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Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.

Objective The Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q) is a novel measure of vision-related quality of life (QOL) and function in children. We aim to determine the validity of the EYE-Q in childhood uveitis. Methods We abstracted medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE-Q, parents and patients completed questionnaires on overall QOL (Pediatric Quality of Life Inventory [PedsQL]), and physical functioning (Childhood Health Assessment Questionnaire [C-HAQ]). Results Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%), and cataracts (49%). Children with vision loss in their better eye (visual acuity [VA] 20/50 or worse) had worse EYE-Q (P = 0.006) and PedsQL (P = 0.028) scores, but not C-HAQ scores. The EYE-Q moderately correlated with logMAR VA (rs = −0.43), PedsQL (rs = 0.43), and C-HAQ (rs = −0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and C-HAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE-Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE-Q had strong test–retest reliability (rs = 0.75). Conclusion The EYE-Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision-related function.

Objective To estimate the relative risk of incident cancer diagnosis among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA. Methods A cohort of biologics-naive patients diagnosed with JIA between 1998 and 2007 and a matched cohort of comparators without JIA were assembled from the PharMetrics Patient-Centric Database. The primary outcome was any incident malignancy, excluding nonmelanoma skin cancer and carcinoma in situ. Claims profiles of patients with any cancer-related diagnosis codes were reviewed to determine outcomes. Incidence rates and 95% confidence intervals (95% CIs) of cancer were calculated and compared between cohorts using Cox proportional hazards regression. Standardized incidence ratios (SIRs) for each cohort compared to the general population were calculated using reference rates from the US Surveillance, Epidemiology, and End-Results (SEER) program. Results The JIA and non-JIA cohorts included 3,605 and 37,689 patients, respectively, with a mean age of 11 years. The incidence rates of cancer were 67.0 (95% CI 1.3–132.5) cases/100,000 person-years (PY) for JIA and 23.2 (95% CI 12.2–34.2) cases/100,000 PY for non-JIA. The risk of cancer associated with biologics-naive JIA was elevated (hazard ratio 2.8, 95% CI 0.9–8.3). The JIA cohort had a significantly elevated SIR of 4.0 (95% CI 2.6–6.0); the non-JIA cohort SIR was not significantly above SEER rates (SIR 1.4, 95% CI 0.6–2.6). Conclusion We found a nearly 3-fold increased risk of cancer in biologics-naive JIA patients, which approached significance despite the small number of outcomes. This finding suggests an elevated underlying risk of cancer in this disease population.

Human neutrophils express both activating and inhibitory Fcgamma receptors (FcgammaR), and their relative expression determines the inflammatory response to immune complexes. Tumor necrosis factor alpha (TNFalpha) up-regulates the expression of stimulatory FcgammaRIIa on neutrophils in vitro, and amplifies immune complex-induced activation of neutrophils in vivo. This study was undertaken to determine whether TNFalpha blockade in patients with rheumatoid arthritis (RA) alters the balance of activating FcgammaR and inhibitory FcgammaR and thereby decreases inflammation.We used fluorescence-activated cell sorting and Western blotting to examine FcgammaR expression on neutrophils in 24 patients with RA, preceding their first infusion of infliximab and immediately prior toor=3 subsequent infusions.In 13 of 24 patients (54.2%), there was a decrease in the expression of the predominant activating FcgammaR, FcgammaRIIa, after treatment with infliximab, an effect that persisted overor=3 months of treatment. Although prior to initiation of infliximab therapy the inhibitory FcgammaR, FcgammaRIIb, was undetectable in neutrophils from 23 of 24 patients with RA, FcgammaRIIb protein was detected by Western blotting in 9 patients (37.5%) at the time of the third infliximab infusion. The induction of inhibitory FcgammaRIIb was always associated with decreased levels of FcgammaRIIa, and improvement following infliximab therapy, measured using the Health Assessment Questionnaire, was significantly associated with down-regulation of FcgammaRIIa.Our findings indicate that TNFalpha inhibition may reduce inflammation in patients with RA by restoring the balance of activating and inhibitory FcgammaR and thereby raising the threshold for immune complex-mediated activation of neutrophils.

Background and Purpose Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. Methods Data from 34 SLE patients (age range, 18–73 years) and 29 age-matched volunteers (age range, 29–64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (Dav) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BDav). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. Results Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BDav and Dav values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BDav and Dav values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the Dav values of the thalamus between the SLE patients and the control subjects. The BDav value in the SLE patient group was robustly correlated with the Dav values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of Dav and FA values in the SLE patient group. Conclusion Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BDav and Dav values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Better understanding of its pathophysiology has led to the development of targeted therapies that have dramatically improved outcomes. The key to therapeutic success lies in identifying individuals who will have severe destructive disease as early as possible, so that effective treatment can be initiated before irreversible damage occurs. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP antibody testing in rheumatoid arthritis, with an emphasis on diagnostic performance, prognostic capability, and relevance to pathogenesis and new treatment paradigms in rheumatoid arthritis.

Objective To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic, persistently antiphospholipid antibody (aPL)–positive individuals (those with positive aPL but no vascular and/or pregnancy events). Methods The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double-blind, placebo-controlled clinical trial in which asymptomatic, persistently aPL-positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo. In a separate observational and parallel study, asymptomatic, persistently aPL-positive individuals who were taking aspirin or declined randomization were followed up prospectively. Results In the APLASA study, 98 individuals were randomized to receive aspirin or placebo (mean ± SD followup period 2.30 ± 0.95 years), of whom 48 received aspirin and 50 received placebo. In the observational study, 74 nonrandomized individuals were followed up prospectively (mean ± SD followup period 2.46 ± 0.76 years); 61 received aspirin and 13 did not. In the APLASA study, the acute thrombosis incidence rates were 2.75 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for the placebo-treated subjects (hazard ratio 1.04, 95% confidence interval 0.69–1.56) (P = 0.83). Similarly, in the observational study, the acute thrombosis incidence rates were 2.70 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for those not treated with aspirin. All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and/or systemic autoimmune disease at the time of thrombosis. Conclusion Our results suggest that asymptomatic, persistently aPL-positive individuals do not benefit from low-dose aspirin for primary thrombosis prophylaxis, have a low overall annual incidence rate of acute thrombosis, and develop vascular events when additional thrombosis risk factors are present.

Objective To assess the association between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus (SLE). Methods The study population consisted of English-speaking adults who met American College of Rheumatology (ACR) criteria for SLE and had at least 1 serum sample stored in the Hospital for Special Surgery Autoimmune Registry and Repository. Demographic and clinical information was obtained, and patients completed the neuropsychological test battery recommended by the ACR, the Center for Epidemiologic Studies Depression Scale, and the Spielberger State-Trait Anxiety Inventory. Cognitive impairment was defined as scores >1.5 SD below the mean of age-matched published normative data on at least 2 neuropsychological tests. Sera were tested for NR2a antibodies by enzyme-linked immunosorbent assay. Performance on neuropsychological tests was compared between NR2a-positive and NR2a-negative patients. Results Of the 93 patients, 24 (25.8%) were positive for NR2a antibodies. Of the 48 patients who were cognitively impaired based on test results, 31% were positive for NR2a antibodies, compared with 20% of those who were not cognitively impaired (P = 0.24). Among antibody-positive patients, the mean ± SD number of neuropsychological tests with abnormal results was 2.3 ± 2.2, compared with 2.0 ± 1.8 in the antibody-negative group (P = 0.59). Similar nonsignificant differences were found when impairment was defined using a more stringent definition (i.e., test scores >2.0 SD below the mean) and using a neuropsychologist's clinical ratings. No association was detected between NR2a antibody positivity and depressive symptoms (P = 0.73) or anxiety (P = 0.42). Conclusion No significant association was found between NR2a antibody positivity and cognitive dysfunction, depressive symptoms, or anxiety. These results indicate that the presence of these antibodies alone does not have a direct effect on cognitive functioning or any other neuropsychiatric manifestation of SLE.

Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice.Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study.RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy.These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.

Systemic lupus erythematosus (SLE) in children is a chronic multi-system disease with wide ranging effects on their quality of life (QOL). While SLE’s impact on different arenas of life and well-being has been extensively examined in the adult population, its effect on children has not received adequate attention. This paper briefly discusses the multi-dimensional aspect of QOL, the biopsychosocial implica-tions of SLE, factors complicating QOL measurement in the affected population, and the different generic and disease-specific scales used for measuring QOL and related constructs, and it also highlights the need for SLE-specific pediatric QOL instruments.

The objective of this study is to assess relationship of systemic lupus erythematosus (SLE) activity with quality of life (QOL) and physical function and determine which is more closely correlated with SLE activity in children; and identify factors critical to children’s QOL. In this cross-sectional study, children with SLE and parents completed corresponding versions of physical function (Childhood Health Assessment Questionnaire -CHAQ), and QOL (Pediatric Quality of Life Inventory -PedsQL Generic/Rheumatology modules) questionnaires. SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), severity, self-concept and socioeconomic status (SES) were measured. For 24 children, CHAQ scores significantly correlated with SLEDAI (rho = 0.4, p = 0.04), SDI (rho = 0.6, p = 0.004), and associated with severity (p = 0.03). PedsQL scores did not significantly correlate with above parameters. Higher self-concept/SES correlated (p, 0.05) with better physical function and QOL. For 19 parents, the only significant correlation was between SLEDAI and Worry domain - Rheumatology module (rho = 0.5, p = 0.01). Lack of strong correlation of disease activity with QOL and physical function suggests that they are different constructs with partial overlap, and should be considered collectively while evaluating the impact of SLE on children/families. Self-concept and SES should be assessed while measuring QOL in children. Larger sample is required to confirm results.

Neuropsychiatric syndromes associated with systemic lupus erythematosus are common, but diverse in etiology and presentation. Cognitive dysfunction is prevalent among these syndromes, but exhibit a significant degree of heterogeneity both within and between patient variability. Earlier studies of SLE-associated cognitive dysfunction addressed its identification and description. Common associations were repeatedly acknowledged, including concomitant or past neuropsychiatric disease, use of corticosteroids, disease activity, emotional disturbance, and antiphospholipid antibodies. The past several years have focused more on elucidating the relative strengths of various risk associations, patterns of cognitive abnormalities, both cross-sectionally and longitudinally (ie, clinical course), and novel means to identify cognitive impairment, both functionally and biologically.

Objective To conduct a pilot study to identify rheumatologists' treatment preferences for first-line rheumatoid arthritis (RA) therapy and determine whether pharmacoeconomic variables modify physician choice(s). Methods A questionnaire describing 3 different RA scenarios was mailed to American College of Rheumatology members within 4 geographic regions of the US. Physicians were asked to identify their choice(s) of first-line therapy for each of the cases, first taking cost into consideration, second without considering the influence of cost, and third identifying the therapy that would be chosen for either themselves or a family member. Results Three hundred seventy-five questionnaires out of a total of 994 (37.7%) were returned between 3/12/00 and 4/25/00. Hydroxychloroquine was the most commonly cited medication for a mild disease activity/severity presentation, and methotrexate for a moderate-to-severe disease activity/severity presentation. For the severe disease activity/severity presentation, when cost was not considered, 217 (65%) rheumatologists included new disease-modifying antirheumatic drugs (leflunomide, etanercept, and infliximab) in their choice of first-line agents; this number decreased to 47 (14%) when cost was a consideration. Conclusion Pharmacoeconomics appear to play a dominant role in rheumatologists' choice of treatment regimens, at times contrary to the physician's perception of the effectiveness of a drug. Future studies should address physician preferences in more depth with respect to cost and its various components.

The Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) is a novel measure of vision-related quality of life (QOL) and function in children. We aim to determine the validity of the EYE-Q in childhood uveitis.We abstracted medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE-Q, parents and patients completed questionnaires on overall QOL (Pediatric Quality of Life Inventory [PedsQL]), and physical functioning (Childhood Health Assessment Questionnaire [C-HAQ]).Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%), and cataracts (49%). Children with vision loss in their better eye (visual acuity [VA] 20/50 or worse) had worse EYE-Q (P = 0.006) and PedsQL (P = 0.028) scores, but not C-HAQ scores. The EYE-Q moderately correlated with logMAR VA (rs = -0.43), PedsQL (rs = 0.43), and C-HAQ (rs = -0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and C-HAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE-Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE-Q had strong test-retest reliability (rs = 0.75).The EYE-Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision-related function.

Patient satisfaction is influenced by multiple factors, and different populations are expected to define satisfaction in terms of their novel perspectives. Despite growing interest in patient satisfaction, an extensive literature search reveals no studies of nursing home residents' satisfaction with respect to medical care. In an initial qualitative study using transcripts of interviews conducted as part of a state quality control mandate, categories are identified that make up this population's construct of satisfaction and dissatisfaction. These categories serve as building blocks for designing future studies investigating these issues and allowing for comparison of nursing home residents' ideas of satisfaction and dissatisfaction to other older patients, including those in an outpatient geriatric setting.

To determine the validity and reliability of a novel questionnaire to measure vision-related quality of life (VRQOL) in children ages 8-18 years for use in juvenile idiopathic arthritis (JIA)-associated uveitis: the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q).Several steps validated the EYE-Q. We interviewed experts and children on how vision affects a child's activities. We developed new items and selected relevant items from existing instruments. We administered initial versions of the EYE-Q to normal-sighted children and those with JIA-associated uveitis. For this study, children with various (or no) ocular conditions were recruited from a clinical population. Visual acuity and contrast sensitivity were performed, and the EYE-Q and Pediatric Quality of Life Inventory (PedsQL) were administered. The EYE-Q was repeated 10 days later. Patients, parents, and physicians rated vision severity.Of 120 patients, 48% were female, 46.7% had no visual impairment, and 53.3% had bilateral eye involvement. The mean age was 11.3 years. There were significant differences in the measures based on visual acuity (P0.001). Children with more severe visual acuity and bilateral eye involvement had worse EYE-Q scores (P0.001). There were significant associations between the EYE-Q and PedsQL (r = 0.375), repeat EYE-Q (r = 0.864), and clinical measures of ocular disease (r = -0.620).Our study provides evidence of the validity and reliability of the EYE-Q in the measurement of VRQOL. The EYE-Q may complement clinical measures of visual impairment and overall QOL and become an important tool in the assessment of QOL in JIA-associated uveitis.

Background Studies of quality of life (QOL) in children with juvenile idiopathic arthritis (JIA) have focused on changes in musculoskeletal function secondary to arthritis. The role of visual functionality as a result of JIA-associated uveitis and its complications has not been examined. We evaluated the individual impact of physical and visual disability on QOL in children with and without uveitis. Methods We administered patient-based questionnaires that measured visual function, physical function, and overall QOL to 27 children with JIA or idiopathic uveitis. Demographic data, assessed joint involvement, and reviewed medical records were recorded. Groups with and without uveitis were compared for differences in arthritis and uveitis disease characteristics with use of the Wilcoxon-Mann-Whitney, χ 2 , and Fisher exact tests. Associations between physical or visual function, and overall QOL were measured with use of Pearson's correlation coefficient. Results Of 27 patients, 85.2% had had arthritis and 51.9% had had uveitis. The group without uveitis had increased morning stiffness ( p = 0.036). Patients with uveitis reported more eye redness ( p = 0.033) and photophobia ( p = 0.013) than those without uveitis. We observed moderate associations between overall QOL and visual function in the uveitis group ( r = −0.579) and overall QOL and physical function in the nonuveitis group ( r = −0.562). Conclusions This study demonstrates that visual impairment is an important component of QOL in children with uveitis. It suggests that QOL studies should incorporate both visual and physical function measures in their analyses, especially because many children with JIA also suffer from uveitis and visual impairment.

Pediatric rheumatic diseases with predominant musculoskeletal involvement such as juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis(JDM) can cause considerable physical functional impairment and significantly affect the children's quality of life (QOL). Physical function, QOL, health-related QOL (HRQOL) and health status are personal constructs used as outcomes to estimate the impact of these diseases and often used as proxies for each other. The chronic, fluctuating nature of these diseases differs within and between patients, and complicates the measurement of these outcomes. In children, their growing needs and expectations, limited use of age-specific questionnaires, and the use of proxy respondents further influences this evaluation. This article will briefly review the different constructs inclusive of and related to physical function, and the scales used for measuring them. An understanding of these instruments will enable assessment of functional outcome in clinical studies of children with rheumatic diseases, measure the impact of the disease and treatments on their lives, and guide us in formulating appropriate interventions.

Objective Pediatric systemic lupus erythematosus (SLE) is a chronic fluctuating disease that significantly impacts quality of life (QOL). There is no pediatric SLE-specific health-related QOL (HRQOL) scale. Our objective was to develop and validate a new pediatric SLE-specific HRQOL scale. Methods We developed the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY) based on results of qualitative research of children with SLE and their parents. SMILEY has parallel child and parent reports with a 5-faces scale for responses. SMILEY comprises 4 domains: effect on self, limitations, social, and burden of SLE. In this cross-sectional study, we examined face, content, construct, and concurrent validity; internal consistency; test–retest reliability; and child-parent agreement for SMILEY. Children ≤18 years of age with SLE and their parents completed corresponding child and parent SMILEY reports, as well as other QOL and physical function scales. Qualified physicians assessed SLE activity, damage, and severity. Results Eighty-six children with SLE and 80 parents participated. SMILEY was found to have face, content, construct, and concurrent validity (Spearman's rank correlation [rs] ≥0.4); test–retest reliability (intraclass correlation coefficient [ICC] 0.9); and internal consistency (α = 0.9). Moderate agreement was found between child and parent SMILEY reports (ICC 0.7, rs = 0.5, P < 0.001). Conclusion SMILEY is a brief, easily understood, valid, and reliable pediatric SLE-specific QOL scale. Because SMILEY assesses children's self-perception of QOL as impacted by SLE, we predict that it will have great utility in clinical practice, clinical trials, and outcomes research.

Systemic lupus erythematosus (SLE) in children is a chronic multisystem disease with wide ranging effects on their quality of life (QOL). While SLE's impact on different arenas of life and well-being has been extensively examined in the adult population, its effect on children has not received adequate attention. This review discusses the multidimensional aspect of QOL, the biopsychosocial implications of SLE, factors complicating QOL measurement in the affected population, and the different generic and disease-specific scales used for measuring QOL and related constructs. Until now, there have not been any pediatric SLE-specific health-related QOL (HRQOL) scales. A section is devoted to a novel instrument developed specifically for measuring QOL in pediatric lupus called the Simple Measure of the Impact of Lupus Erythematosus in Youngsters© (SMILEY©). SMILEY© is a brief, easily understood, valid, reliable and internally consistent pediatric SLE-specific QOL scale and will be a useful adjunct to clinical trials and outcomes research. Lupus (2007) 16, 663—669.

The authors developed an 8-week psychoeducational group intervention for patients with systemic lupus erythematosus (SLE) who reported cognitive dysfunction but were not globally impaired on neuropsychological testing. Results of a nonrandomized, uncontrolled pilot study of this program in 17 women with SLE suggest that metamemory and memory self-efficacy improve after participation. One hundred percent retention throughout the study further suggests that patients with SLE are willing and capable of successfully completing the program.

Nervous system disease in systemic lupus erythematosus (SLE) is manifested by a wide variety of clinical manifestations. Despite the development of a universal classification for neuropsychiatric (NP) lupus in 1999, there continues to be considerable variability in the reported prevalence of NP syndromes between different lupus cohorts. Due to the lack of specificity of individual NP manifestations, non-SLE causes such as complications of therapy and co-morbidities must be considered in advance of attributing the event to one or more primary immunopathogenic mechanisms. These include intracranial microangiopathy, autoantibodies to neuronal and non-neuronal antigens, and the generation of proinflammatory cytokines and mediators. The diagnosis of NP-SLE remains largely one of exclusion and is approached in individual patients by thorough clinical evaluation, supported when necessary by autoantibody profiles, diagnostic imaging, electrophysiologic studies and objective assessment of cognitive performance. Given the diversity in clinical manifestations, the management is tailored to the specific needs of individual patients. In the absence of controlled studies, the use of symptomatic therapies, immunosuppressives, anticoagulants and non-pharmacologic interventions is supported by case series and clinical experience.

Age bias has been reported to result in undertreatment of elderly patients with various medical conditions. We investigated whether a similar bias exists in the treatment of elderly patients with rheumatoid arthritis (ELDRA) compared to matched younger controls (YRA).We performed an analysis of our RA clinical research registry to determine whether any differences exist between ELDRA and YRA patients with respect to use of combination disease modifying antirheumatic drugs (DMARD), biologic agents, corticosteroids, and nonsteroidal antiinflammatory drugs (NSAID). We also determined whether any difference in clinical status could be identified.Forty-nine female ELDRA subjects (age70 yrs) with insurance were matched for sex, insurance status, and duration of disease to YRA subjects (60 yrs). No statistically significant difference was noted in number of DMARD currently in use (1.24 +/- 0.78 vs 1.24 +/- 0.69, p = 1.00), or number of patients using biologic agents (25 vs 30; p = 0.31), corticosteroids (16 vs 11; p = 0.26), or NSAID (26 vs 36; p = 0.06). ELDRA and YRA patients also reported similar pain (judged using a visual analog scale, VAS; 3.5 +/- 2.6 cm vs 3.4 +/- 2.2 cm), fatigue (VAS 3.2 +/- 2.7 cm vs 3.9 +/- 2.9 cm), global assessment (VAS 2.8 +/- 2.2 cm vs 3.5 +/- 2.6 cm), and Health Assessment Questionnaire disability scores (0.82 +/- 0.5 vs 0.73 +/- 0.5).In this cohort of elderly patients with RA, we detected no bias in the use of RA treatment compared with younger controls. Clinical RA measures also showed that these elderly patients with RA were faring at least as well as the younger controls; they were not relatively undertreated.

Paediatric systemic lupus erythematosus (SLE) is associated with significant morbidity and has biopsychosocialimplications resulting from the disease and its treatment. The aim of this study was to identify domains of quality of life (QOL) impacted by SLE in children. Children with SLE and their parents were asked a single open-ended question related to lupus. Themes derived from children’s responsesfocused primarily on coping and maintaining control of their life despite SLE. Themes from the parents’ responses were twofold: a) efforts to cope with their child having SLE; and b) appreciation/sadness in connection with their children’s coping process. Qualitative exploration of differentfacets of QOL in these children is critical for the understandingof specific factors that assist/ease the coping process and formulating interventions for improving children’s/family’s self-efficacy and disease management.

Rheumatoid arthritis (RA) is a prevalent inflammatory joint disease that afflicts up to 1% of the American population. 1 The consequences of this disease may beirreversible joint damage and physical disability, 2 which eventually may lead to work disability. 3 Although therapeutic agents are available to help minimize symptoms and delay disease progression, RA is chronic andincurable. When therapeutic agents fail to controlprogressive joint damage, surgery to repair or replace joints is required.

To determine the incidence of disease flare during the first year of etanercept treatment for 88 patients with rheumatoid arthritis (RA) and compare it with the incidence of flare in those same patients in the year before etanercept use.The outpatient clinic charts of all patients with RA who were prescribed etanercept in or before September 1999, who also had at least one year's follow up in the same outpatient clinic, were surveyed. The primary outcome measure was the number of disease flares in one year before and after etanercept use. The secondary outcome measures included the number of patients who did and did not flare, how flares were treated, and the drug alterations that were necessary during the same two time intervals.The total number of flares for all patients in the year before etanercept treatment was 214 (mean (SD) 2.43 (1.75)). The number of flares in the first year of etanercept treatment decreased to 83 (mean 0.94 (1.07)) (p0.0001). The total number of patients who had at least one flare in the year before etanercept use was 80; eight had no flares. In their first year of etanercept treatment, 50 patients had at least one flare; 38 had no flares (p0.0001). Twenty one patients (24%) stopped using etanercept before completing one year's treatment.This study of patients with RA in the "real world" shows that etanercept is effective in reducing the number of RA flares.

Background Infliximab is a chimeric, monoclonal antibody against tumour necrosis factor (TNF) alpha, recently developed to complement methotrexate therapy in RA patients with a less than optimal response to treatment. To date it has only been studied in clinical trials. Objectives To describe referral patterns, patient response to treatment, and adverse events in a cohort of RA patients treated with infliximab in a real world setting. Methods Patients who had received their first dose of infliximab between 1/00 and 6/00 were included to ensure the possibility of at least 6 months of drug exposure. We evaluated patients at baseline, and followed them prospectively every 2 months for a total of 6 months. Patients completed several questionnaires regarding RA history, treatment, and disease activity (HAQ, pain, fatigue, tender and swollen joint counts) at each infusion. All subjects were contacted between infusions for reporting of side effects. Results 36 patients were treated with infliximab between January 1 – June 30, 2000 (female n = 33, mean age = 63 ± 12.9 y, disease duration = 15.3 ± 10.2 y). They had previously failed an average of 3 DMARDs. 24 patients were on oral steroids at baseline. 16 patients received infliximab without concurrent MTX. 12 of 36 patients discontinued treatment before 6 months. Discontinuation reasons were inadequate response (n = 5), repeated episodes of dyspnea (n = 3), asthma (n = 1), chest tightness (n = 1), phlebitis (n = 1), and patient noncompliance (n = 1). Table 1 shows individual measures of disease activity in 24 patients who completed 6 months of infliximab. We detected a significant improvement in HAQ scores, and trends toward improvement in pain scores and tender joint counts. HAQ scores improved in 19/24, stiffness in 14/24, pain in 13/24, fatigue in 13/24, tender joint counts in 13/24 and swollen joints in 15/24 of patients. Since initiating infliximab therapy, of the 36 patients receiving 198 infusions, 18 patients reported a total of 33 adverse events (headaches n = 8, nausea n = 2, abdominal pain n = 2, chest pain n = 1, chills n = 2, dyspnea n = 3, myalgias n = 3, pruritis n = 4, fatigue n = 3, and rash n = 5). Conclusion Infliximab is often used in more difficult RA patients (older, long-standing RA, multiple DMARD failures). This referral pattern may explain the increased incidence of adverse events and suboptimal clinical response noted in our cohort. However, our results suggest a trend towards rapid, clinically important improvement in measures of disease activity. Ongoing follow-up of this growing group of patients will provide necessary information regarding the appropriate role of infliximab in the treatment of RA.

Background Differences in physician evaluations, heterogeneity of disease and within patient variability contribute to the lack of a uniform definition of RA flare. As a result, a standardised approach to treatment of RA flare is not likely to exist. However, when presented with the same case scenario, rheumatologists’ choice of treatment should establish a standard of care. Objectives To identify physician medication preferences and the role of steroids in the treatment of rheumatoid arthritis (RA) flare. Methods A questionnaire describing two versions of the same case of a previously stable RA patient maintained on 17.5 mg/week of methotrexate (MTX), hydroxycholoroquine and NSAIDs, and presenting with signs and symptoms suggesting an increase in disease activity was developed; the second version included the addition of a standing dose of 5 mg of prednisone. Rheumatologists were asked to identify their choice (s) of first-line therapy for each version of the case. The questionnaire was mailed to rheumatologists (adult practice) (n = 995) who were identified through the ACR membership directory. Only physicians currently in practice were included. Results 375 (37.7%) questionnaires were returned between March 12, 2000 and April 25, 2000. 280 qualified for analysis. The results (A: No baseline steroid use, B: 5 mg/d prednisone) below illustrates the frequency with which rheumatologists cited each drug or drug combination as their first choice of treatment for each scenario. The most common change in medication for both cases was addition/adjustment of prednisone (A: n = 248; B: n = 229, C2 = 4.58, p = 0.03). Of those given oral steroids for a limited amount of time, mean increase in daily dose of prednisone was A: 16.4 ± 12.5 mg, B: 18.3 ± 12.5 mg. Duration of increased dose was highly variable ranging from 1 day (bolus) to 3 months. Some rheumatologists chose to continue increased prednisone indefinitely, (A: n = 19; B: n = 14). There appeared to be no consistent relationship between steroid dose and duration. For both cases there was no difference in the number of rheumatologists who increased MTX dose (A: n = 84; B: n = 85). The number of rheumatologists who added another DMARD to the patient’s regimen were more in group A and differed significantly (x2 = 3.97, p = 0.046) from group B. Similarly, rates of initiation of anti-TNF therapy was higher in group A (x2 = 4.68, p = 0.03). However, rates of addition of leflunomide showed no statistically significant difference. Conclusion Though the cases presented were accepted by rheumatologists as RA flare requiring intervention; no consistency of practice other than an increase in steroids could be identified. Further studies determining optimal therapy for increases in RA activity are necessary.

Background Infliximab is a chimeric monoclonal anti-TNF antibody developed to treat rheumatoid arthritis (RA) patients who have had a less than optimal response to previous therapy. It has been recommended that infliximab be given concomitantly with methotrexate (MTX) to prevent the development of autoantibodies. Objectives To identify clinical response and adverse events in RA patients treated with infliximab for a period of 6 months, with a subgroup analysis of MTX-receiving (MTX-R) and non-receiving (MTX-NR) patients. Methods RA patients receiving infliximab at our ambulatory infusion unit completed questionnaires regarding RA history, treatment, and measures of disease activity (HAQ) at baseline, and at 2 weeks, 8 weeks, and every 2 months thereafter. Patients were queried about side effects experienced between infusions. ANOVA statistics were used for comparison. Results 36 patients were started on infliximab between January–July 2000 (F/M: 33/3, mean age: 63 + 12.9 y, mean disease duration: 15.3+10.2 y) and 24 patients completed 6 months of treatment. Patients had failed an average of 3 DMARDs prior to infliximab. HAQ scores for 24/36 patients who completed 6 months of treatment significantly improved from 1.95+0.60 to 1.21+0.67 (p = 0.0002). In subgroup analysis, the baseline characteristics of MTX-R and MTX-NR groups were similar with respect to age and disease duration. Twenty (56%) patients were not receiving MTX due to history of adverse event, allergic reaction or patient refusal. For patients who completed 6 months of infliximab: in MTX-R group, HAQ scores for 14/24 patients improved from 1.99+0.58 to 1.34+0.54 (p = 0.005); and in MTX-NR group HAQ scores for 10/24 patients improved from 1.89+0.65 to 1.05+0.81 (p = 0.02). During 6 months of follow-up, 3/10 (30%) of MTX-NR and 9/14 (64%) of MTX-R patients had a total of 23 adverse events after 198 infusions. There was no difference between the 2 subgroups with respect to the type of adverse events. Ten MTX-NR patients discontinued treatment before 6 months (adverse events: 7, inadequate response to treatment: 2, and non-compliance:1. Only 2 MTX-R patients discontinued treatment prior to 6 months, due to inadequate response. Conclusion Following 6 months of infliximab treatment, RA patients with long-standing disease demonstrate a clinically important and statistically significant improvement in functional disability as measured by HAQ. However, our subgroup analysis suggests that infliximab administered without MTX carries a higher rate of discontinuation. These findings may be due to patient characteristics or our small sample size. Continuing follow-up of patients receiving infliximab in the absence of MTX will provide a better understanding of the true risk/benefit of infliximab used alone.