Objective. To characterize the effect of anti-tumor necrosis factor (TNF) therapy compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in children with enthesitis-related arthritis (ERA) over the first year after diagnosis. Methods. We conducted a multicenter retrospective comparative effectiveness study of children diagnosed with ERA. We estimated the effect of anti-TNF therapy on clinical variables (active joint count, tender entheses count) and patient-reported pain and global assessment of disease activity over the first year after diagnosis using state-of-the-art comparative effectiveness analytic methods. Results. During the study period, 217 patients newly diagnosed with ERA had a total of 965 clinic visits the first year after disease diagnosis. Children [median age 11.6 yrs, interquartile range 10–14] were treated with anti-TNF monotherapy (n = 33, 15.2%), csDMARD monotherapy (n = 73, 33.6%), or both (n = 52, 23.9%) in the first year after disease diagnosis. There was a statistically significant improvement in the primary outcome, active joint count, over time in children who received an anti-TNF drug versus those who did not (p = 0.03). Additionally, use of anti-TNF therapy versus no anti-TNF therapy was associated with less patient-reported pain (p < 0.01) and improved disease activity over time as assessed by the clinical Juvenile Arthritis Disease Activity Score (p < 0.01). The magnitude of estimated effect on clinical outcomes was uniformly greater, with the exception of tender entheses count, in children treated with an anti-TNF drug versus a csDMARD. Conclusion. During the first year after diagnosis, anti-TNF exposure was associated with benefits for several clinically meaningful outcomes in children with enthesitis-related arthritis.

Objectives Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE. Methods Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels. Pearson’s correlations and Χ2 tests were used to evaluate the relationships between 25OHD, PTH, LL-37, inflammation, disease activity and infection using baseline values collected as part of the APPLE study. Results 201/221 APPLE participants had serum available for analysis. Serum 25OHD was inversely associated with serum PTH, but not LL-37. Serum PTH was not associated with high sensitivity C-reactive protein, carotid intima media thickness or high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol, but was negatively associated with lipoprotein(a) levels. Despite no association with serum 25OHD, LL-37 was negatively associated with total cholesterol, HDL and LDL cholesterol and positively associated with age. There was no significant difference in mean LL-37 levels in participants with reported infection as an adverse event during the 3-year APPLE study. Conclusions Despite links to vitamin D levels in other studies, LL-37 levels were not associated with baseline serum 25OHD concentrations in paediatric patients with pSLE. Despite the lack of correlation with 25OHD, LL-37 levels in this study were associated with cholesterol levels. Some subjects with pSLE have significantly elevated levels of LL-37 of unknown significance. These exploratory results addressing the role of LL-37 levels in pSLE appear worthy of future study.

Objectives: Neuropathic pain (NP) is a consequence of many chronic conditions. This study aimed to develop an unidimensional NP scale with scores that represent levels of NP and distinguish between individuals with NP and non-NP conditions. Methods: A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without NP conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a holdout sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. NP scale scores were evaluated in terms of the reliability, validity, and ability to distinguish between participants with and without conditions typically associated with NP. Results: Of the 42 initial items, 5 were identified for the Patient-Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality Scale. T scores exhibited good discriminatory ability on the basis of receiver-operator characteristic analysis. Score thresholds that optimize sensitivity and specificity were identified. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. Conclusions: The five-item Patient-Reported Outcome Measurement Information System (PROMIS PQ-Neuro) Neuropathic Pain Quality Scale is a short and practical measure that can be used to identify patients more likely to have NP and to distinguish levels of NP. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain).

Abstract The Patient-Reported Outcomes Measurement Information System (PROMIS) initiative is a comprehensive strategy by the National Institutes of Health to support the development and validation of precise instruments to assess self-reported health domains across healthy and disease-specific populations. Much progress has been made in instrument development, but there remains a gap in the validation of PROMIS measures for pediatric chronic pain. The purpose of this study was to investigate the construct validity and responsiveness to change of 7 PROMIS domains for the assessment of children (ages: 8-18) with chronic pain—Pain Interference, Fatigue, Anxiety, Depression, Mobility, Upper Extremity Function, and Peer Relationships. The PROMIS measures were administered at the initial visit and 2 follow-up visits at an outpatient chronic pain clinic (CPC; N = 82) and at an intensive amplified musculoskeletal pain day-treatment program (N = 63). Aim 1 examined construct validity of PROMIS measures by comparing them with corresponding “legacy” measures administered as part of usual care in the CPC sample. Aim 2 examined sensitivity to change in both CPC and amplified musculoskeletal pain samples. Longitudinal growth models showed that PROMIS' Pain Interference, Anxiety, Depression, Mobility, Upper Extremity, and Peer Relationship measures and legacy instruments generally performed similarly with slightly steeper slopes of improvement in legacy measures. All 7 PROMIS domains showed responsiveness to change. Results offered initial support for the validity of PROMIS measures in pediatric chronic pain. Further validation with larger and more diverse pediatric pain samples and additional legacy measures would broaden the scope of use of PROMIS in clinical research.

The study objective was to describe the individual item-level discrepancies between children ages 8–17 years and their parents for the PROMIS® pediatric scales. Contextual effects on item-level informant discrepancies for the pediatric pain interference items were further analyzed conditional on whether the child, the parent, or anyone else in the household experienced chronic pain.

As initial steps in a broader effort to develop and test pediatric pain behavior and pain quality item banks for the Patient-Reported Outcomes Measurement Information System (PROMIS), we used qualitative interview and item review methods to 1) evaluate the overall conceptual scope and content validity of the PROMIS pain domain framework among children with chronic/recurrent pain conditions, and 2) develop item candidates for further psychometric testing. To elicit the experiential and conceptual scope of pain outcomes across a variety of pediatric recurrent/chronic pain conditions, we conducted 32 semi-structured individual and 2 focus-group interviews with children and adolescents (8-17 years), and 32 individual and 2 focus-group interviews with parents of children with pain. Interviews with pain experts (10) explored the operational limits of pain measurement in children. For item bank development, we identified existing items from measures in the literature, grouped them by concept, removed redundancies, and modified the remaining items to match PROMIS formatting. New items were written as needed and cognitive debriefing was completed with the children and their parents, resulting in 98 pain behavior (47 self, 51 proxy), 54 quality, and 4 intensity items for further testing. Qualitative content analyses suggest that reportable pain outcomes that matter to children with pain are captured within and consistent with the pain domain framework in PROMIS.Perspective: PROMIS pediatric pain behavior, quality, and intensity items were developed based on a theoretical framework of pain that was evaluated by multiple stakeholders in the measurement of pediatric pain, including researchers, clinicians, and children with pain and their parents, and the appropriateness of the framework was verified. (C) 2015 by the American Pain Society

To conduct a comparative analysis of eight pediatric self-report scales for ages 8–17 years from the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS®) in six pediatric chronic health conditions, using indicators of disease severity.

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a multi-center, quality-improvement-focused learning network with a mission of improving outcomes for children and adolescents with juvenile idiopathic arthritis (JIA). PR-COIN has developed a population management tool which facilitates pro-active, coordinated health care communications and interventions that can be used in managing JIA patient populations. The population management tool was developed with information technology expertise to link seamlessly to the PR-COIN longitudinal registry. Within the population management tool, on demand reports can be generated using participating site or aggregate, network level data according to demographics, clinical features, disease activity levels, patient reported outcomes (functional ability/CHAQ score, arthritis related pain), medication use, and quality indicators. Drill down capability enables identification of patients. Currently, data from 8 sites, 1161 patients, and 5334 clinical encounters are included in the population management tool (Table 1 ). Individual site usage of the population management tool is variable ranging from infrequent use to regular use at monthly population management meetings. The PR-COIN network is currently developing strategies to promote consistent usage of the tool at sites. Clinicians routinely using information provided through this tool report satisfaction with its functionality and ease of use; furthermore they report enhanced ability to proactively identify and address specific patient needs prior to and during clinic visits, optimizing care. The population management tool allows real-time feedback to sites regarding overall JIA population and individual patient status. Customized, “on demand” population measurement and quality improvement reports generated by the network and participating sites and can be used to identify gaps in patient care and at-risk subpopulations that may benefit from more intensive or between-visit care. Current efforts include developing a care stratification scores that can assist in identifying at risk JIA subpopulations and provision of individual patient reports that can be used to assist in pre-visit planning. Future goals include providing feedback to individual patients about their disease status compared to local and network aggregate data, and customized educational and interventional tools that can be provided to JIA patients and families. Thus, the PR-COIN JIA population management tool can be leveraged to improve JIA network and site performance and individual patient care.

The Childhood Arthritis and Rheumatology Research Alliance (CARRA) previously published an article in Arthritis Care & Research describing the consensus treatment plans (CTPs) for new-onset systemic juvenile idiopathic arthritis (JIA) (1). Since its publication, canakinumab, an interleukin-1 (IL-1) beta monoclonal antibody, was approved for use by US and European regulatory authorities following the publication of studies demonstrating its efficacy and safety in this disease (2). The CARRA systemic JIA workgroup had previously decided that new medications that become commonly available for this disease would be added to the CTPs. The CTPs are meant to be used when treating new-onset systemic JIA patients so that the comparative effectiveness of the CTPs can be studied through data entered into the CARRA registry. Once canakinumab became available for systemic JIA patients, the workgroup decided to revise the IL-1 inhibitor CTP to include this medication so that the patient may start either IL-1 inhibitor (anakinra or canakinumab) at any point during the course of the CTP (Figure 1). This revised IL-1 inhibitor CTP was then circulated via an electronic survey to all CARRA JIA Disease Committee members (n 188) to ensure acceptability. Of these members, 98 responded (52%), of whom 6 were not clinicians and were excluded. Of the remaining 92 members, 90 (98%) agreed with the IL-1 inhibitor CTP as presented and would use it when treating new-onset systemic JIA patients. We anticipate that this new IL-1 inhibitor CTP that allows the use of canakinumab or anakinra will be considered going forward by pediatric rheumatologists for new-onset systemic JIA patients when it is decided that an IL-1 inhibitor is indicated. A pilot study funded by the Arthritis Foundation is currently under way in a limited number of sites to assess the feasibility of using the systemic JIA CTPs in daily practice. In the future, we anticipate that, by widely disseminating the use of these CTPs to all CARRA sites and collecting the resulting data through the CARRA registry, their comparative effectiveness in patients with this disease will be able to be studied. Supported by the Childhood Arthritis and Rheumatology Research Alliance, the Arthritis Foundation, the Wasie Foundation, and Friends of the Childhood Arthritis and Rheumatology Re-

OBJECTIVE:To develop and validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) for use in clinical practice and research.METHODS:Using modified Delphi consensus techniques, 10 items were selected by participants in the international pediatric rheumatology listserv, the Childhood Arthritis and Rheumatology Research Alliance, and the listserv for the pediatric section of the American College of Rheumatology. Validation was performed in a retrospective multicenter cohort of 244 children.RESULTS:In total, 106 physicians representing 14 countries completed the initial questionnaire. Completion rates for the subsequent questionnaires were 84%, 75%, and 77% of the original respondents. Ten items exceeded 80% consensus: arthritis, enthesitis, patient pain assessment, inflammatory markers, morning stiffness, clinical sacroiliitis, uveitis, back mobility, and patient and physician assessments of disease activity. After item analysis, 2 items were eliminated (patient and physician assessments of disease activity). Factor analysis identified 3 primary domains that explained 58% of the variance: peripheral disease, axial disease, and uveitis. The Cronbach's α coefficient was 0.66. The JSpADA had high or moderate correlations with the Juvenile Arthritis Disease Activity Score (r = 0.81), patient and physician assessments of disease activity (r = 0.70 and r = 0.66, respectively), and the Childhood Health Assessment Questionnaire (r = 0.56). The JSpADA discriminated well between subjects with active versus inactive disease (P < 0.001) and was responsive to improvement or worsening in disease activity over time (P < 0.001).CONCLUSION:Using international input and consensus formation techniques, we developed and validated the first disease activity assessment for juvenile spondyloarthritis. Future studies should validate the JSpADA in a prospective multicenter cohort.

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a multi-site quality improvement learning network that aims to improve outcomes for children and adolescents with juvenile idiopathic arthritis. In addition to addressing variations in care practices, PR-COIN has incorporated guidance and tangible contributions from patients and families to its national organizational and governance structure to drive improvement in JIA outcomes. PR-COIN aims to grow this initiative to bring care providers, patients and family members together as co-producers in improving care and outcomes. Various methods supporting family engagement are employed. PR-COIN teams invite interested parents at their respective clinical sites to bring the parent perspective and priorities into local improvement work. To assure a reliable structure, a parent engagement specialist was employed to develop a platform for bringing families and care providers together. National conference calls facilitated by the specialist establish relationships across site representatives and begin goal setting for this group. Parents contribute to shared decision making project efforts. PR-COIN's public website encourages family awareness and involvement in the network's improvement efforts. 7 of 11 sites have welcomed parent contributions to their improvement efforts (e.g. focus groups, advisory activities, etc.). Parents and patients have participated in PR-COIN's biannual conferences, sharing the family perspective and needs associated with JIA care. One parent brings a unique background and skillset as both a pediatrician with QI experience and the parent of a teen with JIA. This distinction prompted appointment to PR-COIN's governing body. We incorporate patient perspectives into clinic process improvements (e.g. pain management, optimizing physical functioning), enhanced and refined PR-COIN's Shared Decision Making tool, supporting stronger, more informed medication choice, and are developing best practices optimizing use of these materials in clinic. Finally our engaged parents are encouraging others to contribute ideas supportive of PR-COIN structure, growth, strategy and improvement efforts. Parents and patients bring unique talents, insight and skills to the operation of quality improvement networks making efforts more relevant to the self-identified needs of JIA families.

Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a multi-site learning network designed to improve outcomes of juvenile idiopathic arthritis (JIA) care. Teams collect point of care data on measures of process of care and outcomes of care for the purposes of analysis to guide improvement activities. Eleven North American pediatric rheumatology centers participate. This report illustrates our improvement in several JIA process quality measures (QMs). Process of care QMs targeted for improvement include measurement of: arthritis-related pain, physician global assessment, joint count, health-related quality of life, physical function, as well as screening for uveitis, medication toxicity, and tuberculosis per guidelines. Outcome measures for JIA include clinical inactive disease, clinical remission on and off medications, no or mild pain level, and optimal physical functioning. Network goals were determined for each process and outcome measure. Data are collected with IRB approval and informed consent, and the shared registry for data entry is the ACR's Rheumatology Clinical Registry. Site-specific and aggregate data are analyzed and displayed monthly via statistical process control charts allowing PR-COIN to track performance over time. Individual centers use established quality improvement methodology to reach and exceed pre-determined goals. Data from 5112 encounters for 1134 JIA patients have been collected since April 2011. QMs with performance meeting or exceeding initial goals include documentation of complete joint count and measurement of arthritis-related pain. For PR-COIN network as a collective unit, QMs improved in six processes—measurement of functional ability, completion of ongoing medication toxicity labs, documentation of complete joint count, medication counseling for newly prescribed DMARDs, documentation of annual medication counseling, and measurement of health-related quality of life. All of these measures had a shift above the baseline mean, demonstrating special cause. In addition, five sites have demonstrated individual improvement in at least one process QM. PR-COIN sites are collectively and individually demonstrating significant improvements in JIA process of care QMs. Quality improvement efforts in PR-COIN are ongoing with the goal of improving the outcome for patients with JIA.

Objective. Patient-reported outcome (PRO) questionnaires record health information directly from research participants because observers may not accurately represent the patient perspective. Patient-reported Outcomes Measurement Information System (PROMIS) is a US National Institutes of Health cooperative group charged with bringing PRO to a new level of precision and standardization across diseases by item development and use of item response theory (IRT).Methods. With IRT methods, improved items are calibrated on an underlying concept to form an item bank for a "domain" such as physical function (PF). The most informative items can be combined to construct efficient "instruments" such as 10-item or 20-item PF static forms. Each item is calibrated on the basis of the probability that a given person will respond at a given level, and the ability of the item to discriminate people from one another. Tailored forms may cover any desired level of the domain being measured. Computerized adaptive testing (CAT) selects the best items to sharpen the estimate of a person's functional ability, based on prior responses to earlier questions. PROMIS item banks have been improved with experience from several thousand items, and are calibrated on over 21,000 respondents.Results. In areas tested to date, PROMIS PF instruments are superior or equal to Health Assessment Questionnaire and Medical Outcome Study Short Form-36 Survey legacy instruments in clarity, translatability, patient importance, reliability, and sensitivity to change.Conclusion. Precise measures, such as PROMIS, efficiently incorporate patient self-report of health into research, potentially reducing research cost by lowering sample size requirements. The advent of routine IRT applications has the potential to transform PRO measurement.