization of receptors from the plasma membrane was virtually eliminated by the K44A and S45N mutants of dynamin I, clearance of transferrin receptors and of CD18 from maturing phagosomes was unaffected by these mutants. This implies that removal of receptors from the phagosomal membrane occurs by a mechanism that is different from the one mediating internalization of the same receptors at the plasma membrane. These results imply that, contrary to prevailing notions, normal dynamin and clathrin function is not required for phagocytosis and reveal the existence of a component of phagocytosis that is independent of actin and Rab5.

Feasibility and effectiveness of an aerobic exercise program in children with fibromyalgia: results of a randomized controlled pilot trial.

OBJECTIVE To determine the feasibility of conducting a randomized controlled trial of a 12-week exercise intervention in children with fibromyalgia (FM) and to explore the effectiveness of aerobic exercise on physical fitness, function, pain, FM symptoms, and quality of life (QOL). METHODS FM patients ages 8-18 years were randomized to a 12-week exercise intervention of either aerobics or qigong. Both groups participated in 3 weekly training sessions. Program adherence and safety were monitored at each session. Data were collected at 3 testing sessions, 2 prior to and 1 after the intervention, and included FM symptoms, function, pain, QOL, and fitness measures. RESULTS Thirty patients participated in the trial. Twenty-four patients completed the program; 4 patients dropped out prior to training and 2 dropped out of the aerobics program. Better adherence was reported in the aerobics group than in the qigong group (67% versus 61%). Significant improvements in physical function, functional capacity, QOL, and fatigue were observed in the aerobics group. Anaerobic function, tender point count, pain, and symptom severity improved similarly in both groups. CONCLUSION It is feasible to conduct an exercise intervention trial in children with FM. Children with FM tolerate moderate-intensity exercise without exacerbation of their disease. Significant improvements in physical function, FM symptoms, QOL, and pain were demonstrated in both exercise groups; the aerobics group performed better in several measures compared with the qigong group. Future studies may need larger sample sizes to confirm clinical improvement and to detect differences in fitness in childhood FM.

Severe Ulcerative Colitis After Rituximab Therapy

B-cell–depletion therapy with rituximab is efficacious against steroid-dependent nephrotic syndrome (NS) in children and adults. Safety data are limited. Results of small studies have suggested that rituximab is usually well tolerated but that adverse events (such as severe mucocutaneous reactions, fatal infusion reactions, progressive multifocal leukoencephalopathy, and bowel perforation) can occur. We report here the first case (to our knowledge) of a pediatric patient with refractory minimal-change NS who developed severe immune-mediated ulcerative gastrointestinal disease 42 days after rituximab therapy. The disease was characterized by deep ulcers throughout the intestines and predominantly affected the colon. The child presented with severe abdominal pain, bloody diarrhea, weight loss, and fever. Her inflammatory markers were significantly elevated. Extensive evaluation revealed no evidence of infections and no characteristics of defined inflammatory bowel disease or Behçet disease. Colonoscopy revealed severe intestinal inflammation with deep ulcers. Histology of the colonic biopsy specimens revealed extensive infiltrates predominantly composed of CD8+ T lymphocytes and evidence of high forkhead box P3 (FOXP3) expression. During this significant gastrointestinal disease, the NS remained quiescent. Corticosteroid therapy successfully controlled the severe immune-mediated intestinal inflammation after rituximab therapy. NS relapsed subsequently when CD19+ and CD20+ B-cell populations recovered.

Sleep and fatigue and the relationship to pain, disease activity and quality of life in juvenile idiopathic arthritis and juvenile dermatomyositis

OBJECTIVES To determine and compare the prevalence of disturbed sleep in JIA and JDM and the relationship of sleep disturbance to pain, function, disease activity and medications. METHODS One hundred fifty-five patients (115 JIA, 40 JDM) were randomly sampled and were mailed questionnaires. Sleep disturbance was assessed by the sleep self-report (SSR) and the childrens sleep habits questionnaire (CSHQ). Fatigue, pain and function were assessed by the paediatric quality of life inventory (PedsQL) and disease activity by visual analogue scales (VASs). Joint counts were self-reported. RESULTS Eighty-one per cent responded, of whom 44% reported disturbed sleep (CSHQ > 41); there were no differences between disease groups. Poor reported sleep (SSR) was highly correlated with PedsQL fatigue (r = 0.56, P < 0.0001). Fatigue was highly negatively correlated with quality of life (r = -0.77, P < 0.0001). The worst pain intensity in the last week was correlated to sleep disturbance (r = 0.32, P = 0.0005). Fatigue was associated with prednisone and DMARD use. CONCLUSIONS Sleep disturbance and fatigue are prevalent among children with different rheumatic diseases. Sleep disturbance and fatigue are strongly associated with increased pain and decreased quality of life. Strategies aimed at improving sleep and reducing fatigue should be studied as possible ways of improving quality of life for children with rheumatic illness.

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

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.

Usability Testing of an Online Self-management Program for Adolescents With Juvenile Idiopathic Arthritis

Background A new bilingual (English and French) Internet-based self-management program, Teens Taking Charge: Managing Arthritis Online, for adolescents with arthritis and their parents was developed following a needs assessment. Objectives This study explored the usability (user performance and satisfaction) of the self-management program for youth with juvenile idiopathic arthritis (JIA) and their parents to refine the health portal prototype. Methods A qualitative study design with semi-structured, audio taped interviews and observation by a trained observer was undertaken with two iterative cycles to determine the usability (ease of use, efficiency, errors, and user satisfaction) of the user interface and content areas of the intervention. A purposive sample of English-speaking (n = 11; mean age = 15.4, standard deviation [SD] 1.7) and French-speaking (n = 8; mean age = 16.0, SD 1.2) adolescents with JIA and one of their respective parents/caregivers were recruited from 2 Canadian tertiary care centers. Descriptive statistics and simple content analyses were used to organize data into categories that reflected the emerging usability themes. Results All of the participants had access to a computer/Internet at home; however, adolescents were more comfortable using the computer/Internet than their parents. Adolescents and parents provided similar as well as differing suggestions on how the website user interface could be improved in terms of its usability (navigation; presentation and control usage errors; format and layout; as well as areas for further content development). There were no major differences in usability issues between English- and French-speaking participants. Minor changes to the website user interface were made and tested in a second cycle of participants. No further usability problems were identified in the second iterative cycle of testing. Teens and parents responded positively to the appearance and theme of the website (ie, promoting self-management) and felt that it was easy to navigate, use, and understand. Participants felt that the content was appropriate and geared to meet the unique needs of adolescents with JIA and their parents as well as English- and French-speaking families. Many participants responded that the interactive features (discussion board, stories of hope, and video clips of youth with JIA) made them feel supported and “not alone” in their illness. Conclusions We describe the usability testing of a self-management health portal designed for English- and French-speaking youth with arthritis and their parents, which uncovered several usability issues. Usability testing is a crucial step in the development of self-management health portals to ensure that the various end users (youth and parents) have the ability to access, understand, and use health-related information and services that are delivered via the Internet and that they are delivered in an efficient, effective, satisfying, and culturally competent manner.

Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in a Canadian multicenter inception cohort

To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies.

Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) encompasses a complex group of disorders with arthritis as a common feature. This article provides the pediatrician with a review of the epidemiology, classification, clinical manifestations, and complications of JIA. It also provides an update on the current understanding of the cause of JIA and recent developments in management and a recent review of the long-term outcome in JIA.

Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: Results of a Canadian multicenter, prospective inception cohort study

OBJECTIVE To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). METHODS Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. RESULTS Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. CONCLUSION Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.