Perceived adherence to prescribed treatment in juvenile idiopathic arthritis over a one-year period

OBJECTIVE: To document perceived adherence to treatment (taking medications and performing exercises) in patients with juvenile idiopathic arthritis (JIA) over a 1-year period and to identify related factors. METHODS: We surveyed parents of patients with JIA at the Montreal Children's Hospital and British Columbia's Children's Hospital in Vancouver. Parents were asked to respond to a series of questionnaires every 3 months over a 12-month period. Perceived adherence was evaluated on a 100-mm visual analog scale (VAS) in the Parent Adherence Report Questionnaire (PARQ). Parental coping, distress, child function, disease severity and duration, perceived helpfulness of treatment, problems encountered, and sociodemographic data were also assessed. RESULTS: The mean age of our sample of 175 children was 10.2 years; mean age at diagnosis was 6.1 years and mean disease duration was 4.1 years. Perceived adherence to medications was consistently high, with average adherence at baseline, 3, 6, 9, and 12 months being 86.1, 91.7, 90.4, 92.0, and 88.8, respectively, on the PARQ VAS. Perceived adherence to exercise was lower but remained steady, with corresponding means of 54.5, 64.1, 61.2, 63.0, and 54.3, respectively. Using generalized estimating equation analysis, factors associated with higher perceived adherence to medications included perceived helpfulness of medications and lower disease severity; those associated with higher perceived adherence to exercise were younger age of the child, child involvement in responsibility for treatment, and higher perceived helpfulness of the treatment. CONCLUSION: Belief in helpfulness of treatment is associated with higher parental perceived adherence to treatment.     

Effects of adherence to treatment on short‐term outcomes in children with juvenile idiopathic arthritis

Objective

To determine the impact of adherence to treatment (medication and prescribed exercise) on outcomes in children with juvenile idiopathic arthritis (JIA).

Methods

In this longitudinal study, we studied parents of patients with JIA at the Montreal Children's Hospital and British Columbia Children's Hospital in Vancouver. Adherence was evaluated on a visual analog scale in the Parent Adherence Report Questionnaire. Outcomes of interest were active joint count, pain, child functional score on the Child Health Assessment Questionnaire, quality of life score on the Juvenile Arthritis Quality of Life Questionnaire, and parental global impression of overall well‐being. The association between adherence to treatment and subsequent outcomes was evaluated using generalized estimating equations and logistic regression.

Results

Mean age and disease duration of our sample of 175 children were 10.2 and 4.1 years, respectively. Moderate adherence to medication was associated with lower active joint count (odds ratio [OR] 0.47, 95% confidence interval [95% CI] 0.22–0.99). Moderate adherence to exercise was associated with better functional score (OR 0.13, 95% CI 0.03–0.54), and lower pain during the last week (OR 0.14, 95% CI 0.04–0.50). Both high and moderate adherence to exercise were associated with parental perception of global improvement.

Conclusion

Improved outcomes in patients who adhered to treatment underscores the need for clinicians to address adherence issues with their patients. Sustaining adherence, particularly to the more time‐consuming treatment of exercise, is a challenge.     

Comparison between children with juvenile idiopathic arthritis and their parents concerning perceived treatment adherence

OBJECTIVE: Adherence to treatment in juvenile idiopathic arthritis (JIA) may be associated with better outcomes. Clinicians must be aware of possible divergence between parents and children regarding adherence, in order to gain a better understanding of adherence and factors associated with it. The objective was to determine the level of agreement between children with JIA and their parents concerning perception of the child's adherence to the treatment regimen (for both medications and exercises). METHODS: Fifty patients and their parents, who attended the JIA clinic at the Montreal Children's Hospital, completed the Child Adherence Report Questionnaire and the Parent Adherence Report Questionnaire. Paired t-tests were used to compare parents' and children's scores for adherence questions and agreements were analyzed by intraclass correlation coefficients (ICCs). RESULTS: Parents reported that their children showed more negative reactions to taking medication and doing exercises, more helpfulness from the medication, and more difficulty to carry out the exercise program than their children reported. ICCs (95% confidence interval) for medications and exercises were, respectively, 0.32 (0.04, 0.56) and 0.77 (0.61, 0.87) for overall adherence, 0.33 (0.05, 0.57) and 0.39 (0.09, 0.62) for perceived difficulty to following treatment, and 0.37 (0.09, 0.60) and 0.45 (0.17, 0.67) for how often children had negative reactions following treatment. Levels of agreement for perceived helpfulness of treatments were quite low. CONCLUSION: Agreement between parents and children concerning adherence was at best moderate, and generally better for the exercise program than for prescribed medications.     

Disease activity and fatigue in juvenile idiopathic arthritis

Objective

To examine the association between parent/proxy‐ and child‐reported fatigue and disease activity in children with polyarticular, extended oligoarticular, and persistent oligoarticular juvenile idiopathic arthritis (JIA).

Methods

We enrolled a cross‐sectional cohort of 309 children recruited from the Seattle Children's Hospital rheumatology clinic from 2009–2011. Parents and children completed the PedsQL Multidimensional Fatigue Scales. The parent/proxy, child, and/or physician provided additional disease activity data at each clinic visit, including active joint count, pain, and the Childhood Health Assessment Questionnaire (C‐HAQ). Disease activity was dichotomized as active or inactive using the American College of Rheumatology provisional criteria for clinically inactive disease. The Juvenile Arthritis Disease Activity Score (JADAS) was also calculated. Linear regression was used to examine the associations between fatigue and disease activity.

Results

Associations among fatigue, clinically inactive disease, and the JADAS were not statistically significant after controlling for pain. In the multivariable models of fatigue, the C‐HAQ and parent/child‐reported disease activity were significantly associated with fatigue; however, only the C‐HAQ remained significantly associated after adjustment for pain. The C‐HAQ and parent/child‐reported disease activity explained 17% and 30% of the variance in fatigue for the parent/proxy‐ and child‐reported multivariable models, respectively.

Conclusion

In this cohort, functional ability, as measured by the C‐HAQ, was significantly associated with fatigue. Child‐ and parent/proxy‐reported pain were important confounders of the relationship between fatigue and disease activity. Routinely incorporating pain and fatigue into interventional and observational trials of JIA will enable better delineation of the relationships between these variables.     

Factors influencing illness representations and perceived adherence in haemophilic patients: a pilot study

Illness representations of chronic patients are important to explain adherence and preventive behaviours. However, it is unclear if the patient's objective health status may influence illness representations and perceived adherence. This study explored if health status and socio‐demographic characteristics influence illness representations and perceived adherence in haemophilic patients. Fifty patients (25 on‐demand and 25 on prophylaxis) ageing from 13–73, completed the Illness Perceptions Questionnaire‐Revised and the Morisky Medication Adherence Scale. Patients' cognitive illness representations were influenced by type of treatment, haemophilia severity, presence of inhibitor and co‐morbidity. Perceived chronicity was influenced by patient's age (P = 0.021). Perceived adherence was not influenced by the health status, but was affected by the relationship status (P = 0.048). Perceived adherence was predicted by perceived chronicity (β = 0.412; P = 0.003) and by emotions (β = ?0.308; P = 0.023). Patient's health status seems to affect cognitive illness representations but not perceived adherence. Perceived chronicity and negative emotions, which affected perceived adherence, were not influenced by the health status. Physician–patient communication addressing perceived chronicity and emotions rather than patients' health status may influence patient's adherence. Psycho‐educational groups could be offered to promote patient's well‐being and adjustment to haemophilia, and improve adherence.     

Parents' preferences for drug treatments in juvenile idiopathic arthritis: A discrete choice experiment

Objective

To examine parents' preferences for drug treatments and health outcomes in juvenile idiopathic arthritis (JIA) and identify demographic and health‐related factors that significantly impact choice.

Methods

A discrete choice experiment was conducted with 105 parents of children with JIA who were cared for by a rheumatologist at The Hospital for Sick Children in Canada. Attributes evaluated included “drug treatment,” “child reported pain from arthritis,” “participation in daily activities,” “side effects,” “days missed from school,” and “cost to you.” Multinomial logit regression was used to estimate the relative importance of each attribute level and interaction term.

Results

Parents made tradeoffs between characteristics of the drug treatments and health outcomes. “Participation in daily activities” was the most important attribute, followed by “child reported pain from arthritis” and “cost to you.” Parents of children with longer disease durations had stronger preferences for improved participation in daily activities, whereas parents of older JIA patients had stronger preferences for improved control of pain.

Conclusion

Parents of children with JIA demonstrated strong preferences for treatments that reduce pain and improve daily functioning regardless of the associated side effects, level of responsibility required for drug administration, and days missed from school. Parents of children with longer disease durations and those who had been prescribed aggressive therapies had a greater preference for treatment effectiveness. These findings support the need for considering parental preferences in decisions regarding the choice of treatment for JIA.     

Feasibility and construct validity of the parent willingness‐to‐pay technique for children with juvenile idiopathic arthritis

Objective

To assess the feasibility and construct validity of the willingness‐to‐pay (WTP) technique for measuring health care preferences in families of children with juvenile idiopathic arthritis (JIA).

Methods

Parents were asked to estimate the monthly US dollar amount they would be willing to pay to obtain for their child the following hypothetical drugs: ARTHRO, which guarantees complete clinical response; and NO‐STOM‐ACHE, a drug that eliminates gastrointestinal (GI) symptoms. A yes/no question was used with random assignment of the starting bids. Parents who agreed to pay the starting bid were then asked whether they would be willing to pay 200% and then 400% of this initial bid. Socioeconomic data and information on medications, disease activity, patient physical function, wellbeing, and health‐related quality of life (HRQOL) were obtained.

Results

Sixty‐two families of children with JIA were interviewed. GI symptoms were present in 54%, and 53% of the children had joints with active arthritis or limited range of motion. Four parents (7%) were unwilling to pay anything for any of the studied medications. The mean amount (median; mean percentage of available family income) families were willing to pay was $395 ($300; 15%) for ARTHRO and $109 ($80; 4%) for NO‐STOM‐ACHE. Correlation and regression analysis supported that, adjusted for the available family income, the WTP for ARTHRO was associated with disease activity, pain, and the HRQOL of the patients. After correction for the starting bids and the available family income, the WTP for NO‐STOM‐ACHE was associated with the patient's HRQOL, pain, and the amount of GI discomfort.

Conclusion

The WTP technique is feasible and has construct validity for measuring health care preferences for children with JIA. Relatively large WTP estimates support a possible important negative impact of the disease on families of children with JIA.

     

Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration

Objective

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

Methods

We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates.

Results

The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIA patients (Mantel‐Cox χ² = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel‐Cox χ² = 9.06, P < 0.002). No other clinical variable was significantly associated with a long‐lasting remission.

Conclusion

Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

     

Exercise adherence improving long‐term patient outcome in patients with osteoarthritis of the hip and/or knee

Objective

To determine the effect of patient exercise adherence within the prescribed physical therapy treatment period and after physical therapy discharge on patient outcomes of pain, physical function, and patient self‐perceived effect in individuals with osteoarthritis (OA) of the hip and/or knee.

Methods

We performed a prospective observational followup study in which 150 patients with OA of the hip and/or knee receiving exercise therapy were followed for 60 months. Data were obtained from a randomized controlled trial, with assessments at baseline and 3, 15, and 60 months of followup. The association between exercise adherence and patient outcomes of pain, physical function, and self‐perceived effect was examined using generalized estimating equations analyses.

Results

Adherence to recommended home exercises and being more physically active were significantly associated with better treatment outcomes of pain, self‐reported physical function, physical performance, and self‐perceived effect. The association between adherence and outcome was consistent over time. Adherence to home activities was only associated with better self‐perceived effect.

Conclusion

Better adherence to recommended home exercises as well as being more physically active improves the long‐term effectiveness of exercise therapy in patients with OA of the hip and/or knee. Both within and after the treatment period, better adherence is associated with better patient outcomes of pain, physical function, and self‐perceived effect. Since exercise adherence declines over time, future research should focus on how exercise behavior can be stimulated and maintained in the long term.     

Patient-Reported Quality of Pain Treatment and Use of Interpreters in Spanish-Speaking Patients Hospitalized for Obstetric and Gynecological Care

BACKGROUND

Assessment and treatment of pain are based largely on patient’s self reports. Patients with limited English proficiency (LEP) may have difficulties communicating their pain symptoms in the presence of language barriers.

OBJECTIVE

To determine whether interpreter use was associated with quality of acute pain treatment among Latina patients with limited English proficiency.

DESIGN

Secondary analysis of two cross-sectional surveys.

PARTICIPANTS

One hundred and eighty-five Latino female patients hospitalized for obstetric and gynecological care who required interpreter services. Patients were classified into two groups according to interpreter availability (''Always'' and ''Not Always'' available).

MAIN MEASURES

Quality of pain treatment was measured by patient report of 1) overall level of pain control during hospitalization; 2) timeliness of pain treatment; and 3) perceived provider helpfulness to treat pain.

KEY RESULTS

Patients who always received interpreters were more likely to report higher levels of pain control (P = 0.02), timely pain treatment (P = 0.02), and greater perceived provider helpfulness to treat their pain (P = 0.005), compared with patients who not always received interpreters.

CONCLUSION

Use of interpreters by LEP patients was associated with better patient reports on quality of pain treatment, and may also improve clinical interactions related to pain.KEY WORDS: interpreters, limited English proficiency, Latinos/Latinas, pain, pain treatment     

Development and preliminary validation of a Children's Arthritis Self‐Efficacy Scale

Objective

To develop a valid and reliable measure of arthritis self‐efficacy for use with school‐age children with juvenile idiopathic arthritis (JIA).

Methods

Construction of the 11‐item Children's Arthritis Self‐Efficacy Scale (CASE) was based on an existing body of knowledge and the results of focus groups with children, their parents, and health professionals. Data for validation of the CASE were collected by self‐administered questionnaires completed by 89 children and 151 caregivers.

Results

Analyses revealed a 3‐factor structure relating to self‐efficacy for managing symptoms, emotional consequences, and activities, explaining 76.5% of the total variance. The CASE demonstrated high internal consistency, concurrent validity, and construct validity.

Conclusion

Preliminary findings suggest that the CASE is worthy of further psychometric testing and may have the potential to help delineate variations in adjustment among children with JIA.

     

Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets

Objective

To determine whether peripheral blood mononuclear cells (PBMCs) from children with recent‐onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures.

Methods

Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second‐line medications, such as methotrexate or biologic agents. RNA was extracted from isolated mononuclear cells, fluorescence labeled, and hybridized to commercial gene expression microarrays (Affymetrix HG‐U133 Plus 2.0). Data were analyzed using analysis of variance at a 5% false discovery rate threshold after robust multichip analysis preprocessing and distance‐weighted discrimination normalization.

Results

Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA patients and healthy controls. Hierarchical clustering of these probe sets distinguished 3 subgroups within the polyarticular JIA group. Prototypical patients within each subgroup were identified and used to define subgroup‐specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor β–inducible genes, and a third with immediate early genes. Correlation of gene expression signatures with clinical and biologic features of JIA subgroups suggested relevance to aspects of disease activity and supported the division of polyarticular JIA into distinct subsets.

Conclusion

Gene expression signatures in PBMCs from patients with recent‐onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.

     

Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis

Objective

To explore biologic correlates to age at onset in patients with juvenile idiopathic arthritis (JIA) using peripheral blood mononuclear cell (PBMC) gene expression analysis.

Methods

PBMCs were isolated from 56 healthy controls and 104 patients with recent‐onset JIA (39 with persistent oligoarticular JIA, 45 with rheumatoid factor–negative polyarticular JIA, and 20 with systemic JIA). RNA was amplified and labeled using NuGEN Ovation, and gene expression was assessed with Affymetrix HG‐U133 Plus 2.0 GeneChips.

Results

A total of 832 probe sets revealed gene expression differences (false discovery rate 5%) in PBMCs from children with oligoarticular JIA whose disease began before age 6 years (early‐onset disease) compared with those whose disease began at or after age 6 years (late‐onset disease). In patients with early‐onset disease, there was greater expression of genes related to B cells and less expression of genes related to cells of the myeloid lineage. Support vector machine analyses identified samples from patients with early‐ or late‐onset oligoarticular JIA (with 97% accuracy) or from patients with early‐ or late‐onset polyarticular JIA (with 89% accuracy), but not from patients with systemic JIA or healthy controls. Principal components analysis showed that age at onset was the major classifier of samples from patients with oligoarticular JIA and patients with polyarticular JIA.

Conclusion

PBMC gene expression analysis reveals biologic differences between patients with early‐and late‐onset JIA, independent of classification based on the number of joints involved. These data suggest that age at onset may be an important parameter to consider in JIA classification. Furthermore, pathologic mechanisms may vary with age at onset, and understanding these processes may lead to improved treatment of JIA.

     

Changes in vascular function and structure in juvenile idiopathic arthritis

Objective

Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health.

Methods

Thirty patients with JIA (age range 7–18 years) were compared to 33 age‐ and sex‐matched controls. Endothelial function (brachial artery flow‐mediated dilation [FMD]), carotid intima‐media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM‐1) and P‐selectin measurements.

Results

Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM‐1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease.

Conclusion

Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease‐related characteristics (inflammation, disease activity, and medications).     

Pain Intensity Variability and Its Relationship With Quality of Life in Youths With Juvenile Idiopathic Arthritis

Objective

To describe variability of pain intensity experienced by youths with juvenile idiopathic arthritis (JIA) and examine factors related to within‐day patterns of pain and the relationship between magnitude of pain variability and quality of life.

Methods

Pain intensity was self‐reported on a visual analog scale (VAS; range 0–100) by 112 youths with JIA ages 8–18 years using electronic diaries 3 times per day for 7 days. Average absolute change in pain (AAC) was computed as a measure of the magnitude of pain variability for each participant. Logistic regression was used to examine the relationship between demographic and disease characteristics and the probability of having high pain variability (AAC ≥10 VAS units). Linear regression was used to examine the relationship between quality of life (assessed by the Pediatric Quality of Life Inventory) and AAC. The generalized estimating equations approach was used to examine the relationship between the time of day and pain intensity.

Results

The mean ± SD AAC was 15.6 ± 10.5. The majority of youths (65%) had high AAC (≥10 VAS units). Disease severity predicted high pain variability (β = 0.02, P = 0.044). Higher AAC predicted lower quality of life (adjusted R² = 0.194, β = ?0.59, P = 0.003). Within‐day patterns of pain intensity varied by JIA subtype and sex.

Conclusion

This study characterized the pain intensity variability experienced by youths with JIA. Pain variability throughout the day was common, varied by JIA subtype and sex, and was related to quality of life. These findings have implications for future pain research, patient education, and development of clinical interventions for this population.

     

Physical Functioning,Pain, and Health‐Related Quality of Life in Adults With Juvenile Idiopathic Arthritis: A Longitudinal 30‐Year Followup Study

Objective

To describe physical functioning, pain, and health‐related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQoL after 30 years of disease.

Methods

Patients (n = 176) clinically examined after 15 years were reassessed using the Health Assessment Questionnaire disability index (HAQ DI), the visual analog scale pain subscale (VAS pain), and the Medical Outcomes Study Short Form 36 (SF‐36) after 23 years and 30 years. Patients with signs of active disease after a minimum of 15 years were clinically examined again at 30 years. Patients were compared to matched controls.

Results

At the 30‐year followup, 82 patients (47%) had HAQ DI scores >0, and the median VAS pain score in patients was 0.6 (range 0–10). Patients had lower SF‐36 physical component summary (PCS) scores compared with controls (P < 0.001), and this was evident for patients both with and without clinical remission (P ≤ 0.01). No group differences were found in SF‐36 mental component summary scores. Patients also scored worse than controls on all SF‐36 subscales (P ≤ 0.01) except mental health. PCS scores worsened significantly between the 15‐ and 30‐year followup time points (P = 0.001). Worse HAQ DI, VAS pain, and patient's global assessment of well‐being scores, and receiving disability/social living allowance at 30 years, were correlated with lower PCS scores. Worse HAQ DI, patient's global assessment of well‐being, and VAS fatigue scores at 15‐year followup predicted lower PCS scores at 30‐year followup.

Conclusion

JIA had a detrimental effect on physical HRQoL as measured by the PCS of the SF‐36. The strongest correlates were physical disability, pain, fatigue, well‐being, and receiving disability/social living allowance.

     

Brief Report: Incidence of Selected Opportunistic Infections Among Children With Juvenile Idiopathic Arthritis

Objective

To compare incidence rates of selected opportunistic infections among children with and children without juvenile idiopathic arthritis (JIA).

Methods

Using US national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We also identified a non‐JIA comparator cohort of children diagnosed as having attention deficit hyperactivity disorder (ADHD). We defined 15 types of opportunistic infection using physician diagnosis or hospital discharge codes; criteria for 7 of these types also included evidence of treatment with specific antimicrobial agents. We calculated infection incidence rates. The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) to compare infection rates.

Results

The JIA cohort included 8,503 children with 13,990 person‐years of followup. The ADHD comparator cohort included 360,362 children with 477,050 person‐years of followup. When all opportunistic infections were considered together as a single outcome, there were 42 infections in the JIA cohort (incidence rate 300 per 100,000 person‐years; IRR 2.4 [95% CI 1.7–3.3] versus ADHD). The most common opportunistic infections among children with JIA were 3 cases of Coccidioides (incidence rate 21 per 100,000 person‐years; IRR 101 [95% CI 8.1–5,319] versus ADHD), 5 cases of Salmonella (incidence rate 35 per 100,000 person‐years; IRR 3.8 [95% CI 1.2–9.5]), and 32 cases of herpes zoster (incidence rate 225 per 100,000 person‐years; IRR 2.1 [95% CI 1.4–3.0]).

Conclusion

Opportunistic infections are rare among children with JIA. Nevertheless, children with JIA had a higher rate of opportunistic infections, including an increased rate of Coccidioides, Salmonella, and herpes zoster compared to children with ADHD.

     

The effects of vigorous exercise training on physical function in children with arthritis: A randomized,controlled, SINGLE‐BLINDED trial

Objective

To examine the effectiveness of high‐intensity aerobic training compared with low‐intensity training in terms of energy cost of locomotion, peak oxygen uptake, peak power, and self‐reported physical function in children with juvenile idiopathic arthritis (JIA).

Methods

Eighty children with JIA, ages 8–16 years, were enrolled in a randomized, single‐blind controlled trial. Both groups participated in a 12‐week, 3‐times–weekly training program consisting of high‐intensity aerobics in the experimental group and qigong in the control group. Subjects underwent exercise testing measuring submaximal oxygen uptake at 3 km/hour (VO _2submax) as the primary outcome, maximal oxygen uptake, and peak power at the beginning and end of the program. Physical function was measured using the Child Health Assessment Questionnaire (C‐HAQ).

Results

The exercise program was well tolerated in both groups. There was no difference in VO _2submax or any other exercise testing measures between the groups through the study period and no indication of improvement. Both groups showed significant improvements in C‐HAQ with no difference between the groups. Adherence was higher in the control group than the experimental group.

Conclusion

Our findings suggest that activity programs with or without an aerobic training component are safe and may result in an important improvement in physical function. The intensity of aerobic training did not seem to provide any additional benefits, but higher adherence in the qigong program may suggest that less intensive regimens are easier for children with JIA to comply with, and provide a degree of benefit equivalent to more intensive programs.     

Development and initial validation of composite parent- and child-centered disease assessment indices for juvenile idiopathic arthritis

Objective

To develop and validate a parent‐centered and a child‐centered composite disease assessment index for juvenile idiopathic arthritis (JIA): the Juvenile Arthritis Parent Assessment Index (JAPAI) and the Juvenile Arthritis Child Assessment Index (JACAI), respectively.

Methods

The JAPAI and the JACAI include 4 measures: parent/child rating of overall well‐being, pain, physical function, and health‐related quality of life (HRQOL). Validation analyses were conducted on nearly 5,000 patients and included assessment of construct validity, discriminant validity, responsiveness to change, and reliability. Besides the 4‐item version, a 3‐item version of both indices, which did not include HRQOL, was tested.

Results

The JAPAI and the JACAI demonstrated good construct validity, yielding high correlations with the Juvenile Arthritis Disease Activity Score and moderate correlations with physician global rating and joint counts. Correlations obtained for the JAPAI and the JACAI and for the 4‐item and the 3‐item versions were comparable. Factorial analysis by principal component analysis showed that both indices are monodimensional. Both the JAPAI and JACAI discriminated well between different disease states and courses and between different levels of American College of Rheumatology Pediatric criteria in a clinical trial, and revealed fair responsiveness to clinical change. Internal consistency was satisfactory, with a Cronbach's alpha of >0.80 in all but 1 of the patient samples tested.

Conclusion

The JAPAI and the JACAI were found to be valid instruments for assessment of disease status in JIA and suitable surrogates of physicians' evaluations. Both indices are potentially applicable in clinical practice, observational studies, and therapeutic trials.     

The limited role of interferon‐γ in systemic juvenile idiopathic arthritis cannot be explained by cellular hyporesponsiveness

Objective

Systemic juvenile idiopathic arthritis (JIA) is an autoinflammatory syndrome in which the myelomonocytic lineage appears to play a pivotal role. Inflammatory macrophages are driven by interferon‐γ (IFNγ), but studies have failed to demonstrate an IFN‐ induced gene signature in active systemic JIA. This study sought to characterize the status of an IFN‐induced signature within affected tissue and to gauge the integrity of IFN signaling pathways within peripheral monocytes from patients with systemic JIA.

Methods

Synovial tissue from 12 patients with active systemic JIA and 9 with active extended oligoarticular JIA was assessed by real‐time polymerase chain reaction to quantify IFN‐induced chemokine gene expression. Peripheral monocytes from 3 patients with inactive systemic JIA receiving anti–interleukin‐1β (anti–IL‐1β) therapy, 5 patients with active systemic JIA, and 8 healthy controls were incubated with or without IFNγ to gauge changes in gene expression and to measure phosphorylated STAT‐1 (pSTAT‐1) levels.

Results

IFN‐induced chemokine gene expression in synovium was constrained in active systemic JIA compared to the known IFN‐mediated extended oligoarticular subtype. In unstimulated peripheral monocytes, IFN‐induced gene expression was similar between the groups, except that lower levels of STAT1, MIG, and PIAS were observed in patients with active disease, while higher levels of PIAS1 were observed in patients with inactive disease. Basal pSTAT‐1 levels in monocytes tended to be higher in systemic JIA patients compared to healthy controls, with the highest levels seen in those with inactive disease. Upon stimulation of monocytes, the fold increase in gene expression was roughly equal between groups, except for a greater increase in STAT1 in patients with inactive systemic JIA compared to controls, and a greater increase in IRF1 in those with active compared to inactive disease. Upon stimulation, the fold increase in pSTAT‐1 was highest in monocytes from patients with inactive systemic JIA.

Conclusion

Monocytes in patients with active systemic JIA retain the ability to respond to IFNγ, suggesting that the lack of an IFN‐induced gene signature in patients with active disease reflects a limited in vivo exposure to IFNγ. In patients with inactive systemic JIA who received treatment with anti–IL‐1β, hyperresponsiveness to IFNγ was observed.