Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

2.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
3.
Curr Rheumatol Rep ; 22(6): 18, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32405775

RESUMO

PURPOSE OF THE REVIEW: Classification criteria define the patient population for clinical trials and translational studies, but also influence current understanding of the disease. This review attempts to delineate the development from the American College of Rheumatology (ACR) 1982 to the European League Against Rheumatism (EULAR)/ACR 2019 classification criteria for systemic lupus erythematosus (SLE). RECENT FINDINGS: The new EULAR/ACR classification criteria use antinuclear antibodies (ANA) as an entry criterion. (Non-infectious) fever is the one new criterion. All criteria items now have individual weights (from 2 to 10) and are structured in domains, within which only the highest item is counted. There is one common attribution rule, counting criteria only if there is no more likely alternative explanation. Ten points are sufficient for classification. The new criteria have reached a sensitivity of 96.1% and a specificity of 93.4%. The new EULAR/ACR 2019 classification criteria for SLE build on the previous criteria sets, adding fever only as a new criteria item. The new structure is reflective of the current diagnostic approach and has led to improved statistical performance.

4.
Rheum Dis Clin North Am ; 45(4): 537-548, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31564295

RESUMO

The treat-to-target principle of controlling inflammatory disease activity by means of disease-modifying antirheumatic drugs or immunosuppressive drugs also pertains to systemic lupus erythematosus (SLE). However, in SLE, intensifying immunosuppression with higher-dose glucocorticoids may worsen outcomes. Therefore, all current recommendations favor better disease control while limiting daily glucocorticoid doses to a maximum of 5 or 7.5 mg of prednisolone daily. Hydroxychloroquine and other prophylactic measures are added, and antiphospholipid syndrome is treated with anticoagulation and not with immunosuppression, which makes the approach of treat to target slightly more complex, mirroring the complexity of the disease.


Assuntos
Antirreumáticos , Lúpus Eritematoso Sistêmico/terapia , Antirreumáticos/classificação , Antirreumáticos/farmacologia , Gerenciamento Clínico , Humanos , Gravidade do Paciente , Planejamento de Assistência ao Paciente , Indução de Remissão/métodos , Exacerbação dos Sintomas
5.
Ann Rheum Dis ; 78(9): 1151-1159, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31383717

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Doenças Reumáticas , Reumatologia , Sociedades Médicas , Humanos
6.
Arthritis Rheumatol ; 71(9): 1400-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31385462

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/análise , Técnicas de Apoio para a Decisão , Técnica Delfos , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sociedades Médicas , Estados Unidos
8.
Immunotherapy ; 10(6): 465-472, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29504436

RESUMO

Giant cell arteritis is a systemic vasculitis of large vessels, manifesting mainly as temporal arteritis or large vessel vasculitis of the aorta and its branches. Glucocorticoid therapy is essential and so far had to be continued over a period of 1.5-2 years, resulting in relevant morbidity through adverse effects. With the approval of tocilizumab, an effective glucocorticoid sparing option is now available. In two randomized controlled trials, a profound reduction of cumulative glucocorticoid dose, prolonged relapse-free remission and reduced number of adverse events in the treatment groups have been demonstrated. Therefore, tocilizumab constitutes a novel therapeutic option in giant cell arteritis. Its differential role in different subgroups, timing of tocilizumab therapy and optimal treatment duration remain to be determined.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Reação de Fase Aguda , Animais , Ensaios Clínicos como Assunto , Aprovação de Drogas , Humanos , Receptores de Interleucina-6/imunologia
9.
Arthritis Care Res (Hoboken) ; 70(3): 428-438, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28544593

RESUMO

OBJECTIVE: To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 antinuclear antibody (ANA) testing for classification of systemic lupus erythematosus (SLE). METHODS: A systematic literature search was conducted in the Medline, Embase, and Cochrane databases for articles published between January 1990 and October 2015. The research question was structured according to Population, Intervention, Comparator, Outcome (PICO) format rules, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed where appropriate. Meta-regression analysis for diagnostic tests was performed, using the ANA titer as independent variable, while sensitivity and specificity were dependent variables. RESULTS: Of 4,483 publications screened, 62 matched the eligibility criteria, and another 2 articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF-ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta-regression gave sensitivity values of 98.4% (95% confidence interval [95% CI] 97.6-99.0%), 97.8% (95% CI 96.8-98.5%), 95.8% (95% CI 94.1-97.1%), and 86.0% (95% CI 77.0-91.9%), respectively. The corresponding specificities were 66.9% (95% CI 57.8-74.9%), 74.7% (95% CI 66.7-81.3%), 86.2% (95% CI 80.4-90.5%), and 96.6% (95% CI 93.9-98.1%), respectively. CONCLUSION: The results of this systematic literature review and meta-regression confirm that IIF-ANAs have high sensitivity for SLE. ANAs at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e., formally test other classification criteria for SLE only if ANAs of at least 1:80 have been found.


Assuntos
Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Testes Sorológicos , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
10.
Z Orthop Unfall ; 155(5): 539-548, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29050054

RESUMO

Background and Objectives Knee osteoarthritis (OA) is a significant public health burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between geographical regions, most likely due to the lack of standardised indication criteria. We set out to define indication criteria for the German healthcare system for TKA in patients with knee OA, on the basis of best evidence and transparent multi-stakeholder consensus. Methods We undertook a complex mixed methods study, including an iterative process of systematic appraisal of existing evidence, Delphi consensus methods and stakeholder conferences. We established a consensus panel representing key German national societies of healthcare providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists, physiotherapists), payers, and patient representatives. A priori defined consensus criteria were at least 70% agreement and less than 20% disagreement among the consensus panel. Agreement was sought for (1) core indication criteria defined as criteria that must be met to consider TKA in a normal patient with knee OA, (2) additional (not obligatory) indication criteria, (3) absolute contraindication criteria that generally prohibit TKA, and (4) risk factors that do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results The following 5 core indication criteria were agreed within the panel: 1. intermittent (several times per week) or constant knee pain for at least 3 - 6 months; 2. radiological confirmation of structural knee damage (osteoarthritis, osteonecrosis); 3. inadequate response to conservative treatment, including pharmacological and non-pharmacological treatment for at least 3 - 6 months; 4. adverse impact of knee disease on patient's quality of life for at least 3 - 6 months; 5. patient-reported suffering/impairment due to knee disease. Additional indication criteria, contraindication criteria, and risk factors for adverse outcome were also agreed by a large majority within the multi-perspective stakeholder panel. Conclusion The defined indication criteria constitute a prerequisite for appropriate provision of TKA in patients with knee OA in Germany. In eligible patients, shared-decision making should eventually determine if TKA is performed or not. The next important steps are the implementation of the defined indication criteria, and the prospective investigation of predictors of success or failure of TKA in the context of routine care provision in Germany.


Assuntos
Artroplastia do Joelho/métodos , Consenso , Osteoartrite do Joelho/cirurgia , Medicina Baseada em Evidências , Alemanha , Humanos , Programas Nacionais de Saúde , Osteoartrite do Joelho/classificação , Osteoartrite do Joelho/diagnóstico
11.
Arthritis Care Res (Hoboken) ; 66(12): 1895-904, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24839085

RESUMO

OBJECTIVE: To identify in a Delphi exercise of international systemic lupus erythematosus (SLE) experts and a systematic literature review the most relevant concepts that impact on the functioning of SLE patients. METHODS: Sixty SLE experts participated in all rounds of a 3-round e-mail-based Delphi exercise; for the literature review, 573 manuscripts out of 4 decades were analyzed. Concepts in the first Delphi round and from the literature were linked to categories of the International Classification of Functioning, Disability and Health (ICF). Categories were voted on individually in a feedback-driven Delphi process, and ranked by frequency in the literature, respectively. RESULTS: In the Delphi exercise, at least 80% of the participants found 30 categories of the domain body functions and structures, and 3 categories in the domain activities and participation and environmental factors important. In general, the categories identified in the literature review overlapped with those in the Delphi exercise with regard to body functions and structures, while showing some differences in other domains. The highest agreement concerned the ICF categories "joints," "skin and related structures," "fatiguability," "immunological system functions," and "handling stress and other psychological demands." Agreement with an earlier patient Delphi exercise was considerable. CONCLUSION: A 3-step Delphi exercise of 60 SLE experts and a literature review identified a wide spectrum of relevant ICF categories with impact on functioning of SLE patients. The categories derived from these approaches overlap with each other and with those of a patient Delphi exercise.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência , Lúpus Eritematoso Sistêmico/diagnóstico , Técnica Delfos , Avaliação da Deficiência , Indicadores Básicos de Saúde , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia
12.
Int J Clin Pharmacol Ther ; 50(6): 413-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22541746

RESUMO

OBJECTIVE: Oxidative stress plays an important role in human disease, but antioxidant therapies are limited. Under physiological conditions superoxide is controlled by the enzyme superoxide dismutase. A recombinant human Cu/Zn superoxide dismutase (rhSOD) might open new therapeutic possibilities. METHODS: Safety profile and pharmacokinetics in plasma and urine were assessed in an open label phase I study with dose-escalation. 18 healthy male volunteers received a single intravenous 10-minute infusion of 150, 300, or 600 mg rhSOD, respectively (n = 6 per dose group). RESULTS: rhSOD was well tolerated. Peak plasma concentrations (cmax; mean ± SD) were reached at the end of infusion, with 32.96 ± 10.31, 51.60 ± 8.23, and 103.90 ± 19.02 µg/ ml, respectively. Non-compartmental halflife was 1.06 ± 0.37, 1.59 ± 0.64, and 1.63 ± 0.28 hours. Urinary excretion (10 h) showed dose-dependent relative increases with 11.28 ± 6.46 (7.5%), 54.93 ± 15.25 (18.3%), and 191.81 ± 104.60 mg (32.0%). CONCLUSIONS: Our results show a good safety profile and predictable pharmacokinetics of rhSOD, suggesting that therapeutic exploratory studies might be safely conducted in humans.


Assuntos
Superóxido Dismutase/farmacocinética , Adulto , Humanos , Infusões Intravenosas , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Superóxido Dismutase/administração & dosagem
13.
Thromb Res ; 129(4): e83-91, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21925716

RESUMO

INTRODUCTION: AZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF). METHODS: Open, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤ 2 before randomization. Study I: 38 patients randomized to AZD0837 (150,250 or 350 mg) or ximelagatran 36 mg twice daily for 10-14 days. Study II: 27 patients randomized to AZD0837 250 mg twice daily or VKA titrated to an INR of 2-3 for 10-14 days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject. RESULTS: Thrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2 µmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls. CONCLUSIONS: Effects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms.


Assuntos
Amidinas/administração & dosagem , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Azetidinas/administração & dosagem , Benzilaminas/administração & dosagem , Trombose/prevenção & controle , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Animais , Antitrombinas/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Suínos , Trombose/complicações , Trombose/diagnóstico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA