Objective
Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been ...reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS.
Methods
A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face‐to‐face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada.
Results
Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS.
Conclusion
Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence‐based guidelines for the treatment of juvenile LS.
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.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This study aimed to describe the proportion of patients with juvenile idiopathic arthritis (JIA) who had experienced an unsuccessful transfer from a pediatric rheumatology team to an adult ...rheumatologist and to compare the characteristics of those who achieved successful transfer to those who did not.
We conducted a systematic chart review of all patients with JIA who attended their final Montreal Children's Hospital JIA clinic appointment between 1992 and 2005. We tracked these patients for the two years after transfer to an adult rheumatologist. We then compared characteristics of patients with successful and unsuccessful transfers of care. Variables pertaining to disease characteristics, disease severity and psychosocial factors were examined. Univariate analyses were performed to determine if any single factor was associated with the outcome of unsuccessful transfer of care.
52% of patients fulfilled our criteria for unsuccessful transfer. Of the variables tested, an active joint count (AJC) of zero at last visit was associated with the outcome of unsuccessful transfer (OR = 2.67 (CI 1.16-6.16; p = 0.0199)).
Despite the presence of a coordinated process of transfer from pediatric to adult health care for the majority of the patients in this study, there was a high rate of unsuccessful transfer and/or sustained follow up which is disheartening. We found that patients with less active disease at the time of transfer, as indicated by a lower AJC, were more likely to be lost to follow up. Recent literature suggests that even in the least severe categories of JIA, 50% of patients persist with active disease into adulthood. Thus educating all JIA patients about the possibility of disease flare in adulthood may improve their adherence to recommendations for sustained follow-up in the adult milieu. This may lead to improvement of longitudinal outcomes for all JIA patients.
Objectives To determine the prevalence of and the risk factors for vertebral fractures in a cohort of children with chronic rheumatic diseases considered at risk for osteopenia. Study design We ...conducted a cross-sectional study of patients with chronic rheumatic diseases at the Montreal Children's Hospital. Results Of the 90 study participants (22 boys, 68 girls), 10 boys and 7 girls (19%) were found to have vertebral fractures. These 17 children had a total of 50 fractures, an average of 2.9 per affected child. Fractures in the upper thoracic region (T5-8) accounted for 55%. Only 56% of all fractures were symptomatic. With multivariate regression, we identified male sex ( P < .01), body mass index z-score ( P < .02), and cumulative glucocorticoid dose ( P < .01) as significant predictors of the number of vertebral fractures. Conclusions Our study examined the prevalence of vertebral fractures in a high-risk pediatric population. Nineteen percent of our cohort had vertebral fractures. Significant risk factors for the development of vertebral fractures include male sex and cumulative glucocorticoid dose. Better understanding of the extent of the problem in this population will allow us to further refine screening guidelines and treatment in these patients.
To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments.
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.
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.
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.
Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether ...genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3), was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8). Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8), as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype 6.4 × 10(-17), OR 2.3 (1.9, 2.9). By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.
Objective
To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to ...patients with granulomatosis with polyangiitis (Wegener's) (GPA).
Methods
The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e‐entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult‐ and pediatric‐specific criteria. Descriptive statistics were used for comparisons.
Results
In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic‐range proteinuria, requirement for dialysis, and end‐stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA‐defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil.
Conclusion
Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female‐to‐male disease prevalence ratios is a provocative finding.
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.
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.
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.
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.
Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of ...Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories.
We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P < 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended (<60%; 157). Localized patients more often maintained their baseline patterns (P < 0.05 for five groups by permutation test) than nonlocalized patients (P < 0.05 for three groups by permutation test) over a five-year follow-up period. We modelled time to zero joints in the discovery cohort using a multivariate Cox proportional hazards model considering joint pattern, degree of localization, and ILAR subtype. Despite receiving more intense treatment, 50% of nonlocalized patients had zero joints at one year compared to six months for localized patients. Overall, localized patients required less time to reach zero joints (partial: P = 0.0018 versus localized by log-rank test; extended: P = 0.0057). Potential limitations include the requirement for patients to be treatment naïve (except NSAIDs), which may skew the patient cohorts towards milder disease, and the validation cohort size precluded multivariate analyses of disease trajectories.
Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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