Kathleen M O'Neil

Publications (23)72.88 Total impact

• Source

  Available from: Claudia Bracaglia

  Dataset: Vasculitis Criteria

  Silvia Magni Manzoni, Loredana Lepore, Jordi Anton, Polyxeni Pratsidou, Stella Garay, Susan Nielsen, Graciela Espada, Angelo Ravelli, Ruben Cuttica, Pierre Quartier, [......], Ricardo Russo, Iris Vilca, Claudia Bracaglia, Paul Brogan, Kjell Tullus, David A Cabral, Arvind Bagga, Rolando Cimaz, Valda Stanevicha, Gerd Horneff
• Article: Validation of the systemic lupus erythematosus responder index for use in juvenile-onset systemic lupus erythematosus.

  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
  [show abstract] [hide abstract]
  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
• Article: Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology.

  Norman T Ilowite, Christy I Sandborg, Brian M Feldman, Alexi A Grom, Laura E Schanberg, Edward H Giannini, Carol A Wallace, Rayfel Schneider, Kathleen Kenney, Beth S Gottlieb, [......], Michael L Miller, Diana Milojevic, Kathleen M O'Neil, Marilynn G Punaro, Natasha M Ruth, Nora G Singer, Richard K Vehe, James Verbsky, Amy Woodward, Lawrence S Zemel
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT). METHODS: The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as [GREATER-THAN OR EQUAL TO] 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision. RESULTS: The panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for [GREATER-THAN OR EQUAL TO] 3 days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined. CONCLUSION: The expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.
  Pediatric Rheumatology 08/2012; 10(1):31. · 1.44 Impact Factor
• Article: Do Adult Disease Severity Subclassifications Predict Use of Cyclophosphamide in Children with ANCA-associated Vasculitis? An Analysis of ARChiVe Study Treatment Decisions.

  Kimberly Morishita, Jaime Guzman, Peter Chira, Eyal Muscal, Andrew Zeft, Marisa Klein-Gitelman, America G Uribe, Leslie Abramson, Susanne M Benseler, Anne Eberhard, [......], Andreas Reiff, Margalit Rosenkranz, Kenneth N Schikler, Rosie Scuccimarri, Nora G Singer, Anne M Stevens, Heather van Mater, Dawn M Wahezi, Andrew J White, David A Cabral
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC). METHODS: We applied the European Vasculitis Study (EUVAS) and Wegener's Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, "cyclophosphamide" and "no cyclophosphamide." Pearson's chi-square and Kendall's rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis. RESULTS: In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p < 0.001, Kendall's tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p < 0.001, Kendall's tau-b 0.689, p < 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC. CONCLUSION: In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.
  The Journal of Rheumatology 08/2012; 39(10):2012-2020. · 3.69 Impact Factor
• Article: Increased sensitivity of the European medicines agency algorithm for classification of childhood granulomatosis with polyangiitis.

  América G Uribe, Adam M Huber, Susan Kim, Kathleen M O'Neil, Dawn M Wahezi, Leslie Abramson, Kevin Baszis, Susanne M Benseler, Suzanne L Bowyer, Sarah Campillo, [......], Eyal Muscal, Lorien Nassi, Egla Rabinovich, Andreas Reiff, Margalit Rosenkranz, Kenneth N Schikler, Nora G Singer, Steven Spalding, Anne M Stevens, David A Cabral
  [show abstract] [hide abstract]
  ABSTRACT: Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.
  The Journal of Rheumatology 05/2012; 39(8):1687-97. · 3.69 Impact Factor
• Article: Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma.

  Suzanne C Li, Kathryn S Torok, Elena Pope, Fatma Dedeoglu, Sandy Hong, Heidi T Jacobe, C Egla Rabinovich, Ronald M Laxer, Gloria C Higgins, Polly J Ferguson, [......], Victoria Cartwright, Michael Cidon, Christi J Inman, Rita Jerath, Kathleen M O'Neil, Sheetal Vora, Andrew Zeft, Carol A Wallace, Norman T Ilowite, Robert C Fuhlbrigge
  [show abstract] [hide abstract]
  ABSTRACT: Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS.
  Arthritis care & research. 04/2012; 64(8):1175-85.
• Article: Assessing the performance of the Birmingham Vasculitis Activity Score at diagnosis for children with antineutrophil cytoplasmic antibody-associated vasculitis in A Registry for Childhood Vasculitis (ARChiVe).

  Kimberly Morishita, Suzanne C Li, Eyal Muscal, Steven Spalding, Jaime Guzman, America Uribe, Leslie Abramson, Kevin Baszis, Susanne Benseler, Suzanne Bowyer, [......], Lorien Nassi, Kathleen M O'Neil, Egla Rabinovich, Suzanne E Ramsey, Andreas Reiff, Margalit Rosenkranz, Kenneth Schikler, Anne Stevens, Dawn Wahezi, David A Cabral
  [show abstract] [hide abstract]
  ABSTRACT: There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician's global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool (www.vasculitis.org). Spearman's rank correlation coefficient (r(s)) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR. A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0-40). The BVAS v.3 correlations were r(s) = 0.379 (95% CI 0.233 to 0.509) with PGA, r(s) = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and r(s) = 0.403 (95% CI 0.253 to 0.533) with ESR. Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.
  The Journal of Rheumatology 02/2012; 39(5):1088-94. · 3.69 Impact Factor
• Article: Inactive disease and remission in childhood-onset systemic lupus erythematosus.

  Rina Mina, Marisa S Klein-Gitelman, Angelo Ravelli, Michael W Beresford, Tadej Avcin, Graciela Espada, B Anne Eberhard, Laura E Schanberg, Kathleen M O'Neil, Clovis A Silva, Gloria C Higgins, Karen Onel, Nora G Singer, Emily von Scheven, Lisa F Imundo, Shannen Nelson, Edward H Giannini, Hermine I Brunner
  [show abstract] [hide abstract]
  ABSTRACT: To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE). Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL). While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL. Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE.
  Arthritis care & research. 01/2012; 64(5):683-93.
• Article: Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

  Carol A Wallace, Edward H Giannini, Steven J Spalding, Philip J Hashkes, Kathleen M O'Neil, Andrew S Zeft, Ilona S Szer, Sarah Ringold, Hermine I Brunner, Laura E Schanberg, [......], Marilynn G Punaro, Peter Chira, Beth S Gottlieb, Gloria C Higgins, Norman T Ilowite, Yukiko Kimura, Stephanie Hamilton, Anne Johnson, Bin Huang, Daniel J Lovell
  [show abstract] [hide abstract]
  ABSTRACT: To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.
  Arthritis & Rheumatism 12/2011; 64(6):2012-21. · 7.87 Impact Factor
• Source

  Available from: Claudia Bracaglia

  Article: EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation.

  Nicolino Ruperto, Seza Ozen, Angela Pistorio, Pavla Dolezalova, Paul Brogan, David A Cabral, Ruben Cuttica, Raju Khubchandani, Daniel J Lovell, Kathleen M O'Neil, [......], Ricardo Russo, Iris Vilca, Kjell Tullus, Rolando Cimaz, Gerd Horneff, Jordi Anton, Stella Garay, Susan Nielsen, Giancarlo Barbano, Alberto Martini
  [show abstract] [hide abstract]
  ABSTRACT: To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis <or=18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, kappa-agreement) using as 'gold standard' the final consensus classification or original treating physician diagnosis. A total of 1183/1398 (85%) samples collected were available for analysis: 827 HSP, 150 c-PAN, 60 c-WG, 87 c-TA and 59 c-other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c-vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with a kappa-agreement of 0.96 for HSP (95% CI 0.84 to 1), 0.88 for c-WG (95% CI 0.76 to 0.99), 0.84 for c-TA (95% CI 0.73 to 0.96) and 0.73 for c-PAN (95% CI 0.62 to 0.84), with an overall kappa of 0.79 (95% CI 0.73 to 0.84). EULAR/PRINTO/PRES propose validated classification criteria for HSP, c-PAN, c-WG and c-TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis.
  Annals of the rheumatic diseases 04/2010; 69(5):790-7. · 8.11 Impact Factor
• Article: Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood.

  David A Cabral, América G Uribe, Susanne Benseler, Kathleen M O'Neil, Philip J Hashkes, Gloria Higgins, Andrew S Zeft, Daniel J Lovell, Daniel J Kingsbury, Anne Stevens, [......], Suzanne C Li, Thomas Mason, Esi Morgan Dewitt, Eyal Muscal, Lorien Nassi, Andreas Reiff, Kenneth Schikler, Nora G Singer, Dawn Wahezi, Amy Woodward
  [show abstract] [hide abstract]
  ABSTRACT: To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4-17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0-49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.
  Arthritis & Rheumatism 11/2009; 60(11):3413-24. · 7.87 Impact Factor
• Article: Treatment of pediatric localized scleroderma: results of a survey of North American pediatric rheumatologists.

  Suzanne C Li, Brian M Feldman, Gloria C Higgins, Kathleen A Haines, Marilynn G Punaro, Kathleen M O'Neil
  [show abstract] [hide abstract]
  ABSTRACT: We surveyed pediatric rheumatologists (PR) in North America to learn how they treat pediatric localized scleroderma (LS), a disease associated with significant morbidity for the growing child. A Web-based survey was sent to the 195 PR members of the pediatric rheumatology research alliance CARRA (Childhood Arthritis and Rheumatology Research Alliance). Members were asked which medications they use to treat LS and which factors modify their treatment strategies. Clinical vignettes were provided to learn the specific treatment regimens used. A total of 158 PR from over 70 clinical centers in the United States and Canada participated in the survey, representing 81% of the CARRA membership. These PR saw over 650 patients with LS in the prior year. Nearly all respondents treated LS with methotrexate (MTX) and corticosteroids; most of them intensify treatment for lesions located on the face or near a joint, and about half intensify treatment for recent disease onset (< 6 months). Most PR reserve topical medications for limited treatment situations. Clinical vignettes showed that PR use a broad range of treatment doses and durations for MTX and corticosteroids. Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease.
  The Journal of Rheumatology 11/2009; 37(1):175-81. · 3.69 Impact Factor
• Article: The localized scleroderma skin severity index and physician global assessment of disease activity: a work in progress toward development of localized scleroderma outcome measures.

  Thaschawee Arkachaisri, Soamarat Vilaiyuk, Suzanne Li, Kathleen M O'Neil, Elena Pope, Gloria C Higgins, Marilynn Punaro, Egla C Rabinovich, Margalit Rosenkranz, Daniel A Kietz, Paul Rosen, Steven J Spalding, Teresa R Hennon, Kathryn S Torok, Elaine Cassidy, Thomas A Medsger
  [show abstract] [hide abstract]
  ABSTRACT: To develop and evaluate a Localized Scleroderma (LS) Skin Severity Index (LoSSI) and global assessments' clinimetric property and effect on quality of life (QOL). A 3-phase study was conducted. The first phase involved 15 patients with LS and 14 examiners who assessed LoSSI [surface area (SA), erythema (ER), skin thickness (ST), and new lesion/extension (N/E)] twice for inter/intrarater reliability. Patient global assessment of disease severity (PtGA-S) and Children's Dermatology Life Quality Index (CDLQI) were collected for intrarater reliability evaluation. The second phase was aimed to develop clinical determinants for physician global assessment of disease activity (PhysGA-A) and to assess its content validity. The third phase involved 2 examiners assessing LoSSI and PhysGA-A on 27 patients. Effect of training on improving reliability/validity and sensitivity to change of the LoSSI and PhysGA-A was determined. Interrater reliability was excellent for ER [intraclass correlation coefficient (ICC) 0.71], ST (ICC 0.70), LoSSI (ICC 0.80), and PhysGA-A (ICC 0.90) but poor for SA (ICC 0.35); thus, LoSSI was modified to mLoSSI. Examiners' experience did not affect the scores, but training/practice improved reliability. Intrarater reliability was excellent for ER, ST, and LoSSI (Spearman's rho = 0.71-0.89) and moderate for SA. PtGA-S and CDLQI showed good intrarater agreement (ICC 0.63 and 0.80). mLoSSI correlated moderately with PhysGA-A and PtGA-S. Both mLoSSI and PhysGA-A were sensitive to change following therapy. mLoSSI and PhysGA-A are reliable and valid tools for assessing LS disease severity and show high sensitivity to detect change over time. These tools are feasible for use in routine clinical practice. They should be considered for inclusion in a core set of LS outcome measures for clinical trials.
  The Journal of Rheumatology 10/2009; 36(12):2819-29. · 3.69 Impact Factor
• Source

  Available from: google.com

  Article: Progress in pediatric vasculitis.

  Kathleen M O'Neil
  [show abstract] [hide abstract]
  ABSTRACT: To examine recent advances in the pathophysiology and therapy of pediatric vasculitis. The past 2 years have been marked by significant progress in extending novel techniques to the investigation of the two most common pediatric vasculitis syndromes, Henoch-Schonlein purpura and Kawasaki disease. Study of other vasculitides, such as Wegener granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis, is impeded by the small number of pediatric patients. Nonetheless, national and international registries are beginning to provide the foundation for generation of testable hypotheses regarding pathogenesis and optimal treatment. Thus, recent data from the study of children suggest that disorders in the control of inflammation, such as those that underlie familial Mediterranean fever and other autoinflammatory diseases, may predispose to vasculitis. Improved knowledge of mechanisms of disease, in turn, should pave the way for more targeted, effective, and tolerable therapies for children with systemic vasculitis. International collaboration to study rare disorders such as pediatric vasculitis are demonstrating disorders of inflammatory regulation that predispose to these diseases and may point toward new treatment approaches.
  Current opinion in rheumatology 07/2009; 21(5):538-46. · 4.60 Impact Factor
• Article: Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis.

  James N Jarvis, Kaiyu Jiang, Mark Barton Frank, Nicholas Knowlton, Amita Aggarwal, Carol A Wallace, Ryan McKee, Brad Chaser, Catherine Tung, Laura B Smith, Julie L McGhee, Yanmin Chen, Jeanette Osban, Kathleen M O'Neil, Michael Centola
  [show abstract] [hide abstract]
  ABSTRACT: We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA. We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients. Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro- and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease. Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.
  Arthritis & Rheumatism 05/2009; 60(5):1488-95. · 7.87 Impact Factor
• Article: Outcome of aspirin treatment of antiphospholipid antibody-positive patients.

  Kathleen M O'Neil
  Current Rheumatology Reports 03/2009; 11(1):1-2.
• Article: Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis.

  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
  [show abstract] [hide abstract]
  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
• Article: Should aspirin be used as a preventive therapy for thrombosis in patients with antiphospholipid antibodies?

  Kathleen M O'Neil
  Nature Clinical Practice Rheumatology 02/2008; 4(1):14-5. · 5.85 Impact Factor
• Article: Primary thrombosis prevention in aPL-positive patients.

  Kathleen M O'Neil
  Current Rheumatology Reports 02/2008; 10(1):59-61.
• Article: Role of complement in antiphospholipid antibody-mediated thrombosis.

  Kathleen M O'Neil
  [show abstract] [hide abstract]
  ABSTRACT: The mechanisms by which an antibody that reacts with phospholipids (universal components of mammalian membranes) causes thrombosis are not immediately obvious. The development of an animal model of antiphospholipid antibody syndrome has moved the field forward in dissecting the pathogenesis of antiphospholipid antibody syndrome and has implicated the complement system in the mechanism of disease. Understanding complement's role in promoting thrombosis will be important in designing safer, more effective approaches to the treatment of patients with antiphospholipid antibodies, and may shed light on which patients are at greatest risk for thrombosis, perhaps permitting primary prophylaxis before irreversible tissue and organ damage occur.
  Current Rheumatology Reports 07/2007; 9(3):205-11.