Objective. The ability to assess quality of care is a necessary component of continuous quality improvement. The assessment typically is accomplished by determination of compliance with a defined set of quality measures (QMs). The objective of this effort was to establish a set of QMs for the assessment of the process of care in juvenile idiopathic arthritis (JIA).Methods. A 12-member working group composed of representatives from the American College of Rheumatology, American Academy of Pediatrics, American Board of Pediatrics, and Association of Rheumatology Health Professionals was assembled to guide the project. Delphi questionnaires were sent to 237 health professionals involved in the care of children with JIA. A total of 471 items in 23 domains were identified. The working group met via 4 live e-meetings during which results from the Delphi questionnaires were distilled to a reduced draft set. Each working group member selected a proposed QM to investigate and present evidence from the literature as to its attributes and appropriateness for inclusion into the set. Nominal group technique was used to come to consensus on a proposed set of QMs.Results. The proposed set contains 12 QMs within 4 health care domains. Each QM consists of a statement of 1) the assessment to be completed, 2) when the first assessment should be completed and a suggested frequency of assessment during followup, 3) recommendations of appropriate tools or methods of assessment, and 4) initial performance goals.Conclusion. Implementation of the proposed QM set will improve the process of care, facilitate continuous quality improvement, and eventuate in improved health outcomes of children with JIA.

We appreciate the long overdue recognition of the clinical importance of pain in the care of childhood arthritis evidenced by Lovell et al in their recent article published in Arthritis Care & Research (1). In contrast with earlier undertreatment and under-recognition of pain, the past decade has witnessed an increasing organizational commitment to help ensure that pain in children is prevented and treated whenever possible (2). Lovell et al recommend assessment of “arthritis-related pain” as a quality of care measure in the treatment of children with juvenile idiopathic arthritis (JIA); they suggest that pain assessment, along with other quality measures, should be routinely implemented in pediatric rheumatology practices as a means of tracking outcomes and generating quality improvement indices. However, additional commentary seems warranted with regard to pain as an index of quality of disease control. The recommended quality care benchmark that at least 80% of patients with JIA are asked about pain using “any validated, reliable, age-appropriate tool” during clinic visits fails to provide guidance as to the selection of an appropriate tool. Given that pain assessment in children contains nuances that, if overlooked, may result in suboptimal assessment and care (3), the absence of specific guidance is a concerning oversight. Providers should be strongly encouraged to obtain self-report of pain in children cognitively able to do so. Most children as young as 5 years of age are capable of validly self-reporting at least current pain if presented with an age-appropriate pain scale (3). With children younger than 5 years, and those who have cognitive or verbal communication deficits, pain assessment is more challenging and requires selecting an observational measure of pain (4). The same pain scale should be used with the child each time to allow for longitudinal comparison. Based on recent psychometric reviews of pediatric pain scales (4,5), we recommend the following measures: for age 8, the Numeric Rating Scale (available at URL: www.usask.ca/childpain/NRS/); for verbal children 5 years of age, including those ages 8 years who do not understand the Numeric Rating Scale, the Faces Pain ScaleRevised (available at URL: www.painsourcebook.ca); and for children unable to self-report pain, the FLACC scale (for normally developing children, available at URL: http://pain consortium.nih.gov/pain_scales/FLACCScale.pdf) or the Non-Communicating Children’s Pain Checklist-Revised (for children ages 3–18 years with cognitive deficits, available at URL: http://pediatricpain.ca/files/02/78/NCCPCR_ 200901.pdf). Unfortunately, only pain intensity was recommended as a quality of care measure by Lovell et al. Although pain intensity is a sensitive measure for evaluating pain treatment outcomes (3), other dimensions may yield a more complete understanding of pain without unduly burdening health care providers. For example, inquiring about the frequency of days with pain, location of the pain, or how much pain has bothered the child in the past week also are clinically relevant questions that provide a richer assessment of the quality of pain management. Further, if pain is endorsed, a determination of the extent of pain interference in physical, academic, and social activities is needed to inform care decisions. Children with JIA reporting minimal pain may nevertheless be quite disabled by their pain, whereas others with intense pain may be able to sustain age-appropriate activities without interruption. Although Lovell et al recommend quality measures assessing health-related quality of life and functioning, these measures may not be sensitive to pain-related activity limitations. The Pediatric Pain Interference Scale is recommended for evaluating pain interference in daily activities; it is a recently developed 8-item measure validated on a sample of more than 3,000 children (6). This measure, along with questions for evaluating other important dimensions of pain, is included as part of a brief pain assessment tool for use in pediatric rheumatology clinics that the authors have helped develop and pilot through the Childhood Arthritis and Rheumatology Research Alliance (7). Results of this work when available will mesh nicely with the recommendations of Lovell et al by establishing a more comprehensive yet practical pain assessment tool to be used as part of quality disease care for children with JIA. A final point for consideration is whether the categorization of pain as a quality measure for disease control is appropriate. Pain is a multidimensional subjective experience that does not have a one-to-one correspondence with disease activity and may be present in children with mild or inactive disease (8). Therefore, it may be more appropriate to classify pain assessment in a category of its own as a measure of comprehensive, quality care for patients with JIA. Assembling initial recommendations for quality care measures in the treatment of JIA to enhance excellence in clinical care is a laudable effort. We hope to complement the work of Lovell et al by suggesting how contemporary pain research can help inform the selection and conceptualization of pain measures when used as indices of quality of care.

OBJECTIVE Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.

Goldbach-Mansky R, Dailey NJ, Canna SW, et al. N Engl J Med. 2006;355:581–592 PURPOSE OF THE STUDY. Neonatal-onset multisystem inflammatory disease (NOMID) is a chronic inflammatory disease that develops in infancy and is characterized by an urticarial rash, arthropathy, and central nervous system disease, including aseptic meningitis, cerebral atrophy, mental retardation, seizures, and vision and hearing loss. Approximately 60% of patients have a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, which is involved in the interleukin 1β (IL-1β) pathway. This study evaluated the effect of anakinra (Kineret, Amgen), an IL-1 receptor antagonist, on the various clinical and laboratory aspects of NOMID. STUDY POPULATION. A cohort of 18 patients aged 4 to 32 years with clinical NOMID (67% with mutations in CIAS1) who had active disease despite treatment with other antiinflammatory agents. METHODS. Patients were given a daily subcutaneous dose of anakinra. The drug was withdrawn from 11 patients at 3 months with the development of a clinical flare. Thereafter, all patients were continued on daily treatments up to 24 months. Clinical and laboratory assessments were made at 1, 3, and 6 months during therapy with anakinra. Primary end points included changes in a disease-specific daily diary score and changes in the serum levels of acute-phase reactants. RESULTS. All patients had an immediate response to anakinra with resolution of rash and conjunctivitis. There was an improvement in diary scores at 3 months that was maintained at 6 months. Serum amyloid A, C-reactive protein, and the erythrocyte sedimentation rate significantly declined with treatment. All the patients had headache at baseline, which resolved or improved with therapy, and cochlear and leptomeningeal lesions were improved on MRI. Serum levels of IL-1β, which were initially higher than those in healthy controls, decreased over the first 6 months of therapy. All the patients who underwent a treatment withdrawal experienced rapid improvement of their symptoms after resuming anakinra. Other than injection-site reactions, which resolved with continued treatment, there were no serious adverse events. CONCLUSIONS. Anakinra may be a safe and effective treatment for patients with NOMID. REVIEWER COMMENTS. This study suggests that anakinra may have a role in the treatment of other diseases in which IL-1β mediates inflammation (eg, systemic juvenile rheumatoid arthritis). Additional studies are needed to determine its long-term effects and clinical application. This study is an example of how specific immunomodulatory therapy may be useful in treating those diseases that have a defined molecular pathophysiologic profile.

Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.

OBJECTIVE:To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open-label, extended-treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept. METHODS:Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3-4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of > or =30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%. RESULTS:At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low-dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population. CONCLUSION:Children with severe, longstanding, methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well-tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.

The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose.

In an 11-year-old child with juvenile rheumatoid arthritis (JRA), the addition of prednisone caused a significant decrease in salicylate serum concentrations. A pharmacokinetic assessment suggested that these changes were not the result of altered compliance or impaired absorption of salicylate but rather an increase in salicylate clearance induced by the corticosteroid.

Leucocyte migration inhibition in patients with ischaemic heart disease was evaluated as an assay for progressive myocardial damage. Abnormal results were observed in 50% of patients with ischaemic cardiac disease. The prevalence of abnormal leucocyte migration inhibition was unrelated to clinical presentation, extent of coronary artery disease, or degree of impairment of left ventricular function. Six of the eight patients with unstable angina pectoris and abnormal leucocyte migration inhibition developed life threatening cardiac complications in the follow-up period compared with five patients with unstable angina and normal tests who developed no complications. A similar association between abnormal leucocyte migration inhibition and complications was not observed in patients with angina pectoris or previous myocardial infarction. Thus, leucocyte migration inhibition may be useful as a prognostic marker in unstable angina and may be an important additional variable to identify a high risk subset.