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Rina Mina,
Marisa S Klein-Gitelman,
Shannen Nelson,
B Anne Eberhard,
Gloria Higgins,
Nora G Singer,
Karen Onel,
Lori Tucker,
Kathleen M O'Neil,
Marilynn Punaro,
Deborah M Levy, Kathleen Haines,
Alberto Martini,
Nicolino Ruperto,
Daniel Lovell,
Hermine I Brunner
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ABSTRACT: OBJECTIVES: This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). METHODS: The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. RESULTS: The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. CONCLUSIONS: The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.
Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
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Michiko Suzuki,
Kristina Wiers,
Elizabeth B Brooks,
Kenneth D Greis, Kathleen Haines,
Marisa S Klein-Gitelman,
Judyann Olson,
Karen Onel,
Kathleen M O'Neil,
Earl D Silverman,
Lori Tucker,
Jun Ying,
Prasad Devarajan,
Hermine I Brunner
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ABSTRACT: Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), alpha1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.
Pediatric Research 02/2009; 65(5):530-6. · 2.70 Impact Factor
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ABSTRACT: 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.
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.
Eighty-six children with SLE and 80 parents participated. SMILEY was found to have face, content, construct, and concurrent validity (Spearman's rank correlation [r(s)] >/=0.4); test-retest reliability (intraclass correlation coefficient [ICC] 0.9); and internal consistency (alpha = 0.9). Moderate agreement was found between child and parent SMILEY reports (ICC 0.7, r(s) = 0.5, P < 0.001).
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.
Arthritis & Rheumatism 11/2007; 57(7):1165-73. · 7.87 Impact Factor
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Chung-E Tseng,
Jill P Buyon,
Mimi Kim,
H Michael Belmont,
Meggan Mackay,
Betty Diamond,
Galina Marder,
Pamela Rosenthal, Kathleen Haines,
Virginia Ilie,
Steven B Abramson
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ABSTRACT: Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares.
In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week.
Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring <or=90 days from randomization revealed that 6 occurred in patients taking placebo and none occurred in patients taking prednisone (P = 0.007). Severe flares resulted in an increase in the prednisone dosage to >40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment.
These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare.
Arthritis & Rheumatism 11/2006; 54(11):3623-32. · 7.87 Impact Factor
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ABSTRACT: To assess the response and adverse events associated with infliximab treatment for refractory, noninfectious pediatric uveitis.
Retrospective noncomparative case series of pediatric patients with refractory uveitis treated with infliximab.
Six patients were identified. Diagnoses of the participants included idiopathic uveitis (n = 1), juvenile rheumatoid arthritis with uveitis (n = 3), idiopathic retinal vasculitis with uveitis (n = 1), and bilateral pars planitis, with vitreitis and papillitis of the left eye (n = 1). Uveitis developed in the patients (5 female, 1 male) at a mean age of 9.0 years (+/-5.0 years; range, 0.9-14.8 years). All patients had bilateral eye involvement. These patients were refractory to or dependent on topical steroids (n = 4), oral prednisone (n = 3), or both, and were also refractory to the following therapies: methotrexate (n = 6), cyclosporine (n = 3), mycophenolate mofetil (n = 3), etanercept (n = 3), and daclizumab (n = 1).
All patients initially received infliximab at doses between 5 and 10 mg/kg at 2- to 4-week intervals, and then were maintained at 4- to 8-week intervals at doses of 5 to 18 mg/kg. Mean follow-up time on treatment has been 48.1 weeks (+/-14.9 weeks; range, 32-74 weeks).
Primary outcome measures included the quantitative measurement of the amount of ocular inflammation in different locations within the eye. Patients were monitored for infusion reactions as well as other potential side effects. The children's clinical status, complete blood counts, and liver function panels were monitored by pediatric rheumatologists every 6 weeks.
All 6 patients showed reduction in their intraocular inflammation after infliximab therapy was initiated. Furthermore, control of ocular inflammation was achieved while receiving infliximab therapy. Topical and systemic corticosteroids were able to be discontinued in all patients except for 1 patient, who is currently weaning off prednisone. The only adverse reactions seen were the development of vitreous hemorrhage in 1 patient and a case of transient upper respiratory infusion reaction. No patient has had to discontinue treatment.
Infliximab seems to be an effective agent for the treatment of refractory pediatric uveitis without apparent serious toxicity in this series of patients.
Ophthalmology 03/2006; 113(2):308-14. · 5.45 Impact Factor
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ABSTRACT: Allergy to polymethyl methacrylate bone-cement or its components is unusual. Because of the potential for an inflammatory response in an allergic patient and the possibility of pain and loosening if a cemented implant is used, it is imperative to identify patients with this allergy to modify their treatment. We report the case of an otherwise healthy 60-year-old woman who needed a total knee arthroplasty and who had an allergy to methyl methacrylate bone-cement identified preoperatively. The appropriate evaluation for a patient who is suspected to have an allergy to bone-cement or its components is reviewed.
The Journal of Arthroplasty 10/2002; 17(6):788-91. · 2.38 Impact Factor
