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1.
Hum Mol Genet ; 27(21): 3813-3824, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085094

RESUMO

Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.

3.
Arthritis Care Res (Hoboken) ; 69(4): 517-527, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27390247

RESUMO

OBJECTIVE: The Sjögren's Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjögren's syndrome by offering recommendations for management. METHODS: Management questions for the systemic manifestations of Sjögren's syndrome were posed by the CPG committee with input from patients and rheumatologists. Clinical questions were assigned to a topic review group that performed systematic reviews and data extraction and drafted guidelines. Quality of evidence and strength of recommendation were rated using the American Society of Clinical Oncology's modification of the Grading of Recommendations Assessment, Development, and Evaluation. Guideline recommendations were reviewed by a consensus expert panel (CEP) composed of 30-40 clinicians from academia and community practices, as well as registered nurses and patients, using a modified Delphi process. A CEP agreement level of 75% was set as a minimum for adoption of a guideline recommendation. RESULTS: Consensus was achieved for 19 recommendations; for 11 additional modules, available data were insufficient to allow a recommendation to be formulated. Of the 19 recommendations, 15 required 1 Delphi round, 2 required 2 rounds, and 2 required 3 rounds. CONCLUSION: Key recommendations include a decision tree for the use of oral disease-modifying antirheumatic drugs for inflammatory musculoskeletal pain, use of self-care measures and advice regarding exercise to reduce fatigue, and the use of rituximab in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex. The CPG committee strongly discouraged the use of tumor necrosis factor inhibitors for sicca symptoms and for the majority of clinical contexts in primary Sjögren's syndrome.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Fadiga/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor Musculoesquelética/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Consenso , Árvores de Decisões , Técnica Delfos , Medicina Baseada em Evidências , Fadiga/diagnóstico , Fadiga/etiologia , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/etiologia , Autocuidado , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Resultado do Tratamento
4.
Ann Rheum Dis ; 76(1): 9-16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27789466

RESUMO

OBJECTIVES: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.


Assuntos
Seleção de Pacientes , Glândulas Salivares/patologia , Sialadenite/patologia , Síndrome de Sjogren/classificação , Síndrome de Sjogren/diagnóstico , Autoanticorpos/sangue , Autoantígenos/imunologia , Biópsia , Ensaios Clínicos como Assunto , Consenso , Humanos , Guias de Prática Clínica como Assunto , RNA Citoplasmático Pequeno/imunologia , Ribonucleoproteínas/imunologia , Saliva/metabolismo , Sensibilidade e Especificidade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/patologia
5.
Arthritis Rheumatol ; 69(1): 35-45, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27785888

RESUMO

OBJECTIVE: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of 5 items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2 , each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, i.e., 96% (95% confidence interval [95% CI] 92-98%) and 95% (95% CI 92-97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well-suited as criteria for enrollment in clinical trials.


Assuntos
Síndrome de Sjogren/classificação , Síndrome de Sjogren/diagnóstico , Conjuntos de Dados como Assunto , Humanos , Internacionalidade , Guias de Prática Clínica como Assunto , Estados Unidos
6.
RMD Open ; 1(1): e000022, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26509054

RESUMO

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

7.
J Okla State Med Assoc ; 100(11): 425-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18183859

RESUMO

Fluoroquinolone antibiotics are widely employed in treating infectious diseases. Lately, reports of either hyperglycemia or hypoglycemia have appeared in the medical literature. Many patients are elderly and have underlying diabetes and renal insufficiency. Of these antibiotics, dysglycemia occurs more frequently with gatifloxacin (Tequin). While hypoglycemia usually occurs within the first three days of treatment, hyperglycemia often occurs later in the treatment course. The hypoglycemia may be profound and difficult to manage. We report 4 patients with hypoglycemia while taking gatifloxacin and review the relevant literature.


Assuntos
Antibacterianos/efeitos adversos , Fluoroquinolonas/efeitos adversos , Hipoglicemia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Fluoroquinolonas/uso terapêutico , Gatifloxacina , Humanos , Hipoglicemia/complicações , Masculino
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