CLOVIS ARTUR ALMEIDA DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Health related quality of life measure in systemic pediatric rheumatic diseases and its translation to different languages: an international collaboration(2014) MOORTHY, Lakshmi Nandini; ROY, Elizabeth; KURRA, Vamsi; PETERSON, Margaret G. E.; HASSETT, Afton L.; LEHMAN, Thomas J. A.; SCOT, Christiaan; EL-GHONEIMY, Dalia; SAAD, Shereen; FEKY, Reem El; AL-MAYOUF, Sulaiman; DOLEZALOVA, Pavla; MALCOVA, Hana; HERLIN, Troels; NIELSEN, Susan; WULFFRAAT, Nico; ROYEN, Annet van; MARKS, Stephen D.; BELOT, Alexandre; BRUNNER, Jurgen; HUEMER, Christian; FOELDVARI, Ivan; HORNEFF, Gerd; SAURENMAN, Traudel; SCHROEDER, Silke; PRATSIDOU-GERTSI, Polyxeni; TRACHANA, Maria; UZIEL, Yosef; AGGARWAL, Amita; CONSTANTIN, Tamas; CIMAZ, Rolando; GIANI, Theresa; CANTARINI, Luca; FALCINI, Fernanda; MANZONI, Silvia Magni; RAVELLI, Angelo; RIGANTE, Donato; ZULIAN, Fracnceso; MIYAMAE, Takako; YOKOTA, Shumpei; SATO, Juliana; MAGALHAES, Claudia S.; LEN, Claudio A.; APPENZELLER, Simone; KNUPP, Sheila Oliveira; RODRIGUES, Marta Cristine; SZTAJNBOK, Flavio; ALMEIDA, Rozana Gasparello de; JESUS, Adriana Almeida de; CAMPOS, Lucia Maria de Arruda; SILVA, Clovis; LAZAR, Calin; SUSIC, Gordana; AVCIN, Tadej; CUTTICA, Ruben; BURGOS-VARGAS, Ruben; FAUGIER, Enrique; ANTON, Jordi; MODESTO, Consuelo; VAZQUEZ, Liza; BARILLAS, Lilliana; BARINSTEIN, Laura; STERBA, Gary; MALDONADO, Irama; OZEN, Seza; KASAPCOPUR, Ozgur; DEMIRKAYA, Erkan; BENSELER, SusaBackground: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases. Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY (c)) to Simple Measure of Impact of Illness in Youngsters (SMILY (c)-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY (c)-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n= 15) and 17 parents participated. The mean age was 12 +/- 4 years, with median disease duration of 21 months (1-172 months). We translated SMILY (c)-Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa. Conclusion: SMILY (c)-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY (c)-Illness with its available translations may be used as useful adjuncts to clinical practice and research.
- International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis(2022) CHALHOUB, Nathalie E.; WENDERFER, Scott E.; LEVY, Deborah M.; ROUSTER-STEVENS, Kelly; AGGARWAL, Amita; I, Sonia Savani; RUTH, Natasha M.; ARKACHAISRI, Thaschawee; QIU, Tingting; MERRITT, Angela; ONEL, Karen; GOILAV, Beatrice; KHUBCHANDANI, Raju P.; DENG, Jianghong; FONSECA, Adriana R.; ARDOIN, Stacy P.; CIURTIN, Coziana; KASAPCOPUR, Ozgur; JELUSIC, Marija; HUBER, Adam M.; OZEN, Seza; KLEIN-GITELMAN, Marisa S.; APPENZELLER, Simone; CAVALCANTI, Andre; FOTIS, Lampros; LIM, Sern Chin; SILVA, Rodrigo M.; RAMIREZ-MIRAMONTES, Julia; ROSENWASSER, Natalie L.; SAAD-MAGALHAES, Claudia; SCHONENBERG-MEINEMA, Dieneke; SCOTT, Christiaan; SILVA, Clovis A.; ENCISO, Sandra; TERRERI, Maria T.; TORRES-JIMENEZ, Alfonso-Ragnar; TRACHANA, Maria; AL-MAYOUF, Sulaiman M.; DEVARAJAN, Prasad; HUANG, Bin; I, Hermine BrunnerObjective To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. Methods Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for >= 4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. Results Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). Conclusion The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
conferenceObject Development and Initial Validation of the MS Score for Diagnosis of Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis(2019) MINOIA, Francesca; BOVIS, Francesca; DAVI, Sergio; HORNE, AnnaCarin; FISCHBACH, Michel; FROSCH, Michael; HUBER, Adam; JELUSIC, Marija; SAWHNEY, Sujata; MCCURDY, Deborah; SILVA, Clovis Artur; RIGANTE, Donato; UNSAL, Erbil; RUPERTO, Nicolino; MARTINI, Alberto; CRON, Randy; RAVELLI, Angelo- Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis(2019) MINOIA, Francesca; BOVIS, Francesca; DAVI, Sergio; HORNE, AnnaCarin; FISCHBACH, Michel; FROSCH, Michael; HUBER, Adam; JELUSIC, Marija; SAWHNEY, Sujata; MCCURDY, Deborah K.; SILVA, Clovis A.; RIGANTE, Donato; UNSAL, Erbil; RUPERTO, Nicolino; MARTINI, Alberto; CRON, Randy Q.; RAVELLI, AngeloObjective To develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA). Methods The clinical and laboratory features of 362 patients with sJIA-associated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. Eighty percent of the study population was used to develop the score and the remaining 20% constituted the validation sample. A Bayesian Model Averaging approach was used to assess the role of each clinical and laboratory variables in the diagnosis of MAS and to obtain the coefficients of selected variables. The final score, named MAS/sJIA (MS) score, resulted from the linear combination of these coefficients multiplied by the values of each variable. The cut-off that best discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. Score performance was evaluated in both developmental and validation samples. Results The MS score ranges from -8.4 to 41.8 and comprises seven variables: central nervous system dysfunction, haemorrhagic manifestations, active arthritis, platelet count, fibrinogen, lactate dehydrogenase and ferritin. A cut-off value >=-2.1 revealed the best performance in discriminating MAS from active sJIA, with a sensitivity of 0.85, a specificity of 0.95 and a kappa value of 0.80. The good performance of the MS score was confirmed in the validation sample. Conclusion The MS score is a powerful and feasible tool that may assist practitioners in making a timely diagnosis of MAS in patients with sJIA.
conferenceObject Validation of Flare Criteria for Children and Adolescents with Systemic Lupus Erythematosus(2017) BRUNNER, Hermine I.; HOLLAND, Michael J.; BERESFORD, Michael W.; RUPERTO, Nicolino; ARDOIN, Stacy P.; APPENZELLER, Simone; SILVA, Clovis A.; NOVAK, Glaucia V.; LOURENCO, Daniela M.; FLORES, Francisco; GOILAV, Beatrice; WENDERFER, Scott E.; LEVY, Deborah M.; RAVELLI, Angelo; KHUBCHANDANI, Raju; AVCIN, Tadej; KLEIN-GITELMAN, Marisa S.; FELDMAN, Brian M.; YING, JunconferenceObject Validation of Clinically Relevant Improvement in Children and Adolescents with cSLE(2017) AYDIN, Pinar Ozge Avar; HOLLAND, Michael J.; APPENZELLER, Simone; ARDOIN, Stacy P.; AVCIN, Tadej; BERESFORD, Michael W.; FELDMAN, Brian M.; FLORES, Francisco; KLEIN-GITELMAN, Marisa S.; GOILAV, Beatrice; KHUBCHANDANI, Raju; LEVY, Deborah M.; RAVELLI, Angelo; RUPERTO, Nicolino; SILVA, Clovis A.; WENDERFER, Scott E.; YING, Jun; BRUNNER, Hermine I.- Measuring Disease Damage and Its Severity in Childhood-Onset Systemic Lupus Erythematosus(2018) HOLLAND, Michael J.; BERESFORD, Michael W.; FELDMAN, Brian M.; HUGGINS, Jennifer; NORAMBUENA, Ximena; SILVA, Clovis A.; SUSIC, Gordana; SZTAJNBOK, Flavio; UZIEL, Yosef; APPENZELLER, Simone; ARDOIN, Stacy P.; AVCIN, Tadej; FLORES, Francisco; GOILAV, Beatrice; KHUBCHANDANI, Raju; KLEIN-GITELMAN, Marissa; LEVY, Deborah; RAVELLI, Angelo; WENDERFER, Scott E.; YING, Jun; RUPERTO, Nicolino; BRUNNER, Hermine I.ObjectiveMethodsTo describe the frequency and types of disease damage occurring with childhood-onset systemic lupus erythematosus (SLE) as measured by the 41-item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity. Information for the SDI was prospectively collected from 1,048 childhood-onset SLE patients. For a subset of 559 patients, physician-rated damage severity measured by visual analog scale (MD VAS damage) was also available. Frequency of SDI items and the association between SDI summary scores and MD VAS damage were estimated. Finally, an international consensus conference, using nominal group technique, considered the SDI's capture of childhood-onset SLE-associated damage and its severity. ResultsConclusionAfter a mean disease duration of 3.8 years, 44.2% of patients (463 of 1,048) already had an SDI summary score >0 (maximum 14). The most common SDI items scored were proteinuria, scarring alopecia, and cognitive impairment. Although there was a moderately strong association between SDI summary scores and MD VAS damage (Spearman's r = 0.49, P < 0.0001) in patients with damage (SDI summary score >0), mixed-effects analysis showed that only 4 SDI items, each occurring in <2% of patients overall, were significantly associated with MD VAS damage. There was consensus among childhood-onset SLE experts that the SDI in its current form is inadequate for estimating the severity of childhood-onset SLE-associated damage. Disease damage as measured by the SDI is common in childhood-onset SLE, even with relatively short disease durations. Given the shortcomings of the SDI, there is a need to develop new tools to estimate the impact of childhood-onset SLE-associated damage.
- Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis(2019) PARDEO, Manuela; WANG, Jianmei; RUPERTO, Nicolino; ALEXEEVA, Ekaterina; CHASNYK, Vyacheslav; SCHNEIDER, Rayfel; HORNEFF, Gerd; HUPPERTZ, Hans-Iko; MINDEN, Kirsten; ONEL, Karen; ZEMEL, Lawrence; MARTIN, Alan; KONE-PAUT, Isabelle; SIAMOPOULOU-MAVRIDOU, Antigoni; SILVA, Clovis A.; PORTER-BROWN, Benjamin; BHARUCHA, Kamal N.; I, Hermine Brunner; BENEDETTI, Fabrizio DeObjective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results. ANC decreased to grade >= 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-165) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.
- Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial(2015) BRUNNER, Hermine I.; RUPERTO, Nicolino; ZUBER, Zbigniew; KEANE, Caroline; HARARI, Olivier; KENWRIGHT, Andrew; LU, Peng; CUTTICA, Ruben; KELTSEV, Vladimir; XAVIER, Ricardo M.; CALVO, Inmaculada; NIKISHINA, Irina; RUBIO-PEREZ, Nadina; ALEXEEVA, Ekaterina; CHASNYK, Vyacheslav; HORNEFF, Gerd; OPOKA-WINIARSKA, Violetta; QUARTIER, Pierre; SILVA, Clovis A.; SILVERMAN, Earl; SPINDLER, Alberto; BAILDAM, Eileen; GAMIR, M. Luz; MARTIN, Alan; RIETSCHEL, Christoph; SIRI, Daniel; SMOLEWSKA, Elzbieta; LOVELL, Daniel; MARTINI, Alberto; BENEDETTI, Fabrizio DeObjective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for 6months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4weeks (8 or 10mg/kg for body weight (BW) <30kg; 8mg/kg for BW 30kg). At week 16, patients with JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30kg: 10mg/kg (n=35) or 8mg/kg (n=34); 30kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.
- American College of Rheumatology Provisional Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus(2018) BRUNNER, Hermine I.; HOLLAND, Michael; BERESFORD, Michael W.; ARDOIN, Stacy P.; APPENZELLER, Simone; SILVA, Clovis A.; FLORES, Francisco; GOILAV, Beatrice; WENDERFER, Scott E.; LEVY, Deborah M.; RAVELLI, Angelo; KHUNCHANDANI, Raju; AVCIN, Tadej; KLEIN-GITELMAN, Marisa S.; FELDMAN, Brian M.; RUPERTO, Nicolino; YING, JunObjective. To validate the preliminary criteria of global flare for childhood-onset SLE (cSLE). Methods. Pediatricians experienced in cSLE care (n = 268) rated unique patient profiles; results of standard cSLE laboratory testing and information about the cSLE flare descriptors were presented as follows: global assessment of patient well-being, physician global assessment of disease activity (MD-global), Disease Activity Index score, protein/creatinine ratio (PCR), and erythrocyte sedimentation rate (ESR). Using rater interpretation of the course of cSLE (baseline versus followup as the gold standard), performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of the preliminary flare criteria was tested. An international consensus conference was held to rank the preliminary flare criteria as per the American College of Rheumatology recommendations and delineate threshold scores for minor, moderate, and major flares. Results. The accuracy of the 2 highest-ranked candidate criteria that consider absolute changes (Delta) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG) (numeric scoring: A = 12, B = 8, C = 1, and D/E = 0), MD-global, PCR, and ESR were confirmed (both AUC >0.93). For the SLEDAI-based criteria (0.5 x Delta SLEDAI + 0.45 x Delta PCR + 0.5 x Delta MD-global + 0.02 x Delta ESR) flare scores >= 6.4/3.0/0.6 constituted major/moderate/minor flares, respectively. For the BILAG-based algorithm (0.4 x Delta BILAG + 0.65 x Delta PCR + 0.5 x Delta MD-global + 0.02 x Delta ESR) flare scores >= 7.4/3.7/2.2 delineated major/moderator/minor flares, respectively. These threshold values (SLEDAI, BILAG) were all >82% sensitive and specific for capturing flare severity. Conclusion. Provisional criteria for global flares in cSLE are available to identify patients who experienced a flare. These criteria also allow for discrimination of the severity of cSLE exacerbations.