Lori B. Tucker

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.

Neutrophil gelatinase–associated lipocalin is a predictor of the course of global and renal childhood‐onset systemic lupus erythematosus disease activity

OBJECTIVE To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). METHODS One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physicians assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. RESULTS Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. CONCLUSION Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.

Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects’ age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean ± standard error (SE) increase of UNGAL (in ng/ml) of 11.5 ± 6.4 or 36.6 ± 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean ± SE): 7.3 ± 6.2 or 21%; renal disease activity: 20.2 ± 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.

Human parvovirus B19-associatedarthritis in children

Human parvovirus B19 (HPV B19) infection has been associated with chronic jointcomplaints in adult patients. We now report 22 children with joint complaints associated with recent HPV B19 infection. These children had either erythema infectiosum or serologic evidence of recent infection. Twenty children had arthritis; two had arthralgias. Eleven children had associated constitutional symptoms. Laboratory findings were generally normal. The duration of joint symptoms was less than 4 months in 14 children; however, six children have had persistent arthritis for 2 to 13 months, which would fulfill criteria for the diagnosis of juvenile rheumatoid arthritis. Although HPV B19 is usually associated with acute arthritis of brief duration, in some children infection with HPV B19 may be associated with the development of chronic arthritis.

Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis.

Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.

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.

Neuropsychiatric Lupus: The Prevalence and Autoantibody Associations Depend on the Definition: Results from the 1000 Faces of Lupus Cohort

OBJECTIVES The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter Canadian cohort. METHODS Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. RESULTS Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n = 586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE (P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were significant. NPSLE was not increased in those with +anti-DNA, La, or ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL) antibody. CONCLUSIONS The prevalence and factors associated with NPSLE varied depending on the definition used, was highest in Aboriginals, and may be higher if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease manifestations, which contributed to a 10% higher prevalence of NPSLE compared to a more strict definition. NPSLE may be less in this database than other publications as its overall prevalence may be decreasing, or because of selection bias inherent to those who enter an observational cohort. NPSLE was associated with aPL and often anti-Ro and varied by ethnicity.

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.

Fitness, fatigue, disease activity, and quality of life in pediatric lupus.

OBJECTIVE To measure aerobic fitness (maximum oxygen consumption [VO(2peak)]), fatigue, quality of life (QOL), and disease activity in young persons with systemic lupus erythematosus (SLE), and to determine an equation for predicting VO(2peak) from the distance walked in 6 minutes (6MW). METHODS Fifteen young patients ages 12-19 years with SLE participated. VO(2) was measured by a graded treadmill exercise test. Submaximal exercise intensity was determined from the ventilatory anaerobic threshold. Submaximal aerobic capacity was measured using the 6MW. Patient questionnaires included measures of fatigue, QOL, and physical activity. Physician questionnaires included the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS Compared with age-matched norms, our patients had moderate impairment in aerobic fitness, with a mean +/- SD VO(2peak) of 31.1 +/- 7.9 ml/minute/kg and a mean 6MW distance Z score of -2.4 +/- 2.3. The regression equation to predict VO(2peak) (ml/minute/kg) from 6MW was as follows: 57.1 + [0.038 x distance (meters)] + (-0.35 x maximal heart rate) (R = 0.67, P = 0.027). Ten subjects (67%) reported significant fatigue. There was no significant correlation of fatigue with fitness measures. Neither fatigue nor fitness was significantly correlated with disease activity, disease damage, or QOL measures. CONCLUSION Young SLE patients have lower aerobic fitness than reference norms. The 6MW may be used as a marker of fitness, but it is preferable to determine VO(2) with a graded exercise test. Fatigue is a significant symptom in young SLE patients. The application of fatigue measures in young persons is exploratory. The relationship between fatigue and aerobic fitness is not clear.